The bipartite entanglement is comprehensively investigated in the mononuclear molecular complex (Et3NH)[Ni(hfac)2L], where HL denotes 2-(2-hydroxy-3-methoxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl and hfacH stands for hexafluoroacetylacetone. From the magnetic point of view, the molecular compound (Et3NH)[Ni(hfac)2L] consists of an exchange-coupled spin-1 Ni2+ magnetic ion and a spin-12 nitronyl-nitroxide radical substituted nitrophenol. The nickel-radical molecular complex affords an experimental realization of a mixed spin-(12, 1) Heisenberg dimer with a strong antiferromagnetic exchange coupling J/kB= 505 K and two distinct g-factors gRad=2.005 and gNi=2.275. By adopting this set of magnetic parameters we demonstrate that the Zeeman splitting of a quantum ferrimagnetic ground-state doublet due to a weak magnetic field may substantially reinforce the strength of bipartite entanglement at low temperatures. The molecular compound (Et3NH)[Ni(hfac)2L] maintains sufficiently strong thermal entanglement even at room temperature, vanishing only above 546 K. Specifically, the thermal entanglement in the nickel-radical molecular complex retains approximately 40% of the maximum value corresponding to perfectly entangled Bell states at room temperature, which implies that this magnetic compound provides suitable platform of a molecular qubit with potential implications for room-temperature quantum computation and quantum information processing.

Drug nanosuspensions offer a promising approach to improve bioavailability for poorly soluble drug candidates. Such formulations often necessitate the inclusion of an excipient to stabilize the drug nanoparticles. However, a rationale to choose the correct excipient for a given drug candidate remains unclear. To gain molecular insight into formulation design, this work first utilizes molecular dynamics simulation to computationally investigate drug-excipient interactions for a number of combinations that have been previously studied experimentally. We find that hydrophobic interactions drive excipient adsorption to drug nanoparticles, and that the fraction of polar surface area serves as a predictor for experimental measurements of nanosuspension stability. To test these ideas prospectively, we applied our model to an uncharacterized drug compound, GDC-0810. Our simulations predicted that salt forms of GDC-0810 would lead to more stable nanosuspensions than the neutral form; therefore, we tested the stability of salt GDC-0810 nanosuspensions and found that the salt form readily formed nanosuspensions even without excipient. To avoid computationally expensive simulations in the future, we extended our model by showing that simple, two-dimensional properties of the single drug molecule can be used to rationalize nanosuspension design without simulation. In all, our work demonstrates how computational tools can provide molecular insight into drug-excipient interactions, and aid in rational formulation design.

We extend a previously developed model for the Stark resonances of the water molecule. The method employs a partial-wave expansion of the single-particle orbitals using spherical harmonics. To find the resonance positions and decay rates, we use the exterior complex scaling approach which involves the analytic continuation of the radial variable into the complex plane and yields a non-hermitian Hamiltonian matrix. The real part of the eigenvalues provides the resonance positions (and thus the Stark shifts), while the imaginary parts $-\Gamma/2$ are related to the decay rates $\Gamma$, i.e., the full-widths at half-maximum of the Breit-Wigner resonances. We focus on the three outermost (valence) orbitals, as they are dominating the ionization process. We find that for forces directed along the three Cartesian co-ordinates, the fastest ionizing orbital always displays a non-monotonic Stark shift. For the case of fields along the molecular axis we show results as a function of the number of spherical harmonics included ($\ell_{\max}=3,4$). Comparison is made with total molecule resonance parameters from the literature obtained with Hartree-Fock and coupled cluster methods.

It’s been reported that Mori Folium (MF) and Eucommiae Cortex (EC) exhibit pharmacological effects on the treatment of immunosuppression. However, the mechanism of MF and EC against immunosuppression remains unclear. This study aims to explore the mechanism of action of MF and EC for the treatment of immunosuppression through network pharmacology, molecular docking, molecular dynamics simulations and animal experiments. As a result, 11 critical components, 9 hub targets, and related-signaling pathways of treatment of immunosuppression were obtained based on network pharmacology. The molecular docking suggested that 11 critical components exhibited great binding affinity to 9 hub targets of immunosuppression. The molecular dynamics simulations results showed that (-)-Tabernemontanine-AR, beta-sitosterol-AR and Dehydrodieugenol-HSP90AA1 complexes are stably bound. Additionally, in the animal experiments, the treated group results compared to the control group suggest that MF and EC have a significant effect on the treatment of immunosuppression. Therefore, the MF and EC treatment for immunosuppression may take effects in a multi-component, multi-target, and multi-pathway manner. The results would provide novel insights into the treatment of immunosuppression in humans.

Organic-organic interactions play important roles in the secondary organic aerosol formation, but the interactions are complex and poorly understood. Here we use environmental molecular beam experiments combined with molecular dynamics simulations to investigate the interactions between methanol and nopinone, as atmospheric organic proxies. In the experiments, methanol monomers and clusters are sent to collide with three types of surfaces, i.e., graphite, thin nopinone coating on graphite and multilayer surfaces, at temperatures between 140 K and 230 K. Methanol monomers are efficiently scattered from the graphite surface, whereas the scattering is substantially suppressed from nopinone surfaces. The desorption from the three surfaces is similar, suggesting that all the surfaces have weak or similar influences on the methanol desorption. The molecular dynamics results show that upon collisions the methanol clusters shatter, and the shattered fragments quickly diffuse and recombine to clusters. The desorption involves a series of processes, including detaching from clusters and desorbing as monomers. The experimental results also show that all trapped methanol molecules completely desorb within a short experimental time scale at temperatures of 180 K and above. At lower temperatures, the desorption rate decreases, and a long experimental time scale is used to resolve the desorption, where three desorption components are identified. The fast component is beyond the experimental detection limit. The intermediate component exhibits multi-step desorption character and has an activation energy of E_a = 0.18 ± 0.03 eV, in good agreement with simulation results. The slow desorption component is related to diffusion processes due to the weak temperature dependence.

Kidneys of mice, rats and humans possess progenitors that maintain daily homeostasis and take part in endogenous regenerative processes following injury, owing to their capacity to proliferate and differentiate. In the glomerular and tubular compartments of the nephron, consistent studies demonstrated that well-characterized, distinct populations of progenitor cells, localized in the parietal epithelium of Bowman capsule and scattered in the proximal and distal tubules, could generate segment-specific cells in physiological conditions and following tissue injury. However, defective or abnormal regenerative responses of these progenitors can contribute to pathologic conditions. The molecular characteristics of renal progenitors have been extensively studied, revealing that numerous classical and evolutionarily conserved pathways, such as Notch or Wnt/β-catenin, play a major role in cell regulation. Others, such as retinoic acid, renin-angiotensin-aldosterone system, TLR2 (Toll-Like Receptor 2) and leptin, are also important in this process. In this review, we summarize the plethora of molecular mechanisms directing renal progenitor responses during homeostasis and following kidney injury. Finally, we will explore how single cell RNA sequencing could bring the characterization of renal progenitors to the next level, while knowing their molecular signature is gaining relevance in the clinic.

Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.

For condensed systems, the incorporation of quantum chemical solvent effects into molecular dynamics simulations has been a major concern. To this end, quantum mechanical/molecular mechanical (QM/MM) techniques are popular and powerful options to treat gigantic systems. However, they cannot be directly applied because of temporal and spatial discontinuity problems. To overcome these problems, in a previous study, we proposed a corrective QM/MM method, size-consistent multipartitioning (SCMP) QM/MM, and successfully demonstrated that, using SCMP, it is possible to perform stable molecular dynamics simulations by effectively taking into account solvent quantum chemical effects. The SCMP method is characterized by two original features: size-consistency of a QM region among all QM/MM partitioning and partitioning update. However, in our previous study, the performance was not fully elicited compared to the theoretical upper bound, and the optimal partitioning update protocol and parameters were not fully verified. To elicit the potential performance, in the present study, we simplified the theoretical framework and modified the partitioning protocol.

The monkeypox virus (MPXV) has become a major threat due to the increasing global caseload and the ongoing multi-country outbreak in non-endemic territories. Due to limited research in this avenue and the lack of intervention strategies, the present study was aimed to virtually screen bioactive phytochemicals against envelope proteins of MPXV via rigorous computational approaches. Molecular docking and molecular dynamic (MD) simulations were used to investigate the binding affinity of 12 phytochemicals against three envelope proteins of MPXV, viz., D13, A26, and H3. Silibinin, oleanolic acid, and ursolic acid were computationally identified as potential phytochemicals that showed strong binding affinity towards all the tested structural proteins of MPXV through molecular docking. The stability of the docked complexes was also confirmed by MD simulations. ADME analysis also computationally confirmed the drug-like properties of the phytochemicals, thereby asserting their suitability for consumption. Hence, this study envisions the candidature of bioactive phytochemicals as promising inhibitors against the MPXV, serving as template molecules that could further be experimentally evaluated for their efficacy against monkeypox.

An important stage in SARS-CoV-2 life cycle is the fusion of spike(S) protein with the ACE2 host-cell receptor. Therefore, to explore conserved features in S protein dynamics and to identify potentially novel regions for drugging, we measured variability derived from 791 viral genomes and studied its properties by MD simulation. The findings indicated that S2 subunit (HR1, CH, and CD domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the RBD domain, which is typically targeted in drug discovery programmes, exhibits more sequence variability and flexibility. Interpretations from MD suggest that the monomer is in constant motion showing transitions up-to-down state, and the trimer cavity may function as a 'bouncing spring' that may facilitates S protein interactions with ACE2. Feasibility of trimer cavity for potential drug target was examined by SBVS screening. Several hits that have already been validated or suggested to inhibit the SARS-CoV-2 virus in cell systems were identified; in particular, the data suggest an action mechanism for such molecules including Chitosan and macrolide types. These findings identify a novel binding-site formed by the S protein, that might assist in future drug discovery programmes aimed at targeting the CoV family of viruses.

The global pandemic caused by the new SARS-COV-2 coronavirus makes it necessary to search for drugs for its control. Within of this research it has been known that the ivermectin drug, a FDA-approved drugs which is formulated as an 80:20 mixture of ivermectin B1a and B1b and used commonly for parasitic infections, has an inhibitory effect on viruses, includes SARS-COV-2 at in vitro level. In the particular case of SARS-COV-2 its mechanism of action remains elusive and controversial. Interestingly, the energy of interaction of ivermectin with any of the proteins the SARS-CoV-2 and the possible structural alterations at the protein level that this drug can cause have not been reported. In this sense, we carried out a bioinformatics study with docking strategies and molecular dynamics to predict the binding and disturbance induced by ivermectin in proteins associated with SARS-CoV-2. We use DockThor and Molegro docking scores. The DockThor server and myPresto software were used to build complexes and dynamics studies, respectively. The results obtained suggested that ivermectin is capable of docking with the 3CL protease and the HR2 domain, and may promote structural changes in these proteins by inducing unfolding/folding. Specifically, ivermectin brings protease to a significantly more deployed conformational state and the HR2 domain to a more compact state compared to the native state. Finally, it is shown that B1a and B1b macrocyclic lactones have a behavior different from to each target protein. These results suggest a possible inhibitory effect against SARS-CoV-2 due to a synergistic role of this drug to spontaneously bind to two important proteins involve in the proliferation of this virus. However, more studies are required on this possible mechanism of action.

