The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are imm...The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are immunological,and others associated as idiopathic,are undiagnosed by all possible means.Some of the rare diseases are congenital in nature,passing from the parent to the child.Many of the undiagnosed diseases are now being diagnosed as genetic and the genes have been implicated as a causative agent.There is a search for newer treatments for such diseases,which is called genomic medicine.Genomic medicine is an emerging medical discipline that involves the use of genomic information about an individual.This is used both for diagnostic as well as therapeutic decisions to improve the current health domain and pave the way for policymakers for its clinical use.In the developing era of precision medicine,genomics,epigenomics,environmental exposure,and other data would be used to more accurately guide individual diagnosis and treatment.Genomic medicine is already making an impact in the fields of oncology,pharmacology,rare,infectious and many undiagnosed diseases.It is beginning to fuel new approaches in certain medical specialties.Oncology is at the leading edge of incorporating genomics,as diagnostics for genetic and genomic markers are increasingly included in cancer screening,and to guide tailored treatment strategies.Genetics and genetic medicine have been reported to play a role in gastroenterology in several ways,including genetic testing(hereditary pancreatitis and hereditary gastrointestinal cancer syndromes).Genetic testing can also help subtype diseases,such as classifying pancreatitis as idiopathic or hereditary.Gene therapy is a promising approach for treating gastrointestinal diseases that are not effectively treated by conventional pharmaceuticals and surgeries.Gene therapy strategies include gene addition,gene editing,messenger RNA therapy,and gene silencing.Understanding genetic determinants,advances in genetics,have led to a better understanding of the genetic factors that contribute to human disease.Family-member risk stratification and genetic diagnosis can help identify family members who are at risk,which can lead to preventive treatments,lifestyle recommendations,and routine follow ups.Selecting target genes helps identify the gene targets associated with each gastrointestinal disease.Common gastrointestinal diseases associated with genetic abnormalities include-inflammatory bowel disease,gastroesophageal reflux disease,non-alcoholic fatty liver disease,and irritable bowel syndrome.With advancing tools and technology,research in the search of newer and individualized treatment,genes and genetic medicines are expected to play a significant role in human health and gastroenterology.展开更多
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
The shift from seedling transplanting to direct-seeding cultivation in rice demands robust root systems for early seedling establishment and yield stability.While the pleiotropic gene OsSP3(also designated TAC4 or SG2...The shift from seedling transplanting to direct-seeding cultivation in rice demands robust root systems for early seedling establishment and yield stability.While the pleiotropic gene OsSP3(also designated TAC4 or SG2)is known to regulate aboveground traits,including tiller angle,grain size,and panicle development,its function in root morphogenesis remains uncharacterized.展开更多
The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The mai...The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.展开更多
AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Com...AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.展开更多
The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can...The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.展开更多
The B-box(BBX)gene family plays a vital role in plant growth,development,and stress responses.This study aimed to characterize the SmBBX gene family in eggplant(Solanum melongena L.),addressing the lack of systematic ...The B-box(BBX)gene family plays a vital role in plant growth,development,and stress responses.This study aimed to characterize the SmBBX gene family in eggplant(Solanum melongena L.),addressing the lack of systematic bioinformatics and functional studies in this species.A total of 33 SmBBX genes were identified through genome-wide analysis.These genes were phylogenetically grouped into five major clades,with shared domain structures,motifs,and genomic architectures among clade members.The gene duplication analysis revealed segmental duplication as the primary mechanism underlying the expansion of SmBBX proteins in eggplant.Additionally,expression profiling across diverse tissues and abiotic stress conditions,combined with the construction of protein—protein interaction networks and luciferase complementation assay,provided valuable insights into the functional roles of SmBBX genes.SmBBX21-2 and SmBBX22 were identified as the key regulators of anthocyanin biosynthesis,activating the expression of SmCHS and SmDFR promoters.Functional validation via heterologous and homologous overexpression demonstrated that SmBBX22 promoted anthocyanin accumulation by upregulating the expression of structural genes(SmCHS,SmF3H,SmF3′5′H,SmDFR,and SmANS)and transcription factors(SmTT8 and SmHY5)important for anthocyanin biosynthesis.Furthermore,the integration of DNA affinity purification sequencing and RNA-seq data revealed the direct transcriptional targets of SmBBX22,including genes involved in secondary metabolism,hormone signaling,and developmental regulation.This highlighted the role of SmBBX22 in phenylpropanoid and flavonoid biosynthesis.This study lays the foundation for understanding the functional roles of BBX genes in eggplant and provides new directions for future research in plant metabolism and stress adaptation.