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尿道下裂的病因学:遗传变异的系统回顾

中国生物化学与分子生物学报 2024年第5期40卷 598-609页

作者：付媛李建婷彭志伟山西医科大学基础医学院生物化学与分子生物学教研室出生缺陷与细胞再生山西省重点实验室太原030001 煤炭环境致病与防治教育部重点实验室太原030001

尿道下裂以尿道口位置异常为特征,是男性中第二常见的先天性异常疾病。其发病率逐年上升,成为我国第四大出生缺陷疾病,不仅给患者带来了生理和心理上的双重困扰,其手术修复和长期的术后管理也占用了大量的社会经济及医疗资源。尿道下裂... 详细信息

尿道下裂以尿道口位置异常为特征,是男性中第二常见的先天性异常疾病。其发病率逐年上升,成为我国第四大出生缺陷疾病,不仅给患者带来了生理和心理上的双重困扰,其手术修复和长期的术后管理也占用了大量的社会经济及医疗资源。尿道下裂既可以是孤立性的,也可以作为综合征的一种表现形式存在。现阶段,用于定义和评估尿道下裂的方法多种多样,为了护理和手术方法的标准化,制定统一的分类标准势在必行。在人类中,阴茎结构的正常发育经历了早期的雄激素非依赖性阶段和晚期的雄激素依赖性性分化阶段,除了遗传改变外,内分泌或外部环境的影响,都可能导致阴茎发育基本要素的损伤或缺失,进而诱发尿道下裂。因此,该病是遗传、内分泌、环境因素及其相互作用的结果,通常认为遗传因素比其他因素更为重要。本文基于不同的人群队列,主要从经典遗传的基因变异方面来阐明尿道下裂的发病原因,回顾了影响生殖结节生长和分化、性腺发育和睾丸分化、雄激素和雌激素产生等正常生物学过程的相关基因,涉及了基因多态性、单核苷酸多态性和拷贝数变异等多种遗传变异,在此基础上总结了与人类尿道下裂相关的候选基因。本文将为尿道下裂的筛查、干预及临床治疗提供理论依据,为提高出生人口质量做出贡献。

关键词：尿道下裂阴茎发育基因变异

神经管闭合的新见解:叶酸不应答型神经管畸形

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中国生物化学与分子生物学报 2024年第5期40卷 575-587页

作者：任文彬李建婷解军山西医科大学基础医学院生物化学与分子生物学教研室出生缺陷与细胞再生山西省重点实验室太原030001 山西医科大学煤炭环境致病与防治教育部重点实验室太原030001

神经管畸形(neural tube defects,NTDs)是一种常见的、严重且复杂的先天性畸形,是遗传、营养和环境因素相互作用的结果。母体妊娠期补充叶酸(folic acid,FA)已被证明是一种非常有效的策略,常用于部分NTDs的初级预防。然而,仍有一部分NTD... 详细信息

神经管畸形(neural tube defects,NTDs)是一种常见的、严重且复杂的先天性畸形,是遗传、营养和环境因素相互作用的结果。母体妊娠期补充叶酸(folic acid,FA)已被证明是一种非常有效的策略,常用于部分NTDs的初级预防。然而,仍有一部分NTDs病例对FA治疗具有抵抗性,称为“FA不应答型NTDs”或“FA抵抗型NTDs”。FA不应答型NTDs的病因复杂,涉及遗传、营养、环境及母体相关因素。本文综述了叶酸不应答型NTDs的相关遗传、营养、环境及母体等风险因素,并揭示了其致病机制的研究进展。其中,遗传因素主要从小鼠突变体及品系、叶酸一碳代谢基因、关键凋亡基因三方面展开阐述,为该类患儿的产前诊断提供了可能的遗传检测位点。营养因素方面,本文主要聚焦目前已报道的肌醇和蛋氨酸,解释其对该种疾病潜在的干预机制,为NTDs患者早期营养干预提供新方向。此外,本文还探讨了叶酸一碳代谢中的辅助因子-维生素B12参与叶酸不应答型NTDs发生的可能机制,增加叶酸联合其他维生素治疗出生缺陷的可能性。最后,本文还综述了环境因素和母体因素在叶酸不应答型NTDs中的研究进展,为高危人群提供孕早期健康指导。总之,本文综述了叶酸不应答型NTDs的相关风险因素及其致病机制的研究进展,为当下该种疾病及同类型出生缺陷的防治提供新的见解。