The SARS-CoV-2 was confirmed to cause the regional outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. The 3C-like protease (3CL^pro), an essential enzyme for viral replication, is a valid target to compacts SARS-CoV and MERS-CoV. In this research, an integrated library consisting of 1000 compounds from Asinex Focused Covalent (AFCL) library and 16 FDA-approved protease inhibitors were screened against SARS-CoV-2 3CL^pro. Top compounds with significant docking scores and making stable interactions with catalytic dyad residues were obtained. The screening results in identification of compound 621 from AFCL library as well as Paritaprevir and Simeprevir from FDA-approved protease inhibitors as potential inhibitors of SARS-CoV-2 3CL^pro. The mechanism and dynamic stability of binding between the identified compounds and SARS-CoV-2 3CL^pro were characterized using 50 nanoseconds (ns) molecular dynamic (MD) simulation approach. The identified compounds are potential inhibitors worthy of further development as SARS-CoV-2 3CLpro inhibitors/drugs. Importantly, the identified FDA-approved therapeutics could be ready for clinical trials to treat infected patients and help to curb the COVID-19.

The antioxidant activity of molecules constitutes an important factor for the regulation of redox homeostasis and reduction of oxidative stress. Cells affected by oxidative stress can undergo genetic alteration, causing structural changes and promoting the onset of chronic diseases, such as cancer. The in silico study performed here was developed to evaluate the antioxidant potential of two molecules, ZINC08706191 (Z91) and ZINC08992920 (Z20), with recognized epithelial anticancer potential. Molecular docking, chemical-quantum calculations and Pearson's correlation were performed. The Z91 and Z20 molecules showed lower binding free energy (ΔG) values for the receptor-ligand interaction than the reference molecules (caffeine – CAF and ascorbic acid – AA), and better results for values of molecular descriptors correlated with ΔG, resulting in a decrease of ΔG. Strong correlations were observed between ΔG values for the five receptors evaluated and ΔG values of the potential epithelial anticancer activity available in literature. These results attest to the significant antioxidant potential of the Z91 and Z20 molecules and their strong relation with the potential epithelial anticancer activity and may be indicated for further analysis in relation to the control of oxidative stress and epithelial anticancer activity.

Borneol and menthol were two terpenes wildly used as penetrate enhancer in transdermal drug delivery. To explore their penetration enhancement effect towards hydrophilic drug, 5-FU was selected as model drug. A method combined vitro permeation studies and coarse grain molecular dynamics was used to investigate their penetration enhancement effect towards 5-FU. As a result, although both borneol and menthol showed a penetration enhancement effect towards 5-FU, they differed a lot in the penetration enhancement mechanism, which was also thought to account for their different penetration enhancement effect. As for menthol, SC bilayer disrupting effect seemed to be its main mechanism. While for borneol, its mechanism seemed to be more complicated. Except for disrupting the SC bilayer, it could also increase the permeation of 5-FU by enhancing the diffusion rate of 5-FU or inducing the formation of transient pore. All of this enable us a molecular understanding of borneol and menthol’s penetration enhancement effect towards hydrophilic drug, which might provide some guidance in the latter research and application.

Interferons were the original prototype cytokine system discovered in 20th-century research. As the name implies, they were originally thought to be synthesised and secreted between cells. Thanks to technological advances, the processes involved in protein secretion can be explained comparatively more clearly at both the genetic and biochemical levels. The discovery of interferon (IFN) occurred when genetic research was still in its infancy. Franklin and Wilkins discovered the structure and function of deoxyribonucleic acid (DNA) at the same time as Crick and Watson; however, Isaacs and Lindemann, two scientists, described the first IFN in 1957. Mutations can be caused by inherent genetic protein synthesis and during infection as well as within IFN regulation pathways affecting cell proliferation. This remains central to host cell IFN synthesis and effects through IFN protein receptor subunits defined by 6 protein domains. Type II IFN is key to immune cell function secreted by a variety of immune cells, mainly natural killer (NK) as well as T cells. Single–stranded and/or double–stranded RNA/DNA viruses, as well as bacterial infections (e.g., Escherichia coli) and fungal infections (e.g., Aspergillus), also affect IFN regulation. Pathogenic proteins utilise intra/extracellular proteins that sense foreign antigens like Toll–like Receptors (TLRs), affected by mutations within the human cellular IFN transduction pathways. Since the discovery of the third IFN type in 2003, when immune cell phenotypes were further characterised, questions remain about the immunological mechanisms contributing to the regulation of the innate and adaptive host immune system. Alterations in the synthesis of type I/II/III host IFNs can differentially and beneficially alter homeostatic cellular pathways in pathological disease, with type I IFN being synthesised in cancer as well as by homeostatic cells. Therefore, considered here are the overall IFN molecular, cell regulatory mechanisms in the context of immune cell research developments.

A self-consistent charge density-functional tight-binding method combined with molecular dynamics simulations is employed to reveal the effect of polymorph on the thermal decomposition stability of 1,1-Diamino-2,2-Dinitroethylene (FOX-7). Two types of heating, constant temperature heating and temperature-programmed heating, are adopted. Potential evolution indicates that γ-FOX-7 possesses the lowest thermal stability, as it is closer to the decomposition state. Crystal form has an important influence on the thermal decomposition of FOX-7, resulting in different decomposition rates and initial reactions. In general, β- and γ-FOX-7 always decompose more completely than α-FOX-7. This work emphases the importance of polymorph dependent initial decay of an energetic polymorphic compound once heated in a volume constrained condition.

CoFe2O4 is a promissing catalytic material for many chemical reactions. We have used ab initio molecular dynamic simulations to study the structure and reactivity of the A- and B-terminations of the low index CoFe2O4 (001) surfaces to water adsorption at room temperature. Upon adsorption, water partly dissociates on both termination with a higher dissociation degree on the A- termination (30% versus 19%). The 2-fold coordinated Fe3+(tet) in the tetrahedral voids and the 5-fold coordinated Fe3+(oct) in the octahedral voids are the main active sites for water dissociation on the A- and B-termination, respectively. Molecular water, hydroxydes and surface OH resulting from proton transfer to surface oxygens are present on the surfaces. Both water free sur- face terminations undergo reconstruction. The outermost Fe3+(tet) on the A-termination and B-termination move towards the nearby unoccupied octahedral voids. In the presence of a thin film of 32 water molecules, the reconstructions are partially and completely lifted on the A- and B-termination, respectively.

Drug discovery has been initially attributed to coincidence or trial and error where the traditional approach was complex, lengthy, and expensive. Conventional drug discovery methods require the costly random screening of synthesized compounds or natural products. Another downside for this approach is the wide dependency on the experimental use of animals for in vi-vo testing. Currently, in silico modeling has become a vital tool for drug discovery and repurposing, and molecular docking is being used to find the best matching between a ligand and a molecule. Practical application of in silico docking will predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana. Originally investigated for its pesticide capability, BEA is now considered as a molecule of interest for its potentially diverse biotechnological applications in the pharmacological industry and the field of medicine. In this manuscript, we will provide an overview of the repurposing of BEA into a potentially superior therapeutic molecule in a broad range of diseases. Furthermore, considerable attention has been given to the fundamental role of in silico techniques to i) further investigate the spectrum of this secondary metabolite and ii) elucidate the pathways of BEA for its promising therapeutic action

Bioluminescence – i.e., the emission of visible light by living organisms - is defined as a biochemical reaction involving, at least, a luciferin substrate, an oxygen derivative, and a specialised luciferase enzyme. In some cases, the enzyme and the substrate are durably associated and form a photoprotein. While this terminology is educatively useful to explain bioluminescence, it gives a false idea that all luminous organisms are using identical or homologous molecular tools to achieve light emission. As usually observed in biology, reality is more complex. To date, 11 different luciferins have indeed been discovered, and several non-homologous luciferases lato sensu have been identified which, all together, confirms that bioluminescence emerged independently multiple times during the evolution of living organisms. While some phylogenetically related organisms may use non-homologous luciferases (e.g., at least four convergent luciferases are found in Pancrustacea), it has also been observed that phylogenetically distant organisms may use homologous luciferases (e.g., parallel evolution observed in some cnidarians, tunicates and echinoderms that are sharing a homologous luciferase-based system). The evolution of luciferases then appears puzzling. The present review takes stock of the diversity of known “bioluminescent proteins”, their evolution and potential evolutionary origins. A total of 134 luciferase and photoprotein sequences have been investigated (from 75 species and 11 phyla), and our analyses identified 12 distinct types – defined as a group of homologous bioluminescent proteins. The literature review indicated that genes coding for luciferases and photoproteins have potentially emerged as new genes or have been co-opted from ancestral non-luciferase/photoprotein genes. In this latter case, the homologous gene’s co-options may occur independently in phylogenetically distant organisms.

An important parameter in the development of a new drug is the drug's affinity to the identified target (protein/enzyme). Predicting the ligand binding to the target (protein/enzyme) by molecular simulation would allow the synthesis to be restricted to the most promising compounds.A restricted hybrid HF-DFT calculation was performed in order to obtain the most stable conformer of each ligand and a series of DFT calculations using the B3LYP levels with 6-31G* basis set has been conducted. The docking studies of the quinolone compounds will be performed with the CLC Drug Discovery Workbench to identify and visualize the ligand-receptor interaction mode.

Introduction of exotic species in new areas through anthropic action is one of the major problems that can affect biodiversity. Branchiomma luctuosum is known for its highly invasive potential and the actual occurrence of species commonly associated with port activity areas is an extra evidence that this anthropogenic activity should not be underestimated. In order to develop suitable molecular markers for future studies on colonization routes and population dynamics of the invading individuals of B. luctuosum, nine highly polymorphic microsatellite loci were isolated and their polymorphism levels were evaluated. These loci showed a range of number of alleles per locus from five to ten and all loci had a high level of genetic diversity, and exhibited significant heterozygote deficiencies probably due to the presence of null alleles. Significant deviations from the Hardy-Weinberg equilibrium were detected at several loci and most of them were related to a heterozygous deficit. Heterozygous deficiency can be expected in this case due to the biology and history of this invasive species, in relation to its recent introduction in Brazilian coast and possible action of multiple introductory events.

Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for the c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards the c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.

Tuberculosis (TB) continues to pose a global health challenge, exacerbated by the rise of drug-resistant strains. The development of new TB therapies is an arduous and time-consuming process. To expedite the discovery of effective treatments, computational structure-based drug re-purposing has emerged as a promising strategy. From this perspective, conditionally essential targets present a valuable opportunity, and the mycobactin biosynthesis pathway stands out as a prime example highlighting the intricate response of Mycobacterium tuberculosis (Mtb) to changes in iron availability. This study focuses on the re-purposing and revival of FDA-approved drugs (library) as potential inhibitors of MbtA, a crucial enzyme in mycobactin biosynthesis in Mtb conserved among all species of mycobacteria. Literature suggests this pathway to be associated with drug efflux pumps, which potentially contribute to drug resistance. This makes it a potential target for antitubercular drug discovery. Herein we utilized cheminformatics and structure-based drug repurposing approaches, viz., molecular docking, dynamics, and PCA analysis, to decode the intermolecular interactions and binding affinity of the FDA-reported molecules against MbtA. The virtual screening revealed ten molecules with significant binding affinities and interactions with MbtA. These drugs, originally designed for different therapeutic indications (4: antiviral, 3: anticancer, 1: CYP450 inhibitor, 1: ACE inhibitor, and 1: leukotriene antagonist), are repurposed as potential MbtA inhibitors. Furthermore, our study explores the binding modes and interactions between these drugs and MbtA, shedding light on the structural basis of their inhibitory potential. Principal component analysis highlighted significant motions in MbtA-bound ligands, emphasizing the stability of the top Protein-Ligand Complexes (PLCs). This computational approach provides a swift and cost-effective method for identifying new MbtA inhibitors, which can subsequently undergo validation through experimental assays. This streamlined process is facilitated by the fact that these compounds are already FDA-approved and have established safety and efficacy profiles. This study has the potential to lay the groundwork for addressing the urgent global health challenge at hand, specifically in the context of combating Antimicrobial Resistance (AMR) and Tuberculosis (TB).

