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TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

Signal Transduction and Targeted Therapy 2024年第3期9卷 1209-1220页

作者： Shuai Song Xiaokai Zhang Zihang Huang Yongchao Zhao Shuyang Lu Linqi Zeng Fengze Cai Tongyao Wang Zhiqiang Pei Xinyu Weng Wei Luo Hao Lu Zilun Wei Jian Wu Peng Yu Li Shen Xiaochun Zhang Aijun Sun Junbo Ge Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghaiChina State Key laboratory of Cardiology Zhongshan HospitalFudan UniversityShanghaiChina Key laboratory of Viral Heart diseases National Health CommissionShanghaiChina Key laboratory of Viral Heart diseases Chinese Academy of Medical SciencesShanghaiChina National Clinical Research Center for Interventional Medicine ShanghaiChina Department of cardiac surgery Zhongshan HospitalFudan UniversityShanghaiChina institutes of Biomedical Sciences Fudan UniversityShanghaiChina shanghai institute of Hypertension Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and ***,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely *** analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l *** investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure *** TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre *** and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac ***,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 ***1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 ***,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 *** conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.

关键词： TEAD1 expression Wnt4

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Association of copy number variation in X chromosome-linked PNPLA4 with heterotaxy and congenital heart disease

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中华医学杂志(英文版) 2024年第15期137卷 2024 Jul 8页

作者： Gao Han Huang Xianghui Chen Weicheng Feng Zhiyu Zhao Zhengshan Li Ping Tan Chaozhong Wang Jinxin Zhuang Quannan Gao Yuan Min Shaojie Yao Qinyu Qian Maoxiang Ma Xiaojing Wu Feizhen Yan Weili Sheng Wei Huang Guoying Children’s Hospital of Fudan University Shanghai China shanghai Key laboratory of Birth Defects Shanghai China Fujian Key laboratory of Neonatal diseases Xiamen Children’s Hospital Xiamen Fujian China Research Unit of Early Intervention of Genetically Related Childhood cardiovascular diseases Chinese Academy of Medical Sciences Shanghai China

Background: Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/***: Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, andPNPLA4 was identified as the leading candidate gene. To validate, we generatedPNPLA4-overexpressing human induced pluripotent stem cell lines as well aspnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular ***: Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, andPNPLA4 in the Xp22.31 was a candidate gene associated with HTX/***4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series ofin vivo andin vitro analyses at the molecular and cellular levels, we revealed that the biological function ofPNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP ***: Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose ofPNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

关键词： PNPLA4 Copy number variations X-chromosome Heterotaxy Congenital heart diseases

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In Situ Sustained Macrophage-Targeted Nanomicelle-Hydrogel Microspheres for Inhibiting Osteoarthritis

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Research 2024年第1期2023卷 1-16页

作者： XiaoXiao Li Xingchen Li Jielai Yang Yawei Du Liang Chen Gang Zhao Tingjun Ye Yuan Zhu Xiangyang Xu Lianfu Deng Wenguo Cui Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025P.R.China

There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release ***,a nanomicellehydrogel microsphere,characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis,is employed for in situ sustained macrophage targeting and regulation,and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug *** 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle,thus keeping it in joints,while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages,and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages.

关键词： micelle release spheres

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Early-life famine exposure,adulthood obesity patterns,and risk of low-energy fracture

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Frontiers of Medicine 2024年第1期18卷 192-203页

作者： Hongyan Qi Chunyan Hu Jie Zhang Lin Lin Shuangyuan Wang Hong Lin Xiaojing Jia Yuanyue Zhu Yi Zhang Xueyan Wu Mian Li Min Xu Yu Xu Tiange Wang Zhiyun Zhao Weiqing Wang Yufang Bi Meng Dai Yuhong Chen Jieli Lu Department of Endocrine and Metabolic diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China shanghai National Clinical Research Center for Endocrine and Metabolic diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People’s Republic of ChinaShanghai National Center for Translational MedicineRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains *** study included 5323 community-dwelling subjects aged⩾40 years from ***-life famine exposure was identified based on the participants’birth *** obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or *** to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in *** interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

关键词： famine obesity body mass index waist-to-hip ratio low-energy fracture

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Bridging buried interface enable 24.67%-efficiency doctor-bladed perovskite solar cells in ambient condition

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Nano Research 2024年第9期17卷 8068-8076页

作者： Jianhui Chang Erming Feng Xiangxiang Feng Hengyue Li Yang Ding Caoyu Long Siyuan Lu Haixia Zhu Wen Deng Jiayan Shi Yingguo Yang Si Xiao Yongbo Yuan Junliang Yang Hunan Key laboratory for Super-microstructure and Ultrafast Process School of PhysicsCentral South UniversityChangsha 410083China Hunan Key laboratory of Nanophotonics and Devices School of PhysicsCentral South UniversityChangsha 410083China Textile and Fashion Collage Hunan Institute of EngineeringXiangtan 411101China shanghai Synchrotron Radiation Facility Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201204China State Key laboratory of Powder Metallurgy Central South UniversityChangsha 410083China