关键词：神经管畸形肌醇小鼠模型叶酸卷尾

低叶酸和维甲酸诱导神经管畸形小鼠模型胎脑的转录物组学分析

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中国生物化学与分子生物学报 2024年第5期40卷 638-646页

作者：曹志华谷小龙解琪李建婷方爱莉刘志贞山西医科大学基础医学院生物化学与分子生物学教研室出生缺陷与细胞再生山西省重点实验室太原030001 煤炭环境致病与防治教育部重点实验室太原030001 山西医科大学第三医院(山西白求恩医院山西医学科学院同济山西医院)麻醉科太原030000

神经管畸形(neural tube defects,NTDs)是一类中枢神经系统相关的重大出生缺陷型疾病。随着孕龄期妇女叶酸增补政策的推广,其发病率逐年下降致临床标本不易获取,因此,建立可靠的动物模型来研究NTDs的致病机制尤为重要。本研究分别通过... 详细信息

神经管畸形(neural tube defects,NTDs)是一类中枢神经系统相关的重大出生缺陷型疾病。随着孕龄期妇女叶酸增补政策的推广,其发病率逐年下降致临床标本不易获取,因此,建立可靠的动物模型来研究NTDs的致病机制尤为重要。本研究分别通过低叶酸联合甲氨蝶呤(methotrexate,MTX)建立的诱导NTDs小鼠模型和维甲酸(retinoic acid,RA)诱导建立的NTDs小鼠模型,对NTDs胎鼠脑组织进行转录物组测序(transcriptome sequencing,RNA-seq)并分析差异表达谱,最后,通过实时荧光定量PCR(real-time quantitative polymerase chain reaction,RT-qPCR)进行结果验证。结果显示,低叶酸联合MTX诱导的胎鼠NTDs发生率为21.7%;RA诱导的胎鼠出现了强烈的致畸现象,畸形率为73.2%。相比正常胎鼠,低叶酸联合MTX诱导的NTDs小鼠组筛选出1443个差异表达基因(differentially expression genes,DEGs);RA诱导NTDs小鼠组筛选出3070个DEGs。对DEGs进行生物信息学分析,GO富集显示,上调基因主要参与前后轴发育、区域化和模式分化过程等生物学过程;KEGG富集显示,上调基因与心肌收缩、心肌病、神经活性配体-受体相互作用等信号通路相关。对2种模型鼠的DEGs进行Veen交集分析,结果显示,共有132个DEGs在2组模型中显著上调,其中包括Hox基因家族。通过RT-qPCR进行验证,发现与RNA-seq的结果一致。本研究对2种NTDs小鼠胎脑进行RNA-seq和差异表达谱分析,发现Hox的异常表达可能导致了NTDs的发生,为后续发病机制的研究提供了探索与思考。

关键词：神经管畸形转录物组测序叶酸维甲酸同源盒基因

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铁电材料负电卡效应的研究进展

现代技术陶瓷 2024年第1期45卷 24-43页

作者：李建厅李俊杰闫汝清白洋齐鲁工业大学大学机械工程学院(山东省科学院) 济南250353 山东机械设计研究院济南250353 成都信息工程大学光电工程学院成都610225 北京科技大学新材料技术研究院北京100083

基于电卡效应的铁电制冷技术具有制冷效率高、绿色环保、操控便捷、易于小型化等优点,具有广阔的制冷应用场景。电卡效应是指铁电等极性材料在外电场作用下电偶极子状态改变引发的等温熵变或绝热温变,包括正电卡效应和负电卡效应。正(负... 详细信息

基于电卡效应的铁电制冷技术具有制冷效率高、绿色环保、操控便捷、易于小型化等优点,具有广阔的制冷应用场景。电卡效应是指铁电等极性材料在外电场作用下电偶极子状态改变引发的等温熵变或绝热温变,包括正电卡效应和负电卡效应。正(负)电卡效应是指对铁电体施加(撤去)电场时,铁电体放热;撤去(施加)电场时,铁电体吸热的现象。正、负电卡效应中从外部环境吸收热量的过程均可用于铁电制冷。除优化热释电系数和击穿场强的传统方案外,正、负电卡效应相结合也被认为是提升铁电材料制冷能力的有效手段。然而,负电卡效应存在研究时间短、材料体系少、物理机制不清晰、调控机理不明确等诸多问题,限制了正、负电卡效应的结合及其应用。本文在回顾电卡效应研究进展的基础上,综述了负电卡效应的物理机制和调控机理,讨论了结合正、负电卡效应提升制冷性能的可行性,并对负电卡效应及正、负电卡效应结合的未来研究进行了展望。本文可为负电卡效应研究及提升铁电材料的制冷能力提供新的思路和方向,推动电卡效应的研究。