Polo-like kinase 1 (PLK1) plays a pivotal role in cell division regulation and emerges as a promising therapeutic target for cancer treatment. Consequently, the development of small-molecule inhibitors targeting PLK1 has become a focal point in contemporary research. The adenosine triphosphate (ATP)-binding site and the polo-box domain in PLK1 present crucial interaction sites for these inhibitors, aiming to disrupt the protein's function. However, designing potent and selective small-molecule inhibitors can be challenging, requiring a deep understanding of protein-ligand interaction mechanisms at these binding sites. In this context, our study leverages the fragment molecular orbital (FMO) method to explore these site-specific interactions in-depth. Through the FMO approach, we used the FMO method to elucidate the molecular mechanisms of small-molecule drug binding to these sites to design PLK1 inhibitors that are both potent and selective. Our investigation further entailed a comparative analysis of various PLK1 inhibitors, each characterized by distinct structural attributes. This comparison enhanced our understanding of the structure-activity relationships of these inhibitors, underscoring the efficacy of the FMO method in identifying critical binding features and predicting binding modes for small-molecule ligands. Furthermore, Our research spotlighted "hot spot" residues instrumental for selective and robust PLK1 binding. Our findings offer profound insights, priming the rational design of innovative potential PLK1 inhibitors with significant implications for developing anticancer therapeutics.

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the N-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.

Three-dimensional structure of six closely related hydrogenases from purple bacteria has been modeled by combining template-based and ab initio modeling approach. The results lead to conclusion that there should be 4Fe3S-cluster in the structure of these enzymes. Thus, these hydrogenases could drive attention for exploring their oxygen tolerance and practical applicability in hydrogen fuel cells. Analysis of 4Fe3S-cluster's microenvironment showed intragroup heterogeneity. Possible function of the C-terminal part of the small subunit in membrane binding has been discussed. Comparison of the built models with existing hydrogenases of the same subgroup (membrane-bound oxygen-tolerant hydrogenases) has been carried out. Analysis of intramolecular interactions in the large subunits showed statistically reliable differences in number of hydrophobic interactions and number of ionic interactions. Molecular tunnels were mapped in the models and compared with structures from PDB. Protein-protein docking showed that these enzymes could exchange electrons in oligomeric state, which is important for oxygen-tolerant hydrogenases. Molecular docking with model electrode compounds showed mostly the same results as with hydrogenases from E.coli, H. marinus, R. eutropha, S. enterica; some interesting results were shown in case of HupSL from Rba. sphaeroides and Rvx. gelatinosus.

Prototype of a family of at least nine members, c-src tyrosine kinase is a therapeutically interesting target, because its inhibition might be of interest not only in a number of malignancies, but also in a diverse array of conditions, from neurodegenerative pathologies to certain viral infections. Computational methods in drug discovery are considerably cheaper than conventional methods and offer opportunities of screening very large numbers of compounds in conditions that would be simply impossible within the wet lab experimental settings. We have explored the use of global QSAR models and molecular ligand docking in the discovery of new c-src tyrosine kinase inhibitors. Using a data set of 1038 compounds from ChEMBL and 19 blocks of molecular descriptors, we have developed over 200 QSAR classification models, based on six machine learning algorithms and 17 feature selection methods. We have selected 49 with reasonably good performance (positive predictive value and balanced accuracy higher than 70% in nested cross validation) and the models were assembled by stacking with a simple majority vote and used for the virtual screening of over the “named” ZINC data set (over 100,000 compounds). 744 compounds were predicted by at least 50% of the QSAR models as active, 147 compounds were within the applicability domain and predicted by at least 75% of the models to be active. The latter 147 compounds were submitted to molecular ligand docking using Vina and Ledock, and a number of 90 were predicted to be active based on the binding energy. External data from CHEMBL and PUBCHEM confirmed that at least 7.83% (in the case of QSAR) or 6.67% (in the case of integrated QSAR and molecular docking) of the compounds are active on the c-src target.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

Dysregulation of the arsenal of cells, growth factors, cytokines, proteases, and proteins involved in wound healing (WH), could delay the healing process. Plants and plant-derived molecules (PDMs) have been used as medicines for skin wounds. This study aimed to select and evaluate the pro-healing capacity of PMDs. Thirty-three PDMs and 10 therapeutic targets (TTs) were chosen for molecular docking and PDMs: aristolochic acid (AA), α-copaene, selinenes, β-caryophyllene (BC), and BCoxide, and TTs: metalloproteinase (MMP) 3, MMP13, and tumor necrosis factor (TNF α) for molecular dynamics. The bests inhibitor was AA, but because of its toxicity, BC and BCoxide were chosen for evaluation in HaCat cells and BALB/c mice excisional model. Both compounds were not toxic, and higher percentages of lesion area closure (LAC) were induced by BC treatment (p<0.05). All mice healed; however, an initial delay of LAC was induced by 0.05, 0.1% BCoxide, 0.1% BC, and allantoin. At the end of treatment, lower numbers of mast cells, level of cellular infiltrates (except 1% BCoxide and 0.05, 0.5%BC), epidermal thickness tendency (except 0.1, 0.5% BCoxide), and higher values of SC-thickness, and collagen fibers only by 0.5% BC treatment compared with untreated control (p<0.05) were observed. Our results show that BC is a promising multitarget candidate for wound healing treatment and optimization campaigns.

Most existing cancer therapies negatively affect normal tissue as well as cancerous tissue. A potentially effective strategy for treating cancer that precludes off-target damage and could be an option for most patients would involve targeting one or more mutations that are ubiquitous in the given patient’s tumor(s). To effect this strategy, one would employ multi-region sequencing of a patient’s primary tumor and metastases to seek out mutations that are shared between all or at least most regions. Once the target or targets are known, one would ideally rapidly generate a molecular switch for at least one of said ubiquitous mutations that can distinguish the mutated DNA, RNA, or protein from the wild-type version and subsequently trigger a therapeutic response. I propose that the therapeutic response involve the replication of an oncolytic virus or intracellular bacterium, as any mutation can theoretically be detected by a vector that enters the cell - and automatic propagation could be very helpful. Moreover, the mutation “signal” can be easily enhanced through transcriptional and translational (if the target is an intracellular protein) enhancement. Importantly, RNA may make the best target for the molecular switches in terms of amplification of the signal and ease of targeting.

Thrombosis has threatened human health in past decades. Bacillus nattokinase is a potential thrombolytic drug without side-effect and low cost and has been introduced into the consumer market as a functional food or dietary supplement. This review firstly summarizes the biodiversity sources and fermentation process of nattokinase, and systematically expounds the structure, cata-lytic mechanism and enzymatic properties of nattokinase; In view of the problems of low fermen-tation yield, insufficient activity and stability of nattokinase, this review discusses the heterologous expression of nattokinase in different microbial hosts, and summarizes the protein and genetic en-gineering progress of nattokinase-producing strains; Finally, this review summarizes the clinical application of nattokinase.

This research aims to find out whether the synthetic 1, 2, 4-triazine and its derivatives have antifungal effects and can protect humans from infection with Candida albicans. Molecular docking and molecular dynamic simulation are widely used in modern drug design to target a We are interested in using molecular docking and molecular dynamics modelling to investigate the interaction between the derivatives of 1, 2, 4-triazine and the resulting lanosterol 14 - demethylase (CYP51) of Candida albicans The inhibition of Candida albicans CYP51 is the main goal of our research. The 1, 2, 4-triazine and its derivatives have been docked to the CYP51 enzyme, which is involved in Candida albicans Multidrug Drug Resistance (MDR). Autodock tools were used to identifying the binding affinities of molecules against the target proteins. Compared to conventional fluconazole, the molecular docking results indicated that each drug has a high binding affinity for CYP51 proteins and forms unbound interactions and hydrogen bonds with their active residues and surrounding allosteric residues. The docking contacts were made using a 10 ns MD simulation with nine molecules. RMSD, RMSF, hydrogen bonds, and the Rg all confirm these conclusions. In addition, these compounds were expected to have a favorable pharmacological profile and low toxicity. The compounds are being offered as scaffolds for the development of new antifungal drugs and as candidates for future in vitro testing.

Auxins are chemical compounds of wide interest, mostly due to their role in plant metabolism and development. Since the latter half of the XX century, synthetic auxins have been used as herbicides, presenting notable advantages, such as low toxicity in humans. As of today, extensive descriptions of syntetic and natural auxins have been made; yet studies centered on the molecular recognition process of auxins are scarce. Herein, we present a comprehensive in silico characterization of auxin receptor TIR1, using structure based methods to aid de novo design of putative ligands. In addition, we conducted binding site characterization using cosolvent molecular dynamics and enhanced sampling simulations with reference ligands. We also present a database of putative auxins and decoy compounds which can aid further studies focusing on synthetic auxin design. To the best of our knowledge, this study is the first of its kind focusing on TIR1.

Abstract: The Willows, belonging to the genus Salix, encompass a vast array of species and hybrids, totaling between 330 to 500 species along with approximately 200 hybrids. These plants are found across continents such as Africa, North America, Europe, and Asia, exhibiting diverse forms ranging from trees to shrubs and prostrate plants. Traditionally, Willows have been utilized in folk medicine due to their rich reservoir of biologically active compounds, with salicin being a notable example, serving as a prodrug for salicylic acid.The chemical composition of Willows is highly diverse, with 322 secondary metabolites identified thus far. These include various classes such as flavonoids (94 types encompassing flavonols, flavones, flavanones, isoflavones, flavan-3-ols like catechins and procyanidins, chalcones, dihydrochalcone, anthocyanins, and dihydroflavonols), phenolic glycosides (76), organic acids (28), non-phenolic glycosides (17), sterols, and terpenes (17), simple phenolics (13), lignans (7), as well as volatiles and fatty acids (69). This rich chemical di-versity underpins the various pharmacological activities exhibited by Willows. The pharmacological properties attributed to Willows are extensive and include analgesic, an-ti-inflammatory, antioxidant, anticancer, cytotoxic, antidiabetic, antimicrobial, antiobesity, neuroprotective, and hepatoprotective effects. These properties make Willows a subject of con-siderable interest in the fields of medicine and pharmacology. In summary, Willows represent a valuable natural resource with a diverse chemical composition and a wide range of pharmacological activities. This study aimed to enhance our comprehension of the medicinal characteristics of willow bark extract, focusing on its antimicrobial properties. This investigation holds significance in validating the traditional usage of willow bark and investi-gating its potential utility in contemporary medicine.

Calicioids form a research field that has encompassed ascomycetous fungi with stalked ascomata similar to those of the lichen genus Calicium. Early generic circumscriptions in calicioid lichens and fungi were mainly based on morphological and secondary chemistry information. After the introduction of molecular data, taxonomy in the group has been reconsidered. Here, based on a broad geographical sampling, Coniocybe Ach. was revised using molecular and morphological features. Three loci (ITS, LSU and rpb1) were compared to infer its phylogenetic position, and a total of 52 new sequences (14 ITS, 24 LSU and 14 rpb1) were produced. Coniocybe was revised and emended to include, apart for its type C. furfuracea, also C. brachypoda and C. confusa. In addition, a new species Coniocybe eufuracea, was described, and a key to the species of Coniocybe provided.

Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG is the leading cause of death for pediatric brain tumors due to its infiltrative nature and inoperability. Radiotherapy has only a palliative effect in stabilizing symptoms. In silico and preclinical studies identified ONC201, as a cytotoxic agent against some human cancer cell lines, including DIPG ones. Single crystal X-ray analysis of the complex of the human mitochondrial caseinolytic serine protease type C (hClpP) and ONC201 (PDB ID: 6DL7) allowed to identify hClpP as its main target. Hyperactivation of hClpP causes damage to mitochondrial oxidative phosphorylation and cell death. In some DIPG patients, receiving ONC201, an acquired resistance was observed. In this context, a wide program was initiated to discover original scaffolds for new hClpP activators to treat ONC201-non-responding patients. Harmaline, a small molecule belonging to the chemical class of β -carboline, was identified through Fingerprints for Ligands and Proteins (FLAP), a structure-based Virtual Screening approach. Molecular dynamics simulations and a deep in vitro investigation showed interesting information on the interaction and activation of hClpP by harmaline.

NSD3 is a member of the NSD histone methyltransferase family of proteins. In recent years, it has been identified as a potential oncogene in certain types of cancer. NSD3 gene encodes three isoforms, the full length, a short (NSD3S) and WHISTLE isoforms. Importantly, NSD3S isoform corresponds to the N-terminal of the full-length protein, lacking the methyltransferase domain. The chromosomal location of NSD3 is frequently amplified across cancer types, such as breast, lung, colon, among others. Recently, this amplification has been correlated to a chromothripsis event, that could explain the different NSD3 alterations found in cancer. Fusion proteins containing NSD3 have also been reported, such as leukemia NSD3-NUP98, and in NUT midline carcinoma (NMC), NSD3-NUT fusion. Its role as an oncogene has been described by modulating different cancer pathways through its methyltransferase activity, or the short isoform of the protein, through protein interactions. Specifically, in this review we will focus on stating the functions that have been characterized as methyltransferase dependent, and those that have been correlated with the expression of the NSD3S isoform. Altogether, there is evidence that both isoforms of NSD3 are relevant for cancer progression, establishing NSD3 as a therapeutic target. However, further functional studies are needed to differentiate NSD3 oncogenic activity as dependent or independent of the catalytic domain of the protein, as well as the contribution of each isoform and its clinical significance in cancer progression.

The methods used to introduce CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas-mediated genome editing into fruit species, as well as the impacts of the application of this technology to activate and knock out of target genes in different fruit trees species including tree development, yield, fruit quality, and tolerance to biotic and abiotic stresses have been firstly described in this review. The application of this gene editing technology could allow the development of new generations of fruit crops with improved traits by targeting different genetic segments or even could facilitate the introduction of traits in elite cultivars without changing other traits. However, at this moment, the scarcity of efficient regeneration and transformation protocols in some species, the fact that many of those procedures are the genotype-dependent or the convenience of segregating the transgenic parts of the CRISPR system represent the main handicaps limiting the potential of genetic editing techniques for fruit trees. Finally, latest news on the legislation and regulations about the use of plants modified through CRISPR/Cas systems has been also discussed.

Birds are highly social and need pairing in order to increase their welfare. Most bird species are monomorphic, therefore, molecular sexing helps to provide appropriate welfare for birds. Moreover, early sex determination can be of great value for bird owners. The aim of this study was to demonstrate that sex identification in birds by molecular methods, using samples collected by minimally invasive methods is fast, efficient and accurate. A total of 100 samples (29 paired samples of feathers - oral swab and 14 tripled samples of feathers - oral swab - blood) from 43 birds were taken into study, as follows: wild birds (Falconiformes, Accipitriformes, landfowl – Galliformes, waterfowl– Anseriformes), companion birds (Passeriformes, Psittaciformes – large, medium and small size parrots). Amplification of CHD1-Z and CHD1-W genes was performed by conventional PCR. The results obtained from feathers were compared to those obtained from oral swabs and with those obtained from blood samples, where was the case. The obtained results show that all types of samples can be used for molecular sexing of all studied species of birds. According to our knowledge, the present study reports for the first time the molecular sex identification in: Red Siskin (Carduelis cucullata) and Goldfinch (Carduelis carduelis major). For higher accuracy, our recommendation is to use minimally invasive samples (swab-feathers) and to test both types of samples, for each bird, instead of blood samples.

This review presents an updated overview of research concerning Leishmania protein structures, primarily sourced from the Protein Data Bank (PDB), that play a role in the metabolic pathways of the Leishmania parasite. Furthermore, we assess the current progress in the identification and development of bioactive chemical agents aimed at addressing this substantially overlooked tropical disease. We have analyzed experimental data obtained from in vitro, in vivo and in silico sources. This data has been categorized into four main areas: a) vector taxonomy and geographic distribution; b) parasite taxonomy and geographic distribution; c) enzymatic functions of proteins engaged in parasite/host interactions throughout various developmental stages (such as oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases, and cytokines); and d) established and experimental treatments employing bioactive chemical compounds. Our objective is to establish a foundational point of reference for research efforts concentrating on the elucidation of interaction mechanisms and the processes of ligand-protein activation/inactivation, specifically linked to Leishmania infections. Consequently, we emphasize enzymes recognized for their involvement in the biochemical pathways incited during Leishmania infection episodes. This review encapsulates the current understanding, offering insights to inform and direct future explorations aimed at targeting proteins and pathways to enhance the management of Leishmania-related diseases.

This study investigates the impact of temperature-induced quantum proton tunneling probability on DNA amplification during polymerase chain reactions (PCR). Using a simulation model based on a Gaussian wavefunction and finite-difference time-domain method, quantum tunneling of protons across square potential barriers is examined. The results unveil consistent probability distributions for quantum tunneling across various PCR temperatures, with distinct oscillation patterns emerging post-barrier crossing. Acknowledging limitations in initial conditions due to temperature-dependent proton energy, the study highlights the need for refined models and experimental validation. These findings accentuate the potential interplay between quantum mechanics and biological systems, prompting further research to understand quantum tunnelling’s comprehensive effect on genetic variations and molecular processes.

Ebola virus is a zoonotic virus comprised of 6 different species designated within the family Filoviridae and genus Ebolavirus. The first recorded outbreak of an Ebola virus (EBOV) was in Yambuku, Zaire (ZEBOV) in 1976, followed by Sudan Ebola virus (SUBOV) later that year. Outbreaks have been increasing throughout the 21st century, and mortality rates can reach up to 90%. Such extraordinary virulence is evidenced with few pathogens, similarly with Marburg virus (MARV) that originated in Uganda and was first detected in Germany in 1967. The virulent nature of filovirus disease has established these related viruses as a formidable global concern. There are currently four types of Ebolaviridae species known to infect humans, with two more recently identified in other animals that are genomically different with respect to cellular pathogenesis or aetiology of disease. Recent advances into understanding the pathogenesis of filovirus disease infections have been remarkable, yet the immunological response to filovirus infection remains unknown. Scientific analysis of cellular mechanisms can provide insight into virulence factors utilised by other pathogenic viruses that also cause febrile illness with occasional haemorrhagic fever in humans. In this review, we aim to provide a brief summary of EBOV proteins and the role of innate and adaptive immune cells known since 2000. We will consider the relevance and implications of immunological proteins measured by CD marker, alongside cytokine, chemokine and other biologically relevant pathways, as well as genetic research. Thorough understanding of immunological correlates affecting host responses to Ebola viruses will facilitate both clinical and applied research knowledge, contributing towards protection against potential public health threats.

Background: Strongyloidiasis, a neglected disease caused by intestinal nematodes of the genus Strongyloides, is endemic to tropical and subtropical areas such as Vietnam. The morphological diagnosis of larvae by Hara Mori culture technique and microscopicare are considered the standard diagnostic procedures in the endemic areas of Strongyloides spp. However, they could only identify the genus, not the species of Strongyloides. DNA-molecular techniques which are highly sensitive and more cost-effective have been increasingly utilized in detection of Strongyloides species. This study aims to determine prevalence and the species of Strongyloides among resident population in Duc Hoa district, Long An province, Southern Vietnam. Methods: A cross-sectional study was conducted using 1,190 stool samples collected in Duc Hoa district, Long An province, Vietnam, from July, 2017 to November 2018. The stool specimens were transported to the Laboratory of Medical Parasitology, Pham Ngoc Thach University of Medicine within two hours of collection at an appropriate temperature of 25 oC. All samples were stored at 2 - 8°C and processed within 48 hours for microscopic examination. Molecular detection was carried out at Laboratory of Molecular Biology, Pham Ngoc Thach University of Medicine, Hochiminh city, VietNam. Results: Of the 1,190 samples tested, Strongyloides spp. larvae were detected in 79 specimens (6.6%) by two classical parasitological methods, namely direct microscopy and the modified Harada-Mori filter paper culture. DNA was extracted from 70 of the 79 samples of Strongyloides spp. larvae, which was subsequently characterized by real-time PCR amplification of the 18S and 28S regions of the rDNA gene. The results showed that 97.1% of the DNA samples were S. stercoralis, 2.9% were co-infections with S. ratti and S. stercoralis, and 2.9% belonged to S. ratti. For all 14 isolates, nucleotide sequencing was compared with other human pathogenic species of Strongyloides whose sequences are available in GenBank. The identity of 12/14 sequences were confirmed as S. stercoralis with a high level of similarity (91.3% - 100%) and over 98% for S. ratti. Between the two co-infection samples, the higher similarity belonged to S. stercoralis. Conclusion: A molecular amplification of small subunit ribosome RNA followed by sequence analysis has been proved to be a suitable method for discrimination of Strongyloides spp. retrieved from stool samples.

Leishmaniasis is a neglected tropical disease and affects more than 350 million people worldwide. However, there are no vaccines for humans, and current treatment is hampered due to its high cost, numerous side effects, and painful administration routes. Ending its epidemics by 2030 has become a United Nations goal, and the multitarget drug strategy emerges as a promising alternative. Flavonoids are an example of multitarget compounds and organic synthesis represents a tool to obtain high yields of these molecules. In our study, we synthesized 17 flavonoid analogs using a scalable, easy-to-reproduce, and inexpensive method. All compounds demonstrated an impressive inhibition capacity against rCPB2.8, rCPB3, and rH84Y, which are highly expressed in the amastigote stage, the target form of the parasite. Compounds 3c, f12a, and f12b stood out as effective against all isoforms and intermolecular interactions were investigated through a molecular modeling study. The compounds were highly potent against the parasite and demonstrated low cytotoxic action against mammalian cells. The results were pioneering, representing an advance in the investigation of the mechanisms behind the antileishmanial action of flavonoid derivatives. Furthermore, compounds have shown to be promising leads for the design of other cysteine protease inhibitors for the treatment of leishmaniasis diseases.

Wildfires have continued to increase in frequency and severity in Southern California due in part to climate change. To gain a further understanding of microbial soil communities’ response to fire and functions that may enhance post-wildfire resilience, soil fungal and bacterial microbiomes were studied from different wildfire areas in the Gold Creek Preserve within the Angeles National Forest using 16S, FITS, 18S, 12S, PITS, and CO1 amplicon sequencing. Sequencing datasets from December 2020 and June 2021 samplings were analyzed using DNA Subway, ranacapa, stats, vcd, EZBioCloud, and mixomics. Significant differences were found among bacterial and fungal taxa associated with different fire areas in the Gold Creek Preserve. There was evidence of seasonal shifts in the alpha diversity of the bacterial communities. In the sparse partial least squares analysis, there were strong associations (r>0.8) between longitude, elevation, and a defined cluster of Amplicon Sequence Variants (ASVs). The Chi-square test revealed differences in fungi:bacteria (F:B) proportions between different trails (p=2*10^-16). sPLS results focused on a cluster of Green Trail samples with high elevation and longitude. Analysis revealed the cluster included the post-fire pioneer fungi Pyronema, and Tremella. Chlorellales algae, and pathogenic Fusarium sequences were elevated. Bacterivorous Corallococcus, which secretes antimicrobials, and bacterivorous flagellate Spumella, were associated with the cluster. There was functional redundancy in clusters that were differently composed, but shared similar ecological functions. These results implied a set of traits for post fire resiliency. These included photo-autotrophy, mineralization of pyrolyzed organic matter and aromatic/oily compounds, pathogenicity and parasitism, antimicrobials, and N-metabolism.

