Canine distemper virus (CDV) poses a substantial threat to diverse carnivores, leading to sys-temic and often fatal diseases. Accurate and prompt diagnosis is paramount for effective man-agement and curbing further transmission. This study evaluates the diagnostic efficacy of drop-let digital PCR (ddPCR) in comparison to conventional reverse transcription (RT-PCR) and quantitative reverse transcription real-time PCR (RT-qPCR). Seventy-six clinical samples were collected from dogs with CDV symptoms diagnosed by specialized veterinarians, and sixteen samples from asymptomatic individuals. Conventional PCR, quantitative real-time PCR, and ddPCR were deployed, and their diagnostic capabilities were meticulously assessed. DdPCR ex-hibited heightened analytical sensitivity, reaching a detection limit of 3 copies/μL, whereas RT-qPCR had a detection limit of 86 copies/μL. The comparative analysis between clinical diagnosis and molecular techniques, including RT-PCR and RT-qPCR, demonstrated low concordance, with Kappa coefficients of 0.268 and 0.324, respectively. In contrast, ddPCR, showed a moderate concordance, with a Kappa coefficient of 0.477. Sensitivity was 42.39% for RT-PCR, 57.89% for RT-qPCR and 72.37% for ddPCR, with 100% of specificity for all methods. This study under-scores ddPCR's superior sensitivity and concordance with clinical CDV diagnosis, even at low viral concentrations, suggesting it as a promising alternative for CDV diagnosis.

Nanostructured polymer dispersed liquid crystals (nano-PDLCs) are transparent and optically isotropic materials, in which submicron-sized liquid crystal (LC) domains are dispersed within a polymer matrix. Nano-PDLCs can induce their birefringence by applying an electric field (E-field) based on reorientation of LC molecules. If nano-PDLCs are utilized as light scattering-less birefringence memory materials, it is necessary to suppress the relaxation of LC molecules orientation after removal of the E-field. We focused on a ferroelectric smectic A (SmA) to suppress the relaxation of LC molecules due to their layered structure and high viscosity. Although nano-PDLCs require a strong E-field to reorient LC molecules due to the anchoring effect on the LC/polymer interface, the required field strength can be reduced by using a ferroelectric smectic A (SmAF) LC with a large dielectric constant. In this study, we fabricated a nano-PDLC by irradiating an ultraviolet light to a mixture comprising of a SmAF LC, photocurable monomers and a photo-initiator and its electro-birefringence effect was evaluated using a polarizing optical microscopy. After removal of an E-field, enhanced memory effect was observed on the sample using SmAFLC comparing to nematic LC based nano-PDLCs. (193 words/ 200 words)

SOCS2, an E3 ubiquitin ligase, regulates the JAK/STAT signaling pathway, essential for cytokine signaling and immune responses. Its dysregulation contributes to cardiovascular diseases (CVDs) by promoting abnormal cell growth, inflammation, and resistance to cell death. This study aimed to elucidate the molecular mechanisms underlying the interactions between Lumbricus-derived proteins and peptides and SOCS2, with a focus on identifying potential therapeutic candidates for CVDs. Utilizing a multifaceted approach, advanced computational methodologies, including 3D structure modeling, protein-protein docking, 100 ns molecular dynamics (MD) simulations, and MM/PBSA calculations, were employed to assess the binding affinities and functional implications of Lumbricus-derived proteins on SOCS2 activity. The findings revealed that certain proteins, such as Lumbricin, Chemoattractive glycoprotein ES20, and Lumbrokinase-7T1, exhibited similar activities to standard antagonists in modulating SOCS2 activity. Furthermore, MM/PBSA calculations were employed to assess the binding free energies of these proteins with SOCS2. Specifically, Lumbricin exhibited an average ΔGbinding of -59.25 kcal/mol, Chemoattractive glycoprotein ES20 showed -55.02 kcal/mol, and Lumbrokinase-7T1 displayed -69.28 kcal/mol. These values suggest strong binding affinities between these proteins and SOCS2, reinforcing their potential therapeutic efficacy in cardiovascular diseases. Further in vitro and animal studies are recommended to validate these findings and explore broader applications of Lumbricus-derived proteins.

The chemical stability of tetramethylammonium (TMA) head groups, both with and without the presence of a choline chloride and ethylene glycol-based deep eutectic solvent (DES), was studied using Density Functional Theory (DFT) calculations and ab initio Molecular Dynamics (MD) simulations. DFT calculations of transition state energetics (ΔEreaction, ΔGreaction, ΔEactivation, and ΔGactivation) for key degradation mechanisms, ylide formation (YF) and nucleophilic substitution (SN2), suggested that the presence of DES enhances the stability of the TMA head groups compared to systems without DES. Ab initio MD simulations across hydration levels (HLs) 1 to 5 indicated that without DES, YF dominates at lower HLs, while SN2 does not occur. In contrast, both mechanisms are suppressed in the presence of DES. Temperature also plays a role: without DES, YF dominates at 298 K, while SN2 becomes prominent at 320 K and 350 K. With DES, both degradation mechanisms are inhibited. These findings suggest DES could improve the chemical stability of TMA head groups in anion exchange membranes.

The hetero Diels-Alder (HDA) reaction between the ambident heterodiene 3-methylene-2,4-chromandione (MCDO) and the non-symmetric methyl vinyl ether (MVE) is investigated within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) computational level. The aim of this study is to gain insight into the molecular mechanism and to elucidate the factors that control the selectivity found experimentally. DFT-based reactivity indices reveal that MCDO exhibits strong electrophilic character, while MVE displays a strong nucleophilic character. Meanwhile, Parr function explains the ortho regioselectivity of this HDA reaction. The highly polar nature of this HDA reaction, supported by the high global electron density transfer (GEDT) taking place at the transition state structures (TSs), accounts for the very low activation energy associated with the most favorable TS-4on. The ambident nature of MCDO allows the formation of two constitutional isomeric cycloadduct. In the case of MVE, the pseudocyclic selectivity is attained by a thermodynamic control. This polar HDA reaction displays an endo stereoselectivity and a complete ortho regioselectivity. A comparative Relative Interacting Atomic Energy (RIAE) analysis of the two diastereomeric TS-4on and TS-6on indicates a highly likeness between them, which explains the low pseudocyclic selectivity under kinetic control.

Brain plasticity is the ability of the brain to change and adapt in response to experience or learning. Its hallmarks are developmental flexibility, complex interactions of genetic and environmental influences, and structure-functional changes comprising neurogenesis, axonal sprouting, and synaptic remodeling. Herein, we review brain plasticity association with non-coding RNAs (ncRNAs). Studies on brain plasticity have important practical implications. Numerous cerebral ncRNAs are linked with neurological disorders, which makes them putative targets for RNA-based diagnostics and therapeutics since molecular characteristics of brain plastic change may reveal disease course and rehabilitative potential of the patient. A new insight into the concept of brain plasticity will provide perspectives on functional recovery following brain damage. The knowledge of this phenomenon will enable physicians to exploit cerebral plastic potential and regulate eloquent networks with timely interventions. Future studies will provide pathophysiologic mechanisms of brain plasticity at macro- and microscopic levels to advance rehabilitation strategies and improve the quality of life in neurological disorders.

Endometrial cancer (EC) poses a significant global health challenge, with increasing prevalence in 26 of 43 countries and over 13,000 deaths projected in the United States by 2024. This rise correlates with aging populations, the obesity epidemic, and changing reproductive patterns, including delayed childbearing. Despite the early diagnosis in 67% of cases, approximately 30% of cases present with regional or distant spread, leading to nearly 20% mortality rates. Unlike many cancers, EC mortality rates are escalating, outpacing therapeutic advancements until recently. One of the reasons for this was the lack of effective therapeutic options for advanced disease until recently. The introduction of immunotherapy has marked a turning point in EC treatment, particularly benefiting patients with defects in mismatch repair proteins (dMMRs). However, dMMR status alone does not ensure a favorable response, underscoring the need for precise patient selection. This review explores the pivotal role of mismatch repair proteins in EC, emphasizing their heterogeneity, the challenges in their assessment, and their potential as predictive biomarkers.

Fusarium wilt, caused by Fusarium oxysporum f.sp. cubense (Foc), is recognized as one of the most devastating diseases affecting banana cultivation worldwide. In India, Foc extensively affects the Malbhog banana (AAB genomic group) production. In this study, we isolated 25 Foc isolates from wilt-affected Malbhog plantations of India. Pathogenicity test confirmed the identity of these isolates as Foc, the primary causative agent of wilt in banana. Morpho-cultural characterization of the Foc isolates showed large variation in colony morphological features, intensity, and pattern of pigmentation, chlamydospores, and conidial size. The molecular identification of these isolates using Race-1 and Race-4 specific primers established their identity as Race- 1 of Foc, with absence of TR- 4. For a more comprehensive understanding of genetic diversity of Foc isolates, we em-ployed ISSR molecular typing which revealed five major clusters. Ahigh96% diversity within Foc population indicated the presence of polymorphic loci in individuals of a given population evi-dent from results of Nei’s genetic diversity, Shannon information index, and polymorphism in-formation content values, apart from analysis of molecular variance (AMOVA). The current findings provide significant insights towards detection of Foc variants, and consequently the deployment of effective management practices to keep the possible epidemic development of disease under control along Malbhog banana growing belts of northeast India.

Numerous varieties of Capsicum annuum L. with multiple valuable traits, such as adaptation to biotic and abiotic stress factors, can be found in south-east Romania, well known for vegetable cultivation and an important area of biodiversity conservation. To obtain useful information toward a sustainable agriculture, management and conservation of local pepper varieties, we analyzed the genetic diversity and we did deep molecular characterization using Whole Genome Resequencing (WGS) for variant/mutation detection. The pepper varieties used in the present study were registered by VRDS in the ISTIS catalog between 1974 and 2019 and maintained in conservative selection, however, no studies have been published yet using WGS analysis in order to characterize this specific germplasm. The genome sequences, annotation and alignments provided in this study offer essential resources for genomic research as well as for future breeding efforts using the C. annuum local varieties.

The knee joint plays a vital role in human movement, bearing mechanical loads during daily and athletic activities. This review explores the knee joint's response to mechanical loading, particularly focusing on mechanotransduction—the process by which cells convert mechanical stimuli into biochemical signals. These signals trigger cellular responses crucial for maintaining joint health, promoting repair, and adapting to mechanical changes. Understanding mechanotransduction is key to developing effective rehabilitation strategies for knee injuries and managing conditions like osteoarthritis. This review synthesizes current research on the cellular and molecular pathways involved in knee joint mechanotransduction, examining how various loading conditions—such as compression, tension, and shear—affect tissues like cartilage, synovium, ligaments, and tendons. The review discusses the impact of mechanotransduction on cellular components such as chondrocytes, synoviocytes, and fibroblasts, which are essential for maintaining tissue integrity and function. It also highlights the role of signaling pathways like MAPK, NF-κB, and Wnt in mediating cellular responses to mechanical stimuli, influencing gene expression, protein synthesis, and metabolism. By understanding these mechanisms, clinicians can develop targeted therapeutic interventions, including controlled loading protocols, exercise regimens, and manual therapies. This review underscores the importance of integrating mechanobiology insights into rehabilitation practices to enhance tissue repair, restore function, and prevent further joint degeneration, ultimately improving knee joint health and patient outcomes.

The bioremediation induced by bacteria offers a promising alternative for the contamination of aromatic hydrocarbons, due to their metabolic processes suitable for the removal of these pollutants, as many of them are carcinogenic molecules and dangerous to human health. Our research focused on isolating a bacterium from the rhizosphere of the tara tree with the ability to degrade polycyclic aromatic hydrocarbons, using draft genomic sequencing and computational analysis. Enterobacter sp. strain UNJFSC 003 possesses 4,460 protein‐coding genes, 2 rRNA genes, 77 tRNA genes, and a GC content of 54.38%. A taxonomic analysis of our strain revealed that it has an average nucleotide identity of 87.8% <95%, indicating that it is a new endemic enterobacterium. Additionally, pangenomic analysis with 15 strains demonstrated that our strain has a phylogenetic relationship with strain FDAARGOS 1428 (E. cancerogenus), with a total of 381 core genes and 4,778 accessory genes. Orthologous methods predicted that strain UNJFSC 003 possesses genes with potential for use in hydrocarbon bioremediation. Genes were predicted in the subpathways for the degradation of homoprotocatechuate and phenylacetate, primarily located in the cytoplasm. Studies conducted through molecular modeling and docking revealed the affinity of the predicted proteins in the degradation of benzo[a]pyrene in the homoprotocatechuate subpathway, specifically hpcB, which has enzymatic activity as a dioxygenase, and hpcC, which functions as an aldehyde dehydrogenase. This study provides information on native strains from the Lomas de Lachay with capabilities for the bioremediation of aromatic hydrocarbons and other compounds.

High-grade advanced ovarian, fallopian tube and primary peritoneal (HGAOC) cancer are malignancies in which, apart from surgical treatment, systemic treatment plays an important role. The improvement in treatment results is associated with the introduction of polyADP-ribose polymerase inhibitors (PARPis). The aim of this study is to present a cross-section of patients treated for HGAOC, in one center, including the distribution of treatment principles following the most up-to-date guidelines. We observed patients who reported to the Department of Gyneacological Oncology between January 2018 and December 2023. We analyzed 437 women with a first diagnosis of HGAOC, who had not been treated before. The introduction of combined treatment with bevacizumab and PARPi into the first line of treatment, regardless of any remnants left during cytoreductive surgery, was introduced in November 2022. Since then, 30% (18/60) of patients (14 with olaparib and 4 with niraparib) have used the above regimen. Previously, in May 2021 - October 2022, it was 27% of patients (13/81 with olaparib and 9/81 with niraparib). Among patients starting treatment in January 2018 - April 2021, only 4.7% (5/106) received the platinum + paclitaxel + olaparib regimen. In both groups – with and without BRCA1/2 pathogenic or likely- pathogenic variant, significantly more patients used PC + PARPi or PC + BEV + PARPi in periods II and III than in period I (p<0.01). The introduction of modern treatment in our center very quickly changed the structure of patient treatment. Carriers of BRCA1/2 pathogenic or likely-pathogenic variant had previously received only chemotherapy, disappeared after the introduction of PARPi, in favor of new therapies. Most patients with no BRCA1/2 pathogenic or likely-pathogenic variant, who used PARPi in therapy in our center – received niraparib and therefore they are beneficiaries of molecular diagnostics in the field of HRD.

