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Deciphering structural and functional roles of disulfide bonds in decorsin

Science China Chemistry 2013年第10期56卷 1485-1492页

作者： wu lingzhi LI Ying YANG Yang QIN Meng School of Geography and Biological Information Nanjing University of Posts and Telecommunications National Laboratory of Solid State Microstructure and Department of Physics Nanjing University Department of Chemistry School of Environmental Science and Engineering Nanjing University of Information Science and Technology

Decorsin, an antagonist of integrin glycoprotein IIb/IIIa, contains Arg-Gly-Asp （RGD） sequence and three disulfide bridges. The function of RGD sequence has already been well defined, but the roles of conserved disulfide bonds in antihemostatic proteins still remain unclear. Herein we use the fusion expression and characterization of mutant decorsin to study the func- tions of disulfide bonds in protein structure, stability and biological activity. The purified protein shows an apparent inhibition of activity to platelet aggregation induced by ADP with IC50 of 500 nM. The removal of cys7-cysl5 （from cysteine to serine） at the N-terminal causes a thirty-fold decrease of the inhibition activity with IC50 of 15 ~tM, whereas the mutation of cys22-cys38 at the C-terminal completely impairs the biological activity of decorsin. The overall secondary and tertiary struc- tures of decorsin are disrupted inevitably without disulfide bonds. Using a domain insertion mutation, the retaining of RGD loop and the adjacent disulfide bond produces a week antihemostatic activity of decorsin. This reveals that the overall structure of decorsin stabilized by the three conserved disulfide bridges is cooperative for antihemostatic function. Our study on the ef- fect of disulfide bonds together with RGD-sequence on the protein function is helpful for structure-based drug design of an- tithrombotic research.

关键词： antihemostatic activity decorsin disulfide bonds disintegrins platelet aggregation inhibitor RGD-sequence

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Neuroprotective effects of human telomerase reverse transcriptase on beta-amyloid fragment 25-35-treated human embryonic cortical neurons

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Neural Regeneration Research 2009年第6期4卷 405-412页

作者： Lingping Kong lingzhi wu Jie Zhang Yaping Liao Huaqiao Wang Department of Anatomy and Brain Research Zhongshan School of Medicine Sun Yat-sen University Guangzhou 510080 Guangdong Province China Meizhou People's Hospital Meizhou 514031 Guangdong Province China Department of Anatomy Preclinical College Guangdong University of Pharmacy Guangzhou 510006 Guangdong Province China Department of Bioscience Bengbu Medical College Bengbu 233030 Anhui Province China

BACKGROUND： Numerous current studies have suggested that human telomerase reverse transcriptase （hTERT） gene has neuroprotective effects and can inhibit apoptosis induced by various cytotoxic stresses; however, the mechanism of action remains unknown. OBJECTIVE： To evaluate the neuroprotective effects and possible mechanism of action of hTERT gene transfection in human embryonic cortical neurons treated with beta-amyloid fragment 25-35 （AI325-35）. DESIGN, TIME AND SETTING： The randomized, controlled and molecular biological studies were performed at the Department of Anatomy and Brain Research, Zhongshan School of Medicine, Sun Yat-sen University, China, from September 2005 to June 2008. MATERIALS： AdEasy-1 Expression System was gifted by Professor Guoquan Gao from Sun Yat-Sen University, China. Human cortical neurons were derived from 12-20 week old aborted fetuses, obtained from the Guangzhou Maternal and Child Health Hospital, China. Mouse anti-Odk5 and mouse anti-p16 monoclonal antibodies （Lab Vision, USA）, and mouse anti-hTERT monoclonal antibody （Epitomics, USA）, were used in this study. METHODS：（1） Recombinant adenovirus vectors, encoding hTERT （Ad-hTERT） and green fluorescent protein （Ad-GFP）, were constructed using the AdEasy-1 Expression System. Human embryonic cortical neurons in the Ad-hTERT group were transfected with Ad-hTERT for 1-21 days. Likewise, human embryonic cortical neurons in the Ad-GFP group were transfected with Ad-GFP for 1-21 days. Human embryonic cortical neurons in the control group were cultured as normal. （2） Human embryonic cortical neurons in the Ad-hTERT group were treated with 10 pmol/L Aβ25-35 for 24 hours. Normal human embryonic cortical neurons treated with 10 pmol/Lβ25.35 for 24 hours served as a model group. Human embryonic cortical neurons in the Ad-GFP and control groups were not treated with Aβ25-35. MAIN OUTCOME MEASURES： Expression of hTERT in human embryonic cortical neurons was evaluated by immunocytochemical staining

