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Paternal transgenerational glucose intolerance with epigenetic alterations in second generation offspring of GDM

Asian Journal of Andrology 2013年第4期15卷 451-452页

作者： Guo-Lian Ding He-Feng Huang Women's Hospital School of Medicine ZhejiangUniversity Hangzhou 310006 China

Gestational diabetes mellitus （GDM） has been shown to be associated withhigh risk of diabetes in offspring. In addi tion to intergenerational transmission （F1 offspring）, intrauterine hyperglycemia also has effects on the second generation （F2 off spring）. However, the mechanisms involved and the possibilities of transgenerational transmission are still unclear. In a recent study published in Diabetes, we have uti lized GDM mouse model to identify hyper glycemic intrauterine environment causing a high risk of diabetes in offspring by alter ing epigenetic modification. Furthermore, the results indicate that the abnormality of phenotype and imprinted genes expression are more obvious in male offspring than that of female. The changes of epigenetics in sperm may contribute to transgenera tional transmission. A growing body of research suggests that exposure to the abnormal environment in uterus can lead to chronic health problems later in life.1 Intrauterine hyperglycemia is a major characteristic of GDM and has been suggested as an important determinative fac tor for the risk of diabetes in adulthood, it1 addition to the effects of genetic factors.2 The mechanism involved in the association between intrauterine hyperglycemia and a high risk of diabetes in offspring remains unclear.3 In mammals, epigenetic reprogram ming is involved in germ cells and early embryonic development.4＇5 Because erasure and establishment of the genomic imprints for some imprinted genes begin when migra tory primordial germ ceils enter the embry onic genital ridge through gametogenesis, epigenetic abnormalities that occur duringthis phase may be involved in transgenera tional transmission.6 In the study, ding et al.7 established a GDM mouse model of intrauterine hypergly cemia. The female （9） and male （or） F1 adults of control and GDM mice were intercrossed to obtain F2 offspring of four groups：（i） C0＂ C9; （ii） CCYGDMg; （iii） GDMCrCg; and （iv） GDMcYGDMg. We found that intrau terine hyperglycemia induced impaired glu cose tolerance （IGT）

关键词： Paternal transgenerational intolerance

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The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis

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Asian Journal of Andrology 2015年第6期17卷 948-953,I0008-I0009页

作者： Guo-Lian Ding Ye Liu Miao-E Liu Jie-Xue Pan Meng-Xi guo Jian-Zhong Sheng He-Feng Huang International Peace Maternity and Child Health Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 China The Key Laboratory of Reproductive Genetics Ministry of Education (Zhejiang University) Hangzhou 310058 China Department of Pathology and Pathophysiology School of MedicineZhejiang University Hangzhou 310058 China

The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring.

关键词： diabetes epigenetic regulation sperm spermatogenesis

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G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes

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Asian Journal of Andrology 2019年第1期21卷 74-79页

作者： Zhi-Hua Wan Yuan-Jie Zhang Lin Chen Yong-lian guo guo-Hao Li ding Wu Yong Wang Department of Urology The Central Hospital of WuhanTongll Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China

Type 2 diabetes mellitus (T2DM)is a common cause of erectile dysfunction (ED).It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2)overexpression contributes to diabetic endothelial dysfunction and oxidative stress,which also underlies ED in T2DM.We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM.T2DM rats were established by feeding with a high-fat diet (HFD)for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ),followed by continuous feeding with a HFD for 6 weeks.GRK2 was inhibited by IP injection of paroxetine,a selective GRK2 inhibitor,after STZ injection.Insulin challenge tests,intracavernous pressure (ICP), GRK2 expression,the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS)pathway,nicotinamide adenine dinucleotide phosphate (NADPH)oxidase subunit gp91phox,nitric oxide (NO),reactive oxygen species (ROS)production,and apoptosis in cavernosal tissue were examined.Less response to insulin injection was observed in T2DM rats 2 weeks after HFD.Markedly increased GRK2 expression,along with impaired Akt/eNOS pathway,reduced NO production,increased gp91phox expression and ROS generation,increased apoptosis and impaired erectile function were found in T2DM rats.inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling,restored NO production,downregulated NADPH oxidase,subsequently inhibited ROS generation and apoptosis,and ultimately preserved erectile function.These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED,and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.