Mutation of a single amino acid residue may significantly affect the structure and function of an entire protein. The effect of single amino acid substitutions can be assessed by examining the physicochemical environment surrounding the amino acid of interest, an emerging form of quantification of which is multidimensional tensors. However, the effect with respect to a protein variant’s inherent dynamics in tensor space is rarely assessed despite the potential importance of this form of analysis in revealing local physicochemical properties of the protein and response to mutation. Using the wild-type and 936 mutant structures of the protein domain 1pga, the present research evaluated the effects of local protein context and single amino acid substitutions on molecular dynamics simulation-derived structural distributions via the use of tensors capturing a range of biochemical properties. It was observed that the extent of simulated physicochemical variation local to a substituted amino acid is positively associated with local mechanical stiffness, loss of protein thermostability and decreased local hydrophobicity. In addition, it was observed that the largest tensor variation occurs in densely-packed, hydrophobic core-associated regions of protein structures. In summary, the pattern of tensor change aligns with prior knowledge about protein stability and physicochemical properties.

Infection-related cardiovascular diseases (CVDs) represent a significant health challenge, necessitating novel therapeutic strategies targeting key receptors involved in inflammation and infection. Antimicrobial peptides (AMPs) offer a promising approach, potentially disrupting pathogenic processes. This study aimed to investigate the efficacy of AMPs as therapeutic agents by examining their interactions with critical CVD-related receptors. A comprehensive computational approach was utilized to assess the interactions between AMPs and receptors associated with CVDs. Molecular docking studies were conducted to evaluate AMP binding to target receptors: ACE2, CRP, MMP9, NLRP3, and TLR4. The top-performing AMPs were further analyzed through 100 ns molecular dynamics (MD) simulations, and their binding affinities were quantified using MM/PBSA calculations. The analysis revealed that Tachystatin, Pleurocidin, and Subtilisin A exhibit strong binding affinities to key CVD-related receptors, including ACE2, CRP, and MMP9. These AMPs demonstrated the potential for disrupting receptor-peptide interactions critical to infection and inflammation. MD simulations confirmed the stability of AMP-receptor complexes, with MM/PBSA calculations showing significant binding energies. Future directions include conducting in vitro and in vivo studies to validate the therapeutic efficacy and safety of these AMPs in clinical settings.

Urinary tract infections (UTIs) affect nearly 50% of women in their lifetime. Uropathogenic Escherichia coli (UPEC) expresses F9/Fml pili tipped with protein FmlH that specifically bind to terminal galactoside and galactosaminoside units in glycoproteins in kidney and bladder cells and colonize host tissues. Traditional UTI treatment using excessive antibiotics has led to the rise of various UPEC antibiotic-resistant strains. An alternative therapeutic approach prevents the initial bacterial attachment on the host cells using competitive FmlH-binding inhibitors. In this study, we have used computer-aided drug design techniques to identify novel glycomimetics that are predicted to bind strongly to UPEC FmlH and inhibit binding to host glycoproteins. We have performed in-silico receptor-based and ligand-based scaffold hopping, and molecular docking to predict novel FmlH-binding glycomimetics with high chemical synthesizability. We have replaced the two major scaffolds of the most potent known FmlH-binding ligand to obtain novel compounds. Additionally, we have applied global machine-learning models to predict ADMET properties of the molecules. Compounds with calculated low ADMET risks were subjected to molecular dynamics simulations and detailed investigation of the FmlH–glycomimetic interactions was performed. We have prepared and supplied a library of 58 novel glycomimetics that can be subjected to further biological activity studies.

Cartilage microfracturation is a surgical technique specifically designed to address chondral defects, which are injuries to the cartilage that covers the ends of bones in joints. These defects can result from traumatic injuries, degenerative conditions such as osteoarthritis, or congenital abnormalities. The primary objective of microfracture surgery is to promote the regeneration of functional cartilage tissue, thereby restoring joint function, alleviating pain, and enhancing mobility. The procedure involves creating small, controlled perforations, or microfractures, in the subchondral bone plate beneath the damaged cartilage. This process, performed with precision to minimize damage to surrounding healthy tissue, penetrates the subchondral bone to reach the bone marrow, which is rich in mesenchymal stem cells (MSCs). MSCs are multipotent cells capable of differentiating into various cell types, including chondrocytes, which are essential for cartilage production. The microfractures provide an access pathway for MSCs, allowing them to migrate from the bone marrow to the defect site. Once at the site, these stem cells differentiate into chondrocytes and initiate the formation of new cartilage tissue. This newly formed tissue helps fill the defect, aiming to restore the smooth surface of the cartilage and improve the joint's structural integrity. Understanding the molecular processes involved in cartilage repair is crucial for optimizing rehabilitation strategies and improving clinical outcomes. These processes include the regulation of various signaling pathways that control stem cell migration, differentiation, and extracellular matrix (ECM) synthesis. Growth factors such as transforming growth factor-beta (TGF-β), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs) play pivotal roles in these pathways, guiding MSCs in their transformation into functional cartilage cells. Additionally, the role of the ECM, composed primarily of collagen type II and proteoglycans like aggrecan, is paramount in providing structural support and biochemical signals. The ECM supports the newly differentiated chondrocytes and helps maintain the cartilage's mechanical properties. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), are crucial in ECM remodeling, ensuring the balance between synthesis and degradation of the matrix to support tissue repair and integrity. Angiogenesis and vascularization are also critical aspects of the molecular repair process. The initial phase of cartilage repair often includes transient vascularization facilitated by vascular endothelial growth factor (VEGF), ensuring that the newly formed tissue receives adequate nutrients and oxygen. However, as the repair tissue matures, it transitions back to an avascular state characteristic of healthy articular cartilage, which is essential for maintaining its mechanical properties and longevity. Rehabilitation strategies following microfracture surgery are meticulously crafted to facilitate recovery and functional restoration. These strategies include early mobilization techniques, controlled mechanical loading, biological augmentation, nutritional support, and advanced therapeutic modalities. Early mobilization with gentle passive range-of-motion exercises promotes synovial fluid circulation within the joint, preventing adhesions and joint stiffness, and delivering essential nutrients and growth factors. Controlled mechanical loading through gradual weight-bearing activities helps condition the repaired tissue, stimulating chondrocyte proliferation and ECM production while ensuring proper integration and function. Biological augmentation, including platelet-rich plasma (PRP) and hyaluronic acid (HA), supports cartilage repair by enhancing cellular activities and ECM formation. PRP, rich in growth factors, promotes cell proliferation and matrix synthesis, while HA injections improve joint lubrication, reduce pain, and provide a scaffold for new tissue growth. Nutritional support, including amino acids, vitamins, minerals, glucosamine, chondroitin sulfate, and antioxidants, plays a vital role in collagen synthesis and overall cartilage maintenance, protecting chondrocytes from oxidative stress and modulating inflammation. Advanced therapeutic modalities such as low-intensity pulsed ultrasound (LIPUS), pulsed electromagnetic fields (PEMF), photobiomodulation therapy, and cryotherapy offer additional benefits by enhancing chondrocyte activity, reducing inflammation, and promoting ECM production. These modalities work through various molecular mechanisms, such as activating signaling pathways and modulating gene expression, to improve the quality and durability of the repaired cartilage. By comprehensively understanding the molecular and practical aspects of cartilage repair, clinicians can develop more effective treatment plans that optimize cartilage healing and improve patient outcomes. The integration of molecular insights with advanced rehabilitation techniques holds the promise of revolutionizing cartilage repair, offering hope for those suffering from debilitating joint conditions. This review aims to bridge the gap between molecular biology and clinical practice, providing a roadmap for optimizing cartilage repair strategies and ensuring long-term success for patients.

Cervical cancer remains a significant global health challenge, ranking as the fourth most common cancer among women. The primary causative agents, Human papillomavirus (HPV) strains 16 and 18, are well-known for their role in cervical carcinogenesis, primarily through the actions of the E6 and E7 oncoproteins. This study aimed to identify a natural compound capable of inhibiting both E6 and E7 oncoprotein activities, thereby offering a potential therapeutic approach using a single agent. This study also comprises an extensive in silico analysis with molecular docking studies by AutoDock Vina and Schrodinger Maestro to analyse the binding affinity, hydrogen bonds interactions of selected compounds against HPV 16 E6 &E7 proteins. GROMACS package and iMODS server was used to perform molecular dynamics simulations of protein-ligand complexes to elucidate stability of the ligands around the receptor at different time points. SwissADME was utilized for the prediction of pharmacokinetic properties while PROTOX-II helped in predicting toxicological data Capsaicin emerged as the most promising candidate, exhibiting binding energies of -7.3 kcal/mol and -5.6 kcal/mol against the HPV 16 E6 and E7 proteins, respectively. Notably, Capsaicin formed a single hydrogen bond with each oncoprotein, indicating a strong and specific interaction. The compound also demonstrated a favourable pharmacokinetic profile, with no violations of drug-likeness rules, and was classified as Toxicity Class 4, suggesting a moderate safety profile. These results, thus branding Capsaicin as a promising lead compound for further investigations in cervical cancer therapy that deserves documentation through well-equipped wet lab experiments followed by clinical studies.

Sect. Tuberculata in the genus Camellia, is named after the "tubercle-like projections on the surface of the capsule and ovary". Due to complex morphological variations in these taxon and insufficient field investigations, the interspecific relationships are unclear, the species definitions are vague, and the names are confusing. This is not conducive to the conservation and study of these species. Therefore, herein, we systematically explored the taxonomic status of five sect. Tuberculata species using morphological, pollen morphology, and molecular phylogenetic methods. The result showed that (1) morphological characteristics for the flower, fruit, and leaves of C. anlungensis and C. leyeensis were similar. Furthermore, the pollen characteristics and pollen wall ornamentation showed that it was no significant difference between the two species. (2) there were significant differences between C. acutiperulata and C. anlungensis in terms of leaf shape (elliptic vs. obovate), calyx characteristics (sepal apex pointed vs. sepal oblong), and fruit shape (subglobose folds with shallow verruculose vs. flat folds and verruculose protuberances with pronounced internal cleavage). (3) C. pyxidiacea and C. rubituberculata differed in flower color (white or few light vs. red), fruit verrucae (obviously deeply cleft vs. shallowly uncracked). (4) a phylogenetic tree based on the chloroplast genome showed that C. anlungensis and C. leyeensis form a single clade (BS = 100%, PP = 1.0) and were on a different branch with C. acutiperulata in clade II, (BS = 100%, PP = 1.0); C. pyxidiacea and C. rubituberculata were clustered on different branches of clade I (BS = 99%, PP = 1.00). Integrated above results, we consider that C. leyeensis should be treated as a homonym of C. anlungensis; C. acutiperulata, C. pyxidiacea, C. rubituberculata respectively as a separate species. Clarifying the taxonomic status of these five species not only advances our understanding of the significance and complexity of the systematic classification of the genus Camellia but also has important implications for diversity conservation and population genetics.

Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. Although the pathophysiology of DWs is multifaceted, evidence revealed that prolonged inflammation with infections, extracellular matrix (ECM) degradation and unnecessary NETosis impair DW healing. This theoretical problem commands the necessity of developing a novel strategy focused on targeting the 'specific' molecular modalities of DW. The primary culprits, matrix metalloproteinase (MMP)-9 and protein kinase C (PKC)-βII, are responsible for impaired angiogenesis, NETosis, and ECM degradation. Thus, there is reinvigorated interest in identifying selective inhibitors for the effective management of DW. The current study exemplified human β-defensin-2 (HBD-2), a biological macromolecule as a dual-inhibitor of MMP-9 and PKC-βII using protein-protein docking and molecular dynamics simulation studies. Residue-residue interactions and binding affinity were investigated using Z-dock. Chemical bonding behavioral changes, structural dynamics, and functional changes were determined using GROMACS by analyzing RMSD, ROG, RMSF, SASA, FEL, and PCA. Overall, the data analysis revealed that HBD-2 possesses strong binding affinity and stability against MMP-9 and PKC-βII, which can be an ideal therapeutic for the accelerated healing of DW. The study provides valuable insights into the molecular mechanisms underlying hBD-2's potential therapeutic effects, offering new avenues for the development of innovative treatment strategies. The clinical relevance of our findings lies in their potential to inform the development of new approaches for diabetic wound management, addressing a significant healthcare concern.

The landscape of clinical management for metastatic melanoma (MM) and other solid tumors has been modernized by the advent of immune checkpoint inhibitors (ICI), including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. While these agents demonstrate efficacy in suppressing tumor growth, they also lead to immune-related adverse events (irAEs), resulting in exacerbation of autoimmune diseases such as Rheumatoid arthritis (RA), Ulcerative colitis (UC), and Crohn’s disease (CD). The immune checkpoint inhibitors offer promising advancements in the treatment of melanoma and other cancers, but they also present significant challenges related to irAEs and autoimmune diseases. Ongoing research is crucial to better understand these challenges and develop strategies for mitigating adverse effects while maximizing therapeutic benefits. In this manuscript, we addressed this challenge using network-based approaches by constructing and analyzing molecular and signaling networks associated with tumor-immune cross-talk.. Our analysis revealed that IL6 is the key regulator responsible for irAEs during ICI therapies. Furthermore, we conducted an integrative network and molecular-level analysis, including virtual screening, of drug libraries, such as the Collection of Open Natural Products (COCONUT) and the Zinc15 FDA-approved library, to identify potential IL-6 inhibitors.. Subsequently, the compound amprenavir was identified as the best molecule that may disrupt essential interactions between IL6 and IL6R responsible for initiating signaling cascades underlying irAEs in ICI therapies.

Selection is a fundamental part of the plant breeding process, enabling the identification and development of varieties with desirable traits. Thanks to advances in genetics and biotechnology, the selection process has become more precise and efficient, resulting in faster breeding progress and better adaptation of crops to environmental challenges. Genetic parameters related to gene additivity and epistasis play a key role and can influence decisions on the suitability of breeding material. In this study, 188 rapeseed doubled haploid lines were assessed in field conditions for resistance to Leptosphaeria spp. Through next-generation sequencing, a total of 133,764 molecular markers (96,121 SilicoDArT and 37,643 SNP) were obtained. The similarity of the DH lines at the phenotypic and genetic levels was calculated. The results indicate that the similarity at the phenotypic level was markedly different than the similarity at the genetic level. Genetic parameters related to additive gene action effects and epistasis (double and triple) were calculated using two methods: based on phenotypic observations only and using molecular marker observations. All evaluated genetic parameters (additive, additive-additive and additive-additive-additive) were statistically significant for both estimation methods. The parameters associated with the interaction (double and triple) had opposite signs depending on the estimation method.

