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Design,synthesis and anti-HBV activity of novel bis(trifluoroethyl)phosphonomethyl ether derivatives of acyclovir

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Chinese Chemical Letters 2009年第5期20卷 507-510页

作者： Peng Lu Sai hong jiang jiang Xia Liu yu she yang ru yun ji State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institute for Biological Sciences Chinese Academy of Science Shanghai 201203 China Fudan University Shanghai 200032 China

A series of novel bis（trifluoroethyl）phosphonomethyl ether derivatives of acyclovir was synthesized and their in vitro anti-HBV activity was evaluated in HepG2 2.2.15 cells. In contrast to acyclovir, most of the described phosphonates emerged as potent inhibitors of HBV replication. Especially, the most active compound 11 with IC50 value of 2.92 μmol/L was 33 times more potent than acyclovir with ICso value of 100 μmol/L.

关键词： Acyclovir Phosphonate Anti-HBV activity

Design, synthesis and in vitro evaluation of L-amino acid esters prodrugs of acyclic nucleoside phosphonates as anti-HBV agent

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Chinese Chemical Letters 2007年第7期18卷 817-819页

作者： Xiao Zhong Fu Sai hong jiang jian Xin yu she yang ru yun ji School of Pharmacy Guiyang Medical College Guiyang 550004 China State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institute for Biological SciencesChinese Academy of Science Shanghai 201203 China Shanghai Fudan-yueda Bio-Tech Co. Ltd. Shanghai 201203 China

A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively.

关键词： Acyclic nucleoside phosphonates L-Amino acid Prodrug Anti-HBV activity

Flame-retardant and Self-healing Biomass Aerogels Based on Electrostatic Assembly

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Chinese Journal of Polymer Science 2020年第12期38卷 1294-1304页

作者： ji-yu yang yu Xia jin Zhao Long-Fei Yi Yong-jiao Song hong Wu Shao-yun Guo Li-juan Zhao jin-Rong Wu College of Chemistry and Materials Science Sichuan Normal UniversityChengdu 610066China State Key Laboratory ofPolymer Materials Engineering Polymer Research InstituteSichuan UniversityChengdu 610065China State Key Laboratory ofPolymer Materials Engineering Collegeof Polymer Science and EngineeringSichuan UniversityChengdu 610065China

It remains a significant challenge to fabricate self-healing aerogels with excellent flame ***,we develop a class of biomass aerogels by electrostatically assembling chitosan(CS),phytic acid(PA),and itaconic acid(IA).The electrostatic interaction between CS and IA is weak and dynamic,so freeze-drying the solution of CS and IA enables the formation of continuous aerogel skeleton with self-healing ability and re-programmability;in comparison,the electrostatic interaction between CS and PA is strong and less dynamic,and thus mixing PA with CS in aqueous solution leads to fine precipitates of high flame retardancy due to the synergistic phosphorus-nitrogen *** the continuous skeleton and the fine precipitates results in self-healing aerogles with UL-4 V-0 rating of flame retardancy aerogels and autoextinguishable ***,the aerogels after burning in flame for 30 s form a skin-core structure,and the carbonized skin protects the integrity of the aerogels and the self-healing ability of the internal ***,this work provides a facile strategy to develop multifunctional aerogels which hold great promise for advanced applications.

关键词： Chitosan Flame retardancy Electrostatic interactions Biomass aerogel Self-healing

一类具有胰岛素增敏作用的苯并吡喃衍生物的设计和合成

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药学学报 2008年第6期43卷 605-610页

作者：汤磊李煜俞娟红杨玉社嵇汝运贵阳医学院药学院贵州贵阳550004 中国科学院上海生命科学研究院上海药物研究所国家新药研究重点实验室上海201203

在化合物1基础上设计合成了10个新型化合物,用3T3-L1前脂肪细胞对这些化合物进行了胰岛素增敏活性筛选。结果表明化合物10在3T3-L1脂肪细胞模型上表现出较强的促3T3-L1细胞分化活性,提示其可能具有较好的胰岛素增敏作用。

关键词：胰岛素增敏剂合成 3T3-L1细胞

Heredity and gene mapping of a novel white stripe leaf mutant in wheat

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Journal of Integrative Agriculture 2021年第7期20卷 1743-1752页

作者： LI Hui-juan jiAO Zhi-xin Nl Yong-jing jiANG yu-mei LI Jun-chang PAN Chao ZHANG jing SUN yu-long AN Jun-hang LIU hong-jie LI Qiao-yun NIU ji-shan National Centre of Engineering and Technological Research for Wheat/National Key Laboratory of Wheat and Maize Crop Science/Henart Agricultural University Zhengzhou 450046P.R.China Shangqiu Academy of Agricultural and Forestry Sciences Shangqiu 476000P.R.China