Molecular iodine (I2) induces apoptotic, antiangiogenic, and antiproliferative effects in breast cancer cells. Little is known about its effects on the tumor immune microenvironment. We studied the effect of oral (5 mg/day) I2 supplementation alone (I2) or together with conventional chemotherapy (Cht+I2) on the im-mune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I2 and Cht+I2 samples showed significant increases in expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I2 groups. Real-time RT-PCR showed that I2 tumors overexpress T-BET (p = 0.019) and interferon-gamma (IFNγ; p = 0.020) and silence tumor growth factor-beta (TGFβ; p = 0.049); whereas in Cht+I2 tumors, GATA3 is silenced (p = 0.014). Preliminary methylation analysis shows that I2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFβ in Cht+I2. In conclusion, our data showed that I2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also participate.

The main aim of this study is to identify inhibitory binding potent of the available commercially alkaloids, against the crystal structure of acetylcholinesterase (AChE) protein by in silico studies. The inhibitory data of the compounds should be compared with the internal ligand as well as standard AChE inhibitor Aricept (which is used for the treatment of all stages of Alzheimer’s disease). AutoDock 4.0 is used for the docking study, conformational orientation site analysis, and, with the help of docking, we have calculated parameters like binding energy and inhibition constant. Docking's study showed that Glabridin, Isorosmanol, Quercetin, Honokiol, Eckol, Sargaquinoic acid, and Ginsedosides revealed strong binding affinity with the enzyme. Moreover, The ADMET profiling and physicochemical properties of the selected compounds are evaluated using the Molinspiration and Data warrior software. By showing a strong binding affinity value, positive bioactivity score, and good pharmacokinetic properties, the top compound was determined. After evaluation with all parameters, the compound Glabridin and Ginsedosides show the most potent inhibitory effect towards the acetylcholinesterase, so this compound could be used as a novel is required to treat Alzheimer's disease.

introduction: Cancer, as clusters of diseases, uncontrolled cell proliferation due to tumor suppressor genes inactivation, oncogenes activation, and external factors.Methods: To review data, electronic databases such as Nature, PubMed/PMC, Science Direct/Elsevier, EMBASE, and Google Scholar were used.Results: Derestricted forms of proto-oncogenes are oncogenes, which had vital roles in various paths of cell cycle modulation. Translocations and chromosomal rearrangement and/or mutations in genes are the major factors for the transformation of proto-oncogene to oncogenes. Herein, to prevent the proliferation of cancerous cells, oncogenes are targeted molecules. From a cancer therapeutic target point of view, oncogene silencing and deletion, mutation of tumor suppressor genes, and retroviral therapy molecular techniques were developed. Conclusion: To establish a cancer-free world, the most commonly used techniques are: Ribose Nucleic Acid interferences, zinc finger nucleases, and CRISPR.Keywords: Cancer, Oncogenes, Proto-oncogenes, molecular technique

Tuberculosis (TB) is a contagious disease, caused by Mycobacterium tuberculosis (MTB) that has infected and killed a lot of people in the past. At present treatments against TB are available at a very low cost. Since these chemical drugs have many adverse effects on health, more attention is now given on the plant-derived phytochemicals as potential agents to fight against TB. In this study, 5 phytochemicals, 4-hydroxybenzaldehyde, benzoic acid, bergapten, psoralen, and p-hydroxybenzoic acid, are selected to test their potentiality, safety, and efficacy against two potential targets, the MTB RNA polymerase and enoyl-acyl carrier protein (ACP) reductase, the InhA protein, using various tools of in silico biology. The molecular docking experiment, drug-likeness property test, ADME/T-test, P450 SOM prediction, pharmacophore mapping, and modeling, solubility testing, DFT calculations, and PASS prediction study had confirmed that all the molecules had the good potentiality to inhibit the two targets. However, two agents, 4-hydroxybenzaldehyde and bergapten were considered as the best agents among the five selected agents and they also showed far better results than the two currently used drugs, that function in these pathways, rifampicin (MTB RNA polymerase) and isoniazid (InhA protein). These two agents can be used effectively to treat tuberculosis.

Some α-Pyrone derivatives isolated from Alternaria phragmospora fungus showed promising anti leukemic activities, while others were inactive. CRM1/XPO1 (chromosome region maintenance 1 protein, also called exportin1 or PO1 in humans) has been chosen as a target for antileukemic molecular docking study for those compounds to understand their modes of interaction and structure activity relationships. The results showed that two (2 and 4), out of six, natural α-Pyrone derivatives exhibited well-established interactions with the amino acids of the receptor, which was in agreement with the experimental anti-leukemic results of these compounds. Moreover, twenty hypothetical chemically modified α-Pyrone derivatives (7-27) have been designed. Compounds 7, 8, 22 and 24 showed more efficient docking properties than the previously considered natural compounds.

There has recently been interest in the development of small-molecule inhibitors of the oligomerization of Bacillus anthracis protective antigen for therapeutic use. Some of the proposed lead compounds have, however, unfavorable solubility in aqueous medium, which prevents their clinical use. In this computational work, we have designed several hundreds of derivatives with progressively higher hydrosolubility and tested their ability to dock the relevant binding cavity. The highest-ranking docking hits were then subjected to 125 ns-long simulations to ascertain the stability of the binding modes. Several of the potential candidates performed quite disappointingly , but two molecules showed very stable binding modes throughout the complete simulations. Besides the identification of these two promising leads, these molecular dynamics simulations allowed the discovery of several insights that shall prove useful in the further improvement of these candidate towards higher potency and stability.

Molecular dynamics simulations were carried out to investigate the atomic structure of a model Cu64Zr36 bulk metallic glass (BMG). It is found that the amount of icosahedral content of the system is significantly increased in a well relaxed structure. While we considered four connection types of vertex-, edge-, face-, and volume-sharing, the huge cluster in the relaxed samples mainly involve volume-type connection and exhibits a remarkable athermal plasticity that great stiffness and great yield strength compared to the as-quenched samples. In addition, the bond-angle distribution of annealed sample shows sharp peaks at specific bond angles which is an evidence of crystallized Laves-phase formed by icosahedral atoms, however the peaks are to be broaden after loading, which indicates decreasing amount of icosahedral content and their shape distortion. These results suggest that icosahedral content in a bulk metallic glasses plays a key role to determine the mechanical properties such as rigidity and maximum stress carrying capacity.

The dark proteome as we define it, is the part of the proteome where 3D structure has not been observed either by homology modeling or by experimental characterization in the protein universe. From the 550.116 proteins available in Swiss-Prot (as of July 2016) 43.2% of the Eukarya universe and 49.2% of the Virus universe are part of the dark proteome. In Bacteria and Archaea, the percentage of the dark proteome presence is significantly less, with 12.6% and 13.3% respectively. In this work, we present the map of the dark proteome in Human and in other model organisms. The most significant result is that around 40%- 50% of the proteome of these organisms are still in the dark, where the higher percentages belong to higher eukaryotes (mouse and human organisms). Due to the amount of darkness present in the human organism being more than 50%, deeper studies were made, including the identification of ‘dark’ genes that are responsible for the production of the so-called dark proteins, as well as, the identification of the ‘dark’ organs where dark proteins are over represented, namely heart, cervical mucosa and natural killer cells. This is a step forward in the direction of the human dark proteome.

In this report we have discussed the important role of molecular modeling, especially the use of the molecular dynamics method, in investigating transport processes in nanoporous materials such as membranes. With the availability of high performance computers, molecular modeling can now be used to study rather complex systems at a fraction of the cost or time requirements of experimental studies. Molecular modeling techniques have the advantage of being able to access spatial and temporal resolution which are difficult to reach in experimental studies. For example, sub-Angstrom level spatial resolution is very accessible as is sub-femtosecond temporal resolution. Due to these advantages, simulation can play two important roles: Firstly because of the increased spatial and temporal resolution, it can help understand phenomena not well understood. As an example, we discuss the study of reverse osmosis processes. Before simulations were used it was thought the separation of water from salt was purely a coulombic phenomenon. However, by applying molecular simulation techniques, it was clearly demonstrated that the solvation of ions made the separation in effect a steric separation and it was the flux which was strongly affected by the coulombic interactions between water and the membrane surface. Additionally, because of their relatively low cost and quick turnaround (by using multiple processor systems now increasingly available) simulations can be a useful screening tool to identify membranes for a potential application. To this end, we have described our studies in determining the most suitable zeolite membrane for redox flow battery applications. As computing facilities become more widely available and new computational methods are developed, we believe molecular modeling will become a key tool in the study of transport processes in nanoporous materials.

In the present work, we provide an electronic structure based method for the “on-the-fly” deter- mination of vibrational sum frequency generation (v-SFG) spectra. The predictive power of this scheme is demonstrated at the air-water interface. While the instantaneous fluctuations in dipole moment are obtained using the maximally localized Wannier functions, the fluctuations in polar- izability are approximated to be proportional to the second moment of Wannier functions. The spectrum henceforth obtained captures the signatures of hydrogen bond stretching, bending, as well as low-frequency librational modes.

Lung cancer is one of the most important health risks worldwide for human. Non-small cell lung cancer (NSCLC) is the most common cause of premature death from malignant disease. This study provides in-depth insights from systems biology analyses to identify molecular to inform systemic drug targeting in NSCLC. Gene expression profiles from non small cell lung cancer were analyzed with genome-scale biomolecular networks (I,e., protein-protein interaction, transcriptional and post transcriptional regulatory networks). The aim of the study was to determine the pathways and expression profile of the genes to discover molecular signature at RNA and protein levels which could serve as potential drug targets for therapeutics innovation and the identification of novel targets. Eight proteins, six TFs and seven miRNAs came into prominence as potential drug targets. The differential expression profiles of these reporter biomolecules were cross-validated by independent RNA-Seq and miRNA-Seq. Risk discrimination performance of the reporter biomolecules NPR3, JUN, PPARG, TP53, CKMT1A, SP3 and TFAP2A were also evaluated. Total 213 drugs and 7 proteins were found for non small cell lung cancer through dgidb. Among these identified drugs seven drugs such as- Gemcitabine, Carboplatin, paclitaxel, Docetaxel, Crizotinib, Bevacizumab and Gemcitabine is used for NSCLC which is approved by National Cancer Institute. The molecular signatures and repurposed drugs presented here permit further attention for experimental studies which are offer significant potential as biomarkers and candidate therapeutics for precision medicine approaches to clinical management of NSCLC.

: Early and accurate detection of infectious diseases is a key step for surveillance, epidemiology, and control, notably timely disease diagnosis, patient management and follow-up. In this study, we aimed to develop hand-held ultra-fast duplex PCR assays coupled to amplicon detection by lateral flow (LF) immunoassay to deliver a rapid, and simple molecular diagnostic test for con-comitant detection and identification of the main Leishmania parasites encountered in Tunisia and the Old World. We selected two DNA targets to amplify L. major/L. tropica and L. infantum/L. tropica group of species DNAs, respectively. We optimized the experimental conditions of a du-plex ultra-fast PCR. The amplification is performed by a portable Palm convection PCR machine within 18 min and the products are detected by a LF cassette within 10 minutes. The test allows the identification of the infecting species according to the position and number of test lines re-vealed. Tested on a selection of DNAs of representative Leishmania strains of the three studied species (N=37), the ultra-fast duplex PCR-LF showed consistent, stable, and reproducible results. The analytical limit of detection of the test was 0.4pg for L. major, 4pg for L. infantum and 40pg for L. tropica.

