Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in...Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their un...Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their unique dimensions and structures.Unfortunately,emerging evidence suggests that NMs may facilitate the transmission of ARGs.It is crucial to elucidate how NMs affect the evolution and dissemination of ARGs.The current review comprehensively examines the role of NMs in the widespread transmission of ARGs in aquatic environments and the underlying mechanisms involved in the process.It aims to clarify the effects and mechanisms of NMs on the horizontal gene transfer processes that are associated with ARGs,including the enhancement of cell membrane permeability,the formation of nanopores on membranes,promotion of mutagenesis,and the generation of reactive oxygen species(ROSs).Furthermore,the trade-off between the removal of ARGs and horizontal transfer has been elucidated.The review aspires to guide future research directions,advance knowledge on the implications of NMs in the field of ARGs' transmission,and provide a theoretical foundation for the development of safer and more effective applications of NMs.展开更多
AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induc...AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.展开更多
Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural pro...Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural products,thereby endangering human health.Extensive studies on Aspergillus fungi have been conducted on growth and development,aflatoxin biosynthesis,and their interactions with environment.Here,we summarized a series of functional genes of the main Aspergillus fungi relative to toxins occurrence in foods,which revealed the signal transduction mechanisms of their involvement in growth and development,toxin production,and response to light,anticipating providing theoretical guidance on developing control and prevention technologies for mycotoxin contamination in agricultural products to ensure food safety.展开更多
Antibiotic contamination has garnered significant attention,particularly given the growing pressures from aquaculture,a key contributor to environmental antibiotic loads.Addressing both antibiotic and nitrogen polluti...Antibiotic contamination has garnered significant attention,particularly given the growing pressures from aquaculture,a key contributor to environmental antibiotic loads.Addressing both antibiotic and nitrogen pollution in such ecosystems is critical.In this study,the aerobic denitrifying bacterium Marinobacter hydrocarbonoclasticus RAD-2,previously isolated in our laboratory,was subjected to a series of concentration gradients(0,20,40,60,80,100 mg/L)to evaluate the single and combined effects of tetracycline(TET)and chlortetracycline(CTC)on the aerobic denitrification process.Among them,the combined effects of antibiotics were set up in a full-factor experimental design(a total of 30 treatment combinations)on the basis of the single-factor experiments of TET and CTC.Results demonstrated that the inhibitory impact of both antibiotics intensified with increasing concentration,with CTC exerting a more pronounced inhibitory effect.Notably,RAD-2 was unable to proliferate at 100 mg/L of TET or 80 mg/L of CTC.High concentrations of either antibiotic significantly suppressed the expression of key denitrification functional genes,including nirX,napA,norB,and nosZ.Furthermore,simultaneous exposure to both antibiotics led to a rapid decline in nitrogen removal efficiency(TET or CTC>60 mg/L),alongside substantial inhibition of bacterial growth and functional gene expression,except for napA.Under specific concentration ranges,the combination of TET and CTC exhibits a certain degree of antagonistic effect.These findings provide critical insights into the restoration of wetland ecosystem health and inform strategies to mitigate the dual challenges of antibiotic and nitrogen pollution in aquaculture effluents.展开更多
Catalpa bungei,a fast-growing timber tree,is threatened by the lepidopteran pest Omphisa plagialis.Previous studies in our laboratory successfully generated transgenic C.bungei lines overexpressing Cry genes(Cry1Ab,Cr...Catalpa bungei,a fast-growing timber tree,is threatened by the lepidopteran pest Omphisa plagialis.Previous studies in our laboratory successfully generated transgenic C.bungei lines overexpressing Cry genes(Cry1Ab,Cry2A,and Cry9-2)that exhibited resistance to O.plagialis,but their potential impact on soil bacterial communities remains unclear.In this study,we analyzed nine transgenic C.bungei lines(three independent lines for each Cry gene)to characterize their rhizosphere bacterial communities using high-throughput sequencing of the 16S ribosomal DNA(rDNA)V4-V5 regions.A total of 628 amplicon sequence variants(ASVs)were shared among all transgenic and wild-type(WT)lines,forming a stable core microbiome dominated by Proteobacteria,Bacteroidota,Acidobacteriota,and Actinobacteriota.Alpha diversity showed no significant differences,while beta diversity revealed minor but distinct compositional shifts.Cry1Ab lines exhibited higher abundances of fast-growing taxa,particularly Proteobacteria and Bacteroidota;Cry2A lines displayed intermediate profiles,whereas Cry9-2 lines were nearly indistinguishable from WT communities.Linear discriminant analysis of the effect size revealed significant enrichment of taxa such as Burkholderiaceae and Ralstonia in the Cry1Ab rhizosphere,in contrast to the higher abundance of Chloroflexi in the WT.Functional predictions indicated consistent metabolic pathways across all treatments,suggesting strong ecological redundancy.This study demonstrates minimal impact on rhizosphere microbial communities in transgenic C.bungei plants.The Cry9-2 construct exhibited superior environmental stability,whereas the Cry1Ab construct caused only slight but ecologically acceptable shifts.These findings support the ecological safety of Bt-transgenic C.bungei and identify Cry9-2 as a particularly favorable candidate for forestry applications.This comparative evaluation of three Cry genes in a tree species provides a framework for future gene-specific biosafety assessments in woody plants.展开更多
