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Toward understanding the role of genomic repeat elements in neurodegenerative diseases

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Neural Regeneration Research 2025年第3期20卷 646-659页

作者： zhengyu An Aidi jiang Jingqi Chen Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan UniversityShanghaiChina Zhangjiang Fudan International Innovation Center ShanghaiChina

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

关键词： Alzheimer's disease ataxia deep learning long-read sequencing neurodegeneration neurodegenerative diseases Parkinson's disease repeat element structural variant

Contribution of neutrophils in the pathogenesis of rheumatoid arthritis

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The Journal of Biomedical Research 2020年第2期34卷 86-93页

作者： Lingshu Zhang Yi Yuan Qiang Xu zhengyu jiang Cong-Qiu Chu Division of Arthritis and Rheumatic Diseases Oregon Health&Science UniversityPortlandOR 97239USA Rheumatology Section VA Portland Healthcare SystemPortlandOR 97239USA Department of Rheumatology and Immunology the First Hospital of Jilin UniversityChangchunJilin 130021China

Neutrophils are major innate immune effector cells for host defense and have been a topic of active research for their participation in the pathogenesis of autoimmune inflammatory diseases including rheumatoid arthritis(RA)due to recently discovered neutrophil extracellular trap(NET) formation. NET formation and other mechanisms leading to the release of neutrophil nuclear and cytoplasmic contents are implicated as a source of citrullinated antigens in RA. Further investigations are required to delineate what factors diverge neutrophils from host defense to autoimmune response in RA.

关键词： neutrophils rheumatoid arthritis NET formation

Medical futility in the era of evidence-based medicine

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The Journal of Biomedical Research 2014年第4期28卷 249-250页

作者： zhengyu jiang Lu Yang Pinhao Guo Shanshan Gong Company Twelve Students Brigadethe Second Military Medical University Department of Foreign Languages the Second Military Medical University

One definition of futility is any treatment that merely preserves permanent unconsciousness or fails to end total dependence of a patient on intensive medical care However, no agreement has ever been reached on what the exact defmition of futility is, as it is not only based on temporary values but also evolves into different subtypes, making it harder to define. The difficulty in dealing with futility problem is how doctors evaluate the futile situation, which is further complicated by lack of standards for specific diseases and experience-based prognosis, leading to subjectivity in evaluation for futility.

关键词： EBM Medical futility in the era of evidence-based medicine

Autonomy and authority in medical futility

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The Journal of Biomedical Research 2014年第6期28卷 433-434页

作者： zhengyu jiang Lu Yang Pinhao Guo Shanshan Gong Company Twelve Students Brigadethe Second Military Medical University Department of Foreign Languages the Second Military Medical University

Medical futility has been proposed for many years to define the procedure that simply prolongs the suffering of patients but heals *** deal with the decision procedure for treatment,two ideas arise：patients＇autonomy and doctors＇*** recognized in 1960s,patients＇autonomy respected patients＇willingness over treatment,requiring specific consent for treatment and right to choose during medical *** idea for futility is doctors＇authority,explained from the paternalistic perspective as well.

关键词： Autonomy and authority in medical futility

Dynamics of Ore-Forming Processesof the Stratabound Skarn Copper Depositsof Tongling, Anhui Province

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Acta Geologica Sinica(English Edition) 1996年第1期70卷 59-73页

作者： Yu Chongwen, jiang Yaosong and Xiao zhengyu China University of Geosciences, Beijing China University ofGeosciences Beijing

The skarn and ore bodies of the stratabound skarn copper deposits of Tongling, Anhui Province, are both controlled by definite stratigraphic horizons, and they are concordant with the strata. They occur as layers and layer-like bodies in permeable carbonate rocks of the Middle-Upper Carboniferous Huanglong and Chuanshan Formations which are underlain by impermeable shale or siliceous rocks of the Upper Devonian Wutong Formation. The authors study the dynamics of ore-forming processes of the ore deposits with the dynamic model of coupled transport and reaction, and the following results are obtained: The salinity gradient and flow rate of the ore-forming fluids can both promote the mixing and reaction of juvenile water and formation water, and the permeable strata are favourable sites for the intense transport-reaction of mixing and the formation of deposits. (2) As isothermal transport-reaction took place along the bedding of strata, the moving transport-reaction front formed at the contact between the ore-forming fluids and the rocks advanced slowly along the permeable strata, and then stratiform skarn and ore bodies concordant with the strata were formed. (3) The gradient transport-reaction taking place across the isotherms in the cross-bedding direction caused the mineralogical composition to alter gradually from magnesian skarn to sulphide ore bodies.

