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plasma metabolites and risk of myocardial infarction:a bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第2期21卷 219-231页

作者： Dong-Hua LI qiang WU Jing-Sheng LAN Shuo CHEN You-Yi huang Lan-Jin WU zhi-Qing QIN Ying huang Wan-Zhong huang Ting ZENG Xin HAO Hua-Bin SU qiang SU Department of Cardiovascular Medicine Minzu Hospital of Guangxi Zhuang Autonomous RegionGuangxiChina Senior Department of Cardiology the Sixth Medical CenterChinese PLA General HospitalBeijingChina Library of Graduate School Chinese PLA General HospitalBeijingChina Department of Cardiology Jiangbin Hospital of Guangxi Zhuang Autonomous RegionGuangxiChina Health Management institute the Second Medical CenterChinese PLA General HospitalBeijingChina

BACKGROUND Myocardial infarction(MI)is a critical cardiovascular event with multifaceted etiology,involving several genetic and environmental *** is essential to understand the function of plasma metabolites in the development of MI and unravel its complex *** This study employed a bidirectional Mendelian randomization(MR)approach to investigate the causal relationships between plasma metabolites and MI *** used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice *** addition,the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite(1400 metabolites)and MI(20,917 individuals with MI and 440,906 individuals without MI)*** variance weighted was the primary method for estimating causal *** estimates are expressed as beta coefficients or odds ratio(OR)with 95%*** We identified 14 plasma metabolites associated with the occurrence of MI(Pplasma metabolites[propionylglycine levels(OR=0.922,95%CI:0.881–0.965,Pplasma metabolites[1-palmitoyl-2-arachidonoyl-GPE(16:0/20:4)levels(OR=1.051,95%CI:1.018–1.084,P=0.002),behenoyl dihydrosphingomyelin(d18:0/22:0)levels(OR=1.076,95%CI:1.027–1.128,P=0.002),1-stearoyl-2-docosahexaenoyl-GPE(18:0/22:6)levels(OR=1.067,95%CI:1.027–1.109,P=0.001),alpha-ketobutyrate levels(OR=1.108,95%

关键词： infarction alterations diagnosis

Dcalycinumines A-E,Alkaloids with Cytotoxic Activities of Nasopharyngeal Carcinoma Cells from Daphniphyllum calycinum

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chinese Journal of Chemistry 2024年第1期42卷 35-42页

作者： Qing Tang xiao-Yong Dai qiang Lin zhi-Peng Ling Yi-Kun Hao Tian-Xi Zhu Ji-Hui Zhang Yi-Bo Hou Yao-Lan Li Lai-qiang huang Jing-Hao Wang Guo-Cai Wang Yu-Bo Zhang Guangdong Clinical Translational Centerfor Targeted Drug Department of PharmacologySchoolof MedicineJinan University GuangzhouGuangdong 510632China institute of Traditional chinese Medicine&Natural Products Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollegeof PharmacyJinan UniversityGuangzhouGuangdong511443China institute of Biopharmaceutical and Health Engineering Shenzhen Key Laboratory of Gene and Antibody TherapyState Key Laboratory of Chemical OncogenomicsShenzhen International Graduate SchoolTsinghua UniversityShenzhenGuangdong 518055China The Guangzhou Key Laboratoryof Basic and Translational research on Chronic Disease Department of PharmacyThe First Affiliated HospitalJinan UniversityGuangzhouGuangdong 510630China

Fivenovel Daphniphyllum alkaloids,named dcalycinumines A-E(1-4,6),andeight previously described Daphniphyllum alkaloids(5,7-13)were isolated from Daphniphyllum *** 1 is the first Daphniphyllum alkaloid possessing a highly rearranged 6/6/6/7/5/6 hexacyclic architecture with a unique 3-methyl-1-azabicyclo[4,4,0]decane ring *** 2 represents a rare diamino Daphniphyllum alkaloid with an unprecedented 6/5/5/6/6/5 carbon skeleton featuring a unique 1-aza-6-azaspiro[4,5]decane unit,whereas 3 also represents a rare diamino Daphniphyllum alkaloid as a possible precursor of *** 4 is the second example of c-22-nor yuzurimine-type *** structures and absolute configurations were elucidated by HRESIMS,NMR spectroscopic analyses,EcD calculations,and single-crystal X-ray ***,compound 1 showed remarkable antitumor activities,which could inhibit the proliferation,migration and invasion of nasopharyngeal carcinoma cells,and promoted nasopharyngeal carcinoma cells apoptosis.