AIM:To identify differentially expressed genes(DEGs)in rabbits with traumatic proliferative vitreoretinopathy(PVR)using high-throughput sequencing(HTS).METHODS:Thirty-six rabbits were randomly allocated to the control...AIM:To identify differentially expressed genes(DEGs)in rabbits with traumatic proliferative vitreoretinopathy(PVR)using high-throughput sequencing(HTS).METHODS:Thirty-six rabbits were randomly allocated to the control group and the PVR group induced by scleral puncture.On the 28th day following modeling,fundus B-ultrasound and fundus photography were performed on all rabbits,and hematoxylin-eosin(HE)staining was conducted on retinal tissues.RNA sequencing(RNA-Seq)combined with bioinformatics analysis was used to screen PVRassociated DEGs.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out for the identified DEGs.S100A6,EDNRB and CEBPD were randomly selected for quantitative reverse transcription polymerase chain reaction(RT-qPCR)validation to verify the reliability of the RNA-Seq results.RESULTS:Fundus B-ultrasound,fundus photography and retinal HE staining confirmed the successful establishment of the traumatic PVR rabbit model.A total of 1587 DEGs were screened,of which 1094 were significantly up-regulated and 493 were significantly down-regulated.GO function enrichment analysis showed that these DEGs were mainly enriched in immune response,extracellular region and inflammatory response.KEGG pathway enrichment analysis showed that DEGs were mainly involved in the cytokine-cytokine receptor interaction and hematopoietic cell lineage pathway.RT-qPCR results showed that S100A6,CEBPD and EDNRB were significantly increased in PVR group.CONCLUSION:A large number of genes exhibit significant differential expression in rabbits with traumatic PVR,among which S100A6,CEBPD and EDNRB may play an important role in traumatic PVR.展开更多
Liquid-solid phase transfer promotes the interaction of perfluoroalkyl acids(PFAAs)with the microbial system of river sediments,which may affect the environmental behavior of antibiotic resistance genes(ARGs)contained...Liquid-solid phase transfer promotes the interaction of perfluoroalkyl acids(PFAAs)with the microbial system of river sediments,which may affect the environmental behavior of antibiotic resistance genes(ARGs)contained in benthic environments.Sediments collected from the receiving water of the largest fluoropolymer production facility in China were analyzed to investigate the impact of PFAAs on microbial communities and ARG profiles.The main contributors to the PFAAs were perfluorooctanoic acid and perfluorobutanoic acid,whose proportions(86.9%-93.4%)in the downstream surface sediments affected by industrial effluents were significantly higher than in the corresponding upstream samples(53.3%).A reduction in microbial diversity and richness was observed in the presence of high concentrations of PFAAs at the downstream sites.144 ARG subtypes,including three high-risk subtypes(bacA,aac(6′)-I and aadA),were identified in sediment samples.The discharge of fluorochemical effluents also results in a reduction of ARG diversity at subtype level.PFAAs exert a pronounced influence on the profile of ARGs in sediment.PFAAs and water quality parameters(e.g.pH and total phosphorus)were key drivers of the microbial community composition in the sediment.The regulation of microbial communities by PFAAs may represent an important pathway by which these compounds affect ARG profiles.展开更多
Insects represent one of the most evolutionarily successful groups,with their diversity hypothesized to be related to the regulatory roles of Hox genes,a set of related genes encoding homeodomain transcription factors...Insects represent one of the most evolutionarily successful groups,with their diversity hypothesized to be related to the regulatory roles of Hox genes,a set of related genes encoding homeodomain transcription factors determining the identity of segments along the anterior-posterior axis of the embryo.However,functional insights into the roles of Hox genes in primitive ametabolous insects,which represent the critical transition from aquatic crustaceans to winged insects,have been limited.In this study,we identified complete protein-coding sequences of 10 Hox genes in the Zygentoma Thermobia domestica,and applied clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease 9(Cas 9)mediated gene knockout(KO)to decipher their functions.We found that the roles of pb,Dfd,and Scr are vital in specifying the appendages of the head in T.domestica,and these roles are relatively conserved in crustaceans and winged insects.Antp is essential for the development of the prothorax segment and the first pair of legs in T.domestica.Ubx and abd-A fully repress appendage development in the abdomen of T.domestica,which implies a functional switch from crustaceans to insects.Additionally,the role of ftz in segmenting the abdomen of T.domestica suggests it has acquired new functions in primitive insects,beyond its traditional Hox-like roles.Although KOs of lab,Hox3,and Abd-B did not result in obvious external phenotypic changes,they led to a significant decrease in hatching rates and substantial deviations in daily survival numbers compared to the negative control.These findings underscore the indispensable roles of all Hox genes during the embryonic development of T.domestica.Our study sheds new light on the functional evolution of Hox genes in ametabolous insects and enhances our understanding of the genetic underpinnings of insect development and diversification.展开更多
