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Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosa:A multicenter retrospective cohort in China

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Chinese medical Journal 2024年第11期137卷 1316-1323页

作者： Han Gao Kangsheng Peng Yadi Shi Shenshen Zhu Ruicong Sun Chunjin Xu Ping Liu Zhi Pang Lanxiang Zhu Weichang Chen Baisui Feng Huili Wu Guangxi Zhou Mingsong Li Junxiang Li Baijing Ding Zhanju Liu Center for IBD Research and Department of Gastroenterology Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200085China Clinical Medicine Sanquan College of Xinxiang Medical UniversityXinxiangHenan 453003China Department of Gastroenterology The First People’s Hospital of Shangqiu City Affiliated to Xinxiang Medical UniversityShangqiuHenan 476100China Department of Gastroenterology Wuhu First People’s HospitalWuhuAnhui 241000China Department of Gastroenterology Suzhou Municipal Hospital Affiliated to Nanjing Medical UniversitySuzhouJiangsu 215008China Department of Gastroenterology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 251006China Department of Gastroenterology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450014China Department of Gastroenterology Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhouHenan 450000China Department of Gastroenterology The Affiliated Hospital of Jining Medical CollegeJiningShandong 272004China Department of Gastroenterology The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510140China Department of Gastroenterology Dongfang Hospital of Beijing University of Chinese MedicineBeijing 100078China

Background:Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis(UC).Here,we developed a novel diagnostic criterion for assessing histological healing in UC ***:We conducted a retrospective cohort study in UC patients,whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji university from January 2017 to May *** identified an inflammatory cell enumeration index(ICEI)for assessing histological healing based on the proportions of eosinophils,CD177^(+)neutrophils,and CD40L^(+)T cells in the colonic lamina propria under high power field(HPF),and the outcomes(risks of symptomatic relapses)of achieving histological remission *** histological inflammation using Kaplan-Meier *** reliability and inter-reader reliability were evaluated by each *** relationships to the changes in the Nancy index and the Geboes score were also assessed for *** ICEI was further validated in a new cohort of UC patients from other nine university ***:We developed an ICEI for clinical diagnosis of histological healing,i.e.,Y=1.701X_(1)+0.758X_(2)+1.347X_(3)-7.745(X_(1),X_(2),and X_(3)represent the proportions of CD177^(+)neutrophils,eosinophils,and CD40L^(+)T cells,respectively,in the colonic lamina propria under HPF).The receiver operating characteristics curve(ROC)analysis revealed that Y<-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve(AUC)was 0.942(95%confidence interval[CI]:0.905-0.979)with a sensitivity of 92.5%and a specificity of 83.6%(P<0.001).The intraclass correlation coefficient(ICC)for the intrareader reliability was 0.855(95%CI:0.781-0.909),and ICEI had good inter-reader reliability of 0.832(95%CI:0.748-0.894).During an 18-month follow-up,patients with histological healing had a substantially better outcome com

关键词： Ulcerative colitis Histological healing Inflammatory cell enumeration index Prognosis

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Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

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Science China(Life Sciences) 2024年第4期67卷 745-764页

作者： Shujie Chen Liujing Huang Bingdong Liu Huimin Duan Ze Li Yifan Liu Hu Li Xiang Fu Jingchao Lin Yinlan Xu Li Liu Dan Wan Yulong Yin Liwei Xie Department of Endocrinology and Metabolism Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyInstitute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China school of Public Health Xinxiang Medical UniversityXinxiang 453003China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Metabo-Profile Biotechnology(Shanghai)Co.Ltd. Shanghai 201315China Institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsSchool of Medical TechnologyGuangdong Medical UniversityDongguan 524023China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China Laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Bioland Laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle ***,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains *** propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging *** investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total ***,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle ***,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/*** butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and *** a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle *** findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关键词： gut microbiota aging satellite cells butyrate Slc16a1(Mct1)

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Sleep-based neuronal oscillations as a physiological biomarker for Alzheimer's disease:is night time the right time?

