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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing key laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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Joint Effects of Multipollutant Mixtures on Mortality in Chengdu,China

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Biomedical and Environmental Sciences 2024年第1期37卷 112-116页

作者： ZHANG Ying TIAN Qi Qi HU Wen Dong ZHANG Shao Bo WANG Shi Gong ZHENG Can Jun Plateau Atmosphere and Environment key laboratory of sichuan province School of Atmospheric SciencesChengdu University of Information TechnologyChengdu 610225SichuanChina Yunnan R&D Institute of Natural Disaster on Chengdu University of Information Technology Kunming 650034YunnanChina Chengdu Plain Urban Meteorology and Environment sichuan Provincial Field Scientific Observation and Research Station Chengdu 610225SichuanChina Chinese Center for disease Control and Prevention National Institute for Communicable Disease Control and PreventionBeijing 102206China

Significant epidemiological research has revealed that exposure to air pollution is substantially associated with numerous detrimental health consequences^([1-3]).The negative health effects of individual air pollutants(e.g.,fine particulate matter:PM_(2.5);nitrogen dioxide:NO_(2);carbon monoxide,CO;or ozone:O_(3))have been widely explored^([4]).However,humans are constantly exposed to multipollutant mixtures in real life,and biological responses to inhaled pollutants are likely to depend on the interplay of pollutant ***,it is critical and imperative to explore the joint effects of multipollutant mixtures on human beings.

关键词： mixtures monoxide consequences

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The multi-kingdom microbiome catalog of the chicken gastrointestinal tract

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Biosafety and health 2024年第2期6卷 101-115页

作者： Yanan Wang Mengqi Qu Yuhai Bi William J.Liu Sufang Ma Bo Wan Yongfei Hu Baoli Zhu Gaiping Zhang George F.Gao International Joint Research Center of National animal Immunology College of Veterinary MedicineHenan Agricultural UniversityZhengzhou 450046China CAS key laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)Beijing 100101China Longhu laboratory Zhengzhou 450046China University of Chinese Academy of Sciences Beijing 100049China NHC key laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China State key laboratory of animal Nutrition and Feeding College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China

Chicken is an important food animal worldwide and plays an important role in human life by providing meat and *** recent significant advances in gut microbiome studies,a comprehensive study of chicken gut bacterial,archaeal,and viral genomes remains *** this study,we constructed a chicken multi-kingdom microbiome catalog(CMKMC),including 18,201 bacterial,225 archaeal,and 33,411 viral genomes,and annotated over 6,076,006 protein-coding genes by integrating 135 chicken gut metagenomes and publicly available metagenome-assembled genomes(MAGs)from ten *** found that 812 and 240 MAGs in our dataset were putative novel species and genera,respectively,far beyond what was previously *** newly unclassified MAGs were predominant in Phyla Firmicutes_A(n=263),followed by Firmicutes(n=126),Bacteroidota(n=121),and Proteobacteria(n=87).Most of the classified species-level viral oper-ational taxonomic units belong to ***,63.24%of chicken gut viromes are predicted to infect two or more hosts,including complete circular ***,we found that diverse auxiliary metabolic genes and antibiotic resistance genes were carried by ***,our CMKMC provides the largest integrated MAGs and viral genomes from the chicken gut to date,functional insights into the chicken gastrointestinal tract microbiota,and paves the way for microbial interventions for better chicken health and productivity.

关键词： Chicken Microbiome Metagenome assembled genomes Archaeome Virome Antibiotic resistance gene

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DNA of neutrophil extracellular traps promote NF-κBdependent autoimmunity via cGAS/TLR9 in chronic obstructive pulmonary disease

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3040-3055页

作者： Jun Chen Tao Wang Xiaoou Li Lijuan Gao Ke Wang Mengxin Cheng Zijian Zeng Lei Chen Yongchun Shen Fuqiang Wen Department of Respiratory and Critical Care Medicine West China HospitalWest China School of Medicineand Division of Pulmonary DiseasesState Key Laboratory of BiotherapySichuan UniversityChengduSichuan 610041China

