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Feedback on a shared big dataset for intelligent TBM Part Ⅱ:Application and forward look

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Underground Space 2023年第4期11卷 26-45页

作者： jian-Bin li Zu-yu Chen xu li liu-jie Jing yun-Pei zhang Hao-Han Xiao Shuang-Jing wang Wen-Kun yang Lei-jie wu Peng-yu li Hai-bo li min Yao li-Tao Fan China Railway Group Co.Ltd Beijing 100089China Department of Geotechnical Engineering China Institute of Water Resources and Hydropower ResearchBeijing 100038China Key Laboratory of Urban Underground Engineering Ministry of EducationBeijing Jiaotong UniversityBeijing 100044China China Railway Engineering Equipment Group Co. LtdZhengzhouHenan 450016China School of Civil Engineering Southeast UniversityNanjing 211189China Xi’an University of Technology Xi’an 710048China

This review discusses the application scenarios of the machine learning-supported performance prediction and the optimization effi-ciency of tunnel boring machines(TBMs).The rock mass quality ratings,which are based on the Chinese code for geological survey,were used to provide"labels"suitable for supervised *** a result,the generation of machine prediction for rock mass grades reason-ably agreed with the ground truth documented in geological *** contrast,the main operational parameters,i.e.,thrust and torque,can be reasonably predicted based on historical ***,18 collapse sections of the Yinsong project have been successfully predicted by several *** studies on the selection of the optimal penetration rate and cost were *** review also presents a summary of the main achievements in response to the initiatives of the Lotus Pool Contest in *** the first time,large and well-documented TBM performance data has been shared for joint scientific ***,the review discusses the technical problems that require further study and the perspectives in the future development of intelligent TBM construction based on big data and machine learning.

关键词： TBM performance prediction TBM rock mass quality rating TBM-supported machine learning Rock mass classification ensemble Tunnel collapse

CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

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Signal Transduction and Targeted Therapy 2021年第1期6卷 95-104页

作者： Ke wang Wei Chen Zheng zhang Yongqiang Deng jian-Qi lian Peng Du Ding Wei yang zhang Xiu-xuan Sun li Gong xu yang Lei He Lei zhang Zhiwei yang jie-jie Geng Ruo Chen Hai zhang Bin wang yu-Meng zhu gang Nan jian-li jiang ling li Jiao wu Peng lin Wan Huang liangzhi Xie Zhao-hui Zheng Kui zhang Jin-lin Miao Hong-Yong Cui min Huang Jun zhang ling fu Xiang-min yang Zhongpeng Zhao Shihui Sun Hongjing Gu Zhe wang Chun-fu wang Yacheng Lu Ying-Ying liu qing-Yi wang huijie Bian Ping zhuZhi-Nan Chen National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Biotechnology Beijing 100071China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Tangdu Hospital Fourth Military Medical UniversityXi’an 710038China MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter Xi’an Jiaotong UniversityXi’an 710049China Sino Biological Inc. Beijing 100176China Department of Clinical Immunology Xijing HospitalFourth Military Medical UniversityXi’an 710032China School of Basic Medicine Fourth Military Medical UniversityXi’an 710032China

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until ***-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike *** ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the *** the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its ***,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike *** loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 *** of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular *** loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type ***,virions are observed in lymphocytes of lung tissue from a COVID-19 *** T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by ***,CD147 mediates virus entering host cells by ***,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.

关键词： ACE2 CD147 intestine

Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

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Zoological Research 2020年第1期41卷 3-19页

