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Candidemia chronicles:Retrospective analysis of candidemia epidemiology,species distribution,and antifungal susceptibility patterns in Bahrain

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World Journal of Virology 2024年第4期13卷 74-88页

作者： Nermin Kamal Saeed Safiya Almusawi Mohammed Al-Beltagi Medical Microbiology Section Department of PathologySalmaniya Medical ComplexGovernmental HospitalsManama 12Bahrain Department of Medical Microbiology Royal College of Surgeons in Ireland-BahrainBusaiteen 15503Bahrain Department of pediatric Faculty of MedicineTanta UniversityTanta 31511Egypt Department of pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain

BACKGROUND Invasive fungal infections,particularly candidemia,pose significant clinical challenges *** local epidemiology,species distribution,and antifungal susceptibility patterns is crucial for effective management despite regional *** To investigate the epidemiology,species distribution,antifungal susceptibility patterns,and associated risk factors of candidemia among patients in Bahrain from 2021 to *** This retrospective study analyzed demographic data,Candida species distribution,antifungal susceptibility profiles,and risk factors among candidemia patients treated at a tertiary care hospital in Bahrain over three *** was collected from medical records and analyzed using descriptive *** A total of 430 candidemia cases were *** mean age of patients was 65.7 years,with a mortality rate of 85.5%.Candida albicans(***)was the most common species,followed by Candida parapsilosis,Candida tropicalis(***),and emerging multidrug-resistant Candida auris(***).Antifungal susceptibility varied across species,with declining susceptibility to azoles observed,particularly among *** and *** risk factors included central venous catheters,broad-spectrum antibiotics,and surgical *** This study highlights the substantial burden of candidemia among older adults in Bahrain,characterized by diverse Candida *** also concerns levels of antifungal resistance,notably in *** findings underscore the importance of local epidemiological surveillance and tailored treatment strategies to improve outcomes and mitigate the spread of multidrug-resistant Candida *** research should focus on molecular resistance mechanisms and optimizing therapeutic approaches to address this growing public health concern.

关键词： Candidemia Fungal infections Antifungal resistance Epidemiology Risk factors Antifungal susceptibility Bahrain

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Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

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World Journal of Psychiatry 2024年第1期14卷 88-101页

作者： Zhong-Yu Huang Zi-Pan Lyu Hong-Gui Li Hua-Zhi You Xiang-Na Yang Cai-Hui Cha center for Medical Research on Innovation and Translation Institute of Clinical MedicineGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510000Guangdong ProvinceChina School of Biological Sciences Nanyang Technological UniversityNanyang Ave 639798Singapore Department of pediatrics First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Nutrition First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of pediatric Traditional Chinese Medicine Clinic Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina Department of Psychology Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely *** presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for *** To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental *** A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy *** in plasma were set as exposures with ASD as the main *** causal relationships were estimated using the inverse variant weight(IVW)*** also performed leave-one-out sensitivity tests to validate the robustness of the *** on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and *** Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and *** Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and *** findings offer perspectives for the discovery of diagnos

关键词： Des-Arg(9)bradykinin Autism spectrum disorder Mendelian randomization Metabolite Enrichment analysis

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Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1166-1186页

作者： Shanshan Rao Zehui He Zun Wang Hao Yin Xiongke Hu Yijuan Tan Tengfei Wan Hao Zhu Yi Luo Xin Wang Hongming Li Zhenxing Wang Xinyue Hu Chungu Hong Yiyi Wang Mingjie Luo Wei Du Yuxuan Qian Siyuan Tang Hui Xie Chunyuan Chen Department of Orthopedics Movement System Injury and Repair Research CenterXiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Angmedicine Changsha 410008China Xiangya School of Nursing Central South UniversityChangsha 410013China Department of pediatric Orthopedics Hunan Children’s HospitalUniversity of South ChinaChangsha 410007China Department of Respiratory Medicine Xiangya HospitalCentral South UniversityChangsha 410008China School of Nursing Xinjiang Medical UniversityUrumqiXinjiang 830000China Department of Rehabilitation Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China

