[ Objective] To open an exit for breeding high-fecundity Small Tail Han sheep according to genotypes. [ Method] By the PCR-RFLP, the polymorphism of ovine BMPR-IB gene was detected in Small Tail Han sheep of basic pop...[ Objective] To open an exit for breeding high-fecundity Small Tail Han sheep according to genotypes. [ Method] By the PCR-RFLP, the polymorphism of ovine BMPR-IB gene was detected in Small Tail Han sheep of basic population and breeding population. And its relationship with litter size was analyzed. [ Result] In the basic population, the frequencies of B ＋ and BB genotypes were 77.78% and 14.81%, respectively, and their litter size per parity was 1.77 and 2.40, respectively. In the breeding population, the frequencies of B ＋ and BB genotypes were 51.79% and 40.18%, respectively, and their litter size per parity was 2.54 and 3.02, respectively. [ Conclusion] The ovine BMPR-IB gene can be used as a molecular Qenetic marker for fecundity traits to establish high-fecundity Small Tail Han sheep.展开更多
In an attempt to generate g.A746G substitution in the BMPR-IB gene,we unexpectedly obtained BMPR-IB homozygous knockout piglets(BMPR-IB^(-/-))and heterogeneous knockout piglets with one copy of the A746G mutation(BMPR...In an attempt to generate g.A746G substitution in the BMPR-IB gene,we unexpectedly obtained BMPR-IB homozygous knockout piglets(BMPR-IB^(-/-))and heterogeneous knockout piglets with one copy of the A746G mutation(BMPR-IB-/746G)via CRISPR/Cas9 editing.Polymerase chain reaction(PCR)and sequencing revealed complex genomic rearrangements in the target region.All BMPR-IBdisrupted piglets showed an inability to stand and walk normally.Both BMPR-IB^(-/-)and BMPR-IB-/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms(ulna,radius)and disordered carpal,metacarpal,and phalangeal bones in the forelimbs.The piglets displayed more severe deformities in the hindlimbs by visual inspection,including fibular hemimelia,enlarged tarsal bone,and disordered toe joint bones.Limb deformities were more profound in BMPR-IB^(-/-)piglets than in the BMPR-IB-/746G piglets.Proteomic analysis identified 139 differentially expressed proteins(DEPs)in the hindlimb fibula of BMPR-IB-/746G piglets compared to the wild-type(WT)controls.Most DEPs are involved in skeletal or embryonic development and/or the TGF-βpathway and tumor progression.Gene Ontology(GO)and protein domain enrichment analysis suggested alterations in these processes.Of the top 50 DEPs,a large proportion,e.g.,C1QA,MYO1H,SRSF1,P3H1,GJA1,TCOF1,RBM10,SPP2,MMP13,and PHAX,were significantly associated with skeletal development.Our study provides novel findings on the role of BMPR-IB in mammalian limb development.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
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 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 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
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
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
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
Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular...Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.展开更多
Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulat...Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.展开更多
Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,...Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.展开更多
The chalcone isomerase gene OsCHI,one of the key genes in the flavonoid biosynthesis pathway,plays an important role in rice(Oryza sativa)resistance to abiotic stresses.This study reveals how the chalcone isomerase ge...The chalcone isomerase gene OsCHI,one of the key genes in the flavonoid biosynthesis pathway,plays an important role in rice(Oryza sativa)resistance to abiotic stresses.This study reveals how the chalcone isomerase gene family member OsCHI3 participates in rice responses to drought stress through the regulation of flavonoid biosynthesis.Overexpression of OsCHI3 increased the tolerance of rice to drought stress.In contrast,CRISPR/Cas9-mediated deletion of OsCHI3 reduced the drought tolerance of rice,an effect that is reversed by exogenous ABA treatment.Transcriptomic and physiological biochemical analyses indicated that flavonoids regulated by OsCHI3 not only scavenge reactive oxygen species(ROS)but also increase drought tolerance in rice by stimulating ABA biosynthesis through the regulation of OsNCED1 and OsABA8ox3 expression.These findings demonstrate that OsCHI3 increases drought stress tolerance in rice by activating the antioxidant defense system and the ABA metabolic pathway,providing new clues for drought-resistant rice breeding research.展开更多
Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating...Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.展开更多
BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),w...BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),with its noninvasive capability to assess tumor characteristics in detail,has shown promise in evaluating treatment response and predicting therapeutic outcomes.This technology holds potential for guiding personalized treatment strategies tailored to individual patient profiles,enhancing the precision and effectiveness of colorectal cancer care.AIM To create a multiparametric MRI-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.METHODS This retrospective study was conducted in a tertiary hospital,analyzing 157 colorectal cancer patients with gene mutations treated between August 2022 and December 2023.Based on chemotherapy outcomes,the patients were categorized into favorable(n=60)and unfavorable(n=50)response groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of