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Maternal High-Fat Diet Impairs Offspring Glucose Metabolism and Programs Hepatic DNA Methylation Linked to NK Cell-Mediated Cytotoxicity Signaling Pathway at Weaning

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Food Science and Human Wellness 2024年

作者： sheng Zheng Ling Zhang Shixuan Zhang Guanyu Hu Yikai Li Jia Zheng Department of Traditional Chinese Orthopedics and Traumatology， Center for Orthopedic Surgery， The Third Affiliated Hospital of Southern Medical University Department of Endocrinology， Peking University First Hospital

Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring. However， the precise epigenetic mechanisms governing these intergenerational effects， particularly during the early stages of offspring development， remain poorly understood. In this study， female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation. Methylated DNA immunoprecipitation (MeDIP) coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age. We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period. DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer (NK) cell-mediated cytotoxicity pathway. MeDIP-PCR validated reduced methylation levels of specific genes within this pathway， including TNFα， PI3K， and SHC1. Consistently， the expressions of TNFα， PI3K， and SHC1 were significantly upregulated， accompanied by elevated serum TNFα and IL-6 levels in offspring from dams fed with high-fat diet. Moreover， we assessed the expressions of genes associated with NK cell activities， uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet. In addition， methylation levels of TNFα， PI3K， and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing. In conclusion， our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns， thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.

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Dependence Tree Structure Estimation via Copula

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International Journal of Automation and computing 2012年第2期9卷 113-121页

作者： Jian Ma Zeng-Qi Sun sheng Chen Hong-Hai Liu Department of Computer Science Tsinghua University Beijing 100084 PRC Electronics and Computer Science Faculty of Physical and Applied Sciences University of Southampton Southampton SO17 1B J UK Faculty of Engineering King Abdulaziz University Jeddah 21589 Saudi Arabia Intelligent Systems and Robotics Research Group School of Creative Technologies University of Portsmouth Portsmouth PO1 2D J UK

We propose an approach for dependence tree structure learning via copula. A nonparametric algorithm for copula estimation is presented. Then a chow-Liu like method based on dependence measure via copula is proposed to estimate maximum spanning bivariate copula associated with bivariate dependence relations. The main advantage of the approach is that learning with empirical copula focuses on dependence relations among random variables, without the need to know the properties of individual variables as well as without the requirement to specify parametric family of entire underlying distribution for individual variables. Experiments on two real-application data sets show the effectiveness of the proposed method.

关键词： Copula empirical copula dependence tree structure learning probability distribution.

Moutan Cortex and Paeoniae Radix Rubra reverse high-fat-diet-induced metabolic disorder and restore gut microbiota homeostasis

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Chinese Journal of Natural Medicines 2017年第3期15卷 210-219页

作者： ZHONG Ling-Jun XIE Zhi-sheng YANG Hua LI Ping XU Xiao-Jun State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases China Pharmaceutical UniversityNanjing 210009China

The present study was designed to investigate the therapeutic effcts of Moutan Cortex(CM,root bark of Paeonia suffruticosa Andr) and Paeoniae Radix Rubra(PR,root of Paeonia veitchii Lynch) on metabolic disorders,focusing on the infuence of CM and PR on the obesity-related gut microbiota *** diet-induced obese(DIO) mouse model was used to test the therapeutic effects of CM and *** mice were orally administered with CM and PR for 6 weeks,and oral glucose tolerance test(OGTT) and insulin tolerance test(ITT) were performed to evaluate the insulin sensitivity of the ***-regulatory element binding proteins(SREBPs) and their target genes were measured by quantitative ***-throughput 16 S ribosomal RNA(16S rR NA) gene sequencing technology was used to determine the composition of gut microbiota,and the metabolites in serum were analyzed by *** results indicated that CM and PR combination alleviated obese and insulin resistance in the DIO mice,leading to increased glucose uptake and gene expression in muscle and liver,and down-regulated SREBPs and their target genes in ***,neither the CM-PR extracts,nor the major components of CM and PR did not affect SREBPs activity in cultured ***,CM and PR significantly modulated the gut microbiota of the high-fat diet(HFD) treated mice,similar to metformin,and CM-PR reversed the overall microbiota composition similar to the normal chow diet(NCD) treated *** conclusion,our results provide novel mechanisms of action for the effects of CM and PR in treating DIO-induced dysregulation of sugar and lipid metabolism.

