With the increasing use of genome sequencing as a surveillance tool for molecular epidemiology of antimicrobial resistance, we are seeing an increased intersection of genomics, microbiology, and clinical epidemiology. Clear nomenclature for AMR gene families and pathogens is critical for communication. For CARD release version 3.0.3 (July 2019), we updated the entire CARD database to reflect the latest pathogen names. In total, we detected 48 name changes or updates, some of which reflect major changes in familiar names.

Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with diverse chemical structures and potent biological activities and toxicities. The chemical identification of these compounds remains a major bottleneck. Strategies that can prioritize the most prolific strains and novel compounds are of great interest. Here, we combine chemical analysis and genomics to investigate the chemodiversity of secondary metabolites based on their pattern of distribution within some cyanobacteria. Planktothrix being a cyanobacterial genus known to form blooms worldwide and to produce a broad spectrum of toxins and other bioactive compounds, we applied this combined approach on four closely related strains of Planktothrix. The chemical diversity of the metabolites produced by the four strains was evaluated using an untargeted metabolomics strategy with high-resolution LC-MS. Metabolite profiles were correlated with the potential of metabolite production identified by genomics for the different strains. Although, the Planktothrix strains present a global similarity in term biosynthetic cluster gene for microcystin, aeruginosin and prenylagaramide for example, we found remarkable strain-specific chemo-diversity. Only few of the chemical features were common to the four studied strains. Additionally, the MS/MS data were analyzed using Global Natural Products Social Molecular Networking (GNPS) to identify molecular families of the same biosynthetic origin. In conclusion, we present an efficient integrative strategy for elucidating the chemical diversity of a given genus and link the data obtained from analytical chemistry to biosynthetic genes of cyanobacteria.

Natural products from plants such as, chemopreventive agents attract huge attention because of their low toxicity and high specificity. The rational drug design in combination with structure based modeling and rapid screening methods offer significant potential for identifying and developing lead anticancer molecules. Thus, the molecular docking method plays an important role in screening a large set of molecules based on their free binding energies and proposes structural hypotheses of how the molecules can inhibit the target. Several peptide based therapeutics have been developed to combat several health disorders including cancers, metabolic disorders, heart-related, and infectious diseases. Despite the discovery of hundreds of such therapeutic peptides however, only few peptide-based drugs have made it to the market. Moreover, until date the activities of cyclic peptides towards molecular targets such as protein kinases, proteases, and apoptosis related proteins have never been explored. In this study we explore the in silico kinase and protease inhibitor potentials of cyclosaplin as well as study the interactions of cyclosaplin with other cancer-related proteins. Previously, the structure of cyclosaplin was elucidated by molecular modeling associated with dynamics that was used in the current study. Docking studies showed strong affinity of cyclosaplin towards cancer-related proteins. The binding affinity closer to 10 indicated efficient binding. Cyclosaplin showed strong binding affinities towards protein kinases such as EGFR, VEGFR2, PKB and p38 indicating its potential role in protein kinase inhibition. Moreover, it displayed strong binding affinity to apoptosis related proteins and revealed the possible role of cyclosaplin in apoptotic cell death. The protein-ligand interactions using LigPlot displayed some similar interactions between cyclosaplin and peptide-based ligands especially in case of protein kinases and a few apoptosis related proteins. Thus, the in silico analyses gave an insight of cyclosaplin as a potential apoptosis inducer and protein kinase inhibitor.

Cyclooxygenases (COX), or prostaglandin endoperoxide synthases (PTGS), are key enzimes in the synthesis of prostaglandins, which are chemical species critical in mediating inflammatory processes. There are two highly homologous COX isoforms: COX-1 and COX-2. COX-1 is involved in the production of prostaglandins, chemical compuounds that take part in physiological processes such as: protection of the gastric epithelium, maintenance of renal flow, platelet aggregation, neutrophil migration and, also, are expressed in the vascular endothelium. Meanwhile, COX-2 is induced by proinflammatory stimuli. It is very frequent the use of nonsteroidal antiinflammatory drugs (NSAIDs) to counteract the symptoms of inflammatory processes. These drugs, in addition to its benefits, can cause side effects on people’s health, such as cardiovascular and respiratory problems, among others. In the past years, it has been recognized the potential of plants secondary metabolites as pharmacological agents, prompting the need for investigations that shed light into its mechanism of action. In this work we have applied computational techniques, based on quantum chemistry and mechanical statistics, to study the protein-ligand interaction involving COX’s and secondary metabolites from natural sources. Our aim is to determine the structure activity interplay in processes involving the participation of secondary plant metabolites such as luteolin, galangin, kaempferol, apigenin, morine and quercetin on the inactivation of COX’s. From molecular docking analysis, we have extracted the energetics of the COX-(1,2)/metabolite coupling. By defining energy based factors, we have determined a procedure that predicts the chemical species with highest stability and selectivity towards inactivation of COX-2 over COX-1. The results are discussed with regard to conformational features of the selected ligands and its intermolecular strong/weak interactions inside the active-sites of the COX’s hosts.

Background: Infections caused by E. coli cause considerable disease burden and range from frequently occurring and relatively innocent urinary tract infection (UTI) to severe bloodstream infection (BSI). The incidence of infections caused by ESBL-producing E. coli (ESBL-PEc) is increasing, justifying surveillance and development of preventive strategies in several domains. Faecal carriage is universal and believed to be the most important reservoir for E. coli from which infections can originate. It is currently unknown to what extent Dutch E. coli carriage strains in the community reflect isolates causing disease. In this study, we will perform comparative genomics to infer the population structures of human-derived ESBL-PEc from community- and hospital-acquired infections and from community-based faecal carriage samples in the Netherlands. Furthermore, we will describe the molecular epidemiology of E. coli isolates causing invasive disease (BSI). Methods: This study uses four different microbiological data sources: 1) ESBL-PEc from patients with community-acquired UTI tested in primary care between May and November 2017, 2) ESBL-PEc from urine cultures obtained from patients hospitalized between January 2014 and December 2016, 3) E. coli from blood cultures obtained from patients hospitalized between January 2014 and December 2016, and 4) ESBL-PEc from faecal samples collected in a national population- prevalence study performed between January 2014 and January 2017. Clinical epidemiological data was collected from all patients and all isolates were subjected to whole genome sequencing. Discussion: The EPIGENEC study (EPIdemiology and GENetics of E. coli) will describe the molecular epidemiology of E. coli BSI and assess the genomic population structure of ESBL-PEc strains from community-acquired and nosocomial infections, and of ESBL-PEc reflecting community-based faecal carriage. Information from these studies may assist in optimizing surveillance strategies and determining targets and potential impact of future new preventive measures.

Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the Kinesin-8 family of motor proteins act as MT-destabilizing factors to control MT length in a spatially and temporally regulated manner. In this review, we focus on recent advances in our understanding of the structure and function of the Kinesin-8 motor domain, and the emerging contributions of the C-terminal tail of Kinesin-8 proteins to regulate motor activity and localization.

Vienna Atomic Line Database (VALD) contains data on atomic and molecular energy levels and parameters of spectral lines required for stellar spectra analysis. Hundreds of millions lines for fine spectral synthesis and for opacity calculations are collected in present version of VALD (VALD3). Critical evaluation of the data and the diversity of extraction tools support high popularity of VALD among users. The data model of VALD3 incorporates obligatory links to the bibliography making our database more attractive as publishing platform for data producers. The VALD data quality and completeness are constantly improving allowing better reproduction of stellar spectra. To illustrate continuous evolution of the data content we present a comparative analysis of the recent experimental and theoretical atomic data for Fe-group elements, which will be included in the next VALD release. This release will also include a possibility for extracting the line data with full isotopic and hyperfine structures.

The application of graph theory in chemical and molecular structure research far exceeds people's expectations, and it has recently grown exponentially. In the molecular graph, atoms are represented by vertices and bonded by edges. Closed forms of multiplicative degree-based topological indices which are numerical parameters of the structure and determine physico-chemical properties of the concerned molecular compound. In this article, we compute and analyze many multiplicative degree-based topological indices of silicon-carbon Si₂C₃-I[p,q] and Si₂C₃-II[p,q].

Recent changes in lung cancer care, including new approvals in first line and the introduction of high throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In this article we review recent results in the scope of personalized medicine in lung cancer. We discuss biomarkers that have a therapeutic predictive value in lung cancer with a focus on recent changes and on the clinical value of large scale sequencing strategies. We review the use of second and third generation EGFR and ALK inhibitors with a focus on secondary resistance alterations. We discuss anti-BRAF and anti-MEK combo, emerging biomarkers as NRG1 and NTRKs fusions and immunotherapy. Finally we discuss the different technical issues of comprehensive molecular profiling and show how large screenings might refine the prediction value of individual markers. Based on a review of recent publications (2012–2018), we address promising approaches for the treatment of patients with lung cancers and the technical challenges associated to the identification of new predictive markers.

Abies beshanzuensis, an extremely endangered species, attracts serious concerns on genetic diversity recovery and population protection. However, little genetic information was known about it till now. In this study, intra-/intergenomic ITS variation, secondary structure, and molecular phylogeny of A.beshanzuensis were determined by nrDNA-ITS marker, and results indicated that, ITS region featured rich polymorphism in ITS1 and highly conservative in 5.8S/ITS2 among intra-/inter-genome, implying rich genetic diversities and the occurrence of non-concerted evolution in ITS region. Predicated 5.8S structure possessed Helices-Loops with 3 motifs (M1/M2/M3) and 5 helices B4-B8, and ITS2 could form conservative Clover-like structure with 5 ribotypes, manifesting genetically structural generalities and individualities. Thirteen ITS pseudogenes were also identified from 76 samples (or clones). Molecular phylogeny revealed that, A.beshanzuensis shared genetically closer relationships with A.fanjingshanensis, A.chensiensis, A.yuanbaoshanensis among genus Abies. The available original data provided rich genetic information on ITS sequence, structure and molecular phylogeny of A.beshanzuensis, which not only updated the databases of ITS sequences as well as secondary structures essential for phylogenetic reference and DNA barcoding analyses, but also contributed to deep exploration of population diversities, origin and evolution as well theoretical direction for population recovery and protection of A.beshanzuensis.

Molecular imaging modalities are used for different type of cancers detection and diagnosis. In recent few years, there has been an increased focus on developing novel nanoparticles as new imaging contrast agents for early detection of cancer. The aim of this review article is to summarize molecular imaging technologies accompanying with using nanoparticles to improve potential imaging for cancer detection and hence valuable therapy in the future. Nanoprobes are rapidly becoming potentially transformative tools on cancer diagnostics for a wide range of imaging modalities such as CT, MRI, SPECT, PET, Ultrasound and Optical imaging. The study results seen in the recent literature are provided and discussed the diagnostic performance of imaging modalities for cancer diagnosis and their future directions. With knowledge of the correlation between the application of nanoparticles and molecular imaging modalities and with the development of targeted contrast agents or nanoprobes, they may provide better cancer diagnosis in the future.

As the interface between human and machine becomes blurred, hydrogel incorporated electronics and devices have emerged to be a new class of flexible/stretchable electronic and ionic devices due to their extraordinary properties, such as soft, mechanically robust and biocompatible. However, heat dissipation in these devices could be a critical issue and remains unexplored. Here, we report the experimental measurements and equilibrium molecular dynamics simulations of thermal conduction in polyacrylamide (PAAm) hydrogels. The thermal conductivity of PAAm hydrogels can be modulated by both the crosslinking density and water content in hydrogels. The crosslinking density dependent thermal conductivity in hydrogels varies from 0.33 to 0.51 Wm^-1K^-1, giving a 54% enhancement. We attribute the crosslinking effect to the competition between the increased conduction pathways and the enhanced phonon scattering effect. Moreover，water content can act as filler in polymers which lead to nearly 40% enhancement in thermal conductivity in PAAm hydrogels with water content vary from 23 to 88 wt%. Furthermore，we find the thermal conductivity of PAAm hydrogel is insensitive to temperature in the range of 25 ^oC – 40 ^oC. Our study offers fundamental understanding of thermal transport in soft materials and provides design guidance for hydrogel-based devices.

This study aims the preparation of QCM sensor for the detection of bilirubin in human plasma. Bilirubin imprinted poly-(2-hydroxyethyl methacrylate-N-methacryloyl-L-tryptophan methyl ester) (PHEMATrp) nanofilm (MIP) on the gold surface of QCM chip was synthesized by molecular imprinting technique. Meanwhile, the non-imprinted PHEMATrp (NIP) nanofilm was synthesized by the same experimental technique to examine the imprinting effect. Characterization of MIP and NIP nanofilms on the QCM chip surface was achieved by atomic force microscopy (AFM), ellipsometry, fourier transform infrared spectrophotometry-attenuated total reflectance (FTIR-ATR) and contact angle measurements (CA). The observations indicated that the nanofilm was almost monolayer. Thereinafter, the imprinted and the non-imprinted QCM chipss were connected to QCM system to investigate kinetic and affinity properties. In order to examine the selectivity of the MIP-PHEMATrp nanofilm, competitive adsorption of bilirubin, cholesterol and estradiol was performed. Limit of detection (LOD) and limit of quantitation (LOQ) values were calculated as 0.45 μg/mL and 0.9 μg/mL, respectively.