Fusarium head blight(FHB),mainly caused by fungus Fusarium graminearum,is a devastating wheat disease worldwide,leading to reduced yield production and compromised grain quality due to contamination by mycotoxins,such...Fusarium head blight(FHB),mainly caused by fungus Fusarium graminearum,is a devastating wheat disease worldwide,leading to reduced yield production and compromised grain quality due to contamination by mycotoxins,such as deoxynivalenol(DON).Manipulating the specific gene expression in microorganisms through RNA interference(RNAi)presents an opportunity for new-generation double-stranded RNA(dsRNA)-based formulations to combat a large number of plant diseases.Here,we applied both spray-induced gene silencing(SIGS)and host-induced gene silencing(HIGS)to target five virulence-related and DON-synthesized genes in F.graminearum,including protein kinase gene Gpmk1,zinc finger protein gene Fg Chy1,transcription factor Fg SR,DON synthesis gene TRI5 and the cell-end marker protein gene Fg Tea A,aiming to effectively control FHB in wheat.Direct spraying of individual or combined small interfering RNA(siRNAs)from the fungus showed reduced expression of target genes and suppressed pathogenic symptoms during F.graminearum infection in wheat leaves,with the combination of all five siRNAs demonstrating superior resistance.Furthermore,we generated transgenic wheat lines expressing chimeric RNAi cassettes targeting these five genes,and two independent lines exhibited strong resistance to FHB and Fusarium crown rot,and the reduced DON accumulation.Notably,the HIGS transgenic lines did not adversely impact plant growth and yield traits.Collectively,our findings support that SIGS and HIGS represent effective strategies targeting key pathogenic genes for bolstering disease resistance in crops.展开更多
Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is re...Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.Methods:In this study,the dataset GSE132903 was retrieved from the GEO database,encompassing both non-demented(ND)control and AD samples.Through the combination of differential expression gene analysis,weighted gene co-expression network analysis,and intersection with mitochondrial database gene sets,four hub genes associated with AD were identified.These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.Results:The hub genes identified through bioinformatics analysis include SYNJ2BP,VDAC1,NUBPL,and COX19.Within the GSE132903 dataset,the expression levels of SYNJ2BP,NUBPL,and COX19 were significantly elevated in the AD group compared to the non-demented(ND)group,whereas VDAC1 expression was reduced in the AD group relative to the ND group.Furthermore,in the hippocampus of APP/PS1 and 5xFAD mouse models,the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.Conclusion:Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.展开更多
As a large family of RNA helicases,DEAD-box(DDX)RNA helicases play crucial roles in almost all cellular RNA processing activities.However,the role of the DDX gene family in cold tolerance of mei(Prunus mume)remains un...As a large family of RNA helicases,DEAD-box(DDX)RNA helicases play crucial roles in almost all cellular RNA processing activities.However,the role of the DDX gene family in cold tolerance of mei(Prunus mume)remains unclear.In this study,we identified 45 DDX genes through whole-genome analysis unevenly distributed across eight chromosomes and scaffolds of mei.Based on the phylogenetic tree and gene structure analysis,the DDX genes were classified into nine subfamilies based on their motif compositions and intron-exon structures.The results of synteny analysis showed that segmental duplication was considered a major factor contributing to the amplification of the PmDDX family.RNA-Seq and qRT-PCR results revealed differential expression of PmDDX genes under cold stress.Among these,PmDDX39 was significantly up-regulated under cold stress,suggesting its positive role in modulating mei cold tolerance.We found that silenced PmDDX39 under cold stress led to greater damage than the wild seedlings via virus-induced gene silencing(VIGS).Conversely,overexpression of PmDDX39 in Arabidopsis enhanced cold stress tolerance.Moreover,dual luciferase and yeast one-hybrid(Y1H)demonstrated that PmDDX39 directly activates the expression of the C-repeat binding factor(PmCBFf)by binding to its promoters.This study provides new insights into the structure,evolution,and functional role of the PmDDX gene family in mei responses to cold stress.展开更多
Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusio...Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusion genes in patients with AML.Methods A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction(RT-PCR)were subjected to NGS analysis.Results Fusion genes were detected in 21 of 72(29.2%)patients.Among the 26 primary refractory patients,11(42.3%)exhibited fusion genes,whereas among the 18 relapsed patients,fusion genes were identified in five(27.8%).Notably,lysine methyltransferase 2A(KMT2A)and nucleoporin 98(NUP98)rearrangements were enriched in refractory/relapsed patients.Additionally,recurrent fusion transcripts involving eukaryotic translation initiation factor 4A1(EIF4A1)were identified.The identification of additional fusion genes resulted in an approximate 20.8%(11/53)reclassification of medium-risk karyotypes to the high-risk category,thereby enhancing diagnostic accuracy.Conclusions Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML;however,its prognostic value requires validation in prospective controlled trials.展开更多
Neurodegenerative diseases(neurodegenerative disorders)are marked by the progressive degeneration of the structure and function of the central nervous system.They may res ult in the deterioration of cognitive,motor,an...Neurodegenerative diseases(neurodegenerative disorders)are marked by the progressive degeneration of the structure and function of the central nervous system.They may res ult in the deterioration of cognitive,motor,and functional abilities.Diseases such as Alzheimer s disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis represent some of the most prominent examples of neurodegenerative disorders.Des pite scientific advancement in understanding disease pathology and prognosis,the therapeutic strategies available for management remain limited.In recent years,microRNAs,small non-coding RNA molecules,have emerged as key players in the pathogenesis of neurodegenerative disorde rs.Therefo re,understanding how these microRNAs affect disease pathology and pathway signaling is essential,and may open microRNAs as new avenues for potential therapeutic intervention.This review explores the role of microRNAs in va rious neurodegenerative diseases,discuss how microRNAs affect signaling pathways,and examine the potential of microRNAs as therapeutic targets.展开更多