Coronaviruses (CoVs) have recently emerged as significant causes of respiratory disease outbreaks. The novel coronavirus pneumonia of 2019, known as COVID-19, are highly infectious and triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding virus-host interactions and molecular targets in host cell death signalling is crucial for treatment development. Small natural compounds like celastrol and curcumin, acting as proteasome inhibitors, can potentially modify NF-κB signalling for treating SARS-CoV-2 infections. Various natural constituents, including alkaloids, flavonoids, terpenoids, diarylheptanoids, and anthraquinones, inhibit viral infection, progression, and amplification of coronaviruses. Derived from medicinal herbs, these compounds possess anti-inflammatory and antiviral properties, impacting the viral life cycle, including entry, replication, assembly, and release of COVID-19 virions. This review focuses on the development of small molecules of non-covalent inhibitors targeting the Main Protease (Mpro, also called 3CLpro) enzyme of SARS-CoV-2. It highlights the design using molecular dynamics (MD) studies and computational methods for further improvements in Mpro inhibitor design. The in-silico approach, which is pivotal in this process, provides an accelerated virtual avenue for exploring and developing potential inhibitors, representing the latest advancements in drug design.

The field of computational protein engineering has been transformed by recent advancements in machine learning, artificial intelligence, and molecular modeling, enabling the design of proteins with unprecedented precision and functionality. Computational methods now play a crucial role in enhancing the stability, activity, and specificity of proteins for diverse applications in bio-technology and medicine. Techniques such as deep learning, reinforcement learning, and transfer learning have dramatically improved protein structure prediction, optimization of binding affin-ities, and enzyme design. These innovations have streamlined the process of protein engineering by allowing the rapid generation of targeted libraries, reducing experimental sampling, and en-abling the rational design of proteins with tailored properties. Furthermore, the integration of computational approaches with high-throughput experimental techniques has facilitated the development of multifunctional proteins and novel therapeutics. However, challenges remain in bridging the gap between computational predictions and experimental validation, and in ad-dressing ethical concerns related to AI-driven protein design. This review provides a compre-hensive overview of the current state and future directions of computational methods in protein engineering, emphasizing their transformative potential in creating next-generation biologics and advancing synthetic biology.

Papaya is a globally important crop, with production primarily based on hermaphrodite plants. Papaya has three sex types: male, female, and hermaphrodite, determined by flower morphology until the flowering stage. In this study, a recombinase polymerase amplification (RPA) assay was developed and optimized to identify the three sexes of papaya. Recombinant uvsX, uvsY, gp32, and Bsu DNA polymerase were used to study the effects of temperature, reaction time, and sensitivity conditions for RPA reaction efficiency. The optimal conditions were found to be 41°C and a 30-minute reaction time, allowing the detection of the target sex from specific DNA markers, even when using crude extract. The study shows that RPA could be used for sex determination in papaya, and the findings could contribute to developing a point-of-need strategy due to their sensitivity and specificity.

AI integration is becoming more important in today’s world and could potentially be very useful in the life sciences and biotechnology. This study evaluates the effectiveness of AI systems in teaching molecular cloning techniques to newcomers in molecular biology, focusing on a comparison between Gemini Advanced (powered by Gemini Ultra 1.0) and ChatGPT (GPT-4o). Molecular or DNA cloning is a lab technique for creating multiple copies of a specific DNA segment. It involves isolating the DNA fragment, inserting it into a vector, and introducing it into a host cell, typically bacteria, which then generates numerous copies of the DNA. This essential technique underpins genetic engineering, allowing for gene study, protein expression, and the creation of genetically modified organisms. The primary objective of this study was to assess whether individuals with limited laboratory experience could effectively acquire a specific molecular biology skill set solely through an AI system, rather than relying on the more traditional ‘learning by shadowing’ approach. Participants with limited lab experience completed these tasks using both Gemini and GPT-4o, and evaluated on quality of instructions, conciseness, scientific accuracy, and user satisfaction. Results indicated that both AI systems demonstrated strengths in delivering clear and comprehensive instructions, but in different ways. Gemini, although more interactive with images and diagrams lacked directness and had a harder time keeping past steps in its “memory”. On the other hand, GPT-4o was much more direct and concise in the steps listed and had more accurate results akin to what is performed in the lab. This study underscores the potential of AI-driven tools to simplify complex biotechnological procedures, making them accessible for learners at all levels.

Crops obtained by genome editing (GE) technologies represent a notable and disruptive shift from genetically modified or transgenic plants, outpacing public perception and regulatory frame-works. Multiple aspects of GE are contributing to the advancement of modern agriculture, in-fluencing the market structure by introducing specific changes within the existing genetic blue-print of an organism. Generally, the GE toolbox includes distinct technologies able to incorporate site-specific and pre-determined genomic modifications, exploiting well-established genetic modification strategies. For these reasons, GE-derived approaches are considered new plant breeding methods, known as new breeding techniques (NBTs). Particularly, CRISPR/Cas-based technologies represent a considerable improvement over prior techniques, being more precise, accurate and straightforward for targeted gene editing, in a reliable and reproducible way, with numerous applications. CRISPR/Cas system exploitation for non-editing purposes has also been widely documented, ranging from cell imaging to expression regulation and DNA assembly. Recently, CRISPR/Cas systems have been employed for target detection and could be used to ef-ficiently identify multiple organic chemicals. High-sensitivity and high-specificity detection are two main points of the CRISPR/Cas technology, without needing complex expertise or technical pipelines. This manuscript aims to provide an overview of the main advances of CRISPR/Cas-based systems into new frontiers of non-editing. The associated implications (e.g., molecular traceability) and their relative impacts are also presented and discussed.

The inhibition of kynurenine aminotransferase II (KATII) is a target for treating several diseases with an excess of kynurenic acid (KYNA). KATII inhibitors exist, but they have adverse side effects, given their irreversible inhibition mechanism. This study aimed to discover potent and safe inhibitors of KATII by using computational and in vitro methods. We identified herbacetin and (-)-Epicatechin as reversible KATII inhibitors from a small library of natural compounds, whose Glide docking scores (-8.66 kcal mol-1 and-8.16 kcal mol-1, respectively) and MM/GBSA binding energies (-50.30 kcal mol-1 and -51.35 kcal mol-1, respectively), which are higher scores than the standard inhibitor, PF-04859989 (-7.12 kcal mol-1 and -38.41 kcal mol-1, respectively). The ADMET analysis showed that herbacetin and (-)-Epicatechin have suitable pharmacokinetic parameters, are moderately bioavailable, and have a safe toxicity profile. Their KATII inhibitory activity is in the range of IC50 values of 5.98± 0.18 µM and 8.76 ± 0.76 µM, respectively. Furthermore, the MTT assay for cell toxicity showed that the two compounds do not alter HepG2 cell viability at their required concentration for KATII inhibition. These results show that herbacetin and(-)-Epicatechin are suitable for KATII inhibition and appropriate candidates for further development of KATII inhibitors.

Phasins are proteins, which are located on the surface of Polyhydroxybutyrate (P3HB) granules and that carry out activities that affect the polymer metabolism. This study aimed to evaluate the effect of inactivating phasins PhbP2 or PhbP3 on the growth rate, production and molecular mass of P3HB in cultures under low or high oxygen transfer rates (OTR). The results reveal that under high OTRₘₐₓ conditions (between 8.1 and 8.9 mmol L⁻¹ h⁻¹ depending on the strain evaluated), the absence of phasins PhbP2 and PhbP3 resulted in a strong negative effect on the growth rate. In contrast, the rates of specific oxygen consumption increased in the case of cultures with strains where phasins were absent. This behavior was not observed under conditions at a low oxygen transfer rate (3.9 ± 0.71 mol L⁻¹ h⁻¹); where both growth and oxygen consumption were the same for the different strains evaluated. It was observed, at high OTRₘₐₓ that the absence of phasin PhbP3 harms the P3HB synthesis, finding a decrease of 30 % in the polymer production at the end of cultivation; however, the molecular weight of the polymer remained constant during the course of cultivation. In summary, it can be concluded that both growth and polymer synthesis were affected when phasin PhbP3 was absent from the P3HB granule, especially at high OTRₘₐₓ.

Different polyurethanes (PUs) were synthesized with polycarbonate polyols of molecular weights 500, 1000 and 2000 Da. Their self-healing abilities at 20 °C were tested and their structural, thermal, and mechanical properties were analyzed. The PUs made with polycarbonates of molecular weights 500 (YC500) and 1000 Da (YC1000) exhibited self-healing at 20 °C and the self-healing time of YC1000 was the shortest. The high mobility of the short polymeric chains, the absence of crystallinity and the low degree of micro-phase separation favored self-healing at 20 °C in YC500. However, the presence of tack and the existence of allophanate species and urethane-carbonate and urea-carbonate hydrogen bonds disfavored self-healing. Consequently, the self-healing time at 20 °C of YC500 was longer than expected. On the other hand, YC1000 exhibited an “equilibrium” between the urethane-carbonate and urea-carbonate hydrogen bonds and carbonate-carbonate interactions among the soft segments, so a particular structural order was produced which was associated to its fastest self-healing at 20 °C. The PU made with the polycarbonate of molecular weight 2000 Da did not exhibit self-healing at 20 °C because its significant micro-phase separation and the presence of semi-crystalline soft domains.

The synthesis of enantiomeric forms of D-amino acids can be achieved by a two-step "hydantoinase process" based on the sequential catalysis of substrates by specific enzymes, D-carbamoylase and D-hydantoinase. In addition to our previously studied D-hydantoinase, we describe here the structural features of D-carbamoylase from Pseudomonas, the encoded gene of which was chemically synthesized and cloned into Escherichia coli. A significant fraction of the overexpressed recombinant protein forms insoluble inclusion bodies, which are partially converted to a soluble state upon treatment with N-lauroylsarcosine or upon incubation of the cells at low temperatures. Analysis of the substrate specificity of the purified His-tag protein showed that D-carbamoylase exhibits the highest activity toward N-carbamoyl-D-alanine and N-carbamoyl-D-tryptophan. Molecular docking analysis revealed the location of the substrate binding site in the three-dimensional structure of D-carbamoylase. Molecular dynamics simulations showed that the binding pocket of the enzyme in complex with N-carbamoyl-D-tryptophan is stabilized within 100 ns. The free energy of binding indicated a possible role of residues Arg176 and Asn173 in the formation of hydrogen bonds between the enzyme and N-carbamoyl-D-tryptophan. The properties of the studied D-carbamoylase and D-hydantoinase support further development of a combined biotechnological process for the production of new drugs and peptide hormones.

Severe acute respiratory infection (SARI) is mainly caused by viral pathogens, with a high prevalence in high-risk populations such as infants and older adults. Co-infections by different viruses are frequent and, in some cases, associated with severe disease outcomes. Purpose: The main purpose of this study was to identify respiratory viruses circulating in Barranquilla during the COVID-19 pandemic peaks and estimate the prevalence of viral co-infections in samples from individuals with different degrees of respiratory infection. Methods: Between August and October 2021, 101 samples were collected from individuals with influenza-like illness (ILI) by the District Health Laboratory of Barranquilla and four local health care institutions and analyzed at Universidad Simón Bolívar. Eighteen respiratory viruses, including SARS-CoV-2, were analyzed via qRT-PCR using nasal swabs or nasopharyngeal aspirate samples. Results: Of the 101 study individuals, 56 were male and 45 were female (55.5% and 44.5%, respectively); 25.7% of individuals were infected with at least one of the evaluated viruses. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) were the two most frequently detected viruses (30.7% and 15.4% of total positives, respectively). Co-infections with two or more respiratory viruses accounted for 42% of the total positive cases. Conclusion: Our findings indicate the presence of different respiratory viruses in swab or nasopharyngeal aspirate samples from individuals with ILI, including coinfection. These results reveal the circulation of several respiratory viruses in the city of Barranquilla, confirming their importance as potential causes of SARI in Colombia and the need for their active surveillance.

This study presents a detailed comparative analysis of Molecular Docking data, focusing on the binding interactions of conventional ligands and natural compounds, Apigenin and Luteolin, with TP-53, pRb, and APOBEC. Utilizing advanced bioinformatics techniques, coupled with Ar-tificial Intelligence software and High-Performance Computing (HPC), we measured and con-trasted the binding energies of these interactions. Additionally, we investigated protein-protein interactions between HPV-16 oncoprotein E6 and tumor suppressors TP-53 and pRb. Our findings demonstrate that the natural compounds Apigenin and Luteolin exhibit significantly higher binding affinities to TP-53, pRb, and APOBEC compared to conventional pharmacological ligands. The binding energies for Apigenin and Luteolin were approximately -6.9 kcal/mol and -6.6 kcal/mol, respectively, indicating their strong potential as therapeutic agents in inhibiting the oncogenic functions of HPV-16. In contrast, conventional ligands showed lower binding affinities, with energies around -4.5 to -5.5 kcal/mol. The study further revealed that the protein-protein interactions between E6 and TP-53, and E6 and pRb, exhibited considerably higher binding en-ergies, approximately -976.7 kcal/mol, due to the multiple interaction sites and the complex nature of protein interfaces. A conversion formula was developed to translate these high-energy inter-actions to a comparable scale for non-protein-protein interactions, highlighting the superior binding potential of natural compounds, which, through the same conversion formula, was shown to be higher than that of interaction between E6 with TP-53 and E6 with pRb. These results underscore the therapeutic promise of Apigenin and Luteolin in preventing HPV-16-related on-cogenesis. By demonstrating their higher binding affinities to crucial tumor suppressors, this study supports the development of natural compound-based therapies. The findings also em-phasize the necessity for further experimental validation to explore these compounds' efficacy in clinical settings. This comprehensive analysis provides a robust framework for understanding the comparative binding interactions and lays the groundwork for innovative therapeutic strategies against HPV-16.

The advancement of computational drug discovery and design necessitates continuous innovation to enhance the accuracy and scope of predictive models for early-stage drug research and development. This article introduces a novel workflow for in silico generation of structural and intermolecular binding affinity data with reasonable accuracy, combining two computational tools: Modeller and Prodigy. By leveraging synthetic structural and biophysical data, this approach addresses the limitations of existing experimental datasets, generating extensive, high-quantity binding affinity data with reasonable accuracy for biomolecular binding pairs, which broadens the horizon of computational biomolecule design and discovery by enabling extensive exploration of the sequence space of biomolecular binding pairs, and narrows the gap between experimental binding affinity data and its unexplored territories. Overall, this article presents a methodological advance to enhance the accuracy and scope of computational biomolecule discovery and design, paves the way for the development of preclinical candidates with improved efficacy and specificity, and holds transformative potential for further advancements in artificial intelligence-enabled biomolecule discovery and design in the future.

This article discusses advances in molecular technologies for detecting foodborne pathogens, specifically Listeria monocytogenes and Salmonella. Although traditional detection methods are reliable, they are time- and labor-intensive. On the other hand, molecular methods include polymerase chain reaction (PCR), quantitative real-time PCR (qPCR), and next-generation sequencing (NGS), which enable rapid, specific, and sensitive detection of pathogens. The introduction of such procedures has significantly improved food safety testing and monitoring. Although challenges such as accessibility and cost remain, future developments in molecular diagnostics will lead to greater implementation in improving pathogen management throughout the food supply chain.