Many neurodegenerative diseases are directly related to the formation of toxic protein aggregates, such as Parkinson’s and Alzheimer’s diseases, which are associated with the aggregation of alpha-synuclein (α-syn) and beta-amyloid (Aβ ), respectively. In this context, protein fibrils are the hallmark of these neurodegenerative diseases. In this sense, planning or designing compounds that are capable of preventing or reducing the formation of protein aggregation in the brain can be of fundamental importance for the curative treatment of these diseases. This work presents an in silico and experimental study to investigate the inhibitory potential of the ligands Octovespin (bioinspired by the wasp venom Polybia Occidentalis) and Fraternine-10 (bioinspired by the wasp venom Parachartergus fraternus wasp) against the aggregation of fibrils of the peptides Aβ(17-42) and α-syn, respectively. Using molecular docking and molecular dynamics simulations with 100 ns, the disaggregation capacity of these ligands was studied. The results obtained indicate that Octovespin and Fraternine-10 interact with the Aβ and α-syn protein fibrils throughout the simulation time. The RMSD values and the interactions with amino acids responsible for fibril aggregation demonstrate that both Octovespin and Fraternine-10 have a significant disaggregation potential, which corroborates the observations in vitro and in vivo. Furthermore, experimental results of Fraternine-10 demonstrate an anti-aggregation effect, indicating that it can promote the disaggregation of fibrils and prevent them from aggregating again to form oligomers. These discoveries qualify these molecules as potential candidates to become medicines against Parkinson’s and Alzheimer’s diseases.

Anthracnose stands as the primary obstacle to lupin cultivation, impeding development despite the considerable agronomic, ecological, and economic potential of such legume crops. This review explores recent efforts to unravel the complexities of anthracnose in domesticated lupins, focusing on both the plant perspective and the causative pathogenic agent, Colletotrichum lupini. Leveraging cutting-edge technologies has yielded crucial insights into various facets of this devastating disease, encompassing plant and pathogen biology, genetic and molecular regulations of the interaction, fungal diversity and population dynamics, and screening of plant genetic resources for anthracnose resistance. The lack of effective disease control measures, relying primarily on the use of disease-free seeds, highlights the need to develop anthracnose-resistant varieties. However, challenges arise from the intricacy of lupin's response to the disease, influenced by polygenic inheritance, in spite of loci with major effects, and environmental factors. The slow pace of genetic improvement underscores the need for more efficient breeding processes, including biotechnological approaches. This review offers a comprehensive overview of current progress and knowledge gaps, stressing the urgent need to further enhance understanding of C. lupini pathogenic mechanisms and lupin‘s resistance. Integrating advanced technologies and accelerated research efforts is paramount for achieving efficient disease management and sustainable lupin cultivation in the face of anthracnose challenges.

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

The major arboviruses belong mainly to the families Bunyaviridae, Togaviridae, and Flaviviridae amongst which chikungunya virus and dengue virus have emerged as a global public health problem. The main objective of the study was to develop a specific, sensitive, and cost-effective molecular multiplex RT-PCR and RT-qPCR assay for the rapid and simultaneous detection of CHIKV and the four serotypes of DENV for arbovirus surveillance. Specific primers of all virus were designed, one step multiplex RT-PCR (mRT-PCR) and RT-qPCR (mRT-qPCR) was developed using reference strains of CHIKV and DENV serotypes. The specificity of the test for all the viruses was confirmed by sequencing. The standard curves showed a high correlation coefficient, R2= 0.99, for DENV-2 and DENV-3; R2= 0.98, for DENV-4 and CHIKV; R2= 0.93, for DENV-1. The limits of detection were calculated to be 10-2 copies/µL for all viruses. The specificity and sensitivity of the newly developed mRT-PCR and mRT-qPCR were validated using positive serum samples collected in India and Burkina Faso. The sensitivity of mRT-PCR and mRT-qPCR are 91%, and 100% respectively. The specificity of both assays was 100% specific. mRT-PCR and mRT-qPCR assays are low cost and a combination of both will be a useful tool for arbovirus surveillance.

Chromoblastomycosis (CBM) and phaeohyphomycosis (FEO) are infections caused by melanized filamentous fungal agents, primarily found in tropical and subtropical regions. Both infections pose significant challenges for the correct identification of the causative agent due to their morphological similarity, making conventional methods of morphological analysis highly subjective. Therefore, molecular techniques are necessary for the precise determination of these species. In this regard, this study aimed to contribute to a new methodology based on PCR-RFLP for the identification of agents causing CBM and FEO. Sequences from the ITS region were used to identify potential restriction enzyme sites in silico, followed by in vitro validation using the selected restriction enzymes. The obtained results were compared with species identification through morphological analyses and sequencing. The results demonstrated that the PCR-RFLP applied in this study accurately identified two major agents of chromoblastomycosis, Fonsecaea pedrosoi and Fonsecaea monophora, as well as Cladophialophora bantiana and Exophiala dermatitidis, both causative agents of phaeohyphomycosis. In this context, the proposed assay can complement current methods for identifying these species, aiding in diagnosis, and contributing to the proper management of these infections.

Hepatocellular carcinoma (HCC) is characterized by uncontrolled cellular proliferation driven by aberrant signal transduction. Cells respond to potential carcinogenic signals by inducing cellular senescence (CS) as a defense mechanism. However, assessing CS levels in various tumors is challenging due to heterogeneity and the lack of universal CS markers. This study integrates single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from HCC samples to analyze gene expression profiles. HCC-specific senescence-related pathways are identified, and genes from these pathways distinguish molecular subtypes associated with senescence in HCC. These subtypes exhibit significant variations in biological and clinical attributes. A specific CS risk model is developed, revealing associations between CS scores and prognosis, clinical staging, immune infiltration, immunotherapy response, and drug sensitivity. The key gene G6PD is identified as a potential senescence-related target in liver cancer. Molecular experiments confirm the effective suppression of HepG2 cell proliferation, invasion, and migration upon G6PD knockdown. In summary, this analysis enhances our understanding of HCC-specific senescence molecular features and introduces a novel senescence-related biomarker, offering promising implications for future research.

In recent years, the emergence of cancer drug resistance is one of the crucial tumor hallmarks which is supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often results in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

In the last two decades, plant taxonomy has bloomed, following the development of a novel technique, namely DNA Barcoding. DNA barcodes are standardized sequences, ideally unique, coding or non-coding, either from the genome of the organism or from its organelles, that are used to identify/classify an organismal group; in short the method includes amplification of the DNA barcode, sequencing and comparison with a reference database containing the relevant sequences from different species. In plants, the use a universal DNA barcode, such as COI which is used in animals, has not been achieved so far. Several DNA barcodes from single loci as well as combinations of barcodes have been successfully used in various settings; additionally, as next generation sequencing becomes affordable, very long sequences- super barcodes, such as the chloroplast genome are being used successfully especially to distinguish between close species. In this review we summarize the work done on DNA barcoding in plants and discuss different approaches used so far.

Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that involve in regulation of cell proliferation, survival, and development. FGFR alterations including amplifications, fusions, rearrangements, and mutations can result downstream activation of tyrosine kinases leading to tumor development. Targeting those FGFR alterations has shown to be effective in cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid neoplasms and there are currently four FGFR inhibitors approved by the Food and Drug Administration (FDA). There have been developments of multiple agents targeting FGFR pathway including selective FGFR inhibitors, ligand traps, monoclonal antibodies, and antibody drug conjugates. However, most of these agents have variable and low responses with some intolerable toxicities and acquired resistances. This review will summarize previous clinical experiences and current developments of agents targeting FGFR pathway and discuss future directions of FGFR targeting agents.

The SARS-CoV-2 have caused a devastating pandemic of all times in the recent human history. However, there is a serious paucity in high quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types and associated outcomes in three phases of the pandemic. Using quality hospital data, we have investigated the SARS-CoV-2 fatality rates, profiles, and types of bacterial co-infections before, during, and after COVID-19 vaccinations. Out of 389 isolates used in different aspects, 298 was examined before and during the pandemic (n=149 before, n=149 during), death rates were 32% during compared to only 7.4% before pandemic with significant association (P value = 0.000000075). Death rate was 34% in co-infected (n = 170) compared to non-co-infected patients (n = 128) indicating a highly significant value (P value = 0.00000000000088). However, analysis of patients without other respiratory problems (n=28) indicated that among the remaining 270 patients, death was 30% in co-infected patients (n=150) and only 0.8% in non-coinfected (n=120) with high significant P value= 0.00000000076. The trending patterns of co-infections before, during, and after vaccinations showed a significant decline in Staphylococcus aureus with concomitant peaks in Gram-negatives in totals of (n= 149 before/n= 149 during): Klebsiella pneumonia (n = 11/49 before/during; E. coli n=10/24, A. baumannii n=8/25, and Ps. Aeruginosa n= 5/16, and S. aureus 13/1. Nevertheless, in post vaccination phase, (n= 91) gender-specific co-infections were examined for potential differences in susceptibility. Methicillin resistant S. aureus (MRSA) dominated both genders followed by E. coli in males and females with the latter gender showing higher rates of isolations in both species. Klebsiella pneumoniae declined to third place mostly in male patients. The drastic decline in K. pneumoniae and Gram-negatives post-vaccination strongly imply a potential co-protection in vaccines. Future analysis would gain more insights into molecular mimicry.

The COVID-19 pandemic has had a substantial impact on global health, notably the virus's association with autoimmune illnesses. Autoimmune illnesses occur when the immune system of the body targets healthy cells, causing damage and inflammation. The potential impact of COVID-19 on autoimmune disorders, the hazards of COVID-19 vaccinations for persons with autoimmune diseases, and the potential risks of COVID-19 vaccines are all discussed in this essay. COVID-19 can cause autoimmune illnesses by causing inflammation, organ and tissue damage, and molecular mimicry, in which the immune system mistakenly assaults healthy cells for the virus. However, not everyone infected with COVID-19 develops autoimmune disorders. While some research has found a link between COVID-19 and autoimmune illnesses, this does not always suggest causation. Other factors, such as genetics and environment, may also play a role in the emergence of autoimmune illnesses. COVID-19 can aggravate existing autoimmune disorders by causing the immune system to attack healthy cells, making management more difficult and increasing the risk of consequences. People with autoimmune disorders, on the other hand, may not be at a higher risk of severe COVID-19 than the general population. Some research has found that persons with autoimmune disorders are more likely to have severe COVID-19, whereas others have found no difference. COVID-19 vaccinations may represent dangers to persons with autoimmune illnesses since they contain antigens that can activate the immune system. Furthermore, due to their already overactive immune systems, some vaccines may not perform as well for people with autoimmune disorders, and some people with autoimmune diseases may have severe reactions to immunizations, producing inflammation and other symptoms. COVID-19 may not be any more hazardous to those with autoimmune illnesses than it is to the general population. The connection between COVID-19 and autoimmune disorders is complicated and under investigation. While some research implies that people with autoimmune disorders have a higher risk of severe COVID-19, others demonstrate no difference in death rates between them and the general population. There are also counterarguments that COVID-19 can induce and exacerbate autoimmune disorders, as well as worries about COVID-19 vaccine hazards for people who have autoimmune diseases. More research is required to completely understand the influence of COVID-19 on autoimmune illnesses, as well as the dangers and benefits of vaccinations for these people.

Allergen immunotherapy (AIT) with aeroallergens is the only disease modifying treatment for patients with different allergic conditions. Despite the effectiveness of AIT has been evidenced in both randomized controlled trials and real word studies, it remains underused in less than 10% of subjects with allergic rhinitis (AR) and/or asthma (A). We aimed to determine the current eligibility for house dust mite (HDM) AIT by means of a Precision Allergy Molecular Diagnosis (PAMD@) model in a selected cohort of youngsters with different allergic phenotypes according to the available evidence. A complex response to both HDM and storage mite allergens was depicted regardless of the subjects´ basal atopic condition. No solely specific IgE binding responses to Der p 1, Der p 2 and/or Der p 23 were found in the studied cohort. Despite patients with A and atopic dermatitis showed significantly higher serum titers to 6 mite allergens than subjects with AR, no specific molecular profile could be regarded as disease specific. Given the increasing complexity of specific IgE responses to the local prevailing aeroallergens, the identification and presence of such molecules are needed in commercially available AIT in the era of precision medicine.