关键词： endothelial dysfunction erectile dysfunction G protein-coupled receptor kinase 2 oxidative stress type 2 diabetes mellitus

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Causative Microorganisms Isolated from Patients with Intra-Abdominal Infections and Their Drug Resistance Profiles:An 11-Year(2011–2021)Single-Center Retrospective Study

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生物医学与环境科学:英文版 2023年第8期36卷 732-742页

作者： ding Rui MA Rui Rui LIU Ya Li ZHAO Ying guo Li Na DOU Hong Tao SUN Hong Li LIU Wen Jing ZHANG Li WANG Yao LI ding ding YI Qiao lian XU Ying Chun Department of Laboratory Medicine State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases Beijing 100730China Graduate School Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Objective To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections(IAIs).Methods A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021.Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.Antimicrobial susceptibility testing(AST)was performed using the VITEK 2 compact system and the Kirby–Bauer method.AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute.Results Of the 2,926 strains identified,49.2%,40.8%,and 9.5%were gram-negative bacteria,gram-positive bacteria,and fungi,respectively.Escherichia coli was the most prevalent pathogen in intensive care unit(ICU)and non-ICU patients;however,a significant decrease was observed in the isolation of E.coli between 2011 and 2021.Specifically,significant decreases were observed between 2011 and 2021 in the levels of extended-spectrumβ-lactamase(ESBL)-producing E.coli(from 76.9%to 14.3%)and Klebsiella pneumoniae(from 45.8%to 4.8%).Polymicrobial infections,particularly those involving co-infection with gram-positive and gram-negative bacteria,were commonly observed in IAI patients.Moreover,Candida albicans was more commonly isolated from hospital-associated IAI samples,while Staphylococcus epidermidis had a higher ratio in community-associated IAIs.Additionally,AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers,while the overall resistance rates(56.9%–76.8%)of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria.Indeed,Enterococcus faecium,Enterococcus faecalis,S.epidermidis,and S.aureus were consistently found to be susceptible to vancomycin,teicoplanin,and linezolid.Similarly,C.albicans

关键词： Intra-abdominal infection Causative microorganisms Antimicrobial susceptibility testing Gram-negative bacteria Gram-positive bacteria

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Arg-gly-asp-mannose-6-phosphate inhibits activation and proliferation of hepatic stellate cells in vitro

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World Journal of Gastroenterology 2006年第8期12卷 1303-1307页

作者： lian-Sheng Wang Ying-Wei Chen ding-guo Li Han-Ming Lu Digestive Disease Laboratory Xinhua Hospital Shanghai Second Medical University Shanghai 200092 China

瞄准：在主要肝的星形细胞在试管内的激活和增长上调查 arg-gly-asp-mannose-6 磷酸盐(RGD-M6P ) 的效果。方法：肝的星形细胞(HSC ) 被肝和 18% Nycodenz 坡度远心沉淀的原位胶原酶灌注从老鼠孤立并且在上有教养非常为有在培养基前包含... 详细信息