关键词： human telomerase reverse transcriptase cortical neuron human embryo Alzheimer's disease beta-amyloid fragment 25-35 Cdk5 p16

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Thermodynamical properties of protein kinase with adenine inhibitors

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Chinese Science Bulletin 2013年第1期58卷 68-73页

作者： wu lingzhi HU Dong TANG LiHua HU XiaoFei QIN Meng School of Geography and Biological Information Nanjing University of Posts and Telecommunications State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast University National Laboratory of Solid State Microstructure Department of PhysicsNanjing University

The protein-based molecular recognition of the adenine ring is essential to understand protein function and drug design as *** this paper,a variety of the adenine-based inhibitors with modified groups of amino groups,nitrogen and oxygen atoms in the aromatic ring are designed,and the binding capability of these adenosine analogues with an aminoglycoside antibiotic kinase [APH(3')-IIIa] are investigated with activity assays and isothermal titration calorimetry(ITC) experiments.1-aminoisoquinoline is one of the weakest substrates bound to APH(3')-IIIa with the lowest affinity(high ki and high kd) and the smallest negative value of free energy change(G) among the inhibitors *** binding process of adenine and 5-nitroisoquinoline to APH(3')-IIIa is an enthalpy-driven event with unfavorable entropy,which is consistent with the energy change induced by the binding of ATP to the ***,the reverse is true for 1-aminoisoquinoline,3-amino-5-nitrobenzisothiazole,5-aminoisoquinoline binding to the enzyme because the entropy is more favorable and the enthalpy makes a lower contribution to the binding *** results suggest that small changes of the adenine ring can lead to significant influence on the ability of these analogues to occupy the adenine-binding region of the enzyme,which can be the potential inhibitors as drug candidates against the bacterial resistance.

关键词：蛋白激酶腺嘌呤抑制剂热力学性质氨基糖苷类抗生素药物设计结合能力异喹啉

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Simultaneously enhanced energy storage performance and luminance resistance in (K_(0.5)Na_(0.5))NbO_(3) -based ceramics via synergistic optimization strategy

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Journal of Advanced Ceramics 2024年第1期13卷 34-43页

作者： Yu Huan Diyu Gui Changxiao Li Tao Wei lingzhi wu Xinjian Wang Xiaozhi Wang Zhenxiang Cheng School of Materials Science and Engineering University of JinanJinan 250022China Yangtze Delta Region Transformation Center for Advanced Technological Achievements Suzhou 215000China Electronic Materials Research Laboratory Key Laboratory of the Ministry of Education and International Center for Dielectric ResearchXi’an Jiaotong UniversityXi’an 710032China Institute for Superconducting and Electronic Materials Australian Institute for Innovative MaterialsUniversity of WollongongInnovation CampusNorth Wollongong 2500Australia

The rapidly advancing energy storage performance of dielectric ceramics capacitors has garnered significant interest for applications in fast charge/discharge and high-power electronic *** the exceptional electrical properties in harsh environments can further promote their practical *** carriers can be excited under luminance irradiation,thereby leading to degradation of energy storage ***,a synergic optimization strategy is proposed to enhance energy storage properties and luminance resistance of(K_(0.5)Na_(0.5))NbO_(3)-base(KNN)***,the introduction of Bi(Zn0.5Ti0.5)O_(3) solid solution and La3+ions disrupts the long-range polar orders and enhances super paraelectric relaxation ***,doping La3+ions can increase the band gap and reduce oxygen vacancy concentration,resulting in excellent luminance ***,the viscous polymer process is employed to suppress the grain growth and promote chemical *** a result,ultrahigh recoverable energy storage density(Wrec)of 8.11 J/cm3 and high efficiency(η)of 80.98%are achieved under an electric field of 568 kV/***,the variations in Wrec andηare only 12.45%and 1.75%,respectively,under 500 W xenon lamp irradiation compared to the performance under a dark *** findings hold great potential in facilitating the practical application of dielectric ceramic capacitors in luminance irradiation environments.