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
The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant ...The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.展开更多
Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we develop...Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.展开更多
Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone...Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.展开更多
Quantitative real-time PCR(qPCR)is widely used for gene expression analysis,but its accuracy critically depends on stable internal reference genes for normalization.In marine invertebrates,especially non-model taxa su...Quantitative real-time PCR(qPCR)is widely used for gene expression analysis,but its accuracy critically depends on stable internal reference genes for normalization.In marine invertebrates,especially non-model taxa such as cephalopods,systematic evaluation of reference genes is limited,leading to potential bias.The cuttlefish Sepiella japonica is ecologically and economically important in China,yet previous molecular studies have often relied on single unvalidated reference genes,which may compromise data reliability.This study aimed to systematically evaluate the stability of five commonly used reference genes(18S,ef-1α,ef-1γ,gapdh,andβ-actin)across multiple tissues and sexes of S.japonica,and to identify the most suitable reference genes and optimal number for qPCR normalization.Fifteen to sixteen tissue types were collected from ten healthy adults(five males and five females).Total RNA was extracted,reverse-transcribed,and analyzed by qPCR.Gene stability was assessed using four algorithms(geNorm,NormFinder,BestKeeper,andΔCt)integrated with RefFinder,and the optimal gene number was determined using geNorm pairwise variation(V_(n/n+1)<0.15).Four transcriptome-derived genes(creld2,cd109,acy1,and miox)were used for validation.The C_(t)values of the five genes ranged from 15.47 to 20.83.β-actin and gapdh showed pronounced variability in expression stability among tissues and sexes,indicating their limited suitability for normalization.18S exhibited the highest expression(mean C_(t):15.47-16.29)and lowest variability but displayed sex-biased expression,whereas ef-1αand ef-1γremained consistently stable across most tissues in both sexes,with ef-1αbeing the most robust and showing no sex-related bias.Although specific rankings varied among tissues and sexes,the comprehensive results indicated that ef-1αand ef-1γpossessed the highest overall stability,followed by 18S,whileβ-actin and gapdh were the least stable.The final comprehensive rankings were ef-1γ>ef-1α>18S>gapdh>β-actin(male)and ef-1α>ef-1γ>18S>gapdh>β-actin(female).geNorm analysis(V2/3<0.15)indicated that two genes,mainly ef-1αand ef-1γ,were generally sufficient for reliable normalization in most tissues.Validation confirmed that normalization using the stable ef-1αand ef-1γaccurately reflected the expression differences among tissues,whereasβ-actin and gapdh can bias or confound statistical analyses.ef-1αand ef-1γare identified as the most reliable reference gene combination for qPCR analysis in S.japonica,while 18S can serve as an auxiliary gene for within-sex comparisons.The use ofβ-actin or gapdh alone is not recommended.This study establishes a systematic framework for selecting reliable reference genes in S.japonica,thereby facilitating robust qPCR normalization and providing a foundation for future gene expression research in S.japonica and other cephalopods.展开更多
Agrobacterium tumefaciens-mediated transformation has been widely adopted for plant genetic engineering and the study of gene function(Krenek et al.,2015).This method is prevalent in the genetic transformation of herb...Agrobacterium tumefaciens-mediated transformation has been widely adopted for plant genetic engineering and the study of gene function(Krenek et al.,2015).This method is prevalent in the genetic transformation of herbaceous plants,with notable applications in species such as Arabidopsis(Yin et al.,2024),soybean(Zhang et al.,2024),rice(Zhang et al.,2020),and Chinese cabbage(Li et al.,2021).However,its application in fruit trees is limited.This is primarily due to their long growth cycles and lack of rapid,efficient,and stable transgenic systems,which severely hinders foundational research involving plant genetic transformation(Mei et al.,2024).Furthermore,for subtropical fruit trees,the presence of recalcitrant seeds adds an extra layer of difficulty to genetic transformation(Umarani et al.,2015),as most methods rely on seed germination as a basis for transformation.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
