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circRNAs deregulation in exosomes derived from BEAS-2B cells is associated with vascular stiffness induced by PM_(2.5)

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Journal of environmental Sciences 2024年第3期137卷 527-539页

作者： Qingping Liu Yaling Zhang Bin Han Mengruo Wang Huaifang Hu Jie Ning Wentao Hu Meiyu Chen Yaxian Pang Yuanyuan Chen Lei Bao Yujie Niu Rong Zhang Department of Toxicology Hebei Medical UniversityShijiazhuang 050017China State key laboratory of environment Health(Incubation) Key Laboratory of Environment and HealthMinistry of EducationKey Laboratory of Environment and Health(Wuhan)Ministry of Environmental ProtectionSchool of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China China CDC key laboratory of environment and Population Health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijing 100021China Occupational Health and environmental Health Hebei Medical UniversityShijiazhuang 050017China Hebei key laboratory of environment and Human Health Hebei Medical UniversityShijiazhuang 050017China

As an environmental pollutant,ambient fine particulate matter (PM_(2.5)) was linked to cardiovascular *** molecular mechanisms underlying PM_(2.5)-induced extrapulmonary disease has not been elucidated *** this study the ambient PM_(2.5)exposure mice model we established was to explore adverse effects of vessel and potential ***-term PM_(2.5)exposure caused reduced lung function and vascular stiffness in *** chronic PM_(2.5)induced migration and epithelial-mesenchymal transition (EMT) phenotype in BEAS-2B *** PM_(2.5)treatment,the circRNAs and mRNAs levels of exosomes released by BEAS-2B cells were detected by competing endogenous RNA (ceRNA) array,which contained 1664 differentially expressed circRNAs (DE-circRNAs) and 308 differentially expressed m RNAs (DE-mRNAs).By bioinformatics analysis on host genes of DE-circRNAs,vascular diseases and some pathways related to vascular diseases including focal adhesion,tight junction and adherens junction were ***,ceRNA network was constructed,and DE-mRNAs in ceRNA network were conducted functional enrichment analysis by Ingenuity Pathway Analysis,which indicated that hsa_circ_0012627,hsa_circ_0053261and hsa_circ_0052810 were related to vascular endothelial ***,it was verified experimentally that Exo^(PM2.5)could induce endothelial dysfunction by increased endothelial permeability and decreased relaxation in *** present study,we investigated in-depth knowledge into the molecule events related to PM_(2.5) toxicity and pathogenesis of vascular diseases.

关键词： Fine particulate matter Vascular stiffness Exosome ceRNA microarray Endothelial dysfunction

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Targeting a disintegrin and metalloprotease(ADAM)17-CD122 axis enhances CD8^(+)T cell effector differentiation and anti-tumor immunity

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3097-3111页

作者： Lina Sun Anjun Jiao Haiyan Liu Renyi Ding Ning Yuan Biao Yang Cangang Zhang Xiaoxuan Jia Gang Wang Yanhong Su Dan Zhang Lin Shi Chenming Sun Aijun Zhang Lianjun Zhang Baojun Zhang Department of Pathogenic Microbiology and Immunology School of Basic Medical SciencesXi’an Jiaotong UniversityXi’anShaanxi 710061China Institute of Infection and Immunity Translational Medicine InstituteXi’an Jiaotong University Health Science CenterXi’anShaanxi 710061China key laboratory of environment and genes related to diseases Ministry of EducationXi’anShaanxi 710061China Xi’an key laboratory of Immune related diseases Xi’anShannxi 710061China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy Cancer InstituteXuzhou Medical UniversityXuzhouJiangsuChina Department of Pediatrics Qilu Hospital of Shandong UniversityJinanChina National key laboratory of Immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou 215123 JiangsuChina key laboratory of Synthetic Biology Regulatory Elements Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou 215123 JiangsuChina

CD8^(+)T cell immune responses are regulated by multi-layer networks,while the post-translational regulation remains largely *** ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane ***,by targeting the sheddase A Disintegrin and Metalloprotease(ADAM)17,we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8^(+)T *** and proteomic analysis revealed the involvement of post-translational regulation in CD8^(+)T cells.T cellspecific deletion of ADAM17 led to a dramatic increase in effector CD8^(+)T cell differentiation and enhanced cytolytic effects to eliminate pathogens and ***,ADAM17 regulated CD8^(+)T cells through cleavage of membrane ***17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8^(+)T ***,inhibition of ADAM17 in CD8^(+)T cells improved the efficacy of chimeric antigen receptor(CAR)T cells in solid *** findings reveal a critical post-translational regulation in CD8^(+)T cells,providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

关键词： immunity stimulation involvement

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The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy

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Science China(Life Sciences) 2024年第8期67卷 1549-1562页

作者： Peidong Zhang Peiwei Li Muya Tang Ryan CGimple Liang Huang Jing Yue Qiuhong Shen Yiwei Du Qian Zhang Zhengnan Yang Haihuai He Kailin Yang Linjie Zhao Shengtao Zhou Department of Obstetrics and Gynecology Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOEState Key Laboratory of BiotherapyWest China Second HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Physician Scientist Training Program Department of MedicineWashington University School of MedicineSt.Louis 63110USA Department of Neurosurgery State Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Department of Radiation Oncology Taussig Cancer CenterCleveland ClinicCleveland 44106USA

Mechanics shape cell and tissue plasticity and maintain their *** cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic ***,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains ***,we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas(TCGA)*** the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway *** subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical *** further found that the responses of two subtypes of cancers,one with the optimal outcome and the other with the worst prognosis,to a classical mechanotherapeutic agent(Fasudil,RhoA/ROCK inhibitor)were totally different,indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic ***,our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.

关键词： pan-cancer cancer mechanics multi-omics immunology

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Precise genome-editing in human diseases:mechanisms,strategies and applications

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1065-1085页

作者： Yanjiang Zheng Yifei Li Kaiyu Zhou Tiange Li Nathan J.VanDusen Yimin Hua key laboratory of Birth Defects and related diseases of Women and Children of moe Department of PediatricsWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Department of Cardiovascular Surgery West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pediatrics Herman B Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisIN 46202USA

Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and *** continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic *** genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo ***,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target *** this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and ***,we discuss the landmark events in the history of precise ***,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human ***,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and ***,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.

关键词： precise generating editing

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The clinical features and potential mechanisms of cognitive disorders in peripheral autoimmune and inflammatory diseases

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Fundamental Research 2024年第2期4卷 226-236页

作者： Ke-qi Fan Tao Huang Jian-shuai Yu Yi-yuan Li Jin Jin moe laboratory of Biosystem Homeostasis and Protection and Life Sciences InstituteZhejiang UniversityHangzhou 310058China Department of Gastroenterology Sir Run Shaw HospitalCollege of Medicine Zhejiang UniversityHangzhou 310016China key laboratory for Developmental genes and Human Disease Ministry of EducationInstitute of Life SciencesJiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China

According to a study from World Health Organization’s Global Burden of Disease,mental and neurological disorders have accounted for 13%of global diseases in recent years and are on the *** conditions or neuroinflammatory disorders are linked by the presence of an exaggerated immune response both peripherally and in the central nervous system(CNS).Cognitive dysfunction(CD)encompasses a complex group of diseases and has frequently been described in the field of autoimmune diseases,especially in multiple non-CNS-related autoimmune *** studies have provided various hypotheses regarding the occurrence of cognitive impairment in autoimmune diseases,including that abnormally activated immune cells can disrupt the integrity of the blood-brain barrier(BBB)to trigger a central neuroinflammatory *** the BBB is intact,autoantibodies and pro-inflammatory molecules in peripheral circulation can enter the brain to activate microglia,inducing CNS inflammation and ***,the mechanisms explaining the association between the immune system and neural function and their contribution to diseases are *** this review,we used clinical statistics to illustrate the correlation between CD and autoimmune diseases that do not directly affect the CNS,summarized the clinical features and mechanisms by which autoimmune diseases trigger cognitive impairment,and explored existing knowledge regarding the link between CD and autoimmune diseases from the perspective of the field of neuroimmunology.

关键词： Autoimmune diseases Neuroinflammation Central nervous system dysfunction Autoantibodies Inflammatory cytokines

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Pseudomonas aeruginosa regulator PvrA binds simultaneously to multiple pseudo-palindromic sites for efficient transcription activation

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Science China(Life Sciences) 2024年第5期67卷 900-912页

作者： Yibo Zhu Bingnan Luo Xingyu Mou Yingjie Song Yonghong Zhou Yongbo Luo Bo Sun Youfu Luo Hong Tang Zhaoming Su Rui Bao Center of Infectious diseases Division of Infectious Diseases in State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of Geriatrics and National Clinical Research Center for Geriatrics West China HospitalSichuan UniversityChengdu 610041China key laboratory of Biodiversity and environment on the Qinghai-Tibetan Plateau Ministry of EducationSchool of Ecology and EnvironmentTibet UniversityLhasa 850000China Shanghai Advanced Research Institute Chinese Academy of SciencesShanghai 201210China College of Life Science Sichuan Normal UniversityChengdu 610101China Accurate Biotechnology(Hunan)Co. LtdChangsha 410006China