关键词： stratabound skarn ore deposit dynamics of ore-forming processes dynamics of coupled transport and reaction transport-reaction of mixing isothermal transport-reaction gradient transport-reaction

Non-small molecule PROTACs(NSM-PROTACs):Protein degradation kaleidoscope

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Acta Pharmaceutica Sinica B 2022年第7期12卷 2990-3005页

作者： Sinan Ma Jianai Ji Yuanyuan Tong Yuxuan Zhu Junwei Dou Xian Zhang Shicheng Xu Tianbao Zhu Xiaoli Xu Qidong You zhengyu jiang State Key Laboratory of Natural Medicines and jiang Su Key Laboratory of Drug Design and Optimization China Pharmaceutical UniversityNanjing 210009China Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical UniversityNanjing 210009China

The proteolysis targeting chimeras(PROTACs)technology has been rapidly developed since its birth in 2001,attracting rapidly growing attention of scientific institutes and pharmaceutical *** present,a variety of small molecule PROTACs have entered the clinical ***,as small molecule PROTACs flourish,non-small molecule PROTACs(NSM-PROTACs)such as peptide PROTACs,nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years,exhibiting the unique characters beyond the small molecule ***,we briefly introduce the types of NSM-PROTACs,describe the advantages of NSM-PROTACs,and summarize the development of NSM-PROTACs so far in *** hope this article could not only provide useful insights into NSM-PROTACs,but also expand the research interest of NSM-PROTACs.

关键词： Non-small molecule PROTACs Protein degradation Peptide PROTACs Nucleic acid PROTACs Antibody PROTACs

Novel Dual-Site-Binding Neuraminidase Inhibitor from Virtual Screening by Pharmacophore and Molecular Dynamics Methods

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Novel Dual-Site-Binding Neuraminidase Inhibitor from Virtual...

2012长三角药物化学研讨会

作者： jiang zhengyu Huang Kun Wu Xiaowen Sun Haopeng You Qidong Department of Medicinal Chemistry China Pharmaceutical University State Key Laboratory of Natural Medicines Department of Medicinal ChemistryChina Pharmaceutical University jiangsu Key Laboratory of Carcinogenesis and Intervention China Pharmaceutical University

Neuraminidase is a significant anti-influenza target that plays crucial role in virus replication cycle. The discovery of 150-cavity in Group-1 neuraminidase provides us a novel mentality of designing inhibitor which can bind with both conserved site and *** order to discover novel dual-site-binding inhibitors,a 3D chemical-feature-based pharmacophore model was established to cover dual-site in ne *** dual-site-binding model was consistent in predicting the binding

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免疫反应代谢调控:脓毒症研究的新方向

中华危重病急救医学 2019年第1期31卷 122-125页

作者：蒋政宇卞金俊邓小明海军军医大学长海医院麻醉学部上海200433

免疫代谢是近年来新的研究热点。揭示不同免疫细胞在不同反应阶段的代谢特征,可为解释众多疾病的发病机制、解决免疫相关性疾病的治疗难点提供新的思路和方向。脓毒症是机体创伤、病原体感染等多种致病因素引起的一种复杂的全身性炎症... 详细信息

免疫代谢是近年来新的研究热点。揭示不同免疫细胞在不同反应阶段的代谢特征,可为解释众多疾病的发病机制、解决免疫相关性疾病的治疗难点提供新的思路和方向。脓毒症是机体创伤、病原体感染等多种致病因素引起的一种复杂的全身性炎症免疫反应,免疫细胞在疾病的不同阶段具有不同的代谢及反应特征。这些代谢特征同时又参与调控免疫细胞的增殖、分化和功能。通过分析近年来免疫细胞代谢反应及炎症调控的相关文献,总结不同免疫细胞亚群免疫反应的代谢调控因素,以及脓毒症患者免疫细胞代谢的相关特点,深入了解不同免疫细胞在脓毒症患者中的代谢状态,以期进一步理解脓毒症免疫紊乱,特别是免疫麻痹阶段的病理生理学机制,从而为临床应用免疫代谢治疗提供理论基础。

关键词：免疫代谢脓毒症免疫麻痹

新型5-氨基-2-(苄基硫代)噻唑-4-甲酰胺类化合物的设计、合成及抗肿瘤活性

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中国药科大学学报 2017年第1期48卷 16-22页

作者：王璐尤启冬姜正羽中国药科大学江苏省药物分子设计与成药性优化重点实验室南京21009 中国药科大学药物化学教研室南京21009

为了寻找具有更好抗肿瘤活性的化合物,设计合成了一系列5-氨基-2-(苄基硫代)噻唑-4-甲酰胺衍生物。以2-氨基-2-氰基-乙酰胺为起始原料,合成了16个化合物DDO-5401~DDO-5416;目标化合物结构经IR、1H NMR和ESI-MS确证;采用MTT法对目标化合... 详细信息

为了寻找具有更好抗肿瘤活性的化合物,设计合成了一系列5-氨基-2-(苄基硫代)噻唑-4-甲酰胺衍生物。以2-氨基-2-氰基-乙酰胺为起始原料,合成了16个化合物DDO-5401~DDO-5416;目标化合物结构经IR、1H NMR和ESI-MS确证;采用MTT法对目标化合物进行5株肿瘤细胞(HCT116、Hep G2、A549、MDA-MB-231、MCF-7)体外抗肿瘤活性测定。合成的化合物对肿瘤细胞尤其是A549细胞表现出了良好的抑制活性;构效关系研究表明,苯环上连有给电子基团的化合物抑制活性要好于连有吸电子基团的化合物。化合物DDO-5413的抑制活性最强,对乳腺癌细胞MDA-MB-231和MCF-7抑制活性好于阳性对照药达沙替尼,值得进一步研究。

关键词： 5-氨基-2-(苄基硫代)噻唑-4-甲酰胺类衍生物合成抗肿瘤活性