作者： Pei zhang jie-Si Chen Qi-Ye li Long-Xiang Sheng Yi-Xing Gao Bing-Zheng Lu Wen-bo zhu Xiao-yu zhan yuan li Zhi-Bing yuan gang xu Bi-Tao Qiu min yan Chun-xue Guo You-Qiong wang Yi-Jun Huang Jing-Xia zhang fu-yu liu Zhong-Wei Tang Sui-Zhen lin David NCooper Huan-ming yang jian wang yu-Qi Gao Wei Yin Guo-jie zhang Guang-Mei yan State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China BGI-Shenzhen ShenzhenGuangdong 518083China Section for Ecology and Evolution Department of BiologyUniversity of CopenhagenCopenhagen DK-2100Denmark Department of Pharmacology Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Institute of Medicine and Hygienic Equipment for High Altitude Region College of High Altitude Military MedicineThird Military Medical UniversityChongqing 400038China Key Laboratory of High Altitude Medicine of People's liberation Army Chongqing 400038China Key Laboratory of High Altitude Environmental Medicine Third Military Medical UniversityMinistry of EducationChongqing 400038China School of Pharmaceutical Sciences Sun Yat-Sen UniversityGuangzhouGuangdong 510006China Guangzhou Cellprotek Pharmaceutical Co.Ltd. GuangzhouGuangdong 510663China Institute of Medical Genetics School of MedicineCardiff UniversityCardiff CF144XNUK James D.Watson Institute of Genome Sciences HangzhouZhejiang 310058China Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China China National Genebank BGI-ShenzhenShenzhenGuangdong 518120China

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

关键词： Acute hypobaric hypoxia Cynomolgus monkeys Brain injury Neuroprotectant Gene regulatory networks

CD 147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2521-2535页

作者： Hong-Yong Cui Shi-jie wang Fei Song xu Cheng gang Nan yu Zhao Mei-Rui Qian Xi Chen Jia-yue li Fen-ling liu yu-Meng zhu Ruo-Fei Tian Bin wang Bin wu yang zhang Xiu-xuan Sun Ting Guo Xiang-min yang Hai zhang ling li Jing xu hui-jie Bian jian-li jiang Zhi-Nan Chen National Translational Science Center for Molecular Medicine and Department of Cell Biology Fourth Military Medical UniversityXi'anChina Department of Urology Shenzhen Institute of Translational MedicineThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People's HospitalShenzhenChina Medical Research Institute School of MedicineWuhan UniversityWuhanChina College of Chemistry and Materials Science Northwest UniversityXi'anChina National Facility for Protein Science Shanghai Zhangjiang LabShanghai Advanced Research InstituteChinese Academy of SciencesShanghaiChina Medical Research Center Southern University of Science and Technology HospitalShenzhenChina

Major gaps in understanding the molecular mechanisms of colorectal cancer(CRC)progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal *** factor 3(TFF3)has been reported to be involved in CRC progression and intestinal mucosal repair;however,how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly ***,we found that the upregulated TFF3 in CRC predicted a worse overall survival ***3 deficiency impaired mucosal restitution and ***147,a membrane protein,was identified as a binding partner for *** binding to CD147,TFF3 enhanced CD147-CD44s interaction,resulting in signal transducer and activator of transcription 3(STAT3)activation and prostaglandin G/H synthase 2(PTGS2)expression,which were indispensable for TFF3-induced migration,proliferation,and ***2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype(PTGER4)and contributed to TFF3-stimulated CRC *** NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 *** ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 *** of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in *** findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression,which widens and deepens the understanding of the molecular function of trefoil factors.

关键词： TFF3 colorectal impaired

3-to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge:Results from a Prospective,Multicenter Study

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Biomedical and Environmental Sciences 2022年第12期35卷 1091-1099页

