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The Role of KDM2A and H3K36me2 Demethylation in Modulating MAPK Signaling During Neurodevelopment

Neuroscience Bulletin 2024年第8期40卷 1076-1092页

作者： Zongyao Ren Haiyan Tang Wendiao Zhang Minghui Guo Jingjie Cui Hua Wang Bin Xie Jing Yu Yonghao Chen Ming Zhang Cong Han Tianyao Chu Qiuman Liang Shunan Zhao Yingjie Huang Xuelian He Kefu Liu Chunyu Liu Chao Chen center for medical Genetics&Hunan Key Laboratory of medical Genetics School of Life Sciencesand Department of PsychiatryThe Second Xiangya HospitalCentral South UniversityChangsha 410028China National Clinical Research center on Mental Disorders The Second Xiangya HospitalCentral South UniversityChangsha 410028China National Clinical Research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410011China Furong Laboratory Changsha 410000China Department of Psychiatry SUNY Upstate Medical UniversitySyracuseNY 13210USA Precision medical center Wuhan Children's Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430014China Department of medical Genetics Hunan Children's HospitalChangsha 410007China

Intellectual disability(ID)is a condition characterized by cognitive impairment and difficulties in adaptive *** our research,we identified two de novo mutations(c.955C>T and c.732C>A)at the KDM2A locus in individuals with varying degrees of *** addition,by using the Gene4Denovo database,we discovered five additional cases of de novo mutations in *** mutations we identified significantly decreased the expression of the KDM2A *** investigate the role of KDM2A in neural development,we used both 2D neural stem cell models and 3D cerebral *** findings demonstrated that the reduced expression of KDM2A impairs the proliferation of neural progenitor cells(NPCs),increases apoptosis,induces premature neuronal differentiation,and affects synapse *** ChIP-Seq analysis,we found that KDM2A exhibited binding to the transcription start site regions of genes involved in *** addition,the knockdown of KDM2A hindered H3K36me2 binding to the downstream regulatory elements of *** integrating ChIP-Seq and RNA-Seq data,we made a significant discovery of the core genes'remarkable enrichment in the MAPK signaling ***,this enrichment was specifically linked to the p38 MAPK ***,disease enrichment analysis linked the differentially-expressed genes identified from RNA-Seq of NPCs and cerebral organoids to neurodevelopmental disorders such as ID,autism spectrum disorder,and ***,our findings suggest that KDM2A plays a crucial role in regulating the H3K36me2 modification of downstream genes,thereby modulating the MAPK signaling pathway and potentially impacting early brain development.

关键词： Intellectual disability KDM2A Neurodevelopmental disorder Cerebral organoids

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Effect of information-motivation-behavioral skills model based perioperative nursing on pain in patients with gallstones

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2232-2241页

作者： Li Ma Ying Yu Bin-Juan Zhao Yan-Nan Yu Yu Li Department of Nursing Xi’an International Medical Center HospitalXi’an 710100Shaanxi ProvinceChina Department of Hepatobiliary Pancreatic and Spleen SurgeryXi’an International Medical Center HospitalXi’an 710100Shaanxi ProvinceChina

BACKGROUND The incidence of cholecystolithiasis is on the *** of information,motivation,and behavioral skills can play a positive role in promoting changes in individual health ***,reports on the effects of information-motivationbehavioral(IMB)skills model based high-quality nursing as a perioperative nursing intervention for patients with gallstones are *** To explore the application of IMB skills model based high-quality nursing in patients with *** Two hundred and sixteen patients with cholecystolithiasis treated at our hospital from January 2022 to January 2023 were enrolled and divided into a control,highquality,and combined nursing groups,with 72 patients in each *** control,high-quality,and combination groups received conventional,high-quality,and IMB skills model based perioperative nursing services,*** in clinical indicators,stress levels,degree of pain,emotional state,and quality of life were observed,and complications and nursing satisfaction among the three groups were *** After nursing,the time to recovery of gastrointestinal function in the high-quality and combined nursing groups was significantly shorter than that of the control group,with the recovery of gastrointestinal function being the fastest in the combined nursing group(P<0.05).After nursing intervention,cortisol and norepinephrine levels in the high-quality and combined nursing groups were closer to normal than those of the control group 24 h after surgery,with the combined nursing group having the closest to normal levels(P<0.05).After 3 and 7 d of intervention,the patients’pain significantly improved,which was more prominent in the highquality and combination ***,the pain score in the combination group was significantly lower than those of the control and high-quality nursing groups(P<0.05).After nursing intervention,the emotional states of all patients improved,and the scores of patients in

关键词： Biliary calculi Information-motivation-behavioral skills model High quality care Perioperative period Pain Application

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STING-mediated IL-6 Inhibits OATP1B1 Expression via the TCF4 Signaling Pathway in Cholestasis

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Journal of Clinical and Translational Hepatology 2024年第8期12卷 701-712页

