In this work,we proposed a strategy for the hydrolysis of native corn starch after the treatment of corn starch in an ionic liquid aqueous solution,and it is an awfully“green”and simple means to obtain starch with l...In this work,we proposed a strategy for the hydrolysis of native corn starch after the treatment of corn starch in an ionic liquid aqueous solution,and it is an awfully“green”and simple means to obtain starch with low molecular weight and amorphous state.X-ray diffraction results revealed that the natural starch crystalline region was largely disrupted by ionic liquid owing to the broken intermolecular and intramolecular hydrogen bonds.After hydrolysis,the morphology of starch changed from particles of native corn starch into little pieces,and their molecular weight could be effectively regulated during the hydrolysis process,and also the hydrolyzed starch samples exhibited decreased thermal stability with the extension of hydrolysis time.This work would counsel as a powerful tool for the development of native starch in realistic applications.展开更多
THE mechanical response and deformation mechanisms of pure nickel under nanoindentation were systematically investigated using molecular dynamics(MD)simulations,with a particular focus on the novel interplay between c...THE mechanical response and deformation mechanisms of pure nickel under nanoindentation were systematically investigated using molecular dynamics(MD)simulations,with a particular focus on the novel interplay between crystallographic orientation,grain boundary(GB)proximity,and pore characteristics(size/location).This study compares single-crystal nickel models along[100],[110],and[111]orientations with equiaxed polycrystalline models containing 0,1,and 2.5 nm pores in surface and subsurface configurations.Our results reveal that crystallographic anisotropy manifests as a 24.4%higher elastic modulus and 22.2%greater hardness in[111]-oriented single crystals compared to[100].Pore-GB synergistic effects are found to dominate the deformation behavior:2.5 nm subsurface pores reduce hardness by 25.2%through stress concentration and dislocation annihilation at GBs,whereas surface pores enable mechanical recovery via accelerated dislocation generation post-collapse.Additionally,size-dependent deformation regimes were identified,with 1 nm pores inducing negligible perturbation due to rapid atomic rearrangement,in contrast with persistent softening in 2.5 nm pores.These findings establish atomic-scale design principles for defect engineering in nickel-based aerospace components,demonstrating how crystallographic orientation,pore configuration,and GB interactions collectively govern nanoindentation behavior.展开更多
Molecular hydrogen(H2)demonstrates selective antioxidant and anti-inflammatory properties with therapeutic potential across musculoskeletal conditions including osteoarthritis,rheumatoid arthritis,exercise-induced mus...Molecular hydrogen(H2)demonstrates selective antioxidant and anti-inflammatory properties with therapeutic potential across musculoskeletal conditions including osteoarthritis,rheumatoid arthritis,exercise-induced muscle damage,chronic pain syndromes,tendinopathies,and muscle atrophy.This review critically evaluates preclinical and clinical evidence for H2 therapy and identifies research gaps.A comprehensive search of PubMed,EMBASE,and Cochrane Library(up to April 2025)yielded 45 eligible studies:25 preclinical and 20 clinical trials.Preclinical models consistently showed reductions in reactive oxygen species,inflammatory cytokines,and improved cell viability.Clinical trials reported symptomatic relief in osteoarthritis,decreased Disease Activity Score 28 in rheumatoid arthritis,and accelerated clearance of muscle damage markers.Delivery methods varied-hydrogen-rich water,gas inhalation,and saline infusion-hindering direct comparison.Mechanistic biomarkers were inconsistently reported,limiting understanding of target engagement.Common limitations included small sample sizes,short durations,and protocol heterogeneity.Despite these constraints,findings suggest H2 may serve as a promising adjunctive therapy via antioxidant,anti-inflammatory,and cytoprotective mechanisms.Future research should prioritize standardized delivery protocols,robust mechanistic endpoints,and longer-term randomized trials to validate clinical efficacy and optimize therapeutic strategies.展开更多
The microbial degradation of aromatic organic pollutants is incomplete due to their metabolic characteristics,which can easily produce certain highly toxic intermediates.Therefore,this article designs a dual template ...The microbial degradation of aromatic organic pollutants is incomplete due to their metabolic characteristics,which can easily produce certain highly toxic intermediates.Therefore,this article designs a dual template molec-ularly imprinted sensor(DTMIP/Fe-Mn@C)for iron manganese metal nanomaterials,prepared Fe-Mn@C com-posite materials by a one pot method were coated on the surface of glassy carbon electrodes and covered with molecularly imprinted membranes through electropolymerization and elution methods,achieving real-time de-tection of specific intermediate products 2-methylbutyric acid(2-MBA)and 3-methylbutyric acid(3-MBA)de-graded by azo dyes.In order to determine the detection sensitivity and intensity range of the sensor,optimization experiments were conducted on various parameters that affect the detection performance,such as the type of func-tional monomer and its composition ratio with the template molecule,detection time window,environmental pH value,etc.Finally,o-Phenylenediamine was determined as the functional monomer,with a molar ratio of 1:1:6 to the template molecules 2-MBA and 3-MBA.Electrochemical testing was conducted in a neutral environment with an incubation time of 5 min and pH=7.The results indicate that the sensor has a relatively wide detection range,high sensitivity,obvious recognition features,and excellent stability for 2-MBA and 3-MBA.This new dual template molecularly imprinted sensor can quickly and accurately determine the safety of highly toxic interme-diates in the degradation process of aromatic organic pollutants,providing a theoretical basis and application potential for trace detection and real-time monitoring.展开更多
Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in...Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in 2015 brought a marked advancement in the taxonomy of CRC,consolidating six classification systems into four novel subtypes,which focus on vital gene expression patterns and clinical and prognostic outcomes.However,nearly a decade of clinical experience with CMS classification has revealed fundamental limitations that underscore the inadequacy of any single classification system for capturing the full spectrum of CRC biology.The inherent challenges of the current paradigm are multifaceted.In the CMS classification,mixed phenotypes that remain unclassifiable constitute 13%of CRC cases.This reflects the remarkable heterogeneity that CRC shows.The tumor budding regions reflect the molecular shift due to CMS 2 to CMS 4 switching,causing further heterogeneity.Moreover,the reliance on bulk RNA sequencing fails to capture the spatial organization of molecular signatures within tumors and the critical contributions of the tumor microenvironment.Recent technological advances in spatial transcriptomics,singlecell RNA sequencing,and multi-omic integration have revealed the limitations of transcriptome-only classifications.The emergence of CRC intrinsic subtypes that attempt to remove microenvironmental contributions,pathway-derived subtypes,and stem cell-based classifications demonstrates the field’s recognition that multiple complementary classification systems are necessary.These newer molecular subtypes are not discrete categories but biological continua,thus highlighting that the vast molecular landscape is a tapestry of interlinked features,not rigid subtypes.Multiple technical hurdles cause difficulty in implementing the clinical translation of these newer molecular subtypes,including gene signature complexity,platform-dependent variations,and the difficulty of getting and preserving fresh frozen tissue.CMS 4 shows a poor prognostic outcome among the CMS subtypes,while CMS 1 is associated with poor survival in metastatic cases.However,the predictive value for definitive therapy remains subdued.Looking forward,the integration of artificial intelligence,liquid biopsy approaches,and real-time molecular monitoring promises to enable dynamic,multi-dimensional tumor characterization.The temporal and spatial complexity can only be captured by complementary molecular taxonomies rather than a single,unified system of CRC classification.Such an approach recognizes that different clinical questions–prognosis,treatment selection,resistance prediction–may require different molecular lenses,each optimized for specific clinical applications.This editorial advocates for a revolutionary change from pursuing a single“best”classification system toward a diverse approach that welcomes the molecular mosaic of CRC.Only through such comprehensive molecular characterization can we hope to achieve the promise of precision oncology for the diverse spectrum of patients with CRC.展开更多
Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor ...Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.展开更多
Compared to the well-studied two-dimensional(2D)ferroelectricity,the appearance of 2D antiferroelectricity is much rarer,where local dipoles from the nonequivalent sublattices within 2D monolayers are oppositely orien...Compared to the well-studied two-dimensional(2D)ferroelectricity,the appearance of 2D antiferroelectricity is much rarer,where local dipoles from the nonequivalent sublattices within 2D monolayers are oppositely oriented.Using NbOCl_(2) monolayer with competing ferroelectric(FE)and antiferroelectric(AFE)phases as a 2D material platform,we demonstrate the emergence of intrinsic antiferroelectricity in NbOCl_(2) monolayer under experimentally accessible shear strain,along with new functionality associated with electric field-induced AFE-to-FE phase transition.Specifically,the complex configuration space accommodating FE and AFE phases,polarization switching kinetics,and finite temperature thermodynamic properties of 2D NbOCl_(2) are all accurately predicted by large-scale molecular dynamics simulations based on deep learning interatomic potential model.Moreover,room temperature stable antiferroelectricity with low polarization switching barrier and one-dimensional collinear polarization arrangement is predicted in shear-deformed NbOCl_(2) monolayer.The transition from AFE to FE phase in 2D NbOCl_(2) can be triggered by a low critical electric field,leading to a double polarization–electric(P–E)loop with small hysteresis.A new type of optoelectronic device composed of AFE-NbOCl_(2) is proposed,enabling electric“writing”and nonlinear optical“reading”logical operation with fast operation speed and low power consumption.展开更多
GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,i...GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).展开更多
Accurate prediction of molecular properties is crucial for selecting compounds with ideal properties and reducing the costs and risks of trials.Traditional methods based on manually crafted features and graph-based me...Accurate prediction of molecular properties is crucial for selecting compounds with ideal properties and reducing the costs and risks of trials.Traditional methods based on manually crafted features and graph-based methods have shown promising results in molecular property prediction.However,traditional methods rely on expert knowledge and often fail to capture the complex structures and interactions within molecules.Similarly,graph-based methods typically overlook the chemical structure and function hidden in molecular motifs and struggle to effectively integrate global and local molecular information.To address these limitations,we propose a novel fingerprint-enhanced hierarchical graph neural network(FH-GNN)for molecular property prediction that simultaneously learns information from hierarchical molecular graphs and fingerprints.The FH-GNN captures diverse hierarchical chemical information by applying directed message-passing neural networks(D-MPNN)on a hierarchical molecular graph that integrates atomic-level,motif-level,and graph-level information along with their relationships.Addi-tionally,we used an adaptive attention mechanism to balance the importance of hierarchical graphs and fingerprint features,creating a comprehensive molecular embedding that integrated hierarchical mo-lecular structures with domain knowledge.Experiments on eight benchmark datasets from MoleculeNet showed that FH-GNN outperformed the baseline models in both classification and regression tasks for molecular property prediction,validating its capability to comprehensively capture molecular informa-tion.By integrating molecular structure and chemical knowledge,FH-GNN provides a powerful tool for the accurate prediction of molecular properties and aids in the discovery of potential drug candidates.展开更多
Molecular recognition of bioreceptors and enzymes relies on orthogonal interactions with small molecules within their cavity. To date, Chinese scientists have developed three types of strategies for introducing active...Molecular recognition of bioreceptors and enzymes relies on orthogonal interactions with small molecules within their cavity. To date, Chinese scientists have developed three types of strategies for introducing active sites inside the cavity of macrocyclic arenes to better mimic molecular recognition of bioreceptors and enzymes.The editorial aims to enlighten scientists in this field when they develop novel macrocycles for molecular recognition, supramolecular assembly, and applications.展开更多
Due to its synergistic effects and reduced side effects,combination therapy has become an important strategy for treating complex diseases.In traditional Chinese medicine(TCM),the“monarch,minister,assistant,envoy”co...Due to its synergistic effects and reduced side effects,combination therapy has become an important strategy for treating complex diseases.In traditional Chinese medicine(TCM),the“monarch,minister,assistant,envoy”compatibilities theory provides a systematic framework for drug compatibility and has guided the formation of a large number of classic formulas.However,due to the complex compositions and diverse mechanisms of action of TCM,it is difficult to comprehensively reveal its potential synergistic patterns using traditional methods.Synergistic prediction based on molecular compatibility theory provides new ideas for identifying combinations of active compounds in TCM.Compared to resource-intensive traditional experimental methods,artificial intelligence possesses the ability to mine synergistic patterns from multi-omics and structural data,providing an efficient means for modeling and optimizing TCM combinations.This paper systematically reviews the application progress of AI in the synergistic prediction of TCM active compounds and explores the challenges and prospects of its application in modeling combination relationships,thereby contributing to the modernization of TCM theory and methodological innovation.展开更多
Background:In this present study,we have screened major phytoconstituents of Nilavembu Kudineer against critical COVID-19 target proteins that cause severe pneumonia globally.In addition,a human receptor protein that ...Background:In this present study,we have screened major phytoconstituents of Nilavembu Kudineer against critical COVID-19 target proteins that cause severe pneumonia globally.In addition,a human receptor protein that facilitates viral entry into the host cell was also targeted.Methods:Phytoconstituents derived from Nilavembu Kudineer formulation were docked against 12 major proteins,which help viral entry,viral proliferation,and a human receptor facilitate the viral entry into the host cells.The major metabolites of Nilavembu Kudineer were retrieved based on literature from the PubChem database.The docked complex was subjected to MD simulation studies to verify its binding mode and the stability of the interactions.The binding energy analysis was performed to estimate the binding affinity between the compounds and their respective receptors using MM/GBSA.Results:Docking studies have shown that three major plants in the polyherbal formulation,Andrographis paniculata,Mollugo cerviana,and Zingiber officinale,have 14 potential compounds that have better binding affinity against COVID-19 proteins and their host receptor protein.MD studies and binding energy calculations also confirmed that these compounds possess better stability and strong binding energy with these proteins.Conclusion:In silico analyses suggest that phytoconstituents from Nilavembu Kudineer possess promising multi-target antiviral activity against COVID-19.These findings provide a rationale for further experimental studies to validate their therapeutic potential for the treatment of COVID-19.展开更多
