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IDH1 mutation inhibits differentiation of astrocytes and glioma cells with low oxoglutarate dehydrogenase expression by disturbingα-ketoglutarate-related metabolism and epigenetic modification

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Life Metabolism 2024年第2期3卷 24-37页

作者： Yuanlin Zhao Ying Yang Risheng Yang Chao Sun Xing Gao Xiwen Gu Yuan Yuan Yating nie Shenhui Xu Ruili Han Lijun Zhang jing Li Peizhen Hu Yingmei Wang Huangtao Chen Xiangmei Cao jing Wu Zhe Wang Yu Gu jing Ye State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of PathologyXijing Hospital and School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi 710032China Department of Pathology Air Force Hospital of Southern Theater CommandGuangzhouGuangdong 510000China Department of Neurology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi 710038China Department of Clinical Diagnosis Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi 710038China Department of Neurosurgery the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710004China Department of Pathology School of Basic Medical SciencesNingxia Medical UniversityYinchuanNingxia 750004China Institute of Analytical Chemistry and Instrument for Life Science The Key Laboratory of Biomedical Information Engineering of Ministry of EducationSchool of Life Science and TechnologyXi’an Jiaotong UniversityXi’anShaanxi 710049China

Isocitrate dehydrogenase(IDH)mutations frequently occur in lower-grade gliomas and secondary *** IDHs exhibit a gain-of-function activity,leading to the production of D-2-hydroxyglutarate(D-2HG)by reducing α-ketoglutarate(α-KG),a central player in metabolism and epigenetic ***,the role ofα-KG homeostasis in IDH-mutated gliomagenesis remains *** this study,we found that low expression of oxoglutarate dehydrogenase(OGDH)was a common feature in IDH-mutated gliomas,as well as *** low expression of OGDH resultedin the accumulation of α-KG and promoted astrocyte ***,IDH1 mutation significantly reducedα-KG levels and increased glutaminolysis and DNA/histone methylation in *** metabolic and epigenetic alterations inhibited astrocyte maturation and led to cortical dysplasia in ***,our results also indicated that reduced OGDH expression can promote the differentiation of glioma cells,while IDH1 mutations impeded the differentiation of glioma cells with low OGDH by reducing the accumulation ofα-KG and increasing ***,we found that l-glutamine increasedα-KG levels and augmented the differentiation-promoting effects of AGI5198,an IDH1-mutant inhibitor,in IDH1-mutant glioma ***,this study reveals that low OGDH expression is a crucial metabolic characteristic of IDH-mutant gliomas,providing a potential strategy for the treatment of IDH-mutant gliomas by targetingα-KG homeostasis.

关键词： α-ketoglutarate IDH1 mutation OGDH l-glutamine gliomas

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

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World Journal of Diabetes 2024年第1期15卷 105-125页

作者： Wei-Long Xu Pei-Pei Zhou Xu Yu Ting Tian Jin-jing bao Chang-Rong Ni Min Zha Xiao Wu Jiang-Yi Yu Department of Endocrinology Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina Department of Pharmacy Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina Department of Pneumology Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal ***-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains *** To investigate the effects of myricetin on DN and explore its potential therapeutic *** Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 ***,blood and urine indexes were assessed,along with examination of renal tissue *** morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and ***,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 *** both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and *** In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and ***,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related ***,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 ***,myricetin modulated the M1-type polarization of the RAW 264.7 *** docking and bioinformatic analyses revealed Akt as the target of *** protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inh

关键词： Myricetin Diabetic nephropathy PI3K/Akt pathway Renal tubulointerstitial fibrosis Macrophage Polarization

Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

Geological conditions and reservoir characteristics of various shales in major shalehosted regions of China

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China Geology 2024年第1期7卷 138-149页

作者： Shu-jing bao Tian-xu Guo Jin-tao Yin Wei-bin Liu Sheng-jian Wang Hao-han Li Zhi Zhou Shi-zhen Li Xiang-lin Chen The Key Laboratory of Unconventional Petroleum Geology China Geological SurveyMinistry of Natural Resources100083 BeijingChina Oil and Gas Survey China Geological Survey100083 BeijingChina Research Institute of Yanchang Petroleum(Group)CO.LTD 710076 Xi’anChina