[Objectives]To investigate the structure and function of the lipoxygenase(LOX)gene family in Physcomitrella patens.[Methods]This study employed bioinformatics methods to identify and predict LOX gene family members.Qu...[Objectives]To investigate the structure and function of the lipoxygenase(LOX)gene family in Physcomitrella patens.[Methods]This study employed bioinformatics methods to identify and predict LOX gene family members.Quantitative real-time PCR(qRT-PCR)was utilized to analyze the expression patterns of LOX genes at different stages of Botrytis cinerea infection.[Results]The P.patens LOX gene family comprises eight putative proteins,including two 12-LOX-type members and six 13-LOX-type members.Among the eight LOX proteins,PpLOX7 exhibited the lowest molecular weight and shortest amino acid sequence.PpLOX7 was identified as a basic protein with an isoelectric point(pI)of 8.54,while all other members were acidic.Subcellular localization analysis indicated that PpLOX7 was localized to the chloroplast,whereas the remaining members were distributed in the cytoplasm.Secondary structure prediction showed that all eight proteins were predominantly composed of random coils andα-helixes.Chromosomal mapping revealed that the LOX genes were distributed across 7 of the 27 chromosomes in P.patens,with PpLOX1 and PpLOX2 tandemly arranged on chromosome 15.The qRT-PCR analysis demonstrated distinct expression patterns among the eight PpLOX genes following B.cinerea infection.PpLOX1-3 and PpLOX7 were upregulated to varying degrees,suggesting their potential involvement in the early defense response of P.patens against B.cinerea.Notably,PpLOX2 exhibited highly significant differential expression,making it a key candidate for further investigation.[Conclusions]This study provides foundational insights into the functional roles of the LOX gene family in P.patens during biotic stress responses.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
文摘The etiopathogenesis of gastrointestinal diseases is varied in nature.Various etiogenic factors described are infective,inflammatory,viral,bacterial,parasitic,dietary and lifestyle change.Rare causative agents are immunological,and others associated as idiopathic,are undiagnosed by all possible means.Some of the rare diseases are congenital in nature,passing from the parent to the child.Many of the undiagnosed diseases are now being diagnosed as genetic and the genes have been implicated as a causative agent.There is a search for newer treatments for such diseases,which is called genomic medicine.Genomic medicine is an emerging medical discipline that involves the use of genomic information about an individual.This is used both for diagnostic as well as therapeutic decisions to improve the current health domain and pave the way for policymakers for its clinical use.In the developing era of precision medicine,genomics,epigenomics,environmental exposure,and other data would be used to more accurately guide individual diagnosis and treatment.Genomic medicine is already making an impact in the fields of oncology,pharmacology,rare,infectious and many undiagnosed diseases.It is beginning to fuel new approaches in certain medical specialties.Oncology is at the leading edge of incorporating genomics,as diagnostics for genetic and genomic markers are increasingly included in cancer screening,and to guide tailored treatment strategies.Genetics and genetic medicine have been reported to play a role in gastroenterology in several ways,including genetic testing(hereditary pancreatitis and hereditary gastrointestinal cancer syndromes).Genetic testing can also help subtype diseases,such as classifying pancreatitis as idiopathic or hereditary.Gene therapy is a promising approach for treating gastrointestinal diseases that are not effectively treated by conventional pharmaceuticals and surgeries.Gene therapy strategies include gene addition,gene editing,messenger RNA therapy,and gene silencing.Understanding genetic determinants,advances in genetics,have led to a better understanding of the genetic factors that contribute to human disease.Family-member risk stratification and genetic diagnosis can help identify family members who are at risk,which can lead to preventive treatments,lifestyle recommendations,and routine follow ups.Selecting target genes helps identify the gene targets associated with each gastrointestinal disease.Common gastrointestinal diseases associated with genetic abnormalities include-inflammatory bowel disease,gastroesophageal reflux disease,non-alcoholic fatty liver disease,and irritable bowel syndrome.With advancing tools and technology,research in the search of newer and individualized treatment,genes and genetic medicines are expected to play a significant role in human health and gastroenterology.