There is currently little information on the effects of Bisphenol S(BPS)and Bisphenol F(BPF),two alternatives to Bisphenol A(BPA),on human endocrine systems;most research on these compounds is conducted on animal mode...There is currently little information on the effects of Bisphenol S(BPS)and Bisphenol F(BPF),two alternatives to Bisphenol A(BPA),on human endocrine systems;most research on these compounds is conducted on animal models.This study examines how BPA,BPS,and BPF bind to the human estrogen receptor alpha using molecular docking and dynamics,as well as the potential endocrine disruption caused by these substances in people.This research uses AutoDock Tools and AutoDock Vina to predict the binding locations of BPS and BPF inside the estrogen receptor’s Ligand-binding Domain(LBD).Gromacs 2021 molecular dynamics simulations were run for 200 ns in order to determine the binding free energies of BPA,BPS,and BPF as well as to evaluate the stability of docking data.Results indicate that BPS and BPF,similarly to BPA,bind stably to the estrogen receptor through hydrogen bonding and hydrophobic interactions,indicating potential endocrine-disrupting effects.BPF exhibited the strongest binding affinity,primarily due to significant hydrophobic interactions involving residues like LEU346 and LEU384.BPA and BPF formed stable hydrogen bonds,whereas BPS displayed slightly lower stability and more varied interactions.Throughout the simulations,all ligands consistently occupied the receptor’s active site,highlighting persistent binding.These findings imply that BPS and BPF may pose comparable health risks to BPA,though their unique interaction patterns suggest different underlying mechanisms.Experimental validation in human systems is critical to corroborate these computational predictions and evaluate the safety of BPA substitutes.展开更多
Glaucoma,a degenerative optic neuropathy,causes retinal ganglion cell(RGC)apoptosis and irreversible vision loss.Current therapies often fail to stop disease progression despite lowering intraocular pressure,the main ...Glaucoma,a degenerative optic neuropathy,causes retinal ganglion cell(RGC)apoptosis and irreversible vision loss.Current therapies often fail to stop disease progression despite lowering intraocular pressure,the main risk factor.Thus,neuroprotective strategies have gained interest.We performed a bibliometric analysis to determine global publishing trends and relationships among prolific authors,publications,institutions,funding agencies,and journals.We also analyzed author keywords to identify research hotspots in glaucoma neuroprotection.Further,based on keyword analysis,we reviewed most recent literature to understand mechanistic pathways underlying glaucomarelated pathophysiological responses leading to RGC loss.Bibliographic data were sourced from Scopus.Basic bibliographic features were characterized using Scopus’s functions.VOSviewer was used for mapping and visualizing bibliometric networks.The analysis included trends in publications since 2000,the most prolific countries,institutions,authors,and the strength of their linkages.A significant increase in publication output over the past two decades was noted.The United States leads in funding support,research output,and citation links,followed by China and the UK.Among the top 10 most cited authors,three are from Japanese institutions.Keyword analysis shows a focus on molecular targets related to ischemia,excitotoxicity,inflammation,and oxidative stress,with fewer emerging drug candidates and limited clinical trials.Based on the most recent literature,emerging molecular targets underlying these key pathophysiological mechanisms are summarized.In conclusion,while pathophysiology and molecular mechanisms are the current focus,there is not much progress in developing new drug candidates and conducting clinical trials.展开更多
Background:Atherosclerosis(AS),the primary pathological foundation of cardiovascular diseases,is characterized by intricate processes including inflammation,lipid metabolism disorders,and pyroptosis.While the traditio...Background:Atherosclerosis(AS),the primary pathological foundation of cardiovascular diseases,is characterized by intricate processes including inflammation,lipid metabolism disorders,and pyroptosis.While the traditional Chinese medicine compound Dingxin Recipe(DXR)has demonstrated definitive clinical efficacy in treating AS,its therapeutic mechanisms remain unclear.This study employed an integrated approach combining network pharmacology,molecular docking,and molecular dynamics simulations(MDS)to investigate DXR’s anti-AS mechanisms.Methods:Active ingredients and targets of DXR were identified and screened using databases such as GeneCards,OMIM,and TCMSP.An“ingredient-target-disease”network was constructed to visualize these interactions.Molecular docking was utilized to assess the binding affinity between key ingredients and their respective targets.Additionally,MDS were conducted to analyze the stability of these complexes,providing robust evidence for further clinical applications and in-depth research.Results:Through network pharmacology analysis,we identified 99 active drug components,934 gene targets,and 1463 disease targets associated with DXR.Protein-protein interaction analysis revealed central regulatory nodes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these components primarily modulate processes such as inflammatory response and transcription factor activation,and are closely linked to the AGERAGE signaling pathway,lipid metabolism,and atherosclerosis pathways.Molecular docking confirmed strong binding potential between the components and their targets,while MDS further validated the stability of these interactions.Conclusion:This study elucidates that the active ingredients in DXR alleviate AS by mitigating inflammatory responses and inhibiting pyroptosis through the suppression of inflammatory factor release.These findings provide a scientific foundation for the clinical application of DXR in AS treatment.展开更多
Euphorbia helioscopia,a natural plant recognized for its anti-tumor properties,has been extensively investigated in various cancers.However,its therapeutic potential in gastric cancer with positive lymph node metastas...Euphorbia helioscopia,a natural plant recognized for its anti-tumor properties,has been extensively investigated in various cancers.However,its therapeutic potential in gastric cancer with positive lymph node metastasis remains underexplored.This study aimed to elucidate the role of E.helioscopia in treating gastric cancer with lymph node metastasis using an integrative approach that combined network pharmacology,molecular docking,and molecular dynamics simulations.Initially,shared target data between E.helioscopia and gastric cancer with positive lymph node metastasis were identified and systematically analyzed.Subsequently,molecular docking was conducted to validate the interactions between key components and targets.Finally,molecular dynamics simulations were employed,with binding free energy calculations performed using the MM-PBSA algorithm.The findings revealed that the primary bioactive compounds of E.helioscopia in this context included quercetin and luteolin,targeting core molecules such as EGFR and MMP9.Key pathways implicated in its mechanism of action included resistance to EGFR tyrosine kinase inhibitors,among others.Molecular docking demonstrated robust binding affinity between the active compounds and critical targets,with molecular dynamics and binding free energy analyses highlighting a particularly stable interaction between luteolin and MMP9.In conclusion,E.helioscopia exhibited a multi-component,multi-target,and multi-pathway therapeutic profile in treating gastric cancer with positive lymph node metastasis.These findings offered valuable theoretical insights supporting its potential clinical application in oncology.展开更多
