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Isolation and Biochemical Characteristics Analyses of Phenoloxidases (POs) in Three Cultured Mollusk Species

Journal of Ocean University of China 2022年第2期21卷 465-472页

作者： SONG Xiangdi jiang jingwei XING Jing ZHAN Wenbin Laboratory of Pathology and Immunology of Aquatic Animals KLMMEOcean University of ChinaQingdao 266003China Laboratory for Marine Fisheries Science and Food Production Processes Qingdao National Laboratory for Marine Science and TechnologyQingdao 266235China

Phenoloxidases(POs)are a group of copper proteins including tyrosinase,catecholase and laccase,which play crucial roles in the innate immune response of *** this research,POs were studied in cultured mollusk species,including scallop Chla-mys farreri,abalone Haliotis discus hannai and clam Scapharca *** POs were isolated from hemocytes using linear-gradient native-PAGE combined with catechol *** PO activities and their characters were *** molecular mass of PO in *** was 576 kDa,and it was 228 kDa in *** *** ***,four POs were detected and their mole-cular masses were 391 kDa,206 kDa,174 kDa and<67 kDa,which were named as 391-PO,206-PO,174-PO and s-PO,***-netic analyses indicated that all of the POs,except for 391-PO had higher affinity to L-DOPA and catechol than to hydroquinone and ***,all of the POs failed to oxidize *** effects of divalent metal ions on POs’activities were assayed,in-cluding Fe^(2+),Mg^(2+),Zn^(2+),Mn^(2+),Cu^(2+)and Ca^(2+)from FeCl_(2),MgSO_(4),ZnSO_(4),MnCl_(2),CuSO_(4)and CaCl_(2).The POs were inhibited by Fe^(2+)at all determined ***,the inhibition assay showed that all of the POs were inhibited by cysteine,ascorbic acid,sodium sulfite,citric acid,ethylenediaminetetraacetic acid disodium(EDTA)and sodium diethyldithiocarbamate(DETC).The inhibition effects of critric acid and EDTA are *** hannai PO and 391-PO were slightly inhibited by sodium azide,and *** hannai PO,391-PO and 174-PO were slightly inhibited by *** conclusion,the POs in the three cultured mollusks are copper-containing laccase-type phenoloxidases with similar biochemical characteristics even though their molecular masses are different.

关键词： Chlamys farreri Haliotis discus hannai Scapharca subcrenata phenoloxidase divalent metal ions inhibitors

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Artificial intelligence and big data facilitated targeted drug discovery

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Stroke & Vascular Neurology 2019年第4期4卷 206-213页

作者： Benquan Liu Huiqin He Hongyi Luo Tingting Zhang jingwei jiang jiangsu Key Lab of Drug Screening China Pharmaceutical UniversityNanjingChina

Different kinds of biological databases publicly available nowadays provide us a goldmine of multidiscipline big *** Cancer Genome Atlas is a cancer database including detailed information of many patients with *** is a database including detailed information of approved,investigational and withdrawn drugs,as well as other nutraceutical and metabolite *** is a chemical compound database including all commercially available compounds as well as other synthesisable *** Data Bank is a crystal structure database including X-ray,cryo-EM and nuclear magnetic resonance protein three-dimensional structures as well as their *** the other hand,artificial intelligence(AI)is playing an important role in the drug discovery *** integration of such big data and AI is making a great difference in the discovery of novel targeted *** this review,we focus on the currently available advanced methods for the discovery of highly effective lead compounds with great absorption,distribution,metabolism,excretion and toxicity properties.

关键词： metabolism targeted drugs

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Big data and artificial intelligence discover novel drugs targeting proteins without 3D structure and overcome the undruggable targets

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Stroke & Vascular Neurology 2020年第4期5卷 381-387页

作者： Huiqin He Benquan Liu Hongyi Luo Tingting Zhang jingwei jiang jiangsu Key Lab of Drug Screening China Pharmaceutical UniversityNanjingChina Institute of Pharmacologic Science China Pharmaceutical UniversityNanjingChina

The discovery of targeted drugs heavily relies on three-dimensional(3D)structures of target *** the 3D structure of a protein target is unknown,it is very difficult to design its corresponding targeted *** the 3D structures of some proteins(the so-called undruggable targets)are known,their targeted drugs are still *** increasing crystal/cryogenicelectron microscopy structures are deposited in Protein Data Bank,it is much more possible to discover the targeted ***,it is also highly probable to turn previous undruggable targets into druggable ones when we identify their hidden allosteric *** this review,we focus on the currently available advanced methods for the discovery of novel compounds targeting proteins without 3D structure and how to turn undruggable targets into druggable ones.