关键词： Daphniphyllum calycinum Natural products Daphniphyllum alkaloid Structural elucidation Biological activity Apoptosis Nasopharyngealcarcinoma

Performance of the walking trail making test in older adults with white matter hyperintensities

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World Journal of Psychiatry 2024年第1期14卷 102-110页

作者： Hong-Yi Zhao zhi-qiang Zhang Yong-Hua huang Hong Li Fang-Yuan Wei Department of Neurology No.984 Hospital of PLABeijing 100094China Department of Neurology The Seventh Medical Center of PLA General HospitalBeijing 100700China Mental Health institute of Inner Mongolia Autonomous Region The Third Hospital of Inner Mongolia Autonomous RegionHohhot 010010Inner Mongolia Autonomous RegionChina Department of Neurosurgery No.984 Hospital of PLABeijing 100094China Department of Hand and Foot surgery Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China Engineering research Center of chinese Orthopaedic and Sports Rehabilitation Artificial Intelligent Ministry of EducationBeijing 100029China

BACKGROUND Several studies have reported that the walking trail making test(WTMT)completion time is significantly higher in patients with developmental coordination disorders and mild cognitive *** hypothesized that WTMT performance would be altered in older adults with white matter hyperintensities(WMH).AIM To explore the performance in the WTMT in older people with *** In this single-center,observational study,25 elderly WMH patients admitted to our hospital from June 2019 to June 2020 served as the WMH group and 20 participants matched for age,gender,and educational level who were undergoing physical examination in our hospital during the same period served as the control *** participants completed the WTMT-A and WTMT-B to obtain their gait parameters,including WTMT-A completion time,WTMT-B completion time,speed,step length,cadence,and stance phase *** matter lesions were scored according to the Fazekas *** neuropsychological assessments were carried out to assess cognitive *** relationships between WTMT performance and cognition and motion in elderly patients with WMH were analyzed by partial Pearson correlation *** Patients with WMH performed significantly worse on the choice reaction test(CRT)(0.51±0.09 s vs 0.44±0.06 s,P=0.007),verbal fluency test(VFT,14.2±2.75 vs 16.65±3.54,P=0.012),and digit symbol substitution test(16.00±2.75 vs 18.40±3.27,P=0.010)than participants in the control *** WMH group also required significantly more time to complete the WTMT-A(93.00±10.76 s vs 70.55±11.28 s,P<0.001)and WTMT-B(109.72±12.26 s vs 82.85±7.90 s,P<0.001).WTMT-A completion time was positively correlated with CRT time(r=0.460,P=0.001),while WTMT-B completion time was negatively correlated with VFT(r=-0.391,P=0.008).On the WTMT-A,only speed was found to statistically differ between the WMH and control groups(0.803±0.096 vs 0.975±0.050 m/s,P<0.001),whereas on the WTMT-B,the WMH group exhibited a sign

关键词： White matter hyperintensities Cognitive dysfunction Motor deficits Gait analysis Trail making test Small vessel disease

Identification and distribution of 13003 landslides in the northwest margin of Qinghai-Tibet plateau based on human-computer interaction remote sensing interpretation

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china Geology 2024年第2期7卷 171-187页

作者： Wei Wang Yuan-dong huang Chong Xu xiao-yi Shao Lei Li Li-ye Feng Hui-ran Gao Yu-long Cui Shuai Wu zhi-qiang Yang Kai Ma National institute of Natural Hazards Ministry of Emergency Management of ChinaBeijing 100085China Key Laboratory of Compound and Chained Natural Hazards Dynamics Ministry of Emergency Management of Chin12eijing 100085China School of Emergency Management Science and Engineering University of Chinese Academy of SciencesBeijing 100049China School of Soil and Water Conservation Beijing Forestry UniversityBeijing 100083China School of Civil Engineering and Architecture Anhui University of Science and TechnologyHuainan 232001China No.3 Bureau of china Metallurgical Geology Bureau Taiyuan 030031China