The performance of organic solar cells is significantly influenced by the acceptor molecular packing properties within the active layers,which is essential for optimizing charge dynamics and photovoltaic performance.H...The performance of organic solar cells is significantly influenced by the acceptor molecular packing properties within the active layers,which is essential for optimizing charge dynamics and photovoltaic performance.However,achieving precise control over this packaging structure presents a considerable challenge.Herein,we propose a dual additive strategy utilizing dibenzofuran and halogenated naphthalene to systematically manipulate molecular packing orientation and enhance the long-range molecular packing order of the acceptors.Dibenzofuran is crucial in promoting crystallinity within the material,facilitating the formation of an ordered structure,while halogenated naphthalene regulates the orientation of the molecules,ensuring proper alignment.Specifically,the combination of dibenzofuran and 1-chloronaphthalene promotes edge-on molecular packing and enhances the formation of nanofibrillar structures with improved order,leading to improved charge transport and device performance.Implementing this strategy in devices composed of PM6 and L8-BO has yielded a power conversion efficiency of 19.58%,accompanied by long-term stability.Similarly,1-fluoronaphthalene has also demonstrated effectiveness in improving molecular orientation and overall device efficiency,demonstrating the robustness of this dual additive strategy.By addressing the challenges associated with molecular packing and orientation in active layers,our result contributes valuable insights into optimizing organic solar cells for practical applications.展开更多
Objective To evaluate the antibacterial potential of bioactive compounds from Persicaria hydropiper(L.)(P.hydropiper)against bacterial virulence proteins through molecular docking(MD)and experimental validation.Method...Objective To evaluate the antibacterial potential of bioactive compounds from Persicaria hydropiper(L.)(P.hydropiper)against bacterial virulence proteins through molecular docking(MD)and experimental validation.Methods Six bioactive compounds from P.hydropiper were investigated:catechin(CAT1),hyperin(HYP1),ombuin(OMB1),pinosylvin(PSV1),quercetin 3-sulfate(QSF1),and scutellarein(SCR1).Their binding affinities and potential binding pockets were assessed through MD against four bacterial target proteins with Protein Data Bank identifiers(PDB IDs):topoisomerase IV from Escherichia coli(E.coli)(PDB ID:3FV5),Staphylococcus aureus(S.aureus)gyrase ATPase binding domain(PDB ID:3U2K),CviR from Chromobacterium violaceum(C.violaceum)(PDB ID:3QP1),and glycosyl hydrolase from Pseudomonas aeruginosa(P.aeruginosa)(PDB ID:5BX9).Molecular dynamics simulations(MDS)were performed on the most promising compound-protein complexes for 50 nanoseconds(ns).Drug-likeness was evaluated using Lipinski's Rule of Five(RO5),followed by absorption,distribution,metabolism,excretion,and toxicity(ADMET)analysis using SwissADME and pkCSM web servers.Antibacterial activity was evaluated through disc diffusion assays,testing both individual compounds and combinations with conventional antibiotics[cefotaxime(CTX1,30μg/disc),ceftazidime(CAZ1,30μg/disc),and piperacillin(PIP1,100μg/disc)].Results MD revealed strong binding affinity(ranging from-9.3 to-5.9 kcal/mol)for all compounds,with CAT1 showing exceptional binding to 3QP1(-9.3 kcal/mol)and 5BX9(-8.4 kcal/mol).MDS confirmed the stability of CAT1-protein complexes with binding free energies of-84.71 kJ/mol(5BX9-CAT1)and-95.59 kJ/mol(3QP1-CAT1).Five compounds(CAT1,SCR1,PSV1,OMB1,and QSF1)complied with Lipinski's RO5 and showed favorable ADMET profiles.All compounds were non-carcinogenic,with CAT1 classified in the lowest toxicity class(VI).In antibacterial assays,CAT1 demonstrated significant activity against both gram-positive bacteria[Streptococcus pneumoniae(S.pneumoniae),S.aureus,and Bacillus cereus(B.cereus)][zone diameter of inhibition(ZDI):10-22 mm]and gram-negative bacteria[Acinetobacter baumannii(A.baumannii),E.coli,and P.aeruginosa](ZDI:14-27 mm).Synergistic effects were observed when CAT1 was combined with antibiotics and the growth inhibitory indices(GII)was 0.69-1.00.Conclusion P.hydropiper bioactive compounds,particularly CAT1,show promising antibacterial potential through multiple mechanisms,including direct inhibition of bacterial virulence proteins and synergistic activity with conventional antibiotics.The favorable pharmacological properties and low toxicity profiles support their potential development as therapeutic agents against bacterial infections.展开更多
Porous molecular sieve catalysts,including aluminosilicate zeolites and silicoaluminophosphate(SAPO)molecular sieves,have found widespread use in heterogeneous catalysis and are expected to play a key role in advancin...Porous molecular sieve catalysts,including aluminosilicate zeolites and silicoaluminophosphate(SAPO)molecular sieves,have found widespread use in heterogeneous catalysis and are expected to play a key role in advancing carbon neutrality and sustainable development.Given the ubiquitous presence of water during catalyst synthesis,storage,and application,the interactions between water and molecular sieves as well as their consequent effects on frameworks and catalytic reactions have attracted considerable attention.These effects are inherently complex and highly dependent on various factors such as temperature,water phase,and partial pressure.In this review,we provide a comprehensive overview of the current understanding of water-molecular sieve interactions and their roles in catalysis,based on both experimental and theoretical calculation results.Special attention is paid to water-induced reversible and irreversible structural changes in aluminosilicate and SAPO frameworks at the atomic level,underscoring the dynamic and labile nature of these frameworks in water environments.The influence of water on catalytic performance and reaction kinetics in molecular sieve-catalyzed reactions is discussed from two perspectives:(1)its participation in reaction through hydrogen bonding interactions,such as competitive adsorption at active sites,stabilization of ground and transition states,and proton transfer bridge;(2)its role as a direct reactant forming new species via reactions with other vip molecules.Recent advancements in this area provide valuable insights for the rational design and optimization of catalysts for water-involved reactions.展开更多
Molecular medicine,which delves into the intricacies of biomolecular structure,function,and role,is pivotal for advancing precise diagnostics and personalized treatment.Nucleic acids,a class of star functional molecul...Molecular medicine,which delves into the intricacies of biomolecular structure,function,and role,is pivotal for advancing precise diagnostics and personalized treatment.Nucleic acids,a class of star functional molecules,are notable for their versatile applications in molecular diagnostics,gene therapy,and drug development.Therefore,in this study,we review the extensive use of nucleic acid aptamers in medicinal practice.Furthermore,the expanding field of molecular medicine has catalyzed advancements in traditional Chinese medicine(TCM),as evidenced by scientific endeavors to integrate modern technologies.Therefore,TCM has experienced rapid modernization by leveraging artificial intelligence,nucleic acid molecular medicine,and bioelectronic medicine.展开更多
文摘In this work,we proposed a strategy for the hydrolysis of native corn starch after the treatment of corn starch in an ionic liquid aqueous solution,and it is an awfully“green”and simple means to obtain starch with low molecular weight and amorphous state.X-ray diffraction results revealed that the natural starch crystalline region was largely disrupted by ionic liquid owing to the broken intermolecular and intramolecular hydrogen bonds.After hydrolysis,the morphology of starch changed from particles of native corn starch into little pieces,and their molecular weight could be effectively regulated during the hydrolysis process,and also the hydrolyzed starch samples exhibited decreased thermal stability with the extension of hydrolysis time.This work would counsel as a powerful tool for the development of native starch in realistic applications.
