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
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
Aiming to solve the steering instability and hysteresis of agricultural robots in the process of movement,a fusion PID control method of particle swarm optimization(PSO)and genetic algorithm(GA)was proposed.The fusion...Aiming to solve the steering instability and hysteresis of agricultural robots in the process of movement,a fusion PID control method of particle swarm optimization(PSO)and genetic algorithm(GA)was proposed.The fusion algorithm took advantage of the fast optimization ability of PSO to optimize the population screening link of GA.The Simulink simulation results showed that the convergence of the fitness function of the fusion algorithm was accelerated,the system response adjustment time was reduced,and the overshoot was almost zero.Then the algorithm was applied to the steering test of agricultural robot in various scenes.After modeling the steering system of agricultural robot,the steering test results in the unloaded suspended state showed that the PID control based on fusion algorithm reduced the rise time,response adjustment time and overshoot of the system,and improved the response speed and stability of the system,compared with the artificial trial and error PID control and the PID control based on GA.The actual road steering test results showed that the PID control response rise time based on the fusion algorithm was the shortest,about 4.43 s.When the target pulse number was set to 100,the actual mean value in the steady-state regulation stage was about 102.9,which was the closest to the target value among the three control methods,and the overshoot was reduced at the same time.The steering test results under various scene states showed that the PID control based on the proposed fusion algorithm had good anti-interference ability,it can adapt to the changes of environment and load and improve the performance of the control system.It was effective in the steering control of agricultural robot.This method can provide a reference for the precise steering control of other robots.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
BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to th...BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.展开更多
Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from cli...Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.展开更多
Several quantitative trait genes(QTGs)related to rice heading date,a key factor for crop development and yield,have been identified,along with complex interactions among genes.However,a comprehensive genetic interacti...Several quantitative trait genes(QTGs)related to rice heading date,a key factor for crop development and yield,have been identified,along with complex interactions among genes.However,a comprehensive genetic interaction network for these QTGs has not yet been established.In this study,we use 18K-rice lines to identify QTGs and their epistatic interactions affecting rice heading date.We identify 264 pairs of interacting quantitative trait loci(QTL)and construct a comprehensive genetic network of these QTL.On average,the epistatic effects of QTL pairs are estimated to be approximately 12.5%of additive effects of identified QTL.Importantly,epistasis varies among different alleles of several heading date genes.Additionally,57 pairs of interacting QTGs are also significant in their epistatic effects on 12 other agronomic traits.The identified QTL genetic interactions are further validated using near-isogenic lines,yeast two-hybrid,and split-luciferase complementation assays.Overall,this study provides a genetic network of rice heading date genes,which plays a crucial role in regulating rice heading date and influencing multiple related agronomic traits.This network serves as a foundation for understanding the genetic mechanisms of rice quantitative traits and for advancing rice molecular breeding.展开更多
Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric ...Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopathological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitationand hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.展开更多
With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of th...With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of these biological processes do not fully explain the onset,progression,and development of these conditions.Therefore,exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research.This review summarizes the potential common pathogeneses of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Huntington’s disease,frontotemporal lobar dementia,and Lewy body disease.Research findings have indicated that several common biological processes,including aging,genetic factors,progressive neuronal dysfunction,neuronal death and apoptosis,protein misfolding and aggregation,neuroinflammation,mitochondrial dysfunction,axonal transport defects,and gut microbiota dysbiosis,are involved in the pathogenesis of these six neurodegenerative diseases.Based on current information derived from diverse areas of research,these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases.Furthermore,promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed.Hence,these potential common biological processes may represent only very small,limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases.In clinical treatment,interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases.Therefore,future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks,rather than isolating individual biological processes.Based on this,therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions,as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.展开更多
Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major ...Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.展开更多
Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Ge...Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Genetic variants that regulate gene expression,known as expression quantitative trait loci(eQTL),are primarily shaped by human migration history and evolutionary forces,likewise,regulation of gene expression in principle could have been influenced by these events.Therefore,a comprehensive understanding of how human evolution impacts eQTL offers important insights into how phenotypic diversity is shaped.Recent studies,however,suggest that eQTL is enriched in genes that are selectively constrained.Whether eQTL is minimally affected by selective pressures remains an open question and requires comprehensive investigations.In addition,such studies are primarily dominated by the major populations of European ancestry,leaving many marginalized populations underrepresented.These observations indicate there exists a fundamental knowledge gap in the role of genomics variation on phenotypic diversity,which potentially hinders precision medicine.This article aims to revisit the abundance of eQTL across diverse populations and provide an overview of their impact from the population and evolutionary genetics perspective,subsequently discuss their influence on phenomics,as well as challenges and opportunities in the applications to precision medicine.展开更多
The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KC...The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.展开更多
Pediatric inflammatory bowel disease(IBD)is a chronic and heterogeneous disease.IBD is commonly classified into Crohn’s disease and ulcerative colitis.It is linked to serious symptoms and complications.The onset of I...Pediatric inflammatory bowel disease(IBD)is a chronic and heterogeneous disease.IBD is commonly classified into Crohn’s disease and ulcerative colitis.It is linked to serious symptoms and complications.The onset of IBD commonly occurs during adolescence.Despite the significant number of cases globally(~5 million),the causes of pediatric IBD,which constitutes 25%of IBD patients,are not yet fully understood.Apart from environmental factors,genetic factors contribute to a higher risk of developing IBD.The predisposition risk of IBD can be investigated using genetic testing.Genetic mechanisms of pediatric IBD are highly complex which resulted in difficulty in selecting effective treatment or patient management.Genetic variation of IBD would serve as a basis for precision medicine and allow for the discovery of more robust treatment avenues for this condition in pediatric patients.This review aims to discuss the genetics of pediatric IBD,and current development in the screening,diagnosis,and treatment based on genetic profiling of pediatric IBD subjects toward more personalized management of this disease.展开更多
Chronic kidney disease(CKD)affects a significant fraction of the global population and is closely associated with elevated cardiovascular risk and poor clinical outcomes.Its pathophysiology entails complex molecular a...Chronic kidney disease(CKD)affects a significant fraction of the global population and is closely associated with elevated cardiovascular risk and poor clinical outcomes.Its pathophysiology entails complex molecular and cellular disturbances,including reduced nitric oxide bioavailability,persistent low-grade inflammation,oxidative stress,endothelial dysfunction,altered mineral metabolism,genetic predispositions,and uremic toxin accumulation.As current pharmacological treatments provide only partial risk reduction,complementary approaches are imperative.Exercise training,both aerobic and resistance,has emerged as a potent non-pharmacological intervention targeting these underlying molecular pathways.Regular exercise can enhance nitric oxide signaling,improve antioxidant defenses,attenuate inflammation,facilitate endothelial repair via endothelial progenitor cells,and stabilize muscle metabolism.Additionally,accumulating evidence points to a genetic dimension in CKD susceptibility and progression.Variants in genes such as APOL1,PKD1,PKD2,UMOD,and COL4A3–5 shape disease onset and severity,and may modulate response to interventions.Exercise may help buffer these genetic risks by inducing epigenetic changes,improving mitochondrial function,and optimizing crosstalk between muscle,adipose tissue,and the vasculature.This review synthesizes how exercise training can ameliorate key molecular mediators in CKD,emphasizing the interplay with genetic and epigenetic factors.We integrate evidence from clinical and experimental studies,discussing how personalized exercise prescriptions,informed by patients’genetic backgrounds and nutritional strategies(such as adequate protein intake),could enhance outcomes.Although large-scale trials linking molecular adaptations to long-term endpoints are needed,current knowledge strongly supports incorporating exercise as a cornerstone in CKD management to counteract pervasive molecular derangements and leverage genetic insights for individualized care.展开更多