Chronic obstructive pulmonary disease(COPD)is characterised by persistent airway inflammation even after cigarette smoking *** extracellular traps(NETs)have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke(CS).However,whether and how NETs contribute to sustained airway inflammation in COPD remain *** study aimed to elucidate the immunoregulatory mechanism of NETs in COPD,employing human neutrophils,airway epithelial cells(AECs),dendritic cells(DCs),and a long-term CS-induced COPD mouse model,alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice(cGAS-^(−/−)TLR9^(−/−));Additionally,bronchoalveolar lavage fluid(BALF)of COPD patients was *** from COPD patients released greater cigarette smoke extract(CSE)-induced NETs(CSE-NETs)due to mitochondrial respiratory chain *** CSE-NETs,containing oxidatively-damaged DNA(NETs-DNA),promoted AECs proliferation,nuclear factor kappa B(NF-κB)activation,NF-κB-dependent cytokines and type-I interferons production,and DC maturation,which were ameliorated/reversed by silencing/inhibition of cGAS/*** the COPD mouse model,blocking NETs-DNA-sensing via cGAS^(−/−)and TLR9^(−/−)mice,inhibiting NETosis using mitoTEMPO,and degrading NETs-DNA with DNase-I,respectively,reduced NETs infiltrations,airway inflammation,NF-κB activation and NF-κBdependent cytokines,but not type-I interferons due to IFN-α/βreceptor *** NETs components(myeloperoxidase and neutrophil elastase activity)in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels,but not type-I interferon *** conclusion,NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced ***,targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.

关键词： inflammation TLR9 neutrophil

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Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice

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Zoological Research 2024年第3期45卷 551-566页

作者： Chen Ling Su-Su Liu Yu-Ya Wang Gui-Tao Huo Yan-Wei Yang Nan Xu Hong Wang Yong Wu Yu-Fa Miao Rui Fu Yu-Wei Zhao Chang-Fa Fan College of Life Sciences Northwest UniversityProvincial Key Laboratory of Biotechnology of Shaanxi ProvinceXi’anShaanxi 710069China Division of animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China National Center for Safety Evaluation of Drugs National Institutes for Food and Drug Control(NIFDC)Beijing 100176China Division of HIV/AIDS and Sexually Transmitted Virus Vaccines Institute for Biological Products ControlNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China Division of laboratory animal Monitoring Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China

Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic *** etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and ***,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic ***,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle *** symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in ***-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene *** murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the *** on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to ***,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

关键词： HRAS THBS1 HCC driver factor NASH Fibrosis Cirrhosis HCC Treatment evaluation

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应用物联网技术加速畜禽精准饲喂:从概念到实施

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Science Bulletin 2024年第14期69卷 2156-2160页

作者：苏家宜谭碧娥蒋宗勇吴德 C.M.Nyachoti Sung Woo Kim 印遇龙王婧 key laboratory of Hunan province for the Products Quality Regulation of Livestock and Poultry College of Animal Science and TechnologyHunan Agricultural UniversityChangsha 410128China Institute of animal Science Guangdong Academy of Agricultural SciencesGuangzhou 510640China key laboratory for animal disease-Resistant Nutrition of the Ministry of Education of China and Animal Nutrition InstituteSichuan Agricultural UniversityChengdu 611130China Department of animal Science University of ManitobaWinnipeg R3T 2N2Canada Department of animal Science North Carolina State UniversityRaleigh 27695USA laboratory of animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-Ecological Processes in Subtropical RegionNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410128China Yuelushan laboratory Changsha 410128China

Maximizing sow reproductive performance is vital for ensuring healthy piglet supply,feed efficiency,and profitability,which requires understanding factors such as nutrition,disease control,genetics,herd management,and their *** is well documented that most reproductive issues in sows stem from extreme fluctuations in body reserves[1].Thus,optimizing reproduction should prioritize regulating body reserves and making continuous nutritional adjustments throughout a sow’s life[1,2].However,the traditional one-size-fits-all feeding strategy may not meet individual sow needs under varying *** feeding strategy leads to nutrient under-or over-feeding,which may result in a lack of performance and health issues on the one hand,and economic loss and negative environmental effects on the other.