Scalable deposition of high-efficiency perovskite solar cells(PSCs)is critical to accelerating their commercial ***,a significant number of defects are distributed at the buried interface of perovskite film fabricated by scalable deposition,exhibiting much negative influence on the efficiency and stability of ***,2-(N-morpholino)ethanesulfonic acid potassium salt(MESK)is incorporated as the bridging layer between the tin oxide(SnO_(2))electron transport layer(ETL)and the perovskite film deposited via scalable two-step doctor *** experiment and simulation results demonstrate that MESK can passivate the trap states of Sn suspension bonds,thereby enhancing the charge extraction and transport of the SnO_(2)***,the strong interaction with uncoordinated Pb ions can modulate the crystal growth and crystallographic orientation of perovskite film and passivate buried *** employing MESK interface bridging,PSCs fabricated via scalable doctor blading in ambient condition achieve a power conversion efficiency(PCE)of 24.67%,which is one of the highest PCEs for doctor-bladed PSCs,and PSC modules with an active area of 11.35 cm^(2)achieve a PCE of 19.45%.Furthermore,PSCs exhibit excellent long-term stability,and the unpackaged target device with a storage of 1680 h in ambient condition(25℃and humidity of 30%relative humidity(RH))can maintain more than 90%of the initial *** research provides a strategy for constructing a high-performance interface bridge between SnO_(2)ETL and perovskite film,and achieving efficient and stable large-area PSCs and modules fabricated via scalable doctor-blading process in ambient condition.

关键词： perovskite solar cells doctor blading buried interface defect passivation orientation regulation

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Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFRβ

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Frontiers of Medicine 2024年第3期18卷 465-483页

作者： Fei Xu Han Chen Changyi Zhou Tongtong Zang Rui Wang Shutong Shen Chaofu Li Yue Yu Zhiqiang Pei Li Shen Juying Qian Junbo Ge Department of Cardiology and laboratory of Heart Valve Disease West China HospitalSichuan UniversityChengdu610041China Department of Cardiology Zhongshan HospitalFudan UniversityResearch Unit of Cardiovascular Techniques and DevicesChinese Academy of Medical SciencesShanghai200032China shanghai institute of cardiovascular diseases Shanghai200032China National Clinical Research Center for Interventional Medicine&shanghai Clinical Research Center for Interventional Medicine(19MC1910300) Shanghai200032China

Atherosclerosis is a chronic artery disease that causes various types of cardiovascular *** smooth muscle cells(VSMCs),the main components of atherosclerotic plaque,switch from contractile to synthetic phenotypes during *** is crucial in regulating VSMC phenotypes in atherosclerosis,and it can be reversely regulated by ***,the specific effects of deubiquitinases on atherosclerosis have not been thoroughly *** this study,RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases,which revealed that silencing OTUB1 inhibited PDGF-BB-stimulated VSMC phenotype *** in vivo studies using Apoe−/−mice revealed that knockdown of OTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque ***,VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencing OTUB1 in *** RNA-sequencing data indicated that knocking down OTUB1 influenced VSMC differentiation,adhesion,and *** spectrometry of ubiquitinated protein confirmed that proteins related to cell growth and migration were differentially ***,we found that OTUB1 recognized the K707 residue ubiquitylation of PDGFRβwith its catalytic triad,thereby reducing the K48-linked ubiquitylation of PDGFRβ.Inhibiting OTUB1 in VSMCs could promote PDGFRβdegradation via the ubiquitin–proteasome pathway,so it was beneficial in preventing VSMCs’phenotype *** findings revealed that knocking down OTUB1 ameliorated VSMCs’phenotype switch and atherosclerosis progression,indicating that OTUB1 could be a valuable translational therapeutic target in the future.

关键词： atherosclerosis vascular smooth muscle cell ubiquitylation deubiquitinase OTUB1 PDGFRβ

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Diagnostic performance of intravascular ultrasound-based fractional flow reserve in evaluating of intermediate left main stenosis

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Journal of Geriatric Cardiology 2024年第1期21卷 34-43页

作者： Yong-Gang SUI Cheng YANG Chang-Dong GUAN Yan-Lu XU Na-Qiong WU Wei-Xian YANG Yong-Jian WU Ke-Fei DOU Yue-Jin YANG Shu-Bin QIAO Wei YU Bo XU Sheng-Xian TU Jie QIAN Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Catheterization Laboratories Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Biomedical Instrument institute School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghaiChina National Clinical Research Center for cardiovascular diseases BeijingChina

BACKGROUND The recently introduced ultrasonic flow ratio(UFR),is a novel fast computational method to derive fractional flow reserve(FFR)from intravascular ultrasound(IVUS)*** the present study,we evaluate the diagnostic performance of UFR in patients with intermediate left main(LM)*** This is a prospective,single center study enrolling consecutive patients with presence of intermediated LM lesions(diameter stenosis of 30%-80%by visual estimation)underwent IVUS and FFR *** independent core laboratory assessed offline UFR and IVUS-derived minimal lumen area(MLA)in a blinded *** Both UFR and FFR were successfully achieved in 41 LM patients(mean age,62.0±9.9 years,46.3%diabetes).An acceptable correlation between UFR and FFR was identified(r=0.688,P50%(AUC=0.66,Pdiseases,UFR was proved to be associated with acceptable correlation and high accuracy with pressure wire-based FFR as standard *** present study supports the use of UFR for functional evaluation of intermediate LM stenosis.