关键词： structure overcome drugs

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The Role of Standards for Communicable Disease Prevention and Control in Protecting People’s Health and Safety During COVID-19

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China CDC weekly 2020年第42期2卷 823-826页

作者： Lan Feng jingwei jiang Yuan Ma Jinxing Lu National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina

World Standards Day was established by the International Organization for Standardization(ISO)on October 14 to enhance awareness on the significance of international standardization to respond to the needs of businesses,industries,governments and consumers *** its rejoining the ISO in 1978,China held various presentations,symposiums,and commemorative events for World Standards Day in major and medium-sized cities nationwide to publicize the role of standardization in societal development and enhance the awareness of standardization among the people.

关键词： nationwide sized awareness

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Impeding the combination of astrocytic ASCT2 and NLRP3 by talniflumate alleviates neuroinflammation in experimental models of Parkinson's disease

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Acta Pharmaceutica Sinica B 2023年第2期13卷 662-677页

作者： Yang Liu Ting Liu Yuanzhang Zhou Wenjie Li Min Wang Nanshan Song Wenbin Zhang jingwei jiang Shengtao Yuan Jianhua Ding Gang Hu Ming Lu jiangsu Key Laboratory of Neurodegeneration Department of PharmacologyNanjing Medical UniversityNanjing 211166China Department of Pharmacology School of Medicine and Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China Department of Geriatrics Affiliated Brain Hospital of Nanjing Medical UniversityNanjing 210029China Department of Neurosurgery Affiliated Brain Hospital of Nanjing Medical UniversityNanjing 210029China jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 211198China

Alanine-serine-cysteine transporter 2(ASCT2)is reported to participate in the progression of tumors and metabolic *** is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial ***,it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson’s disease(PD).In this study,we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with *** further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP+or LPS/ATP *** ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic(DA)neuron damage in PD models in vitro and in ***,the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasometriggered *** a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug *** is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD ***,these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD,broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.

关键词： ASCT2 NLRP3 Astrocytes Inflammation Neurodegeneration Drug screening Talniflumate Parkinson’s disease

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Isolation and identification of a novel coronavirus from wild bird

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Progress in Natural Science:Materials International 2006年第12期16卷 1275-1280页

作者： ZHANG Guihong**, FU Jiadong**, REN Tao, CAO Weisheng, LUO Kaijiang, XU Chenggang, XIN Chaoan, jiang jingwei and LIAO Ming***(Veterinary Medicine College of South Agriculture University, Guangzhou 510642, China) [a]Veterinary Medicine College of South Agriculture University Guangzhou China

A novel coronavirus strain was isolated from laryngotracheal swab of wild partridge and designated as partridge/GD/S14/2003 (S14). Its whole genomic sequence was obtained (GenBank Accession number: AY646283) through RT-PCR amplification, cloning, nucleotide sequencing, and analysis by the DNASTAR program. To investigate the origin of the virus, we further analyzed the nucleotide sequences of the main structural proteins, and compared those with other available virus isolates. Our results showed that the highest nucleotide homologies between the S1 gene of S14 strain and those of nephrogenic-type strains JX1-99 and TJ2-96 were 94.6% and 93.4%, respectively. In addition, a relatively high genetic identity, 85% and 84.3%, respectively, was detected between S1 gene of S14 and those of strains QXIBV and LX4. The results suggested that the S14 strain may be originated from or related to nephrogenic-type and proventriculus-type infectious bronchitis virus (IBV). The highest nucleotide homology between the S2 gene of S14 strain and those of QXIBV and LX4 was 85% and 84.3%, respectively and all of them belonged to group II coronaviruses. The highest nucleotide homology between the M gene of S14 strain and those of strains SAIB20 and GD6-98 was 90.6% and 90.2%, respectively by which S14 belonged to group III. Although they displayed high level of genetic identity in S1 and S2 gene, there was lower homology of M coding sequences between S14 and BJ, and between S14 and QXIBV strains. Phylogenetic analysis of N gene indicated that group I strains might evolve from RNA recombination between strain H52 and Gray; while group II strains from strain H120 and D1466. S14 strain had the highest N gene homology with strain QXIBV which was 95.7%, thus classified as a group III member. Strains SAIB20 and GD6-98 which were closely related to the M gene of S14 strain belonged to group I and IV, respectively. A possible role of partridge S14 strain may play in the process of coronavirus evolu

关键词： wild bird coronavirus structural protein genes virus evolution.