Researchers from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences,with collaborators,identified two sorghum genes(SbSLT1 and SbSLT2)that block Striga-a parasitic plant,also k...Researchers from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences,with collaborators,identified two sorghum genes(SbSLT1 and SbSLT2)that block Striga-a parasitic plant,also known as“witchweed,”that causes$1.5 billion annual losses in Africa by draining crop nutrients.Published in Cell(February 12,2025),the study shows that these genes regulate strigolactones(SLs).展开更多
Objective To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease(DKD)through bioinformatics analysis,and to identify related Chinese medicines.Methods Data from sequencing mi...Objective To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease(DKD)through bioinformatics analysis,and to identify related Chinese medicines.Methods Data from sequencing microarrays GSE30528,GSE30529,and GSE1009 in the Gene Expression Omnibus(GEO)were employed.Differentially expressed genes(DEGs)with adjusted P<0.05 from GSE30528 and GSE30529 were identified.Combining these DEGs with the human autophagy gene database,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and protein-protein interaction(PPI)network analysis were conducted on the obtained DKD autophagy-related genes.Subsequently,the least absolute shrinkage and selection operator(LASSO)regression and support vector machinerecursive feature elimination(SVM-RFE)algorithms were adopted to select autophagy-related genes.The diagnostic capability of these genes was assessed through analysis with the external validation set from microarray GSE1009,and relevant Chinese medicines were inversely predicted using the SymMap database.Results A total of 2014 DEGs were selected from GSE30528 and GSE30529,leading to the identification of 37 DKD autophagy-related genes.GO analysis indicated 681 biological mechanisms,including autophagy regulation and plasma membrane microdomain activity.KEGG enrichment analysis identified 112 related signaling pathways.PPI network analysis showed a marked enrichment of autophagy-related genes in DKD.Through LASSO regression and SVM-RFE,four core diagnostic genes for autophagy in DKD were identified:protein phosphatase 1 regulatory subunit 15A(PPP1R15A),hypoxia inducible factor 1 alpha subunit(HIF1α),deleted in liver cancer 1(DLC1),and ceroid lipofuscinosis neuronal 3(CLN3).The external validation set demonstrated high diagnostic efficiency for these genes.Finally,146 kinds of potential Chinese medicines were predicted using the SymMap database,with heatclearing and detoxifying medicine and blood-activating and stasis-eliminating medicine accounting for the largest proportion(25/146 and 13/146,respectively).Conclusion This study analyzed and validated bioinformatics sequencing databases to elucidate the potential molecular mechanisms of DKD autophagy and predicted key diagnostic genes,potential therapeutic targets,and related Chinese medicines,laying a solid foundation for clinical research and application.展开更多
The effects of disinfectants and plasmid-based antibiotic resistance genes(ARGs)on the growth of microorganisms and the plasmid-mediated transfer of ARGs in the water and biofilm of the drinkingwater distribution syst...The effects of disinfectants and plasmid-based antibiotic resistance genes(ARGs)on the growth of microorganisms and the plasmid-mediated transfer of ARGs in the water and biofilm of the drinkingwater distribution system under simulated conditionswere explored.The heterotrophic plate count of the water in reactors with 0.1 mg/L NaClO and NH_(2)Cl was higher than in the control groups.Therewas no similar phenomenon in biofilm.In thewater of reactors containing NaClO,the aphA and bla geneswere lower than in the antibiotic resistant bacteria group,while both genes were higher in the water of reactors with NH_(2)Cl than in the control group.Chloramine may promote the transfer of ARGs in the water phase.Both genes in the biofilm of the reactors containing chlorine were lower than the control group.Correlation analysis between ARGs and water quality parameters revealed that the copy numbers of the aphA gene were significantly positively correlated with the copy numbers of the bla gene in water and significantly negatively correlated in biofilm(p<0.05).The results of the sequencing assay showed that bacteria in the biofilm,in the presence of disinfectant,were primarily Gram-negative.1.0 mg/L chlorine decreased the diversity of the community in the biofilm.The relative abundance of some bacteria that may undergo transfer increased in the biofilm of the reactor containing 0.1 mg/L chlorine.展开更多
基金supported by the National Natural Science Foundation of China,No.82471327the Natural Science Foundation of ShandongProvince,No.ZR2024MH200(both to SL).
文摘Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
基金supported by the State Key Laboratory of Urban Water Resource and Environment (Harbin Institute of Technology) (No.2022TS13)the key projects of National Natural Science Foundation of China (No.2019YFC0408503)the Key Research Program of Wuhan (No.2022022202015015)。
文摘Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their unique dimensions and structures.Unfortunately,emerging evidence suggests that NMs may facilitate the transmission of ARGs.It is crucial to elucidate how NMs affect the evolution and dissemination of ARGs.The current review comprehensively examines the role of NMs in the widespread transmission of ARGs in aquatic environments and the underlying mechanisms involved in the process.It aims to clarify the effects and mechanisms of NMs on the horizontal gene transfer processes that are associated with ARGs,including the enhancement of cell membrane permeability,the formation of nanopores on membranes,promotion of mutagenesis,and the generation of reactive oxygen species(ROSs).Furthermore,the trade-off between the removal of ARGs and horizontal transfer has been elucidated.The review aspires to guide future research directions,advance knowledge on the implications of NMs in the field of ARGs' transmission,and provide a theoretical foundation for the development of safer and more effective applications of NMs.