Hainan Island is one of the largest islands in China and is located in the Indo-Burma biodiversity hotspot region.Despite its ecological significance,comprehensive population genetic studies of key marine organisms al...Hainan Island is one of the largest islands in China and is located in the Indo-Burma biodiversity hotspot region.Despite its ecological significance,comprehensive population genetic studies of key marine organisms along the entire coastline of Hainan Island have not been reported.This study examined the genetic diversity and population structure of the widely distributed oyster Saccostrea malabonensis around Hainan Island with analyzing mitochondrial COI gene sequences.The impacts of geographical,environmental and anthropogenic factors on genetic differentiation were also investigated.The results revealed a significant AT bias in the COI gene sequences,with transitions as the main mutation type.A total of 103 variable sites and 107 haplotypes were identified from480 COI sequences,with haplotype diversities from 0.067 to 0.782,and nucleotide diversities between 0.00011 and 0.00278.AMOVA analysis indicated that 86.65%of the variation occurred within one population while 13.35%among different populations.The average genetic distance across 16 populations was 0.00169,and the average genetic differentiation index was 0.13353.Distinct population patterns can be observed.The populations of Tonghai Village(THV)and Gangmen Mountain(GMM)in Lingshui showed similar genetic structures while those of Wanquan River Estuary(WQRE,Qionghai)and Wuzhizhou Island(WZZI,Sanya)displayed divergent evolutionary trends.Cluster analysis grouped the 480 individuals of S.malabonensis into six subpopulations.These findings are helpful for developing conservation strategies and genetic breeding programs,and are also helpful for understanding the evolutionary history of this oyster species in Hainan Island.展开更多
Avian metapneumovirus(aMPV),a paramyxovirus,causes acute respiratory diseases in turkeys and swollen head syndrome in chickens.This study established a reverse genetics system for aMPV subtype B LN16-A strain based on...Avian metapneumovirus(aMPV),a paramyxovirus,causes acute respiratory diseases in turkeys and swollen head syndrome in chickens.This study established a reverse genetics system for aMPV subtype B LN16-A strain based on T7 RNA polymerase.Full-length cDNA of the LN16-A strain was constructed by assembling 5 cDNA fragments between the T7 promoter and hepatitis delta virus ribozyme.Transfection of this plasmid,along with the supporting plasmids encoding the N,P,M2-1,and L proteins of LN16-A into BSR-T7/5 cells,resulted in the recovery of aMPV subtype B.To identify an effective insertion site,the enhanced green fluorescent protein(EGFP)gene was inserted into different sites of the LN16-A genome to generate recombinant LN16-As.The results showed that the expression levels of EGFP at the site between the G and L genes of LN16-A were significantly higher than those at the other two sites(between the leader and N genes or replacing the SH gene).To verify the availability of the site between G and L for foreign gene expression,the VP2 gene of very virulent infectious bursal disease virus(vvIBDV)was inserted into this site,and recombinant LN16-A(rLN16A-vvVP2)was successfully rescued.Single immunization of specificpathogen-free chickens with rLN16A-vvVP2 induced high levels of neutralizing antibodies and provided 100%protection against the virulent aMPV subtype B and vvIBDV.Establishing a reverse genetics system here provides an important foundation for understanding aMPV pathogenesis and developing novel vector vaccines.展开更多
Wheat rusts continue to cause significant losses worldwide despite major efforts given to their genetic control. This is due to frequent evolution and selection of virulence in pathogen overcoming the deployed race-sp...Wheat rusts continue to cause significant losses worldwide despite major efforts given to their genetic control. This is due to frequent evolution and selection of virulence in pathogen overcoming the deployed race-specific resistance genes. Although the life of effective race-specific resistance genes can be prolonged by using gene combinations, an alternative approach being implemented at CIMMYT is to deploy varieties that posses adult plant resistance （APR） based on combinations of minor, slow rusting genes. When present alone, the APR genes do not confer adequate resistance especially under high disease pressure; however, combinations of 4 or 5 minor genes usually result in ＂near-immunity＂ or a high level of resistance. Although only a few APR genes are catalogued, various APR QTLs are now known and could lead to further characterization of additional genes. Four characterized genes have pleiotropic effects in conferring partial APR to all 3 rusts and powdery mildew, thus simplifying the task of breeding wheat varieties that are resistant to multiple diseases. Significant progress was made recently in developing high-yielding wheat germplasm that possesses high levels of APR to all three rusts by implementing a Mexico- Kenya shuttle breeding scheme. Parents with APR to Ug99 were hybridized with high-yielding parents that had adequate to high levels of APR to leaf rust and yellow rust. Segregating populations and advanced lines from these crosses were selected under high rust pressures in Mexico （leaf rust and yellow rust） and Kenya （Ug99 stem rust and yellow rust） to identify high- yielding progenies that possess high to adequate APR to all three rusts. International distribution of these high-yielding wheats is underway through CIMMYT intemational yield trials and screening nurseries. It is expected that several wheat varieties with APR to three rusts will be released and grown in various countries in the near-future that will allow determining the durability of resistance.展开更多
Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations ...Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations in DNA mismatch repair(MMR)genes,including MLH1,MSH2,MSH6 and PMS2.These mutations lead to microsatellite instability(MSI)and defective DNA repair mechanisms,resulting in increased cancer risk.Early detection of LS is crucial for effective management and cancer prevention.Endoscopic surveillance,particularly regular colonoscopy,is recommended for individuals with LS to detect CRC at early stages.Additionally,universal screening of CRC for MMR deficiency can help identify at-risk individuals.Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis,making informed decisions regarding surveillance and prevention,and offering reproductive options to reduce the transmission of pathogenic variants of the offspring.The aim of this review is to outline current strategies for the diagnosis,surveillance,and management of LS,with a focus on the role of genetic counseling,endoscopic screening,and emerging therapeutic approaches to mitigate cancer risk in affected individuals.展开更多
Information about whether genetic information requires special treatment in law varies around the world and many aspects are not clear.In this study,we draw upon knowledge gained from various disciplines,such as genet...Information about whether genetic information requires special treatment in law varies around the world and many aspects are not clear.In this study,we draw upon knowledge gained from various disciplines,such as genetics,medicine,law,philosophy,psychology,sociology,anthropology,insurance,and economics,which have all contributed to the study of genetic information,and discrimination based on genetic traits.With this in mind,we are able to set this research study into perspective.We make no claim on behalf of any field of study.Nevertheless,we say the development in the field of genetics is in its infancy and that knowledge of an individual genome would be essential not only for counseling but could also be used for stigmatization and discrimination.The purpose of the study is to help provide useful links concerning legal and ethical issues in human genetics and particularly where it deals with the laws,regulations,and policies concerning genetic information.We deal with the legal and ethical aspects in human genetics that influence genetic information.We examine government policies and the existing legislation in Papua New Guinea(PNG)that deal with genetic information and analyze discrimination cases due to genetic traits and describe its magnitude in PNG.This study places importance on the examination of qualitative data collected by a questionnaire survey from individual subjects representing various organizations in PNG including Department of Health,Insurance companies,General Federation of Employers’Associations,Trade Unions,and professional workers such as lawyers,District Court magistrates,medical doctors,healthcare workers,students,and private individuals.The study was conducted in towns in PNG although the majority of the participants live in the National Capital District.A sample of individuals(patients)were enrolled in a cross-sectional questionnaire survey.Individual information was obtained to describe the situation of the area.However,this study did not use administrative records based on health information from the Department of Health which describes the prevalence of genetically disordered individuals.All selected individuals or subjects were interviewed or completed a questionnaire.The data were assessed to characterize the study subsets.The findings of this study are made available to clinical practice in law,medical and public health,and private and public institutions including insurance companies,employers’federation,mining companies,and workers’unions in PNG,and academics and researchers.Educational programs on the basic principles of genetics,ethics,and law in relation to insurance will have to be developed to improve the knowledge of insurance,medical,and the cost of long-term care.展开更多
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.
文摘Aiming to solve the steering instability and hysteresis of agricultural robots in the process of movement,a fusion PID control method of particle swarm optimization(PSO)and genetic algorithm(GA)was proposed.The fusion algorithm took advantage of the fast optimization ability of PSO to optimize the population screening link of GA.The Simulink simulation results showed that the convergence of the fitness function of the fusion algorithm was accelerated,the system response adjustment time was reduced,and the overshoot was almost zero.Then the algorithm was applied to the steering test of agricultural robot in various scenes.After modeling the steering system of agricultural robot,the steering test results in the unloaded suspended state showed that the PID control based on fusion algorithm reduced the rise time,response adjustment time and overshoot of the system,and improved the response speed and stability of the system,compared with the artificial trial and error PID control and the PID control based on GA.The actual road steering test results showed that the PID control response rise time based on the fusion algorithm was the shortest,about 4.43 s.When the target pulse number was set to 100,the actual mean value in the steady-state regulation stage was about 102.9,which was the closest to the target value among the three control methods,and the overshoot was reduced at the same time.The steering test results under various scene states showed that the PID control based on the proposed fusion algorithm had good anti-interference ability,it can adapt to the changes of environment and load and improve the performance of the control system.It was effective in the steering control of agricultural robot.This method can provide a reference for the precise steering control of other robots.