Tetracycline repressor(TetR)family regulators(TFRs)are the largest group of DNA-binding transcription factors and are widely distributed in bacteria and *** play vital roles in controlling the expression of various genes and regulating diverse physiological ***,a TFR protein Pseudomonas virulence regulator A(PvrA),was identified from Pseudomonas aeruginosa as the transcriptional activator of genes involved in fatty acid utilization and bacterial ***,we show that PvrA can simultaneously bind to multiple pseudo-palindromic sites and upregulate the expression levels of target ***-electron microscopy(cryo-EM)analysis indicates the simultaneous DNA recognition mechanism of PvrA and suggests that the bound DNA fragments consist of a distorted B-DNA double *** crystal structure and functional analysis of PvrA reveal a hinge region that secures the correct domain motion for recognition of the promiscuous ***,our results showed that mutations disrupting the regulatory hinge region have differential effects on biofilm formation and pyocyanin biosynthesis,resulting in attenuated bacterial ***,these findings will improve the understanding of the relationship between the structure and function of the TetR family and provide new insights into the mechanism of regulation of *** virulence.

关键词： Pseudomonas aeruginosa transcription regulator TetR protein-structure virulence

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Dietary exposure to sulfamethazine,nanoplastics and their binary mixture disrupts the spermatogenesis of marine medaka(Oryzias melastigma)

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Acta Oceanologica Sinica 2024年第08期 104-110页

作者： Yuting Zhang Ruanni Chen Zhiqiang Chen Xiaoyu Fu Ziyi Wu Jinwan Chen Lingtian Xie Humin Zong Jingli Mu Fujian key laboratory on Conservation and Sustainable Utilization of Marine Biodiversity College of Geography and Oceanography Minjiang University College of environmental and Safety Engineering Fuzhou University SCNU environmental Research Institute Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment South China Normal University National Marine environmental Monitoring Center

In the coastal environment, the co-occurrence of antibiotic and nanoplastic pollution is common. Investigating their individual and combined toxicity to marine organisms is of great necessity. In the present study, the reproductive toxicity of sulfamethazine（SMZ） and nanoplastics（polystyrene, PS） via the dietary route on the spermatogenesis of marine medaka（Oryzias melastigma） was examined. After 30 d of dietary exposure, SMZ alone decreased the gonadosomatic index（GSI） value（～35%） and the proportion of undifferentiated type A spermatogonia(Aund)（～40%）, probably by disrupting the testicular sex hormone production, the spermatogenesis-related growth factor network and the balance of apoptosis. Individual exposure to PS did not affect the GSI value or the proportions of germ cells at different developmental stages, but dysregulated the expression of several spermatogenesis-related genes. Interestingly, the presence of PS alleviated the decreased GSI value caused by SMZ. This alleviation effect was achieved by enhancing the spermatogonia differentiation instead of reversing the suppressed self-renewal of Aund, suggesting that the mixture of PS and SMZ could cause reproductive effects in a different way. These findings expand our knowledge of threats of ubiquitous antibiotic and nanoplastic pollution to fish reproduction and population.

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Transcriptomics and physiological analyses reveal that sulfur alleviates mercury toxicity in rice(Oryza sativa L.)

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Journal of environmental Sciences 2024年第1期135卷 10-25页

作者： Yingmei Huang Jicai Yi Xiaomin Li Fangbai Li National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China Guangdong Key Laboratory of Integrated Agro-Environmental Pollution Control and ManagementInstitute of Eco-Environmental and Soil SciencesGuangdong Academy of SciencesGuangzhou 510650China Guangzhou Institute of Geochemistry Chinese Academy of SciencesGuangzhou 510640China University of Chinese Academy of Sciences Beijing 100049China College of Life Sciences South China Agricultural UniversityGuangzhou 510642China SCNU environmental Research Institute Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety&MOE Key Laboratory of Theoretical Chemistry of EnvironmentSouth China Normal UniversityGuangzhou 510006China

Mercury(Hg)is one of the most dangerous contaminants and has sparked global concern since it poses a health risk to humans when consumed through ***(S)is a crucial component for plant growth,and S may reduce Hg accumulation in rice ***,the detailed effects of S and the mechanisms underlying S-mediated responses in Hg-stressed rice plants remain ***,to investigate the effects of S addition on rice growth,Hg accumulation,physiological indexes,and gene expression profiles,rice seedlings were hydroponically treated with Hg(20μmol/L Hg Cl_(2))and Hg plus elemental sulfur(100 mg/L).S application significantly reduced Hg accumulation in Hg-stressed rice roots and alleviated the inhibitory effects of Hg on rice growth.S addition significantly reduced Hg-induced reactive oxygen species generation,membrane lipid peroxidation levels,and activities of antioxidant enzymes while increasing glutathione content in *** analysis of roots identified 3,411,2,730,and 581 differentially expressed genes in the control(CK)***,CK ***+S,and Hg ***+S datasets,*** pathway of S-mediated biological metabolism fell into six groups:biosynthesis and metabolism,expression regulation,transport,stimulus response,oxidation reduction,and cell wall *** majority of biological process-related genes were upregulated under Hg stress compared with CK treatment,but downregulated in the Hg+S *** results provide transcriptomic and physiological evidence that S may be critical for plant Hg stress resistance and will help to develop strategies for reduction or phytoremediation of Hg contamination.

