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Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

Oncology Research 2024年第2期32卷 325-337页

作者： JIE ZHAO XUANTAO YANG HAIXI ZHANG XUEZHONG GU Department of Hematology The First People’s Hospital of Yunnan ProvinceYunnan Province Clinical Research Center for Hematologic DiseaseYunnan Province Clinical Center for Hematologic DiseaseKunming650032China Department of Pathology The First People’s Hospital of Yunnan ProvinceKunming650032China

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence *** is a new-generation proteasome inhibitor that is used as the first-line therapy for ***,the development of drug resistance is a pervasive obstacle to treating ***,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic *** elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM *** gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion *** upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion ***,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion ***,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor ***,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion *** suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor *** studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

关键词： Multiple myeloma Carfilzomib Drug resistance Major histocompatibility complex TNFRSF1A

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Asymmetric Drying and Wetting Trends in Eastern and western China

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Advances in Atmospheric Sciences 2024年第2期41卷 221-232页

作者： Wen WU Fei JI Shujuan HU Yongli HE College of Atmospheric Sciences Lanzhou UniversityLanzhou 730000China Collaborative Innovation center for western Ecological Safety Lanzhou UniversityLanzhou 730000China

As an important factor that directly affects agricultural production, the social economy, and policy implementation,observed changes in dry/wet conditions have become a matter of widespread concern. However, previous research has mainly focused on the long-term linear changes of dry/wet conditions, while the detection and evolution of the non-linear trends related to dry/wet changes have received less attention. The non-linear trends of the annual aridity index, obtained by the Ensemble Empirical Mode Decomposition(EEMD) method, reveal that changes in dry/wet conditions in China are asymmetric and can be characterized by contrasting features in both time and space in China. Spatially, most areas in western China have experienced transitions from drying to wetting, while opposite changes have occurred in most areas of eastern China. Temporally, the transitions occurred earlier in western China compared to eastern China. Research into the asymmetric spatial characteristics of dry/wet conditions compensates for the inadequacies of previous studies, which focused solely on temporal evolution;at the same time, it remedies the inadequacies of traditional research on linear trends over centennial timescales. Analyzing the non-linear trend also provides for a more comprehensive understanding of the drying/wetting changes in China.

关键词： aridity index EEMD dry/wet conditions asymmetric evolution

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非洲铁路沿线土地利用变化及影响因素研究——以亚吉铁路埃塞俄比亚段为例

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Journal of Geographical Sciences 2024年第6期34卷 1128-1156页

作者：赵胜波祁俊衡李冬雪王兴平 School of Architecture Southeast UniversityNanjing 210096China School of Architecture and Planning Yunnan UniversityKunming 650504China center for International Collaboration and Research on development and Planning of Sustainable Industrial Parks Southeast UniversityNanjing 210096China

Railways are a crucial part of the African transport network and have a significant impact on the socio-economy and urban development. Previous studies have mainly considered the impacts of railways in Africa from the perspective of economy, politics, security, and natural environment with few attempts to consider land use. Based on Landsat remote sensing data for the 10 km buffer zone along the Ethiopian section of the Addis Ababa–Djibouti Railway(ADR) in 2013, 2017, and 2021, we studied the land use change(LUC) in the area and explored its influencing factors using the ordinary least square model(OLS) and geographical weighted regression model(GWR). There were six key results.(1) Farmland,forest, grassland, and others(including sandy land and bare land) were the primary types of land use, but from 2013 to 2021, the area of built-up land and farmland increased, whereas the area of forest, grassland, and other land decreased.(2) There was a noticeable pattern in the degree of change in the area of built-up land, farmland, and forest as the buffer distance increased along the railway. This pattern indicated a gradual shift in land use and LUC gradients.(3) The land use structure and its changes in the areas surrounding different stations displayed obvious differences.(4) The construction and operation of the ADR is one of the direct factors affecting landscape change along the railway.(5) The distance from the train station, whether the station provides a passenger service, the population size, and the distance from the central city had a positive effect on the expansion of built-up land surrounding the station. The factor of whether the station provides a freight service had a negative correlation with the expansion of built-up land. Socio-economic factors have gradually replaced railway factors as the main driving force of the expansion of built-up land around the stations.(6) The effect strength of different factors on the expansion of built-up land varied in the

关键词： land use change railway influencing factor Africa

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Tropical cyclone genesis over the western north Pacific in La Ni?a decay summers: Comparison between 2018 and 2021

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Science China Earth Sciences 2024年第10期67卷 3098-3109页