基金Supported by the National Natural Science Fundation of China(No.82101107No.81471575).
文摘AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.
基金supported by the key project of National Natural Sciences Foundation of China(U22A20551,32030085)the Major Project of Hubei Hongshan Laboratory,China(2021hszd015)+2 种基金the Hubei Province Major Science and Technology Special Project,China(2023BBA002)the National Natural Sciences Foundation of China(U22A20551)the National Natural Science Foundation of China Excellent Youth Fund(32422072)。
文摘Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural products,thereby endangering human health.Extensive studies on Aspergillus fungi have been conducted on growth and development,aflatoxin biosynthesis,and their interactions with environment.Here,we summarized a series of functional genes of the main Aspergillus fungi relative to toxins occurrence in foods,which revealed the signal transduction mechanisms of their involvement in growth and development,toxin production,and response to light,anticipating providing theoretical guidance on developing control and prevention technologies for mycotoxin contamination in agricultural products to ensure food safety.
基金supported by the Science Fund for Distinguished Young Scholars of Zhejiang Province(No.LR22C190001)the National Natural Science Foundation of China(No.41401556).
文摘Antibiotic contamination has garnered significant attention,particularly given the growing pressures from aquaculture,a key contributor to environmental antibiotic loads.Addressing both antibiotic and nitrogen pollution in such ecosystems is critical.In this study,the aerobic denitrifying bacterium Marinobacter hydrocarbonoclasticus RAD-2,previously isolated in our laboratory,was subjected to a series of concentration gradients(0,20,40,60,80,100 mg/L)to evaluate the single and combined effects of tetracycline(TET)and chlortetracycline(CTC)on the aerobic denitrification process.Among them,the combined effects of antibiotics were set up in a full-factor experimental design(a total of 30 treatment combinations)on the basis of the single-factor experiments of TET and CTC.Results demonstrated that the inhibitory impact of both antibiotics intensified with increasing concentration,with CTC exerting a more pronounced inhibitory effect.Notably,RAD-2 was unable to proliferate at 100 mg/L of TET or 80 mg/L of CTC.High concentrations of either antibiotic significantly suppressed the expression of key denitrification functional genes,including nirX,napA,norB,and nosZ.Furthermore,simultaneous exposure to both antibiotics led to a rapid decline in nitrogen removal efficiency(TET or CTC>60 mg/L),alongside substantial inhibition of bacterial growth and functional gene expression,except for napA.Under specific concentration ranges,the combination of TET and CTC exhibits a certain degree of antagonistic effect.These findings provide critical insights into the restoration of wetland ecosystem health and inform strategies to mitigate the dual challenges of antibiotic and nitrogen pollution in aquaculture effluents.
基金funded by the Chinese Academy of Forestry-Special funds for basic scientific research service expenses of the central level public welfare research institutes(Grant No.CAFYBB2020QD001)the National Natural Science Foundation of China(Grant Nos.32101550,32271917)+1 种基金Jiangsu Agricultural Science and Technology Innovation Fund(Grant No.CX(24)3052)National Forestry and Grassland Administration’s Center for Science and Technology Development Projects(Grant No.KJZXSA202202).
文摘Catalpa bungei,a fast-growing timber tree,is threatened by the lepidopteran pest Omphisa plagialis.Previous studies in our laboratory successfully generated transgenic C.bungei lines overexpressing Cry genes(Cry1Ab,Cry2A,and Cry9-2)that exhibited resistance to O.plagialis,but their potential impact on soil bacterial communities remains unclear.In this study,we analyzed nine transgenic C.bungei lines(three independent lines for each Cry gene)to characterize their rhizosphere bacterial communities using high-throughput sequencing of the 16S ribosomal DNA(rDNA)V4-V5 regions.A total of 628 amplicon sequence variants(ASVs)were shared among all transgenic and wild-type(WT)lines,forming a stable core microbiome dominated by Proteobacteria,Bacteroidota,Acidobacteriota,and Actinobacteriota.Alpha diversity showed no significant differences,while beta diversity revealed minor but distinct compositional shifts.Cry1Ab lines exhibited higher abundances of fast-growing taxa,particularly Proteobacteria and Bacteroidota;Cry2A lines displayed intermediate profiles,whereas Cry9-2 lines were nearly indistinguishable from WT communities.Linear discriminant analysis of the effect size revealed significant enrichment of taxa such as Burkholderiaceae and Ralstonia in the Cry1Ab rhizosphere,in contrast to the higher abundance of Chloroflexi in the WT.Functional predictions indicated consistent metabolic pathways across all treatments,suggesting strong ecological redundancy.This study demonstrates minimal impact on rhizosphere microbial communities in transgenic C.bungei plants.The Cry9-2 construct exhibited superior environmental stability,whereas the Cry1Ab construct caused only slight but ecologically acceptable shifts.These findings support the ecological safety of Bt-transgenic C.bungei and identify Cry9-2 as a particularly favorable candidate for forestry applications.This comparative evaluation of three Cry genes in a tree species provides a framework for future gene-specific biosafety assessments in woody plants.