Aging increases the risks of various diseases and the vulnerability to *** senescence is a hallmark of aging that contributes greatly to aging and aging-related *** study demonstrates that extracellular vesicles from human urine-derived stem cells(USC-EVs)efficiently inhibit cellular senescence in vitro and in *** intravenous injection of USC-EVs improves cognitive function,increases physical fitness and bone quality,and alleviates aging-related structural changes in different organs of senescence-accelerated mice and natural aging *** anti-aging effects of USC-EVs are not obviously affected by the USC donors’ages,genders,or health *** analysis reveals that USC-EVs are enriched with plasminogen activator urokinase(PLAU)and tissue inhibitor of metalloproteinases 1(TIMP1).These two proteins contribute importantly to the anti-senescent effects of USC-EVs associated with the inhibition of matrix metalloproteinases,cyclin-dependent kinase inhibitor 2A(P16INK4a),and cyclin-dependent kinase inhibitor 1A(P21cip1).These findings suggest a great potential of autologous USC-EVs as a promising anti-aging agent by transferring PLAU and TIMP1 proteins.

关键词： Extracellular vesicles Urine-derived stem cells Cellular senescence Anti-aging PLAU TIMP1 Senescence-accelerated mice Natural aging mice

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Clinical and molecular characterization of 10 Chinese children with congenital adrenal hyperplasia due to 11beta‑hydroxylase deficiency

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World Journal of pediatrics 2024年第4期20卷 422-433页

作者： Wen‑Li Lu Xiao‑Yu Ma Jiao Zhang Jun‑Qi Wang Ting‑Ting Zhang Lei Ye Yuan Xiao Zhi‑Ya Dong Wei Wang Shou‑Yue Sun Chuan‑Yin Li Rong‑Gui Hu Guang Ning Li‑Dan Zhang Department of pediatrics Ruijin HospitalShanghai Jiao Tong University School of MedicineNo.197Ruijin 2nd RdHuangpu DistrictShanghai 200025China Department of pediatric Genetic and Metabolic Endocrinology West China Second University HospitalSichuan UniversityNo.20Section 3Renmin South RoadSichuan 610041China Department of Endocrine and Metabolic Diseases Shanghai Clinical Center for Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Cancer center School of MedicineShanghai Tenth People’s HospitalTongji UniversityYanchang Zhong Lu 301St RdJing’an DistrictShanghai 200031China

Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase *** this study,we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature,which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal *** Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively *** examined the effects of gene mutations on protease activity and constructed threedimensional structure prediction models of *** We describe 10 patients with 11beta-hydroxylase gene mutations(n=5,46,XY;n=5,46,XX),with 10 novel mutations were *** patients received treatment at an early stage,with an average age of 2.08±1.66 years,whereas male patients received treatment significantly later,at an average age of 9.77±3.62 *** most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C>*** mutations lead to spatial conformational changes that affect protein *** Our study found that there was no significant correlation between each specific mutation and the severity of clinical *** patients with the same gene pathogenic variant may have mild or severe clinical *** correlation between genotype and phenotype needs further ***-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.

关键词： 11β-hydroxylase deficiency CYP11B1 Enzymatic activity Phenotype-genotype correlation Threedimensional protein simulations

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Transcriptomic Landscape Analysis Reveals a Persistent DNA Damage Response in Metabolic Dysfunction-associated Steatohepatitis Post-dietary Intervention

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 765-779页

作者： Zi-Yuan Zou Tian-Yi Ren Jia-Qi Li Ting-Ying Jiao Meng-Yu Wang Lei-Jie Huang Shuang-Zhe Lin Yuan-Yang Wang Xiao-Zhen Guo Ye-Yu Song Rui-Xu Yang Cen Xie Jian-Gao Fan center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina University of Chinese Academy of Sciences BeijingChina Human Phenome Institute School of Life SciencesFudan UniversityShanghaiChina Department of Gastroenterology Ningbo No.2 HospitalNingboZhejiangChina Shanghai Key Laboratory of pediatric Gastroenterology and Nutrition ShanghaiChina

Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)and its more advanced form,metabolic dysfunction-associated steatohepatitis,have emerged as the most prevalent liver diseases ***,lifestyle modification is the foremost guidelinerecommended management strategy for ***,it remains unclear which detrimental signals persist in MASLD even after disease ***,we aimed to examine the persistent changes in liver transcriptomic profiles following this ***:Male C57BL/6J mice were divided into three groups:Western diet(WD)feeding,chow diet(CD)feeding,or diet reversal from WD to *** 16 weeks of feeding,RNA sequencing was performed on the mice’s livers to identify persistent alterations characteristic of ***,RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were ***:WD-induced MASLD triggered persistent activation of the DNA damage response(DDR)and its primary transcription factor,P53,long after the resolution of the hepatic phenotype through dietary *** levels of P53 might promote apoptosis,thereby exacerbating metabolic dysfunction-associated steatohepatitis,as they strongly correlated with hepatocyte ballooning,an indicator of apoptosis ***,P53 knockout in mice led to downregulated expression of apoptosis signaling in the ***,P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease(AEN).Consistently,P53,AEN,and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary ***:The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to *** findings provide new insights into the mechanisms of MASLD relapse,highlighting DDR signaling as a promising target to prevent MASLD recu

关键词： Apoptosis DNA Damage Metabolic dysfunction-associated steatotic liver disease RNA-Seq Tumor suppressor protein P53 Western Diets

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Respiratory Viruses and Mycoplasma Pneumoniae Surveillance Among Hospitalized Children with Acute Respiratory Infections—Wuhan City,Hubei Province,China,September-November 2023

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China CDC weekly 2024年第8期6卷 139-142页

作者： Ying Li Yi Yan Jiaming Huang Yue Shi Hui Du Chao Xiong Kai Chen Di Liu Xiaoxia Lu Computational Virology Group Center for Bacteria and Viruses Resources and BioinformationWuhan Institute of VirologyChinese Academy of SciencesWuhan CityHubei ProvinceChina Department of Respiratory Medicine Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan CityHubei ProvinceChina pediatric Respiratory Disease Laboratory Institute of Maternal and Child HealthWuhan Children's HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan CityHubei ProvinceChina University of Chinese Academy of Sciences BeijingChina CAS Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan CityHubei ProvinceChina Data center Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan CityHubei ProvinceChina

Summary What is already known about this topic?Acute respiratory infections(ARIs)are a significant contributor to illness and death in *** has been a notable rise in the occurrence of ARIs and the associated pathogens in China,which has garnered worldwide *** is added by this report?This study conducted a retrospective analysis of the clinical characteristics of children with ARIs in Wuhan City from September to November 2023.

关键词： November Wuhan Hubei

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Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children

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World Journal of pediatrics 2024年第9期20卷 901-914页

作者： Ying-Shuo Wang Yun-Lian Zhou Guan-Nan Bai Shu-Xian Li Dan Xu Li-Na Chen Xing Chen Xiao-Yan Dong Hong-Min Fu Zhou Fu Chuang-Li Hao Jian-Guo Hong En-Mei Liu Han-Min Liu Xiao-Xia Lu Zheng-Xiu Luo Lan-Fang Tang Man Tian Yong Yin Xiao-Bo Zhang Jian-Hua Zhang Hai-Lin Zhang De-Yu Zhao Shun-Ying Zhao Guo-Hong Zhu Ying-Xue Zou Quan Lu Yuan-Yuan Zhang Zhi-Min Chen Department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Child Health Care Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of pediatric Pulmonology and Immunology West China Second University HospitalSichuan UniversityChengdu 610041China Department of pediatrics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China Department of Pulmonology Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Department of Pulmonary and Critical Care Medicine Kunming Children’s HospitalKunming 650034China Department of Respiratory Medicine Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Pulmonology Children’s Hospital of Soochow UniversitySuzhou 215003China Department of pediatrics Shanghai General Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200080China Department of Respiratory Medicine Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430015China Department of Respiratory Medicine Children’s Hospital of Nanjing Medical UniversityNanjing 210008China Department of Respiratory Medicine Shanghai Children’s Medical CenterShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Respiratory Medicine Children’s Hospital of Fudan UniversityShanghai 201102China Department of pediatric Pulmonology Xinhua HospitalShanghai Jiaotong University School of MedicineShanghai 201102China Department of pediatric Respiratory Medicine The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027China National Clinical Research center for Respiratory Diseases Beijing Children’s HospitalCapital Medical UniversityBeijing 100045China Departmen

