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Selective N-terminal modification of peptides and proteins:Recent progresses and applications

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Chinese Chemical Letters 2022年第1期33卷 80-88页

作者： Hongfei Jiang wujun chen Jie Wang Renshuai Zhang The Affiliated Hospital of Qingdao University and Qingdao Cancer Institute Qingdao 266071China

Numerous strategies for linking desired chemical probes with target peptides and proteins have been developed and applied in the field of biological *** for site-specific modification of native amino acid residues in test tubes and biological contexts represent novel biological tools for understanding the role of peptides and *** N-terminal modification strategies have been broadly studied especially in the last 10 years,as N-terminal positions are typically solvent exposed and provide chemically distinct sites for many peptide and protein targets,making N terminus distinct from other functional groups.A growing number of chemical and enzymatic techniques have been developed to modify N-terminal amino acids,and those techniques have the potential in the fields of medicine,basic research and applied materials *** review focuses on appraising modification methodologies with the potential for biological applications from the past 10 years.

关键词： N-terminal modification N-terminal ligation Terminus modification Peptide modification Protein modification

Nanozyme-activating prodrug therapies:A review

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Chinese Chemical Letters 2024年第2期35卷 138-150页

作者： Yudong Wu wujun chen Chao Wang Dongming Xing The Affiliated Hospital of Qingdao University Qingdao UniversityQingdao 266071China School of Life Sciences Tsinghua UniversityBeijing 100084China

Enzyme prodrug therapies(EPTs)have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired target site,thus achieving localized,site-specific therapeutic *** effective strategies(e.g.,antibody-,viral-,gene-,as well as polymer-directed EPT)have been developed for enzyme localization to locally activate systemically administered benign ***,intrinsic limitations(e.g.,complex intracellular environment and catalyst instability)make the practical application of EPT strategies a task that presents itself as highly *** a promising alternative to natural enzyme,nanozyme has attracted substantial attention since its discovery in 2007,mainly due to the advantages of robust catalytic activity,high stability,low cost,and facile ***,nanozyme-activated prodrug strategies bring a new opportunity for targeted therapy,referred to as nanozyme-activating prodrug *** review focuses on recently reported nanozyme-activated prodrug strategies,aiming to provide some new insights into the potential applications in site-specific drug synthesis.

关键词： Enzyme prodrug therapy Nanozyme Prodrug activation Chemotherapy Drug synthesis

Distance-directed Target Searching for a Deep Visual Servo SMA Driven Soft Robot Using Reinforcement Learning

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Journal of Bionic Engineering 2020年第6期17卷 1126-1138页

作者： Wuji Liu Zhongliang Jing Han Pan Lingfeng Qiao Henry Leung wujun chen School of Aeronautics and Astronautics Shanghai Jiao Tong UniversityShanghai 200240China Deparment of Elecrical and Computer Engineering University of CalgaryCalgary AB 72N 1N4Canada School of Naval Architecture Ocean&Civil EngineeringShanghai Jiao Tong UniversityShanghai 200240China

Performing complex tasks by soft robots in constrained environment remains an enormous challenge owing to the limitations of flexible mechanisms and control *** this paper,a novel biomimetic soft robot driven by Shape Memory Alloy(SMA)with light weight and multi-motion abilities is *** adapt deep learning to perceive irregular targets in an unstructured *** at the target searching task,an intelligent visual servo control algorithm based on Q-leaming is proposed to generate distance-directed end effector *** particular,a threshold reward system for the target searching task is proposed to enable a certain degree of tolerance for pointing *** addition,the angular velocity and working space of the end effector with load and without load based on the established coupling kinematic model are *** framework enables the trained soft robot to take actions and perform target *** experiments under different conditions demonstrate the convergence of the learning process and effectiveness of the proposed algorithm.