基金The National Natural Science Foundation of China(Grant No.12462006)Beijing Institute of Structure and Environment Engineering Joint Innovation Fund(No.BQJJ202414).
文摘THE mechanical response and deformation mechanisms of pure nickel under nanoindentation were systematically investigated using molecular dynamics(MD)simulations,with a particular focus on the novel interplay between crystallographic orientation,grain boundary(GB)proximity,and pore characteristics(size/location).This study compares single-crystal nickel models along[100],[110],and[111]orientations with equiaxed polycrystalline models containing 0,1,and 2.5 nm pores in surface and subsurface configurations.Our results reveal that crystallographic anisotropy manifests as a 24.4%higher elastic modulus and 22.2%greater hardness in[111]-oriented single crystals compared to[100].Pore-GB synergistic effects are found to dominate the deformation behavior:2.5 nm subsurface pores reduce hardness by 25.2%through stress concentration and dislocation annihilation at GBs,whereas surface pores enable mechanical recovery via accelerated dislocation generation post-collapse.Additionally,size-dependent deformation regimes were identified,with 1 nm pores inducing negligible perturbation due to rapid atomic rearrangement,in contrast with persistent softening in 2.5 nm pores.These findings establish atomic-scale design principles for defect engineering in nickel-based aerospace components,demonstrating how crystallographic orientation,pore configuration,and GB interactions collectively govern nanoindentation behavior.
文摘Molecular hydrogen(H2)demonstrates selective antioxidant and anti-inflammatory properties with therapeutic potential across musculoskeletal conditions including osteoarthritis,rheumatoid arthritis,exercise-induced muscle damage,chronic pain syndromes,tendinopathies,and muscle atrophy.This review critically evaluates preclinical and clinical evidence for H2 therapy and identifies research gaps.A comprehensive search of PubMed,EMBASE,and Cochrane Library(up to April 2025)yielded 45 eligible studies:25 preclinical and 20 clinical trials.Preclinical models consistently showed reductions in reactive oxygen species,inflammatory cytokines,and improved cell viability.Clinical trials reported symptomatic relief in osteoarthritis,decreased Disease Activity Score 28 in rheumatoid arthritis,and accelerated clearance of muscle damage markers.Delivery methods varied-hydrogen-rich water,gas inhalation,and saline infusion-hindering direct comparison.Mechanistic biomarkers were inconsistently reported,limiting understanding of target engagement.Common limitations included small sample sizes,short durations,and protocol heterogeneity.Despite these constraints,findings suggest H2 may serve as a promising adjunctive therapy via antioxidant,anti-inflammatory,and cytoprotective mechanisms.Future research should prioritize standardized delivery protocols,robust mechanistic endpoints,and longer-term randomized trials to validate clinical efficacy and optimize therapeutic strategies.
基金supported by the Bingtuan Industrial Technology Research Institute,Bingtuan New materials Research Institute innovation platform project,Research initiation project of Shihezi University(No.RCZK202330)the Science and Technology Program-Regional Innovation Guidance Program(No.2023ZD080)Tianchi Talent Project(No.CZ002735).
文摘The microbial degradation of aromatic organic pollutants is incomplete due to their metabolic characteristics,which can easily produce certain highly toxic intermediates.Therefore,this article designs a dual template molec-ularly imprinted sensor(DTMIP/Fe-Mn@C)for iron manganese metal nanomaterials,prepared Fe-Mn@C com-posite materials by a one pot method were coated on the surface of glassy carbon electrodes and covered with molecularly imprinted membranes through electropolymerization and elution methods,achieving real-time de-tection of specific intermediate products 2-methylbutyric acid(2-MBA)and 3-methylbutyric acid(3-MBA)de-graded by azo dyes.In order to determine the detection sensitivity and intensity range of the sensor,optimization experiments were conducted on various parameters that affect the detection performance,such as the type of func-tional monomer and its composition ratio with the template molecule,detection time window,environmental pH value,etc.Finally,o-Phenylenediamine was determined as the functional monomer,with a molar ratio of 1:1:6 to the template molecules 2-MBA and 3-MBA.Electrochemical testing was conducted in a neutral environment with an incubation time of 5 min and pH=7.The results indicate that the sensor has a relatively wide detection range,high sensitivity,obvious recognition features,and excellent stability for 2-MBA and 3-MBA.This new dual template molecularly imprinted sensor can quickly and accurately determine the safety of highly toxic interme-diates in the degradation process of aromatic organic pollutants,providing a theoretical basis and application potential for trace detection and real-time monitoring.
文摘Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in 2015 brought a marked advancement in the taxonomy of CRC,consolidating six classification systems into four novel subtypes,which focus on vital gene expression patterns and clinical and prognostic outcomes.However,nearly a decade of clinical experience with CMS classification has revealed fundamental limitations that underscore the inadequacy of any single classification system for capturing the full spectrum of CRC biology.The inherent challenges of the current paradigm are multifaceted.In the CMS classification,mixed phenotypes that remain unclassifiable constitute 13%of CRC cases.This reflects the remarkable heterogeneity that CRC shows.The tumor budding regions reflect the molecular shift due to CMS 2 to CMS 4 switching,causing further heterogeneity.Moreover,the reliance on bulk RNA sequencing fails to capture the spatial organization of molecular signatures within tumors and the critical contributions of the tumor microenvironment.Recent technological advances in spatial transcriptomics,singlecell RNA sequencing,and multi-omic integration have revealed the limitations of transcriptome-only classifications.The emergence of CRC intrinsic subtypes that attempt to remove microenvironmental contributions,pathway-derived subtypes,and stem cell-based classifications demonstrates the field’s recognition that multiple complementary classification systems are necessary.These newer molecular subtypes are not discrete categories but biological continua,thus highlighting that the vast molecular landscape is a tapestry of interlinked features,not rigid subtypes.Multiple technical hurdles cause difficulty in implementing the clinical translation of these newer molecular subtypes,including gene signature complexity,platform-dependent variations,and the difficulty of getting and preserving fresh frozen tissue.CMS 4 shows a poor prognostic outcome among the CMS subtypes,while CMS 1 is associated with poor survival in metastatic cases.However,the predictive value for definitive therapy remains subdued.Looking forward,the integration of artificial intelligence,liquid biopsy approaches,and real-time molecular monitoring promises to enable dynamic,multi-dimensional tumor characterization.The temporal and spatial complexity can only be captured by complementary molecular taxonomies rather than a single,unified system of CRC classification.Such an approach recognizes that different clinical questions–prognosis,treatment selection,resistance prediction–may require different molecular lenses,each optimized for specific clinical applications.This editorial advocates for a revolutionary change from pursuing a single“best”classification system toward a diverse approach that welcomes the molecular mosaic of CRC.Only through such comprehensive molecular characterization can we hope to achieve the promise of precision oncology for the diverse spectrum of patients with CRC.