chemotherapy efficacy.A predictive nomogram was constructed using significant variables,and its performance was assessed using the area under the receiver operating characteristic curve(AUC)in both training and validation sets.RESULTS Univariate analysis identified that tumor differentiation,T2 signal intensity ratio,tumor-to-anal margin distance,and MRI-detected lymph node metastasis as significantly associated with chemotherapy response(P<0.05).Multivariate Logistics regression confirmed these four parameters as independent predictors.The predictive model demonstrated strong discrimination,with an AUC of 0.938(sensitivity:86%;specificity:92%)in the training set,and 0.942(sensitivity:100%;specificity:83%)in the validation set.CONCLUSION We established and validated a multiparametric MRI-based model for predicting chemotherapy response in colorectal cancer patients with gene mutations.This model holds promise for guiding individualized treatment strategies.展开更多
Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological bi...Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.展开更多
Heat stress causes overgrowth,leaf dryness and fruit malformation,which negatively impacts cucumber quality and yield.Yet,in spite of the devastating consequences of this abiotic stress,few genes for heat tolerance in...Heat stress causes overgrowth,leaf dryness and fruit malformation,which negatively impacts cucumber quality and yield.Yet,in spite of the devastating consequences of this abiotic stress,few genes for heat tolerance in cucumber have been identified.Here,the heat injury indices of 88 cucumber accessions representing diverse ecotypes were collected in two open-field environments,with naturally occurring high temperatures over two years.Seventeen of the 88 accessions were identified as highly heat-tolerant.Using a genome-wide association study,five loci(gHII3.1,gHII3.2,gHII3.3,gHII4.1 and gHII6.1)on three chromosomes associated with heat tolerance were detected.Pairwise linkage disequilibrium correlation,sequence polymorphisms,and qRT-PCR analyses at these loci,identified five candidate genes predicted to be casual for heat stress response in cucumber.CsaV3_3G04883,CsaV3_4G029050 and CsaV3_6G005370 each had nonsynonymous SNPs,and were significantly up-regulated by heat stress in the heat-tolerant genotypes.CsaV3_3G031890 was also induced by heat stress,but in the heatsensitive genotypes,and sequence polymorphism was only found in the promoter region.Identifying these candidate genes lays a foundation for understanding cucumber thermotolerance mechanisms.Our study is one of the few to examine heat stress in adult cucumber plants and it therefore fills a critical gap in knowledge.It is also an important first-step towards accelerating the breeding of robust heat-tolerant varieties.展开更多
Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment proc...Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria(ARB)disinfection and ARGs degradation and even promote the proliferation of ARGs.Problematically,ARB and ARGs in effluent pose potential risks if they are not further treated.Photocatalytic oxidation is considered a promising disinfection technology,where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid(DNA)for ARB elimination and subsequent degradation of ARGs.This reviewaims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant(AR)from wastewater in recent years.We discuss the sources and transfer of ARGs in wastewater.The overall removal efficiencies of ultraviolet radiation(UV)/chlorination,UV/ozone,UV/H_(2)O_(2),and UV/sulfate-radical based system for ARB and ARGs,as well as the experimental parameters and removal mechanisms,are systematically discussed.The contribution of photocatalytic materials based on TiO_(2) and g-C_(3)N_(4) to the inactivation of ARB and degradation of ARGs is highlighted,producingmany free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer(HGT)in wastewater.Finally,based on the reviewed studies,future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.展开更多
The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers...The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed.Beyond these vectors,polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities,such as improving the stability,cellar uptake and endosomal escape of nucleic acid drugs,along with precise delivery to targeted tissues.This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery,focusing on key cationic polymers,nanocarrier types,and preparation methods.It also highlights targeted diseases,strategies to improve delivery efficiency,and potential future directions in this research area.The review is hoped to inspire the development,optimization,and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.展开更多
基金supported by Agricultural Stock Breeding Project of Shandong Province(Breeding of New Breeds of Excellent Local Mutton Sheep)
文摘[ Objective] To open an exit for breeding high-fecundity Small Tail Han sheep according to genotypes. [ Method] By the PCR-RFLP, the polymorphism of ovine BMPR-IB gene was detected in Small Tail Han sheep of basic population and breeding population. And its relationship with litter size was analyzed. [ Result] In the basic population, the frequencies of B ＋ and BB genotypes were 77.78% and 14.81%, respectively, and their litter size per parity was 1.77 and 2.40, respectively. In the breeding population, the frequencies of B ＋ and BB genotypes were 51.79% and 40.18%, respectively, and their litter size per parity was 2.54 and 3.02, respectively. [ Conclusion] The ovine BMPR-IB gene can be used as a molecular Qenetic marker for fecundity traits to establish high-fecundity Small Tail Han sheep.