关键词： biomimetic soft robot SMA deep visual servo Q-leaming

Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection

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Journal of Pharmaceutical Analysis 2023年第3期13卷 255-261页

作者： wujun chen Bing Liang Xiaolin Wu Ling Li Chao Wang Dongming Xing Cancer Institute Department of OrthopedicsThe Affiliated Hospital of Qingdao UniversityQingdaoShandong266071China Qingdao Cancer Institute Qingdao UniversityQingdaoShandong266071China Department of Pharmacy The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiGuangdong519000China School of Life Sciences Tsinghua UniversityBeijing100084China

On December 22,2021,the United States Food and Drug Administration approved the first main protease inhibitor,i.e.,oral antiviral nirmatrelvir(PF-07321332)/ritonavir(Paxlovid),for the treatment of early severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** inhibits SARSCoV-2 infection,but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene *** chiral structure of nirmatrelvir plays a key role in its antiviral *** boosts the efficacy of nirmatrelvir by inactivating cytochrome P4503A4 expression and occupying the plasma protein binding *** resistance protein 1 inhibitors may increase the efficacy of ***,Paxlovid has many *** patients treated with Paxlovid experience a second round of coronavirus disease 2019(COVID-19)symptoms soon after ***,the antiviral activity of nirmatrelvir metabolites,such as compounds 12e18,is similar to or higher than that of ***,we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.

关键词： Nirmatrelvir Pharmacology Pharmacokinetics Toxicology Derivatives COVID-19

New insights into the suppression of inflammation and lipid accumulation by JAZF1

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Genes & Diseases 2023年第6期10卷 2457-2469页

作者： wujun chen Yingjie Zhong Yang Yuan Meng Zhu Wenchao Hu Ning Liu Dongming Xing Cancer Institute Department of NeurosurgeryThe Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao Cancer InstituteQingdaoShandong 266071China Department of Endocrinology Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdaoShandong 266035China School of Life Sciences Tsinghua UniversityBeijing 100084China

Atherosclerosis is one of the leading causes of disease and death *** identification of new therapeutic targets and agents is ***1 is expressed in many tissues and is found at particularly high levels in adipose tissue(AT).JAZF1 suppresses inflammation(including IL-1β,IL-4,IL-6,IL-8,IL-10,TNFα,IFN-γ,IAR-20,COL3A1,laminin,and MCP-1)by reducing NF-κB pathway activation and AT immune cell ***1 reduces lipid accumulation by regulating the liver X receptor response element(LXRE)of the SREBP-1c promoter,the cAMP-response element(CRE)of HMGCR,and the TR4 *** and CRE sites are present in many cytokine and lipid metabolism gene promoters,which suggests that JAZF1 regulates these genes through these ***-κB is the center of the JAZF1-mediated inhibition of the inflammatory ***1 suppresses NF-κB expression by suppressing TAK1 ***,TAK1 inhibition also decreases lipid accumulation.A dual-targeting strategy of NF-κB and TAK1 could inhibit both inflammation and lipid ***-target compounds(including prodrugs)1–5 exhibit nanomolar inhibition by targeting NF-κB and TAK1,EGFR,or ***,the NF-κB suppressing activity of these compounds is relatively low(IC50>300 nM).Compounds 6–14 suppress NF-κB expression with IC50 values ranging from 1.8 nM to 38.6 ***-276 is a highly selective,orally bioavailable TAK1 *** structural modifications of compounds using a prodrug strategy may enhance NF-κB *** review focused on the role and mechanism of JAZF1 in inflammation and lipid accumulation for the identification of new anti-atherosclerotic targets.

关键词： Atherosclerosis CRE JAZF1 LXRE NF-κB TAK1

miR-135b:An emerging player in cardio-cerebrovascular diseases

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药物分析学报（英文版） 2024年第10期14卷 1407-1417页

作者： Yingchun Shao Jiazhen Xu wujun chen Minglu Hao Xinlin Liu Renshuai Zhang Yanhong Wang Yinying Dong The Affiliated Hospital of Qingdao University Qingdao UniversityQingdao Cancer InstituteQingdao266071China The Affiliated Hospital of Qingdao University Qingdao UniversityQingdao Cancer InstituteQingdao266071China Department of Radiation Oncology The Affiliated Hospital of Qingdao UniversityQingdao266071China

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and *** studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular *** is involved in regulating the pathological process of myocardial infarction,myocardial ischemia/reperfusion injury,cardiac hypertrophy,atrial fibrillation,diabetic cardiomyopathy,atherosclerosis,pulmonary hyperten-sion,cerebral ischemia/reperfusion injury,Parkinson's disease,and Alzheimer's ***,miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular ***,the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been ***,in this review,we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular *** targeting miR-135b for the treatment of diseases and related patents,highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases,have been discussed.