关键词： Sulfur Mercury Transcriptomics Detoxification

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Heavy metals potentially drive co-selection of antibiotic resistance genes by shifting soil bacterial communities in paddy soils along the middle and lower Yangtze River

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Pedosphere 2024年第3期34卷 606-619页

作者： Ya ZHANG Hao WANG Minghui HU Rui CAI Yuqing MIAO Xiancan ZHU Anhui Provincial key laboratory of Molecular Enzymology and Mechanism of Major Metabolic diseases Anhui Provincial Key Laboratory of the Conservation and Exploitation of Biological ResourcesCollege of Life SciencesAnhui Normal UniversityWuhu 241000(China) School of Geography and Tourism Anhui Normal UniversityWuhu 241003(China)

Heavy metals(HMs)and antibiotic resistance have become serious environmental problems affecting soil and human *** microorganisms play key roles in pollutant degradation and biogeochemical cycling processes;however,the interactions among HMs,soil microbial communities,and antibiotic resistance genes(ARGs)in agricultural soils remain *** quantitative real-time polymerase chain reaction and NovaSeq sequencing,we evaluated heavy metal contents,abundances of ARGs,soil bacterial community structure and functions,and their correlations in paddy soils at 43 sampling sites along the middle and lower reaches of the Yangtze River,central and eastern *** results showed the co-occurrence of HMs,ARGs,and HM resistance genes across all paddy ***,significant positive associations were detected between HMs and resistance ***,czcA,and int1 were positively correlated with bacterial community *** Mantel test showed that bacterial community composition and functions were significantly associated with HMs and resistance genes,such as Cd,Cr,Zn,copA,czcA,int1,and ***,HMs and ARGs were the major factors shaping soil bacterial communities;thus,HMs triggered proliferation of HM and antibiotic resistances by influencing the mobile genetic element(int1)and soil microbial *** study revealed that HMs potentially drive the co-selection of ARGs by shifting soil bacterial community structure and functions,thereby increasing the potential risks to human health as well as ecological environment in the paddy soils along the middle and lower reaches of the Yangtze River.

关键词： agricultural ecosystem ecological risk heavy metal resistance microbial community soil contamination soil pollution

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Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants

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Chronic diseases and Translational Medicine 2024年第2期10卷 118-129页

作者： Huan Zhang Yuxi Chen Peng Xu Dan Liu Naqiong Wu Laiyuan Wang Xingbo Mo Jiangsu key laboratory of Preventive and Translational Medicine for Geriatric diseases Department of EpidemiologySchool of Public HealthMedical College of Soochow UniversitySuzhouJiangsuChina Cardiometabolic Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina key laboratory of Cardiovascular Epidemiology&Department of Epidemiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina moe key laboratory of Geriatric diseases and Immunology School of Public HealthCenter for Genetic Epidemiology and GenomicsMedical College of Soochow UniversitySuzhouJiangsuChina

Background Genome-wide association studies(GWAS)have identified more than a thousand loci for blood pressure(BP).Functional genes in these loci are cell-type *** aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms(RNAm-SNPs).Methods Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium,we identified associations between RNAm-SNPs and *** association between RNAm-SNPs,gene expression,and BP were *** A total of 355 RNAm-SNPs related to m6A,m1A,m5C,m7G,and A-to-I modification were associated with *** related genes were enriched in the pancreatic secretion pathway and renin secretion *** BP GWAS signals were significantly enriched with m6A-SNPs,highlighting the potential functional relevance of m6A in physiological processes influencing ***,m6A-SNPs in CYP11B1,PDE3B,HDAC7,ACE,SLC4A7,PDE1A,FRK,MTHFR,NPPA,CACNA1D,and HDAC9 were *** methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were ***-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection(AD)cases and *** scRNA-seq study,we identified ARID5A,HLA-DPB1,HLA-DRA,IRF1,LINC01091,MCL1,MLF1,MLXIPL,NAA16,NADK,RERG,SRM,and USP53 as differential expression genes for AD in aortic *** The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs,gene expression,and *** identified BP-associated genes in aortic cells were associated with AD.

关键词： aortic dissection blood pressure genome-wide association study RNA modification single-cell

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