基金supported by the National Natural Science Foundation of China(31560304)National Key Research Programs of China(2016ZX08006-003)。
文摘In an attempt to generate g.A746G substitution in the BMPR-IB gene,we unexpectedly obtained BMPR-IB homozygous knockout piglets(BMPR-IB^(-/-))and heterogeneous knockout piglets with one copy of the A746G mutation(BMPR-IB-/746G)via CRISPR/Cas9 editing.Polymerase chain reaction(PCR)and sequencing revealed complex genomic rearrangements in the target region.All BMPR-IBdisrupted piglets showed an inability to stand and walk normally.Both BMPR-IB^(-/-)and BMPR-IB-/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms(ulna,radius)and disordered carpal,metacarpal,and phalangeal bones in the forelimbs.The piglets displayed more severe deformities in the hindlimbs by visual inspection,including fibular hemimelia,enlarged tarsal bone,and disordered toe joint bones.Limb deformities were more profound in BMPR-IB^(-/-)piglets than in the BMPR-IB-/746G piglets.Proteomic analysis identified 139 differentially expressed proteins(DEPs)in the hindlimb fibula of BMPR-IB-/746G piglets compared to the wild-type(WT)controls.Most DEPs are involved in skeletal or embryonic development and/or the TGF-βpathway and tumor progression.Gene Ontology(GO)and protein domain enrichment analysis suggested alterations in these processes.Of the top 50 DEPs,a large proportion,e.g.,C1QA,MYO1H,SRSF1,P3H1,GJA1,TCOF1,RBM10,SPP2,MMP13,and PHAX,were significantly associated with skeletal development.Our study provides novel findings on the role of BMPR-IB in mammalian limb development.
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.
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 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 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.
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,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,No.82101340(to FJ).
文摘Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.
基金supported by the National Natural Science Foundation of China,Nos.82271411(to RG),51803072(to WLiu)grants from the Department of Finance of Jilin Province,Nos.2022SCZ25(to RG),2022SCZ10(to WLiu),2021SCZ07(to RG)+2 种基金Jilin Provincial Science and Technology Program,No.YDZJ202201ZYTS038(to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University,No.2022qnpy11(to WLuo)The Project of China-Japan Union Hospital of Jilin University,No.XHQMX20233(to RG)。
文摘Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,and Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022).
文摘Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.
基金supported by Science and Technology Innovation Program of Hunan province(2024NK1010,2023NK1010,2023ZJ1080)the National Natural Science Foundation of China(U21A20208).
文摘The chalcone isomerase gene OsCHI,one of the key genes in the flavonoid biosynthesis pathway,plays an important role in rice(Oryza sativa)resistance to abiotic stresses.This study reveals how the chalcone isomerase gene family member OsCHI3 participates in rice responses to drought stress through the regulation of flavonoid biosynthesis.Overexpression of OsCHI3 increased the tolerance of rice to drought stress.In contrast,CRISPR/Cas9-mediated deletion of OsCHI3 reduced the drought tolerance of rice,an effect that is reversed by exogenous ABA treatment.Transcriptomic and physiological biochemical analyses indicated that flavonoids regulated by OsCHI3 not only scavenge reactive oxygen species(ROS)but also increase drought tolerance in rice by stimulating ABA biosynthesis through the regulation of OsNCED1 and OsABA8ox3 expression.These findings demonstrate that OsCHI3 increases drought stress tolerance in rice by activating the antioxidant defense system and the ABA metabolic pathway,providing new clues for drought-resistant rice breeding research.
基金Dean's Office Howard University College of Medicine,Grant/Award Number:Bridge Fund/Pilot Study AwardNational Center on Minority Health and Health Disparities,Grant/Award Number:RCMI/IDC Award U54MD007597National Institute of Child Health and Human Development,Grant/Award Number:R03HD095417 and R16HD116702。
文摘Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.
基金Supported by Shenzhen High-level Hospital Construction Fund.