关键词：铁电制冷技术电卡效应负电卡效应物理机制

Cost of Multicast Logical Key Tree Based on Hierarchical Data Processing

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Wuhan University Journal of Natural Sciences 2006年第5期11卷 1172-1176页

作者： ZHOU Fucai XU jian li ting School of Information Seienee and Engineering Northeastern University Shenyang 110004 Liaoning China

How to design a multicast key management system with high performance is a hot issue now. This paper will apply the idea of hierarchical data processing to construct a common analytic model based on directed logical key tree and supply two important metrics to this problem： re-keying cost and key storage cost. The paper gives the basic theory to the hierarchical data processing and the analyzing model to multieast key management based on logical key tree. It has been proved that the 4-ray tree has the best performance in using these metrics. The key management problem is also investigated based on user probability model, and gives two evaluating parameters to re-keying and key storage cost.

关键词： multicast logical key tree hierarchical data processing

组蛋白去甲基化酶KDM5A调控H3K4me3参与神经管畸形发生的分子机制

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中国生物化学与分子生物学报 2024年第5期40卷 629-637页

作者：李建婷解琪谷小龙曹志华彭志伟赵虹刘志贞解军山西医科大学基础医学院生物化学与分子生物学教研室出生缺陷与细胞再生山西省重点实验室太原030001 煤炭环境致病与防治教育部重点实验室太原030001

神经管畸形(NTDs)的病因与防治是出生缺陷领域研究的重点,叶酸可以预防神经管畸形但其机制不明。本文借助低叶酸细胞模型和低叶酸NTDs小鼠模型通过染色质免疫共沉淀、Cut&Tag等技术,探讨了组蛋白去甲基化酶lysine demethylase 5A(KDM5A... 详细信息

神经管畸形(NTDs)的病因与防治是出生缺陷领域研究的重点,叶酸可以预防神经管畸形但其机制不明。本文借助低叶酸细胞模型和低叶酸NTDs小鼠模型通过染色质免疫共沉淀、Cut&Tag等技术,探讨了组蛋白去甲基化酶lysine demethylase 5A(KDM5A)及其调控的下游组蛋白H3K4me3修饰在叶酸缺乏导致的NTDs发生中的潜在分子机制。结果显示,低叶酸的细胞模型中,qRT-PCR、Western印迹结果显示,KDM5A分子表达明显下降(P<0.05)。作为组蛋白H3K4me3调控的上游关键酶,进一步通过染色质免疫共沉淀ChIP、ChIP-qPCR实验证实,叶酸缺乏下组蛋白H3K4me3在神经发育基因Axin 2和Atoh 1基因启动子区富集增加(P<0.05)。通过构建KDM5A基因敲除细胞模型,借助Cut&Tag试验证实,KDM5A基因敲除后H3K4me3主要富集在神经发育基因上。最后在低叶酸导致的NTDs小鼠模型的脑组织中,RT-qPCR、Western印迹以及ChIP-qPCR实验显示,E9.5 d的NTDs胎鼠脑组织中KDM5A表达下降(P<0.05),Axin2、Atoh1表达升高(P<0.05),Axin2、Atoh 1基因启动子区的H3K4me3富集增多(P<0.05)。综上所述,KDM5A蛋白在叶酸缺乏导致的NTDs中发挥重要作用,其可通过调控下游H3K4me3进而调控神经发育靶基因Axin2、Atoh 1异常表达,介导NTDs的发生。本研究从叶酸缺乏介导KDM5A调控组蛋白修饰来探讨NTDs的发病机制,为降低出生缺陷,促进生殖健康提供依据。

关键词：神经管畸形叶酸组蛋白去甲基化酶5A 组蛋白H3K4me3

Reshaping force for deformed casing repairing with hydraulic rolling reshaper and its influencing factors

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Petroleum Science 2024年第4期21卷 2745-2757页

作者： Hong-Fei li Min Luo ting-ting Xu Qiao-Zhen li Cong-jian Huang School of Mechanical Science and Engineering Northeast Petroleum University