瞄准：在主要肝的星形细胞在试管内的激活和增长上调查 arg-gly-asp-mannose-6 磷酸盐(RGD-M6P ) 的效果。方法：肝的星形细胞(HSC ) 被肝和 18% Nycodenz 坡度远心沉淀的原位胶原酶灌注从老鼠孤立并且在上有教养非常为有在培养基前包含 10% 胎儿的牛的浆液(FBS/DMEM ) 的 DMEM 的 24 h 的 ated 塑料盘子与 2% FBS/DMEM 被用代替另一 24 h。然后， HSC 在有分别地转变生长因素 beta1， M6P， RGD，或 RGD-M6P 的 2% FBS/DMEM 是有教养的。房间形态学在转换显微镜下面被观察，平滑肌 alpha 肌动朊(alpha-SMA ) 被免疫细胞化学检测，在上层清液的类型 III 职业人员骨胶原(PC III ) 被放射性免疫测定决定，并且 HSC 的增长率被流动血细胞计数估计。结果：RGD-M6P 显著地禁止了词法转变和 alpha-SMA， HSC 在试管内并且也的 PC III 表达式戏剧性地阻止了 HSC 在试管内的增长。如此的效果与 RGD 或 M6P 的那些显著地不同。结论：新混合物， RGD-M6P，在主要有教养的 HSC 在试管内上有戏剧的效果，能在 TGFbeta1 引起的文化禁止 HSC 的转变，压制 PC III 的表示和 HSC 的减少增长率。RGD-M6P 能作为在 HSC 指向的一个选择的药搬运人被使用，它可以是肝纤维变性的预防和处理的一条新途径。

关键词：甘露糖细胞活化肝星形细胞病理机制

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基于改进整型遗传算法的稀疏矩形平面阵列优化

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国防科技大学学报 2023年第2期45卷 105-111页

作者：国强王亚妮袁鼎戚连刚哈尔滨工程大学信息与通信工程学院黑龙江哈尔滨150001

为了降低固定稀疏率、固定孔径的稀疏矩形阵列的峰值旁瓣电平,提出一种改进整型遗传算法。该算法在整型遗传算法的基础上,提出了等间隔采样的交叉策略、多点变异策略以及优良基因重组的策略。采取等间隔采样的基因交叉方式,可以有效发... 详细信息

为了降低固定稀疏率、固定孔径的稀疏矩形阵列的峰值旁瓣电平,提出一种改进整型遗传算法。该算法在整型遗传算法的基础上,提出了等间隔采样的交叉策略、多点变异策略以及优良基因重组的策略。采取等间隔采样的基因交叉方式,可以有效发挥整型编码的优势,从而提高算法的运行效率;为了提高种群的多样性,防止算法陷入局部最优,采用了多点变异策略;采用优良基因重组技术,加快了算法的收敛速度。仿真结果表明,相比传统的二进制和实数编码,整型编码更为直接高效;与用于稀疏矩形阵列优化的相关算法相比,本文所提算法获得了更优的旁瓣电平,证实了算法的有效性和优越性。

关键词：矩形平面阵列峰值旁瓣电平整型遗传算法稀疏阵列优化

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Triad mode resonant interactions in suspended cables

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Science China(Physics,Mechanics & Astronomy) 2016年第3期59卷 75-88页

作者： Tie ding guo Hou Jun Kang lian Hua Wang Yue Yu Zhao College of Civil Engineering Hunan University Hunan Provincial Key Lab on Damage Diagnosis for Engineering Structures Hunan University

A triad mode resonance, or three-wave resonance, is typical of dynamical systems with quadratic nonlinearities. Suspended cables are found to be rich in triad mode resonant dynamics. In this paper, modulation equations for cable's triad resonance are formulated by the multiple scale method. Dynamic conservative quantities, i.e., mode energy and Manley-Rowe relations, are then constructed. Equilibrium/dynamic solutions of the modulation equations are obtained, and full investigations into their stability and bifurcation characteristics are presented. Various bifurcation behaviors are detected in cable's triad resonant responses, such as saddle-node, Hopf, pitchfork and period-doubling bifurcations. Nonlinear behaviors, like jump and saturation phenomena, are also found in cable's responses. Based upon the bifurcation analysis, two interesting properties associated with activation of cable's triad resonance are also proposed, i.e., energy barrier and directional dependence. The first gives the critical amplitude of high-frequency mode to activate cable's triad resonance, and the second characterizes the degree of difficulty for activating cable's triad resonance in two opposite directions, i.e., with positive or negative internal detuning parameter.