Background Mycoplasma pneumoniae(***)is a significant contributor to community-acquired pneumonia among *** 1968,when a strain of *** resistant to macrolide antibiotics was initially reported in Japan,macrolide-resistant ***(MRMP)has been documented in many countries worldwide,with varying incidence *** infections lead to a poor response to macrolide antibiotics,frequently resulting in prolonged fever,extended antibiotic treatment,increased hospitalization,intensive care unit admissions,and a significantly higher proportion of patients receiving glucocorticoids or second-line *** 2000,the global incidence of MRMP has gradually increased,especially in East Asia,which has posed a serious challenge to the treatment of *** infections in children and attracted widespread attention from ***,there is still no global consensus on the diagnosis and treatment of MRMP in *** We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world’s first consensus on the diagnosis and treatment of pediatric MRMP pneumonia,based on evidence *** evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,CNKI,Medline,and the Cochrane *** used variations in terms for“macrolide-resistant”,“Mycoplasma pneumoniae”,“MP”,“***”,“pneumonia”,“MRMP”,“lower respiratory tract infection”,“Mycoplasma pneumoniae infection”,“children”,and“pediatric”.Results Epidemiology,pathogenesis,clinical manifestations,early identification,laboratory examination,principles of antibiotic use,application of glucocorticoids and intravenous immunoglobulin,and precautions for bronchoscopy are *** and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory *** the resistance rate to mac

关键词： Child Macrolide-resistant Mycoplasma pneumoniae Recommendation Diagnosis Treatment

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Selenoprotein-p and insulin resistance in children and adolescents with obesity

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World Journal of Clinical pediatrics 2024年第3期13卷 40-52页

作者： Amany Elbarky Kholoud Gamal Ismail Yousef Fouad Yousef Rasha Mohamed Gamal Elshafiey Radwa Mahmoud Elsharaby Asmaa El-Kaffas Mohammed Al-Beltagi Gastroenterology and Clinical Nutrition Unit Pediatric DepartmentFaculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of pediatric Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of Clinical Pathology Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of Paediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671ManamaBahrain

BACKGROUND Insulin resistance and obesity present significant challenges in pediatric *** P1(SEPP1)serves as a biomarker for assessing selenium levels in the *** its association with metabolic syndrome is established in adults,its relevance in children remains *** To ascertain SEPP1 blood levels in children and adolescents diagnosed with obesity and to assess its correlation with insulin resistance and adiposity *** 170 children participated in this study,including 85 diagnosed with obesity and an equal number of healthy counterparts matched for age and *** participant underwent a comprehensive medical evaluation,encompassing a detailed medical history,clinical examination,and anthropometric measurements like waist circumference and waist-to-height ***,routine blood tests were conducted,including serum SEPP1,visceral adiposity index(VAI),and Homeostatic Model Assessment of Insulin Resistance(HOMA-IR)*** Our findings revealed significantly lower serum SEPP1 levels in children with obesity compared to their healthy ***,notable negative correlations were observed between serum SEPP1 levels and body mass index,VAI,and *** The study suggests that SEPP1 could serve as a valuable predictor for insulin resistance among children and adolescents diagnosed with *** highlights the potential utility of SEPP1 in pediatric metabolic health assessment and warrants further investigation.

关键词： Obesity Childhood obesity Selenium status Selenoprotien P1 Insulin resistance

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Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause Kathrin Landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr Angela Schulz Martina Strnadová Akhil Velluva Heba Zabri Torsten Schöneberg Doreen Thor Simone Prömel Rudolf Schönheimer Institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German center for Diabetes Research(DZD e.V.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany center for pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for Metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany Department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of Medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

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PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

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Zoological Research 2024年第3期45卷 535-550页

作者： Laidong Yu Fangfang Zeng Mengshu Fan Kexuan Zhang Jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang Jialong Yuan Xinxin Pang Yan Huang Yangzhou Zhang Jia-Da Li Zhuohua Zhang Zhonghua Hu Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China center for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China National Clinical Research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Provincial Clinical Research center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Key Laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China MOE Key Lab of Rare pediatric Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China Department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain *** abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric *** 17(PCDH17)is associated with major mood disorders,including bipolar disorder and ***,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain *** this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory *** overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in ***,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)***,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine ***,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

关键词： Synapse development Dendritic spine Mood disorder Actin cytoskeleton Animal behavior

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