The periphery of the Qinghai-Tibet plateau is renowned for its susceptibility to ***,the northwestern margin of this region,characterised by limited human activities and challenging transportation,remains insufficiently explored concerning landslide occurrence and *** the planning and construction of the Xinjiang-Tibet Railway,a comprehensive investigation into disastrous landslides in this area is essential for effective disaster preparedness and mitigation *** using the human-computer interaction interpretation approach,the authors established a landslide database encompassing 13003 landslides,collectively spanning an area of 3351.24 km^(2)(36°N-40°N,73°E-78°E).The database incorporates diverse topographical and environmental parameters,including regional elevation,slope angle,slope aspect,distance to faults,distance to roads,distance to rivers,annual precipitation,and *** statistical characteristics of number and area of landslides,landslide number density(LND),and landslide area percentage(LAP)are *** authors found that a predominant concentration of landslide origins within high slope angle regions,with the highest incidence observed in intervals characterised by average slopes of 20°to 30°,maximum slope angle above 80°,along with orientations towards the north(N),northeast(NE),and southwest(SW).Additionally,elevations above 4.5 km,distance to rivers below 1 km,rainfall between 20-30 mm and 30-40 mm emerge as particularly susceptible to landslide *** study area’s geological composition primarily comprises Mesozoic and Upper Paleozoic *** fault and human engineering activities have different degrees of influence on landslide ***,the significance of the landslide database,the relationship between landslide distribution and environmental factors,and the geometric and morphological characteristics of landslides are *** landslide H/L ratios in the study area are

关键词： Landslides Human-computer interaction interpretation Landslide database Spatial distribution Earthquake Rainfall Human engineering activity Qinghai-Tibet plateau Geological hazards survey engineering

A multicenter prospective study on the management of hepatoblastoma in children:a report from the chinese Children's Cancer Group

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World Journal of Pediatrics 2024年第6期20卷 590-601页

作者： Meng-Jie Tang xiao-Li Ma Xiang-Ling He Wei-Hua Pan xiao-Hong Zhang Sha-Yi Jiang Ju Gao Fu Li Wei Yao Song Gu Wei-Ling Zhang qiang Zhao Shi-Hao huang Yong-Jun Fang Wei Liu Hui-Zhong Niu Chun-Mei Wang Li-Rong Sun Hui Gao Yun-Peng Dai Shun-Gen huang zhi-Yong Zhong Xi-Ge Wang Zhong-Rong Li Liang-Chun Yang Ye-Ming Wu Huan-Min Wang Xin Sun xiao-Jun Yuan Department of Pediatric Hematology/Oncology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang RoadYangpu DistrictShanghai 200092China Medical Oncology Department Pediatric Oncology CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of Hematology/Oncology Children's Medical CenterHunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 41005China Department of Pediatric surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Hematology/Oncology Guangzhou Women and Children's Medical CenterNational Children's Medical Center for South Central RegionGuangzhou 510623China Department of Hematology Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200062China Department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041China Department of Hematology/Oncology Qilu Children's Hospital of Shandong UniversityJinan 250022China Department of Pediatric surgery Children's Hospital of Fudan UniversityShanghai 201102China Department of general surgery Shanghai Children's Medical Center(National Children's Medical Center-Shanghai)Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Pediatrics Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Hematology/Oncology Children's Hospital of Nanjing Medical UniversityNanjing 210008China Department of Hematology/Oncology Henan Children's HospitalZhengzhou 450018China Department of Pediatric general surgery Hebei Children's Hospital of Hebei Medical UniversityShijiazhuang City 050031China Children's hospital the First Affliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Paediatric

Background This study aimed to identify survival risk factors in chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the chinese Children's Cancer Group(CCCG)in *** A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was *** demographics,treatment protocols,and other related information were *** regression models and Kaplan-Meier curve methods were *** The 4-year event-free survival(EFS)and overall survival(OS)were 76.9 and 93.5%,*** 4-year EFS rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,*** 4-year 0S was 100%,97.3%,94.4%,and 86.8%,*** regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 *** with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 ***≥8 years,R+,and E+were independent risk factors for *** with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

关键词： Alpha-fetoprotein Hepatoblastoma Multicenter Prospective study Survival

Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure

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World Journal of Gastroenterology 2001年第5期7卷 706-709页

作者： xiao-Ping Chen~2 Yi-Long Xue~1 Xin-Jian Li~1 Zuo-Yun Zhang~1 Yan-Ling Li~1 zhi-qiang huang~2 1 institute of Basic Medical Sciences,2 Department of Hepatobiliary surgery,pla general hospital,beijing 100853,china institute of Basic Medical Sciences PLA General Hospital Beijing 100853 China.