作者： Yunyun LIU Zhensong GONG China Meteorological Administration Key Laboratory for Climate Prediction studies National Climate Centre Collaborative Innovation center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science &Technology

As the primary interannual signal of variability in the tropical ocean-atmosphere interaction, the El Ni?o-Southern Oscillation has a considerable impact on tropical cyclone(TC) activity over the western North Pacific(WNP). Both 2018 and2021 were La Ni?a decay years, but TC activity over the WNP during the two summers(June–August) showed notable differences. In 2018, summer TC activity was unusually high with a total of 18 TCs, and the region of TC genesis was mainly in the central and eastern WNP. In contrast, only 9 TCs were generated in summer 2021, and the region of TC genesis was primarily in the western WNP. By comparing the characteristics of the large-scale environmental conditions over the regions of TC genesis, the thermal factors of the tropical oceans, and the activity of the Madden-Julian Oscillation(MJO), this study revealed the possible causes for the marked differences in TC genesis over the WNP during the two summers, which both had a similar background of La Ni?a decay. The Indian Ocean Basin Mode(IOBM) transitioned of a cold anomaly in the winter of 2017/2018and persisted until summer 2018. At the same time, the Pacific Meridional Mode(PMM) maintained a positive phase, leading to eastward and northward displacement of the western Pacific Subtropical High in summer, and eastward extension of the tropical monsoon trough, which presented conditions conducive to TC genesis over the Northwest Pacific. Moreover, the days when the MJO stagnated in phases 5 and 6 in the summer of 2018 increased by approximately 150% relative to climatological state,providing dynamic conditions favorable for TC formation. In 2021, the IOBM quickly turned to a warm anomaly in March and persisted until summer, whereas the PMM became a negative phase in January and remained so until summer. At the same time,the MJO stagnated in phases 2 and 3 for up to 47 days, with the center of convection located over the western Maritime Continent, producing conditions unconducive to TC ge

关键词： Tropical cyclone La Niña events Indian Ocean Basin Mode Pacific Meridional Mode Madden-Julian Oscillation western Pacific Subtropical High Monsoon trough

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Evolutionary Diversity of Coxsackievirus A6 Causing Severe Hand,Foot,and Mouth Disease—China,2012-2023

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China CDC weekly 2024年第20期6卷 442-449页

作者： Huanhuan Lu Jinbo Xiao Wenhui Wang Dongmei Yan Tianjiao Ji Qian Yang Haiyan Wei Yanhua Du Yunting Zeng Jun Guo Jianhua Chen Hanri Zeng Yingying Liu Shuaifeng Zhou Hong Ji Jianxing Wang Xiaofang Zhou Yong Zhang National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases World Health Organization Polio Reference Laboratory for the Western Pacific RegionKey Laboratory of Laboratory BiosafetyNational Health and Key Laboratory of Laboratory Biosafety of the National Health CommissionNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Linyi center for Disease Control and Prevention Linyi CityShandong ProvinceChina Henan Provincial center for Disease Control and Prevention Zhengzhou CityHenan ProvinceChina Shaanxi Provincial center for Disease Control and Prevention Xi’an CityShaanxi ProvinceChina Hainan Provincial center for Disease Control and Prevention Haikou CityHainan ProvinceChina Guizhou Provincial center for Disease Control and Prevention Guiyang CityGuizhou ProvinceChina Gansu Provincial center for Disease Control and Prevention Lanzhou CityGansu ProvinceChina Guangdong Provincial center for Disease Control and Prevention Guangzhou CityGuangdong ProvinceChina Hebei Provincial center for Disease Control and Prevention Shijiazhuang CityHebei ProvinceChina Hunan Provincial center for Disease Control and Prevention Changsha CityHunan ProvinceChina Jiangsu Provincial center for Disease Control and Prevention Nanjing CityJiangsu ProvinceChina Shandong Provincial center for Disease Control and Prevention Jinan CityShandong ProvinceChina yunnan Provincial center for Disease Control and Prevention Kunming CityYunnan ProvinceChina