China is home to shales of three facies:Marine shale,continental shale,and marine-continental transitional *** types of shale gas are associated with significantly different formation conditions and major controlling *** study compared the geological characteristics of various shales and analyzed the influences of different parameters on the formation and accumulation of shale *** general,shales in China’s several regions exhibit high total organic carbon(TOC)contents,which lays a sound material basis for shale gas *** strata generally show high degrees of thermal *** contrast,continental shales manifest low degrees of thermal evolution,necessitating focusing on areas with relatively high degrees of thermal evolution in the process of shale gas surveys for these *** shales of the Wufeng and Silurian formations constitute the most favorable shale gas reservoirs since they exhibit the highest porosity among the three types of *** shales are followed by those in the Niutitang and Longtan *** contrast,the shales of the Doushantuo,Yanchang,and Qingshankou formations manifest low ***,the shales of the Wufeng and Longmaxi formations exhibit high brittle mineral *** a low siliceous mineral content,the shales of the Doushantuo Formation feature a high carbonate mineral content,which can increase the shales’brittleness to some *** marine-continental transitional shales,where thin interbeds of tight sandstone with unequal thicknesses are generally found,it is recommended that fracturing combined with drainage of multiple sets of lithologic strata should be employed to enhance their shale gas production.

关键词： Shale gas Marine shale Continental shale Marine-continental transitional shale Neoproterozoic-Cretaceous strata Geological conditions Reservoir characteristics Petroleum geological survey engineering

CCDC181 is required for sperm flagellum biogenesis and male fertility in mice

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Zoological Research 2024年第5期45卷 1061-1072页

作者： Xiang-Jun Zhang Xiao-Ning Hou Jian-Teng Zhou bao-Lu Shi jing-Wei Ye Meng-Lei Yang Xiao-Hua Jiang Bo Xu Li-Min Wu Qing-Hua Shi Division of Reproduction and Genetics First Affiliated Hospital of University of Science and Technology of China(USTC)Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Basic Medical SciencesDivision of Life Sciences and MedicineBiomedical Sciences and Health Laboratory of Anhui ProvinceInstitute of Health and MedicineHefei Comprehensive National Science CenterUniversity of Science and Technology of ChinaHefeiAnhui 230001China

The structural integrity of the sperm flagellum is essential for proper sperm *** defects can result in male infertility,yet the precise mechanisms underlying this relationship are not fully ***181,a coiled-coil domain-containing protein,is known to localize on sperm flagella and at the basal regions of motile *** this knowledge,the specific functions of CCDC181 in flagellum biogenesis remain *** this study,Ccdc181 knockout mice were *** absence of CCDC181 led to defective sperm head shaping and flagellum ***,the Ccdc181 knockout mice exhibited extremely low sperm counts,grossly aberrant sperm morphologies,markedly diminished sperm motility,and typical multiple morphological abnormalities of the flagella(MMAF).Additionally,an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified,with CCDC181 regulating the localization of LRRC46 within sperm *** findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

关键词： Male infertility CCDC181 MMAF Spermiogenesis Flagellum biogenesis

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低功耗海上救援个人示位标的设计与实现

湖南大学学报（自然科学版） 2024年第8期51卷 47-56页

作者：廖密聂桂根赵静贺喜武汉大学卫星导航定位技术研究中心湖北武汉430079 湖北珞珈实验室湖北武汉430079

设计和实现了一种改进的海上救援个人示位标,该示位标具备北斗导航定位能力和北斗短报文通信功能,同时具备人体生命体征监测上报和触水启动的功能,并支持COSPAS-SARSAT卫星搜救系统.为延长示位标的工作时间,设计了一种动态电源管理方法... 详细信息

设计和实现了一种改进的海上救援个人示位标,该示位标具备北斗导航定位能力和北斗短报文通信功能,同时具备人体生命体征监测上报和触水启动的功能,并支持COSPAS-SARSAT卫星搜救系统.为延长示位标的工作时间,设计了一种动态电源管理方法,实现了对不同功能电路电源通道的控制.同时,针对示位标的待机模式和工作模式,设计了超低功耗待机电路和低功耗软件控制设计方案,减少了电能的浪费.最后,分别在山东省威海市和浙江省宁波市至舟山市附近海域对原型样机进行了实际场景测试.原型样机的测试结果表明:示位标在待机状态下,电流为2.3μA,待机时间超过5年;示位标在接收北斗信息状态下,电流为79 mA;示位标在发送状态下,7 000 mAh 7.4 V电池可发送200次求救信息.与现有产品相比,本文提出的海上救援个人示位标具有更低的待机功耗.

