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Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3

Bone Research 2024年第2期12卷 438-452页

作者： Bowen Fu Jianlin Shen Xuenong Zou Nian Sun Ze Zhang Zengping Liu Canjun Zeng Huan Liu Wenhua Huang guangdong Medical Innovation Platform for Translation of 3D Printing Application The Third Affiliated HospitalSouthern Medical UniversityGuangzhou 510630 GuangdongChina guangdong Engineering Research Center for Translation of Medical 3D Printing Application Guangdong Provincial Key Laboratory of Digital Medicine and BiomechanicsNational Key Discipline of Human AnatomySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510145 GuangdongChina Department of Foot and Ankle Surgery Center for Orthopedic SurgeryThe Third Affiliated HospitalSouthern Medical UniversityGuangzhou 510630 GuangdongChina Department of Orthopedics Affiliated Hospital of Putian UniversityPutian 351100 FujianChina Central Laboratory Affiliated Hospital of Putian UniversityPutian 351100 FujianChina guangdong provincial Key Laboratory of Orthopedics and Traumatology Department of Spinal SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080 GuangdongChina Nanfang hospital Southern Medical UniversityGuangzhou 510515 GuangdongChina Guangzhou Blood Center Guangzhou 510095 GuangdongChina Department of Orthopedics The Affiliated Traditional Chinese Medicine HospitalSouthwest Medical UniversityLuzhou 646000 SichuanChina

Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes and other molecules *** study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane(PDMS)*** demonstrated that epigenetic Parkin regulation by histone deacetylase 3(HDAC3)represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte *** found that ECM stiffening accelerated cultured chondrocyte senescence in vitro,while the stiffness ECM downregulated HDAC3,prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis(OA)in ***,intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in *** findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals,promoted the Parkin acetylation and hyperactivated mitophagy,and damaged chondrocyte *** results may provide new insights into chondrocyte regulation by the mechanical properties of ECM,suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.

关键词： chondrocyte osteoarthritis stiffness

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BioTreasury:a community-based repository enabling indexing and rating of bioinformatics tools

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Science China(Life Sciences) 2024年第2期67卷 221-229页

作者： Qi Zhao Xin Zhou Jingxing Wu Jieyi Cai Xiaoqiong Bao Lin Tang Chaoye Wang Chunlei Liu Yukai Wang Yuyan Teng Mohan Zheng Weiping Mu Zhixiang Zuo Yubin Xie Xiaotong Luo Jian Ren School of Life Sciences State Key Laboratory of Oncology in South ChinaCancer CenterGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhou 510060China Institute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China guangdong Institute of Gastroenterology Department of General SurgeryGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesThe Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510275China

The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis ***,to aid scientists in making informed choices,a community-based platform that indexes and rates bioinformatics tools is urgently *** this study,we introduce Bio Treasury(http://***),an integrated communitybased repository that provides an interactive platform for users and developers to share their experiences in various bioinformatics *** Treasury offers a comprehensive collection of well-indexed bioinformatics software,tools,and databases,totaling over 10,000 *** the past two years,we have continuously improved and maintained Bio Treasury,adding several exciting features,including creating structured homepages for every tool and user,a hierarchical category of bioinformatics tools and classifying tools using large language model(LLM).Bio Treasury streamlines the tool submission process with intelligent ***,Bio Treasury provides a wide range of social features,for example,enabling users to participate in interactive discussions,rate tools,build and share tool collections for the *** believe Bio Treasury can be a valuable resource and knowledge-sharing platform for the biomedical *** empowers researchers to effectively discover and evaluate bioinformatics tools,fostering collaboration and advancing bioinformatics research.

关键词： bioinformatics tools index tool database rating system large language model tool collections shari

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Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model

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Zoological Research 2024年第1期45卷 108-124页

作者： Huanpeng Lu Jinwei Chai Zijian Xu Jiena Wu Songzhe He Hang Liao Peng Huang Xiaowen Huang Xi Chen Haishan Jiang Shaogang Qu Xueqing Xu Department of Neurology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China guangdong provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence GuangzhouGuangdong 510515China Key Laboratory of Mental Health of the Ministry of Education Southern Medical UniversityGuangzhouGuangdong 510515China Department of Dermatology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Neurology Ganzhou Hospital-Nanfang HospitalSouthern Medical UniversityGanzhouJiangxi 341001China

Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its *** peptides may thus present therapeutic potential for *** this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for *** vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant *** the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway *** focal adhesion kinase(FAK)and p38 were also identified as regulatory *** the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated *** the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative *** findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.