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funded by the Major Science and Technology Projects of Zhejiang Province,China(Grant No.2021C02063-5)the Key Research and Development Projects of Hainan Province,China(Grant No.ZDYF2023XDNY086)+2 种基金the State Key Laboratory for Quality and Safety Hazard Factors and Risk Prevention and Control of Agricultural Products Jointly Constructed by the Ministry and the Province,China(Grant No.2010DS700124)the Zhejiang Province Vanguard Leading Goose Project,China(Grant Nos.2023C02055 and 2022C02034)the Jiaxing Nanhu District Science and Technology Plan Project,China(Grant No.2023017).
文摘The shift from seedling transplanting to direct-seeding cultivation in rice demands robust root systems for early seedling establishment and yield stability.While the pleiotropic gene OsSP3(also designated TAC4 or SG2)is known to regulate aboveground traits,including tiller angle,grain size,and panicle development,its function in root morphogenesis remains uncharacterized.
基金Supported by the National Natural Science Foundation of China(No.32172979)the Natural Science Foundation of Fujian Province(No.2021J05159)the 2023 Special Program for Promoting High-Quality Development of Marine and Fishery Industry in Fujian Province(No.PJHYF-L-2023-2)。
文摘The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金Supported by the National Natural Science Foundation of China(No.81873686)Natural Science Foundation of Hunan Province(No.2023JJ30715)+4 种基金Scientific Research Project of Hunan Provincial Health Commission(No.A202303018385)Health Research Project of Hunan Provincial Health Commission(No.W20243024)Distinguished Professor of the Lotus Scholars Award Program of Hunan ProvinceSublimation Scholars Project of Central South UniversityWisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(No.YX202109).
文摘AIM:To conduct a genetic analysis of Han-Chinese patients with isolated congenital ptosis(ICP)and identify the genetic variants related to the condition.METHODS:Sixty-five unrelated patients with ICP were enrolled.Comprehensive clinical examinations,whole exome sequencing(WES),and Sanger sequencing were used to reveal the potential genetic causes.Combined with public and in-house control databases,multiple bioinformatics prediction tools,and conservation analysis,the potential variants were further analyzed.AlphaFold 3,an accurate modelling prediction tool,was utilized to generate three-dimensional structural models of both wild-type and mutated proteins.RESULTS:Three novel heterozygous variants in the zinc finger homeobox 4 gene(ZFHX4),c.5145C>A(p.N1715K),c.10382C>T(p.A3461V),and c.10795G>A(p.A3599T),were identified in three patients,respectively.Bioinformatics analyses suggested that these variants are likely to exert deleterious effects,supporting their potential involvement in the pathogenesis of ptosis.CONCLUSION:The novel heterozygous ZFHX4 variants are identified as disease-associated variants in three patients with ptosis,suggesting that ZFHX4 may be a disease-causing gene for autosomal dominant ICP with incomplete penetrance or a susceptibility gene.These findings expand the variant spectrum of ZFHX4,improve understanding of the pathogenesis of ZFHX4-related ptosis,and may contribute to the genetic counseling and disease management,as well as the development of experimental treatments.
基金Hongguang Wu,Both authors contributed equally to this work and share first authorshipLing Dong,Both authors contributed equally to this work and share first authorship。
文摘The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.
基金supported by grants from Shanghai Agriculture Applied Technology Development Program(Grant No.2022-02-08-00-12-F01109)the National Natural Science Foundation of China(Grant No.32272721).