Covid-19 is one of humanity’s biggest threat in the 21st century with WHO figures reporting 636 million cases and up to 6.6 million deaths globally. SARS-CoV-2, the virus that causes the Covid-19 disease, is characterized by high mutation which contributes to its rapid spread. While several vaccines have been produced to minimize the severity of the coronavirus and diverse treatment regimens have been approved by the US FDA under Emergency Use Authorization (EUA), SARS-CoV-2 viral mutations continue to derail the efforts of scientists as the emerging variants evade the recommended therapies. Nonetheless, diverse computational models exist that offer an opportunity to overcome the barriers involved in developing new drugs. In this review, the focus is on the use of various virtual screening techniques like molecular docking, molecular dynamics simulations, QSAR, pharmacophore modeling, and homology modeling in repurposing SARS-CoV-2 therapeutics. The results have been promising from the computer-aided drug design (CADD) studies in suggesting potential compounds for treatment of Covid-19 and helping in bringing the pandemic under control.

The development of microbial products for cancer treatment has been in the spotlight in recent years. In order to accelerate the lengthy and expensive drug development process, in silico screening tools are systematically employed, especially during the initial discovery phase. Moreover, considering the steadily increasing number of molecules approved by authorities for commercial use, there is a demand for faster methods to repurpose such drugs. Here we present a review on virtual screening web tools, publicly available databases of molecular targets and libraries of ligands, with the aim to facilitate the discovery of potential anticancer drugs based on microbial products. We provide an entry-level step-by-step description of the workflow for virtual screening of microbial metabolites with known protein targets, as well as two practical examples using freely available web tools. The first case presents a virtual screening study of drugs developed from microbial products using Caver Web, a web tool that performs docking along a tunnel. The second case comprises a comparative analysis between a healthy isocitrate dehydrogenase 1, a mutant that results in cancer, using the recently developed web tool PredictSNP^Onco. In summary, this review provides the basic and essential background information necessary for virtual screening experiments, which may accelerate the discovery of novel anticancer drugs.

Infectious diseases are a global health problem affecting billions of people. Developing rapid and sensitive diagnostic tools is key for successful patient management and curbing disease spread. Currently available diagnostics are very specific and sensitive but time-consuming and require expensive laboratory settings and well-trained personnel; thus, they are not available in resource-limited areas, for the purposes of large-scale screenings and in case of outbreaks and epidemics. Developing new, rapid, and affordable point-of-care diagnostic assays is urgently needed. This review focuses on CRISPR-based technologies and their perspectives to become platforms for point-of-care nucleic acid detection methods and as deployable diagnostic platforms that could help to identify and curb outbreaks and emerging epidemics. We describe the mechanisms and function of different classes and types of CRISPR-Cas systems, including pros and cons for developing molecular diagnostic tests and applications of each type to detect a wide range of infectious agents. Many Cas proteins (Cas9, Cas12, Cas13, Cas14) have been leveraged to create highly accurate and sensitive diagnostic tools combined with technologies of signal amplification and fluorescent, potentiometric, colorimetric, or lateral flow assay detection. In particular, the most advanced platforms -- SHERLOCK/v2, DETECTR, or CRISPR-Chip -- enable detection of attomolar amounts of pathogenic nucleic acids with specificity comparable to that of PCR but with minimal technical settings. Further developing CRISPR-based diagnostic tools promises to dramatically transform molecular diagnostics, making them easily affordable and accessible virtually anywhere in the world. The burden of socially significant diseases, frequent outbreaks, recent epidemics (MERS, SARS and the ongoing coronoviral nCov-2019 infection) urgently need the developing of express-diagnostic tools. Recently devised CRISPR-technologies represent the unprecedented opportunity to reshape epidemiological surveillance and molecular diagnostics.

Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: small duct type and large duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes–inflammation and proliferation–have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Precise HDV-RNA detection and quantification are pivotal for accurate diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three assays: Hepatitis Delta RT-PCR system, EurobioPlex HDV assay, and the RoboGene HDV RNA Quantification kit 2.0, testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. Finally, all HDV-RNA positive samples were genotyped using a next-generation sequencing strategy. Qualitative results indicated a 100% concordance between tests. Quantitative results correlated well between tests, r2=0.703 (Vircell-vs-Eurobio), r2=0.833 (Vircell-vs-RoboGene), r2=0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results in terms of correlation and bias. The three assays demonstrate promising performance. Their accuracy, reflected in concordance rates and quantitative analysis, makes them suitable for clinical practice. However, in the absence of assay harmonization, quantitative HDV RNA monitoring should be performed in the same laboratory and assay to avoid variability.

The emergence of diverse infections worldwide, which is a serious global threat to human existence, necessitate the urgent development of novel therapeutic candidates that can combat these diseases with efficacy. Isatin, a secondary metabolite from tryptophan is considered a privileged scaffold and favorable pharmacophore with a unique structural moiety and varied chemical and biological properties resulting in its widespread applications by medicinal chemists. Molecular hybridization is one of the most common and important techniques use in the synthesis of their bioactive hybrids in drug discovery. This review containing published articles from 2005 to 2022 focuses on isatin hybrids which have been synthesized and reported in the literature alongside a discussion on their biological properties. The purpose of this review is to set up the direction for the design and development of isatin-hybrids with tailored biological properties as effective therapeutic candidates inspired by nature.

Alzheimer's disease (AD), which is characterized by the development of β-amyloid plaques and neurofibrillary tangles in the brain parenchyma, can result in synaptic and neuronal loss. Clinical signs, including deteriorating memory deficiency, may lead to catastrophic effects for the elderly. Research on brain imaging and its application in the study of AD has advanced extraordinarily over the past 30 years. However, widely used imaging methods are only capable of identifying structural or metabolic alterations at the anatomical level in the brain and can only be utilized for drawing inferential distinctions. As a disease with a complex pathophysiological mechanism, AD has many different molecular pathological features and molecular biomarkers. Therefore, molecular imaging for AD pathology indicators provides a practical method for the early diagnosis and impartial assessment of AD. The present review discusses the pathogenesis of AD, as well as the detection methods and principles of molecular imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) techniques. Meanwhile, various tracers and probes applied in molecular imaging that detect Aβ deposits, tau protein accumulation, and neurotransmitters are also reviewed. Molecular pathological tracers provide the possibility to accurately quantify brain changes through molecular imaging.

Matrix asphalt material has poor road performance, which is improved by adding polymer modified agents. The original asphalt material experiment research has a certain limitation in that it cannot truly expose the mechanism and influence of modifiers on asphalt materials. To explore the gain effect of the modified agent on the asphalt material's road performance, the molecular dynamic simulation technology is used to explain its mechanism in the micro dimension. The three parameters of the free volume score, radial distribution function and average directional shift diffusion coefficient are analysed to improve the performance of the modifier on asphalt material, an exploration of the microdimension shows that the amount of SBS modifiers is 6% and the amount of rubber modified asphalt material is 22%. The improvement of materials is better than that of rubber modifiers.

Bulbophyllum is one of the largest genera and presents some of the most intricate taxonomic problems in the family Orchidaceae, including species of ornamental and medical importance. The lack of knowledge regarding the characterization of Bulbophyllum chloroplast (cp) genomes has imposed current limitations on our study. Here, we reported the complete cp genomes of seven Bulbophyllum species, including B. ambrosia, B. crassipes, B. farreri, B. hamatum, B. shanicum, B. triste and B. violaceolabellum, and compared with related taxa to provide a better understanding of their genomic information on taxonomy and phylogeny. A total of 28 Bulbophyllum cp genomes exhibit typical quadripartite structures with lengths ranging from 145,092 bp to 165,812 bp and GC content of 36.60% to 38.04%. Each genome contained 125–132 genes, encompassing 74–86 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The genome arrangements, gene contents and length were similar with differences observed in ndh gene composition. A total of 18–49 long repeats and 38–80 simple sequence repeats (SSRs) were detected and the single-nucleotide (A/T) was dominant in Bulbophyllum cp genomes, with an obvious A/T preference. An analysis of relative synonymous codon usage (RSCU) revealed Leucine (Leu) was the most frequently used codon, while cysteine (Cys) was the least used. Six highly variable regions including ndhF-trnLUAG, trnTUGU-trnLUAA, trnFGAA-ndhJ, rps15-trnNGUU, rbcL-accD and psbI-trnSGCU were identified based on the ranking of the Pi values, had the potential to serve as DNA markers for species identification and phylogeny of the genus Bulbophyllum. Phylogenetic analysis based on the complete cp genome sequences and 68 protein-coding genes strongly supported 28 Bulbophyllum species can be divided into four branches and sects. Brachyantha, Cirrhopetalum, Leopardinae defined by morphology were non-monophyly. Our results enriched the genetic resources of Bulbophyllum species, providing valuable information to illustrate the complicated taxonomy, phylogeny and evolution process of the genus.

Telomeres are specialized structures at the ends of linear chromosomes that protect them from degradation and fusion. Telomere replication is a complex process that involves both DNA polymerases and a specialized enzyme called telomerase. Telomerase is a ribonucleoprotein complex that synthesizes telomeric DNA by using an internal RNA template. However, telomerase alone cannot fully replicate the telomeric DNA, and requires the cooperation of other factors, such as shelterin, CST, and DNA repair proteins. Moreover, telomere replication is tightly regulated by various mechanisms, such as cell cycle checkpoints, telomere length homeostasis, and telomere position effect. Dysregulation of telomere replication can lead to genomic instability, cellular senescence, and cancer. Therefore, understanding the molecular details of telomere replication is crucial for elucidating the role of telomeres in aging and disease.

Quercetin (QUA), a flavonoid compound, is ubiquitously found in plants and has demonstrated a diverse range of biological activities. The primary objective of the present study is to assess the potential antiemetic properties of QUA using an in vivo and in silico approach. In this experiment, emesis was induced in 4-day-old chicks by orally administering copper sulfate pentahydrate (CuSO4.5H2O) at a dose of 50 mg/kg (orally). Domperidone (6 mg/kg), ondansetron (5 mg/kg), and hyoscine (21 mg/kg) were treated as positive controls (PCs), and distilled water was employed as a negative control (NC). QUA was administered orally at two distinct doses (25 and 50 mg/kg). Additionally, QUA (50 mg/kg) and PCs were administered separately or in combination to assess their antagonistic or synergistic effects on the chicks. The binding affinity of QUA and referral ligands towards 5HT3, D2, D3, and M1–M5 receptors was estimated, and ligand-receptor interactions were visualized through various computational tools. In vivo findings indicate that QUA (25 and 50 mg/kg) has a significant effect on reducing the number of retches (16.50 ± 4.65 and 10.00 ± 4.19 times) and increasing the chick latency period (59.25 ± 4.75 and 94.25 ± 4.01 seconds), respectively. Additionally, QUA (50 mg/kg) in combination with domperidone and ondansetron exhibited superior antiemetic effects, reducing the number of retches and increasing the onset of emesis-inducing time. Furthermore, it is worth noting that QUA demonstrated the strongest binding affinity towards the D2 receptor with a value of -9.7 kcal/mol through the formation of hydrogen and hydrophobic bonds. In summary, the study found that QUA exhibited antiemetic activity in chicks, potentially by interacting with the D2 receptor pathway.

Abrstract: Bacillus spp. it is a genus that is used to biocontrol post-harvest diseases in various vegetables and fruits during transportation and storage. It suppresses the development of pathogens such as gray mold (Botrytis cinerea) in strawberry cultivation. In this work, the molecular characterization of Bacillus spp. species was carried out. in three cities in Peru: Huaura, Chanchamayo and Cañete. The samples were collected from rhizospheric soil from crop areas, subsequently processed for microbiological isolation, molecular analysis using the 16S rRNA gene and bioinformatic analysis. In total, 14 strains were obtained where they were identified with a minimum of 92.05% and a maximum of 100% similarity: 8 strains of Bacillus subtilis, 4 strains of Bacillus licheniformis, 1 strain of Bacillus paralicheniformis and 1 strain of Bacillus cereus, all the strains were related by constructing a phylogenetic tree.