The exact, non perturbative, response theory developed within the field of nonequilibrium molecular dynamics, also known as TTCF (Transient Time Correlation Function) applies to quite general dynamical systems. Its key element is called dissipation function, because it represents the power dissipated by external fields acting on the particle system of interest, whose coupling with the environment is given by deterministic thermostats. This theory has been initially developed for time independent external perturbations, and then it has been extended to time dependent perturbations. It has also been applied to dynamical systems of different nature, and to oscillator models undergoing phase transitions, which cannot be treated withe.g. linear response theory. The present work includes time dependent stochastic perturbations, in the theory, using the Karhunen-Loeve theorem. This leads to three different investigations of a given process. One in which a single realization of the stochastic coefficients is fixed, and averages are taken only over the initial conditions, as in a deterministic process. In the second, the initial condition is fixed, and averages are taken with respect to the distribution of stochastic coefficients. In the last investigations, one averages over both initial conditions and stochastic coefficients. We conclude illustrating the applicability of the resulting exact response theory with simple examples.

Hyperlipidemia (HLP) is a metabolic disease caused by abnormal lipid metabolism. Recently, the prevalence of HLP caused by poor dietary habits in the population has been increasing yearly. In addition, the current clinical use of lipid-lowering drugs has significant ameliorating effects on lipid levels but these actions are accompanied by certain side effects. However, bioactive marine substances have been verified to have various physiological activities such as hypoglycemic, antioxidant, antithrombotic, and effects on blood pressure. Therefore, marine biological sources of hypolipidemic active substances have attracted much attention. Moreover, some of the identified active substances have been found to induce hypolipidemia by inhibiting cholesterol synthesis and absorption, or by improving the composition of intestinal microorganisms. This article introduces the sources and classification of marine-derived hypolipidemic active substances, and describes current progress in research on the main mechanism of the hypolipidemic activity of these substances.

We measured the anelastic, dielectric and structural properties of the metal-free molecular perovskite (ABX$_{3}$) (MDABCO)(NH$_{4}$)I$_{3}$, which has already been demonstrated to become ferroelectric below $T_{\text{C}}=$ 448~K. Both the dielectric permittivity measured in air on discs pressed from powder and the complex Young's modulus measured on resonating bars in vacuum show that the material starts deteriorating with loss of mass just above $T_{\text{C}}$, introducing defects and markedly lowering $T_{\text{C}}$. The elastic modulus softens of 50\% when heating through the initial $T_{\mathrm{C}}$, contrary to usual ferroelectrics, which are stiffer in the paraelectric phase. This suggests improper ferroelectricity, where the primary order parameter of the transition is not the electric polarization, but the orientational order of the MDABCO molecules. The degraded material presents thermally activated relaxation peaks in the elastic energy loss, whose intensities increase together with the decrease of ~$T_{\mathrm{C}}$. The peaks are much broader than pure Debye, due to the general loss of crystallinity, also apparent from X-ray diffraction, but their relaxation times have parameters typical of point defects. It is argued that the major defects should be of the Schottky type, mainly due to the loss of (MDABCO)$^{2+} $ and I$^{-}$, leaving charge neutrality, and possibly also (NH$_{4}$)$^{+}$ vacancies. The focus is on an anelastic relaxation process peaked around 200~K at $\sim 1$~kHz, whose relaxation time follows the Arrhenius law with $\tau $$_{0}$~$\sim $\ $10^{-13}$\ s and $E\simeq 0.4$~eV. This peak is attributed to I vacancies (V$_{\text{X}}$) hopping around MDABCO vacancies (V$_{\text{A}}$) and its intensity presents a peculiar dependence on temperature and content of defects. The phenomenology is thoroughly discussed in terms of lattice disorder introduced by defects and of partition of V$_{\text{X}}$ among sites that are far from and close to the cation vacancies. A method is proposed for calculating the relative concentrations of V$_{\text{X}}$, that are untrapped, paired with V$_{\text{A}}$ or forming V$_{\text{X}}$--V$_{\text{A}}$--V$_{\text{X}}$ complexes.

Avipoxvirus (APV), a linear dsDNA virus belonging to the subfamily Chordopoxvirinae of the family Poxviridae, infects more than 278 species of domestic and wild birds. It is responsible for causing the avian pox disease, which is characterized by its cutaneous and diphtheric forms. With a high transmission capacity, it can cause high economic losses and damage to the ecosys-tem. Several diagnostic methods are available and vaccination of birds can be an effective pre-ventive measure. To update the molecular characterization and phylogenetic analysis of viruses isolated in Portugal between 2017 and 2023, ten APV-positive samples were analyzed. A P4b gene fragment was amplified by PCR and the nucleotide sequence of the amplicons was deter-mined by Sanger sequencing. The sequences obtained were aligned using ClustalW, and a max-imum likelihood phylogenetic tree was constructed. With this study, it was possible to verify that the analyzed sequences are distributed in subclades A1, A2, B1, and B3. Since some of them are quite similar to others from different countries and obtained in different years, it is possible to conclude that there have been several viral introductions in Portugal. Finally, it was possible to successfully update the data on avipoxviruses in Portugal.

The dengue virus (DENV) is an arbovirus belonging to the Flaviviridae family; the species comprises four antigenically distinct serotypes (DENV–1, DENV–2, DENV–3, and DENV–4), which are further subdivided into genotypes. The virus is transmitted to humans through mosquito bites, primarily from the Aedes spp. genus. Dengue is endemic in various parts of the world, including tropical and subtropical regions of Asia, Latin America, Africa, and Oceania. In Brazil, the state of Tocantins, located in north-central Brazil, has experienced a significant number of arboviral disease cases, particularly dengue. This study aimed to monitor DENV circulation within the state by conducting full genome sequencing of viral genomes recovered from 61 patients between June 2021 and July 2022. During this period, both DENV-1 and DENV-2 serotypes were identified. Our findings confirm the circulation of DENV serotypes 1 and 2 in Tocantins, affecting males and females equally, with younger age groups (4 to 43 years old) being the most susceptible. Phylogenetic analysis revealed that the circulating viruses belong to DENV–1 genotype V American and DENV–2 genotype III Southeast Asian/American. The Bayesian analysis of DENV-1 Genotype V sequenced here is closely related to genomes previously sequenced in the state of São Paulo. Regarding DENV-2 genotype III genomes, these are clustered in a distinct, well-supported subclade, along with previously reported isolates from the states of Goiás and São Paulo. In both cases, our results suggest that multiple introductions of these genotypes occurred in the Tocantins state. This observation highlights the significant impact of major population centers in Brazil on virus dispersion, including other Latin-American countries and the USA. In the SNP analysis, DENV-1 displayed 122 distinct missense mutations, while DENV-2 had 44, with significant mutations predominantly occurring in the envelope and NS5 proteins. The analyses performed here reveal the concomitant circulation of distinct DENV-1 and -2 genotypes in some Brazilian states, underscoring the dynamic evolution of the DENV and the ongoing significance of surveillance efforts in supporting public health policies.

In this paper we present methodology for precise calibration of Molecular Beam Epitaxy (MBE) growth process and achieving run to run stability of growth parameters. We present the analysis of the influence of fluxes stability during the growth of long wavelength quantum cascade laser structures designed for the range λ ~ 12–16 µm on wavelength accuracy with respect to desired emission wavelength. The active region of the lasers has a complex structure of nanometer thickness InxGa1-xAs/InyAl1-yAs superlattice. As a consequence, the compositional and thickness control of the structure via bulk growth parameters is rather difficult. To deal with this problem we employ methodology based on double-superlattice test structures, that precede the growth of the actual structures. The test structures are analyzed by high-resolution X-ray diffraction which allows to calibrate the growth of the complex active region of quantum cascade laser structures. We also study theoretically the effect of individual flux changes on emission wavelength and gain parameters of the laser. The results of simulations allow for determination of flux stability tolerance, preserving acceptable parameters of the laser and provide means of emission wavelength control. The proposed methodology was verified by the growth of laser structures for emission at around 13.5 μm.

Background: Diabetic patients are more likely to experience morbidity and mortality as a result of microvascular complications such as retinopathy, neuropathy, nephropathy, and stroke. There are many synthetic anti-diabetic agents available which are expensive and have undesirable pathological effects. Thus, it is essential to look for cost-effective, natural, and safe antidiabetic agents. The aim of this study was to screen phytoconstituent and evaluate the in-vitro and in-silico α-amylase inhibitory activity of ethanolic extract of Adhatoda vasica leaves. Method: The extraction of Adhatoda vasica leaves was performed with ethanol through Soxhlet extraction process. Different concentrations (0.1 mg/ml to 1 mg/ml) of ethanolic extract, Acarbose, and Sitagliptin, were prepared and all concentrations were evaluated for α-amylase inhibitory activity through the spectrophotometric method. Molecular docking (AutodockVina 1.2.0) and toxicity profiling (SToPToX web server) studies were performed. Results: The plant extract showed highest inhibition of α-amylase (56.763±0.0035) at a concentration of 1 mg/ml. This inhibitory activity was supported by the in-silico study. Vasicoline (C5) and quercetin (C9), active constitute of plant Adhatoda vasica, showed the best binding energy of 8.3 and 8.0 Kcal/mol respectively with α-amylase enzyme (PDBID: 4W93). Toxicity study revealed the safety profile of plant extract. Conclusion: It was concluded that Adhatoda vasica leaves possess some bioactive compounds which are responsible for controlling blood glucose levels and its identification, purification, and isolation may lead to the development of newer therapeutic agent with lesser side effects.

Norepinephrine (NE) uptake through the NE transporter (NET) is the primary mechanism to ter-minate the action of this neurotransmitter. Dysregulation of brain NE levels is associated with various conditions, including attention deficits, depression, and Alzheimer's disease. Recently, we identified an interaction between the related dopamine (DA) transporter (DAT) and G protein βγ subunits. Activation of Gβγ in cells and brain slices leads to DA efflux through DAT. However, the potential interaction between Gβγ and NET has not been reported. Here, we used a combina-tion of molecular modeling approaches to elucidate the structural details of the NET/Gβγ inter-action, supported by experimental evidence. Through 1.5µs of molecular dynamic simulation, we observed a favorable NET/Gβγ interaction mediated by the intracellular carboxy terminus of NET. As a consequence, the binding energy of NE for NET also changes resulting in alterations of the electrostatic profile of NET. We propose that these changes mediate the NE efflux effect. Fi-nally, we provide experimental evidence demonstrating that Gβγ physically interacts with NET and that the Gβγ activator mSIRK induces NE efflux through the transporter. These findings identified a novel interaction between Gβγ and NET and highlighted its potential implications in the regulation of NE neurotransmission and associated disorders.

The chemical feedback between building blocks in templated polymerization of diblock copolymers and their consecutive micellization was studied for the first time by means of coarse-grained molecular dynamics simulations. Using a stochastic polymerization model, we were able to reproduce the experimental findings on the effect of chemical feedback on the polymerization rates at low and high solution concentrations. The size and shape of micelles were computed using a newly development software in python conjugated with graph theory. In full agreement with the experiments, our simulations revealed that micelles formed by the templated micellization are more spherical and have lower radius of gyration than those formed by the traditional two-step micellization method. Understanding the underlying mechanisms in templated reaction/assembly of polymers will help for rational design of new synthetic supramolecular materials.

The amino acid composition of the active site in an enzyme is influential on its substrate selectivity. For CYP2E1, the role of PHE residues in the formation of effective orientations for its activity toward aromatic substrates remains unclear. In this study, molecular docking and molecular dynamics analysis were performed toward the interactions between PHEs in the active site of human CYP2E1 and various aromatic compounds as confirmed CYP2E1 substrates. The results indicated that the orientation of 1-methylpyrene (1-MP) in the active site was highly modulated by the PHEs, PHE478 contributing to the binding free energy most significantly. Furthermore, by building a random forest model the relationship between each of 19 molecular descriptors of PCB congeners (from molecular docking, quantum mechanics, and physicochemical properties) and established human CYP2E1-dependent mutagenicity of a series of polychlorinated biphenyls (PCBs), which have been proven to be human carcinogens and endocrinal disrupters, was investigated. The presence of PHEs did not appear to significantly modify the electronic or structural feature of each bound ligand (PCB), instead, the flexibility of the molecular conformation of PHEs contributed substantially to the effective binding energy and orientation. It is supposed that PHE residues adjust their own conformation to permit a suitable space for the ligand binding and form an orientation favorable for a biochemical reaction. This study has provided some insights into the role of PHEs in guiding the interactive adaptation of the active site of human CYP2E1 for the binding and metabolism of aromatic substrates.

Antibiotic resistance among bacterial pathogens is recognized as a major threat to human health worldwide. The emergence of multidrug-resistant bacteria can also be found in the community settings, apart from hospital environment, which indicates that reservoirs of antibiotic resistance genes do exist outside the hospital. The growth of antibiotic resistance is a consequence of bacterial adaptations in response to selective pressures. To survive in this hostile environment, bacteria develop defence mechanisms such as chemical modification of antibiotics, enzyme-catalysed antibiotic degradation, altered permeability, antibiotic efflux, mutation of target sites and biofilm formation, resulting in resistance to nearly all currently available antibiotics used in the clinical practice. The present review summarizes insights into the molecular mechanisms underlying the antibiotic resistance which is useful for planning strategies to combat antibiotic resistance and devise innovative therapeutic tools to fight against multidrug-resistant bacterial species.