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Interpretation of the Protocol for Prevention and Control of COVID-19 in China (Edition 7)

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China CDC weekly 2020年第47期2卷 902-905页

作者： Canjun Zheng Zhaorui Chang Fengfeng Liu Mengjie Geng Hui Chen jingwei jiang Sheng Zhou Lu Ran Zhongjie Li Zijian Feng George F.Gao Liping Wang Division of Infectious Disease Key Laboratory of Surveillance and Early Warning on Infectious DiseaseChina CDCBeijingChina National Center for Tuberculosis Control and Prevention China CDCBeijingChina National Institute for Communicable Disease Control and Prevention China CDCBeijingChina Chinese Center for Disease Control and Prevention BeijingChina

After coronavirus disease 2019(COVID-19),previously known as pneumonia of unknown etiology(PUE)and 2019 novel coronavirus(2019-nCoV),was first discovered in Wuhan City,Hubei Province,the Chinese government took measures to stop the spread of the epidemic nationwide and interrupted local transmission in China(1–2).Although there have been several localized outbreaks that were caused by overseas importation of the virus—including Heilongjiang,Jilin,Beijing,Liaoning,and other provincial-level administrative divisions(PLADs)—these outbreaks have been stopped within two to four weeks and were limited in scope to less than ten cases or a few hundred cases for each *** the COVID-19 pandemic still uncontrolled globally,the threat of importing the virus continues unabated and still threatens China’s population,virtually all of which is susceptible.

关键词： nationwide globally administrative

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A novel inhibitor of ARfl and ARv7 induces protein degradation to overcome enzalutamide resistance in advanced prostate cancer

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4165-4179页

作者： Yan Li Ya Chu Guangjiang Shi Xiaobin Wang Wanli Ye Chun Shan Dajia Wang Di Zhang Wei He jingwei jiang Shuqian Ma Yuhong Han Zhili Zhao Shijia Du Zhen Chen Zhiyu Li Yong Yang Chen Wang Xi Xu Hongxi Wu Center for New Drug Safety Evaluation and Research State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 211198China School of Life Science and Technology China Pharmaceutical UniversityNanjing 211198China School of Pharmacy China Pharmaceutical UniversityNanjing 211198China jiangsu Key Lab of Drug Screening China Pharmaceutical UniversityNanjing 211198China

Enzalutamide(ENZ) is a second-generation androgen receptor(AR) antagonist used for the treatment of castration-resistant prostate cancer(CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance(ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR(ARfl)or dominantly active androgen receptor splice variant 7(ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

关键词： Drug resistance Enzalutamide Castration-resistant prostate cancer Androgen receptorsplice variant7 Heterodimers Degradation

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凸轮机构混合弹流润滑特性分析

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润滑与密封 2019年第11期44卷 39-44页

作者：杨福芹姜敬伟青岛科技大学机电工程学院

针对凸轮机构在混合弹流润滑状态下容易过早形成胶合和磨损等问题,对处于混合弹流润滑状态下的凸轮机构润滑特性进行研究。基于载荷分担思想,联立凸轮机构参数方程和弹流润滑理论方程,采用数值解法对凸轮机构推程中的摩擦因数、膜厚和... 详细信息

针对凸轮机构在混合弹流润滑状态下容易过早形成胶合和磨损等问题,对处于混合弹流润滑状态下的凸轮机构润滑特性进行研究。基于载荷分担思想,联立凸轮机构参数方程和弹流润滑理论方程,采用数值解法对凸轮机构推程中的摩擦因数、膜厚和油膜承载占比进行求解,得到6种运动规律凸轮机构的摩擦因数、膜厚和油膜承载占比随凸轮转动的变化曲线,并探究基圆半径、当量弹性模量和转速对凸轮机构混合润滑特性的影响。研究结果表明:增大基圆半径和转速有利于降低推程中的摩擦因数,且使膜厚和油膜承载占比增大,从而有利于改善润滑状况;增大当量弹性模量对推程膜厚影响不大,但会增大摩擦因数,使油膜承载占比减小,从而不利于润滑状况的改善。

关键词：凸轮机构载荷分担混合润滑摩擦因数承载占比

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“明股实债”税法实践中的“股”“债”认定逻辑

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上海市经济管理干部学院学报 2019年第2期17卷 37-45页

作者：蒋经纬华东政法大学国际法学院

“名股实债”一词源于实务界,多适用于房地产领域,其协议内容随着监管和实践的需要不断地发展完善。2013年,国家税务总局颁布了《国家税务总局关于企业混合性投资业务企业所得税处理问题的公告》(以下简称“41号公告”),其主要目的是为... 详细信息

“名股实债”一词源于实务界,多适用于房地产领域,其协议内容随着监管和实践的需要不断地发展完善。2013年,国家税务总局颁布了《国家税务总局关于企业混合性投资业务企业所得税处理问题的公告》(以下简称“41号公告”),其主要目的是为了解决对混合性投资的税法适用问题。然而41号公告并未实现对这一问题解决的愿望,文章将继续对其进行探讨并结合案例研究,提出相应的对策和建议。

关键词：明股实债税法混合型投资

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