基金Supported by the National Natural Science Foundation of China(No.82260210)the Natural Science Foundation of Jiangxi Province(No.20252BAC250122)+2 种基金the Science and Technology Planning Project of Jiangxi Provincial Health Commission(No.202510055)Jiangxi Province Graduate Innovation Special Fund(No.YC2025-B211)Jiangxi Association for Science Education(No.2025KXJYS019).
文摘AIM:To identify differentially expressed genes(DEGs)in rabbits with traumatic proliferative vitreoretinopathy(PVR)using high-throughput sequencing(HTS).METHODS:Thirty-six rabbits were randomly allocated to the control group and the PVR group induced by scleral puncture.On the 28th day following modeling,fundus B-ultrasound and fundus photography were performed on all rabbits,and hematoxylin-eosin(HE)staining was conducted on retinal tissues.RNA sequencing(RNA-Seq)combined with bioinformatics analysis was used to screen PVRassociated DEGs.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out for the identified DEGs.S100A6,EDNRB and CEBPD were randomly selected for quantitative reverse transcription polymerase chain reaction(RT-qPCR)validation to verify the reliability of the RNA-Seq results.RESULTS:Fundus B-ultrasound,fundus photography and retinal HE staining confirmed the successful establishment of the traumatic PVR rabbit model.A total of 1587 DEGs were screened,of which 1094 were significantly up-regulated and 493 were significantly down-regulated.GO function enrichment analysis showed that these DEGs were mainly enriched in immune response,extracellular region and inflammatory response.KEGG pathway enrichment analysis showed that DEGs were mainly involved in the cytokine-cytokine receptor interaction and hematopoietic cell lineage pathway.RT-qPCR results showed that S100A6,CEBPD and EDNRB were significantly increased in PVR group.CONCLUSION:A large number of genes exhibit significant differential expression in rabbits with traumatic PVR,among which S100A6,CEBPD and EDNRB may play an important role in traumatic PVR.
基金supported by the National Key Research and Develop-ment Program of China(No.2021YFC3200805)the National Natu-ral Science Foundation of China(Nos.52325001 and 52170009).
文摘Liquid-solid phase transfer promotes the interaction of perfluoroalkyl acids(PFAAs)with the microbial system of river sediments,which may affect the environmental behavior of antibiotic resistance genes(ARGs)contained in benthic environments.Sediments collected from the receiving water of the largest fluoropolymer production facility in China were analyzed to investigate the impact of PFAAs on microbial communities and ARG profiles.The main contributors to the PFAAs were perfluorooctanoic acid and perfluorobutanoic acid,whose proportions(86.9%-93.4%)in the downstream surface sediments affected by industrial effluents were significantly higher than in the corresponding upstream samples(53.3%).A reduction in microbial diversity and richness was observed in the presence of high concentrations of PFAAs at the downstream sites.144 ARG subtypes,including three high-risk subtypes(bacA,aac(6′)-I and aadA),were identified in sediment samples.The discharge of fluorochemical effluents also results in a reduction of ARG diversity at subtype level.PFAAs exert a pronounced influence on the profile of ARGs in sediment.PFAAs and water quality parameters(e.g.pH and total phosphorus)were key drivers of the microbial community composition in the sediment.The regulation of microbial communities by PFAAs may represent an important pathway by which these compounds affect ARG profiles.
基金National Natural Science Foundation of China(Nos.32170425,32470443,32300388).
文摘Insects represent one of the most evolutionarily successful groups,with their diversity hypothesized to be related to the regulatory roles of Hox genes,a set of related genes encoding homeodomain transcription factors determining the identity of segments along the anterior-posterior axis of the embryo.However,functional insights into the roles of Hox genes in primitive ametabolous insects,which represent the critical transition from aquatic crustaceans to winged insects,have been limited.In this study,we identified complete protein-coding sequences of 10 Hox genes in the Zygentoma Thermobia domestica,and applied clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease 9(Cas 9)mediated gene knockout(KO)to decipher their functions.We found that the roles of pb,Dfd,and Scr are vital in specifying the appendages of the head in T.domestica,and these roles are relatively conserved in crustaceans and winged insects.Antp is essential for the development of the prothorax segment and the first pair of legs in T.domestica.Ubx and abd-A fully repress appendage development in the abdomen of T.domestica,which implies a functional switch from crustaceans to insects.Additionally,the role of ftz in segmenting the abdomen of T.domestica suggests it has acquired new functions in primitive insects,beyond its traditional Hox-like roles.Although KOs of lab,Hox3,and Abd-B did not result in obvious external phenotypic changes,they led to a significant decrease in hatching rates and substantial deviations in daily survival numbers compared to the negative control.These findings underscore the indispensable roles of all Hox genes during the embryonic development of T.domestica.Our study sheds new light on the functional evolution of Hox genes in ametabolous insects and enhances our understanding of the genetic underpinnings of insect development and diversification.