;Yams are economic and medicinal crops with a long growth cycle, spanning between 9-11 months due to the prolonged tuber dormancy. Tuber dormancy has constituted a major constraint in yam production and genetic improvement. In this study, we performed non-targeted comparative metabolomic profiling of tubers of two white yam genotypes, (Obiaoturugo and TDr1100873), to identify metabolites and associated pathways that regulate yam tuber dormancy using gas chromatography-mass spectrometry (GC-MS). Yam tubers were sampled between 42 days after physiological maturity (DAPM) till tuber sprouting. The sampling points include 42-DAPM, 56-DAPM, 87DAPM, 101-DAPM, 115-DAPM, and 143-DAPM. A total of 949 metabolites were annotated, 559 in TDr1100873 and 390 in Obiaoturugo. 39 differentially accumulated metabolites (DAMs) were identified across the studied tuber dormancy stages in the two genotypes. 27 DAMs were conserved between the two genotypes, whereas, 5 DAMs were unique in the tubers of TDr1100873 and 7 DAMs were in the tubers of Obiaoturugo. The differentially accumulated metabolites (DAMs) spread across 14 major functional chemical groups. Amines and biogenic polyamines, amino acids and derivatives, Alcohols, flavonoids, alkaloids, phenols, esters, coumarins and phytohormone positively regulated yam tuber dormancy induction and maintenance, whereas, fatty acids, lipids, nucleotides, carboxylic acids, sugars, terpenoids, benzoquinones, and benzene derivatives positively regulated dormancy breaking and sprouting in tubers of both yam genotypes. Metabolite set enrichment analysis (MSEA) revealed that 12 metabolisms were significantly enriched during yam tuber dormancy stages. Metabolic pathway topology analysis further revealed that six metabolic pathways (linoleic acid metabolic pathway, phenylalanine metabolic pathway, galactose metabolic pathway, starch and sucrose metabolic pathway, alanine-aspartate-glutamine metabolic pathways and purine metabolic pathway) exerted significant impact on yam tuber dormancy regulation. This result provides vital insights into molecular mechanisms regulating yam tuber dormancy.

The outbreak of Coronavirus, as well as its emerging potential consequences, has become a global challenge worldwide, demanding effective and controlled therapeutic strategies. Potential drug candidates could achieve that with minimal toxicity. The current investigation selected 2-Deoxy-D-glucose prescribed by Defense Research and Development Organization (DRDO), India. The derivative and modified form was tested through in silico analysis against COVID-19 main protease complex with N3 inhibitor. The derived form of 2-Deoxy-D-glucose was generated by replacing the hydroxy group with a hydrogen atom, and Cypate 2-Deoxy-D-glucose was chosen as a derivative against the COVID-19 main protease complex. A molecular docking approach was adopted to identify the stable and competent form among the modified and derivative forms of 2-Deoxy-D-glucose based on binding energy. By further promoting the stabilized complex, these compounds' toxicity was also scrutinized through ADMET analysis to predict the potential candidate. The current investigation suggested that the modified version of 2-Deoxy-D-glucose was more stable with minimal toxicity against COVID-19 main protease.

The permeation of dioxin-like pollutants, namely, chlorinated dibenzodioxins and dibenzofurans, through lipid membranes has been simulated using classic molecular dynamics (CMD) combined with the umbrella sampling approach. The most toxic forms of chlorinated dibenzodioxin and dibenzofuran, 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF), and a dioleyl-phosphatidylcholine (DOPC) lipid membrane of 50 Å wide have been chosen for our study. The free energy profile shows the penetration process is largely favoured thermodynamically (DG≈-12 kcal/mol), with a progressively decrease of the free energy until reaching the energy minima at distances of 8Å and 9.5Å from the centre of the membrane for, respectively, TCDD and TCDF. At the centre of the membrane, both molecules display subtle local maxima with free energy differences of 0.5 and 1 kcal/mol with respect to the energy minima for TCDD and TCDF, respectively. Furthermore, the intermolecular interactions between the molecules and the lipid membrane have been characterized at the minima and the local maxima using hybrid quantum mechanics/molecular mechanics energy decomposition analysis (QM/MM-EDA). Total interaction energies of -17.5 and -16.5 kcal/mol have been found at the energy minima for TCDD and TCDF, respectively. In both cases, the dispersion forces govern the molecule-membrane interactions, no significant changes have been found at the local maxima, in agreement with the classical free energy profile. The small differences found in the results obtained for TCDD and TCDF point out the adsorption and diffusion processes through the cell membrane are not related to the different toxicity shown by these pollutants.

2-Methylquinazolin-4(3H)-one was prepared by reaction of anthranilic acid, acetic anhydride and ammonium acetate. The reaction of 2-methylquinazolin-4(3H)-one with N-aryl-2-chloroacetamides in acetone in the presence of potassium carbonate gave nine N-aryl-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide compounds. The structures of these compounds were elucidated on the basis of their IR, 1H-NMR, 13C-NMR and HR-MS spectral data. These synthesized compounds containing the 2-methyl-3,4-dihydroquinazolin-4-one moiety exhibited excellent activity against Aedes aegypti mosquito larvae with LC50 values in the range of 2.085-4.201 μg/mL after 72 h exposure. Interestingly, these compounds did not exhibit toxicity to the non-target organism Diplonychus rusticus. In silico molecular docking revealed acetylcholine binding protein (AChBP) and acetylcholinesterase (AChE) to be potential molecular targets. These data indicated the larvicidal potential and environmental friendliness of these N-aryl-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide derivatives.

Antarctica is one of the most inhospitable continents on the planet, with lichens and mosses being the most common terrestrial organisms in ice-free areas. Antarctica is represented by only two species of Angiosperms, Deschampsia antarctica Desv. (Poaceae) and Colobanthus quitensis (Kunth) Bartl. (Caryophyllaceae). In this study, we characterized fungi isolated from the leaves of this grass species. The fungi were isolated from 4 individual plants from Half Moon Island (246 leave fragments investigated), and 7 from King George Island - Keller Peninsula (with 111 leave fragments investigated) Antarctica. Neoascochyta paspali, Phaeosphaeria elongata, Pyrenophora cf. chaetomioides and Alternaria sp. were associated with the plant and identified through analysis of the sequences of the internal transcribed spacer region (ITS) of the rDNA and nuclear ribosomal large subunit rRNA gene (LSU) as well as macro and micro-morphological characteristics. The isolates showed a better growth rate ranging from 10–20°C. An interesting result was that the fungi are already recognize as both plant pathogens and endophytic fungi. The results demonstrate that D. antarctica is an interesting fungal source. Those species might provide important information about the relationship on the endemic Antarctic biota.

Whole-genome sequencing has advanced our understanding of the population structure of the pathogenic species complex Cryptococcus gattii, which has allowed for the phylogenomic specification of previously described major molecular type groupings and novel lineages. Recently, isolates collected in Mexico in the 1960s were determined to be genetically distant from other known molecular types and were classified as VGVI. We sequenced four clinical isolates and one veterinary isolate collected in the southwestern U.S. and Argentina during 2012-2021. Phylogenomic analysis groups these genomes with those of the Mexican VGVI isolates, expanding VGVI into a clade and establishing this molecular type as a clinically important population. These findings also potentially expand the known Cryptococcus ecological range with a previously unrecognized endemic area.

Molecular communication (MC) is a promising bio-inspired paradigm for exchanging molecule information among nanomachines. This paper proposes a synchronisation-assist photolysis MC system that aims to transmit the bio-sensing signal of the tumour microenvironment, facilitated by mitigating redundant molecules for improved bit error rate (BER) performance. Benefits from bio-compatible MC, biosensors could transmit bio-sensing signals of the tumour in $vivo$ instead of converting them to electrical signals. Due to diffusion motion's slow and stochastic nature, inter-symbol interference (ISI), resulting from previous symbols' residual information molecules, inevitably occurs in diffusion-based MC. ISI is one of the challenges in diffusion-based MC, which significantly impacts signal detection. Inspired by on-off keying (OOK) modulation, the proposed modulation implements a switch of molecules and light alternatively. The light emitted is triggered by a synchronisation signal, and the photolysis reactions could reduce the redundant molecules. An expression for the relevant channel impulse response (CIR) is derived from a hybrid channel model of diffusion and photolysis-reaction. This paper implements the maximum posterior estimation scheme to find the optimal decision threshold and analysis the BER performance in terms of different time intervals of the system. Numerical simulations demonstrate that the proposed method can improve the channel capacity and BER performance. We believe that our work may pave the way for MC application in bio-sensing.

Systematics plays the most crucial role in biodiversity conservation which is at stake due to anthropogenic activities and environmental degradations. The ever-increasing decline of classical taxonomic expertise drives the need to develop molecular marker-based tools for quick, efficient, and reliable detection of organisms, to assess their ecological impacts for deepening our understanding of systematic and evolutionary relationships between organisms which is central to biology. The pace of alpha taxonomy has quickened by its integration with an increasingly fashionable and novel concept called DNA barcoding which utilizes a short genetic marker or barcode to categorize species for enhanced biodiversity assessment. As a supplementary but not complete alternative of systematics research, DNA barcoding, however, not error-free, brings precision in identification by solving existing problems of classical taxonomy and phylogenetics, irrespective of the growth stage of organisms, particularly for known taxa rather than unknown ones. Mitochondrial gene Cytochrome C Oxidase 1 (COI) serves as a universal animal barcode but there is no such universal barcode for plants and developing a suitable one is more challenging. With the recent advancement of Next Generation Sequencing (NGS), DNA metabarcoding technology is advancing rapidly. Still, ambiguity and error prevail with the correct identification of species due to some problems. After extensive analysis of the existing DNA barcoding papers, this review discusses commonly used DNA barcodes in plants and animals, their roles, advantages, limitations to solve existing problems of conservation biology and add the author’s views and recommendations.

Metamorphosis is a critical process for most anurans to transition from water to land. The appearance of air-breathing lungs occurs during the change in oxygen medium from water to air. Revealing the structural construction and molecular switches of lung organogenesis is essential to understand the realization of air-breathing function. In this study, histology and transcriptomics were combinedly conducted to explore these issues in Microhyla fissipes lungs during metamorphosis. During the pro-metamorphic phase, histological structure improving of the alveolar wall was accompanied by robust substrate metabolism and protein turnover. The lungs, at the metamorphic climax phase, are characterized by an increased number of cilia in the alveolar epithelial cells and collagenous fibers in the connective tissues, corresponding to the transcriptional upregulation of cilia and extracellular matrix-related genes. The post-metamorphic lungs strengthen the contracting function, as suggested by the thickened muscle layer and the upregulated expression of genes involved in muscle contraction. The blood–gas barrier is fully developed in adult lungs whose transcriptional features are tissue growth and differentiation regulation and immunity. Importantly, significant transcriptional switches of pulmonary surfactant protein and hemoglobin facilitate air-breathing. Our results illuminated four key steps of lung development for amphibians to transition from water to land.

ATP Synthase is an essential molecule in cell and molecular biology. It is responsible for the production of ATP during cellular respiration, a molecule that provides the energy required to drive a number of cellular processes. In this paper, I explore the rotational physics of ATP Synthase’s rotor, a part of the protein that spins during the production of ATP. Firstly, I discuss some elementary rotational kinematics of the rotor. I then derive two alternate formulations for the total linear acceleration of the rotor. Finally, I derive formulas for the moment of inertia, angular momentum, net torque, and kinetic energy of the rotor. Through this, I hope to provide a theoretical and mathematical insight into the mechanics of ATP Synthase during the production of ATP.

The exploration of alternative antimalarial therapeutics is a requisite for the emergence of resistance against Artemisinin. Considering the required cost and time length of classical small molecule drug discovery process, phytochemical screening of traditionally used medicinal plant which are repertoire of active compounds with antimalarial activity has become popular. To investigate the antimalarial property of traditionally used medicinal plants, a number of Erythrina spp have been reviewed systematically where less studied E. fusca has been selected for further analysis. Phytochemical investigation yielded five compounds namely; Phaseolin, Phytol, β-amyrin, Lupeol, and Stigmasterol. In-vitro antimalarial drug sensitivity HRP-II ELISA was carried out against chloroquine (CQ) sensitive 3D7 and CQ-resistant Dd2 strains. Extracts showed significant antimalarial activity against 3D7 and Dd2 strains (IC₅₀ 4.94 – 22 µg/mL) and these compounds have been reported here for the first time. Molecular docking analysis showed high binding energy (−9.0 ± 0.32 kcal/mole) indicating high degree of interaction between Phaseolin and 14 clinically important Plasmodium falciparum proteins at the active site. Stable interaction was also observed between ligand and protein from molecular dynamics simulation analysis with high free energy (−75.156 ± 11.459) that substantiates the potential of Phaseolin as an antimalarial drug candidate.