Introduction:Coxsackievirus A6(CVA6)has emerged as a significant pathogen responsible for severe cases of hand,foot,and mouth disease(HFMD).This study aims to delineate the demographic characteristics and analyze the viral evolution of severe HFMD associated with CVA6,thereby assisting in its surveillance and ***:In this investigation,74 strains of CVA6 were isolated from samples collected from severe HFMD cases between 2012 and *** VP1 gene sequences of CVA6 were amplified and analyzed to assess population historical dynamics and evolutionary characteristics using BEAST,DnaSP6,and ***:A significant portion(94.4%)of severe CVA6-associated HFMD cases(51 out of 54,with 20 lacking age information)were children under 5 years *** the 74 CVA6 strains analyzed,72 belonged to the D3a sub-genotype,while only two strains were D2 *** average genetic distance between VP1 sequences prior to 2015 was 0.027,which increased to 0.051 when compared to sequences *** population dynamics analysis indicated three significant population expansions of severe CVA6-associated HFMD during 2012-2013,2013-2014,and 2019-2020,resulting in the formation of 65 distinct *** with the MCC tree findings,transitioning between regional haplotypes required multiple base substitutions,showcasing an increase in population diversity during the evolutionary process(from 14 haplotypes in 2013 to 55 haplotypes over the subsequent decade).Conclusions:CVA6,associated with severe HFMD,is evolving and presents a risk of outbreak ***,enhanced surveillance of severe HFMD is imperative.

关键词： thereby subsequent finding

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Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2726-2737页

作者： Bo Liu Honghui Liu Pu Han Xiaoyun Wang Chunmei Wang Xinxin Yan Wenwen Lei Ke Xu Jianjie Zhou Jianxun Qi Ruiwen Fan Guizhen Wu Wen-xia Tian George F.Gao Qihui Wang College of Veterinary Medicine Shanxi Agricultural University030801 JinzhongChina CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)100101 BeijingChina School of Life Sciences Yunnan University650504 KunmingYunnan ProvinceChina NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)102206 BeijingChina Savaid Medical School University of Chinese Academy of Sciences101408 BeijingChina

Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its *** suggests that highly conserved epitopes are crucial for the development of neutralizing ***,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its ***-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S *** neutralization mechanism interpreted via flow cytometry and western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S ***,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus *** to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in *** intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

关键词： doses prevention conserved

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A simple and efficient CRISPR/Cas9 system permits ultra-multiplex genome editing in plants

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The Crop Journal 2024年第2期12卷 569-582页

作者： Suting Wu Htin Kyaw Zhijun Tong Yirong Yang Zhiwei Wang Liying Zhang Lihua Deng Zhiguo Zhang Bingguang Xiao William Paul Quick Tiegang Lu Guoying Xiao Guannan Qin Xue'an Cui Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China Key Laboratory of Genetics Breeding and Multiple Utilization of CropsMinistry of EducationCollege of AgricultureFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina Key Laboratory of Biological Breeding for Fujian and Taiwan Crops Ministry of Agriculture and Rural AffairsCollege of AgricultureFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina School of Biosciences The University of SheffieldFirth CourtWestern BankSheffield S102TNUK Key Laboratory of Tobacco Biotechnological Breeding National Tobacco Genetic Engineering Research CenterYunnan Academy of Tobacco Agricultural SciencesKunming 650021YunnanChina

The development and maturation of the CRISPR/Cas genome editing system provides a valuable tool for plant functional genomics and genetic *** available genome-editing tools have a limited number of targets,restricting their application in genetic *** this study,we developed a novel CRISPR/Cas9 plant ultra-multiplex genome editing system consisting of two template vectors,eight donor vectors,four destination vectors,and one primer-design software *** combining the advantages of Golden Gate cloning to assemble multiple repetitive fragments and Gateway recombination to assemble large fragments and by changing the structure of the amplicons used to assemble sg RNA expression cassettes,the plant ultra-multiplex genome editing system can assemble a single binary vector targeting more than 40 genomic loci.A rice knockout vector containing 49 sg RNA expression cassettes was assembled and a high co-editing efficiency was *** plant ultra-multiplex genome editing system advances synthetic biology and plant genetic engineering.

关键词： CRISPR/Cas9 Multiplex genome editing Assembly system Plant

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A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

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Genes & Diseases 2024年第4期11卷 400-410页

作者： Han Chan Fenfen Ni Bo Zhao Huimin Jiang Juanjuan Ding Li Wang Xiaowen Wang Jingjing Cui Shipin Feng Xiaojie Gao Xueying Yang Huan Chi Hao Lee Xuelan Chen Xiaoqin Li Jia Jiao Daoqi Wu Gaofu Zhang Mo Wang Yupeng Cun Xiongzhong Ruan Haiping Yang Qiu Li Department of Nephrology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of Nephrology Shenzhen Children's HospitalShenzhenGuangdong 518034China Department of Nephrology Kunming Children's HospitalKunming Medical UniversityKunmingYunnan 650228China Department of Nephrology Wuhan Children's HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanHubei 430015China Department of Nephrology Chengdu Women and Children Central HospitalChengduSichuan 610073China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Department of Nephrology John Moorhead Research LaboratoryUniversity College London Medical SchoolRoyal Free CampusUniversity College LondonLondon NW32PFUnited Kingdom