关键词：共振相互作用和弦悬索非线性动力学系统分岔特性倍周期分岔非线性行为三波共振

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一种基于极值个体引导的鲸鱼优化算法

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软件导刊 2022年第12期21卷 76-83页

作者：丁浩王联国甘肃农业大学信息科学技术学院甘肃兰州730000

针对鲸鱼优化算法易陷入局部最优、收敛速度慢等问题,提出一种基于极值个体引导的鲸鱼优化算法。首先采用非线性方式动态调整参数C,以平衡全局搜索能力与局部搜索能力;然后在包围捕食阶段,利用群体最优个体和邻域最优个体共同引导鲸鱼... 详细信息

针对鲸鱼优化算法易陷入局部最优、收敛速度慢等问题,提出一种基于极值个体引导的鲸鱼优化算法。首先采用非线性方式动态调整参数C,以平衡全局搜索能力与局部搜索能力;然后在包围捕食阶段,利用群体最优个体和邻域最优个体共同引导鲸鱼进行搜索,以当前位置为基点,使鲸鱼个体向群体最优鲸鱼游动的同时,在邻域最优个体周围形成小范围聚拢,以增强算法的全局搜索能力,防止算法陷入局部最优;在搜索猎物阶段,采用邻域最优个体引导鲸鱼进行搜索,提升算法收敛速度和优化精度;最后选取23个包括单峰、多峰及固定维度在内的测试函数对改进算法进行测试。仿真实验结果表明,改进算法具有更高的寻优精度,且秩和检验验证结果具有显著性差异,即改进算法具有更佳的寻优性能。

关键词：鲸鱼优化算法极值个体引导动态调整

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考虑主播影响力的制造商销售渠道选择研究

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合肥工业大学学报（自然科学版） 2023年第4期46卷 568-576页

作者：朱晓东郭亚捷丁莲南京信息工程大学管理工程学院江苏南京210044

直播电商作为新兴的互联网经济受到广泛关注,文章研究制造商在传统销售模式中增设直播销售渠道后的渠道选择问题,考虑直播电商主播影响力的因素,比较分析不同渠道下供应链成员的利润。研究表明:传统销售模式中,制造商在直销渠道下的利... 详细信息

直播电商作为新兴的互联网经济受到广泛关注,文章研究制造商在传统销售模式中增设直播销售渠道后的渠道选择问题,考虑直播电商主播影响力的因素,比较分析不同渠道下供应链成员的利润。研究表明:传统销售模式中,制造商在直销渠道下的利润最高;制造商增设直播销售渠道后的利润总是高于制造商在传统销售模式下的利润。新销售模式中,在直销渠道和零售渠道下,直播电商主播影响力越大,对制造商扩大产品的市场需求越有利;在代理渠道下,消费者对直播渠道的支付意愿折损决定了直播渠道的市场扩大效用。

关键词：直播电商主播影响力 Stackelberg博弈销售渠道线上双渠道

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Compact millimeter-wave air-filled substrate-integrated waveguide crossover employing homogeneous cylindrical lens

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Frontiers of Information Technology & Electronic Engineering 2023年第9期24卷 1366-1374页

作者： Chun GENG Jiwei lian Dazhi ding Qian Xuesen College Nanjing University of Science and TechnologyNanjing 210094China School of Microelectronics(School of Integrated Circuits) Nanjing University of Science and TechnologyNanjing 210094China State Key Laboratory of Millimeter Waves Southeast UniversityNanjing 210096China

We propose a new method to design crossovers by employing an embedded homogeneous cylindrical lens(HCL).Compared with traditional crossover designs,this strategy introduces an HCL within the air-filled substrate-integrated waveguide(SIW)crossover cavity to direct the incident waves in the desired direction.According to ray-tracing analysis,the added HCL can efficiently concentrate the electromagnetic wave propagating from the input to the output without increasing the fabrication complexity or footprint.

关键词： waveguide millimeter crossover

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