文摘BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),with its noninvasive capability to assess tumor characteristics in detail,has shown promise in evaluating treatment response and predicting therapeutic outcomes.This technology holds potential for guiding personalized treatment strategies tailored to individual patient profiles,enhancing the precision and effectiveness of colorectal cancer care.AIM To create a multiparametric MRI-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.METHODS This retrospective study was conducted in a tertiary hospital,analyzing 157 colorectal cancer patients with gene mutations treated between August 2022 and December 2023.Based on chemotherapy outcomes,the patients were categorized into favorable(n=60)and unfavorable(n=50)response groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of chemotherapy efficacy.A predictive nomogram was constructed using significant variables,and its performance was assessed using the area under the receiver operating characteristic curve(AUC)in both training and validation sets.RESULTS Univariate analysis identified that tumor differentiation,T2 signal intensity ratio,tumor-to-anal margin distance,and MRI-detected lymph node metastasis as significantly associated with chemotherapy response(P<0.05).Multivariate Logistics regression confirmed these four parameters as independent predictors.The predictive model demonstrated strong discrimination,with an AUC of 0.938(sensitivity:86%;specificity:92%)in the training set,and 0.942(sensitivity:100%;specificity:83%)in the validation set.CONCLUSION We established and validated a multiparametric MRI-based model for predicting chemotherapy response in colorectal cancer patients with gene mutations.This model holds promise for guiding individualized treatment strategies.
基金supported by Hunan Provincial Key Research and Development Program,No.2021SK2002(to BW)the Natural Science Foundation of Hunan Province of China(General Program),No.2021JJ30938(to YL)。
文摘Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
基金supported by Beijing Joint Research Program for Germplasm Innovation and New Variety Breeding(Grant No.G20220628003-03)Chongqing Municipal People's Government and Chinese Academy of Agricultural Sciences strategic cooperation project,Key-Area Research and Development Program of Guangdong Province(Grant No.2020B020220001)+3 种基金the Earmarked Fund for Modern Agro-industry Technology Research System(Grant No.CARS-23)Science and Technology Innovation Program of the Chinese Academy of Agricultural Science(Grant No.CAAS-ASTIP-IVFCAAS)Central public-interest Scientific Institution Basal Research Fund(Grant No.Y2017PT52)the Key Laboratory of Biology and Genetic Improvement of Horticultural Crops,Ministry of Agriculture,P.R.China。
文摘Heat stress causes overgrowth,leaf dryness and fruit malformation,which negatively impacts cucumber quality and yield.Yet,in spite of the devastating consequences of this abiotic stress,few genes for heat tolerance in cucumber have been identified.Here,the heat injury indices of 88 cucumber accessions representing diverse ecotypes were collected in two open-field environments,with naturally occurring high temperatures over two years.Seventeen of the 88 accessions were identified as highly heat-tolerant.Using a genome-wide association study,five loci(gHII3.1,gHII3.2,gHII3.3,gHII4.1 and gHII6.1)on three chromosomes associated with heat tolerance were detected.Pairwise linkage disequilibrium correlation,sequence polymorphisms,and qRT-PCR analyses at these loci,identified five candidate genes predicted to be casual for heat stress response in cucumber.CsaV3_3G04883,CsaV3_4G029050 and CsaV3_6G005370 each had nonsynonymous SNPs,and were significantly up-regulated by heat stress in the heat-tolerant genotypes.CsaV3_3G031890 was also induced by heat stress,but in the heatsensitive genotypes,and sequence polymorphism was only found in the promoter region.Identifying these candidate genes lays a foundation for understanding cucumber thermotolerance mechanisms.Our study is one of the few to examine heat stress in adult cucumber plants and it therefore fills a critical gap in knowledge.It is also an important first-step towards accelerating the breeding of robust heat-tolerant varieties.
基金supported by the National Natural Science Foundation of China (Nos.52100182 and 52300204)the the Science and Technology Innovation Program of Hunan Province (No.2023RC3122).
文摘Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria(ARB)disinfection and ARGs degradation and even promote the proliferation of ARGs.Problematically,ARB and ARGs in effluent pose potential risks if they are not further treated.Photocatalytic oxidation is considered a promising disinfection technology,where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid(DNA)for ARB elimination and subsequent degradation of ARGs.This reviewaims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant(AR)from wastewater in recent years.We discuss the sources and transfer of ARGs in wastewater.The overall removal efficiencies of ultraviolet radiation(UV)/chlorination,UV/ozone,UV/H_(2)O_(2),and UV/sulfate-radical based system for ARB and ARGs,as well as the experimental parameters and removal mechanisms,are systematically discussed.The contribution of photocatalytic materials based on TiO_(2) and g-C_(3)N_(4) to the inactivation of ARB and degradation of ARGs is highlighted,producingmany free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer(HGT)in wastewater.Finally,based on the reviewed studies,future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.
基金supported by National Natural Science Foundation of China(82104082)Natural Science Foundation of Qinghai Province(2024-ZJ-911).
文摘The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed.Beyond these vectors,polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities,such as improving the stability,cellar uptake and endosomal escape of nucleic acid drugs,along with precise delivery to targeted tissues.This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery,focusing on key cationic polymers,nanocarrier types,and preparation methods.It also highlights targeted diseases,strategies to improve delivery efficiency,and potential future directions in this research area.The review is hoped to inspire the development,optimization,and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.