A cryptic invader of the genus Persicaria is recently increasing in the damper, northern parts of La Palma and Gran Canaria in the Canary Islands (Spain) and locally behaves as an invasive species. Examination of historical herbarium specimens showed this species to be present in Gran Canaria since the 1960’s and the same probably applies to La Palma. Up to now, this species had been assigned to the Old World weed P. maculosa. However, morphologically these plants clearly correspond with P. hydropiperoides, a common and widespread weed native to the New World, and morphologically similar indeed to P. maculosa. Diagnostic features for these two species, as well as for another similar species (P. decipiens, originally described from the Canary Islands), are compared, thoroughly discussed and copiously illustrated. The current distribution, ecology and naturalization status of P. hydropiperoides in the Canary Islands are also assessed. The variability of P. hydropiperoides is discussed, more precisely the taxonomic position of a southern ‘race’ of it that is sometimes referred to as a distinct species, P. persicarioides. In addition to our morphology-based study, a molecular phylogenetic analysis has been conducted on the nuclear ITS region and the plastid DNA region trnL-F.

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein’s amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein-protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.

Silybum Marianum, is a plant belonging to the family Asteraceae. For many centuries it has been used a natural remedy for many diseases like Liver and Biliary tract diseases. It is effective as an anti-oxidant and is used in a variety of diseases. This study was conducted to check the effects of Silybum Marianum on PARP protein (4UND protein).The Molecular Docking techniques was chosen to check the effects of different chemical constituents of Silybum marianum on DNA damaging protein. For this purpose, different PARP inhibitor drugs were taken as standard. The Molecular Docking of the chemical constituents of Silybum marianum was performed using 4UND protein with the help of PyRx software along with BIOVIA Drug Discovery studio software. The result of molecular docking showed that some of the chemical constituent have higher binding affinity than standard PARP inhibitor drugs.

Muscle is one of the most critical organs for mammals, which governs multiple movement and physiological functions. Circular RNA (circRNA) is a kind of novel endogenous RNA without 5'-Caps and 3'-poly(A) structures formed by pre-mRNA's back-splicing. RNA binding proteins (RBPs) control the production and degradation of circRNA, help nucleus-cytoplasm transport and locate circRNA, and regulate circRNA translation. Therefore, circRNAs and the chaperoned RBPs play critical roles in muscle growth, development, and disease progression. In this review, we systematically characterize the possible molecular mechanism of circRNA-protein interactions. Also, we summarize the latest researches on circRNA-protein interactions in muscle development and diseases. Besides, we provide several valid prediction methods and experimental verification approaches. Our review reveals the importance of circRNAs and their protein chaperones and provides a reference for further study in this field.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC), and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). Total 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. The 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP) were found to have difference in gene expression in intestinal- and diffuse-type GC. Total 463 direct relationships with 3 molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathways networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

Brucella abortus is a facultative intracellular Gram-negative bacterium that causes chronic persistent infections in humans and livestock. In this study, conventional bio-typing, multiple-locus variable-number tandem repeat analysis (MLVA), and whole-genome sequencing-single-nucleotide polymorphism (WGS-SNP) were used to investigate the molecular epidemiology characteristics of Brucella abortus strains in China and their relationships to world lineages. A total of 100 strains were collected from 1953 to 2013, suggesting that B. abortus circulated in China in the past five decades. Moreover, most strains were mainly distributed in the northwest area. During this period, seven biovars were found, indicating that B. abortus displayed a high diversity of biovars and that the main epidemic areas are in the northern provinces. Strains have high genetic diversity, and bruce07 is the most helpful locus for genotyping of this population. Moreover, 17 MLVA-11 genotypes were found; 13 of them are of known genotypes and four are unassigned genotypes, indicating that B. abortus in this study had several geographic origins. Still, strains from unassigned genotypes may originate from China. Many shared MLVA-16 genotypes were observed in strains from the same provinces in Northern China, which confirmed a brucellosis outbreak within northern regions. WGS-SNP analysis showed that eight Chinese strains formed a ladder-like phylogram (C. Ⅶ) with strains from nine countries, including Uganda, Iraq, Russia, Georgia, Spain, Italy, Egypt, Mongolia, and China; strains were introduced to these countries from a single source. Notably, Chinese strains were closely related to strains from Russia and Mongolia; frequent animal (cattle) trade and exchanges may promote this process. We will provide new and insightful information for strength surveillance and control of B. abortus brucellosis in China.

The natural products and conventional chemotherapeutic drugs are believed to increase the cure rates of anti-cancer treatment while reducing their toxicity. The current study investigates the cytotoxic and apoptogenic effects of bioactive compounds from Monotheca buxifolia on Hep G2 cell lines. The effect on the viability of Hep G2 cells was evaluated by MTT assay; Morphological changes were studied, the apoptotic activity was demonstrated through Annexin-V-FITC/ PI, a molecular dynamics simulation study was conducted to explore the binding pattern of the compounds in the active site of the PPRAδ protein. The isolated compounds lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of hepatocellular cancer cells, as determined by MTT assay and annexin V-FITC/PI. The IC50 value for lauric acid was 56.4584 ± 1.20 µg/ml, that for oleanolic acid was 31.9421 ± 1.03 µg/ml, and that for bis(2-ethylhexyl) phthalate was 83.8019 ± 2.18 µg/ml. After 24 h of treatment, 29.5% of Hep G2 cells treated with lauric acid, 52.1% of those treated with oleanolic acid, and 22.4% of those treated with bis(2-ethylhexyl) phthalate were apoptotic. Morphological assay and Hoechst staining microscopy revealed the morphological alterations of cell membrane accompanied by nuclear condensation after treatment. The high fluctuation indicates the high potency and adopting various interactions, and vice versa, the oleanolic acid showed highly residues fluctuation, which remains stable in the active site of PPARδ protein and involved in various interactions while remaining locally fluctuated in the binding site the other two compounds. In conclusion, a significant apoptogenic effect was exhibited by lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate against HepG2 cells in inducing apoptosis. Our findings indicate that these bioactive compounds hold promise as potential therapeutic for hepatocellular carcinoma.

Mutation in the ethionamide (ETH) activating enzyme, EthA, is the main factor determining resistance to this drug, used to treat TB patients infected with MDR and XDR Mycobacterium tuberculosis isolates. Many mutations in EthA of ETH resistant (ETH-R) isolates have been described but their roles in resistance remain uncharacterized, partly because structural studies on the enzyme are lacking. Thus, we took a two-tier approach to evaluate two mutations (Y50C and T453I) found in ETH-R clinical isolates. First, we used a combination of comparative modeling, molecular docking, and molecular dynamics to build an EthA model in complex with ETH that has hallmark features of structurally characterized homologs. Second, we used free energy computational calculations for the reliable prediction of relative free energies between the wild type and mutant enzymes. The ΔΔG values for Y50C and T453I mutant enzymes in complex with FADH₂-NADP-ETH were 3.34 (+/−0.55) and 8.11 (+/−0.51) kcal/mol, respectively, compared to the wild type complex. The positive ΔΔG values indicate that the wild type complex is more stable than the mutants, with the T453I complex being the least stable. These are the first results shedding light on the molecular basis of ETH resistance, namely reduced complex stability of mutant EthA.

COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target. This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta'-(4-Methoxy-1,3- phenylene)bis(2'-hydroxy-4',6'-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of D-amino acid substituted peptides, a variety of computational methods were applied. Ten prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple meteorite, spark discharge, and hydrothermal vent studies. Some previously reported early Earth polypeptide analogs were focused on in this study. Tripeptides composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in the minimal folding energy of peptides, while the chemical classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show a significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed ten prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Primordial simple polypeptides were modeled to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. We found peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets. Intriguingly, amongst 129 D-amino acid residues, mutation sensitivity profiles presented that the ratio of more to less stable residues was about 1. In conclusion, some combinations of a mixture of L- and D-amino acids can potentially act as essential building blocks of life.

Molecular visualisation is fundamental in the current scientific literature, textbooks and dissemination materials, forming an essential support for presenting results, reasoning on and formulating hypotheses related to molecular structure. Visual exploration has become easily accessible on a broad variety of platforms thanks to advanced software tools that render a great service to the scientific community. These tools are often developed across disciplines bridging computer science, biology and chemistry. Here we first describe a few Swiss Army knives geared towards protein visualisation for everyday use with an existing large user base, then focus on more specialised tools for peculiar needs that are not yet as broadly known. Our selection is by no means exhaustive, but reflects a diverse snapshot of scenarios that we consider informative for the reader. We end with an account of future trends and perspectives.

Cysteine cathepsins, a class of proteinaceous enzymes, regulate a wide variety of metabolic processes in human including protein breakdown and turnover and immune functions. Eleven cysteine cathepsins have been identified so far and a wide array of studies related to identifying their specific functions, regulation and distribution patterns in tissues have been conducted. However, in recent past, the association of cysteine cathepsins in occurrence and progression of cancers have been identified and this has caused unrest in scientists triggering them to investigate the physiology, biochemical pathways and interactions of these cathepsins in cancer metastasis and therefore has become a noteworthy topic of intensive research. This review focusses and collects together the published work on molecular functional and structural characterization studies that have been done so far on in vitro expression of genes encoding for cysteine cathepsins in the Escherichia coli bacterial expression system. Accordingly, it was found out that all cathepsins except for cathepsins K, C, H, X and W have been expressed this way and the majority of them were found to be expressed in E. coli BL21(DE3) pLysS expression host via pET3 expression vector. In addition, it was also noted that in most of the expression studies, the substrate that was used to validate the enzymatic activity of the recombinant enzyme that was produced was a cysteine residue along with a benzyloxy-carbonyl salt. Through this review, the authors suggest that there is a very high need that all cysteine cathepsins need to be characterized both structurally and functionally on a molecular platform to better understand their interactions including the biochemical pathways. It is also momentous that the mass production of the recombinant forms of these enzymes are facilitated via expression in such bacterial expression systems and in turn, would also provide a strong platform for the development and progression of studies related to human physiology including oncological studies such as cancer metastasis. Moreover, as per biochemical features of the enzymes that could be identified, the production of efficient inhibitors or inducers as per the necessity to improve health and promote wellbeing among the mankind could be facilitated.

Collisions of low energy electrons with molecules are important for understanding many aspects of the environment and technologies. Understanding the processes that occur in these types of collisions can give insights into plasma etching processes, edge effects in fusion plasmas, radiation damage to biological tissues and more. A radical update of the previous expert system for computing observables relevant to these processes, Quantemol-N, is presented. The new Quantemol Electron Collision (QEC) expert system simplifyies the user experience, improving reliability and implements new features. The QEC GUI interfaces the Molpro quantum chemistry package for molecular target setups and to the sophisticated UKRmol+ codes to generate accurate and reliable cross-sections. These include elastic cross-sections, super elastic cross-sections between excited states, electron impact dissociation, scattering reaction rates, dissociative electron attachment, differential cross-sections, momentum transfer cross-sections, ionization cross sections and high energy electron scattering cross-sections. With this new interface we will be implementing dissociative recombination estimations, vibrational excitations for neutrals and ions, and effective core potentials in the near future.

In this research, atomistic molecular dynamics simulations are combined with mesoscopic phase-field computational methods in order to investigate phase-transformation in polycrystalline Aluminum microstructure. In fact, microstructural computational modeling of engineering materials could help to optimize their mechanical properties for industrial applications (e.g. directional solidification for turbine blades). As a result, a multiscale modeling approach is developed to find a relation between manufacturing variables (e.g. temperature) and microstructural properties of crystalline materials (e.g. grain size), which could be used to develop an advanced manufacturing process for sensitive applications. The results show that atomistic modeling of grain growth could be used as a first-principle approach in order to study phase transformation's kinetics, which could capture morphology of polycrystalline materials more accurately. On the other hand, phase-field mesoscopic approach needs less computational efforts, but still it relies on semi-empirical data to capture accurate phase transformation regimes, which makes this approach suitable for rapid examining of new manufacturing conditions as well as its effects on microstructural properties of polycrystalline materials.

We have synthesized quinoxaline analogs (1-25), characterized by 1HNMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent analog among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure- activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

Bufadienolides-like chemicals, which mostly composed the active ingredient of Chansu, had been widely discovered to possess anti-inflammatory, tumor-suppressing and antipain activity, but the mechanisms of action were not clearly illuminated. In this research, in order to explore the potential mechanism of bufadienolides-like chemicals on breast cancer, a serious of bioinformatics analysis, included (1) differentially expressed genes identification combined with gene set variation analysis, (2) tissue specific co-expression network construction, (3) differentially regulated sub-networks detection with disease phenome, (4) hub gene selection and it’s relation to survival probability, and (5) similar small molecule detection were performed with gene expression profiles of bufadienolides-like chemicals. Results indicated bufadienolides-like chemicals had the most same target with valproic, estradiol and etc, could disturbed the pathways in RNA splicing, apoptotic process, cell migration, extracellular matrix organization, adherens junction organization, synaptic transmission, Wnt signaling, AK-STAT signaling, BMP signaling pathway and unfolded protein response, and had the potential ability to be used as anticancer, hormones and vasoprotectives agents.