关键词： miR-135b Myocardial injury Brain injury Cardiovascular diseases Cerebrovascular diseases

Computation method of zero-stress state of pneumatic stressed membrane structure

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Science China(Technological Sciences) 2012年第4期55卷 717-724页

作者： ZHAO JunZhao chen wujun FU GongYi LI RuiXiong Space Structures Research Center Shanghai Jiaotong UniversityShanghai 200030

The whole analysis process of pneumatic stressed membrane structure contains nine states and seven analysis *** zero-stress state is the corner-stone of analysis and design of pneumatic stressed structure,and has significant impact on the pre-stressed state and load *** to the logical model of the whole numerical analysis process of pneumatic stressed structure,a numerical analysis method to solve the zero-stress state from the elasticized equilibrium state was firstly proposed,called linear compatibility matrix M-P inverse ***,the pneumatic membrane stressed structure was transferred into grid structure by using membrane link to simulate membrane ***,on the basis of equilibrium matrix theory of pin joint structure and small deformation assumption,compatibility equation of system was ***,the unstressed length and elongation of links were calculated from the tension and material parameters of elasticized equilibrium ***,using compatibility matrix M-P inverse,the nodal displacement was calculated by solving compatibility equation,the configuration of zero-stress state could be obtained through reverse superposition,and the stress was *** to the algorithm,the program was coded with *** correctness and efficiency of this method were verified by several numerical examples,and it could be found that one elasticized equilibrium state corresponded to one configuration of the zero-stress *** work has theoretical significance and practical guidance value for pneumatic membrane structural design.

关键词： pneumatic stressed membrane structure elasticized equilibrium state the whole analysis process zero-stress state compatibility matrix M-P inverse

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新型体育场径环向索网罩蓬整体提升过程模拟分析

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建筑结构学报 2008年第2期29卷 32-38页

作者：任涛陈务军付功义上海交通大学空间结构研究中心上海200030

根据两节点索单元建立索网非线性平衡方程,用M-P广义逆求解体系运动方程,采用方程特解修正索网运动,建立了索网由无应力态至初始预应力形成过程的分析方法。基于初始形态,采用非线性悬链线索单元列式,由索张力与无应力长度结合控制迭代... 详细信息

根据两节点索单元建立索网非线性平衡方程,用M-P广义逆求解体系运动方程,采用方程特解修正索网运动,建立了索网由无应力态至初始预应力形成过程的分析方法。基于初始形态,采用非线性悬链线索单元列式,由索张力与无应力长度结合控制迭代,实现了索网整体提升控制过程的数值模拟分析,据此编制相应计算程序。最后,进行了一座新型大型体育场马鞍形径环向单层索网罩棚的整体提升张拉过程模拟分析,跟踪整体提升张拉结构从零状态至初始状态以及索张力逐渐导入与形态变化过程,当完成最后一根索的张拉时,所有索内力及节点位置均达到控制目标值,且精度高。结果表明本文分析方法有效,对大型索网结构设计与施工有理论指导意义和参考价值。

关键词：体育场罩蓬施工模拟分析非线性有限元机构运动

Biaxial tensile properties and elastic constants evaluation of envelope material for airship

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Journal of Southeast University(English Edition) 2014年第4期30卷 467-474页

作者：陈建稳陈务军上海交通大学空间结构研究中心上海200030

This paper presents an experimental study to determine the tensile properties of the envelope fabric Uretek3216L under biaxial cyclic *** the biaxial cyclic tests were carefully carried out on the envelope material to obtain the stress-strain data and the corresponding nonlinearity and orthotropy of the material were analyzed. Then for some determination options with different stress ratios the least squares method minimizing the strain terms was used to calculate the elastic constants from the experimental *** the influences of the determination options with different stress ratios and the reciprocal relationship on the elastic constants were *** show that the orthotropy of the envelope material can be attributed to the unbalanced crimp of their constitutive yarns in warp and weft directions and the elastic constants vary noticeably with the determination options as well as the normalized stress *** real design practice it is more reasonable to use constants determined for specific stress states in particular stress ratios depending on the project＆#39;s *** calculating the structures with two limitative sets of elastic constants instead of using only one set is recommendable in light of the great variety of the constant＆#39;s values.

关键词： coated fabric airship tensile property reciprocal relationship elastic constant stress ratio