关键词： potassium-sodium niobate energy storage performance illumination resistance oxygen vacancy viscous polymer processing

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Unveiling the cellular microstructure-property relations in martensitic stainless steel via laser powder bed fusion

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International Journal of Minerals,Metallurgy and Materials 2024年第11期31卷 2476-2487页

作者： lingzhi wu Cong Zhang Dil Faraz Khan Ruijie Zhang Yongwei Wang Xue Jiang Haiqing Yin Xuanhui Qu Geng Liu Jie Su Collaborative Innovation Center of Steel Technology University of Science and Technology BeijingBeijing 100083China Department of Physics University of Science and Technology BannuBannu 28100Pakistan Beijing Advanced Innovation Center for Materials Genome Engineering University of Science and Technology BeijingBeijing 100083China Beijing Key Laboratory of Materials Genome Engineering University of Science and Technology BeijingBeijing 100083China Institute for Advanced Materials and Technology University of Science and Technology BeijingBeijing 100083China Institute for Special Steel Research Central Iron and Steel Research InstituteBeijing 100081China

Laser powder bed fusion(LPBF)is a widely recognized additive manufacturing technology that can fabricate complex components rapidly through layer-by-layer ***,there is a paucity of research on the effect of laser scanning speed on the cellular microstructure and mechanical properties of martensitic stainless *** study systematically investigated the influence of laser scanning speed on the cellular microstructure and mechanical properties of a developed Fe11Cr8Ni5Co3Mo martensitic stainless steel produced by *** results show that increasing the laser scanning speed from 400 to 1000 mm/s does not lead to a noticeable change in the phase fraction,but it reduces the average size of the cellular microstructure from 0.60 to 0.35μ*** scanning speeds of 400 and 1000 mm/s both had adverse effects on performances of sample,resulting in inadequate fusion and keyhole defects *** optimal scanning speed for fabricating samples was determined to be 800 mm/s,which obtained the highest room temperature tensile strength and elongation,with the ultimate tensile strength measured at(1088.3±2.0)MPa and the elongation of(16.76±0.10)%.Furthermore,the mechanism of the evolution of surface morphology,defects,and energy input were clarified,and the relationship between cellular microstructure size and mechanical properties was also established.

关键词： laser powder bed fusion martensitic stainless steel cellular microstructure mechanical properties strengthening mechanism

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Identification of a class of potent USP25/28 inhibitors with broad-spectrum anti-cancer activity

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Signal Transduction and Targeted Therapy 2023年第1期8卷 3-5页

作者： Jin Peng Kun Jiang Xiao Sun lingzhi wu Jiewei Wang Xiaomei Xi Xu Tan Tingbo Liang Changheng Tan Pumin Zhang Zhejiang Provincial Key Laboratory of Pancreatic Diseases The First Affiliated Hospital of Zhejiang UniversityHangzhouZhejiang 310003China Shanghai Institute of Materia Medica Shanghai 200216China Chaser Therapeutics Inc.HangzhouZhejiang Province 310018China Beijing Advanced Innovation Center for Structural Biology School of Pharmaceutical SciencesTsinghuaPeking Center for Life SciencesTsinghua UniversityBeijingChina

Dear Editor,An increasing body of evidence suggests that USP28 could be a target for cancer treatment^(1-4).To identify its inhibitors,we screened a 100-thousand synthetic compound library and found 3 lead compounds,CT1001-1003,that showed significant inhibitory activity(Supplementary Fig.1a).The optimization of these compounds led to CT1018,a much stronger inhibitor(Supplementary Fig.1b).