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the *** conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy ***,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for *** significant SNPs were observed between SSNSWR and SDNS/***,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through ***,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/*** study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

关键词： Frequentrelapse Genome-wide association study Human leukocyte antigen region Steroid-sensitive nephrotic syndrome

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Blocking the PD-1 signal transduction by occupying the phosphorylated ITSM recognition site of SHP-2

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Science China Life Sciences 2024年

作者： Wenjie Li Wenyi Mei Hewei Jiang Jie Wang Xiaoli Li Lina Quan Yanyan Diao Yanni Ma Sisi Fan Zhuwei Xie Mengdie Gong Huan Zhu Dewen Bi Feng Zhang Lei Ma Jian Zhang Yufeng Gao Aris Paschalidis Honghuang Lin Fangfang Liu Kangdong Liu Mingliang Ye Zhenjiang Zhao Yajun Duan Zhuo Chen Yufang Xu Weilie Xiao Shengce Tao Lili Zhu Honglin Li Innovation center for AI and Drug Discovery East China Normal University Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science&Technology Shanghai center for Systems Biomedicine Key Laboratory of Systems Biomedicine (Ministry of Education)Shanghai Jiao Tong University Lingang Laboratory Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Characteristic Plant Extraction LaboratoryYunnan Provincial Center for Research&Development of Natural ProductsState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanSchool of Pharmacy and School of Chemical Science and TechnologyYunnan University CAS Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of Sciences Department of Cardiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of China Department of Infectious Diseases The First Affiliated Hospital of Anhui Medical University Department of Medicine University of Massachusetts Chan Medical School Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical ScienceCollege of MedicineZhengzhou University

Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for immunotherapy. Here, we identify a natural pentacyclic triterpenoid, Pygenic Acid A(PA), as a PD-1 signaling inhibitor. PA exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of T cells to promote immune responses by disrupting the PD-1 signaling transduction. Furthermore, we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling transduction. Subsequently, mechanistic studies suggest that PA binds to a new druggable site in the phosphorylated PD-1 ITSM recognition site of SHP-2, inhibiting the recruitment of SHP-2 by PD-1. Taken together, our findings demonstrate that PA has a potential application in cancer immunotherapy and occupying the phosphorylated ITSM recognition site of SHP-2 may serve as an alternative strategy to develop PD-1 signaling inhibitors. In addition, our success in target recognition provides a paradigm of target identification and confirmation for natural products.

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Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation

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World Journal of Diabetes 2024年第5期15卷 958-976页

作者： Hong Xu Li-Bo Zhang Yi-Yi Luo Ling Wang Ye-Pin Zhang Pei-Qi Chen Xue-Ying Ba Jian Han Heng Luo Department of Ophthalmology The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina Precision Medicine center of Chuxiong Yi Autonomous Prefecture The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina Department of Endocrinology The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina Department of Pathology The People’s Hospital of Chuxiong Yi Autonomous Prefecture&The Fourth Affiliated Hospital of Dali UniversityChuxiong Yi Autonomous Prefecture 675000Yunnan ProvinceChina

BACKGROUND Synaptotagmins(SYTs)are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and ***,few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy(DR)through Ca2+/glucose transporter-1(GLUT1)and the possible regulatory mechanism of *** To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of *** DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells(ARPE-19).Bioinformatics analysis,reverse transcriptase-polymerase chain reaction,western blot,flow cytometry,ELISA,HE staining,and TUNEL staining were used for *** Six differentially expressed proteins(SYT2,SYT3,SYT4,SYT7,SYT11,and SYT13)were found between the DR and control groups,and SYT4 was highly *** induces SYT4 overexpression,manipulates Ca2+influx to induce GLUT1 fusion with the plasma membrane,promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake,induces ARPE-19 cell apoptosis,and promotes DR *** deficiency inhibits the proteasomal degradation of SYT4 in DR,resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane,and these effects were blocked by oe-Parkin ***,dysregulation of the myelin transcription factor 1(Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process,and this process was inhibited in the oe-MYT1-treated *** Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

关键词： Diabetic retinopathy Glucose transporter-1 Synaptotagmin 4 Parkin Myelin transcription factor 1

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