基金Supported by the National Natural Science Fundation of China(No.82101107No.81471575).
文摘AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.
基金Supported by the Research Grants of the National Research,Development and Innovation Office,No.K125377,No.K134863 and No.K143549New National Excellence Program of the Ministry of Human Capacities,No.UNKP-20-5-SZTE-161,No.UNKP-22-3-SZTE-233,No.UNKP-23-5-SZTE-719,No.UNKP-22-4-SZTE-296 and No.UNKP-22-3-SZTE-278+1 种基金Janos Bolyai Research Grant,No.BO/00723/22the Géza Hetényi Research Grant by Albert Szent-Györgyi Medical School,University of Szeged.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2022A1515111123(to JQ)。
文摘Complex genetic architecture is the major cause of heterogeneity in epilepsy,which poses challenges for accurate diagnosis and precise treatment.A large number of epilepsy candidate genes have been identified from clinical studies,particularly with the widespread use of next-generation sequencing.Validating these candidate genes is emerging as a valuable yet challenging task.Drosophila serves as an ideal animal model for validating candidate genes associated with neurogenetic disorders such as epilepsy,due to its rapid reproduction rate,powerful genetic tools,and efficient use of ethological and electrophysiological assays.Here,we systematically summarize the advantageous techniques of the Drosophila model used to investigate epilepsy genes,including genetic tools for manipulating target gene expression,ethological assays for seizure-like behaviors,electrophysiological techniques,and functional imaging for recording neural activity.We then introduce several typical strategies for identifying epilepsy genes and provide new insights into gene-gene interactions in epilepsy with polygenic causes.We summarize well-established precision medicine strategies for epilepsy and discuss prospective treatment options,including drug therapy and gene therapy for genetic epilepsy based on the Drosophila model.Finally,we also address genetic counseling and assisted reproductive technology as potential approaches for the prevention of genetic epilepsy.
基金supported by the National Natural Science Foundation of China(32222064 and 32341030)the Natural Science Foundation of Shanghai(22ZR1445800)Zhejiang Provincial Natural Science Foundation of China(LQ24C130008).
文摘Several quantitative trait genes(QTGs)related to rice heading date,a key factor for crop development and yield,have been identified,along with complex interactions among genes.However,a comprehensive genetic interaction network for these QTGs has not yet been established.In this study,we use 18K-rice lines to identify QTGs and their epistatic interactions affecting rice heading date.We identify 264 pairs of interacting quantitative trait loci(QTL)and construct a comprehensive genetic network of these QTL.On average,the epistatic effects of QTL pairs are estimated to be approximately 12.5%of additive effects of identified QTL.Importantly,epistasis varies among different alleles of several heading date genes.Additionally,57 pairs of interacting QTGs are also significant in their epistatic effects on 12 other agronomic traits.The identified QTL genetic interactions are further validated using near-isogenic lines,yeast two-hybrid,and split-luciferase complementation assays.Overall,this study provides a genetic network of rice heading date genes,which plays a crucial role in regulating rice heading date and influencing multiple related agronomic traits.This network serves as a foundation for understanding the genetic mechanisms of rice quantitative traits and for advancing rice molecular breeding.
基金Supported by A Grant from the Department of Biotechnology,New Delhi, India under the 7th FP of the Indo-EU Joint Collaborative Project on "FUNCFOOD"
文摘Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopathological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitationand hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.
基金supported by the National Natural Science Foundation of China,No.82160255(to RX)the Natural Science Foundation of Jiangxi Province,No.20212BAB216026(to HL)+2 种基金Science and Technology Plan Project of Health Commission of Jiangxi Province,No.202110016(to HL)Science and Technology Plan Project of Jiangxi Provincial Administration of Traditional Chinese Medicine,No.2022B975(to HL)a grant from Jiangxi Province Key Laboratory of Neurology,No.2024SSY06081(to RX).