The purpose of this article is to highlight the new advancements in molecular and diagnostic genetic testing as well as properly classify all ovarian cancers. In this article we address statistics, histopathological classification, molecular pathways implicated in ovarian cancer, genetic screening panels and details about the genes, and also candidate genes. We hope to bring new information in the medical field as to better prevent and diagnose ovarian cancer.

Rapeseed (Brassica napus L.) is one of the most important oil crops in China. Improving oil production of rapeseed is an important way to ensure the safety of edible oil in China. Oil production is an important index to reflect the quality of rapeseed and is determined by oil content and yield. Applying nitrogen is an important way to ensure a high yield. However, increasing nitrogen application would decrease oil content. Thus, it is critical to screen elite germplasm resources with stable or improved oil content under high nitrogen and to investigate the molecular mechanisms of nitrogen regulation of oil accumulation. In this paper, we review the effects of nitrogen levels on rapeseed yields and oil content, aiming to reveal the mechanisms of nitrogen regulation in oil accumulation and thereby provide a theoretical basis for breeding varieties with high oil content.

The emergence of multi-drug resistant bacteria has severely increased the burden on the global health system, and such pathogen infections are considered a great threat to human well-being. Antimicrobial peptides, due to their potent antimicrobial activity and low possibility of inducing resistance, are increasingly becoming the focus of much interest. Herein, a novel dermaseptin peptide, named Dermaseptin-SS1 (SS1), was identified from a skin secretion-derived cDNA library of the South/Central American tarsier leaf frog, Phyllomedusa tarsius, using a ‘shotgun’ cloning strategy. Chemically-synthesised peptide SS1 was found to be broadly effective against Gram-negative bacteria with low haemolytic activity in vitro. A designed synthetic analogue of SS1, named peptide 14V5K, showed a lower salt sensitivity with more rapid bacteria-killing compared to SS1. Both peptides employed the membrane-targeting mechanism to kill Escherichia coli. The antiproliferative activity of SS1 and its analogues, against lung cancer cell lines, was found to be significant.

In bilaterians organism, the signaling of pyramidal neurons (PyrNs) is linked to the relative (prevalent) molecular chirality and physiological, perceptual, cognitive, and psychological functions and dysfunctions, providing the coupling of the central nervous system downstream and upstream evolutionary and developmental processes. The most apparent and discriminating morphological specificity of PyrNs is the geometry of the cell body. However, the question "why/how PyrNs soma gains the shape of quasi-tetrahedral symmetry" has never been explicitly articulated. If the basic function of PyrNs is sensory space perception, supporting the orientation, and movement coordination, then the pyramidal shape of soma is the best evolutionary-selected geometry to perform sensory-motor coupling. In biology, the impact of chiral symmetry (handedness) is evident at all levels of biological organization, from the prevalent symmetry of biological molecules to the morphology and function of bilateral organisms. How the tetrahedral symmetry of biomolecules is linked to the morphology and functions of bilateral organisms remains a challenging question. Cell chirality represents an intermediate point connecting two poles of biochirality. In this holistic perspective, examining the PyrNs' morphology-circuitry-function link is crucial to understanding the complex interaction between genetic, epigenetic, and environmental factors in the evolution of the CNS. The predictive power of our hypothesis can be partially expressed by the statement that the most integral and reliable biomarker of the neurodegenerative (including aging) and mental (including all variants of psychiatric illness) disorders would be the detection of the hemispheric asymmetry of D-amino acids (D-AAs) level in pyramidal neurons (PyrNs).

The etiology of autism spectrum disorder (ASD) has not yet been completely elucidated. Through time, multiple attempts have been made to uncover the causes of ASD. Different theories have been proposed, such as that it is caused by “Gods Wrath,” alternations in the gut–brain axis with an emphasis on gut dysbiosis, post vaccine complications, and genetic or even autoimmune causes. In this review we present data covering over 170 000 participants at age ranging from 2 to 14 years focusing on human cell changes rather than using animal models found in previous studies. The male/female ratio was 4:1. Data collection occurred in many countries covering ethnically diversified subjects. Moreover, we aim to show how the progress in genetic techniques influence the explanation found in medical White Papers based on the human genetic samples we have observed from our studies

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history. Whereas the role of selection on, and drift of, non-coding DNA elements on HPV diversification is poorly understood. More than a thousand complete genomes representing Alphapapillomavirus types, lineages and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the 4 nucleotides (A,C,G,T), codon usage, trimer usage and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages

Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph nodes. The clinical course and manifestations are unpredictable: spontaneous remission can occur in approximately two thirds of patients; up to 20% of patients have chronic course of the lung disease (called Ad-vanced Pulmonary Sarcoidosis) resulting in progressive loss of lung function, sometimes life-threatening that can lead to respiratory failure and death. The immunopathology mechanism leading from granuloma formation to the fibrosis in APS still remains elusive. Recent studies have provided new insights into the genetics factors and immune components involved in the clinical manifestation of the disease. In this review we aim to summarize the clinical-prognostic charac-teristics and molecular pathways which are believed to be associated with the development of APS

Traditional medicine is one of the main bases for studying and discovering natural sources of phytometabolites with antiviral properties. This research aims to demonstrate that the medicinal plants used as a treatment of viral diseases in the La Libertad region have, in fact, antiviral ac-tivity. The study evaluated the ethnobotany of the 8 most widely used medicinal plants in the region (Azadirachta indica A. Juss. “paraíso”, Caesalpinia spinosa (Molina) Kuntze “tara”, Citrus limon (L.) Osbeck “limón”, Clinopodium pulchellum (Kunth) Govaerts “panizara”, Cordia lutea Lam. “overo”, Ocimum basilicum L. “albahaca”, Schinus molle L. “molle”, and Taraxacum campylodes G.E. Haglund “diente de león”). The phytometabolites responsible for the antiviral activity were identified by LC-MS and evaluated in silico against the viral proteins NS2B/NS3 (DENV-2), NS5B (HCV), and ICP27 (HSV-1) using molecular docking in Autodock Vina and UCSF Chimera. The presence of five polyphenols (chlorogenic acid, gallic acid, caffeic acid, rosmarinic acid, and rutin) was found and, in the in silico test, the antiviral activity of chlorogenic acid stood out against DENV-2 and HCV, rutin against HCV and HSV-1, rosmarinic acid against DENV-2 and HCV. Therefore, it is verified that the medicinal plants studied have antiviral activity, which supports their use in traditional medicine

Andalusia is a Spanish region that is home to numerous minority varieties due to its diversity and territorial extension, offering the local viticulture the possibility of diversifying its wine production. The molecular identification of 98 specimens from six areas with a winemaking tradition in Andalusia was carried out between the years 2020 and 2022. Thirteen microsatellite markers were used in this study, including the nine recommended by the OIV. 31 different genotypes were obtained, 20 of which corresponded to profiles of already described varieties (11 of them are of minority cultivation in Andalusia: 'Rojal Tinto', 'Beba', 'Zurieles', 'Rome', 'Hebén', 'Mollar Cano', 'Listán Prieto', 'Listán del Condado', 'Jarrosuelto', 'Negra Dorada' and 'Mantúo de Pilas'), while the other 11 profiles did not match with previously identified varieties. This profiles were integrated into the database of the IFAPA “Rancho de la Merced” Germplasm Bank. The eco-geographical groups of the new identified genotypes were determined through analysis of genetic diversity. The presence of the Grapevine Fanleaf Virus, the Grapevine Fleck Virus and the Grapevine Leafroll associated Viruses was also analyzed using an ELISA test due to the necessity of having certifiable clones of the new varieties for their potential interest in being authorized for its cultivation in Spain.

To improve the wear resistance of polyimide (PI), surface modification was developed. In this study, the tribological properties of graphene (GN), graphene oxide (GO), and KH550-grafted graphene oxide (K5-GO) modified PI were evaluated by molecular dynamics (MD) at the atomic level. The findings indicated that the addition of nanomaterials can significantly enhance the friction performance of PI. The friction coefficient of PI composites decreased from 0.253 to 0.232, 0.136, and 0.079 after coating GN, GO and K5-GO, respectively. Among them, the K5-GO/PI exhibited the best surface wear resistance. Importantly, the mechanism behind the modification of PI was thoroughly revealed by observing the wear state, analyzing the changes of interfacial interactions, interfacial temperature, and relative concentration.

The interaction between hard-core soft-shell colloids are characterized by having two characteristic distances: one associated with the penetrable, soft corona and another one corresponding to the impenetrable core. Isotropic core-softened potentials with two characteristic length scales have long been applied to understand the properties of such colloids. Those potentials usually show waterlike anomalies, and recent findings have indicated the existence of multiple anomalous regions in the 2D limit under compression, while in 3D only one anomalous region is observed. In this direction, we perform Molecular Dynamics simulations to unveil the details about the structural behavior in the quasi-2D limit of a core-softened colloid. The fluid was confined between highly repulsive solvophobic walls, and the behavior at distinct wall separation and colloid density was analyzed. Our results indicated a straight relation between the 2D or 3D-like behavior and the layers separation. We can relate that if the system behaves as independent 2D-layers, it will have a 2D-like behavior. However, for some separations the layers are connected, with colloids hopping from one layer to another – having then a 3D-like structural behavior. Those findings fill the gap in the depiction of the anomalous behavior from 2D to 3D.

Lupinus mutabilis Sweet (Fabaceae), “tarwi” or “chocho”, is an important grain legume in the Andean region. In Peru, studies on tarwi have been mainly focused on morphological features, however, the have not been molecularly characterized. Currently, it is possible to explore genetic parameters of plants with reliable and modern methods like genotyping-by-sequencing (GBS). We here for the first time used single nucleotide polymorphisms (SNPs) markers to infer the genetic diversity and population structure of 89 accessions of tarwi from nine Andean regions of Peru. A total of 5922 SNPs distributed along all chromosomes of tarwi were identified. STRUCTURE analysis revealed that this crop is grouped into two clusters. A dendrogram was generated using the UPGMA clustering algorithm and, similar to the principal coordinate analysis (PCoA), it showed two groups that correspond to the geographic origin of the tarwi samples. AMOVA showed a reduced variation between clusters (7.59 %) and indicated that variability within populations is 92.41 %. Population divergence (Fst) between clusters 1 and 2 revealed low genetic difference (0.019). We also detected a negative Fis for both populations, demonstrating that, similar to other Lupinus species, tarwi also depends on cross-pollination. SNPs markers were powerful and effective for the genotyping process in this germplasm. We hope that this information is the beginning of the path towards a modern genetic improvement and conservation strategies of this important Andean legume.

Vesicular stomatitis virus (VSV) is an arbovirus causing vesicular stomatitis (VS) in livestock. There are two serotypes recognized: New Jersey (NJ) and Indiana (IND). The virus can be transmitted directly by contact or by vectors. In Ecuador, in the year 2018, an outbreak of Vesicular Stomatitis (VS) in cattle, caused by VSV-NJ and VSV-IND, was recorded with 399 cases reported distributed over 18 provinces. We determined the phylogenetic relationships among 67 strains. For the construction of phylogenetic trees, the viral phosphoprotein gene was sequenced, and trees were constructed based on the Maximum Likelihood method using 2004 outbreak strains from Ecuador (Genbank) and the 2018 sequences (this article). We built a haplotype network for VSV-NJ to trace the origin of the 2004 and 2018 epizootics through topology and mutations connections. These analyses suggested two different origins, one related with the 2004 outbreak and the other from an enzootic transmission source in 2018. Our analysis also suggests different transmission patterns with several small and independent outbreaks, most probably transmitted by vectors in the Amazon, and in the Andes and Coast region by the movement of livestock. We recommend further research for vectors and vertebrate reservoirs in Ecuador to clarify the mechanisms of the reemergence of the virus.