关键词： Cath-KP Peptide Parkinson’s disease Oxidative stress Neuroprotection

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Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

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Neural Regeneration Research 2024年第5期19卷 1064-1071页

作者： Mingxiang Ding Lei Jin Boyang Wei Wenping Cheng Wenchao Liu Xifeng Li Chuanzhi Duan Neurosurgery Center Department of Cerebrovascular SurgeryThe National Key Clinical SpecialtyThe Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular DiseaseGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationThe Neurosurgery Institute of Guangdong ProvinceZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Cerebrovascular Intervention Zhongshan City People’s HospitalZhongshanGuangdong ProvinceChina

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective *** is a crucial mechanism underlying early brain injury after subarachnoid *** studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and ***,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid *** this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation *** results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological *** explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral *** TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological ***,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte *** summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

关键词： astrocyte early brain injury inflammasome NLRC4 pyroptosis subarachnoid hemorrhage tumor necrosis factor-stimulated gene-6(TSG-6)

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Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series

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World Journal of Clinical Cases 2024年第9期12卷 1560-1568页

作者： Jin-Long Zhao Xiao Jin He-Tao Huang Wei-Yi Yang Jia-Hui Li Ming-Hui Luo Jun Liu Jian-Ke Pan The Second Clinical Medical College Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Chinese Medicine The First Affiliated HospitalJinan UniversityGuangzhou 510630Guangdong ProvinceChina The Second School of Clinical Medical Sciences Guangzhou University of Chinese MedicineGuangdong Academy of Traditional Chinese MedicineGuangzhou 510405Guangdong ProvinceChina The Second Affiliated hospital Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine)Guangzhou 510120Guangdong ProvinceChina The Affiliated TCM hospital Guangzhou Medical UniversityGuangzhou 510405Guangdong ProvinceChina The Research Team on Bone and Joint Degeneration and Injury Guangdong Provincial Academy of Chinese Medical SciencesGuangzhou 510405Guangdong ProvinceChina

BACKGROUND Unicompartmental knee arthroplasty(UKA)has great advantages in the treatment of unicompartmental knee osteoarthritis,but its revision rate is higher than that of total knee *** To summarize and analyse the causes of revision after *** This is a retrospective case series study in which the reasons for the first revision after UKA are *** analysed the clinical symptoms,medical histories,laboratory test results,imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after *** A total of 13 patients,including 3 males and 10 females,underwent revision surgery after *** average age of the included patients was 67.62 *** prosthesis was used for 3 d to 72 *** main reasons for revision after UKA were improper suturing of the surgical opening(1 patient),osteophytes(2 patients),intra-articular loose bodies(2 patients),tibial prosthesis loosening(2 patients),rheumatoid arthritis(1 patient),gasket dislocation(3 patients),anterior cruciate ligament injury(1 patient),and medial collateral ligament injury with residual bone cement(1 patient).CONCLUSION The causes of primary revision after UKA were gasket dislocation,osteophytes,intra-articular loose bodies and tibial prosthesis *** of these factors may greatly reduce the rate of revision after UKA,improve patient satisfaction and reduce medical burden.

关键词： Unicompartmental knee arthroplasty Total knee arthroplasty Causes Revision Case series

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Early identification of stroke through deep learning with multi-modal human speech and movement data

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Neural Regeneration Research 2025年第1期20卷 234-241页

作者： Zijun Ou Haitao Wang Bin Zhang Haobang Liang Bei Hu Longlong Ren Yanjuan Liu Yuhu Zhang Chengbo Dai Hejun Wu Weifeng Li Xin Li School of Computer Science and Engineering Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Neurology Guangdong Neuroscience InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Emergency Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina

Early identification and treatment of stroke can greatly improve patient outcomes and quality of *** clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are commonly used for stroke screening,accurate administration is dependent on specialized *** this study,we proposed a novel multimodal deep learning approach,based on the FAST,for assessing suspected stroke patients exhibiting symptoms such as limb weakness,facial paresis,and speech disorders in acute *** collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements,facial expressions,and speech tests based on the *** compared the constructed deep learning model,which was designed to process multi-modal datasets,with six prior models that achieved good action classification performance,including the I3D,SlowFast,X3D,TPN,TimeSformer,and *** found that the findings of our deep learning model had a higher clinical value compared with the other ***,the multi-modal model outperformed its single-module variants,highlighting the benefit of utilizing multiple types of patient data,such as action videos and speech *** results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke,thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.