A synopsis of current knowledge of the diversity of the New Zealand landhopper fauna is provided. A combination of morphological and molecular analysis was employed on material from across New Zealand. Thirteen new endemic genera soon to be formally described have been discovered, including four belonging to the widespread families Talitridae and Arcitalitridae. These are families that had not been previously reported from New Zealand. We document the existence of at least 48 new provisional native species. This number far exceeds the 28 species currently described. Some described species are now shown to be species complexes and a few of these are very diverse with numerous cryptic species. Six changes to the existing taxonomy are proposed. Dallwitzia simularis (Hurley, 1957) is transferred from Makawidae Myers and Lowry, 2020 to Talitridae Rafinesque, 1815; Kellyduncania hauturu (Duncan, 1994) is reinstated as a member of Dana Lowry, 2011 and Kellyduncania (Lowry and Myers, 2019) is relegated to a synonym of Dana Lowry, 2011; Kanikania Duncan, 1994 is transferred from Makawidae Myers and Lowry, 2020 to Arcitalitridae Myers and Lowry, 2020; Parorchestia longicornis is transferred to Kanikania Duncan, 1994; Waematau kaitaia (Duncan, 1994) is transferred to Kohuroa Lowry, Myers and Nakano, 2019; and Waematau unuwhao (Duncan, 1994) is transferred to Omaiorchestia Lowry and Myers, 2019. This reduces the number of described genera from 17 to 16.

The present study aimed to undertake a detailed investigation of pathological epidemiology and molecular confirmation of Ehrlichia canis among pet dogs in smart city Bhubaneswar, Odisha, a state in eastern India. A total of 178 dogs were screened for Ehrlichiosis on the basis of history, clinical signs, blood, and buffy coat smear examination, resulting in only 56 dogs (31.46%) screening positive. The epidemiological study recorded an increase in incidences among dogs less than one year of age (41%), males (68%), German Shepherds (25%), dogs more than 20 kg body weight (75%), summer months (55%) and dogs housed on pukka houses with exposure to the outside (59%). The majority of the infected dogs had a history of tick infestation (79%) at some point in their life. Clinical signs showed non-typical manifestations like fever, lethargy, diarrhoea, epistaxis, hind limb edema, and corneal opacity. Haematological studies revealed anaemia and thrombocytopenia along with neutrophilia with relative lymphopenia and monocytosis. A decreasing trend was observed in the levels of total protein and albumin with an increase in the levels of globulin, AST, ALT, BUN, and creatinine. The ultrasonography studies revealed hepatosplenomegaly along with hyper-echogenicity in various organs. Pro-teinuria and haematuria were consistent, along with the presence of bile salts in the urine of affected dogs. Molecular confirmation from n-type PCR data using Ehrlichia-specific primers targeting p28 gene (843 bp) was done, and the identified gene sequences submitted to NCBI databases have accession numbers OQ383671-OQ383674 and OP886674-OP886677. Ticks collected from dogs were identified morphologically through microscopy and scanning electron microscopy as Rhipicephalus sanguineus.

This review focuses on the pivotal role of radiotracers in breast cancer imaging, emphasizing their importance in accurate detection, staging, and treatment monitoring. Radiotracers, labeled with radioactive isotopes, are integral to various nuclear imaging techniques, including positron emission tomography (PET) and positron emission mammography (PEM). The most widely used radiotracer in breast cancer imaging is 18F-fluorodeoxyglucose (18F-FDG), which highlights areas of increased glucose metabolism, a hallmark of many cancer cells. This allows for the identification of primary tumors, metastatic sites, and assessment of tumor response to therapy. In addition to 18F-FDG, this review will explore newer radiotracers targeting specific receptors, such as estrogen receptors or HER2, which offer more personalized imaging options. These tracers provide valuable insights into the molecular characteristics of tumors, aiding in tailored treatment strategies. By integrating radiotracers into breast cancer management, clinicians can enhance early disease detection, monitor therapeutic efficacy, and guide interventions, ultimately improving patient outcomes. Ongoing research aimed at developing more specific and sensitive tracers will also be highlighted, underscoring their potential to advance precision medicine in breast cancer care.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder marked by progressive motor and non-motor symptoms. Traditional treatments primarily manage symptoms rather than address the disease's root causes, highlighting the need for novel therapeutic approaches. Natural phytochemicals, particularly phenolic compounds, have shown potential due to their neuroprotective effects. Antiaris africana is commonly used in traditional African medicines to treat several illnesses including neurodegenerative disorders. However, its neuroprotective mechanism remains elusive. This study aimed to employ network pharmacology-based prediction to identify key targets and pathways through which A. africana exerts its effects on PD. Targets associated with Parkinsonism were identified and analyzed for interaction with compounds from A. africana. Protein-protein interaction (PPI) networks were constructed, and key hub genes were identified using Cytoscape. Functional enrichment analysis highlighted significant pathways involved in PD. Molecular docking was performed to evaluate the binding affinities of the compounds to PD-related targets. Our results reveal that compounds such as caffeic acid, chlorogenic acid, catechin, ellagic acid, epigallocatechin, gallic acid, isoquercitrin, kaempferol, quercetin, quercitrin, and rutin interact with key proteins implicated in PD, including APP, EGFR, CASP3, ESR1, AKT1, and MAPK8. Notably, rutin exhibited strong binding affinity for EGFR, and chlorogenic acid showed potential in modulating the APP pathway. These findings suggest that phenolic compounds in A. africana may exert neuroprotective effects through multiple molecular mechanisms, offering potential therapeutic strategies for PD. This study underscores the importance of integrating molecular docking and network pharmacology to elucidate the therapeutic potential of natural compounds in complex diseases like Parkinson's disease

The formula Chong-Lou-Yao-Fang (CLYF) is an herbal medicinal formulation developed by the indigenous Naxi people for treating liver cancer. This study is to reveal the biological activity, potential targets, and molecular mechanisms of CLYF for cancer treatment through network pharmacology, molecular docking and in vitro experiments. 35 key compounds were screened from 176 active ingredients in CLYF, which played a vital role in the treatment of cancer, 20 core targets were filtered through protein–protein interaction (PPI) network analysis. The enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that PI3K-Akt, MAPK, hepatitis B, hepatitis C might be effective in liver cancer treatment. Mo-lecular docking revealed stable binding between EGFR, TP53, and AKT1 with active ingredients. Experiments with cell cultures confirmed that CLYF-A suppressed the proliferation of HepG2 cells, which is consistent with the network pharmacology approach undertaken and the predictions of molecular docking. CLYF-A also induced significant apoptosis and cell cycle arrest in HepG2 cells, which was associated with the loss of mitochondrial membrane potential. This study explored the biological activity, potential targets, and molecular mechanisms of CLYF for cancer treatment. Our results may provide a scientific basis for the clinical use of CLYF for cancer treatment and have important implications for developing pharmaceutical preparations, which also need more phar-macological experiments.

Accurate assessment of shale gas reserves hinges on a detailed characterization of gas and water distribution within shale reservoirs. Despite its importance, the nanoscale behavior of water and methane in deep shale formations, especially under elevated temperatures and pressures, remains poorly understood. This study proposes a novel molecular modeling approach to represent the complex nanocomposite porous media found in deep shale matrices. Leveraging quantitative data from experimental analyses of shale pore composition, we developed a molecular model that accurately reflects the intricate pore-slit structure within a composite of kerogen and illite, common constituents of shale. Employing a hybrid grand canonical Monte Carlo and molecular dynamics simulation technique, we investigated the micro-scale distribution and preferential adsorption sites of water and methane within the shale matrix. Our research further elucidates the impact of water on the pore structure of shale and delineates the co-occurrence patterns of water and methane. The simulations reveal that water and methane share similar adsorption preferences on kerogen surfaces, while methane does not exhibit specific adsorption preferences on water-bearing illite. We also find that the presence of water significantly alters the illite pore space, leading to a reduction in larger pore volumes and a concomitant increase in smaller pores. The decrease in methane content with increasing water content is more pronounced in the shrinkage cracks compared to the kerogen matrix pores and is particularly notable in the macropores of illite. The findings underscore the differential sensitivity of methane content to water levels across various shale pore types. These insights contribute to a deeper theoretical understanding of gas and water distribution mechanisms in deep shale reservoirs, offering valuable support for the evaluation of deep shale gas resource potential.

Ti-Al based alloys, particularly TiAl and Ti3Al two-phase alloys, have garnered significant attention as potential replacements for various high-temperature structural materials due to their exceptional properties, including low density, oxidation resistance, and high strength at elevated temperatures. Despite these advantages, experimental studies on the microstructure evolution of Ti-Al based alloys under complex conditions remain challenging to observe and characterize. This review article examines the current research on molecular dynamics (MD) simulations of Ti-Al based alloys, focusing on two-phase Ti-Al alloys, Ti-Al amorphous alloys, Ti-Al composite materials, and the welding and multi-layer/film applications of Ti-Al alloys. The review highlights the unique capabilities of MD simulations in predicting the behavior of Ti-Al based alloys and addresses existing scientific challenges. Furthermore, the article discusses future research directions and development prospects in this field.

The elderly population is particularly susceptible to myocardial damage caused by heat stress (HS). With the continuous increase in global temperatures, this poses an undeniable challenge to human health. This study aimed to investigate the therapeutic effect of Shikimic Acid (SA) in treating HS-induced myocardial damage through network pharmacology, molecular docking, molecular dynamics (MD) simulations, and in vitro experiments. Network pharmacology analysis revealed that SA alleviates the inflammatory response in the heart muscle associated with HS by targeting 60 disease-related targets, such as TP53, TNF, and IL-6. The tumor proteoglycan, the PI3K-Akt signaling pathway, and hepatitis B were identified as the primary therapeutic pathways. Molecular docking and MD simulation results confirmed that SA can stably bind to both TNF (-6.642 kcal/mol) and IL-6 (-7.261 kcal/mol), and the complexes of Shikimic Acid-IL-6 and Shikimic Acid-TNF did not undergo significant changes within 100 ns. In addition, the in vitro experiment showed that 250 μM SA significantly increased the survival rate of HL-1 cells exposed to 43°C for 2 h by 71.1% and promoted the proliferation of HL-1 cells by 30.7%. Overall, these findings provide substantial evidence for the therapeutic potential of SA in HS-induced myocardial damage.

This study employs a comprehensive computational approach to identify and evaluate potential inhibitors of gamma D crystallin (CRYGD), a key protein implicated in cataract formation. A library of compounds, including natural products and FDA-approved drugs, was screened using molecular docking simulations and binding energy calculations. The top-scoring compounds were further assessed for drug-likeness properties and potential toxicity. Molecular dynamics simulations were conducted on the most promising candidates to investigate their interactions with CRYGD at the atomic level. The study identified CNP0185903, CID 3741, and CNP0151361 as the most promising compounds, with CNP0151361 demonstrating the most favorable combination of binding affinity, structural stabilization, and conformational modulation of CRYGD. These findings provide a foundation for the development of novel pharmacological interventions for cataract treatment, potentially offering alternatives or complements to current surgical approaches.

This study provides a comprehensive analysis of the conformational dynamics of pseudo-endocannabinoid receptors (p-CBRs) CB₁ and CB₂ in response to ligand binding. The ligands studied include N-arachidonoyl dopamine (NADA), Cannabidiol (CBD), known agonists (FUB-MDMB and E3R), and inverse agonists (Taranabant and AM630). Using homology models based on crystal structures (PDB ID: 5U09 for CB₁ and 5ZTY for CB₂), molecular docking, and molecular dynamics (MD) simulations, the research validates the structural integrity and dynamic behaviours of these pseudo-receptors. Induced-fit docking revealed NADA as having the highest binding affinity for both receptors, with docking scores of −13.92 kcal/mol for CB₁ and −13.32 kcal/mol for CB₂, facilitated by key hydrogen bond interactions. MD simulations over 250 ns at ~298 K showed successful equilibration, indicating the most stable interaction for NADA, thereby further validating the models. CB₁ and CB₂ exhibited distinct conformational responses to ligands, with Cα RMSD and Cα RMSF analyses suggesting a more rigid binding pocket for CB₁ and a flexible binding pocket for CB₂. These findings highlight the significance of receptor behaviour and dynamics in the development of cannabinoid-based therapeutics, supporting the potential of CBD and NADA as modulators for CB₁ and CB₂, respectively.

The Anterior Cruciate Ligament (ACL) is a crucial stabilizing ligament in the knee, essential for maintaining knee joint stability and proper biomechanical function. ACL rupture is one of the most common injuries, especially prevalent among athletes participating in high-demand sports that involve pivoting, cutting, and jumping. Such injuries not only lead to immediate functional impairment but also predispose individuals to long-term consequences, including osteoarthritis if left untreated. ACL reconstruction using a graft, whether autograft or allograft, has become the gold standard treatment method aimed at restoring knee stability and function. However, the postoperative healing process of the graft within the bone tunnel presents significant challenges due to its complexity. This healing involves a coordinated sequence of molecular and cellular events, including inflammation, proliferation, and remodeling phases. These phases are governed by a myriad of molecular signals, growth factors, and cellular interactions that ultimately determine the success of the graft integration and the restoration of ligamentous function. The review article "Molecular Biology of ACL Graft Healing: Early Mechanical Loading Perspective" delves deeply into these intricate biological processes. It provides a comprehensive analysis of the underlying molecular mechanisms that facilitate graft healing. Furthermore, it emphasizes the critical role of early mechanical loading in this context. Mechanical loading, when applied appropriately, has been shown to positively influence graft healing by enhancing cellular responses, collagen fiber alignment, and overall biomechanical properties of the graft. By exploring the impact of early mechanical loading, the review sheds light on how mechanical stimuli can be optimized to improve clinical outcomes. This understanding is vital for developing effective rehabilitation protocols that promote faster and more robust graft healing. The article offers valuable insights for clinicians and researchers, aiming to bridge the gap between molecular biology and practical rehabilitation strategies in ACL reconstruction. Overall, this review underscores the importance of an integrated approach that considers both the biological and mechanical aspects of ACL graft healing. Such an approach holds promise for advancing patient care and improving the success rates of ACL reconstruction surgeries.

Recent advancements in molecular diagnostics have highlighted the potential of circulating cell-free DNA (ccfDNA) as a biomarker in various diseases. This study aims to explore the role of ccfDNA in the early diagnosis, prognosis, and therapeutic monitoring of diseases, with a focus on oncology. We conducted a comprehensive review and analysis of current literature, combined with experimental approaches involving advanced genomic sequencing and bioinformatics techniques. Our research systematically characterizes the molecular composition of ccfDNA, including its origins, size distribution, and methylation patterns, across different disease states. Furthermore, we investigate the dynamics of ccfDNA release and clearance in the bloodstream, elucidating mechanisms that could influence its diagnostic accuracy. In the context of cancer, we analyze the correlation between tumor-derived ccfDNA and disease progression, response to therapy, and overall survival. Our findings indicate that ccfDNA holds promise as a non-invasive biomarker for early disease detection, real-time monitoring of treatment efficacy, and potentially, predicting relapse. This study contributes to the growing field of liquid biopsies and opens new avenues for personalized medicine, emphasizing the need for standardized protocols in ccfDNA analysis to maximize its clinical utility. The implications of our findings extend beyond oncology, suggesting potential applications of ccfDNA in other pathological conditions.