The reaction of [Co2(CO)8] with an equimolar amount of P(OPh)3] in toluene solution yields in situ generated [Co2(CO)7{P(OPh)3}] 1. Subsequent heating of 1 provides in a condensation reaction an alternative synthetic access to the tetranuclear cluster [{Co4(μ2-CO)3(CO)8{P(OPh)3}] 2. Compound 2 has been characterized by IR and 31P NMR spectroscopy, the tetranuclear cluster framework has be ascertained by a single-crystal X-ray diffraction study performed at 100 K.

Molecular motors play a vital role in the transport of material within the cell. A family of motors of growing interest are burnt bridge ratchets (BBRs). BBRs rectify spatial fluctuations into directed motion by creating and destroying motor-substrate bonds. It has been shown that the motility of a BBR can be optimized as a function of the system parameters. However, the amount of energy input required to generate such motion and the resulting efficiency has been less well characterized. Here, using a deterministic model, we calculate the efficiency of a particular type of BBR, namely a polyvalent hub interacting with a surface of substrate. We find that there is an optimal burn rate and substrate concentration that leads to optimal efficiency. Additionally, the substrate turnover rate has important implications on motor efficiency. We also consider the effects of force-dependent unbinding on the efficiency and find that under certain conditions the motor works more efficiently when bond breaking is included. Our results provide guidance for how to optimize the efficiency of BBRs.

Habituation is the most ancient and fundamental form of learning. As a firewall that protects our brain from sensory overload, it is indispensable for higher cognitive processes. Studies in humans and animal models provide a growing body of evidence that habituation is affected in autism and related monogenic neurodevelopmental disorders (NDDs). An integrated application of habituation assessment in NDDs and their animal models has currently unexploited potential for fundamental neuroscience and medical care.With the aim to gain mechanistic insights, we systematically retrieved genes that have been demonstrated in the literature to underlie habituation. We identified 258 evolutionarily conserved genes across species, describe the biological processes they converge on, and highlight regulatory pathways and drugs that may alleviate the habituation deficits associated with their dysregulation. We also summarize current habituation paradigms and extract the most decisive arguments from the literature that support the crucial role of habituation for cognition in health and disease. We conclude that habituation is a conserved, quantitative, cognition- and disease-relevant process that can connect preclinical and clinical work, and hence is a powerful tool to advance research, diagnostics,’’ and treatment of NDDs.

Pancreatic cancer leads the most common lethal tumor in America. This lethality is related to limited treatment options. Conventional treatments involve a non-specific use of chemotherapeutical agents like 5-FU, capecitabine, gemcitabine, cisplatine, oxaliplatine, or irinotecan, that produce several side effects. This review we focus on the use of targeted nanoparticles as an alternative to the standard treatment for the pancreatic cancer. The principal objective of the use of nanoparticles is the reduction in side effects that conventional treatments produce, mostly because of their nonspecificity. Currently, several molecular markets of pancreatic cancer cells have been studied to target nanoparticles and improve the actual treatment. Therefore, properly functionalizated nanoparticles with specific aptamers or antibodies can be used to recognize pancreatic cancer cells and once cancer is recognized, these nanoparticles can attack the tumor by drug delivery, hyperthermia, or gene therapy.

In this theoretical study we report on molecular electrostatic potential (MEP) of titled molecules confined by repulsive potentials of cylindrical symmetry mimicking a topology. Our calculations show that the spatial restriction significantly changes the picture of MEP of molecules in quantitative and qualitative sense. In particular, the drastic changes of MEP as a function of the strength of spatial confinement are observed for the BrCN molecule. This preliminary study is the first step in the investigations of the behavior of MEP of molecular systems under the orbital compression.

Colorectal cancer is a major threat to the society causing the death through metastasis to several patients with stage IV. Computational tools provide a relatively quick procedure in order to evaluate several molecules for their drug activity. Prenylated flavonoids are well known for their anticancer properties even in colon cancer. Here, we provided altered structures of chalcones, based on theoretical studies that are showing better binding affinities to several colon cancer related proteins. Using molecular docking and dynamics, alongside with density function theory and ADMET studies we are representing two new derivatives of Xanthohumol prenylated flavonoids having promising results against this disease.

There are currently worldwide efforts to reduce sugar intake due to the various adverse health effects linked with the overconsumption of sugars. Artificial sweeteners have been used as an alternative to nutritive sugars in numerous applications; however, their long-term effects on human health remain controversial. This led to a shift in consumer preference towards non-caloric sweeteners from natural sources. Thaumatins are a class of intensely sweet proteins found in arils of the fruits of the West-African plant Thaumatococcus danielli. Thaumatins’ current production method through aqueous extraction from this plant and uncertainty of the harvest from tropical rainforests limits its supply while the demand is increasing. Despite successful recombinant expression of the protein in several organisms, no large-scale bioproduction facilities exist. We present preliminary process design, process simulation, and economic analysis for a large-scale (50 metric tons/year) production of thaumatin II variant by several different molecular farming platforms.

Most malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and can be cured by chemotherapy, with yolk sac tumors (OYSTs) having the worse prognosis among MOGCTs. These tumors are rare and can benefit in the next future from specific therapeutic strategies after failure of platinum-based first-line and salvage regimens. In collaboration with EORTC SPECTA, we have developed a project to explore the molecular characteristics of OYST. The pilot part of the project was performed using retrospective samples and ten OYST patients including relapsed and disease free patients. The molecular analysis was performed using FoundationOne CDx. For each patient, the following variables are described in the molecular report provided by FMI (Fondation Medicine Incorporation): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (patient's tumor type and other tumor types), tumor mutational burden (TMB) and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 were analyzed. Four patients (40%) had a molecular alteration, according to the FMI test. A subset of three patients (33.3% of all patient) harbored targetable (KRAS, KIT, ARID1A) oncogenic mutations. Two patients at relapse harbored a targetable mutation. In this retrospective study, we were able to identify clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate if they could benefit from specific therapeutic strategies after failure of platinum-based first-line and salvage regimens and if the presence of a molecular alteration could be linked to patients’ outcome.

Space missions have always assumed that the risk of spacecraft malfunction far outweighs the risk of human system failure. This assumption breaks down for longer duration exploration missions and exposes vulnerabilities in space medical system. Space agencies can no longer buy down the majority of human system risk through the crew member selection process and emergency re-supply or evacuation. No mature medical solutions exist to close the risk gap. With recent advances in biotechnology, there is promise in augmenting a space pharmacy with a biologically-based space foundry for on-demand manufacturing of high-value medical products. Here we review the challenges and opportunities of molecular pharming, the production of pharmaceuticals in plants, as the basis of a space medical foundry to close the risk gap in current space medical systems. Plants have long been considered an important life support object in space and can now also be viewed as programmable factories in space. Advances in molecular pharming-based space foundries will have widespread application in promoting simple and accessible pharmaceutical manufacturing on Earth.

The commercial cultivation of microalgae began in the 1960s and Chlorella was one of the first target organisms. The species has long been considered a potential source of renewable energy, an alternative for phytoremediation, and more recently, as a growth and immune stimulant. However, Chlorella vulgaris, which is one of the most studied microalga, has never been comprehensively profiled chemically. In the present study, comprehensive profiling of the Chlorella vulgaris metabolome grown under normal culture conditions was carried out, employing tandem LC-MS/MS to profile the ethanolic extract and GC-MS for fatty acid analysis. The fatty acid profile of C. vulgaris was shown to be rich in omega-6, -7, -9, and -13 fatty acids, with omega-6 being the highest, representing more than sixty percent (>60%) of the total fatty acids. This is a clear indication that this species of Chlorella could serve as a good source of nutrition when incorporated in diets. The profile also showed that the main fatty acid composition was that of C₁₆-C₁₈ (>92%), suggesting that it might be a potential candidate for biodiesel production. LC-MS/MS analysis revealed carotenoid constituents comprising violaxanthin, neoxanthin, lutein, β-carotene, vulgaxanthin I, astaxanthin, and antheraxanthin, along with other pigments such as the chlorophylls. In addition to these, amino acids, vitamins, and simple sugars were also profiled, and through mass spectrometry-based molecular networking, 48 phospholipids were putatively identified.

Background: COVID-19, a member of corona virus family is spreading its tentacles across the world due to lack of drugs at present. Associated with its infection are cough, fever and respiratory problems causes more than 15% mortality worldwide. It is caused by a positive, single stranded RNA virus from the enveloped coronaviruse family. However, the main viral proteinase (Mpro/3CLpro) has recently been regarded as a suitable target for drug design against SARS infection due to its vital role in polyproteins processing necessary for coronavirus reproduction.Objectives: The present in silico study was designed to evaluate the effect of Eucalyptol (1,8 cineole), a essential oil component from eucalyptus oil, on Mpro by docking study.Methods: In the present study, molecular docking studies were conducted by using 1-click dock and swiss dock tools. Protein interaction mode was calculated by Protein Interactions Calculator.Results: The calculated parameters such as RMSD, binding energy, and binding site similarity indicated effective binding of eucalyptol to COVID-19 proteinase. Active site prediction further validated the role of active site residues in ligand binding. PIC results indicated that, Mpro/eucalyptol complexes forms hydrophobic interactions, hydrogen bond interactions and strong ionic interactions.Conclusions: Therefore, eucalyptol may represent potential treatment potential to act as COVID-19 Mpro inhibitor. However, further research is necessary to investigate their potential medicinal use.

Molecular engineering research is the fundamental way and the only way for the development of biomaterials. Based on molecular engineering, the biocompatibility of natural conformation and polymer biomaterials was studied. In this paper, we discuss that natural conformation is the basis of protein biological function, and that the synergistic action of peptide chain and side group is the motive force for protein to construct natural conformation and complete biological function. On the basis of the influence of the adsorption of polymer biomaterials on the natural conformation of proteins, the relationship between biocompatibility of biomaterials and protein conformation is further explained. Studies have shown that bismuth molecular materials can only be applied in the market and have their functionality if they have good biocompatibility. Therefore, the biocompatibility evaluation of new materials has important practical significance.

Levan is a fructan-type exopolysaccharide, which is produced by many microbes from sucrose via extracellular levansucrases. The hydrocolloid properties of levan depend on its molecular weight, while it is unknown why and to which extent levan is functionally diverse in dependence of its size. The aim of our study was to get deeper insights into the size-dependent, functional variability of levan. For this purpose, levans of different sizes were produced using the water kefir isolate Gluconobacter albidus TMW 2.1191 and subsequently rheologically characterized. Three levan types could be identified, which are similarly branched, but significantly differ in their molecular size and rheological properties among each other. The smallest levan (< 107 Da) produced without adjustment of the pH exhibited Newton-like flow behavior up to a specific concentration of 25% (w/v). On the contrary, larger levans (> 108 Da) produced at pH ≥ 4.5 were shear-thinning and showed a gel like behavior at ≥ 5% (w/v). A third (intermediate) levan variant was obtained via production in buffers at pH 4.0 and exhibited the properties of a viscoelastic fluid at ≥ 5% (w/v). Our study reveals that the variable size and composition of levan are controllable and more decisive for its functionality than the amount of exerted levan.

Reducing carbohydrates digestion by having low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107, an eight-herb formula that is modified from the RCM-104, has indicated significant weight-loss action in clinical trials. However, no research has been conducted to study its effect on the activity of porcine pancreatic alpha-amylase (PPA), which is involved in carbohydrate absorption. In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were also detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact.

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.