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ccdc141 is required for left-right axis development by regulating cilia formation in the Kupffer's vesicle of zebrafish

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Journal of Genetics and Genomics 2024年第9期51卷 934-946页

作者： Pengcheng Wang Wenxiang Shi Sijie Liu Yunjing Shi Xuechao Jiang Fen Li Sun Chen Kun Sun Rang Xu Department of Pediatric Cardiology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of Cardiovascular Medicine Heart Failure CenterRuijin HospitalRuijin Hospital Lu Wan BranchShanghai Jiao Tong University School of MedicineShanghai 200025China Scientific Research center Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of Pediatric Cardiology Shanghai Children's Medical CenterShanghai Jiao Tong University School of MedicineShanghai 200127China

Laterality is a crucial physiological process intricately linked to the cilium-centrosome complex during embryo *** in the process can result in severe organ ***-coil domain containing 141(CCDC141)has been previously known as a centrosome-related gene,but its role in left-right(LR)asymmetry has not been *** this study,we utilize the zebrafish model and human exome analysis to elucidate the function of ccdc141 in laterality *** knockdown of ccdc141 in zebrafish disrupts early LR signaling pathways,cilia function,and Kupffer's vesicle *** ccdc141-knockdown embryos exhibiting aberrant LR patterns,ccdc141-null mutants show no apparent abnormality,suggesting a genetic compensation response *** parallel,we observe a marked reduction inα-tubulin acetylation levels in the ccdc141 *** treatment with histone deacetylase(HDAC)inhibitors,particularly the HDAC6 inhibitor,rescues the ccdc141 crispant ***,exome analysis of 70 patients with laterality defects reveals an increased burden of CCDC141 mutations,with in-vivo studies verifying the pathogenicity of the patient mutation *** findings highlight the critical role of ccdc141 in ciliogenesis and demonstrate that CCDC141 mutations lead to abnormal LR patterns,identifying it as a candidate gene for laterality defects.

关键词： Left-right axis Cilia WES Laterality defects Zebrafish CCDC141

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Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

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Neural Regeneration Research 2024年第3期19卷 536-541页

作者： Georges Jourdi Samuel Fleury Imane Boukhatem Marie Lordkipanidzé Research center Montreal Heart InstituteMontrealQCCanada Faculty of Pharmacy Universitéde MontréalMontrealQCCanada UniversitéParis Cité INSERMInnovative Therapies in HaemostasisParisFrance Service d’Hématologie Biologique AP-HPHôpital LariboisièreParisFrance

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical *** p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and *** cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and *** is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic *** p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open *** this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative *** also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis biomarker dementia diabetic neuropathy nerve growth factor receptor(NGFR) neurodegeneration p75^(NTR) schizophrenia

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Interaction between ozone and paternal smoking on fetal congenital heart defects among pregnant women at high risk a multicenter maternal-fetal medicine study

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World Journal of Pediatrics 2024年第6期20卷 621-632页

作者： Huan Wang Yan-Ping Ruan Sheng Ma Ya-Qi Wang Xiao-Yu Wan Yi-Hua He Jing Li Zhi-Yong Zou Institute of Child and Adolescent Health School of Public HealthNational Health Commission Key Laboratory of Reproductive HealthPeking UniversityNo.38 Xueyuan RdHaidian DistrictBeijing 100191China Echocardiography Medical center Beijing Anzhen Hospital.Capital Medical UniversityMaternal-Fetal Medicine center in Fetal Heart DiseaseBeijing Anzhen HospitalNo.2 Anzhen RdChaoyang DistrictBeijing 100029China

Background Evidence remains limited on the association between maternal ozone(O,)exposure and congenital heart defects(CHDs)in offspring,and few studies have investigated the interaction and modification of paternal smoking on this *** Using a sample including pregnant women at high risk of fetal CHD(with metabolic disease,first-trimester viral infection,family history of CHD,etc.)from a maternal-fetal medicine study covering 1313 referral hospitals in China during 2013-2021,we examined the associations between maternal O_(3)exposure during 3-8 weeks of gestational age and fetal CHD in offspring and investigated the interaction and modification of paternal smoking on this *** was diagnosed by fetal echocardiograms,maximum daily 8-hour average O,exposure data at a 10 km×10 km spatial resolution came from the Tracking Air Pollution in China dataset,and paternal smoking was collected using *** regression models were used to estimate adjusted odds ratios(ORs)and 95%confidence intervals(CIs).Results Among 27,834 pregnant women at high risk of fetal CHD,17.4%of fetuses were diagnosed with *** 10μg/m^(3)increase in maternal O_(3)exposure was associated with a 17%increased risk of CHD in offspring(OR=1.17,95%CI=1.14-1.20).Compared with paternal nonsmoking and maternal low O_(3)exposure,the ORs(95%CI)of CHD for smoking and low O_(3)exposure,nonsmoking and high O_(3)exposure,and smoking and high O_(3)exposure were 1.25(1.08-1.45),1.81(1.56-2.08),and 2.23(1.84-2.71),*** smoking cessation seemingly mitigated the increased risk of *** Maternal O_(3)exposure and paternal smoking were interactively associated with an increased risk of fetal CHD in offspring,which calls for effective measures to decrease maternal exposure to O_(3)pollution and secondhand smoke for CHDprevention.