Consumer perception of beef is heavily influenced by overall meat quality, a critical factor in the cattle industry. Genomics has the potential to improve important beef quality traits and identify genetic markers and causal variants associated with these traits by genomic selection (GS), and genome-wide association studies (GWAS) approaches. Transcriptomics, proteomics, and metabolomics provide insights into underlying genetic mechanisms by identifying differentially expressed genes, proteins, and metabolic pathways linked to quality traits, complementing GWAS data. Leveraging these functional genomics techniques can optimize beef cattle breeding for enhanced quality traits to meet high-quality beef demand. This paper provides a comprehensive overview of the current state applications of the omics technologies in uncovering functional variants underlying beef quality complexities. By highlighting the latest findings from GWAS, GS, transcriptomics, proteomics, and metabolomics studies, this work seeks to serve as a valuable resource fostering a deeper understanding of the complex relationships between genetics, gene expression, protein dynamics, and metabolic pathways in shaping beef quality.

This study investigates the use of artificial intelligence (AI) and ethnobotanical knowledge to identify natural compounds with potent antiviral activity against HPV-16. Through molecular docking simulations, we evaluated the binding affinities of various essential oil components, in-cluding Apigenin, against the key antigenic determinants of HPV-16 (E6, E7 oncoproteins, and L1 major capsid protein). Apigenin exhibited strong binding affinities, particularly to E6 Oncopro-tein. To further enhance these findings, we employed an AI-driven reverse engineering approach to predict a natural compound with superior efficacy. The AI identified Luteolin, a flavonoid with additional hydroxyl groups, as a promising candidate. Comparative docking studies demon-strated that Luteolin possesses significantly stronger binding affinities to all three HPV-16 targets, surpassing the efficacy of Apigenin. This work highlights the potential of AI in accelerating the discovery and optimization of natural antiviral agents, providing a powerful tool for pharmaco-logical and ethnopharmacological screenings. Our findings suggest that AI-guided identification of natural compounds can lead to the development of more effective antiviral therapies, warranting further experimental validation and potential synthesis in laboratory settings.

Xyleborus beetles, a diverse group of ambrosia beetles, present significant challenges to forestry and agriculture due to their damaging burrowing behavior and symbiotic relationships with fungi. This review synthesizes current knowledge on the biology, ecology, and management of Xyleborus. We explore the beetles' life cycle, reproductive strategies, habitat preferences, and feeding habits, emphasizing their ecological and economic impacts. Control and management strategies, including preventive measures, chemical and biological control, and integrated pest management (IPM), are critically evaluated. Recent advances in molecular genetics and behavioral studies offer insights into genetic diversity, population structure, and host selection mechanisms. Despite progress, managing Xyleborus effectively remains challenging. This review identifies future research needs and highlights innovative control methods, such as biopesticides and pheromone-based trapping systems.

The anterior cruciate ligament (ACL) is a critical structure within the knee joint, primarily responsible for maintaining stability and enabling the knee to perform a wide range of movements essential for both everyday activities and athletic performance. It functions as a key stabilizer by preventing excessive forward movement of the tibia relative to the femur and by controlling rotational forces that occur during activities such as pivoting, cutting, and jumping. The biomechanical integrity provided by the ACL is crucial, especially during dynamic activities that place significant strain on the knee joint, making it indispensable for athletes and active individuals. However, due to its pivotal role and the considerable mechanical demands placed upon it, the ACL is particularly vulnerable to injury. ACL injuries are prevalent, especially among athletes involved in high-risk sports such as soccer, basketball, football, and skiing, where rapid changes in direction, sudden stops, and direct impacts are common. The incidence of ACL injuries is a significant concern in sports medicine, not only because of the immediate impact on an athlete's career but also due to the long-term health implications associated with such injuries. These injuries often result in complex, multifaceted complications, including persistent joint instability that can compromise the structural and functional integrity of the knee, leading to recurrent injuries and reduced performance levels. One of the more insidious consequences of ACL injuries is the loss of proprioception, the body's ability to sense the position, movement, and action of the joints. Proprioception is vital for coordinated movement and balance, and its impairment can lead to a diminished capacity to control knee movements, further increasing the risk of re-injury. Additionally, the long-term sequelae of ACL injuries often include the development of post-traumatic osteoarthritis, a degenerative condition characterized by the gradual breakdown of joint cartilage and underlying bone. This condition not only causes chronic pain and stiffness but can also significantly impair an individual's quality of life, limiting their ability to engage in physical activities and, in severe cases, leading to disability. Despite the remarkable progress made in the fields of orthopedic surgery and sports rehabilitation, the recovery process following an ACL injury remains challenging. Surgical techniques, such as ACL reconstruction, have evolved to offer more reliable outcomes, and rehabilitation protocols have been refined to promote quicker and more effective recovery. However, the reality is that many patients do not achieve the level of recovery needed to return to their pre-injury level of activity or to maintain long-term knee health. This suboptimal recovery is often attributed to the complex interplay of neurophysiological and molecular factors that are not yet fully understood. Neurophysiologically, the recovery from an ACL injury involves not only the physical repair of the ligament but also the re-establishment of neuromuscular control and the adaptation of the central nervous system (CNS) to the altered mechanics of the knee. The CNS plays a crucial role in modulating the body's response to injury, influencing the way muscles activate and coordinate to protect the injured joint. However, disruptions in neuromuscular control post-injury can lead to compensatory movement patterns that may predispose individuals to further injury or hinder their recovery. Understanding these neurophysiological changes is essential for developing rehabilitation strategies that address not just the mechanical aspects of recovery but also the re-training of the neuromuscular system. On the molecular level, the healing process of the ACL involves a cascade of cellular and biochemical events that are critical for tissue repair and regeneration. These processes include the inflammatory response, cell proliferation, and the remodeling of the extracellular matrix, all of which are regulated by various molecular signals and pathways. Advances in molecular biology have begun to unravel the complexities of these processes, offering insights into how they can be manipulated to enhance healing and reduce the risk of complications such as fibrosis or improper tissue regeneration. By integrating molecular biology with clinical practice, there is potential to develop targeted therapies that can optimize the healing environment, improve surgical outcomes, and accelerate the recovery process. This review aims to provide a comprehensive examination of the neurophysiological aspects of ACL injury and the rehabilitation process, while also exploring the potential contributions of molecular biology to improving treatment outcomes. By delving into the intricate mechanisms that underlie ACL injury and recovery, the review seeks to highlight the challenges that remain in the field and to propose new directions for research that could lead to more effective and individualized treatment approaches. The ultimate goal is to enhance our understanding of ACL injuries and to develop strategies that not only restore knee function but also preserve long-term joint health, allowing individuals to return to their desired level of activity with confidence.

Cyclocarya paliurus tea, also known as "sweet tea", a health substitute tea with Cyclocarya paliurus leaves as raw material, is famous for its unique nutritional benefits and flavor. However, due to the unique "bittersweet" of Cyclocarya paliurus tea, it is still unable to fully satisfy consumers' high-quality taste experience and oral pleasure. The taste and sensory quality of Cyclocarya paliurus tea are mainly determined by secondary metabolites. Therefore, this study aimed to explore the metabolites in Cyclocarya paliurus leaves during their growth process, particularly the composition and variation of sweet and bitter taste compounds, by combining multi-platform metabolomics analysis with an electronic tongue system and molecular docking simulation technology. The results indicated that there were significant differences in the contents of total phenols, flavonoids, polysaccharides and saponins of C. paliurus leaves in different growing months, among which the bioactive components in leaves harvested in July were the highest, and the best balance between sweetness and bitterness was achieved. A total of 575 secondary metabolites were identified as potential active metabolites related to sweet/bitter taste using nontargeted metabolomics based on UHPLC-MS/MS analysis. Molecular docking technology was utilized to study the interactions between candidate metabolites and the sweet receptor T1R2/T1R3 and the bitter receptor T2R4/T2R14. Six key compounds with high sweetness and low bitterness were successfully identified by using computational simulation analysis, including cis-Anethole, Gluconic acid, beta-D-Sedoheptulose, Asparagine, Proline, and Citrulline, which may serve as candidates for taste modification in Cyclocarya paliurus leaves. These findings provide a new perspective for understanding the sweet and bitter taste characteristics metabolites that contribute to the distinctive sensory quality of Cyclocarya paliurus leaves.

The genus Chaetogaster belongs to the subfamily Naidinae (Naididae), includes mostly species of small size and is diverse and abundant in surface coarse sediments in streams. The aim of the present study is to initiate an inventory of lineages of Chaetogaster in Switzerland. We used 135 specimens collected at six sites in four streams of four cantons. We sequenced the cytochrome c oxidase (COI) gene from all specimens and ITS2 and rDNA 28S from all or several specimens of each lineage delimited using COI data and preserved a voucher of almost all sequenced specimens. We could delimit one lineage (=species) for Chaetogaster diaphanus (Gruithuisen, 1828), three within Chaetogaster diastrophus (Gruithuisen, 1828), one for Chaetogaster langi Brestcher, 1896, one for Chaetogaster setosus Svetlov, 1925 and three unidentified Chaetogaster spp. Two lineages of Chaetogaster spp. could correspond to a new morphological group, but this should be confirmed on more specimens. We described the three C. diastrophus lineages and two Chaetogaster spp. as new species for science. The prospects of the present work are to complete the data of the molecular diversity of this genus in Switzerland and to describe on a molecular/morphological basis the new Chaetogaster species that we will probably find.

Textile wastewater containing dyes pose significant environmental hazards. Advanced oxidative processes, especially the heterogeneous photo-Fenton process, are effective in degrading a wide range of contaminants due to high conversion rates and ease of catalyst recovery. This study evaluates the photocatalytic degradation of azo dyes Acid Red 18 (AR18), Acid Red 66 (AR66) and Orange 2 (OR2) using magnetite as a catalyst. The magnetic catalyst was synthesized via a hydrothermal process at 150°C. Experiments were conducted at room temperature, investigating the effect of catalyst dosage, pH, and initial concentrations of H2O2 and AR18 dye. Kinetic and thermodynamic studies were performed at 25, 40 and 60°C for the three azo dyes (AR18, AR66 and OR2) and the effect of the dye structures on the photocatalytic efficiency was investigated. At 25 °C for 0.33 mmol.L-1 of dyes at pH 3.0, using 1.4 g.L-1 of catalyst and 60 mg.L-1 of H2O2 under a UV radiation of 16.7 mW.cm-2 the catalyst showed a 62,3% degradation for AR18, 79.6% for AR66, and 83.8% for OR2 in 180 minutes of reaction. The oxidation of azo dyes under these conditions is spontaneous and endothermic. The pseudo-first order kinetic constants indicated a strong temperature dependence with an order of reactivity of the type: OR2 &gt; AR66 &gt; AR18, which is associated to the characteristics of molecular complexity (size, steric hindrance, aromatic conjugation), electrostatic repulsion and the nature of the acid-base interactions on the catalytic surface.

Detecting IgE sensitizations in the serum of allergic dogs is commonly done using allergen extracts, but these are difficult to standardize. This article details the development and validation of the Pet Allergy Xplorer (PAX; Nextmune, Stockholm, Sweden), the first multiplex macroarray for the detection of IgE sensitization in dogs using allergen extracts and molecular components; the PAX is derived from the Allergy Xplorer (ALEX2; MacroArray Diagnostics, Vienna, Austria). The selection of allergens, cartridge processing, strategy for identifying and blocking IgE directed against cross-reactive carbohydrate determinants (CCD), and the method used for determining the positivity threshold are described. The validation of the PAX included evaluations of the specificity of its anti-IgE monoclonal antibody, specificity of IgE binding to target allergens, assay precision, and internal consistency. Additionally, the influence of possible confounding factors, such as sample type, the influence of hemolysis, lipemia, bilirubinemia, and elevated CCD-IgE, was tested. Finally, the sensitization rates of 23,858 European dogs to 145 environmental and Hymenoptera venom allergens were summarized. The PAX is accurate and reproducible and has a unique CCD-detection and blocking strategy; its molecular allergens offer a unique window on allergen cross-reactivity.

Knee joint injuries, including those affecting the anterior cruciate ligament (ACL), meniscus, and cartilage, present significant challenges in sports medicine and orthopedics. Understanding the cellular and molecular mechanisms underlying these injuries is essential for developing effective therapeutic strategies. This systematic review explores the cell biology of knee joint injuries, focusing on the effects of early mechanical loading. We examine the types of knee injuries, cellular responses to mechanical loading, signaling pathways involved, and implications for treatment and rehabilitation. This comprehensive synthesis aims to provide insights into optimizing rehabilitation protocols and developing novel therapeutic approaches.

Mesoscopic modeling of complex system involve thermodynamic nonequilibrium of discrete scaling. Furthers from quantum correlation on a chip retrieved quantum nonlinear optics with single photons enabled by strongly interacting atoms. Accompanied by mesofractals as development of meso & micro size fractal structures is required to mimic various biological systems for various functions. Showed through fluorapatite in gelatin-based nanocomposite, fractal in DNA knots driven by balance of fission & fusion in mtDNA/mitochondrial DNA mechanism, for optical engines for light energy detection described the proportional integral derivative [PI(D)]-controller set in microbial cells to HCCI/Homogeneous Charge Compression Ignition.

Solvent accessible surface area (SASA) of amino acid residues plays a significant role in inter-residue, protein-ligand, and protein-protein interactions. Affecting the exposure and interactions of hydrophobic and hydrophilic regions, driving protein folding. While previous SASA calculations are accurate with respect to the chosen parameters of simulation, they do not account for the dynamic behavior of peptides in solution under physiological conditions and cannot be used to compare populations within phi,psi dihedral angle space (phi,psi space). Molecular dynamics trajectories obtained at 310 K, 1 atm, and 150 mM NaCl for the Ac-Ala-Xaa-Ala-NH2 model peptides simulated using the CHARMM36m force field and TIP3Pm water as implemented in GROMACS 2022 were used to study SASA. The more balanced parametrization of CHARMM36m, resulted in increased sampling of beta region compared to alpha, alphaL, and epsilon regions were observed. There are statistically significant differences in SASA for the backbone and side chain comparing the beta, alpha, alphaL, epsilon and contiguous regions of phi,psi space. Differences occur in sampled phi,psi space particularly in the alphaL and epsilon regions of phi,psi space as a function of side chain size and chemical properties. The epsilon region of phi,psi space is not significantly sampled for multiple amino acids while the alphaL region is.