文摘Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.
基金supported by the National Natural Science Foundation of China (Grant No.11574244 for G.Y.G.)the XJTU Research Fund for AI Science (Grant No.2025YXYC011 for G.Y.G.)the Hong Kong Global STEM Professorship Scheme (for X.C.Z.)。
文摘Compared to the well-studied two-dimensional(2D)ferroelectricity,the appearance of 2D antiferroelectricity is much rarer,where local dipoles from the nonequivalent sublattices within 2D monolayers are oppositely oriented.Using NbOCl_(2) monolayer with competing ferroelectric(FE)and antiferroelectric(AFE)phases as a 2D material platform,we demonstrate the emergence of intrinsic antiferroelectricity in NbOCl_(2) monolayer under experimentally accessible shear strain,along with new functionality associated with electric field-induced AFE-to-FE phase transition.Specifically,the complex configuration space accommodating FE and AFE phases,polarization switching kinetics,and finite temperature thermodynamic properties of 2D NbOCl_(2) are all accurately predicted by large-scale molecular dynamics simulations based on deep learning interatomic potential model.Moreover,room temperature stable antiferroelectricity with low polarization switching barrier and one-dimensional collinear polarization arrangement is predicted in shear-deformed NbOCl_(2) monolayer.The transition from AFE to FE phase in 2D NbOCl_(2) can be triggered by a low critical electric field,leading to a double polarization–electric(P–E)loop with small hysteresis.A new type of optoelectronic device composed of AFE-NbOCl_(2) is proposed,enabling electric“writing”and nonlinear optical“reading”logical operation with fast operation speed and low power consumption.
文摘GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).
基金supported by Macao Science and Technology Development Fund,Macao SAR,China(Grant No.:0043/2023/AFJ)the National Natural Science Foundation of China(Grant No.:22173038)Macao Polytechnic University,Macao SAR,China(Grant No.:RP/FCA-01/2022).
文摘Accurate prediction of molecular properties is crucial for selecting compounds with ideal properties and reducing the costs and risks of trials.Traditional methods based on manually crafted features and graph-based methods have shown promising results in molecular property prediction.However,traditional methods rely on expert knowledge and often fail to capture the complex structures and interactions within molecules.Similarly,graph-based methods typically overlook the chemical structure and function hidden in molecular motifs and struggle to effectively integrate global and local molecular information.To address these limitations,we propose a novel fingerprint-enhanced hierarchical graph neural network(FH-GNN)for molecular property prediction that simultaneously learns information from hierarchical molecular graphs and fingerprints.The FH-GNN captures diverse hierarchical chemical information by applying directed message-passing neural networks(D-MPNN)on a hierarchical molecular graph that integrates atomic-level,motif-level,and graph-level information along with their relationships.Addi-tionally,we used an adaptive attention mechanism to balance the importance of hierarchical graphs and fingerprint features,creating a comprehensive molecular embedding that integrated hierarchical mo-lecular structures with domain knowledge.Experiments on eight benchmark datasets from MoleculeNet showed that FH-GNN outperformed the baseline models in both classification and regression tasks for molecular property prediction,validating its capability to comprehensively capture molecular informa-tion.By integrating molecular structure and chemical knowledge,FH-GNN provides a powerful tool for the accurate prediction of molecular properties and aids in the discovery of potential drug candidates.
文摘Molecular recognition of bioreceptors and enzymes relies on orthogonal interactions with small molecules within their cavity. To date, Chinese scientists have developed three types of strategies for introducing active sites inside the cavity of macrocyclic arenes to better mimic molecular recognition of bioreceptors and enzymes.The editorial aims to enlighten scientists in this field when they develop novel macrocycles for molecular recognition, supramolecular assembly, and applications.
基金supported by the National Key Research and Development Program of China(No.2024YFC3506900)Science and Technology Program of Tianjin(No.24ZXZSSS00460)Special Project for Technological Innovation in New Productive Forces of Modern Chinese Medicines(No.24ZXZKSY00010)。
文摘Due to its synergistic effects and reduced side effects,combination therapy has become an important strategy for treating complex diseases.In traditional Chinese medicine(TCM),the“monarch,minister,assistant,envoy”compatibilities theory provides a systematic framework for drug compatibility and has guided the formation of a large number of classic formulas.However,due to the complex compositions and diverse mechanisms of action of TCM,it is difficult to comprehensively reveal its potential synergistic patterns using traditional methods.Synergistic prediction based on molecular compatibility theory provides new ideas for identifying combinations of active compounds in TCM.Compared to resource-intensive traditional experimental methods,artificial intelligence possesses the ability to mine synergistic patterns from multi-omics and structural data,providing an efficient means for modeling and optimizing TCM combinations.This paper systematically reviews the application progress of AI in the synergistic prediction of TCM active compounds and explores the challenges and prospects of its application in modeling combination relationships,thereby contributing to the modernization of TCM theory and methodological innovation.
文摘Background:In this present study,we have screened major phytoconstituents of Nilavembu Kudineer against critical COVID-19 target proteins that cause severe pneumonia globally.In addition,a human receptor protein that facilitates viral entry into the host cell was also targeted.Methods:Phytoconstituents derived from Nilavembu Kudineer formulation were docked against 12 major proteins,which help viral entry,viral proliferation,and a human receptor facilitate the viral entry into the host cells.The major metabolites of Nilavembu Kudineer were retrieved based on literature from the PubChem database.The docked complex was subjected to MD simulation studies to verify its binding mode and the stability of the interactions.The binding energy analysis was performed to estimate the binding affinity between the compounds and their respective receptors using MM/GBSA.Results:Docking studies have shown that three major plants in the polyherbal formulation,Andrographis paniculata,Mollugo cerviana,and Zingiber officinale,have 14 potential compounds that have better binding affinity against COVID-19 proteins and their host receptor protein.MD studies and binding energy calculations also confirmed that these compounds possess better stability and strong binding energy with these proteins.Conclusion:In silico analyses suggest that phytoconstituents from Nilavembu Kudineer possess promising multi-target antiviral activity against COVID-19.These findings provide a rationale for further experimental studies to validate their therapeutic potential for the treatment of COVID-19.