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Neural Regeneration Research 2024年第7期19卷 1417-1418页

作者： Jonathan Witton Erica S.Brady Michael T.Craig Department of Clinical and Biomedical Sciences Faculty of Health and Life SciencesUniversity of ExeterExeterEnglandUK Gladstone Institute for Neurological Disease San FranciscoCAUSA school of psychology and Neuroscience College of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowScotlandUK

Dementia is a devastating syndrome characterized by memory problems,confusion,and behavior changes that prevent people from performing everyday *** is the leading cause of dependency and disability amongst older people,resulting in a global economic cost of ~$1.3 *** 58 million people are currently afflicted by dementia worldwide,with Alzheimer s disease(AD) causing most(60-70%) of these cases.

关键词： Alzheimer everyday performing

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TRPM2 Mediates Hepatic Ischemia–Reperfusion Injury via Ca^(2+) -Induced Mitochondrial Lipid Peroxidation through Increasing ALOX12 Expression

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Research 2024年第1期2023卷 351-368页

作者： Cheng Zhong Jing Yang Yiyin Zhang Xiaoxiao Fan Yang Fan Ning Hua Duguang Li Shengxi Jin Yirun Li Peng Chen Yongle Chen Xiaobo Cai Yi Zhang Linhua Jiang Wei Yang Peilin Yu Hui Lin Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouP.R.China Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital Zhejiang University School of MedicineHangzhou 310000P.R.China Department of Physiology and Pathophysiology and Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province Xinxiang Medical University453003 XinxiangHenanP.R.China school of Biomedical Sciences Faculty of Biological SciencesUniversity of LeedsLS29JT LeedsUK Department of Toxicology and Department of medical Oncology of Second Affiliated Hospital Zhejiang University School of MedicineHangzhouP.R.China Zhejiang Engineering Research Center of Cognitive Healthcare Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310020P.R.China College of Biomedical Engineering and Instrument Science Zhejiang UniversityHangzhou 310058P.R.China

Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and *** recent advances in understanding of the pathophysiology of hepatic IR injury,effective interventions and therapeutics are still ***,we examined the role of transient receptor potential melastatin 2(TRPM2),a Ca^(2+)-permeable,non-selective cation channel,in mediating hepatic IR *** data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction,inflammation,and cell death in ***,RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related ***,as a ferroptosis inducer,(1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed ***,TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca^(2+)-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase(ALOX12),which results in mitochondrial lipid peroxidation during hepatic IR ***,hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion,both in vitro and in ***,these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca^(2+)-induced ALOX12 expression,indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases,such as during liver resection and transplantation.

关键词： TRPM2 Lipid Hepatic

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Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1319-1333页

作者： Zhi-Tao Chen Chen-Chen Ding Kai-Lei Chen Yang-Jun Gu Chi-Cheng Lu Qi-Yong Li Division of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical CollegeHangzhou 310000Zhejiang ProvinceChina Pediatric psychology The Affiliated Mental Health Centre&Hangzhou Seventh People’s HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina school of Medicine Zhejiang Shuren UniversityHangzhou 310000Zhejiang ProvinceChina school of Medicine Zhejiang Chinese Medical University Zhejiang Shuren CollegeHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with poor *** studies have implicated the gut microbiota in CCA,but evidence for causal mechanisms is *** To investigate the causal relationship between gut microbiota and CCA *** We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and *** variants were used as instrumental *** sensitivity analyses assessed result *** Fifteen gut microbial taxa showed significant causal associations with CCA *** genetically predicted abundance of genus Eubacteriumnodatum group,genus Ruminococcustorques group,genus Coprococcus,genus Dorea,and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic *** intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae,genus Alistipes,order Enterobacteriales,and phylum *** effects against CCA were suggested for genus Collinsella,genus Eisenbergiella,genus Anaerostipes,genus Paraprevotella,genus Parasutterella,and phylum *** analyses indicated these findings were reliable without *** This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA *** experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

关键词： Cholangiocarcinoma Mendelian randomization Gut microbiota Instrumental variables Sensitivity analyses

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Targeting ferroptosis and ferritinophagy:new targets for cardiovascular diseases