关键词： Moutan Cortex Paeoniae Radix Rubra Insulin resistance Gut microbiota

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GAS VARIFOCAL LENS

Chinese Physics Letters 1985年第11期2卷 509-512页

作者： XIE Bang-li XIA sheng-jie chow Quan-tie Institute of Mechanics Academia SinicaBeijing

The stable laminar flow established by an air stream sucked through a heated tube acts as an optically thin tens with variable focal length depending on the dimensions of the tube,tube-temperature and flow velocity.

关键词： flow dimensions heated

Therapy and Prevention of Postoperative Urosepsis of Ureter Endoscopic Lithotripsy for "Non-infection"

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Chinese Medical Sciences Journal 2016年第1期31卷 49-53页

作者： Jun Shen Fa Sun Fang-min Chen Zhi-ping Wu sheng-wen Li Medical Center Tsinghua University Department of Urology the Affiliated Hospital of Guizhou Medical University Department of Urology the First Hospital of Tsinghua University

Objective To analyze the risk factors causing postoperative urosepsis in ureter endoscopic lithotripsy without infection preoperatively,in order to make a more effective and safer preventive and therapeutic *** From January 2010 to January 2015,5 ureteral calculus patients undergoing ureter endoscopic lithotripsy with holmium laser were retrospectively enrolled in this clinical *** patients suffered urosepsis postoperatively confirmed by the clinical presentations and laboratory results,while they had no infection in their blood and urine *** delay,5 patients were treated by anti-inflammation and *** The vasopressor drug was stopped gradually after 12-36 *** body temperature was recovered to normal in 2 or 3 days,and the blood and urine test results were not abnormal in 7 *** last,5patients were all *** Stone and operation themselves are potential factors to cause urosepsis after ureter endoscopic *** for patients who had not presented infection preoperatively,careful preparation preoperatively,corrective manipulation,low pressure irrigation,drainage and controlling time during operation,and early diagnosis,appropriate treatment postoperatively are the key to cure and prevent urosepsis.

关键词： lithotripsy non-infection ureter urosepsis

轻断食对2型糖尿病模型大鼠胰岛素抵抗及胰岛β细胞功能的作用及其机制研究

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新疆医科大学学报 2024年第10期47卷 1348-1353页

作者：吾热叶提·阿不都乃比王攀霞蒋升艾比拜·玉素甫省部共建中亚高发病成因与防治国家重点实验室新疆医科大学第一附属医院内分泌科乌鲁木齐830054 新疆喀什市人民医院内分泌科新疆喀什844000

目的探讨轻断食对2型糖尿病大鼠胰岛素抵抗以及胰岛β细胞AMPK-mTOR-ULK1自噬信号通路的影响及其可能的机制。方法46只雄性Wistar大鼠中随机选取6只作为正常对照组(给予普通饲料饲养4 w),其余40只大鼠建立2型糖尿病模型(给予高脂饲料饲... 详细信息