关键词： feeding extreme reserves

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Non-coding RNAs expression in SARS-CoV-2 infection:pathogenesis,clinical significance,and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第1期9卷 55-78页

作者： Xiaoxing Liu Wandi Xiong Maosen Ye Tangsheng Lu Kai Yuan Suhua Chang Ying Han Yongxiang Wang Lin Lu Yanping Bao Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)100191 BeijingChina Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research Peking University100871 BeijingChina key laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan University570228 HaikouChina key laboratory of animal Models and human disease Mechanisms of the Chinese Academy of Sciences&Yunnan province KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences650204 KunmingYunnanChina National Institute on Drug Dependence and Beijing key laboratory of Drug Dependence Peking UniversityBeijing 100191China Institute of Brain Science and Brain-inspired Research Shandong First Medical University&Shandong Academy of Medical Sciences250117 JinanShandongChina Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina School of Public health Peking University100191 BeijingChina

The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future *** non-coding RNAs(ncRNAs)display aberrations in the context of ***,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease *** this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long ***,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment *** addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel *** an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.

关键词： invasion therapeutic infection

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First identification of a novel Aichivirus D in goats with diarrhea

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Journal of Integrative Agriculture 2024年第4期23卷 1442-1446页

作者： Chen Yang Keha-mo Abi Hua Yue Falong Yang Cheng Tang College of animal&Veterinary Sciences Southwest Minzu UniversityChengdu 610041China key laboratory of Qinghai-Tibetan Plateau animal Genetic Resource Reservation and Utilization Chengdu 610041China

Kobuvirus comprises 6 officially recognized species,namely Aichivirus A-F,and can be further divided into 20 genotypes through VP1 gene phylogenetic analysis(https://***/report/chapter/picornaviridae/picornaviridae/kobuvirus).Aichivirus A in human,Aichivirus B in bovine,Aichivirus C in porcine and caprine,Aichivirus D in yak have been proved to be associated with diarrhea(Chen Y S et al.2013;Yang et al.2015;Zhu et al.2016;Zhai et al.2017;Wang et al.2020;Abi et al.2022;Yan et al.2023).

关键词： corn diarrhea official

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A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Science China(Life Sciences) 2024年第4期67卷 765-777页

作者： Hui Zhao Lin-Lin Liu Jian Sun Lian Jin Hai-Bing Xie Jian-Bo Li Hui Xu Dong-Dong Wu Xiao-Lin Zhuang Min-Sheng Peng Ya-Jun Guo Wei-Zhu Qian Newton OOtecko Wei-Jie Sun Liang-Hu Qu Jie He Zhao-Li Chen Rong Liu Ce-Shi Chen Ya-Ping Zhang State key laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic Medicine Kunming Medical UniversityKunming 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China The Third Affiliated Hospital Kunming Medical UniversityKunming 650118China key laboratory of animal Models and human disease Mechanisms of the Chinese Academy of Sciences and Yunnan province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China State key laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The key laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National Engineering Research Center for Antibody Medicine and Shanghai key laboratory of Cell Engineering and Antibody Shanghai 201203China Department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

human-specific insertions play important roles in human phenotypes and *** we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome ***,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee *** have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in *** addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in *** of Insert-446 prevented cell proliferation and migration in cancer and normal *** results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B *** findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

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B cell development and antibody responses in human immune system mice:current status and future perspective

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Science China(Life Sciences) 2024年第4期67卷 645-652页

作者： Tao Zhang Wentao Liu Yong-Guang Yang key laboratory of Organ Regeneration&Transplantation of the Ministry of Education The First Hospital of Jilin UniversityChangchun 130061China National-Local Joint Engineering laboratory of animal Models for human diseases Jilin UniversityChangchun 130061China International Center of Future Science Jilin UniversityChangchun 130061China

humanized immune system(HIS)mice have been developed and used as a small surrogate model to study human immune function under normal or disease *** variations are found between models,most HIS mice show robust human T cell ***,there has been unsuccessful in constructing HIS mice that produce high-affinity human antibodies,primarily due to defects in terminal B cell differentiation,antibody affinity maturation,and development of primary follicles and germinal *** this review,we elaborate on the current knowledge about and previous attempts to improve human B cell development in HIS mice,and propose a potential strategy for constructing HIS mice with improved humoral immunity by transplantation of human follicular dendritic cells(FDCs)to facilitate the development of secondary follicles.

关键词： humanized immune system mouse humoral immunity germinal center B cell follicular dendritic cell

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