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 1-22页

作者： Yi LUAN Yang YANG Ying LUAN Hui LIU Han XING Jinyan PEI Hengdao LIU Bo QIN Kaidi REN Clinical Systems Biology Research Laboratories Translational Medicine Centerthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China State Key Laboratory for Artificial Microstructures and Mesoscopic Physics School of PhysicsPeking UniversityBeijing100871China school of Laboratory Medicine Xinxiang Medical UniversityXinxiang453003China Quality Management Department Henan No.3 Provincial People’s HospitalZhengzhou450052China Department of Cardiology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Center for Translational Medicine the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou UniversityZhengzhou450052China Henan Engineering Research Center for Application&Translation of Precision Clinical Pharmacy Zhengzhou UniversityZhengzhou450052China

Cardiovascular diseases(CVDs)are a leading factor driving mortality ***,an essential trace mineral,is important in numerous biological processes,and its role in CVDs has raised broad discussion for ***-mediated cell death,namely ferroptosis,has attracted much attention due to its critical role in cardiomyocyte damage and ***,ferritinophagy is the upstream mechanism that induces ferroptosis,and is closely related to *** review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy,and the regulatory pathways and molecular targets involved in ferritinophagy,and to determine their roles in ***,we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating ***,this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

关键词： Cardiovascular disease Iron Ferroptosis Ferritinophagy Therapeutic target

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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

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The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

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Neural Regeneration Research 2024年第5期19卷 1084-1091页

作者： Yijing Zhao Tong Li Zige Jiang Chengcheng Gai Shuwen Yu Danqing Xin Tingting Li Dexiang Liu Zhen Wang Department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Neurosurgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina Department of medical psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao UniversityJinanShandong ProvinceChina

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal ***,the precise mechanism underlying the role of H2S in this situation remains *** this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal *** also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ***,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these *** findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

关键词： chemokine(C-X-C motif)ligand 11 cystathionineβsynthase H2S hypoxic ischemic brain injury inflammation L-cysteine lipopolysaccharide microglia miR-9-5p neuroprotection

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Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer

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Chinese Journal of Cancer Research 2024年第3期36卷 306-321页

作者： Zhifei Li Huan Zhao Huihui Hu Haili Shang Yongjing Ren Wenhui Qiu Hao Su Huifang Lyu Xiaobing Chen Department of Oncology the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Precision Therapy of Gastrointestinal CancerZhengzhou Key Laboratory for Precision Therapy of Gastrointestinal CancerZhengzhou 450008China Henan university of Traditional Chinese Medicine Zhengzhou 450046China State Key Laboratory of Esophageal Cancer Prevention&Treatment Key Laboratory of Advanced Drug Preparation TechnologiesMinistry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China The First Affiliated Hospital of xinxiang medical university Xinxiang 453000China Department of Oncology the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008China

Gastric cancer is one of the most prevalent cancers worldwide,and human epidermal growth factor receptor 2(HER2)-positive cases account for approximately 20%of the total ***,trastuzumab+chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer,and the combination has exhibited definite efficacy in HER2-targeted ***,the emergence of drug resistance during treatment considerably reduces its effectiveness;thus,it is imperative to investigate the potential mechanisms underlying *** the present review article,we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases,aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.

关键词： HER2 gastric cancer trastuzumab drug resistance

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Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

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Neural Regeneration Research 2024年第5期19卷 1133-1141页

作者： Baicheng Zhao Hang Zhang Ying Liu Gaoyu Zu Yuxiao Zhang Jiayi Hu Shuai Liu Linya You Department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghaiChina Shanghai Key Laboratory of Brain Functional Genomics(Ministry of Education) Affiliated Mental Health Center(ECNU)School of Psychology and Cognitive ScienceEast China Normal UniversityShanghaiChina Shanghai Changning Mental Health Center ShanghaiChina NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai ShanghaiChina Key Laboratory of medical Imaging Computing and Computer Assisted Intervention of Shanghai ShanghaiChina

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/***1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual *** previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and ***,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory *** test this,we knocked out Brpf1 in forebrain excitatory neurons using *** found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in *** findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

关键词： behavioral test Brpf1 CAMKIIa-Cre intellectual disability miniature excitatory postsynaptic current mRNA-Seq

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