作者： wang Jing Ya ZONG Xing yu wu Gui hui QI yuan lin li hui Zhen JI Xin yu TONG lin zhang Lei yanG ming bo yanG Pu Ye li Ji Ke XIAO fu Rong zhang lin Song HU yun Hong liU Hong De xu shou Fang SUN Sheng wu Wei MAO Ya li min qing HOU Hao Hua GONG Zhao yuan GUO yang JIAO li Wen QIN Jin wang Ding Yi wang Fang GUAN li liN gang MA yan wang yan Ping SHI Nan Nan Community Health Service Management Center Dongcheng DistrictBeijing 100700China Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing 100700China Public Health Clinical Center of Chengdu Chengdu 610066SichuanChina Yiyuan TCM Hospital Zibo 256199ShandongChina Institute of Information on Traditional Chinese Medicine China Academy of Chinese Medical SciencesBeijing 100700China Xi’an Eighth Hospital Xi’an 710000ShaanxiChina Harbin Infectious Disease Hospital Harbin 150000HeilongjiangChina Hospital(T.C.M)Affiliated to Southwest Medical University Luzhou 646000SichuanChina Xingtai Hospital of Chinese Medicine Xingtai 054000HebeiChina Shijiazhuang Fifth Hospital Shijiazhuang 050000HebeiChina Jiamusi Infectious Disease Hospital Jiamusi 154000HeilongjiangChina Chengde Hospital of Traditional Chinese Medicine Chengde 067040HebeiChina Hanzhong Central Hospital Hanzhong 723000ShaanxiChina Ankang Hospital of Traditional Chinese Medicine Ankang 725000ShaanxiChina Department of Traditional Chinese medicine Dazhou Central HospitalDazhou 635000SichuanChina China National Medicines Corporation Ltd Beijing 100077China Beijing University of Chinese Medicine Beijing 101121China Infectious Disease Hospital of Heilongjiang Province Harbin 150030HeilongjiangChin

Objective Coronavirus disease 2019(COVID-19)and tuberculosis(TB)are major public health and social issues *** long-term follow-up of COVID-19 with pulmonary TB(PTB)survivors after discharge is *** study aimed to comprehensively describe clinical outcomes,including sequela and recurrence at 3,12,and 24 months after discharge,among COVID-19 with PTB *** From January 22,2020 to May 6,2022,with a follow-up by August 26,2022,a prospective,multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in *** outcomes,including sequela,recurrence of COVID-19,and PTB survivors,were collected via telephone and face-to-face interviews at 3,12,and 24 months after *** Thirty-two COVID-19 with PTB survivors were *** median age was 52(45,59)years,and 23(71.9%)were *** them,nearly two-thirds(62.5%)of the survivors were moderate,three(9.4%)were severe,and more than half(59.4%)had at least one comorbidity(PTB excluded).The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6%at 3 months to 15.8%at 24 months,with anxiety having a higher proportion over a *** and amnesia recovered at the 12-month follow-up,while anxiety,fatigue,and trouble sleeping remained after ***,one(3.1%)case presented two recurrences of PTB and no re-positive COVID-19during the follow-up *** The proportion of long symptoms in COVID-19 with PTB survivors decreased over time,while nearly one in six still experience persistent symptoms with a higher proportion of *** recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

关键词： COVID-19 Pulmonary tuberculosis Long-term Sequela Recurrence Re-positive

Frontiers in high entropy alloys and high entropy functional materials

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Rare Metals 2024年第10期43卷 4639-4776页