关键词： artificial intelligence deep learning diagnosis early detection FAST screening stroke

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Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

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Journal of Sport and Health Science 2024年第2期13卷 222-232页

作者： Xinyi Jin Yilin Chen Hongliang Feng Mingqing Zhou Joey W.Y.Chang Yaping Liu Alice Pik Shan Kong Xiao Tan Yun-Kwok Wing Yannis Yan Liang Jihui Zhang guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China guangdong provincial Key Laboratory of Coronary Heart Disease Prevention Guangdong Cardiovascular InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China School of Medicine South China University of TechnologyGuangzhou 510641China Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhou 510180China The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510282China guangdong Mental Health Center Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510120China Li Chiu Kong Family Sleep Assessment Unit Department of PsychiatryFaculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Psychiatry Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Medical Sciences Uppsala UniversityUppsala 75185Sweden Department of Big Data in Health Science Zhejiang University School of Public HealthHangzhou 310058China Key Laboratory of Neurogenetics and Channelopathies of guangdong Province and the Ministry of Education of China Guangzhou 510260China

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort ***:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK *** duration(short:8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and *** was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death ***:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were *** with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes *** increased risk among short sleepers seems to be protected against by *** with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did ***:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

关键词： Light physical activity Sleep duration Triaxial accelerometer Type 2 diabetes UK Biobank

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Paeoniflorin,the Main Monomer Component of Paeonia lactiflora,Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation

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Chinese Journal of Integrative Medicine 2024年第5期30卷 433-442页

作者： CHEN Pu ZHOU Jun RUAN An-min MA Yu-feng WANG Qing-fu Department of Orthopaedic Surgery Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China Department of Orthopaedic Surgery Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China Department of Orthopaedic Surgery Beijing Longfu HospitalBeijing 100010China

Objective:To explore the mechanism of paeoniflorin(PF)on osteoarthritis(OA)synovial inflammation from network pharmacology to experimental ***:Targets of OA were constructed by detecting the database of network database platforms(Therapeutic Target database,Drug Bank and Gene Cards),and the targets of PF were constructed by Pub Chem and Herbal Ingredients'Targets *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of these co-targeted genes were conducted via Database for Annotation,Visualization,and Integrated Discovery(DAVID)database,and protein-protein interaction(PPI)networks were conducted via the search tool for the retrieval of interacting genes(STRING)*** counting kit-8(CCK-8)assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes(FLS),quantitative real-time polymerase chain reaction(q PCR),enzyme-linked immunosorbent assay(ELISA)and Western blot were used to verify the potential mechanism of PF in synovial ***:Twenty-six co-targeted genes were *** enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm,and the biological processes mainly involved'cellular response to hypoxia''lipopolysaccharide(LPS)-mediated signaling pathway'and'positive regulation of gene expression'.KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with'hypoxia-inducible factor-1(HIF-1)signaling pathway'and'tumornecrosis factor(TNF)signaling pathway'.The PPI network showed that the top 3 hub genes were TP53,TNF,and *** docking results showed that PF was well docking with ***-8 showed no potential toxicity of 10,20 and 50μmol/L PF on human OA *** PF significantly decreased the expression levels of interleukin-1β,interleukin-6,TNF-αmatrix metalloproteinase 13(MMP13),and a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5)and TNF

关键词： paeoniflorin osteoarthritis synovial inflammation tumor necrosis factor-α network pharmacology Paeonia lactiflora

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Changing the 3-decade routine of preoperative radiotherapy for locally advanced rectal cancer: New wine for new bottle?

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中华医学杂志(英文版) 2024年第16期137卷 1891-1893页

作者： Dou Ruoxu Zhang Jianwei Wang Jianping Deng Yanhong Department of Gastrointestinal Surgery The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai Guangdong China Department of Medical Oncology The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Biomedical Innovation Center The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Department of General Surgery The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China guangdong provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China

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Epigenetic and transcriptional landscapes during cerebral cortex development in a microcephaly mouse model

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Journal of Genetics and Genomics 2024年第4期51卷 419-432页

作者： Qing Yang Qiang Cao Yue Yu Xianxin Lai Jiahao Feng Xinjie Li Yinan Jiang Yazhou Sun Zhong-Wei Zhou Xin Li School of Medicine Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdong 518107China Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjin 300072China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China guangdong provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China

The cerebral cortex is a pivotal structure integral to advanced brain functions within the mammalian central nervous *** methylation and hydroxymethylation play important roles in regulating cerebral cortex ***,it remains unclear whether abnormal cerebral cortex development,such as microcephaly,could rescale the epigenetic landscape,potentially contributing to dysregulated gene expression during brain *** this study,we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type(WT)mice and Mcph1 knockout(Mcph1-del)mice with severe ***,we discover a global reduction of 5′-hydroxymethylcytosine(5hmC)level,primarily in TET1-binding regions,in Mcph1-del mice compared to WT mice during juvenile and adult ***,genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain ***,genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult *** findings reveal that aberrant cerebral cortex development in the early stages profoundly alters the epigenetic regulation program,which provides unique insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.

关键词： Microcephaly Epigeneticmodification Tet1 Cerebral cortexdevelopment DNA hydroxymethylome Transcriptome

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