基金financially supported by the National Key R&D Program of China(2022YFD1400105)the Jiangsu Agricultural Science and Technology Innovation Fund(CX(22)2005)+3 种基金the Jiangsu Key R&D Plan(Modern Agriculture),China(BE2022346)the China Agricultural Research System Program(CARS-03)the National Science Fund for Excellent Young Scholars(Overseas),Chinathe Start-Up Grant from Nanjing Agricultural University,China。
文摘Fusarium head blight(FHB),mainly caused by fungus Fusarium graminearum,is a devastating wheat disease worldwide,leading to reduced yield production and compromised grain quality due to contamination by mycotoxins,such as deoxynivalenol(DON).Manipulating the specific gene expression in microorganisms through RNA interference(RNAi)presents an opportunity for new-generation double-stranded RNA(dsRNA)-based formulations to combat a large number of plant diseases.Here,we applied both spray-induced gene silencing(SIGS)and host-induced gene silencing(HIGS)to target five virulence-related and DON-synthesized genes in F.graminearum,including protein kinase gene Gpmk1,zinc finger protein gene Fg Chy1,transcription factor Fg SR,DON synthesis gene TRI5 and the cell-end marker protein gene Fg Tea A,aiming to effectively control FHB in wheat.Direct spraying of individual or combined small interfering RNA(siRNAs)from the fungus showed reduced expression of target genes and suppressed pathogenic symptoms during F.graminearum infection in wheat leaves,with the combination of all five siRNAs demonstrating superior resistance.Furthermore,we generated transgenic wheat lines expressing chimeric RNAi cassettes targeting these five genes,and two independent lines exhibited strong resistance to FHB and Fusarium crown rot,and the reduced DON accumulation.Notably,the HIGS transgenic lines did not adversely impact plant growth and yield traits.Collectively,our findings support that SIGS and HIGS represent effective strategies targeting key pathogenic genes for bolstering disease resistance in crops.
基金Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01 and 2023-PT330-01Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-034National Natural Science Foundation of China,Grant/Award Number:82161138027。
文摘Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.Methods:In this study,the dataset GSE132903 was retrieved from the GEO database,encompassing both non-demented(ND)control and AD samples.Through the combination of differential expression gene analysis,weighted gene co-expression network analysis,and intersection with mitochondrial database gene sets,four hub genes associated with AD were identified.These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.Results:The hub genes identified through bioinformatics analysis include SYNJ2BP,VDAC1,NUBPL,and COX19.Within the GSE132903 dataset,the expression levels of SYNJ2BP,NUBPL,and COX19 were significantly elevated in the AD group compared to the non-demented(ND)group,whereas VDAC1 expression was reduced in the AD group relative to the ND group.Furthermore,in the hippocampus of APP/PS1 and 5xFAD mouse models,the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.Conclusion:Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.
基金supported by the Fundamental Research Funds for the Central Universities(Grant No.QNTD202503)Forestry and Grassland Science and Technology Innovation Youth Top Talent Project of China(Grant No.2020132608)Beijing High-Precision Discipline Project,Discipline of Ecological Environment of Urban and Rural Human Settlements.
文摘As a large family of RNA helicases,DEAD-box(DDX)RNA helicases play crucial roles in almost all cellular RNA processing activities.However,the role of the DDX gene family in cold tolerance of mei(Prunus mume)remains unclear.In this study,we identified 45 DDX genes through whole-genome analysis unevenly distributed across eight chromosomes and scaffolds of mei.Based on the phylogenetic tree and gene structure analysis,the DDX genes were classified into nine subfamilies based on their motif compositions and intron-exon structures.The results of synteny analysis showed that segmental duplication was considered a major factor contributing to the amplification of the PmDDX family.RNA-Seq and qRT-PCR results revealed differential expression of PmDDX genes under cold stress.Among these,PmDDX39 was significantly up-regulated under cold stress,suggesting its positive role in modulating mei cold tolerance.We found that silenced PmDDX39 under cold stress led to greater damage than the wild seedlings via virus-induced gene silencing(VIGS).Conversely,overexpression of PmDDX39 in Arabidopsis enhanced cold stress tolerance.Moreover,dual luciferase and yeast one-hybrid(Y1H)demonstrated that PmDDX39 directly activates the expression of the C-repeat binding factor(PmCBFf)by binding to its promoters.This study provides new insights into the structure,evolution,and functional role of the PmDDX gene family in mei responses to cold stress.
基金supported by the National Natural Science Foundation of China(No.82100164,82302692)the Capital Medical University Research Cultivation Fund(No.PYZ22099)the Guangdong Provincial Medical Science and Technology Research Fund Project(No.A2024190).
文摘Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusion genes in patients with AML.Methods A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction(RT-PCR)were subjected to NGS analysis.Results Fusion genes were detected in 21 of 72(29.2%)patients.Among the 26 primary refractory patients,11(42.3%)exhibited fusion genes,whereas among the 18 relapsed patients,fusion genes were identified in five(27.8%).Notably,lysine methyltransferase 2A(KMT2A)and nucleoporin 98(NUP98)rearrangements were enriched in refractory/relapsed patients.Additionally,recurrent fusion transcripts involving eukaryotic translation initiation factor 4A1(EIF4A1)were identified.The identification of additional fusion genes resulted in an approximate 20.8%(11/53)reclassification of medium-risk karyotypes to the high-risk category,thereby enhancing diagnostic accuracy.Conclusions Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML;however,its prognostic value requires validation in prospective controlled trials.