文摘The B-box(BBX)gene family plays a vital role in plant growth,development,and stress responses.This study aimed to characterize the SmBBX gene family in eggplant(Solanum melongena L.),addressing the lack of systematic bioinformatics and functional studies in this species.A total of 33 SmBBX genes were identified through genome-wide analysis.These genes were phylogenetically grouped into five major clades,with shared domain structures,motifs,and genomic architectures among clade members.The gene duplication analysis revealed segmental duplication as the primary mechanism underlying the expansion of SmBBX proteins in eggplant.Additionally,expression profiling across diverse tissues and abiotic stress conditions,combined with the construction of protein—protein interaction networks and luciferase complementation assay,provided valuable insights into the functional roles of SmBBX genes.SmBBX21-2 and SmBBX22 were identified as the key regulators of anthocyanin biosynthesis,activating the expression of SmCHS and SmDFR promoters.Functional validation via heterologous and homologous overexpression demonstrated that SmBBX22 promoted anthocyanin accumulation by upregulating the expression of structural genes(SmCHS,SmF3H,SmF3′5′H,SmDFR,and SmANS)and transcription factors(SmTT8 and SmHY5)important for anthocyanin biosynthesis.Furthermore,the integration of DNA affinity purification sequencing and RNA-seq data revealed the direct transcriptional targets of SmBBX22,including genes involved in secondary metabolism,hormone signaling,and developmental regulation.This highlighted the role of SmBBX22 in phenylpropanoid and flavonoid biosynthesis.This study lays the foundation for understanding the functional roles of BBX genes in eggplant and provides new directions for future research in plant metabolism and stress adaptation.
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.
文摘The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.
基金supported partially by the Australian Government through the Australian Research Council Centres of Excellence funding scheme(project CE200100029)。
文摘Background:Tandem gene repeats naturally occur as important genomic features and determine many traits in living organisms,like human diseases and microbial productivities of target bioproducts.Methods:Here,we developed a bacterial type-II toxin-antitoxin-mediated method to manipulate genomic integration of tandem gene repeats in Saccharomyces cerevisiae and further visualised the evolutionary trajectories of gene repeats.We designed a tri-vector system to introduce toxin-antitoxin-driven gene amplification modules.Results:This system delivered multi-copy gene integration in the form of tandem gene repeats spontaneously and independently from toxin-antitoxin-mediated selection.Inducing the toxin(RelE)expressing via a copper(II)-inducible CUP1 promoter successfully drove the in-situ gene amplification of the antitoxin(RelB)module,resulting in~40 copies of a green fluorescence reporter gene per copy of genome.Copy-number changes,copy-number increase and copy-number decrease,and stable maintenance were visualised using the green fluorescence protein and blue chromoprotein AeBlue as reporters.Copy-number increases happened spontaneously and independent on a selection pressure.Increased copy number was quickly enriched through toxin-antitoxin-mediated selection.Conclusion:In summary,the bacterial toxin-antitoxin systems provide a flexible mechanism to manipulate gene copy number in eukaryotic cells and can be exploited for synthetic biology and metabolic engineering applications.
基金supported by the Ministry of Health National Medical Research Council (to JL)the National University of Singapore (to JJEC)
文摘Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.
文摘Quantitative real-time PCR(qPCR)is widely used for gene expression analysis,but its accuracy critically depends on stable internal reference genes for normalization.In marine invertebrates,especially non-model taxa such as cephalopods,systematic evaluation of reference genes is limited,leading to potential bias.The cuttlefish Sepiella japonica is ecologically and economically important in China,yet previous molecular studies have often relied on single unvalidated reference genes,which may compromise data reliability.This study aimed to systematically evaluate the stability of five commonly used reference genes(18S,ef-1α,ef-1γ,gapdh,andβ-actin)across multiple tissues and sexes of S.japonica,and to identify the most suitable reference genes and optimal number for qPCR normalization.Fifteen to sixteen tissue types were collected from ten healthy adults(five males and five females).Total RNA was extracted,reverse-transcribed,and analyzed by qPCR.Gene stability was assessed using four algorithms(geNorm,NormFinder,BestKeeper,andΔCt)integrated with RefFinder,and the optimal gene number was determined using geNorm pairwise variation(V_(n/n+1)<0.15).Four transcriptome-derived genes(creld2,cd109,acy1,and miox)were used for validation.The C_(t)values of the five genes ranged from 15.47 to 20.83.