关键词：海上救援个人示位标超低功耗待机动态电源管理

Deciphering the population structure and genetic basis of growth traits from whole-genome resequencing of the leopard coral grouper(Plectropomus leopardus)

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Zoological Research 2024年第2期45卷 329-340页

作者： Shao-Xuan Wu Qi-Fan Zeng Wen-Tao Han Meng-Ya Wang Hui Ding Ming-Xuan Teng Ming-Yi Wang Pei-Yu Li Xin Gao Zhen-Min bao Bo Wang jing-Jie Hu MOE Key Laboratory of Marine Genetics and Breeding College of Marine Life Sciences/Key Laboratory of Tropical Aquatic Germplasm of Hainan ProvinceSanya Oceanographic InstitutionOcean University of ChinaQingdaoShandong/SanyaHainan 266100/572025China Hainan Seed Industry Laboratory SanyaHainan 572025China Southern Marine Science and Engineer Guangdong Laboratory GuangzhouGuangdong 511458China

The leopard coral grouper(Plectropomus leopardus)is a species of significant economic *** artificial cultivation of *** has thrived in recent decades,the advancement of selective breeding has been hindered by the lack of comprehensive population genomic *** this study,we identified over 8.73 million single nucleotide polymorphisms(SNPs)through whole-genome resequencing of 326 individuals spanning six distinct ***,we categorized 226 individuals with high-coverage sequencing depth(≥14×)into eight clusters based on their genetic profiles and phylogenetic ***,four of these clusters exhibited pronounced genetic differentiation compared with the other *** identify potentially advantageous loci for ***,we examined genomic regions exhibiting selective sweeps by analyzing the nucleotide diversity(θπ)and fixation index(FST)in these four *** these high-coverage resequencing data,we successfully constructed the first haplotype reference panel specific to *** achievement holds promise for enabling high-quality,***,we combined low-coverage sequencing data with imputation techniques for a genome-wide association study,aiming to identify candidate SNP loci and genes associated with growth traits.A significant concentration of these genes was observed on chromosome 17,which is primarily involved in skeletal muscle and embryonic development and cell ***,our detailed investigation of growth-related SNPs across the eight clusters revealed that cluster 5 harbored the most promising candidate SNPs,showing potential for genetic selective breeding *** findings provide a robust toolkit and valuable insights into the management of germplasm resources and genome-driven breeding initiatives targeting ***.

关键词： Plectropomus leopardus Whole-genome resequencing Growth Haplotype reference panel Single nucleotide polymorphisms

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国家资历框架的国际研究:现状与启示

中国行政管理 2024年第7期40卷 39-49页

作者：邱茜鲍静谢晶首都经济贸易大学工商管理学院北京100070 中国行政管理学会北京100017 中国人事科学研究院北京100101

国家资历框架(National Qualifications Framework,简称NQF)作为一种能将国家范围内的各级各类学习成果按照知识、技能和能力的要求进行统编而构建的连续性的资历体系,对于融通衔接各级各类教育、建设学习型社会、促进个体终身教育与学... 详细信息

国家资历框架(National Qualifications Framework,简称NQF)作为一种能将国家范围内的各级各类学习成果按照知识、技能和能力的要求进行统编而构建的连续性的资历体系,对于融通衔接各级各类教育、建设学习型社会、促进个体终身教育与学习、推动国家人力资源管理体系和能力现代化具有十分重要的现实意义。本文在分析代表性国家资历框架发展现状的基础上,将国际上现有的国家资历框架划分为衔接型资历框架、区域一体型资历框架和分轨型资历框架三种类型。通过总结其成功的共性经验、分析其实践过程中出现的问题,阐述了为什么建设国家资历框架、怎样更好地建设国家资历框架等问题,旨在为探索一条适合我国的国家资历框架的发展之路提供参考。

关键词：国家资历框架衔接型资历框架区域一体型资历框架分轨型资历框架

Improvement and security analysis of multi-ring discrete modulation continuous variable quantum secret sharing scheme

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Chinese Physics B 2024年第7期33卷 189-197页

作者：姜欢窈聂敏杨光孙爱晶张美玲裴昌幸 School of Communications and Information Engineering&School of Artificial Intelligence Xi'an University of Posts and TelecommunicationsXi'an 710121China State Key Laboratory of Integrated Service Networks Xidian UniversityXi'an 710071China

In order to avoid the complexity of Gaussian modulation and the problem that the traditional point-to-point communication DM-CVQKD protocol cannot meet the demand for multi-user key sharing at the same time, we propose a multi-ring discrete modulation continuous variable quantum key sharing scheme(MR-DM-CVQSS). In this paper, we primarily compare single-ring and multi-ring M-symbol amplitude and phase-shift keying modulations. We analyze their asymptotic key rates against collective attacks and consider the security key rates under finite-size effects. Leveraging the characteristics of discrete modulation, we improve the quantum secret sharing scheme. Non-dealer participants only require simple phase shifters to complete quantum secret sharing. We also provide the general design of the MR-DM-CVQSS *** conduct a comprehensive analysis of the improved protocol's performance, confirming that the enhancement through multi-ring M-PSK allows for longer-distance quantum key distribution. Additionally, it reduces the deployment complexity of the system, thereby increasing the practical value.

关键词： discrete modulation continuous variable quantum secret sharing scheme