基金1RO1EY032959-01 from NIH,Leonard A Mann Chair Endowment Fund,from the University of Dayton(to AS)Knights Templar Eye Foundation grant(to MS)。
文摘Neurodegenerative diseases(neurodegenerative disorders)are marked by the progressive degeneration of the structure and function of the central nervous system.They may res ult in the deterioration of cognitive,motor,and functional abilities.Diseases such as Alzheimer s disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis represent some of the most prominent examples of neurodegenerative disorders.Des pite scientific advancement in understanding disease pathology and prognosis,the therapeutic strategies available for management remain limited.In recent years,microRNAs,small non-coding RNA molecules,have emerged as key players in the pathogenesis of neurodegenerative disorde rs.Therefo re,understanding how these microRNAs affect disease pathology and pathway signaling is essential,and may open microRNAs as new avenues for potential therapeutic intervention.This review explores the role of microRNAs in va rious neurodegenerative diseases,discuss how microRNAs affect signaling pathways,and examine the potential of microRNAs as therapeutic targets.
文摘Researchers from the Institute of Genetics and Developmental Biology(IGDB)of the Chinese Academy of Sciences,with collaborators,identified two sorghum genes(SbSLT1 and SbSLT2)that block Striga-a parasitic plant,also known as“witchweed,”that causes$1.5 billion annual losses in Africa by draining crop nutrients.Published in Cell(February 12,2025),the study shows that these genes regulate strigolactones(SLs).
基金National Natural Science Foundation of China(82170747),and Shanghai Key Laboratory of Traditional Chinese Clinical Medicine(20DZ2272200).
文摘Objective To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease(DKD)through bioinformatics analysis,and to identify related Chinese medicines.Methods Data from sequencing microarrays GSE30528,GSE30529,and GSE1009 in the Gene Expression Omnibus(GEO)were employed.Differentially expressed genes(DEGs)with adjusted P<0.05 from GSE30528 and GSE30529 were identified.Combining these DEGs with the human autophagy gene database,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and protein-protein interaction(PPI)network analysis were conducted on the obtained DKD autophagy-related genes.Subsequently,the least absolute shrinkage and selection operator(LASSO)regression and support vector machinerecursive feature elimination(SVM-RFE)algorithms were adopted to select autophagy-related genes.The diagnostic capability of these genes was assessed through analysis with the external validation set from microarray GSE1009,and relevant Chinese medicines were inversely predicted using the SymMap database.Results A total of 2014 DEGs were selected from GSE30528 and GSE30529,leading to the identification of 37 DKD autophagy-related genes.GO analysis indicated 681 biological mechanisms,including autophagy regulation and plasma membrane microdomain activity.KEGG enrichment analysis identified 112 related signaling pathways.PPI network analysis showed a marked enrichment of autophagy-related genes in DKD.Through LASSO regression and SVM-RFE,four core diagnostic genes for autophagy in DKD were identified:protein phosphatase 1 regulatory subunit 15A(PPP1R15A),hypoxia inducible factor 1 alpha subunit(HIF1α),deleted in liver cancer 1(DLC1),and ceroid lipofuscinosis neuronal 3(CLN3).The external validation set demonstrated high diagnostic efficiency for these genes.Finally,146 kinds of potential Chinese medicines were predicted using the SymMap database,with heatclearing and detoxifying medicine and blood-activating and stasis-eliminating medicine accounting for the largest proportion(25/146 and 13/146,respectively).Conclusion This study analyzed and validated bioinformatics sequencing databases to elucidate the potential molecular mechanisms of DKD autophagy and predicted key diagnostic genes,potential therapeutic targets,and related Chinese medicines,laying a solid foundation for clinical research and application.
基金supported by the Natural Science Foundation of China(No.52070145,51778453).
文摘The effects of disinfectants and plasmid-based antibiotic resistance genes(ARGs)on the growth of microorganisms and the plasmid-mediated transfer of ARGs in the water and biofilm of the drinkingwater distribution system under simulated conditionswere explored.The heterotrophic plate count of the water in reactors with 0.1 mg/L NaClO and NH_(2)Cl was higher than in the control groups.Therewas no similar phenomenon in biofilm.In thewater of reactors containing NaClO,the aphA and bla geneswere lower than in the antibiotic resistant bacteria group,while both genes were higher in the water of reactors with NH_(2)Cl than in the control group.Chloramine may promote the transfer of ARGs in the water phase.Both genes in the biofilm of the reactors containing chlorine were lower than the control group.Correlation analysis between ARGs and water quality parameters revealed that the copy numbers of the aphA gene were significantly positively correlated with the copy numbers of the bla gene in water and significantly negatively correlated in biofilm(p<0.05).The results of the sequencing assay showed that bacteria in the biofilm,in the presence of disinfectant,were primarily Gram-negative.1.0 mg/L chlorine decreased the diversity of the community in the biofilm.The relative abundance of some bacteria that may undergo transfer increased in the biofilm of the reactor containing 0.1 mg/L chlorine.