The Chagas disease (CD) is an endemic infectious disease in a large part of Latin America. This disease is characterized by the fact of being caused by the parasite Trypanosoma cruzi. Some symptoms of this disease are cardiopathies and gastrointestinal problems. Therefore, the commonly used treatment consists of nitro drugs such as benznidazole and nifurtimox, which target the nitroreductase enzyme that docks to the coenzyme flavin mononucleotide (FMN) and an oxidation-reduction reaction is generated. From this reaction, the nitro chemical function of benznidazole and nifurtimox is reduced to amine. This amine in turn interacts with the parasite´s DNA. In vitro tests experimentally help in the study of the parasite resistance to the drug benznidazole. This fact could explain how nonsynonymous mutations in the nitroreductase (NTR) enzyme do not allow the anchorage of the FMN coenzyme and as a consequence the parasite susceptibility to benznidazole decreases as the drug cannot be reduced. The structural relations from the hybrid Quantum Mechanics-Molecular Mechanics (QM/MM) allow to detect the small changes generated in the system, considering a charge distribution associated with the structure, angle changes, interaction distances, potential surface calculations between the wildtype enzyme and the mutation found.

The global polyvinyldene flouride market is estimated to reach $937,278.5 thousand by 2019, therefore to develop new membranes and gain pioneering ideas, which could create innovative business opportunities, a fundamental knowledge about membrane properties fabricated from recent commercially available PVDF polymers is highly mandatory. In this study, we successfully prepared nine non-woven supported PVDF membranes using a phase inversion precipitation method starting from a 15 wt% PVDF solution in N-methyl-2-pyrrolidone. Various membrane morphologies were obtained by using (1) PVDF polymers with diverse molecular weight in a range from 300.000 Da to 700.000 Da and (2) different temperatures of the coagulation bath (20, 40, and 60 ±2°C) used for the films precipitation. Environmental Scanning Electron Microscope (ESEM) was used for surface and cross-section morphologies characterization. Atomic Force Microscope (AFM) was employed to investigate surface roughness, while Contact Angle (CA) instrument was used for membranes wettability studies. Fourier Transform Infrared Spectroscopy (FTIR) results show that the fabricated membranes are formed by a mixture of TGTG’ chains in α phase crystalline domains and all-TTTT trans planar zigzag chains characteristic to β phase. Moreover, generated results indicate that the phases content and membrane morphologies depend on the polymer molecular weight and conditions used for the membranes preparation. The diversity of fabricated membranes could be applied by the End User Industries for different applications.

In the dynamic landscape of drug discovery, Computer-rAided Drug Design (CADD) emerges as a transformative force, bridging the realms of biology and technology. This paper overviews CADD's historical evolution, categorization into structure-based and ligand-based approaches, and its crucial role in rationalizing and expediting drug discovery. As CADD advances, incorporating diverse biological data and ensuring data privacy become paramount. Challenges persist, demanding the optimization of algorithms and robust ethical frameworks. Integrating Machine Learning and Artificial Intelligence amplifies CADD's predictive capabilities, yet ethical considerations and scalability challenges linger. Collaborative efforts and global initiatives, exemplified by platforms like Open Source Malaria, underscore the democratization of drug discovery. The convergence of CADD with personalized medicine offers tailored therapeutic solutions, though ethical dilemmas and accessibility concerns must be navigated. Emerging technologies like quantum computing, immersive technologies, and green chemistry promise to redefine the future of CADD. The trajectory of CADD, marked by rapid advancements, anticipates challenges in ensuring accuracy, addressing biases in AI, and incorporating sustainability metrics. The paper concludes by highlighting the need for proactive measures in navigating the ethical, technological, and educational frontiers of CADD to shape a healthier, brighter future in drug discovery.

Polyphenol ellagic acid (EA) possesses anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic and cardio protection activities, remarking it an interesting multi-targeting profile. EA also controls the central nervous system (CNS) since it was proven to reduce the immobility time of mice in both the forced swimming and the tail-suspension tests, with an efficiency comparable to that of classic antidepressants. Interestingly, the anti-depressant-like effect was almost nulled by the concomitant administration of selective antagonists of the noradrenergic receptors, suggesting the involvement of these cellular targets in the central effects elicited by EA and its derivatives. By in silico and in vitro studies, we discuss how EA engages with human α2A-ARs and α2C-AR catalytic pockets, comparing EA behaviour with those ones of known agonist and antagonist. Structurally, the hydrophobic residues surrounding α2A-AR pocket confer specificity on the intermolecular interactions and hence lead to favourable binding of EA in the α2A-AR, with respect to α2C-AR. Moreover, EA seems to better accommodate within α2A-ARs into TM5 area, closely to S200 and S204 which play a crucial role for activation of aminergic GPCRs such as the α2-AR, highlighting its promising role as a partial agonist. Consistently, EA mimics clonidine in inhibiting noradrenaline exocytosis from hippocampal nerve endings in an yohimbine-sensitive fashion that confirms the engagement of naïve α2-ARs in the EA-mediated effect.

The Neurodegenerative Diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to have an exponential growth thanks to numerous advancements in tech, shifts in the understanding of the disease as a phenomenon, and the change of perspective regarding gene editing and the upsides of this action. The aim of this paper is to analyse the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease and Amyotrophic Lateral Sclerosis. We intend through this review to focus on the newest treatment, diagnosis and predictions plans regarding this large group of diseases, in order to obtain a better accuracy analysing and spotting the emerging signs that could lead to a better outcome in order to increase both the quality and the life span of the patient. Moreover, this review could provide future evidence of possible novelty therapies that target the specific genes and could be useful to be taken into consideration when the classical approaches fail to shed light.

Polyaromatic hydrocarbons (PAHs) are widespread in the interstellar medium (ISM). The abundance and relevance of PAHs call for a clear understanding of their formation mechanisms, which, to date, have not been completely deciphered. Of particular interest is the formation of benzene, the basic building block of PAHs. It has been shown that ionization of neutral clusters can lead to an intra-cluster ionic polymerization process that results in molecular growth. Ab initio molecular dynamics (AIMD) studies in clusters consisting of 3–6 units of acetylene modeling ionization events under ISM conditions have shown maximum aggregation of three acetylene molecules forming bonded C6H6+ species: the larger the number of acetylene molecules, the higher the production of C6H6+. These results lead to the question of whether clusters bigger than those studied thus far promote aggregation beyond three acetylene units, and whether larger clusters can result in higher C6H6+ production. In this study, we report results from AIMD simulations modeling the ionization of 10 and 20 acetylene clusters. The simulations show aggregation of up to four acetylene units producing bonded C8H8+. Interestingly, C8H8+ bicyclic species were identified, setting precedent for their astrochemical identification. Comparable reactivity rates were shown with 10 and 20 acetylene clusters.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

Understanding the interplay among organophosphorus flame-retardants (OPFRs), microplastics, and freshwater organisms is crucial for unravelling the dynamics within freshwater environments and foreseeing the potential impacts of organic pollutants and plastic contamination. For that purpose, the present research assessed the exposure impact of 10 mg L–1 flame-retardant alumin-ium diethylphosphinate (ALPI), 10 μg mg–1liver microplastics polyurethane (PU), and the combina-tion of ALPI and PU on the freshwater planarian Girardia tigrina. The exposure of G. tigrina to both ALPI and PU revealed a sequential effect, i.e., a decrease in locomotor activity, while other molecular biomarkers (oxidative stress biomarkers and metabolic response) remained unaffected. Despite this fact, it was possible to observe that the range (min-max) of responses of exposed or-ganisms were altered, in the particular case of electron transport system, cholinesterase activity, glutathione S-transferase, catalase and levels of total glutathione and proteins, showing that the energetic costs for detoxification and antioxidant capacity might be causing less energy allocated for the planarian activity. By examining the physiological, behavioural, and ecological responses of planarians to these pollutants, insights can be gained into broader ecosystem-level effects and inform strategies for mitigating environmental risks associated with OPFRs and microplastic pol-lution in freshwater environments.

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.

The Herpotrichiellaceae family is an important group of dematiaceous filamentous fungi, associated with a variety of pathogenic fungal species causing Chromoblastomycosis (CBM) and Phaeohyphomycosis (PHM), both with polymorphic clinical manifestations and worldwide incidence. Currently, the identification of this family and determination of the causative agent is challenging due to the subjectivity of morphological identification methods, necessitating the use of molecular techniques to complement diagnosis. In this context, genetic sequencing of the Internal Transcribed Spacer (ITS) has become the norm due to a lack of alternative molecular tools for identifying these agents. Therefore, this study aimed to develop PCR-Multiplex methodologies to address this gap. Sequences from the ITS and Large subunit (LSU) of ribosomal DNA were used, and after manual curation and in vitro analyses, primers were synthesized for the identification of the aforementioned targets. The primers were optimized and validated in vitro, resulting in two PCR-Multiplex methodologies: one for identifying the Herpotrichiellaceae family and the bantiana clade, and another for determining the species Fonsecaea pedrosoi and Fonsecaea monophora. Ultimately, the assays developed in this study aim to complement other identification approaches for these agents, reducing the need for sequencing, improving the management of these infections, and enhancing the accuracy of epidemiological information.

The shikimate pathway is crucial for the biosynthesis of aromatic amino acids in plants and represents a promising target for developing new herbicides. This work aimed to identify inhibitors of shikimate dehydrogenase (SDH), a key enzyme of the shikimate pathway that catalyzes the conversion of 3-dehydroshikimate to shikimate. Virtual screening and molecular docking were performed on the SDH active site of Arabidopsis thaliana (AtSDH), and 6-nitroquinazoline-2,4-diol (NQD) was identified as a potential inhibitor. In vitro assays showed that NQD decreased the activity of AtSDH by reducing Vmax while keeping KM unchanged, indicating noncompetitive inhibition. In vivo, hydroponic experiments revealed that NQD reduced the root length of soybean and maize. Additionally, NQD increased the total protein content and certain amino acids. Soybean roots uptake NQD more efficiently than maize roots. Furthermore, NQD reduced shikimate accumulation in glyphosate-treated soybean roots, suggesting its potential to restrict the flow of metabolites along the shikimate pathway in soybean. Simultaneous treatment of maize seedlings with glyphosate and NQD accumulated gallic acid in the roots, indicating that NQD inhibits SDH in vivo. Overall, the data indicate that NQD inhibits SDH both in vitro and in vivo, providing valuable insights into the potential development of herbicides targeting SDH.

A sedentary lifestyle associated with unregulated diets rich in high-calorie foods have contributed to the great prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) latterly, with up to 60% in high-risk population and 25% in the general population. The absence of specific pharmacological strategies for this syndrome represents one of the major problems in the management of MASLD patients. Lifestyle interventions and adherence to a healthy diet are the main cornerstones of current therapies. The identification of nutraceuticals useful in the treatment of MASLD appears to be one of the most promising strategies for the development of new effective and safe treatments for this disease. The onion, one of the most widely studied foods in the field of nutraceuticals, serves as an inexhaustible reservoir of potent compounds with various beneficial effects. The following preliminary study analyses, mediating in silico studies, the iteration of a library of typical onion compounds with 3-hydroxy-3-methylglutaryl-coenzyme A reductase, Liver receptors X α and β as well as Peroxisome proliferator-activated receptors α and γ. In this study fort the first time promising smart molecules from the onion that could have a beneficial action in MASLD patients were identified.

Nereis as a mudflat organism has a variety of uses, in the history of China as a Chinese herbal record, because of its body contains rich amino acids, fatty acids and other nutrients, it can be used for therapeutic treatment and treatment can also be used as health care products. acids, fatty acids and other nutrients, it can be used for therapeutic treatment and treatment can also be used as health care products. In modern times, more and more researchers have studied the protease extract of Nereis as a mudflat organism. In modern times, more and more researchers have studied the protease extracted from the body of nereis and found that there are a variety of functional proteins in nereis, including superoxide dismutase, superoxide dismutase, superoxide dismutase and superoxide dismutase. More and more researchers have studied the proteases extracted from the body of nereis and found that there are a variety of functional proteins in nereis, including superoxide dismutase, adenylate cyclase, glycosidase, and plasminase. In this paper, the functional proteases in the extracts of nereis were summarized, and the functions and characteristics of proteases in nereis were discussed from the perspective of molecular structure.

MIPs inspired by antigen-antibody interactions have received substantial interest as a biomimetic artificial receptor system in environmental applications. Herein, we present a molecularly imprinted surface plasmon resonance (SPR) sensor integrated with Au nanoparticles for the identification of bisphenol A (BPA), an endocrine-disrupting chemical. The synthetic wastewater samples were analyzed to ensure the method's reliability and feasibility. Under ideal conditions, the suggested approach performed well in terms of analytical performance to BPA, with a wide linear range of 0.1 to 10 ppb and LOD of 10 ng/L. The sensor results and the Langmuir adsorption model have good agreement. It has also been shown that repeated use of the biosensor can be achieved. According to selectivity studies, BPA adsorbed within the imprinted cavities favorably compared to 4-nitrophenol and phenol. The produced BPA-imprinted SPR sensor provides improved sensitivity based on the signal amplification strategy, unconjugated sensing without the need for labeling, real-time sensing, low sample consumption rates, quantifiable assessment, and very good kinetic rate constant calculation in actual samples. Also, because the produced sensor is reusable with relative standard deviations (RSD)<1.25, indicating the sensor's accuracy, the SPR-based biomimetic BPA sensor is simple to practice and may be an economical option.