关键词： stenosis flow fractional

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Applications of artificial intelligence to lipid nanoparticle delivery

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Particuology 2024年第7期90卷 88-97页

作者： Ye Yuan Yuqi Wu Jiabei Cheng Kaiyuan Yang Yilin Xia Hongguang Wu Xiaoyong Pan institute of Image Processing and Pattern Recognition Shanghai Jiao Tong UniversityKey Laboratory of System Control and Information ProcessingMinistry of Education of ChinaChina Songjiang Research institute Songjiang District Central HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Lipid nanoparticles(LNPs)are nanocarriers composed of four lipid components and can be used for gene therapy,protein replacement,and vaccine ***,LNPs also face several challenges,such as toxicity,immune activation,and low delivery *** overcome these challenges,artificial intelligence can be used to optimize the design and formulation of LNPs,as well as to predict their properties and ***,antibody-targeted conjugation can be used to enhance the specificity and selectivity of LNPs by attaching an antibody that recognizes a specific antigen on the cell surface to LNPs.

关键词： Artificial intelligence Lipid nanoparticles Antibody Targeted conjugation

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The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development

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Journal of Molecular Cell Biology 2024年第1期16卷 43-53页

作者： Xiaozhen Song Ruixing Hu Yi Chen Man Xiao Hong Zhang Shengnan Wu Qing Lu Molecular Diagnostic laboratory Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200040China Bio-X institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China laboratory of Development and diseases and State Key laboratory for Medical Genomics Shanghai Institute of HematologyRuĳin HospitalShanghai JiaoTong University School of MedicineShanghai 200025China

TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways,contributing to immune responses,tumor progression,and embryonic *** mutations within the coiled-coil(CC)domain and WD40 repeat domain of TRAF7 could cause brain tumors,while germline pathogenic mutations contribute to severe developmental ***,the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains *** this study,we employed zebrafish as an in vivo model ***7 knock down caused defects in zebrafish embryonic *** determined the crystal structure of TRAF7 CC domain at 3.3Åresolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic ***,disease-causing mutations in TRAF7 CC region could impair the trimer formation,consequently impacting early embryonic development of ***,our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.

关键词： TRAF7 coiled-coil domain crystal structure trimerization embryonic development

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Prediction of the short-term efficacy of anti-VEGF therapy for neovascular age-related macular degeneration using optical coherence tomography angiography

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Eye and Vision 2024年第3期10卷 21-30页

作者： Huixun Jia Bing Lu Zhi Zhao Yang Yu Fenghua Wang Minwen Zhou Xiaodong Sun Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of Medicine100 Hai Ning RoadShanghai200080People’s Republic of China shanghai Key laboratory of Ocular Fundus diseases ShanghaiChina National Clinical Research Center for Eye diseases ShanghaiChina shanghai Engineering Center for Visual Science and Photomedicine ShanghaiChina shanghai Engineering Center for Precise Diagnosis and Treatment of Eye diseases ShanghaiChina Clinical Research institute Shanghai Jiao Tong University School of MedicineShanghaiChina

Background To evaluate whether the specific choroidal neovascularization(CNV)characteristics measured using optical coherence tomography angiography(OCTA)can predict the 6-month prognosis of neovascular age-related macular degeneration(nAMD)after anti-vascular endothelial growth factor(anti-VEGF)*** Patients with type 1,type 2,or mixed-type neovascularization(NV)were prospectively *** underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept(0.5 mg)and were switched to a pro re nata(PRN)treatment *** images were evaluated for eyes that underwent follow-up assessments for more than 6 *** lesions were manually segmented,and the CNV area,vessel area,greatest vascular caliber(GVC),and greatest linear dimension(GLD)were compared between responders and *** masked graders independently measured the above-mentioned parameters using OCTA,and consistency was assessed using the intraclass correlation coefficient(ICC)*** logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area,GLD,and GVC on the 6-month response to anti-VEGF *** Among the 60 eyes of 60 patients with nAMD,39 were responders and 21 were *** proportion of CNV types was significantly different between responders and non-responders(P=0.009).Patients with type 2 or mixed NV seemed more likely to respond to the treatment(28.2%vs.0.0%,and 30.8%vs.23.8%,respectively).The change in GVC showed a significant difference between responders(−4.98±17.17μm)and non-responders(11.01±14.10μm)after three monthly intravitreal anti-VEGF *** logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC,injection number,and CNV type(adjusted OR=1.083;P=0.008).Conclusions Type 2 and mixed-type NV were significantly associated with a better response to anti-VEGF *** i

关键词： Age-related macular degeneration Choroidal neovascularization Optical coherence tomography angiography Anti-VEGF

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