关键词： Congenital heart defects Fetal heart development Ozone exposure Tobacco smoking

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New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis

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World Journal of Clinical Cases 2024年第6期12卷 1050-1062页

作者： Tsvetelina Velikova Boris Krastev Milena Gulinac Miroslav Zashev Vasko Graklanov Milena Peruhova Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Medical center Nadezhda Medical Center NadezhdaSofia 1407Bulgaria General and Clinical Pathology Medical University of PlovdivPlovdiv 4002Bulgaria Department of General Surgery University Hospital“Heart and Brain”Burgas 8000Bulgaria First Department of Internal Diseases Medical University of PlovdivPlovdiv 4000Bulgaria Department of Hematology University Hospital“St.George”Plovdiv 4000Bulgaria Division of Gastroenterology University Hospital“Heart and Brain”Burgas 1000Bulgaria

Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 *** this revolutionary immunotherapy gains prominence in cancer treatment,understanding,diagnosing,and effectively managing IMC becomes *** represents a unique challenge due to its immune-mediated nature and potential for severe ***,a precise picture of IMC pathophysiology is currently ***,we aimed to summarize the existing data while acknowledging the need for further *** comprehensive review explores the mechanisms underlying ICIs,gastrointestinal adverse effects,and,in particular,IMC’s incidence,prevalence,and *** review also emphasizes the importance of recognizing IMC’s distinct clinical and histopathological features to differentiate it from other forms of ***,this paper highlights the urgentneed for evolving diagnostic methods,therapeutic strategies,and a multidisciplinary approach to effectively manage IMC.

关键词： Immune-checkpoint inhibitors Immune-checkpoint inhibitor-mediated colitis Inhibitor-mediated colitis management Immunotherapy-associated colitis Checkpoint inhibitor-induced colitis Gastrointestinal adverse effects Checkpoint inhibitor toxicity Inhibitor-mediated colitis therapy

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An unexpected cellular fountain of youth:platelets provide factors rejuvenating brain functions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 16-18页

作者： Harald F.Langer Department of Cardiology AngiologyHaemostaseology and Medical Intensive CareUniversity Medical Centre MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany German Centre for Cardiovascular Research(DZHK) Partner Site Heidelberg/MannheimMannheimGermany European center for Angioscience Medical Faculty MannheimHeidelberg UniversityMannheimGermany Cardiovascular systems biology Medical Clinic IUniversity Heart Center LübeckLübeckGermany

In a recent manuscript published in Nature,Schroer et *** that platelets and in particular platelet derived PF-4(CXCL4)are a novel factor,which can rejuvenate the mammalian neuronal system.1 These findings have the potential to trigger an entire new field of research opening new platelet-derived candidate effector molecules for supporting regeneration.

关键词： supporting platelets finding

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Advancing CRISPR base editing technology through innovative strategies and ideas

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Science China Life Sciences 2024年

作者： Xiongwei Fan Yang Lei Liren Wang Xiushan Wu Dali Li The center for heart Development College of Life Science Hunan Normal University Shanghai Frontiers Science Research Base of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Guangdong Provincial Key Laboratory of Pathogenesis Targeted Prevention and Treatment of Heart Disease

The innovation of CRISPR/Cas gene editing technology has developed rapidly in recent years. It is widely used in the fields of disease animal model construction, biological breeding, disease diagnosis and screening, gene therapy, cell localization, cell lineage tracking, synthetic biology, information storage, etc. However, developing idealized editors in various fields is still a goal for future development. This article focuses on the development and innovation of non-DSB editors BE and PE in the platform-based CRISPR system. It first explains the application of ideas for improvement such as “substitution”, “combination”, “adaptation”, and “adjustment” in BE and PE development and then catalogues the ingenious inversions and leaps of thought reflected in the innovations made to CRISPR technology. It will then elaborate on the efforts currently being made to develop small editors to solve the problem of AAV overload and summarize the current application status of editors for in vivo gene modification using AAV as a delivery system. Finally, it summarizes the inspiration brought by CRISPR/Cas innovation and assesses future prospects for development of an idealized editor.