文摘There is currently little information on the effects of Bisphenol S(BPS)and Bisphenol F(BPF),two alternatives to Bisphenol A(BPA),on human endocrine systems;most research on these compounds is conducted on animal models.This study examines how BPA,BPS,and BPF bind to the human estrogen receptor alpha using molecular docking and dynamics,as well as the potential endocrine disruption caused by these substances in people.This research uses AutoDock Tools and AutoDock Vina to predict the binding locations of BPS and BPF inside the estrogen receptor’s Ligand-binding Domain(LBD).Gromacs 2021 molecular dynamics simulations were run for 200 ns in order to determine the binding free energies of BPA,BPS,and BPF as well as to evaluate the stability of docking data.Results indicate that BPS and BPF,similarly to BPA,bind stably to the estrogen receptor through hydrogen bonding and hydrophobic interactions,indicating potential endocrine-disrupting effects.BPF exhibited the strongest binding affinity,primarily due to significant hydrophobic interactions involving residues like LEU346 and LEU384.BPA and BPF formed stable hydrogen bonds,whereas BPS displayed slightly lower stability and more varied interactions.Throughout the simulations,all ligands consistently occupied the receptor’s active site,highlighting persistent binding.These findings imply that BPS and BPF may pose comparable health risks to BPA,though their unique interaction patterns suggest different underlying mechanisms.Experimental validation in human systems is critical to corroborate these computational predictions and evaluate the safety of BPA substitutes.
基金Supported by the Ministry of Higher Education(Malaysia)(No.FRGS/1/2023/SKK15/IMU/01/1)International Medical University[No.PHMS I-2023(01)].
文摘Glaucoma,a degenerative optic neuropathy,causes retinal ganglion cell(RGC)apoptosis and irreversible vision loss.Current therapies often fail to stop disease progression despite lowering intraocular pressure,the main risk factor.Thus,neuroprotective strategies have gained interest.We performed a bibliometric analysis to determine global publishing trends and relationships among prolific authors,publications,institutions,funding agencies,and journals.We also analyzed author keywords to identify research hotspots in glaucoma neuroprotection.Further,based on keyword analysis,we reviewed most recent literature to understand mechanistic pathways underlying glaucomarelated pathophysiological responses leading to RGC loss.Bibliographic data were sourced from Scopus.Basic bibliographic features were characterized using Scopus’s functions.VOSviewer was used for mapping and visualizing bibliometric networks.The analysis included trends in publications since 2000,the most prolific countries,institutions,authors,and the strength of their linkages.A significant increase in publication output over the past two decades was noted.The United States leads in funding support,research output,and citation links,followed by China and the UK.Among the top 10 most cited authors,three are from Japanese institutions.Keyword analysis shows a focus on molecular targets related to ischemia,excitotoxicity,inflammation,and oxidative stress,with fewer emerging drug candidates and limited clinical trials.Based on the most recent literature,emerging molecular targets underlying these key pathophysiological mechanisms are summarized.In conclusion,while pathophysiology and molecular mechanisms are the current focus,there is not much progress in developing new drug candidates and conducting clinical trials.
基金supported by the National Natural Science Foundation of China(82374367)Jiangxi Provincial Natural Science Foundation(20242BAB26163,20232BAB206144)+4 种基金Jiangxi Province Key Laboratory of Traditional Chinese Medicine for Cardiovascular Diseases(20242BCC32096)NATCM’s Project of High-level Construction of Key TCM Disciplines(zyyzdxk-2023113)Project of Key Discipline Construction Fund of Jiangxi University of Chinese Medicine(2023jzzdxk032)Science and Technology Innovation Team Development Program of Jiangxi University of Chinese Medicine(CXTD22011)National Traditional Chinese Medicine Inheritance and Innovation Center Construction Project.
文摘Background:Atherosclerosis(AS),the primary pathological foundation of cardiovascular diseases,is characterized by intricate processes including inflammation,lipid metabolism disorders,and pyroptosis.While the traditional Chinese medicine compound Dingxin Recipe(DXR)has demonstrated definitive clinical efficacy in treating AS,its therapeutic mechanisms remain unclear.This study employed an integrated approach combining network pharmacology,molecular docking,and molecular dynamics simulations(MDS)to investigate DXR’s anti-AS mechanisms.Methods:Active ingredients and targets of DXR were identified and screened using databases such as GeneCards,OMIM,and TCMSP.An“ingredient-target-disease”network was constructed to visualize these interactions.Molecular docking was utilized to assess the binding affinity between key ingredients and their respective targets.Additionally,MDS were conducted to analyze the stability of these complexes,providing robust evidence for further clinical applications and in-depth research.Results:Through network pharmacology analysis,we identified 99 active drug components,934 gene targets,and 1463 disease targets associated with DXR.Protein-protein interaction analysis revealed central regulatory nodes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these components primarily modulate processes such as inflammatory response and transcription factor activation,and are closely linked to the AGERAGE signaling pathway,lipid metabolism,and atherosclerosis pathways.Molecular docking confirmed strong binding potential between the components and their targets,while MDS further validated the stability of these interactions.Conclusion:This study elucidates that the active ingredients in DXR alleviate AS by mitigating inflammatory responses and inhibiting pyroptosis through the suppression of inflammatory factor release.These findings provide a scientific foundation for the clinical application of DXR in AS treatment.
基金The Gansu Province University Industrial Support Plan(Grant No.2023CYZC-05)the Cuiying Technology Innovation Project of Lanzhou University Second Hospital(Grant No.CY2022-MS-B04)+1 种基金the Doctoral Students Training Research Fund of Lanzhou University Second Hospital(Grant No.YJS-BD-32)the Gansu Province Drug Regulatory Science Research Project in 2024(Grant No.2024GSMPA032).
文摘Euphorbia helioscopia,a natural plant recognized for its anti-tumor properties,has been extensively investigated in various cancers.However,its therapeutic potential in gastric cancer with positive lymph node metastasis remains underexplored.This study aimed to elucidate the role of E.helioscopia in treating gastric cancer with lymph node metastasis using an integrative approach that combined network pharmacology,molecular docking,and molecular dynamics simulations.Initially,shared target data between E.helioscopia and gastric cancer with positive lymph node metastasis were identified and systematically analyzed.Subsequently,molecular docking was conducted to validate the interactions between key components and targets.Finally,molecular dynamics simulations were employed,with binding free energy calculations performed using the MM-PBSA algorithm.The findings revealed that the primary bioactive compounds of E.helioscopia in this context included quercetin and luteolin,targeting core molecules such as EGFR and MMP9.Key pathways implicated in its mechanism of action included resistance to EGFR tyrosine kinase inhibitors,among others.Molecular docking demonstrated robust binding affinity between the active compounds and critical targets,with molecular dynamics and binding free energy analyses highlighting a particularly stable interaction between luteolin and MMP9.In conclusion,E.helioscopia exhibited a multi-component,multi-target,and multi-pathway therapeutic profile in treating gastric cancer with positive lymph node metastasis.These findings offered valuable theoretical insights supporting its potential clinical application in oncology.