关键词： cancer spectrum inhibitors

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吴灵芝教授治疗脑瘫足内翻(脾虚肝亢证)经验

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中国中医药现代远程教育 2024年第8期22卷 68-70页

作者：谢莹吴灵芝安徽中医药大学第二附属医院儿科安徽合肥230061

吴灵芝教授认为,脑瘫足内翻(脾虚肝亢证)主要见于痉挛型四肢瘫、痉挛型双瘫以及痉挛型偏瘫,其病机为脾虚生痰、血少筋强、阴急阳缓,宜从肝脾论治;临床治疗上针药并用,辅以肌内效贴加强疗效,诸法并用以达健脾化痰、养血柔筋、平衡阴阳之... 详细信息

吴灵芝教授认为,脑瘫足内翻(脾虚肝亢证)主要见于痉挛型四肢瘫、痉挛型双瘫以及痉挛型偏瘫,其病机为脾虚生痰、血少筋强、阴急阳缓,宜从肝脾论治;临床治疗上针药并用,辅以肌内效贴加强疗效,诸法并用以达健脾化痰、养血柔筋、平衡阴阳之效,可有效降低踝部内侧肌张力,促进踝部内、外侧肌张力平衡,改善足内翻角度。

关键词：痿证脑瘫偏枯足内翻脾虚肝亢证针药结合肌内效贴吴灵芝

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介电泳技术在生物信号检测和相分离阻变材料中的应用

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中国科学：技术科学 2016年第3期46卷 235-242页

作者：武灵芝董帅南京邮电大学地理与生物信息学院南京210046 东南大学物理系南京211189

介电泳是操纵微纳米级粒子的强大工具,已经在生物细胞和无机微粒的分离、检测、操控方面得到了广泛的应用.本文突破对介电泳技术的传统定位,简要介绍介电泳效应的两例新的应用.首先是和新兴的纳米孔技术结合,利用介电泳的富集效应,在微... 详细信息

介电泳是操纵微纳米级粒子的强大工具,已经在生物细胞和无机微粒的分离、检测、操控方面得到了广泛的应用.本文突破对介电泳技术的传统定位,简要介绍介电泳效应的两例新的应用.首先是和新兴的纳米孔技术结合,利用介电泳的富集效应,在微纳环境下对单分子行为进行操控,解决目前纳米孔基因测序面临的通量低等难题.其次在某些相分离固体材料中,介电泳可以通过调节电子相的几何结构引起渗流,从而实现电致阻变效应.这些研究不仅扩大了介电泳技术的应用范围,且具有多学科技术交叉融合的特点,为生物检测技术的开发创新以及新型功能材料的设计提供了新的思路.

关键词：介电泳技术生物分子操纵纳米孔相分离锰氧化物阻变材料

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水深数据质量等级评定方法研究

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海洋测绘 2023年第5期43卷 73-77页

作者：邬凌智交通运输部北海航海保障中心天津300220

针对电子航海图中CATZOC/QoBD属性如何赋值这一问题,在详细介绍国际海道测量组织(IHO)相关标准开发情况和深入分析其在我国适用性的基础上,提出了符合我国国情的水深数据质量等级评定方法。对标国际并结合国内实际,从基本赋值原则、降... 详细信息

针对电子航海图中CATZOC/QoBD属性如何赋值这一问题,在详细介绍国际海道测量组织(IHO)相关标准开发情况和深入分析其在我国适用性的基础上,提出了符合我国国情的水深数据质量等级评定方法。对标国际并结合国内实际,从基本赋值原则、降级因素、测算程序和步骤等3个方面,提出了具体可行的国内CATZOC/QoBD属性赋值思路和建议,可为我国水深数据质量等级的评定和电子航海图中水深数据置信度等级设置提供参考。

关键词：海洋测绘电子航海图水深数据水深数据质量数据质量评估与分级置信度类别

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体验设计在日用陶瓷设计中的应用

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中国陶瓷 2008年第9期44卷 35-36页

作者：吴凌之广州美术学院广州510260

随着体验经济的到来,人们过去对乏味的物质生活追求已被精神生活和心理体验的追求所代替。体验设计作为一种关注人类情感和体验的设计方法,将给日用陶瓷设计带来新的活力。

关键词：体验经济体验设计日用陶瓷设计

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