PPR is a highly contagious viral disease and one of the deadliest affecting wild goats, sheep and small ruminants, however goats are generally more sensitive. The causative agent is the Peste des Petits Ruminants virus (PPRv) which is a single-stranded RNA virus of negative polarity belonging to the Paramyxoviridae family. In February 2020, an active outbreak of PPR was re-ported in a herd of a transhumant farmer in the village of Ngainth Pathé (department of Kounguel, Kaffrine region,Senegal). Of the ten (10) swabs collected from goats, eight (8) came back positive by real-time PCR. The most positive sample was amplified, purified and amplicon sent for sequencing. Phylogenetic analysis showed that the sequence of the PPR virus obtained belonged to lineage IV. These results confirm those found in the latter countries and reinforce the hypothesis of the importance of animal mobility between these neighboring countries. In perspective, following the discovery of this lineage IV in Senegal, a study on its dispersion is underway throughout the national territory. The results that will emerge from this study, asso-ciated with detailed data on animal movements and epidemiological data, will provide appro-priate and effective information to improve PPR surveillance and control strategies with a view to its eradication.

In our previous work, we demonstrated the potential of the amphiphilic cyclic peptide [W4R4] as a promising antimicrobial agent. The extensive data accumulated on the antimicrobial activity of this peptide and its homologs presented an opportunity to unravel the molecular mechanisms governing their action and establish crucial structure-activity relationships (SAR). To achieve this, we employed a comprehensive approach involving peptide synthesis, in vitro biological testing, and molecular modeling to systematically analyze the SAR of a series of cyclic peptides derived from the [W4R4] scaffold. Minimal modifications were introduced to the original peptide by incorporating either one aromatic hydrophobic residue (W) or one polar positively charged residue (R) while maintaining the sequential W/R arrangement. Additionally, we introduced an "intermediate" substitution by incorporating 2,5-diketopiperazine (DKP), possessing both aromatic and polar properties, into the macrocycle [W4R4] between the W and R residues. Notably, this study marked the first synthesis and evaluation of the [W4R4(DKP)] peptide. Structural, dynamic, hydrophobic, and membrane-binding properties of four cyclic peptides ([W4R4], [W5R4], [W4R5], [W4R4(DKP)]) were explored using molecular dynamics simulations within a DOPC/DOPG lipid bilayer that mimics the bacterial membrane. The results obtained revealed distinct SAR profiles for all peptides, enabling the establishment of correlations between their antimicrobial activity and structural/dynamic parameters. These parameters included the degree of conformational plasticity, the depth of immersion into the bi-layer, and the population of the membrane binding mode characterized by the embedding of the hydrophobic peptide pattern into the acyl chain region of lipids. In particular, the peptide [W4R5] exhibited an optimal "activity/binding to the bacterial membrane" pattern. This work highlights the significance of our multidisciplinary approach in efficiently deciphering finely regulated SAR profiles for a series of homologous peptides with diverse activities. Furthermore, this research provides a solid foundation for the rational design of novel antimicrobial peptides.

Insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising treatment option for individuals with diabetes. It has been reported that the incorporation of fatty acid moieties into insulin icodec plays a crucial role in its prolonged action, as these fatty acid chains facilitate the formation of stable hexameric structures, thereby delaying insulin absorption and promoting sustained release. Yet, the underlying biophysics still is elusive of the roles of the three site-specific mutations (Y14A\_E, Y37B\_H, F46B\_H) of insulin icodec in its prolonged activity. Thus, through a comprehensive structural and biophysical analysis of the insulin (both native and icodec) structures bound to its receptor, this article delves deep into the biophysics underlying the molecular design of insulin icodec, and identified a delicate biophysical mechanism through which two missense mutations of insulin icodec (Y37B\_H and F46B\_H) contribute to its prolonged duration of action. Overall, this structural and biophysical investigation provides valuable insights into the mechanisms underlying the relationship between three site-specific mutations and prolonged duration of action of insulin icodec, while understanding these modifications at a structural and biophysical level can aid in the rational design of future long-acting insulin analogues, offering further enhanced therapeutic options for diabetic patients.

The gel prepared by Nemipterus virgatus (N. virgatus) surimi alone still has some defects in texture and taste. Complexing with polysaccharides is an efficient strategy to enhance the gel properties. The main objective of the study was to analyze the relationship between the gel quality and molecular interaction of N. virgatus surimi gel after complexing with tapioca starch. The results make clear that the gel strength, hardness, and chewiness of surimi gel were increased by molecular interaction with tapioca starch. At the appropriate addition amount (12%, w/w), the surimi gel had excellent gel strength (17.48 N), water holding capacity (WHC) (89.01%), lower cooking loss rate (CLR) (0.95%), and shorted T2 relaxation time. Microstructure analysis indicated that the addition of tapioca starch made the surimi gel evenly distributed in the gel network structure, resulting in a significant reduction in cavities diameter, and the minimum diameter could be reduced to 20.33 μm. In addition, tapioca starch enhanced the hydrogen bond and hydrophobic interaction in the gel system and promoted the transformation of α-helix to β-sheet (P&lt;0.05). Correlation analysis showed that the increased physicochemical properties of surimi gel was closely related to the enhanced non-covalent interactions. In conclusion, the non-covalent complexation with tapioca starch is an efficient strategy to enhance the gel quality of surimi gel.

The genus Colias Fabricius, 1807 includes numerous taxa and forms with uncertain status and taxonomic position. Among such taxa are Colias mongola Alphéraky, 1897 and Colias tamerlana Staudinger, 1897, interpreted in the literature either as conspecific forms, as subspecies of different but morphologically somewhat similar Colias species, or as distinct species-level taxa. Based on mitochondrial and nuclear DNA markers, we reconstruct a phylogeographic pattern of the taxa in question. We recover and include in our analysis DNA barcodes of the century-old type specimens, the lectotype of C. tamerlana deposited in the Natural History Museum (Museum für Naturkunde), Berlin, Germany (ZMHU), the paralectotype of C. tamerlana and the lectoptype of C. mongola deposited in the Zoological Institute, Russian Academy of Sciences, Saint-Petersburg, Russia (ZISP). Our analysis grouped all specimens within four (HP_I-HP-IV) deeply divergent but geographically poorly structured clades which did not support nonconspecifity of C. mongola–C. tamerlana. We also show that all studied females of the widely distributed haplogroup HP_II were infected with a single Wolbachia strain belonging to the supergroup B, while the males of this haplogroup, as well as all other investigated specimens, were not infected. Our data underline the relevance of large-scale sampling dataset analysis and the need of testing for Wolbachia infection to avoid erroneous phylogenetic reconstructions and species misidentification.

Lily database online genomic resource composed of Korean Lily Germplasm Collection, Transcriptome Sequences, molecular markers, transcription factors (TF) and DEGs data. A total of ~0.23 gb of RNA-sequences data were mined for gene identification, marker development and gene expression analysis. As a result, 47,863 SSR, 20,929 SNP and 1213 COS-marker were developed. A total of 1327 TF genes were identified and characterized. This is the first unique, user-friendly, genomic resource database for Lilium species. It is a relational database based on a ‘three-tier architecture’ that catalogs all the information in MySQL table and a user-friendly query interface and data visualization page developed using JavaScript, PHP and HTML code. The search parameters are highly flexible, user can be retrieved data by using either single or multiple search parameters. Data present in this database can be used for germplasm characterization, gene discovery, population structure analysis, QTL mapping and accelerating the lily variety improvements. This database can be accessed through this link: http://www.genomicsres.org/lilidb/.

Crossostephium chinense is a wild species with strong salt tolerance, which has great potential to improve the salt tolerance of cultivated chrysanthemums. Conversely, the unique salt-tolerant molecular mechanisms of Cr. chinense are still unclear. This study performed a comparative physiological and transcriptome analysis of Cr. chinense, Chrysanthemum lavandulifolium and their hybrids. The physiological results showed that Cr. chinense maintained a higher superoxide dismutase (SOD) activity, to alleviate the oxidative damage to membrane. KEGG enrichment analysis showed that the plant hormone signaling transduction and the MAPK signaling pathway were mostly enriched in Cr. chinense and hybrids under salt stress. Further weighted gene co-expression network analysis (WGCNA) of DEGs suggested that the abscisic acid (ABA) signaling transduction may play a significant role in the salt-tolerant mechanisms of Cr. chinense and hybrids. The tissue-specific expression patterns of the candidate genes related to ABA signaling transduction and MAPK signaling pathway indicated that genes related to ABA signaling transduction performed significant expression levels under salt stress. This study provides a theoretical foundation for future research into the molecular mechanism of salt tolerance in chrysanthemums under salt stress.

Leucyl-aminopeptidase (LAP), an important metallopeptidase, hydrolyses amino acid residues from the N-terminal of polypeptides and proteins, acting preferentially on the peptide bond formed by N- terminus leucine. A new leucyl-aminopeptidase was found in Bacillus cereus CZ. Its gene (bclap) contained a 1485 bp ORF encoding 494 amino acids with a molecular weight of 54 kDa. The bcLAP protein was successfully expressed in E. coli BL21(DE3). Optimal activity is obtained at pH 9.0 and 58°C. The bcLAP displays a moderate thermostability and an alkaline pH adaptation range. Enzymatic activity is dramatically enhanced by Ni2+. EDTA significantly inhibits the enzymatic activity, and bestatin and SDS also show strong inhibition. The three-dimensional model of bcLAP monomer and homohexamer is simulated by Phyre2 server and SWISS-MODEL server. The docking of bestatin, Leu-Trp, Asp-Trp and Ala-Ala-Gly to bcLAP is performed using AutoDock4.2.5 , respectively. Molecular docking results show that the residues Lys260, Asp265, Lys272, Asp283, Asp342, Glu344, Arg346, Gly372, His437 are involved in the hydrogen bonding with the ligands and zinc ions. There may be two nucleophilic catalytic mechanisms in bcLAP, one involving His 437 or Arg346 and the other involving His437 and Arg346. The bcLAP can hydrolyse the peptide bonds in Leu-Trp, Leu-Trp and Ala-Ala-Gly.

Since 2019, notable global viral outbreaks have occurred necessitating further research and healthcare system investigations. Following the COVID—19 pandemic, an unexpected duality has occurred of SARS–CoV–2 and monkeypox virus (MPXV) infections. Monkeypox virus is of the Orthopoxviridae genus, belonging to the family Poxviridae. Zoonotic transmission (animal to human transmission) may occur. The Orthopoxviridae genus includes other Orthopoxviruses (OPXV) present in animal host reservoirs that include cowpox viruses (CPXV), vaccinia virus (VACV) and variola virus (VARV), with the latter being causal agent of smallpox and excessive mortality. The aim in this review is to present facts about MPXV specific pathogenesis, epidemiology, and immunology alongside historical perspectives. Monkeypox virus was rarely reported outside Africa before April 2000. Early research since 1796 contributed towards eradication of VARV leading to immunisation strategies. The World Health Organisation (WHO) announcement that VARV had been eradicated was confirmed in 1980. On the 23rd of July 2022, the WHO announced MPXV as a health emergency. Therefore, concern due to propagation of MPXV causing MPOX disease requires clarity. Infected hosts display symptoms like extensive cellular initiated rashes and lesions. Infection with MPXV makes it difficult to differentiate from other diseases or skin conditions. Anti–viral therapeutic drugs were typically prescribed for smallpox and MPOX disease; however, the molecular and immunological mechanisms with cellular changes remain of interest. Furthermore, no official authorised treatment exists for MPOX disease. Some humans across the globe may be considered at risk. Historically, presenting symptoms of MPOX resemble other viral diseases. Symptoms include rashes or lesions like Streptococcus, but also human herpes viruses (HHV) including Varicella zoster (VZV).

Copepods are the most abundant metazoans on Earth, exhibit remarkable species diversity and global distribution. Accurate species identification of copepods presents a challenge due to their cryptic nature, necessitating meticulous examination and differentiation. To address this challenge, innovative approaches utilizing molecular markers have emerged, enabling more reliable and precise species identification. Mitochondrial genes, which are characterized by high variability, have proven invaluable in uncovering taxonomically significant variations among copepod species. In this study, we present the first complete mitochondrial genome analysis of the marine calanoid copepod Bestiolina similis (Sewell, 1914). Recent investigations employing whole mitochondrial genome-based phylogenetic analyses have generated considerable interest in exploring the deep branching patterns of arthropods. The complete mitochondrial genome of B. similis spans 23,704 base pairs and includes 13 protein-coding genes and 20 transfer RNA genes. The nucleotide composition of the mitochondrial genome is characterized by 43.42% adenine, 43.22% thymine, 6.48% guanine, and 6.88% cytosine. Maximum likelihood-based phylogenetic analysis of the mitochondrial genome were constructed of the available copepod species. Mitochondrial ge-nome-based phylogenies often reveal intriguing and distinctive topologies compared to traditional phylogenetic approaches. However, the sequencing of copepod mitochondrial genomes, particularly within the calanoid copepods remains limited. Therefore, this study aims to construct a phylogenetic tree based on the extracted mitochondrial genome, incorporating available data, to enhance our understanding of the evolutionary relationships among calanoid copepods.