Protein dynamics play a crucial role in biological function, encompassing motions ranging from atomic vibrations to large-scale conformational changes. Recent advancements in experimental techniques, computational methods, and artificial intelligence have revolutionized our understanding of protein dynamics. Nuclear magnetic resonance spectroscopy provides atomic-resolution insights, while molecular dynamics simulations offer detailed trajectories of protein motions. The integration of machine learning, exemplified by AlphaFold2, has accelerated structure prediction and dynamics analysis. These approaches have revealed the importance of protein dynamics in allosteric regulation, enzyme catalysis, and intrinsically disordered proteins. The shift towards ensemble representations of protein structures and the application of single-molecule techniques have further enhanced our ability to capture the dynamic nature of proteins. Understanding protein dynamics is essential for elucidating biological mechanisms, designing drugs, and developing novel biocatalysts, marking a significant paradigm shift in structural biology and drug discovery.

The vaccine industry has undoubtedly contributed massively in the medical world, with hundreds of millions of lives saved as a result of the successful development of prophylactic and therapeutic vaccines against various infectious and oncological diseases. Simultaneously, there has been an ongoing evolutionary battle between polymorphic microbes and the human immune system, and various microbes have developed counter-responses against the human host immune system, by creating diverse “holes” of vulnerability in the innate immune system. Such mechanisms may have resulted due to the lower prophylactic and therapeutic focus upon sharpening the innate immune lines as directly as necessary. The overall objective of vaccine-development should be the sharpening of all immune departments that are targeted by various microbial agents for the purpose of transient innate immune suppression and the distribution of the microbial count/load at a systemic level. Likewise, it could be viable for the clinical research community to start focusing upon filling in the “gaps” of vulnerability that are now present in the pathways responsible for the proper natural immune activation and proportionate signalling toward the adaptive immune system. Perhaps, through such a process, the “road” toward the adaptive immune system, which is “old” and filled with “holes”, could be gradually transformed into a perfectly uniform “highway”, with all the required signals transmitted robustly from the innate to the adaptive immune system, before microbes manage to translate the various pathogenic proteins that transiently prevent such transmission altogether, until it becomes too late for the immune response to possibly develop in a proportionate and non-harmful manner to the organism. Such a scenario would be possible, given that it is almost impossible for human evolutionary growth to eventually stall and not risk experiencing a decrease as a result. Simultaneously, it is important for human society to bind by the principles of maintaining a healthy and nature-friendly lifestyle, given the philosophical quote of “We are what we eat.” The overall objective should be the facilitation of human and animal immune evolution over viral and bacterial molecular self-camouflaging from all possible directions, as a sharper human and animal evolutionary growth resulting from such actions could “cost” the sharper evolutionary growth of microbes as such, given that evolutionary patterns are based upon the models observed in Physics, in Newton’s Third Law of Motion, as well as in the First Law of Thermodynamics, which concerns the Conservation of Energy.

Background: The World Health Organization identifies lung and prostatic cancers as solid tumors with significant global lethality, both being auxotrophic cancers for L-arginine aminoacid. The aim of the study: The study aims to detect L-arginase-expressing bacteria from various soil environments in Egypt using 16S rRNA and characterize its anticancer activity. Methodology: A hundred samples of Egyptian grassland soil were gathered at a depth of 11–20 cm, close to wheat mills. Using fast plate assay screening and spectrophotometric analysis, the presence of bacteria generating L-arginase was verified. The major soil bacterial isolates were identified by morphological characterization, biochemical responses, and 16SrRNA sequencing methods. The anticancer activity of the test enzyme was assessed using MTT assay. Results: On the MAA medium, only the bacterial isolates capable of using L-arginine as the only metabolic source for carbon and nitrogen were cultivated. Bacillus cereus DSM 360 was shown to be the prevailing bacterial isolate generating L-arginase using molecular detection and biochemical reactions. When Co+2, Ni+2, and Mn+2 metal ions were present as co-factors, bacterial L-arginase demonstrated remarkable anticancer action against auxotrophic tumors for L-arginine. The total protein content was 0.349 mg, while total enzyme activity was 8.174 U with 61% enzyme recovery. As well as the specific activity reached 23.4212 U/mg. Using the mass spectrometer, the molecular weight of the bacterial L-arginase was revealed to be 37 KDa. The bacterial L-arginase's IC50 values were 3.12 U/ml for the lung cancer cell line, 3.91 U/ml for prostatic cancer cell line, 0.91 U/ml for acute promyelocytic leukemia cancer cell line and 2.73 U/ml for kidney cancer cell line. The enzyme under test showed kinetic characteristics of 7.36 mmol/l and 6.14 μmol/min for Km and Vmax, respectively. The half-life time (T1/2) was 90.17 min at 50°С, while being 86.53 min at 60°С. The test enzyme was thermostable at 60°С for 1 hour. Conclusion: The study showed a potential strategy by identifying and determining a newly discovered bacterial L-arginase enzyme as an anticancer agent in Egypt's soil settings.

Genetic similarity determines the extent to which two genotypes share common genetic material. It can be measured in various ways, such as comparing DNA sequences, proteins, or other genetic markers. The significance of genetic similarity is multifaceted and encompasses various fields, including evolutionary biology, medicine, forensic science, animal and plant breeding, and anthropology. Genetic similarity is an important concept with wide application across different scientific disciplines. In the presented study, six measures for calculating genetic similarity were compared: Euclidean, Jaccard, Kulczyński, Sokal and Michener, Nei, and Rogers. The research material included 21 rapeseed genotypes (ten interspecific Brassicaceae hybrids of F2 generation, and 11 of their parental forms) and 146 alleles, obtained using 21 ISSR molecular markers. The results indicate that the research material was divided into two identical groups using any of the proposed methods, despite differences in the values of genetic similarity coefficients. Two of the presented measures of genetic similarity (Sokal and Michener, and Euclidean) were the same.

The Amazonian shrub Myrciaria dubia (Kunth) McVaugh, known as "camu-camu", produces vitamin C-rich fruits of growing commercial interest. However, sustainable utilization requires assessment and protection of the genetic diversity of the available germplasm. We hypothesized that the ex situ M. dubia germplasm bank assembled from eight river basins across the Peruvian Amazon would harbor substantial genetic diversity and have a genetic population structure. This study aimed to (1) develop new polymorphic microsatellite markers, (2) characterize genetic diversity and validate the hypothesis in the ex situ germplasm, and (3) construct a core subset representing maximum allelic variability. Sixteen polymorphic microsatellite loci were developed using an enrichment approach. The evaluation of 336 genotypes from 43 accessions originating from eight river basins of the germplasm bank corroborated this hypothesis, revealing high gene diversity, with observed heterozygosity ranging from 0.468 to 0.644 and expected heterozygosity from 0.684 to 0.817 at the river basin level. Analysis of molecular variance showed a higher genetic variation within accessions and river basins, at 73% and 86%, respectively, than among accessions and river basins, at 27% and 14 %, respectively. Bayesian clustering detected the presence of ten genetic clusters, with several degrees of admixture among river basins. The Putumayo River basin showed a clear genetic homogeneity. A core collection of 84 genotypes was constructed, thus covering 86.7% of the global allelic diversity. These results have important implications for M. dubia conservation strategies and breeding programs, in demonstrating a need for genetic connectivity between populations but preserving unique genetic resources in isolated basins. These results validate the expected levels of diversity and population subdivision in a crop and stress the need to secure genetically diverse germplasms, underscoring the importance of thorough genetic characterization for ex situ germplasm management.

It is often said in human society that it all starts from the mind, and this is true. The answer to the question “Why is it that pets require much fewer years to fully develop than humans?” could be headed to the Theory of Relativity and the perceived time according to the levels of instinct and rationality. It is perhaps no wonder that the French language translates the word “mind” as “l’esprit”, which also means “spirit” in the English language. Given that the Theory of Relativity applies to all physical matter, the theory applies to chemistry, biology and psychology as well. The level of instinct is proportional with the perceived speed of time and implicitly, to the speed of time itself for the whole organism, given that the nervous system coordinates all bodily functions. A pet may experience a few years as humans experience over a decade, making their perceived lifetime to be approximately equal to the human’s. The same applies to the perception of space and its components. This aspect would emphasise upon the fact that all life on Earth shows the same degree of value with regards to uniqueness. Nevertheless, the values represented by the hierarchy of competences among living organisms at the same time differs based on species. Honour of uniqueness and hierarchy of competences represent two scientific concepts that never overcross. As a result, there is no evidence to suggest that scientific facts as such constitute a form of contradiction to philosophical and religious ideas, given that religion refers to animals as companions of humans. With regards to the clock of the living organism; there are three kinds of clocks in a living organism: the emotional clock, the cognitive clock and the molecular clock. These three categories actually constitute the temporal layers of our dimension, so they are in a relationship of interdependence. When one has a feeling that time is slower or quicker, they are not fully experiencing that change in the time speed, but only partially. And one can profoundly experience the change of perceived time speed when they experience profound feelings, which sweep them away from reality. Complete, deep mental focus can bring about this profound change in perception, which will make the individual feel as if they are in a different form of reality. When one is more instinctive, the person in cause perceives time as slower and sees more opportunities within the same frame of time and space. When one experiences the “Fight or flight” mode, the person in the cause finds themselves to be in danger and has two options; to try to prevail over the danger or to flee it. Whilst experiencing such a mode, people are much more alert and therefore, time passes more slowly and the physical space dilates. When people are relaxed, however, time and space become smaller, and when they are in a deep state of resting, they become very small. And where there is a smaller dimension, there is a greater speed, just as the circulating air gains speed when it crosses narrow passages.

Pancreatic cancer is a serious and aggressive type of cancer that affects the digestive system and has a low chance of survival. Although traditional treatment methods have achieved some efficacy, the survival rate of patients remains low. Therefore, exploring novel treatment strategies is important. This article looks at the research done on bioactive compounds and plant extracts for treating pancreatic cancer. Bioactive compounds, such as naringenin and ziyuglycoside II, have significant anticancer activity and exert anti-pancreatic-cancer effects by inducing cell apoptosis, inhibiting the cell cycle, and blocking signaling pathways. Plant extracts, such as epigallocatechin-3-gallate and resveratrol, also demonstrate good anti-pancreatic cancer activity and inhibit tumor growth and metastasis. Additionally, the combined application of bioactive compounds and plant extracts may result in improved therapeutic effects. This article aims to provide a theoretical basis for the application of bioactive compounds and plant extracts in the treatment of pancreatic cancer and to help guide future medical research and practice.

This paper reports results of analysis of field ion emission mechanism from tungsten-epoxy composite emitters that are compared to tungsten nano-field emitters. In this context, the mechanism of emission from this type of emitters is described based on a theory of induced conductive channels. The tungsten emitters were prepared using the electrochemical polishing technique and coated with a layer of the epoxy resin. Field ion microscope (FIM) analyses are reported including the study of the emission-ion density distributions from both the uncoated and coated emitters. Two forms of emission patterns have been observed in the ion emission microscopy technique describing the differences in the emission mechanism of both types of emitters. The observed results show: (a) the expected crystalline surface atomic distribution images of the field ion microscopy in the case of uncoated tungsten tips, and (b) randomly distributed emission spots that describe the locations of the induced conductive channels inside the resin coating layer.

Bagaza virus (BAGV) is a flavivirus that affects avian species. In Europe, it was detected for the first time in Spain in 2010, exhibiting high genetic relatedness to Israel turkey meningoencephalomyelitis virus (ITMV) isolates from Israel. After a period of epidemiological silence, BAGV re-emerged causing important outbreaks in 2019 and 2021. This study aims to characterize the newly detected strains and to elucidate if these recent outbreaks were caused by single or different virus introductions into the country. Hence, Spanish BAGV isolates from 2019 (n=3) and 2021 (n=1) outbreaks, obtained from red-legged partridges in Cádiz, were sequenced and further characterized. The phylogenetic analyses showed that they belong to two different genotypes: BAGV Genotype 1 and 2. Isolates from 2019 belong to BAGV-Genotype 1, closely related to isolates from Senegal, where BAGV has been circulating since decades. In turn, the 2021 isolate belong to BAGV-Genotype 2, closely related to those detected in Spain in 2010. Additionally, the comparison of the viral polyproteins of several BAGV isolates from both genotypes support and confirm the phylogenetic findings. To conclude, BAGV has been introduced into Spain in at least three independent occasions, with alternating genetic clades, thus confirming that BAGV is able to occasionally reach southern Europe.

This study presents a comprehensive approach to calculating the free energy of hydration of methane using Molecular Dynamics simulations. We employed the Free Energy Perturbation (FEP) method to determine the Gibbs free energy associated with transferring a methane molecule into water. Simulations were conducted in a cubic simulation box containing one methane molecule and 1000 TIP4P water molecules. The forward and backward routes were both analyzed, providing consistent free energy differences, which validates the robustness of our methodology. The Gibbs free energy profiles demonstrated characteristic energy barriers and stabilization points, indicative of the interaction dynamics in the solvation process. The results demonstrate the robustness of the FEP method implemented in LAMMPS, yielding free energy in close agreement with experimental data and previous computational studies. The calculated free energy differences for methane hydration exhibited deviations of 13% and 8% for the forward and backward routes, respectively, compared to experimental values. These findings underscore the accuracy and efficiency of using LAMMPS for free energy calculations, contributing to the broader understanding of solvation thermodynamics. Additionally, radial distribution functions were analyzed to provide insights into the structural arrangement of water molecules around methane, revealing strong interaction between methane's carbon atom and water molecules.

Over the past decade, the production of biofuels from lignocellulosic biomass has steadily increased to offset the use of fuels from petroleum. To make biofuels cost-competitive, however, it is necessary to add value to the “ligno-” components (up to 30% by mass) of the biomass. The properties of lignin, in terms of molecular weight (MW), chemical functionality, and mineral impurities often vary from biomass source and biorefinery process, resulting in a challenging precursor for product development. Activated carbon (AC) is a feasible target for the lignin-rich byproduct streams because it can be made from nearly any biomass and it has a market capacity large enough to use much of the lignin generated from the biorefineries. However, it is not known how the variability in the lignin affects the key properties of AC, because until now, they could not be well controlled. In this work, various fractions of ultraclean (< 0.6 % ash) lignin are created with refined MW distributions using Aqueous Lignin Purification using Hot Agents (ALPHA) and used as precursors for AC. AC is synthesized via zinc chloride activation and characterized for pore structure and adsorption capacity. We show that AC surface area and the adsorption capacity increase when using lignin with increasing MW, and furthermore, that reducing the mineral content of lignin can significantly enhance the AC properties. The surface area of the AC from the highest MW lignin can reach ~1830 m2/g (absorption capacity). Furthermore, the single step activation carbonization using zinc chloride allows for minimal carbon burnoff (< 30%) capturing most of the lignin carbon compared to traditional burn off methods in biorefineries for heat generation.