作者： Yan Guo Hongjia Zhang Nan Zhao Ying Peng Dongya Shen Yubin Chen Xiaoxun Zhang Can-E Tang Jin Chai Department of Endocrinology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Gastroenterology Institute of Digestive Diseases of PLACholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver DiseaseThe First Affiliated Hospital(Southwest Hospital)to Third Military Medical University(Army Medical University)ChongqingChina Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Cardiac Surgery Xiangya HospitalCentral South UniversityChangshaHunanChina National Clinical Research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Background and Aims Organic anion-transporting polypeptides(OATPs)play a crucial role in the transport of bile acids and *** our previous study,interleukin 6(IL-6)reduced OATP1B3 levels in cholestatic ***,it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic *** study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying *** The effect of stimulator of interferon genes(STING)signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent *** assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma,we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α,IL-1β,and *** elucidate the mechanism by which IL-6 inhibits OATP1B1 expression,we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western *** interaction mechanism betweenβ-catenin/TCF4 and OATP1B1 was investigated by knocking downβ-catenin/TCF4 through siRNA *** The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model,with IL-6 exhibiting the most potent inhibitory effect on ***-6 downregulatedβ-catenin/TCF4,leading to decreased OATP1B1 ***-downβ-catenin/TCF4 counteracted theβ-catenin/TCF4-mediated repression of *** STING-mediated IL-6 up-regulation may inhibit OATP1B1,leading to reduced transport of bile acids and bilirubin by *** may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.

关键词： Inflammation Bile acid Bilirubin Cholestasis STING IL-6 β-catenin TCF4

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First-line immunotherapy for advanced non-small cell lung cancer:current progress and future prospects

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Cancer Biology & Medicine 2024年第2期21卷 117-124页

作者： Jingyi Wang Lin Wu The Second Department of Thoracic Oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China xiangya Lung Cancer center Xiangya HospitalCentral South UniversityChangsha 410008China

Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung ***,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic *** therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research ***,ICI therapy has been shown to improve the prognosis of lung cancer patients.

关键词： lung cancer mortality

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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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Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第1期18卷 68-80页

作者： Yanling Liu Xi He Yanchun Yuan Bin Li Zhen Liu Wanzhen Li Kaixuan Li Shuo Tan Quan Zhu Zhengyan Tang Feng Han Ziqiang Wu Lu Shen Hong Jiang Beisha Tang Jian Qiu Zhengmao Hu Junling Wang Department of Neurology Xiangya HospitalCentral South UniversityJiangxiNational Regional Center for Neurological DiseasesNanchang330038China Provincial Laboratory for Diagnosis and Treatment of Genitourinary System Disease Department of UrologyXiangya HospitalCentral South UniversityChangsha410078China Department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhou310002China Department of Neurology Xiangya HospitalCentral South UniversityChangsha410078China National Clinical Research center for Geriatric Diseases Xiangya HospitalCentral South UniversityChangsha410008China Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangsha410008China center for medical Genetics School of Life SciencesCentral South UniversityChangsha410008China Engineering Research center of Hunan Province in Cognitive Impairment Disorders Central South UniversityChangsha410078China Hunan international Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases Changsha410078China Hunan Key Laboratory of Molecular Precision Medicine Xiangya HospitalCentral South UniversityChangsha410078China

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons,and it demonstrates high clinical heterogeneity and complex genetic architecture.A variation within TRMT2B(c.1356G>T;p.K452N)was identified to be associated with ALS in a family comprising two patients with juvenile ALS(JALS).Two missense variations and one splicing variation were identified in 10 patients with ALS in a cohort with 910 patients with ALS,and three more variants were identified in a public ALS database including 3317 patients with ALS.A decreased number of mitochondria,swollen mitochondria,lower expression of ND1,decreased mitochondrial complex I activities,lower mitochondrial aerobic respiration,and a high level of ROS were observed functionally in patient-originated lymphoblastoid cell lines and TRMT2B interfering HEK293 ***,TRMT2B variations overexpression cells also displayed decreased *** conclusion,a novel JALS-associated gene called TRMT2B was identified,thus broadening the clinical and genetic spectrum of ALS.

关键词： TRMT2B amyotrophic lateral sclerosis mitochondrial complex I tRNA methylation reactive oxygen species

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Viral-mediated gene therapy in pediatric neurological disorders

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World Journal of Pediatrics 2024年第6期20卷 533-555页

作者： Jing Peng Wei-Wei Zou Xiao-Lei Wang Zhi-Guo Zhang Ran Huo Li Yang Department of Pediatrics Clinical Research Center for Chidren Neurodevelopmental disablities of Hunan ProvinceXiangya HospitalCentral South UniversityChangsha 410008China Reproductive Medicine center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefeiChina State Key Laboratory of Reproductive Medicine Nanjing Medical UniversityNanjingChina