Reactions in water between the Cu2(µ-EGTA) chelate (EGTA = ethylene-bis(oxyethyleneimino)tetraacetate(4-) ion) and 2,6-diaminopurine (Hdap) in molar ratios 1:1 and 1:2 yield only blue crystals of the ternary compound [Cu4(μ-EGTA)2(μ-H(N3)dap)2(H2O)2]·7H2O (1) that has been studied by single crystal X-ray diffractometry, various physical methods (thermal stability, spectral and magnetic properties), as well as DFT theoretical calculations. In the crystal, uncoordinated water is disordered. The tetranuclear complex molecule also has some irrelevant disorder in an EGTA-ethylene moiety. In the complex molecule, both bridging organic molecules act as binucleating ligands. There are two distorted five- (type 4+1) and two six- (type 4+1+1) Cu(II) centres. Each half EGTA acts as a tripodal tetradentate Cu(II) chelator, with mer-NO2+O(ether, distal) conformation. Hdap exhibits the tautomer H(N3)dap, with the dissociable H-atom on its less basic N-heterocyclic atom. These features favour the efficient cooperation between Cu-N7 or Cu-N9 bonds with appropriate O-EGTA atoms, as N6-H···O or N3-H···O interligand interactions respectively. Bridging role of both organics determines the tetranuclear dimensionality of the complex in 1. In this crystal, such molecules associate in zig-zag chains, built by alternating ,-interactions between the five- or six-atom rings of Hdap ligands of adjacent molecules. DFT theoretical calculations (using two different theoretical models and characterized by the quantum theory of “atoms in molecules”) reveal the importance of these ,-interactions between Hdap ligands, as well as that corresponding to the referred hydrogen bonds in the contributed tetranuclear molecule.

Adipose tissue has acquired considerable importance due to its role in maintaining body homeostasis. Beyond storing energy, adipose tissue is essential in numerous processes of energy metabolism, food intake, endocrine and immunological functions as well as neromodulatory functions by secreting hormones that participate in the regulation of homeostasis and being responsive to soluble proteins secreted by other tissues. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favouring the secretion of deleterious adipocytokines that benefit a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases. Obesity is a disease that has increased rapidly in recent decades and is caused by environmental, hormonal, and genetic factors, which probably work in combination. Environmental factors that contribute to the increase in obesity include decreased physical activity, associated with increased screen time, increased accessibility and consumption of foods rich in fats and sugars. Weight loss should be recommended for all obese patients and overweight patients with comorbidities. For many patients who need to lose weight for medical reasons, the initial goal is to lose 5-10% of their body weight in the first 6 months. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity and in Chile, the Chilean Society of Metabolic and Bariatric Surgery led the process of adopting the adult obesity clinical practice guideline, which establishes changes in the approach to managing obesity as a chronic disease, with an emphasis on multifactorial lifestyle interventions that include dietary changes, increased physical activity, and behavioural modifications. Pharmacotherapy, medical devices, and bariatric surgery are other options for patients who need additional interventions, so the objective of this review is to know the pathophysiological mechanisms of obesity from its origin to the current treatments available for treatment.

The illicit use of fentanyl has led to hundreds of thousands of opioid-related deaths worldwide. Therefore, the detection of fentanyl by law enforcement and recreational users is of utmost importance. However, current detection methods are expensive, time-consuming, require special storage conditions and necessitate complex instrumentation that is generally unportable and requires skilled personnel to operate. An alternative approach would be using molecularly imprinted polymers (MIPs) as the recognition component of a handheld sensor, testing strip, or color-based assay. In this work, a molecularly imprinted polymer was made by using methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA) as the functional monomer and cross-linking monomer respectively, and benzylfentanyl (Bfen) as the template. The use of benzylfentanyl is advantageous because it closely resembles the structure of fentanyl but does not have any physiological effects as a narcotic. Important studies herein determined the optimum ratio of the template:functional monomer, with subsequent evaluations of selectivity versus the commonly encountered narcotics such as heroin, cocaine, and methamphetamine. The data obtained from the HPLC analysis showed that the Bfen-MIP was successful in selectively binding the template and actual fentanyl, better than other common narcotics.

The protein extract of Ulva australis hydrolyzed with alcalase and flavourzyme investigated multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of U. australis hydrolysate from cation-exchange chromatography showed significantly high TAC, collagenase inhibitory and antibacterial effects against Propionibacterium acnes, and only Q3 fraction from anion-exchange chromatography showed high multi-functional activities. The eight peptides among 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results to screen molecular docking on target proteins, and were synthesized. Thr-Gly-Thr-Trp (TGTW) showed ABTS [2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. Effect TAC as Trolox equivalence was dependent on the concentration of TGTW. The Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) possessing collagenase inhibitory activity increased according to the increase of concentration and the IC50 values of them were 0.95 mM and 0.84 mM, respectively. Peptides, RDRF and His-Ala-Val-Tyr (HAVY) showed anti-P. acnes effects with IC50 values of 8.57 mM and 13.23 mM, respectively. These results suggest that the U. australis hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.

Epigenetic alterations are heritable and enduring modifications in gene expression that play a pivotal role in immune evasion. These include alterations to noncoding RNA, DNA methylation, and histone modifications. DNA methylation plays a crucial role in normal cell growth and development but alterations in methylation patterns such as hypermethylation or hypomethylation can enable tumor and viral cells to evade host immune responses. Histone modifications can also inhibit immune responses by promoting the expression of genes involved in suppressing normal immune function. In the case of T-cell lymphoma, adult T-cell Lymphomas (ALT) also undergo immune evasion through the exceptional function of its accessory and regulatory genes. Epigenetic therapies are emerging as a promising adjunct to traditional immunotherapy and chemotherapy regimens. Clinical trials are currently investigating the use of epigenetic therapies in combination with immunotherapies and chemotherapies for more effective treatment of ATL and other cancers. This review highlights epigenetic alterations that are widely found in T cell malignancies.

Lead (Pb) is a non-essential, highly toxic, and persistent element widely recognised as one of the most concerning pollutants, and it is listed in the Priority List of Hazardous Substances. Widespread environmental contamination from Pb is a serious issue for human health and wildlife. The liver, a key compartment for metal detoxification and excretion, is also the organ in which Pb mainly accumulates in fish. Herein, we investigated for the first time the morphological and functional injuries induced in zebrafish (Danio rerio) liver by two very low and environmentally relevant concentrations of Pb (2.5 and 5 μg/L) after 48, 96, and 192 hours of exposure. We showed significant histological alterations in all the exposed samples, also demonstrating that the extent of injuries increased with dose and exposure time. The most common modifications observed were congestion of blood vessels and sinusoids, cytoplasmic vacuolizations, parenchyma dyschromia, and macrophage proliferation. Pb administration also resulted in a significant increase in lipid content and the upregulation of key genes involved in metal detoxification (mtf1) and the defensive response against oxidative stress (sod1 and cat). We showed that even very low doses of Pb can disrupt liver morphology and function.

Antibiotic therapy is a cornerstone of modern medicine, yet the development of antibiotic re-sistance threatens to render these therapies ineffective. The gut microbiota, a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a critical role in modulating anti-biotic efficacy and resistance. This review delves into the intricate relationship between gut mi-crobiota, antibiotic therapy, and resistance, and discusses the potential applications of gut mi-crobiota research in guiding personalized antibiotic therapy and resistance mitigation strategies. Recent advancements in metagenomics, metatranscriptomics, and metabolomics have demon-strated the potential for tailored antibiotic regimens that minimize collateral damage to com-mensal bacteria and reduce the risk of resistance. Adjuvant therapies such as probiotics, prebi-otics, and synbiotics have shown promise in restoring gut microbial balance and mitigating the adverse effects of antibiotic therapy. We address the challenges associated with this emerging field including the need for standardized methodologies, ethical considerations, and interdisci-plinary collaboration. With continued interdisciplinary collaboration and the implementation of standardized methodologies, gut microbiota research can contribute to the global fight against antibiotic resistance and improve patient outcomes.

Piroplasmosis, caused by Babesia spp. and Theileria spp., poses significant constraints for livestock production and upgradation in Bangladesh. Besides examining blood smears, few molecular reports are available from some selected areas in the country. Therefore, the actual scenario of piroplasmosis in Bangladesh is deficient. This study aimed to screen the piroplasms in different livestock species by molecular tools. A total of 276 blood samples were collected from cattle, gayals (Bos frontalis) and goats in five geographies of Bangladesh. Thereafter, screening was conducted through a polymerase chain reaction, and species were confirmed by sequencing. The prevalence of Babesia bigemina, B. bovis, B. naoakii, B. ovis, Theileria annulata and T. orientalis was 49.28%, 0.72%, 1.09%, 32.26%, 6.52% and 46.01%, respectively. The highest prevalence (79/109; 72.48%) of co-infections was observed with B. bigemina and T. orientalis. The phylogenetic analyses revealed that the sequences of B. bigemina, B. bovis, B. naoakii, B. ovis and T. annulata were included in one clade in the respective phylogram. In contrast, the sequences of T. orientalis were separated into two clades, corresponding to Type 5 and 7. To the best of our knowledge, this is the first molecular report on piroplasms in gayals and goats in Bangladesh.

The emergence of drug-resistant tuberculosis forced the development of new drugs and screnning of more effective or less toxic analogs. Mycolic acids biosynthesis is targeted by several antituberculosis drugs toped by the isoniazid being one of the most important in tuberculosis therapy. Recently, perchlozone, acting on another step in FAS-II cycle, received official approval and was included in the Russian national clinical guidelines. Using the serial dilution method on agar 7H10 plates for perchlozone and Sensititre MYCOTB microdilution plate we analyzed the phenotypic properties of primary M. tuberculosis clinical isolates and analyzed the molecular determinants of resistance to isoniazid, ethionamide and perchlozone. We found a wide variation in the MIC of perchlozone from 2 to 64 mg/L, correlating with the overall resistance profile: the MIC was higher for MDR and pre-XDR isolates. The cross-resistance between the ethionamide and the perchlozone was driven by mutations in ethA gene encoding monooxygenase responsible for activation of both drugs. Presumably susceptible to perchlozone wild-type strains had MICs ranged 2–4 mg/L, and the breakpoint estimated to be at 4 or 8 mg/L. In conclusion, susceptibility to perchlozone retained for a part of MDR strains, as does suceptibility to ethionamide, providing the possibility of therapy for such cases based on phenotypic or molecular analysis.

Emergence of multi drug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis poses a serious threat to TB control as the available treatment options are less effective in these cases. Therefore, new strategies are required for identification of new drugs and drug targets. The M. tuberculosis dihydrodipicolinate synthase is a putative drug target with no potent inhibitor. Here in this study, we have used a comprehensive computational approach to identify small molecule inhibitors and validated them in vitro. As similar structures tend to have similar functions, therefore 3 approaches, namely, (a) known inhibitor-based approach, (b) substrate analogues, (c) product analogues were used for compound screening from various chemical libraries. The fourth approach we have taken is fragment library screening.In vitro studies revealed that β-hydroxypyruvic acid tartronic acid are inhibitors of Mtb-rDapA with maximum inhibition 48% and 51% at 500µM concentrations respectively. We have also observed that β-hydroxypyruvic acid is a time dependent inhibitor of Mtb-rDapA. Further, thermal shift assays showed that β-hydroxypyruvic acid interacts with Mtb-rDapA and the thermal stability of Mtb-rDapA shifted by 3˚C. Among the product analogues of Mtb-DapA, dipicolinic acid showed to bind to Mtb-rDapB shifting thermal stability of Mtb-rDapB by 0.5˚C in binding. Additionally, we have designed a new approach by combining substrate and product analogues to achieve better inhibitions. In vitro assays validated that this combination approach increased maximum inhibition up to 100%. We envision that these compounds would serve as potent leads for tuberculosis drug discovery.

This study reports a computational investigation on the antioxidant activity of five plant food benzoic acid derivatives, namely gallic acid (GA), para-hydroxybenzoic acid (PHBA), protocatechuic acid (PCA), syringic acid (SA), and vanillic acid (VA). Based on computed thermodynamics parameters, a detailed comparative debate is developed concerning their free radical scavenging activity in the gas phase and polar solutions (in water and methanol solvents). This discussion goes on to elucidate both the most preferred mechanism and the order of antioxidant activity for these molecules in each environment. Paradoxically, calculations using the harmonic oscillator model of aromaticity (HOMA) suggest that H abstraction radicals gain in stability as the central benzene ring loses in structural aromaticity. Finally, spin densities and fukui function f⁰ seem to be good indicators of the local reactivity of these compounds towards free radicals.