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Impact of COVID-19 pandemic on cardiovascular health in sedentary and athletes:Consensus,uncertainties,and ways for mitigation

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Sports Medicine and Health Science 2024年第3期6卷 205-208页

作者： John C.Quindry Lei Xi School of Integrative Physiology and Athletic Training University of MontanaMissoulaMT59812USA Pauley heart center Department of Internal MedicineSchool of MedicineVirginia Commonwealth UniversityRichmondVA23298-0204USA

More than 4 years has elapsed since the World Health Organization(WHO)ofﬁcially announced the coronavirus disease 2019(COVID-19)as a pandemic outbreak in March 11,*** the ongoing investigations and political debates upon the origin,exacerbation,resurgence,andﬁnal control of COVID-19,medical and scientiﬁc consensus indicates that the now endemic COVID-19 virus is one of the worst public health crises in our *** every person on earth has been directly or indirectly impacted by the adverse effects of the highly contagious viral pathogen-SARS-CoV-2(severe acute respiratory syndrome coronavirus 2).Indeed,the population reach of the COVID-19 infection includes governmental response measures(e.g.,lockdowns and social distancing,mandates for masks and face coverings,vaccines,etc.)that have restricted entrenched societal routines,personal mobility,and ***,the host of health problems linked to this viral infection linger to this day,with selective groups of people experiencing a higher risk for untoward medical outcomes and/or elevated levels of vulnerability to the post-acute sequelae of COVID-19(***-COVID).For example,a 2021 study by Logue et *** initial evidence that 10%–30%of individuals in United States may experience prolonged symptoms following SARS-CoV-2 infection,including cardiovascular abnormalities.1 Similarly,a 2021 retrospective cohort study in England suggest that the incidence of major adverse cardiovascular events(*** failure,myocardial infarction,ischemic stroke.

关键词： cardiovascular routine Impact

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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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Myocarditis–A silent killer in athletes:Comparative analysis on the evidence before and after COVID-19 pandemic

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Sports Medicine and Health Science 2024年第3期6卷 232-239页

作者： Jonathan Van Name Kainuo Wu Lei Xi Virginia Commonwealth University School of Medicine(M.D.Class 2024) RichmondVA23298USA Pauley heart center Division of CardiologyDepartment of Internal MedicineVirginia Commonwealth UniversityRichmondVA23298-0204USA

Myocarditis is a rare cardiomyocyte inﬂammatory process,typically caused by viruses,with potentially devastating cardiac sequalae in both competitive athletes and in the general *** into myocarditis prevalence in the Coronavirus disease 2019(COVID-19)era suggests that infection with Severe acute respiratory syndrome coronavirus(SARS-CoV-2)is an independent risk factor for myocarditis,which is conﬁrmed mainly through cardiovascular magnetic resonance *** studies indicated that athletes have a decreased risk of myocarditis after recent COVID-19 infection compared to the general ***,given the unique nature of competitive athletics with their frequent participation in high-intensity exercise,athletes possess distinct factors of susceptibility for the development of myocarditis and its subsequent severe cardiac complications(e.g.,sudden cardiac death,fulminant heart failure,etc.).Under this context,this review focuses on comparing myocarditis in athletes versus non-athletes,owing special attention to the distinct clinical presentations and outcomes of myocarditis caused by different viral pathogens such as cytomegalovirus,Epstein-Barr virus,human herpesvirus-6,human immunodeﬁciency virus,and Parvovirus B19,both before and after the COVID-19 pandemic,as compared with *** illustrating distinct clinical presentations and outcomes of myocarditis in athletes versus non-athletes,we also highlight the critical importance of early detection,vigilant monitoring,and effective management of viral and non-viral myocarditis in athletes and the necessity for further optimization of the return-to-play guidelines for athletes in the COVID-19 era,in order to minimize the risks for the rare but devastating cardiac fatality.

关键词： COVID-19 Myocarditis Cardiovascular symptomatology Athlete susceptibility Return-to-play Sudden cardiac death Viral pathogens High-intensity exercise

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Cardiovascular abnormalities of long-COVID syndrome:Pathogenic basis and potential strategy for treatment and rehabilitation

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Sports Medicine and Health Science 2024年第3期6卷 221-231页

作者： Kainuo Wu Jonathan Van Name Lei Xi Virginia Commonwealth University School of Medicine(M.D.Class 2024) RichmondVA23298USA Pauley heart center Division of CardiologyDepartment of Internal MedicineVirginia Commonwealth UniversityRichmondVA23298-0204USA

Cardiac injury and sustained cardiovascular abnormalities in long-COVID syndrome,***-acute sequelae of coronavirus disease 2019(COVID-19)have emerged as a debilitating health burden that has posed challenges for management of pre-existing cardiovascular conditions and other associated chronic comorbidities in the most vulnerable group of patients recovered from acute COVID-19.A clear and evidence-based guideline for treating cardiac issues of long-COVID syndrome is still *** this review,we have summarized the common cardiac symptoms reported in the months after acute COVID-19 illness and further evaluated the possible pathogenic factors underlying the pathophysiology process of *** mechanistic understanding of how Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)damages the heart and vasculatures is critical in developing targeted therapy and preventive measures for limiting the viral *** the currently available therapeutic interventions,a considerable portion of patients recovered from severe COVID-19 have reported a reduced functional reserve due to ***,a rigorous and comprehensive cardiac rehabilitation program with individualized exercise protocols would be instrumental for the patients with long-COVID to regain the physicalﬁtness levels comparable to their pre-illness baseline.

关键词： Long-COVID syndrome Cardiac rehabilitation Exercise intolerance Inﬂammation Hypoxia inducible factor 1 SARS-CoV-2 tropism

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