文摘With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of these biological processes do not fully explain the onset,progression,and development of these conditions.Therefore,exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research.This review summarizes the potential common pathogeneses of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Huntington’s disease,frontotemporal lobar dementia,and Lewy body disease.Research findings have indicated that several common biological processes,including aging,genetic factors,progressive neuronal dysfunction,neuronal death and apoptosis,protein misfolding and aggregation,neuroinflammation,mitochondrial dysfunction,axonal transport defects,and gut microbiota dysbiosis,are involved in the pathogenesis of these six neurodegenerative diseases.Based on current information derived from diverse areas of research,these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases.Furthermore,promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed.Hence,these potential common biological processes may represent only very small,limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases.In clinical treatment,interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases.Therefore,future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks,rather than isolating individual biological processes.Based on this,therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions,as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.
文摘Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.
基金supported by the Ministry of Higher Education(MOHE)Malaysia through Fundamental Research Grant Scheme(FRGS)with project code:FRGS/1/2021/STG01/UCSI/01/.SX was funded by the National Natural Science Foundation of China(NSFC)grants 32030020 and 32288101funded by the NSFC grant 32270665.
文摘Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries,supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli.Genetic variants that regulate gene expression,known as expression quantitative trait loci(eQTL),are primarily shaped by human migration history and evolutionary forces,likewise,regulation of gene expression in principle could have been influenced by these events.Therefore,a comprehensive understanding of how human evolution impacts eQTL offers important insights into how phenotypic diversity is shaped.Recent studies,however,suggest that eQTL is enriched in genes that are selectively constrained.Whether eQTL is minimally affected by selective pressures remains an open question and requires comprehensive investigations.In addition,such studies are primarily dominated by the major populations of European ancestry,leaving many marginalized populations underrepresented.These observations indicate there exists a fundamental knowledge gap in the role of genomics variation on phenotypic diversity,which potentially hinders precision medicine.This article aims to revisit the abundance of eQTL across diverse populations and provide an overview of their impact from the population and evolutionary genetics perspective,subsequently discuss their influence on phenomics,as well as challenges and opportunities in the applications to precision medicine.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82273458 to Jinfei Chen)the Start-up Fund for the Recruited Talents of the First Affiliated Hospital of Wenzhou Medical University(Grant No.2021QD025 to Jinfei Chen)。
文摘The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.
文摘Pediatric inflammatory bowel disease(IBD)is a chronic and heterogeneous disease.IBD is commonly classified into Crohn’s disease and ulcerative colitis.It is linked to serious symptoms and complications.The onset of IBD commonly occurs during adolescence.Despite the significant number of cases globally(~5 million),the causes of pediatric IBD,which constitutes 25%of IBD patients,are not yet fully understood.Apart from environmental factors,genetic factors contribute to a higher risk of developing IBD.The predisposition risk of IBD can be investigated using genetic testing.Genetic mechanisms of pediatric IBD are highly complex which resulted in difficulty in selecting effective treatment or patient management.Genetic variation of IBD would serve as a basis for precision medicine and allow for the discovery of more robust treatment avenues for this condition in pediatric patients.This review aims to discuss the genetics of pediatric IBD,and current development in the screening,diagnosis,and treatment based on genetic profiling of pediatric IBD subjects toward more personalized management of this disease.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(grant number:NRF-2022R1A2C1092743).
文摘Chronic kidney disease(CKD)affects a significant fraction of the global population and is closely associated with elevated cardiovascular risk and poor clinical outcomes.Its pathophysiology entails complex molecular and cellular disturbances,including reduced nitric oxide bioavailability,persistent low-grade inflammation,oxidative stress,endothelial dysfunction,altered mineral metabolism,genetic predispositions,and uremic toxin accumulation.As current pharmacological treatments provide only partial risk reduction,complementary approaches are imperative.Exercise training,both aerobic and resistance,has emerged as a potent non-pharmacological intervention targeting these underlying molecular pathways.Regular exercise can enhance nitric oxide signaling,improve antioxidant defenses,attenuate inflammation,facilitate endothelial repair via endothelial progenitor cells,and stabilize muscle metabolism.Additionally,accumulating evidence points to a genetic dimension in CKD susceptibility and progression.Variants in genes such as APOL1,PKD1,PKD2,UMOD,and COL4A3–5 shape disease onset and severity,and may modulate response to interventions.Exercise may help buffer these genetic risks by inducing epigenetic changes,improving mitochondrial function,and optimizing crosstalk between muscle,adipose tissue,and the vasculature.This review synthesizes how exercise training can ameliorate key molecular mediators in CKD,emphasizing the interplay with genetic and epigenetic factors.We integrate evidence from clinical and experimental studies,discussing how personalized exercise prescriptions,informed by patients’genetic backgrounds and nutritional strategies(such as adequate protein intake),could enhance outcomes.Although large-scale trials linking molecular adaptations to long-term endpoints are needed,current knowledge strongly supports incorporating exercise as a cornerstone in CKD management to counteract pervasive molecular derangements and leverage genetic insights for individualized care.