Hydraulic rolling reshaper is an advanced reshaping tool to solve the problem of casing deformation,which has been widely used in recent years. When it is used for well repair operation, the reshaping force provided by ground devices is generally determined by experience. However, too large reshaping force may destroy the deformed casing, and too small reshaping force may also prolong the construction period and affect the repairing effect. In this paper, based on Hertz contact theory and elastic-plastic theory, combined with the process parameters of shaping, and considering the structural characteristics of the deformed casing and reshaper, we propose a mathematical model for calculating the reshaping force required for repairing deformed casing by hydraulic rolling reshaper. Meanwhile, the finite element model and numerical method of hydraulic rolling reshaper repairing deformed casing are established by using the finite element method, and the reliability of the mathematical model is verified by several examples. On this basis, the control variable method is used to investigate the influence of each parameter on the reshaping force, and the influence degree of each parameter is explored by orthogonal simulation test and Pearson correlation analysis. The research results not only provide an important theoretical basis for the prediction of reshaping force in on-site construction, but also provide a reference for the subsequent improvement of the shaping process.

关键词： Hydraulic rolling reshaper Reshaping force Deformed casing Casing reshaping Hertz contact theory

Numerical Study on the Effect of Gap Diffraction on the Hydrodynamic Performance of A Floating Breakwater

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China Ocean Engineering 2024年第4期38卷 663-675页

作者： BIAN Xiang-qian JI Chun-yan XU Sheng GUO jian-ting HUO Fa-li School of Naval Architecture and Ocean Engineering Jiangsu University of Science and TechnologyZhenjiang 212100China

Two-dimensional(2D)flume experiments are useful in investigating the performances of floating breakwaters(FBs),including hydrodynamic performances,motion responses,and mooring *** a reasonable gap between the flume wall and the FBs is a critical step in 2D flume ***,research on the effect of the gap on the accuracy of 2D FB experimental results is *** address this issue,a numerical wave tank is developed using CFD to estimate the wave-FB interaction of a moored dual-cylindrical FB,and the results are compared to experimental data from a previously published *** is good agreement between them,indicating that the numerical model is sufficiently *** numerical model is then applied to explore the effect of gap diffraction on the performance of FBs in2D *** was discovered that the nondimensional gap length L_(Gap)/W_(Pool)should be smaller than 7.5%to ensure that the relative error of the transmission coefficient is smaller than 3%.The influence of the gap is also related to the entering wave properties,such as the wave height and period.

关键词： floating breakwater diffraction effect gap hydrodynamic performance model experiments CFD numerical simulation

Pathogen-induced methylglyoxal negatively regulates rice bacterial blight resistance by inhibiting OsCDR1 protease activity

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Molecular Plant 2024年第2期17卷 325-341页

作者： Zheng-Wei Fu jian-Hui li Xiang Gao Shi-Jia Wang ting-ting Yuan Ying-Tang Lu State Key Laboratory of Hybrid Rice College of Life SciencesRenmin Hospital of Wuhan UniversityWuhan UniversityWuhan 430072China Key Laboratory of Biology and Genetic Improvement of OilCrops Ministry of Agriculture and Rural AffairsOilCrops Research Institute of the Chinese Academy of Agricultural SciencesWuhan 430062China

Xanthomonas oryzae ***(Xoo)causes bacterial blight(BB),a globally devastating disease of rice(Oryza sativa)that is responsible for significant crop *** and sugar metabolites are important for pathogen infection,providing energy and regulating events associated with defense responses;howev-er,the mechanisms by which they regulate such events in BB are *** an inevitable sugar metabolite,methylglyoxal(MG)is involved in plant growth and responses to various abiotic stresses,but the underlying mechanisms remain *** and how MG functions in plant biotic stress responses is almost completely ***,we report that the Xoo strain PXO99 induces OsWRKY62.1 to repress transcrip-tion of OsGLY Il genes by directly binding to their promoters,resulting in overaccumulation of *** negatively regulates rice resistance against Pxo99:osglyll2 mutants with higher MG levels are more sus-ceptible to the pathogen,whereas OsGLYIl2-overexpressing plants with lower MG content show greater resistance than the wild *** of OsGLYll2 to prevent excessive MG accumulation confers broad-spectrum resistance against the biotrophic bacterial pathogens Xoo and Xanthomonas oryzae *** and the necrotrophic fungal pathogen Rhizoctonia solani,which causes rice sheath *** evidence shows that MG reduces rice resistance against PXO99 through CONSTITUTIVE DISEASE RESISTANCE 1(OsCDR1).MGmodifies the Arg97 residue of OsCDR1to inhibit its aspartic protease activ-ity,which is essential for OsCDR1-enhanced *** together,these findings illustrate how Xoo promotes infection by hijacking a sugar metabolite in the host plant.

关键词： Oryza sativa bacterial blight OsWRKY62.1 methylglyoxal OsCDR1