AIM: To evaluate the efficacy and safety of the TECA-I bioartificial liver support system (BALSS) in treating canines with acute liver failure (ALF). METHODS: Ten canines with ALF induced by 80% liver resection received BALSS treatment (BALSS group). Blood was perfused through a hollow fiber tube containing 1X10(10) porcine *** canines with ALF were treated with BALSS without porcine hepatocytes (control group), and five canines with ALF received drug treatment (drug group). Each treatment lasted 6 hours. RESULTS: BALSS treatment yielded beneficial effects for partial liver resection induced ALF canines with survival and decreased plasma ammonia, ALT, AST and BIL. There was an obvious decrease in PT level and increase in PA level, and there were no changes in the count of lymphocytes, immunoglobulins (IgA, IgG and IgM) and complement (C3 and C4) levels after BALSS treatment. In contrast, for the canines with ALF in non-hepatocyte BALSS group (control group) and drug group, there were no significant changes in ammonia, ALT, AST, BIL, PT and PA levels. ALF canines in BALSS group, control group and drug group lived respectively an average time of 108.0h +/- 12.0h, 24.0h +/- 6.0h and 20.4h +/- 6.4h,and three canines with ALF survived in BALSS group. CONCLUSION: TECA-I BALSS is efficacious and safe for ALF canines induced by partial liver resection.

关键词： Liver, Artificial Animals Blood Coagulation Dogs Hepatectomy Hepatocytes Kidney Liver Liver Failure, Acute Lung Myocardium Swine

Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

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World Journal of Gastroenterology 2024年第24期30卷 3086-3105页

作者： Miao-Miao Lin Shan-Shan Yang Qiu-Yue huang Guang-Hui Cui xiao-Fen Jia Yao Yang Zong-Ming Shi Hui Ye Xue-zhi Zhang Department of Integrated Traditional chinese and Western Medicine Peking University First HospitalBeijing 100034China institute of Integrated Traditional chinese and Western Medicine Peking UniversityBeijing 100034China

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric *** infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to *** has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in *** In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected *** vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,*** most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm *** assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm *** violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP *** effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain ***-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD *** HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the *** had str

关键词： Qingre Huashi decoction Helicobacter pylori Drug resistance Biofilm Metabolomics

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-qiang Li Yong-Feng Yang xiao xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo huang Dai Zhang Wei-Hua Yue institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan Key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina 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 650223China institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern institute for Brain research Peking UniversityBeijing 100871China chinese institute for Brain research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer’s disease mice

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Protein & Cell 2024年第4期15卷 261-284页

作者： He-Zhou huang Wen-Qing Ai Na Wei Ling-Shuang Zhu zhi-qiang Liu Chao-Wen Zhou Man-Fei Deng Wen-Tao Zhang Jia-Chen Zhang Chun-Qing Yang Ya-Zhuo Hu zhi-Tao Han Hong-Hong Zhang Jian-Jun Jia Jing Wang Fang-Fang Liu Ke Li Qi Xu Mei Yuan Hengye Man Ziyuan Guo Youming Lu Kai Shu Ling-qiang Zhu Dan Liu Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Medical Genetics School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pathology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450002China Department of Pathology School of Basic MedicineZhengzhou UniversityZhengzhou 450002China The Second Affiliated hospital Department of NeurologyHengyang Medical SchoolUniversity of South ChinaHengyang 421001China beijing Key Laboratory of Aging and Geriatrics National Clinical Research Center for Geriatric DiseaseInstitute of GeriatricsChinese PLA General Hospital and Chinese PLA Medical AcademyBeijing 100853China Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Neurology Union HospitalHuazhong University of Science and TechnologyWuhan 430022China Department of Biology Boston UniversityBostonMA 02215USA Center for Stem Cell and Organoid Medicine(CuSTOM) Division of Developmental BiologyCincinnati Children’s Hospital Medical CenterCincinnatiOH 45229USA

Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family *** genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of ***,the underlying mechanisms of social isolation in AD progression remain *** the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD *** also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related ***,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious ***,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its ***,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD *** together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.

关键词： Alzheimer’s disease memory impairment synaptic disorder tau pathology