基金the Hainan Provincial Natural Science Foundation of China(No.325RC675)the Starting Research Fund from the Hainan University(No.KYQD(ZR)-21004)。
文摘Hainan Island is one of the largest islands in China and is located in the Indo-Burma biodiversity hotspot region.Despite its ecological significance,comprehensive population genetic studies of key marine organisms along the entire coastline of Hainan Island have not been reported.This study examined the genetic diversity and population structure of the widely distributed oyster Saccostrea malabonensis around Hainan Island with analyzing mitochondrial COI gene sequences.The impacts of geographical,environmental and anthropogenic factors on genetic differentiation were also investigated.The results revealed a significant AT bias in the COI gene sequences,with transitions as the main mutation type.A total of 103 variable sites and 107 haplotypes were identified from480 COI sequences,with haplotype diversities from 0.067 to 0.782,and nucleotide diversities between 0.00011 and 0.00278.AMOVA analysis indicated that 86.65%of the variation occurred within one population while 13.35%among different populations.The average genetic distance across 16 populations was 0.00169,and the average genetic differentiation index was 0.13353.Distinct population patterns can be observed.The populations of Tonghai Village(THV)and Gangmen Mountain(GMM)in Lingshui showed similar genetic structures while those of Wanquan River Estuary(WQRE,Qionghai)and Wuzhizhou Island(WZZI,Sanya)displayed divergent evolutionary trends.Cluster analysis grouped the 480 individuals of S.malabonensis into six subpopulations.These findings are helpful for developing conservation strategies and genetic breeding programs,and are also helpful for understanding the evolutionary history of this oyster species in Hainan Island.
基金supported by the grants from the National Key Research and Development Program of China(2022YFD1800604)the China Agriculture Research System(CARS-41)the Heilongjiang Touyan Innovation Team Program,China。
文摘Avian metapneumovirus(aMPV),a paramyxovirus,causes acute respiratory diseases in turkeys and swollen head syndrome in chickens.This study established a reverse genetics system for aMPV subtype B LN16-A strain based on T7 RNA polymerase.Full-length cDNA of the LN16-A strain was constructed by assembling 5 cDNA fragments between the T7 promoter and hepatitis delta virus ribozyme.Transfection of this plasmid,along with the supporting plasmids encoding the N,P,M2-1,and L proteins of LN16-A into BSR-T7/5 cells,resulted in the recovery of aMPV subtype B.To identify an effective insertion site,the enhanced green fluorescent protein(EGFP)gene was inserted into different sites of the LN16-A genome to generate recombinant LN16-As.The results showed that the expression levels of EGFP at the site between the G and L genes of LN16-A were significantly higher than those at the other two sites(between the leader and N genes or replacing the SH gene).To verify the availability of the site between G and L for foreign gene expression,the VP2 gene of very virulent infectious bursal disease virus(vvIBDV)was inserted into this site,and recombinant LN16-A(rLN16A-vvVP2)was successfully rescued.Single immunization of specificpathogen-free chickens with rLN16A-vvVP2 induced high levels of neutralizing antibodies and provided 100%protection against the virulent aMPV subtype B and vvIBDV.Establishing a reverse genetics system here provides an important foundation for understanding aMPV pathogenesis and developing novel vector vaccines.