β-actin and gapdh showed pronounced variability in expression stability among tissues and sexes,indicating their limited suitability for normalization.18S exhibited the highest expression(mean C_(t):15.47-16.29)and lowest variability but displayed sex-biased expression,whereas ef-1αand ef-1γremained consistently stable across most tissues in both sexes,with ef-1αbeing the most robust and showing no sex-related bias.Although specific rankings varied among tissues and sexes,the comprehensive results indicated that ef-1αand ef-1γpossessed the highest overall stability,followed by 18S,whileβ-actin and gapdh were the least stable.The final comprehensive rankings were ef-1γ>ef-1α>18S>gapdh>β-actin(male)and ef-1α>ef-1γ>18S>gapdh>β-actin(female).geNorm analysis(V2/3<0.15)indicated that two genes,mainly ef-1αand ef-1γ,were generally sufficient for reliable normalization in most tissues.Validation confirmed that normalization using the stable ef-1αand ef-1γaccurately reflected the expression differences among tissues,whereasβ-actin and gapdh can bias or confound statistical analyses.ef-1αand ef-1γare identified as the most reliable reference gene combination for qPCR analysis in S.japonica,while 18S can serve as an auxiliary gene for within-sex comparisons.The use ofβ-actin or gapdh alone is not recommended.This study establishes a systematic framework for selecting reliable reference genes in S.japonica,thereby facilitating robust qPCR normalization and providing a foundation for future gene expression research in S.japonica and other cephalopods.
基金funded by the Key-Area Research and Development Program of Guangdong Province(Grant No.2022B0202070002)the Guangxi Science and Technology Major Program(Grant No.GuikeAA23023007-2)+1 种基金the Guangdong Province Modern Agricultural Industry Technology System Innovation Team Construction Project(2024CXTD19)Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515010303)。
文摘Agrobacterium tumefaciens-mediated transformation has been widely adopted for plant genetic engineering and the study of gene function(Krenek et al.,2015).This method is prevalent in the genetic transformation of herbaceous plants,with notable applications in species such as Arabidopsis(Yin et al.,2024),soybean(Zhang et al.,2024),rice(Zhang et al.,2020),and Chinese cabbage(Li et al.,2021).However,its application in fruit trees is limited.This is primarily due to their long growth cycles and lack of rapid,efficient,and stable transgenic systems,which severely hinders foundational research involving plant genetic transformation(Mei et al.,2024).Furthermore,for subtropical fruit trees,the presence of recalcitrant seeds adds an extra layer of difficulty to genetic transformation(Umarani et al.,2015),as most methods rely on seed germination as a basis for transformation.
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 and Technology Program of Guizhou Provence(Qiankehejichu-ZK[2023]Yiban 271).
文摘[Objectives]To investigate the structure and function of the lipoxygenase(LOX)gene family in Physcomitrella patens.[Methods]This study employed bioinformatics methods to identify and predict LOX gene family members.Quantitative real-time PCR(qRT-PCR)was utilized to analyze the expression patterns of LOX genes at different stages of Botrytis cinerea infection.[Results]The P.patens LOX gene family comprises eight putative proteins,including two 12-LOX-type members and six 13-LOX-type members.Among the eight LOX proteins,PpLOX7 exhibited the lowest molecular weight and shortest amino acid sequence.PpLOX7 was identified as a basic protein with an isoelectric point(pI)of 8.54,while all other members were acidic.Subcellular localization analysis indicated that PpLOX7 was localized to the chloroplast,whereas the remaining members were distributed in the cytoplasm.Secondary structure prediction showed that all eight proteins were predominantly composed of random coils andα-helixes.Chromosomal mapping revealed that the LOX genes were distributed across 7 of the 27 chromosomes in P.patens,with PpLOX1 and PpLOX2 tandemly arranged on chromosome 15.The qRT-PCR analysis demonstrated distinct expression patterns among the eight PpLOX genes following B.cinerea infection.PpLOX1-3 and PpLOX7 were upregulated to varying degrees,suggesting their potential involvement in the early defense response of P.patens against B.cinerea.Notably,PpLOX2 exhibited highly significant differential expression,making it a key candidate for further investigation.[Conclusions]This study provides foundational insights into the functional roles of the LOX gene family in P.patens during biotic stress responses.
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.