基金the financial support from the National Natural Science Foundation of China(62275057)the Guangxi Natural Science Foundation(2023GXNSFFA026004)+2 种基金the Guangxi Talent Program("Highland of Innovation Talents")the Shenzhen High-tech Development Special Plan-Pingshan Districts Innovation Platform Project(29853M-KCJ-2023-002-04)Industry and Energy(MOTIE),Republic of Korea(Project No.:RS-2025-02413058)。
文摘The performance of organic solar cells is significantly influenced by the acceptor molecular packing properties within the active layers,which is essential for optimizing charge dynamics and photovoltaic performance.However,achieving precise control over this packaging structure presents a considerable challenge.Herein,we propose a dual additive strategy utilizing dibenzofuran and halogenated naphthalene to systematically manipulate molecular packing orientation and enhance the long-range molecular packing order of the acceptors.Dibenzofuran is crucial in promoting crystallinity within the material,facilitating the formation of an ordered structure,while halogenated naphthalene regulates the orientation of the molecules,ensuring proper alignment.Specifically,the combination of dibenzofuran and 1-chloronaphthalene promotes edge-on molecular packing and enhances the formation of nanofibrillar structures with improved order,leading to improved charge transport and device performance.Implementing this strategy in devices composed of PM6 and L8-BO has yielded a power conversion efficiency of 19.58%,accompanied by long-term stability.Similarly,1-fluoronaphthalene has also demonstrated effectiveness in improving molecular orientation and overall device efficiency,demonstrating the robustness of this dual additive strategy.By addressing the challenges associated with molecular packing and orientation in active layers,our result contributes valuable insights into optimizing organic solar cells for practical applications.
基金Research Grants of Senior Research Fellowship in favor of first author(Gloak Majumdar)from Council of Scientific and Industrial Research(CSIR,New Delhi,Government of India)(CSIR-SRF)with Award No.09/1151/(0008)2020-EMR-I.
文摘Objective To evaluate the antibacterial potential of bioactive compounds from Persicaria hydropiper(L.)(P.hydropiper)against bacterial virulence proteins through molecular docking(MD)and experimental validation.Methods Six bioactive compounds from P.hydropiper were investigated:catechin(CAT1),hyperin(HYP1),ombuin(OMB1),pinosylvin(PSV1),quercetin 3-sulfate(QSF1),and scutellarein(SCR1).Their binding affinities and potential binding pockets were assessed through MD against four bacterial target proteins with Protein Data Bank identifiers(PDB IDs):topoisomerase IV from Escherichia coli(E.coli)(PDB ID:3FV5),Staphylococcus aureus(S.aureus)gyrase ATPase binding domain(PDB ID:3U2K),CviR from Chromobacterium violaceum(C.violaceum)(PDB ID:3QP1),and glycosyl hydrolase from Pseudomonas aeruginosa(P.aeruginosa)(PDB ID:5BX9).Molecular dynamics simulations(MDS)were performed on the most promising compound-protein complexes for 50 nanoseconds(ns).Drug-likeness was evaluated using Lipinski's Rule of Five(RO5),followed by absorption,distribution,metabolism,excretion,and toxicity(ADMET)analysis using SwissADME and pkCSM web servers.Antibacterial activity was evaluated through disc diffusion assays,testing both individual compounds and combinations with conventional antibiotics[cefotaxime(CTX1,30μg/disc),ceftazidime(CAZ1,30μg/disc),and piperacillin(PIP1,100μg/disc)].Results MD revealed strong binding affinity(ranging from-9.3 to-5.9 kcal/mol)for all compounds,with CAT1 showing exceptional binding to 3QP1(-9.3 kcal/mol)and 5BX9(-8.4 kcal/mol).MDS confirmed the stability of CAT1-protein complexes with binding free energies of-84.71 kJ/mol(5BX9-CAT1)and-95.59 kJ/mol(3QP1-CAT1).Five compounds(CAT1,SCR1,PSV1,OMB1,and QSF1)complied with Lipinski's RO5 and showed favorable ADMET profiles.All compounds were non-carcinogenic,with CAT1 classified in the lowest toxicity class(VI).In antibacterial assays,CAT1 demonstrated significant activity against both gram-positive bacteria[Streptococcus pneumoniae(S.pneumoniae),S.aureus,and Bacillus cereus(B.cereus)][zone diameter of inhibition(ZDI):10-22 mm]and gram-negative bacteria[Acinetobacter baumannii(A.baumannii),E.coli,and P.aeruginosa](ZDI:14-27 mm).Synergistic effects were observed when CAT1 was combined with antibiotics and the growth inhibitory indices(GII)was 0.69-1.00.Conclusion P.hydropiper bioactive compounds,particularly CAT1,show promising antibacterial potential through multiple mechanisms,including direct inhibition of bacterial virulence proteins and synergistic activity with conventional antibiotics.The favorable pharmacological properties and low toxicity profiles support their potential development as therapeutic agents against bacterial infections.
文摘Porous molecular sieve catalysts,including aluminosilicate zeolites and silicoaluminophosphate(SAPO)molecular sieves,have found widespread use in heterogeneous catalysis and are expected to play a key role in advancing carbon neutrality and sustainable development.Given the ubiquitous presence of water during catalyst synthesis,storage,and application,the interactions between water and molecular sieves as well as their consequent effects on frameworks and catalytic reactions have attracted considerable attention.These effects are inherently complex and highly dependent on various factors such as temperature,water phase,and partial pressure.In this review,we provide a comprehensive overview of the current understanding of water-molecular sieve interactions and their roles in catalysis,based on both experimental and theoretical calculation results.Special attention is paid to water-induced reversible and irreversible structural changes in aluminosilicate and SAPO frameworks at the atomic level,underscoring the dynamic and labile nature of these frameworks in water environments.The influence of water on catalytic performance and reaction kinetics in molecular sieve-catalyzed reactions is discussed from two perspectives:(1)its participation in reaction through hydrogen bonding interactions,such as competitive adsorption at active sites,stabilization of ground and transition states,and proton transfer bridge;(2)its role as a direct reactant forming new species via reactions with other vip molecules.Recent advancements in this area provide valuable insights for the rational design and optimization of catalysts for water-involved reactions.
基金supported by the National Natural Science Foundation of China(T2188102)Hangzhou Institute of Medicine(2024ZZBS02,Hangzhou,China).
文摘Molecular medicine,which delves into the intricacies of biomolecular structure,function,and role,is pivotal for advancing precise diagnostics and personalized treatment.Nucleic acids,a class of star functional molecules,are notable for their versatile applications in molecular diagnostics,gene therapy,and drug development.Therefore,in this study,we review the extensive use of nucleic acid aptamers in medicinal practice.Furthermore,the expanding field of molecular medicine has catalyzed advancements in traditional Chinese medicine(TCM),as evidenced by scientific endeavors to integrate modern technologies.Therefore,TCM has experienced rapid modernization by leveraging artificial intelligence,nucleic acid molecular medicine,and bioelectronic medicine.