目的探讨轻断食对2型糖尿病大鼠胰岛素抵抗以及胰岛β细胞AMPK-mTOR-ULK1自噬信号通路的影响及其可能的机制。方法46只雄性Wistar大鼠中随机选取6只作为正常对照组(给予普通饲料饲养4 w),其余40只大鼠建立2型糖尿病模型(给予高脂饲料饲养,每5天腹腔注射1次STZ 25 mg/kg体重,共4 w)。40只2型糖尿病大鼠模型建立成功后,根据干预的不同分为模型组、模型+轻断食组、模型+运动干预组、模型+药物干预组、模型+运动+轻断食组。所有干预组大鼠同时每5天腹腔注射1次小剂量STZ 25 mg/kg体重,正常对照组同时每5天腹腔注射1次生理盐水0.5 mL/100 g体重。干预结束行简易糖耐量试验(OGTT),检测各组大鼠空腹血糖、空腹血清胰岛素水平,计算出胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β),评价干预效果。Western-blot法检测干预前、后大鼠胰腺组织中AMPK-mTOR-ULK1信号通路及自噬相关蛋白腺苷酸活化蛋白激酶(AMPK)、磷酸化-AMPK(p-AMPK)、哺乳动物类雷帕霉素靶蛋白(mTOR)、磷酸化-mTOR(p-mTOR)、UNC-51样激酶1(ULK1)、微管相关蛋白轻链3(LC3)、卷曲螺旋状Myosin样Bcl-2相互作用蛋白-1(Beclin-1)的表达水平。结果与模型组大鼠比较,模型+轻断食组、模型+运动+轻断食组大鼠的空腹血糖、空腹胰岛素及服糖后2 h血糖水平、HOMA-IR水平显著降低(P均<0.05);大鼠胰腺组织Beclin-1、p-AMPK、ULK1表达均显著降低,p-mTOR表达明显升高(P<0.05)。与模型组大鼠比较,模型+运动+轻断食组的HOMA-β水平显著升高(P<0.05),大鼠胰腺组织中的LC3表达显著降低(P<0.05)。结论轻断食干预对2型糖尿病大鼠具有改善胰岛素抵抗、提升胰岛β细胞功能的作用,并影响细胞自噬AMPK-mTOR-ULK1信号通路。

关键词：轻断食 2型糖尿病胰岛素抵抗胰岛β细胞功能自噬

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上海暴雨的分析

同济大学学报 1957年第1期 139-149页

作者：周善生

本文根据上海37年(1919—1955)自记雨量计记录,取用37组最大暴雨强度,取其平均值,在对数坐标轴内作出强度和历时的关系曲线,然后按照曲线外形,分裂为二,分别用雨条直线来配合。而在对数坐标轴内,频率和雨力的关系曲线,也分裂为二,分别... 详细信息

本文根据上海37年(1919—1955)自记雨量计记录,取用37组最大暴雨强度,取其平均值,在对数坐标轴内作出强度和历时的关系曲线,然后按照曲线外形,分裂为二,分别用雨条直线来配合。而在对数坐标轴内,频率和雨力的关系曲线,也分裂为二,分别用二次曲线和直线来配合,综合而成均方差很小的上海暴雨公式,以供市政规划设计的应用。

关键词：暴雨一次次序对数降雨暴雨公式暴雨分析上海

Knockdown of NPY expression in the dorsomedial hypothalamus enhances hepatic insulin sensitivity

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Knockdown of NPY expression in the dorsomedial hypothalamus ...

中华医学会第十三次全国内分泌学学术会议

作者： LIN LI HONG LI sheng BI Sir Run Run Shaw Hospital affiliated to the Zhejiang University School of Medicine Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine

Hypothalamic neuropeptide Y(NPY)has been implicated in control of energy balance,and we reported that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow(RC)and ameliorated high-fat diet-induced hyperphagia and ***,the functional role of DMH NPY knockdown of in-

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羌蛮獠混杂:唐代黎属羁縻州的部族分布

安徽史学 2017年第6期 56-61,152页

作者：郭声波暨南大学历史地理研究中心广东广州510632

唐代控制大渡河下游及其附近地区的黎州都督府,统属50多个羁縻州,担负着维持川滇走廊交通大道"清溪道"安全的使命。由于境内羁縻部族的分布比较复杂,以前学术界对黎州都督府统属的境域范围不太清楚。史籍记载黎州东南分布着"粟蛮",正南... 详细信息

唐代控制大渡河下游及其附近地区的黎州都督府,统属50多个羁縻州,担负着维持川滇走廊交通大道"清溪道"安全的使命。由于境内羁縻部族的分布比较复杂,以前学术界对黎州都督府统属的境域范围不太清楚。史籍记载黎州东南分布着"粟蛮",正南分布着"邛部六姓蛮",西南分布着"五部落蛮",但具体地望仍不太明确。文章在之前对黎属羁縻州分布初步研究基础上,从有关部族与羁縻州的对应关系入手,结合文献、地名、语言资料,基本复原了这些部族的具体分布,揭示了羌、蛮、獠混杂而居的特点,进一步明确了黎属羁縻州的境域范围。

关键词：大渡河诸羌邛部川诸蛮婆笼川獠蛮黎属羁縻州