Background Due to the broad application of next-generation sequencing,the molecular diagnosis of genetic disorders in pediatric neurology is no longer an unachievable ***,treatments for neurological genetic disorders in children remain primarily *** the other hand,with the continuous evolution of therapeutic viral vectors,gene therapy is becoming a clinical *** this perspective,we wrote this review to illustrate the current state regarding viral-mediated gene therapy in childhood neurological *** sources We searched databases,including PubMed and Google Scholar,using the keywords"adenovirus vector,""lentivirus vector,"and"AAv"for gene therapy,and"immunoreaction induced by gene therapy vectors,""administration routes of gene therapy vectors,"and"gene therapy"with"NCL,""SMA,""DMD,""congenital myopathy,""MPS""leukodystrophy,"or"pediatric metabolic disorders".We also screened the database of *** using the keywords"gene therapy for children"and then filtered the results with the ones aimed at neurological *** time range of the search procedure was from the inception of the databases to the *** We presented the characteristics of commonly used viral vectors for gene therapy for pediatric neurological disorders and summarized their merits and drawbacks,the administration routes of each vector,the research progress,and the clinical application status of viral-mediated gene therapy on pediatric neurological *** Viral-mediated gene therapy is on the brink of broad clinical ***-mediated gene therapy will dramatically change the treatment pattern of childhood neurological disorders,and many children with incurable diseases will meet the dawn of a ***,the vectors must be optimized for better safety and efficacy.

关键词： Gene therapy Neurological disorders Pediatrics Viral vectors

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Association between abnormal default mode network homogeneity and sleep disturbances in major depressive disorder

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General Psychiatry 2024年第2期37卷 234-241页

作者： Muzhi Huang Yangpan Ou Huabing Li Feng Liu Ping Li Jingping Zhao Bing Lang Wenbin Guo Department of Psychiatry The Second Xiangya Hospital of Central South University National Clinical Research Center for Mental Disordersand National Center for Mental DisordersChangshaHunanChina Department of Radiology The Second Xiangya Hospital of Central South UniversityChangshaHunanChina Department of Radiology Tianjin Medical University General HospitalHepingTianjinChina Qiqihar medical University QiqihaerHeilongjiangChina

Background Sleep disturbance is a common comorbidity of major depressive disorder(MDD).However,network homogeneity(NH)changes of the default mode network(DMN)in MDD with sleep disturbances are *** The purpose of this study was to probe the abnormal NH in the DMN in MDD with sleep disturbances and to reveal the differences between MDD with or without sleep *** Twenty-four patients with MDD and sleep disturbances(Pa_s),33 patients with MDD without sleep disturbances(Pa_ns)and 32 healthy controls(HCs)were recruited in this ***-state functional imaging data were analysed using *** Compared with Pa_ns and HCs,Pa_s showed decreased NH in the left superior medial prefrontal cortex and increased NH in the right *** was a negative correlation between NH in the left superior medial prefrontal cortex and sleep disturbances(r=−0.42,p=0.001)as well as a positive correlation between NH in the right precuneus and sleep disturbances(r=0.41,p=0.002)in patients with *** MDD with sleep disturbances is associated with abnormal NH in the DMN,which could differentiate pa_s from pa_*** DMN may play a crucial role in the neurobiological mechanisms of MDD with sleep disturbances.

关键词： sleep medial cortex

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Roles of THEM4 in the Akt pathway:a double-edged sword

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 541-556页

作者： Wen XIE Weidong LIU Lei WANG Bin ZHU Cong ZHAO Ziling LIAO Yihan LI Xingjun JIANG Jie LIU Caiping REN NHC Key Laboratory of Carcinogenesis Department of NeurosurgeryXiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China The Key Laboratory of Carcinogenesis and Cancer Invasion of the Ministry of Education Cancer Research InstituteSchool of Basic Medical ScienceCentral South UniversityChangsha 410078China Department of Critical Care Medicine Hainan Hospital of Chinese PLA General HospitalHainan Province Clinical Medical CenterSanya 572013China

The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of *** superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding *** studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its ***,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous *** these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially *** work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

关键词： Protein kinase B(Akt) Thioesterase superfamily member 4(THEM4) Tumor proliferation Tumor metastasis

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BET inhibitors potentiate melanoma ferroptosis and immunotherapy through AKR1C2 inhibition

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Military medical Research 2024年第4期11卷 620-624页

作者： Yu Meng Hui-Yan Sun Yi He Qian Zhou Yi-Huang Liu Hui Su Ming-Zhu Yin Fu-Rong Zeng Xiang Chen Guang-Tong Deng Department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008China National Engineering Research center of Personalized Diagnostic and Therapeutic Technology Changsha 410008China Furong Laboratory Changsha 410008China Hunan Key Laboratory of Skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research center for Geriatric Disorders Xiangya HospitalChangsha 410008China Department of Breast Reconstruction Tianjin Medical University Cancer Institute and HospitalTianjin 300202China Department of Oncology Xiangya HospitalCentral South UniversityChangsha 410008China

Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great pote... 详细信息

关键词： Melanoma Bromodomain and extra terminal domain(BET)inhibitor Ferroptosis Cell death AKR1C2 Immunotherapy

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