Periodontal disease, a multifactorial inflammatory condition affecting the supporting structures of the teeth, has been increasingly recognized for its association with various systemic diseases. Understanding the molecular comorbidities of periodontal disease is crucial for elucidating shared pathogenic mechanisms and potential therapeutic targets. In this study, we conducted comprehensive literature and biological database mining utilizing tools such as DisGeNET2R, Romin, and Rentrez R libraries to identify diseases sharing associated genes, proteins, or molecular pathways with periodontitis. Our analysis revealed significant molecular overlaps between periodontal disease and several systemic conditions, including cardiovascular diseases, diabetes mellitus, rheumatoid arthritis, and inflammatory bowel diseases. Shared molecular mechanisms implicated in the pathogenesis of these diseases and periodontitis encompassed dysregulation of inflammatory mediators, immune response pathways, oxidative stress pathways, and alterations in the extracellular matrix. Furthermore, network analysis unveiled key hub genes and proteins that play pivotal roles in the crosstalk between periodontal disease and its comorbidities, offering potential targets for therapeutic intervention. Insights gained from this integrative approach shed light on the intricate interplay between periodontal health and systemic well-being, emphasizing the importance of interdisciplinary collaboration in developing personalized treatment strategies for patients with periodontal disease and associated comorbidities.

Rice, a globally important food crop, faces significant challenges due to salt and drought stress. These abiotic stresses severely impact rice growth and yield, manifesting as reduced plant height, decreased tillering, reduced biomass, and poor leaf development. Recent advances in molecular biology and genomics have uncovered key physiological and molecular mechanisms that rice employs to cope with these stresses, including osmotic regulation, ion balance, antioxidant re-sponses, signal transduction, and gene expression regulation. Transcription factors such as DREB, NAC, and bZIP, as well as plant hormones like ABA and GA, have been identified as crucial reg-ulators. Utilizing CRISPR/Cas9 technology for gene editing holds promise for significantly en-hancing rice stress tolerance. Future research should integrate multi-omics approaches and smart agriculture technologies to develop rice varieties with enhanced stress resistance, ensuring food security and sustainable agriculture in the face of global environmental changes.

B-cell lymphoid malignancies is a heterogeneous group of hematologic cancers, where Bruton's tyrosine kinase (BTK) inhibitors have received FDA approval for several subtypes. The first-in-class covalent BTK inhibitor, ibrutinib, binds to the C481 amino acid residue to block the BTK enzyme and prevent the downstream signaling. Resistance to covalent BTK inhibitors can occur through mutations at the BTK binding site (C481S) but also other BTK sites and the phospholipase C gamma 2 (PLCγ2) resulting in downstream signaling. To bypass the C481S mutation, non-covalent BTK inhibitors, such as pirtobrutinib, were developed and are active against both wild-type and the C481S mutation. In this review, we discuss the molecular and genetic mechanisms which contribute to acquisition of resistance to covalent and non-covalent BTK inhibitors. In addition, we discuss the new emerging class of BTK degraders, which utilize the evolution of proteolysis-targeting chimeras (PROTACs) to degrade the BTK protein and constitute an important avenue of overcoming resistance. The moving landscape of resistance to BTK inhibitors and the development of new therapeutic strategies highlight the ongoing advances, that are being made towards the pursue of cure of B-cell lymphoid malignancies.

Any homeostatic protometabolism would have required orchestration of disparate biochemical pathways into integrated circuits. Extraordinarily specific moieties were also required. Assembly Theory conflated with its cousins—Complexity Theory, Chaos theory, Quantum Mechanics, Irreversible Nonequilibrium Thermodynamics and Molecular Evolution theory— collectively have great naturalistic appeal in hopes of their providing the needed exquisite steering and controls. They collectively offer the best hope of circumventing the need for active selection required to formally orchestrate bona fide formal organization (as opposed to the mere self-ordering of chaos theory) [1]. This paper focuses specifically on Assembly Theory’s contribution to life-origin models.

Here, we present a general framework for computing the infrared anharmonic vibrational spectra of polyatomic molecules using the Born-Oppenheimer molecular dynamics (BOMD) with the software PyRAMD. To account for the nuclear quantum effects, we suggest using the simplified Wigner sampling (SWS) approach [\textit{Phys. Chem. Chem. Phys.}, 2023, \textbf{25}, 18406-18423] simultaneously coupled with the Andersen and Berendsen thermostats. We propose a new criterion for selecting the parameter of the SWS based on the molecules' harmonic vibrational frequencies and usage of the large-time-step blue shift correction, allowing for a decrease in computational expenses. For the Fourier transform of the dipole moment autocorrelation function, we propose to use the regularized least-squares analysis, which allows us to obtain higher frequency resolution than the direct application of fast Fourier transform. Finally, we suggest the usage of the pre-parameterized scaling factors for the IR spectra from BOMD, also providing the scaling factors for the spectra at the BLYP-D3(BJ)/6-31G, PBE-D3(BJ)/6-31G, and PBEh-3c levels of theory.

In vitro cancer cell cytotoxicity (IC50 values) of (E)-3-(4’-methylbenzylidene)-4-chromanone (IIIb) showed &gt;50.0 decreases in comparison to those of the respective tetralone derivative (IIIc). On the other hand, such a decrease was not observed in the analogous 4-OCH3 (IIc and IIIc) derivatives. Since the compounds can be considered cyclic chalcone analogs, kinetics and diastereoselectivity of non-enzyme catalyzed reactions with reduced glutathione (GSH) and N-acetylcysteine (NAC) of IIIb and IIIc were investigated to assess the possible role of thiol-reactivity in the increased cytotoxicity of IIIb. Reactivity of the compounds and stereochemical outcome of the reactions were evaluated using high-pressure liquid chromatography-mass spectrometry (HPLC-MS). Molecular modeling calculations were performed to rationalize the observed differences in the thiol-reactivities of the chromanones (III) and the previously investigated tetralones (II). The results indicated possible role of spontaneous thiol-reactivity of compounds III in their recorded biological effects.

In recent decades, there has been a rising demand for anti-aging interventions aimed at postponing or potentially reversing indicators of skin aging. The use of collagen-based nutraceutical supplements has gained popularity as they have shown promise in enhancing skin health and reducing signs of aging. The aim of this randomized, placebo-controlled, blinded study was to investigate the effects of 2.5 g COLLinstant® LMW, a novel cosmeceutical containing low molecular weight (≤ 1000 Da) collagen peptides, on skin aging and health. The trial was conducted in 80 healthy women aged 30 years and older. They received a daily oral dose of either the food supplement (n = 40) or placebo (n = 40) for six weeks. Skin assessment was performed based on validated objective methods, such as Visioface 1000D (skin wrinkling), cutometry (elasticity and fatigue) and corneometry (skin hydration) at baseline (T0), and at week 6 (T6). After 6 weeks, participants that received collagen had significant improvements in biometric skin wrinkle parameters from baseline, with a reduction in volume by 46%, in area by 44%, and in depth by 9%, along with a greater increase in skin moisturization (by 34%) than those in the placebo group (p &lt; 0.001). The food supplement did not significantly modify skin firmness or fatigue and had only slight beneficial effects on skin elasticity. The investigational product was well tolerated. The observed effects aligned closely with the subjective assessments reported by study participants. The study provides substantiated evidence supporting the efficacy of low molecular weight collagen peptides in restoring altered skin biometric parameters, as objectively assessed. Thus, regular supplementation with this nutraceutical may contribute to achieving smoother and more radiant skin.

The formation of atroposelective biaryl compounds in plants and fungi is well understood; however, the polyketide aglycone synthesis and dimerization in bacteria remain unclear. Thus, the biosynthetic gene cluster (BGC) responsible for antibacterial setomimycin production from Streptomyces nojiriensis JCM3382 was examined in comparison with the BGCs of spectomycin, julichromes, lincolnenins, and huanglongmycin. Setomimycin BGC includes post-PKS assembly/cycling enzymes StmD (C-9 ketoreductase), StmE (aromatase), and StmF (thioesterase) as key components. The heterodimeric TcmI-like cyclases StmH and StmK are proposed to aid in forming the setomimycin monomer. In addition, StmI (P-450) is predicted to catalyze biaryl coupling of two monomeric setomimycin units, with StmM (ferredoxin) specific to setomimycin BGC. The roles of StmL and StmN, part of the nuclear transport factor 2 (NTF-2)-like protein family and unique to setomimycin BGCs, could particularly interest biochemists and combinatorial biologists. α-Glucosidase, a key enzyme in type 2 diabetes, hydrolyzes carbohydrates into glucose, thereby elevating blood glucose levels. This study aimed to assess the α-glucosidase inhibitory activity of EtOAc extracts of JCM 3382 and setomimycin. The JCM 3382 EtOAc extract and setomimycin exhibited greater potency than the standard inhibitor, acarbose, with IC50 values of 285.14 ± 2.04 μg/mL and 231.26 ± 0.41 μM, respectively. Kinetic analysis revealed that setomimycin acts as a competitive inhibitor of α-glucosidase. Molecular docking demonstrated two hydrogen bonds with maltase-glucoamylase chain A residues Thr205 and Lys480 (binding energy = −6.8 kcal·mol⁻¹), two π-π interactions with Trp406 and Phe450, and one π-cation interaction with Asp542. Residue-energy analysis highlighted Trp406 and Phe450 as key in setomimycin's binding to maltase-glucoamylase. These findings suggest that setomimycin is a promising candidate for further enzymological research and potential antidiabetic therapy.

Benzazoles, such as benzoxazoles and benzothiazoles, are compounds with important biological and pharmacological activities and important intermediaries in synthesis. This report presents the synthesis of a butanamide derived from linking 5-chloro-2-aminobenzoxazole and 2-aminobenzothiazole via 4-chlorobutanoyl chloride. The corresponding compound N-(benzothiazol-2-yl)-4-((5-chlorobenzoxazol-2-yl)aminobutanamide was obtained 76 % yield global using accessible starting materials and methodology in two reaction steps. Furthermore, we made docking studies of this compound on 3-TOP protein to explore its potential as an antidiabetic agent.

Nucleation is a fundamental and general process at the initial stage of first order phase transition. Although various models based on the classical nucleation theory (CNT) have been proposed to explain the energetics and kinetics of nucleation, detailed understanding on nanoscales are still required. Here we focus on homogeneous bubble nucleation, in which evaluation of the size dependence of bubble free energy is the key issue. We propose application of a formula in stochastic thermodynamics, the Jarzynski’s equality, for data analysis of molecular dynamics (MD) simulation to evaluate the free energy of bubble nucleation. As a test case, we performed a series of MD simulations with Lennard-Jones (LJ) fluid system. By applying an external spherical force field to equilibrated LJ liquid, we evaluated the free energy change during bubble growth as the Jarzynski’s ensemble average of required works. A fairly smooth free energy curve was obtained as a function of bubble radius in metastable liquid of mildly negative pressure conditions.

Oral drug absorption is the primary route for drug administration. However, this process hinges on multiple factors, including the drug’s physicochemical properties, formulation characteristics, and gastrointestinal physiology. Given its intricacy and the exorbitant costs associated with experimentation, the trial-and-error method proves prohibitively expensive. Theoretical models have emerged as a cost-effective alternative by assimilating data from diverse experiments and theoretical considerations. These models fall into three categories: data-driven models, encompassing classical pharmacokinetics, quantitative-structure models (QSAR), and machine/deep learning. Mechanism-based models include quasi-equilibrium, steady-state, and physiologically based pharmacokinetics, alongside first principles such as molecular dynamics and continuum models. This review provides an overview of recent modeling endeavors across these categories, evaluating their respective advantages and limitations. Additionally, a primer on partial differential equations and their numerical solutions is included in the supplementary materials, recognizing their utility in modeling physiological systems despite their mathematical complexity limiting their widespread application in this field.

Atypical Polypoid Adenomyoma (APA) is a benign uterine lesion that occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Our work consists of a systematic review of the literature, including the description and analysis of a case study, and assesses the main immunohistochemical and molecular markers that contribute to making a differential diagnosis against endometrial adenocarcinoma. This allows offering patients conservative treatment compared to the radical management required for endometrial cancer, due to the significant physical and psychological consequences that one procedure or another can have on women's health. The goal of this research is to carry out an adequate diagnosis of APA by providing the necessary information to guide clinical management, establish patient prognosis, and minimize the emotional impact associated with the disease, all in combination with clinical and histopathological findings and complementary imaging tests. In conclusion, an appropriate immunohistochemical and molecular approach, along with the presumptive histological diagnosis, determine the correct classification of the lesion as APA and not as other malignant pathologies, which allows establishing a treatment protocol adjusted to the biological reality of this pathology.

An H-bond involves the sharing of a hydrogen atom between an electronegative atom to which it is covalently bound (the donor) and another electronegative atom serving as an electron acceptor. Such bonds represent a critically important geometrical force in biological macromolecules and, as such, have been characterized extensively. H-bond formation invariably leads to a weakening within the acceptor moiety due to the pulling exerted by the donor hydrogen. This phenomenon can be compared to a spring connecting two masses; pulling one mass stretches the spring, similarly affecting the bond between the two masses. Herein, we describe the opposite phenomenon when investigating the energetics of the C-H...O=C bond. This bond underpins the most prevalent protein transmembrane dimerization motif (GxxxG) in which a glycine C-H on one helix forms a hydrogen bond with a carbonyl in a nearby helix. We use isotope-edited FT-IR spectroscopy and corroborating computational approaches to demonstrate a surprising strengthening of the acceptor C=O bond upon binding with the glycine C-H. We show that electronic factors associated with the C-H bond strengthen the C=O oscillator by increasing the s-character of the -bond, lowering the hyperconjugative disruption of the -bond. In addition, a reduction of the acceptor C=O bond’s polarity is observed upon the formation of the C-H...O=C bond. Our findings challenge the conventional understanding of H-bond dynamics and provide new insights into the structural stability of inter-helical protein interactions.

Mosquitoes genus Aedes are the most important arthropod disease vector. Dengue Virus (DENV) and Chikungunya Virus (CHIKV) are the main arboviruses distributed in the world. Based on entomo-virological surveillance, appropriating public health strategies can be addressed to contain cases and control outbreaks. This study aims to show the potential performance of two new molecular methods for detecting DENV serotypes and CHIKV in mosquitoes. Mosquitoes were collected in urban areas and sylvatic areas between July to August 2023, DENV and CHIKV were screened using new multiplex RT-PCR and RT-q PCR. A total of 2150 mosquitoes were trapped including 976 Aedes (959 Ae. egypti, 6 Ae. furcifer and 11 Ae. Vittatus) and 1174 Culex from 39 pools of a maximum of 30 mosquitoes each, tested by molecular screening, 7.7% (3/39) were positive for DENV, DENV-1 was detected in one pool (1/3), and DENV-3 in two pools (2/3). All the pools were negative for CHIKV. The overall minimum infection rate (MIR) of DENV in this study was 3.07 (95% CI: 2.24 —19.86). This study shows the usefulness of our new molecular tools in DENV serotypes and CHIKV surveillance.