作者： Wen-Tao zhang xue-Qian wang Feng-Qi zhang Xiao-Ya Cui Bing-Bing Fan Jia-ming Guo Zhi-min Guo Rui Huang Wen Huang xu-bo li Meng-Ru li yan Ma Zhi-Hua Shen Yong-gang Sun De-zhuang wang Fei-yang wang li-Qiang wang Nan wang Tian-li wang Wei wang Xiao-yang wang Yi-Han wang fu-jie yu yu-Zhen Yin ling-Kun zhang Yi zhang jian-yang zhang Qi Zhao yu-Ping Zhao Xin-Dong zhu Yasir Sohail Ya-Nan Chen Tao Feng Qi-Long Gao Hai-yan He Yong-jiang Huang Zeng-Bao Jiao Hua Ji Yao jiang Qiang li Xiao-ming li Wei-Bing liao Huai-Jun lin hui liu Qi liu qing-Feng liu Wei-Di liu Xiong-Jun liu yang Lu Yi-Ping Lu Wen Ma xue-Fei Miao jie Pan qing wang Hong-hui wu yuan wu Tao yang Wei-ming yang Qian yu Jin-yu zhang Zhi-gang Chen liang Mao yang Ren Bao-Long Shen xun-li wang Zhe Jia He zhu Zhen-Duo wu Si Lan School of Materials Science and Engineering Nanjing University of Science and TechnologyNanjing 210094China jiangsu Key Laboratory for Advanced Metallic Materials School of Materials Science and EngineeringSoutheast UniversityNanjing 211189China Department of Physics City University of Hong KongHongKong 999077China School of Materials Science and Engineering Tianjin UniversityTianjin 300072China School of Physics and Microelectronics Zhengzhou UniversityZhengzhou 450001China Department of Mechanical Engineering Research Institute for Advanced ManufacturingThe Hong Kong Polytechnic UniversityHong Kong 100872China Center of Electron Microscopy and State Key Laboratory of Silicon Materials School of Materials Science and EngineeringZhejiang UniversityHangzhou 310027China Key Laboratory of Solidification Control and Digital Preparation Technology(liaoning Province) School of Materials Science and EngineeringDalian University of TechnologyDalian 116024China Institute of Advanced Wear&Corrosion Resistance and functional Materials Jinan UniversityGuangzhou 510632China School of Mechanics and Civil Engineering China University of Mining and TechnologyXuzhou 221116China School of Physical Sciences Great Bay UniversityDongguan 523000China School of Materials Science and Engineering Harbin Institute of TechnologyHarbin 150001China State Key Laboratory of Materials-Oriented Chemical Engineering College of Chemical EngineeringNanjing Tech UniversityNanjing 211816China Beijing Advanced Innovation Center for Materials Genome Engineering Research Institute for Carbon NeutralityUniversity of Science and Technology BeijingBeijing 100083China Department of Mechanical Engineering The University of Hong KongHong Kong 999077China School of Computing Macquarie UniversitySydney 2113Australia Key Laboratory of Optoelectronic Devices and Systems of ministry of Education and Guangdong Province College of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhen 518060China State Key Laborato

Owing to their exceptional properties,high-entropy alloys(HEAs)and high-entropy materials have emerged as promising research areas and shown diverse ***,the recent advances in the field are comprehensively reviewed,organized into five *** first section introduces the background of HEAs,covering their definition,significance,application prospects,basic properties,design principles,and *** subsequent section focuses on cutting-edge high-entropy structural materials,highlighting developments such as nanostructured alloys,grain boundary engineering,eutectic systems,cryogenic alloys,thin films,micro-nano-lattice structures,additive manufacturing,high entropy metallic glasses,nano-precipitate strengthened alloys,composition modulation,alloy fibers,and refractory *** the following section,the emphasis shifts to functional materials,exploring HEAs as catalysts,magneto-caloric materials,corrosion-resistant alloys,radiation-resistant alloys,hydrogen storage systems,and materials for ***,the review encompasses functional high-entropy materials outside the realm of alloys,including thermoelectric,quantum dots,nanooxide catalysts,energy storage materials,negative thermal expansion ceramics,and high-entropy wave absorption *** paper concludes with an outlook,discussing future directions and potential growth areas in the *** this comprehensive review,researchers,engineers,and scientists may gain valuable insights into the recent progress and opportunities for further exploration in the exciting domains of high-entropy alloys and functional materials.

关键词： High entropy alloys Cutting-edge structural materials Cutting-edgefunctional materials

Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

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Zoological Research 2021年第2期42卷 250-251页

Open Access This is an open-access article distributed under the terms of theCreative Commons Attribution Non-Commercial license(http:1/***/licenses/by-nc/4.0/).which permits unrestrictednon-commercial use,*** reprodu... 详细信息

关键词： Open Creative Access

New sustainable polymers with on-demand depolymerization property

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Science China Chemistry 2024年第9期67卷 2803-2841页