基金financial resources from the Durable Rust Resistant Wheat Project led by Cornell University,USAsupported by the Bill & Melinda Gates Foundation+6 种基金ICAR-IndiaUSDA-ARS and USAID,USAGRDC AustraliaAgrovegetal-Spainthe Northwestern Mexican Farmer Association (Patronato) and CONFUPRO,MexicoSDC,SwitzerlandCIMMYT and INIFAP
文摘Wheat rusts continue to cause significant losses worldwide despite major efforts given to their genetic control. This is due to frequent evolution and selection of virulence in pathogen overcoming the deployed race-specific resistance genes. Although the life of effective race-specific resistance genes can be prolonged by using gene combinations, an alternative approach being implemented at CIMMYT is to deploy varieties that posses adult plant resistance （APR） based on combinations of minor, slow rusting genes. When present alone, the APR genes do not confer adequate resistance especially under high disease pressure; however, combinations of 4 or 5 minor genes usually result in ＂near-immunity＂ or a high level of resistance. Although only a few APR genes are catalogued, various APR QTLs are now known and could lead to further characterization of additional genes. Four characterized genes have pleiotropic effects in conferring partial APR to all 3 rusts and powdery mildew, thus simplifying the task of breeding wheat varieties that are resistant to multiple diseases. Significant progress was made recently in developing high-yielding wheat germplasm that possesses high levels of APR to all three rusts by implementing a Mexico- Kenya shuttle breeding scheme. Parents with APR to Ug99 were hybridized with high-yielding parents that had adequate to high levels of APR to leaf rust and yellow rust. Segregating populations and advanced lines from these crosses were selected under high rust pressures in Mexico （leaf rust and yellow rust） and Kenya （Ug99 stem rust and yellow rust） to identify high- yielding progenies that possess high to adequate APR to all three rusts. International distribution of these high-yielding wheats is underway through CIMMYT intemational yield trials and screening nurseries. It is expected that several wheat varieties with APR to three rusts will be released and grown in various countries in the near-future that will allow determining the durability of resistance.
文摘Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations in DNA mismatch repair(MMR)genes,including MLH1,MSH2,MSH6 and PMS2.These mutations lead to microsatellite instability(MSI)and defective DNA repair mechanisms,resulting in increased cancer risk.Early detection of LS is crucial for effective management and cancer prevention.Endoscopic surveillance,particularly regular colonoscopy,is recommended for individuals with LS to detect CRC at early stages.Additionally,universal screening of CRC for MMR deficiency can help identify at-risk individuals.Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis,making informed decisions regarding surveillance and prevention,and offering reproductive options to reduce the transmission of pathogenic variants of the offspring.The aim of this review is to outline current strategies for the diagnosis,surveillance,and management of LS,with a focus on the role of genetic counseling,endoscopic screening,and emerging therapeutic approaches to mitigate cancer risk in affected individuals.
文摘Information about whether genetic information requires special treatment in law varies around the world and many aspects are not clear.In this study,we draw upon knowledge gained from various disciplines,such as genetics,medicine,law,philosophy,psychology,sociology,anthropology,insurance,and economics,which have all contributed to the study of genetic information,and discrimination based on genetic traits.With this in mind,we are able to set this research study into perspective.We make no claim on behalf of any field of study.Nevertheless,we say the development in the field of genetics is in its infancy and that knowledge of an individual genome would be essential not only for counseling but could also be used for stigmatization and discrimination.The purpose of the study is to help provide useful links concerning legal and ethical issues in human genetics and particularly where it deals with the laws,regulations,and policies concerning genetic information.We deal with the legal and ethical aspects in human genetics that influence genetic information.We examine government policies and the existing legislation in Papua New Guinea(PNG)that deal with genetic information and analyze discrimination cases due to genetic traits and describe its magnitude in PNG.This study places importance on the examination of qualitative data collected by a questionnaire survey from individual subjects representing various organizations in PNG including Department of Health,Insurance companies,General Federation of Employers’Associations,Trade Unions,and professional workers such as lawyers,District Court magistrates,medical doctors,healthcare workers,students,and private individuals.The study was conducted in towns in PNG although the majority of the participants live in the National Capital District.A sample of individuals(patients)were enrolled in a cross-sectional questionnaire survey.Individual information was obtained to describe the situation of the area.However,this study did not use administrative records based on health information from the Department of Health which describes the prevalence of genetically disordered individuals.All selected individuals or subjects were interviewed or completed a questionnaire.The data were assessed to characterize the study subsets.The findings of this study are made available to clinical practice in law,medical and public health,and private and public institutions including insurance companies,employers’federation,mining companies,and workers’unions in PNG,and academics and researchers.Educational programs on the basic principles of genetics,ethics,and law in relation to insurance will have to be developed to improve the knowledge of insurance,medical,and the cost of long-term care.