Indole derivatives are key components of natural products and possesses a wide range of biological and pharmaceutical applications. Here we present the synthesis of a new indole derivative namely 2-(1-ethyl-5-nitro-1H-indole-7-carbonyl) butyl 4-methylbenzenesulfonate (5). The structural elucidation of 5 was accomplished through comprehensive spectroscopic analysis, including Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). Our molecular docking study revealed that compound 5 exhibits strong affinity towards Tyrosinase, making it a promising candidate as an antioxidant agent. Keywords: Indole derivative; Tosyl group; Molecular docking; Antioxidant agent.

The de-oxygenation process in water used in well injection operations is an important matter to eliminate corrosion in petroleum industry. This study used molecular dynamics simulations to understand the behavior of siloxane surface through studding the surface properties with two functional groups attached to the end of siloxane and their effect on de-oxygenation process. The simulations were performed using LAMMPS to characterize of surface properties. Jmol software was used to generate siloxane chains with (8, 20, and 35) repeat units. Firstly, we evaluated properties such as total energy, surface tension and viscosity. Then, we used siloxane as a membrane to compare the efficiency of de-oxygenation for the both types of functional groups. The results indicated that longer chains length increased total energy, viscosity while decreased surface tension. Replacing methyl groups with trifluoromethyl (CF3) groups increased all the above mentioned properties in varying proportions. Trifluoromethyl (CF3) groups showed better removal efficiency than methyl (CH3) groups but allowed more water to pass. Furthermore, the simulations were run using the class II potential developed by Sun, Rigby, and others within an explicit-atom (EA) model.

The self-assembly is an intriguing process of great importance in general soft matter and thus re-ceives an ever-growing scientific interest. Its most trivial example is the entropy-driven crystalli-zation of hard spheres. Past works have established the similarities and differences in the phase behavior of monomers and chains made of hard spheres. In the present work, inspired by the dif-ference in the melting points of the pure components, we study, through Monte Carlo simulations, the phase behavior of athermal mixtures composed of fully flexible polymers and individual monomers of uniform size. We analyze how the relative number fraction and the packing density affect crystallization and the established ordered morphologies. A synergetic effect is observed in the crystallization leading to synchronous crystallization of the two species. Structural analysis of the resulting ordered morphologies shows perfect mixing and thus no phase separation, which could split the system into polymer-rich and monomer-rich domains. Due to the constraints imposed by chain connectivity, the local environment of the individual spheres is systematically more spherical and more symmetric compared to the one of spheres belonging to chains. In general, increasing polymer content leads to reduction of the degree of crystallinity. According to the present findings, relative concentration is another determining factor to control the phase behavior of hard colloidal systems based on polymers.

Oral mucositis (OM) is one of the common adverse events associated with cancer treatment that decreases quality of life and affects treatment outcome. However, the medications used to manage OM are generally only palliative, and our knowledge of the syndrome is limited. The etiology of the syndrome is thought to be complex and multifactorial. We investigated the trends and characteristics of OM and estimated molecular initiating events (MIEs) associated with the development of the syndrome using FDA Adverse Event Reporting System. The study of trends and characteristics suggested that OM is significantly more likely to occur in females and nonelderly patients and is likely to be induced by protein kinase inhibitors such as afatinib and everolimus. Next, we used Toxicity Predictor, an in-house quantitative structure–activity relationship system, to estimate OM-associated MIEs. The results revealed that agonist activity of human pregnane X receptor, thyroid-stimulating hormone-releasing hormone receptor, and androgen receptor may be associated with OM development. Our study findings are expected to help avoid the risk of OM induction during the drug discovery process and clinical use of antineoplastic agents.

Exploiting the van der Waals model of liquids, it is possible to derive analytical formulas for the thermodynamic functions governing solvation, the transfer of a solute molecule from a fixed position in the ideal gas phase to a fixed position in the liquid phase. The solvation Gibbs free energy change consists of two contributions: (a) the high number density of all liquids and the repulsive interactions due to the basic fact that each molecule has its own body lead to the need of spending free energy to create a cavity suitable to host the solute molecule; (b) the ubiquitous intermolecular attractive interactions lead to a gain in free energy for turning on attractions between the solute molecule and surrounding liquid molecules. Also the solvation entropy change consists of two contributions: (a) there is an entropy loss in all liquids because the cavity presence limits the space accessible to liquid molecules during their continuous translations; (b) there is an entropy gain in all liquids, at room temperature, due to the liquid structural reorganization as a response to the perturbation represented by solute insertion. The latter entropy contribution proves to be balanced by a corresponding enthalpy term. This scenario emerged from the van der Waals model is in qualitative agreement with experimental results.

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 65 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2, and altered expression of growth factor receptors and microRNAs. These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelets/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș, including patients with lung cancer. The parameters analyzed included: histopathological type (NSCLC - squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters and associated comorbidities. Results: 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5,30 versus 2,60, p&lt;0,001; 217 versus 136, p&lt; 0.001, respectively). NLR and PLR differs between men and women (p = 0.005, respectively p=0.056). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusion: The NLR and PLR values ​​may serve as new predictive biomarkers for the diagnostic of disease in patients with lung cancer, especially those with NSCLC.

Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting of the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (&lt;-9.00 kcal/mol), surpassing that of RdRp-Ribavirin (&lt;-7.00 kcal/mol) along with promising ADMET score predictions (&lt;4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. This study highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.

Keywords: Chronic Obstructive Pulmonary Disease (COPD), Long Non-Coding RNAs (lncRNAs), Molecular Pathogenesis, Inflammation, Lung Cancer, Diagnostic Biomarkers

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

The theories of Evolution and Big Bang have brought a major impact upon the scientific and societal perception upon the origins, abilities and roles of mankind on Earth. It is conclusively evident that Mother Nature and the physical realm is autonomous and all phenomena in the world occur without an imposition against the “free will” of such events and patterns. Nevertheless, this extent of freedom does not imply that life on Earth represents an accident and has no purpose. By careful analysis of ancient religious texts, it can be suggested even otherwise, that it is especially free will that is offered as a gift from outside of the physical dimensions of existence, with the purpose of a continuous edification and improvement of the overall life conditions and of the human perception. It may be that the multi-generational focus on improvement and progress have been misattributed as a long-term evolution of species, that humans came from animal ancestors and that there is a blurred line associating humans with animals. Furthermore, it may be that scientists based their suggestions that no outside Creator would have brought the Earth into existence on physical perspectives, when the extra-dimensional process of Creation implies that all elements of the physical existence undergo a process of Creation from the outside, where time, space and physical matter do not exist, in spite of such elements possibly reflecting unseen elements of the meta-physical world. Finally, there is the following example that deserves attention within the scientific community; just because all living cells - human, animal and plant - contain DNA chromosomes, ribosomes, mitochondria and a plasma membrane, it does not indicate that humans are animals, just as this does not indicate that plants are animals. In Science, there is a golden statement, that correlation does not imply causation. This example is in complete agreement with the verses of the Book of Genesis in the Holy Scriptures regarding the origins of life; namely, that animals could have been created by an Author of all life on Earth so that man would experience companionship. Another major accordance with the teachings of the Holy Scriptures is the fact that life emerged from the water, and not from the soil, although the soil constituted the second principal means of the commencement and extension of life. Namely, after life first emerged in the seas and the oceans from bacteria, a few bacteria were passed from the marine water into the nearby soil on islands and surrounding land through the circulatory air above the sea level. Afterward, the first life forms emerged from the soil, via the transferred bacteria. Eastern Orthodox Christianity regards water as the principal environment of both physical and spiritual birth. Overall, an improved scientific perception of the timeline of life on Earth may be reached via an approach that combines molecular biology with quantum physics, given that the three layers of Science - Biology, Chemistry and Physics - together with their foundational layer of Mathematics, are in fact situated in a relationship of complete harmony.

The causal networks are important for understanding the signaling alterations in diseases. To reveal the network pathways affected in epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) have been analyzed. The network pathways in GC were analyzed in Ingenuity Pathway Analysis (IPA). The analysis of the probe sets of which gene expression has significant differences between diffuse- and intestinal-type GC in RNA Sequencing publicly available data identified 1099 causal networks in diffuse- and intestinal-type GC. Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of regulation of EMT by growth factors pathway, coronavirus pathogenesis pathway, and vorinostat. The network had RNA-RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-217, mir-223, mir-25, mir-27, and mir-34. These molecular networks revealed in the study may lead to the identification of drug targets for GC.

Protein glycation impacts enzymatic activity, disrupts metabolic processes, and is associated with chronic degenerative diseases. The human glycolytic enzyme triosephosphate isomerase (HsTIM, TPI1, or HsTPI) is associated with various disorders, such as enzymopathies originating from mutations. It also possesses moonlighting functions and is now recognized as a cancer marker. Previous reports of HsTPI mutants have demonstrated a significant increase of methyl-glyoxal (MGO) due to trioses accumulation. We compared how catalytic activity exerts differen-tial kinetic and structural stability effects due to mutations by tracking fluorescent argpyrimi-dine adduct (ARGp) through interaction with Arginine-MGO. Circular dichroism and fluores-cence spectroscopy were explored in HsTPI-WT and mutants HsTPI-C217K “Like-WT”, HsTPI-N16D accumulated in cancer, and HsTPI-E104D human deficiency mutant, by cysteines accessibility and time loss of activity and unfolding propensity in mutant enzymes with aggre-gates refractory to proteolysis in the C217K. Our study sheds new light on the increased suscep-tibility of mutants to generate MGO adducts due to TPI isomerization of MGO precursor sub-strates. Nevertheless, mutations enhance a negative feedback cycle, in which accumulated MGO access promotes accelerated loss of activity that leads to unfolding and aggregation. The cumu-lative and accelerated increase in MGO adducts, which probably are responsible for the patho-logical state in this TPI variant, are partially reversed by adding MGO-scavenger molecules.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Abstract: Chronic Obstructive Pulmonary Disease (COPD) is a continually advancing respiratory disorder, characterized by enduring airflow limitation along with long-lasting inflammation in the airways. An expanding pool of evidence is emphasizing how mitochondrial dysfunction directly impacts the development and progression of COPD. This comprehensive review delves deeper into the intricate cellular and molecular biology of mitochondria within the framework of COPD, spotlighting significant alterations in structure and function that accompany mitochondrial dysfunction. In this narrative, we delve into the observed changes in mitochondrial shape, behavior, and respiratory chain complex alterations seen in individuals afflicted with COPD. The discussion includes implications on cellular signaling pathways and how this affects the natural process of programmed cellular death (apoptosis) and cellular aging, particularly in reference to COPD. Additionally, we consolidate ongoing therapeutic strategies, honing in on the management of COPD through a focus on mitochondrial dysfunction. Prominent among these strategies is the potential role of antioxidants and mitochondrial biogenesis inducers, which are emerging as promising fields of intervention. Furthermore, we embark on an overview of the possible use of mitochondrial biomarkers as innovative tools in diagnosing COPD, evaluating disease progression, and monitoring the efficacy of COPD treatments. As we unravel the rather complex interplay between mitochondrial biology and COPD, this review highlights the critical importance of formulating treatments that target mitochondrial dysfunction. The ultimate goal of these strategic interventions is to slow down the rate of COPD progression and significantly improve patient outcomes. Lastly, though our understanding of the nexus between COPD and mitochondrial dysfunction has significantly enhanced, ample scope remains for further investigation. Improved insights into the mechanisms of mitochondrial dysfunction, discovered biomarkers, and targeted therapies could encompass a revolutionary step towards comprehensive disease management. The future of COPD treatment seems to lean towards a combination of strategies, prioritizing not only the management of symptoms but also focused on preserving and restoring lung function, improving physical capacity, and enhancing quality of life for COPD patients.

Single particle tracking is a powerful technique to investigate the motion of molecules or particles. Here we review methods for analyzing the reconstructed trajectories, step needed for deciphering the underlying mechanisms driving the motion. First, we review the traditional analysis based on the mean square displacement (MSD), highlighting sometimes-neglected factors potentially affecting results accuracy. We then report methods that exploit distributions of parameters other than displacements, e.g. angles, velocities, and times and probabilities of reaching a target, discussing how they are more sensitive in characterizing heterogeneities and transient behaviors masked in MSD analysis. Hidden Markov Models are also used for this purpose, and these allow identifying different states, their populations and the switching kinetics. Finally, we discuss a rapidly expanding field: trajectory analysis based on machine learning. Various approaches, from random forest to deep learning, are used to classify trajectory motions, which can be identified by motion models or by model-free sets of trajectory features, either previously defined or automatically identified by the algorithms. We also review free software available for some of the analysis methods. We emphasize that approaches based on combined different methods, including classical statistics and machine learning, may be the way to obtain the most informative and accurate results.

Brucellosis is a zoonoses caused by bacteria of the genus Brucella, which causes economic losses in livestock and threatens public health. A cross-sectional study was conducted to determine the prevalence of Brucella species and risk factors in smallholder dairy cattle in six regions of Tanzania from July 2019 to October 2020. Dairy cattle (n=2048) were sampled from 1371 farms. DNA ex-tracted from blood and vaginal swabs was tested for Brucella using qPCR targeting the IS711 gene and positives were tested for the alkB marker for B. abortus and BMEI1172 marker for B. melitensis. The molecular prevalence was 3.5% (95% CI: 2.8-4.4) with the highest prevalence 8.1% (95%CI: 4.6-13.0) in Njombe region. B. melitensis was the predominant species detected (66.2%). Logistic regression revealed PCR positivity in dairy cattle was higher in the animals with a history of abortion (OR: 3.17, 95%CI: 1.05-9.62) and farms without dogs around (OR: 2.68, 95%CI: 1.12-5.90). Further studies are recommended to understand the source of B. melitensis and the implications to veterinary public health. Livestock keepers should be informed of the risks and biosecurity practices to reduce introduction and control Brucella. Cattle and small ruminant vaccination pro-grams could be implemented to control brucellosis in high-risk populations in the country.

The study is based on information as the property of matter and its evolution from chemical to digital information. Consequences of these forms of information include molecular, modular, cel-lular, non-human, and human individual interactions, as well as human-machine interaction, and the formation of corresponding modules through self-organizing selective processes. The function of modular structures is decision-making and is analogous to the behavior of an intelligent agent. The evolutionary modular model is proposed based on the interaction of evolutionary factors (matter, energy, information, self-organization, natural selection, and heritability) among themselves and with the arrow of time. In conclusion, we realize that the essence of the evolution of living organ-isms is modular evolution. Modules through which the survival and reproduction of living organ-isms is ensured, are formed by two basic molecular processes, which are molecular recognition or information and modular self-organization.