作者： yangyang Sun Zesheng An yanshan Gao Rongrong Hu Ye liu Hua Lu Xiao-Bing Lu xuan Pang Anjun Qin Yong Shen Youhua Tao yu-Zhong wang Junpeng wang gang wu Guang-Peng wu Tie-Qi xu Xing-Hong zhang yuetao zhang Zhenbiao zhang jian-bo zhu Miao Hong Zhibo li State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China State Key Laboratory Base of Eco-Chemical Engineering College of Chemical EngineeringQingdao University of Science and TechnologyQingdao266042China State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun 130012China State Key Laboratory of Luminescent Materials and Devices Guangdong Provincial Key Laboratory of Luminescence from Molecular AggregatesSouth China University of TechnologyGuangzhou 510640China State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart MaterialsDalian University of TechnologyDalian 116024China Beijing National Laboratory for Molecular Sciences Center for Soft Matter Science and EngineeringKey Laboratory of Polymer Chemistry and Physics of Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China The Collaborative Innovation Center for Eco-Friendly and Fire-Safety Polymeric Materials(MoE) National Engineering Laboratory of Eco-Friendly Polymeric Materials(Sichuan)College of ChemistryState Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610064China School of Polymer Science and Polymer Engineering the University of AkronAkronOH 44325USA MOE Key Laboratory of Macromolecular Synthesis and functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China State and Local Joint Engineering Laboratory for Novel functional Polymeric Materials Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationSuzhou Key Laboratory of Macromolecular Design and Precision SynthesisCollege of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China

To combat the crisis of today's synthetic polymers arising from unsustainable production and disposal,it is essential for the synthetic polymer community to reshape the current polymer industry with sustainable *** an emerging class of sustainable polymers,the development of chemically depolymerizable polymers(CDPs),which can undergo closed-loop depolymerization/repolymerization cycles to reproduce virgin polymers without the loss of properties from recovered monomers,offers an ideal solution to preserve finite natural resources,provides a feasible solution to the end-of-life issue of polymer waste,and thereby establishes a circular materials ***,two grand key challenges have been encountered in the establishment of practically useful CDPs:how to balance polymerization and depolymerization ability and how to unify conflicted depolymerizability and physical ***,this critical review article presents our vision for summarizing feasible strategies to overcome the above two significant challenges and the design principles for constructing an ideal CDP by highlighting selected major progress made in this rapidly expanding field.

关键词： chemically depolymerizable polymers sustainable polymers depolymerization monomer recovery degradation plastics

Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese

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National Science Review 2019年第2期6卷 257-274页

作者： Deng-Feng zhang yu Fan min xu Guihong wang Dong wang Jin li li-li Kong Hejiang Zhou Rongcan Luo Rui Bi Yong wu Guo-Dong li ming li Xiong-jian Luo Hong-yan jiang liwen Tan Chunjiu Zhong Yiru Fang Chen zhang Nengyin Sheng Tianzi jiang Yong-gang Yao Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & yunnan Province Kunming Institute of ZoologyChinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Kunming College of life Science University of Chinese Academy of Sciences Center for Neurodegenerative Diseases Department of Neurology Beijing Tiantan Hospital Capital Medical University Brainnetome Center Institute of AutomationChinese Academy of Sciences National Laboratory of Pattern Recognition Institute of Automation Chinese Academy of Sciences CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Department of Psychiatry the First Affiliated Hospital of Kunming Medical University Mental Health Institute of the Second Xiangya Hospital Central South University Department of Neurology Zhongshan Hospital Fudan University Division of Mood Disorders Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences KIZ–CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of Zoology Chinese Academy of Sciences

Alzheimer’s disease is the most common neurodegenerative disease,and has a high level of genetic heritability and population *** this study,we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer’s disease,followed by independent validation,imaging analysis and function *** identified an exome-wide significant rare missense variant rs3792646(p.K420Q)in the C7 gene in the discovery stage(P=1.09×10-6,odds ratio=7.853)and confirmed the association in different cohorts and a combined sample(1615 cases and 2832 controls,Pcombined=2.99×10-7,odds ratio=1.930).The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood,thus resulting in an earlier age of disease *** of the mutant p.K420Q disturbed cell viability,immune activation and β-amyloid *** analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal *** findings suggested that C7 is a novel risk gene for Alzheimer’s disease in Han Chinese.

关键词： Alzheimer’s disease whole-exome sequencing C7 neuroimaging complement system