Spotted leaf(spl)mutant is a type of leaf lesion mimic mutants in *** obtained some lesion mimic mutants from ethyl methane sulfonate(EMS)-mutagenized wheat(Triticum aestivum L.)cultivar Guomai 301(wild type,WT),and one of them was named as white stripe leaf(wsl)mutant because of the white stripes on its *** we report the heredity and gene mapping of this novel wheat mutant *** are many small scattered white stripes on the leaves of wsl throughout its whole growth *** the plants grew,the white stripes became more severe and the necrotic area *** mutant wsl grew only weakly before the jointing stage and gradually recovered after *** length and width of the flag leaf,spike number per plant and thousand-grain weight of wsl were significantly lower than those of the *** analysis indicated that the trait of white stripe leaf was controlled by a recessive gene locus,named as wsl,which was mapped on the short arm of chromosome 6 B by SSR marker *** SSR markers in the F2 population of wsl×CS were linked to wsl in the order of Xgpw1079–Xwmc104–Xgwm508-wsl–Xgpw7651 at 7.1,5.2,8.7,and 4.4 c M,respectively and three SSR markers in the F2 population of wsl×jimai 22 were linked to wsl in the order of Xgwm508–Xwmc494–Xgwm518-wsl at 3.5,1.6 and 8.2 c M,*** comparison to the reference genome sequence of Chinese Spring(CS),wsl is located in a 91-Mb region from 88 Mb(Xgwm518)to 179 Mb(Xgpw7651)on chromosome 6 *** wsl is a novel germplasm for studying the molecular mechanism of wheat leaf development.

关键词： wheat(Triticum aestivum L.) mutant white stripe leaf(wsl) heredity gene mapping

Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy

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Cellular & Molecular Immunology 2012年第5期9卷 417-422页

作者： juan Zhao ji-yuan Zhang hong-Wei yu yu-Lan He jing-jing Zhao juan Li yue-Ke Zhu Qin-Wei Yao jin-Huan Wang Hai-Xia Liu Shu-yun Shi Zheng-sheng Zou Xiang-sheng Xu Chun-Bao Zhou Fu-sheng Wang Qing-Hua Meng Department of Hepatology Beijing You An HospitalCapital Medical UniversityBeijingChina Research Center for Biological Therapy The Institute of Translational HepatologyBeijing 302 HospitalBeijingChina Department of Infectious Disease Beijing 302 HospitalBeijingChina juan Zhao and ji-yuan Zhang contributed equally to this work.

Acute-on-chronic liver failure （ACLF） is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells （mDCs） and the efficacy of methylprednisolone （MP） treatment for hepatitis B virus （H BV）-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at lO-day intervals; 26 patients received conservative medical （CM） management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/ transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.

关键词： acute-on-chronic liver failure methylprednisolone myeloid dendritic cells plasmacytoid dendritic cells

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline(updated version)

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Military Medical Research 2020年第3期7卷 249-282页

作者： Ying-Hui jin Qing-yuan Zhan Zhi-Yong Peng Xue-Qun Ren Xun-Tao Yin Lin Cai yu-Feng yuan ji-Rong yue Xiao-Chun Zhang Qi-Wen yang jianguang ji jian Xia Yi-Rong Li Fu-Xiang Zhou Ya-Dong Gao Zhui yu Feng Xu Ming-Li Tu Li-Ming Tan Min yang Fang Chen Xiao-Ju Zhang Mei Zeng yu Zhu Xin-Can Liu jian yang Dong-Chi Zhao yu-Feng Ding Ning Hou Fu-Bing Wang Hao Chen Yong-Gang Zhang Wei Li Wen Chen yue-Xian Shi Xiu-Zhi yang Xue-Jun Wang Yan-Jun Zhong Ming-juan Zhao Bing-Hui Li Lin-Lu Ma Hao Zi Na Wang yun-yun Wang Shao-Fu yu Lu-Yao Li Qiao Huang hong Weng Xiang-Ying Ren Li-Sha Luo Man-ru Fan Di Huang hong-yang Xue Lin-Xin yu jin-Ping Gao Tong Deng Xian-Tao Zeng hong-Jun Li Zhen-Shun Cheng Xiao-Mei Yao Xing-Huan Wang Center for Evidence-Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China National Clinical Research Center for Respiratory Diseases China-Japan Friendship HospitalBeijing 100029China Department of Pulmonary and Critical Care Medicine China-Japan Friendship HospitalBeijing 10029China Leishenshan Hospital in Wuhan Wuhan 430200China Department of Critical Care Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Institutes of Evidence-based Medicine and Knowledge Translation Henan UniversityKaifeng 475000HenanChina Department of Medical Imaging Guizhou Provincial People’s HospitalGuiyang 550002China Departments of Orthopedics Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Hepatobiliary Surgery Zhongnan Hospital of Wuhan UniversityWuhan 430071China National Clinical Research Center for Geriatrics West China Hospital of Sichuan UniversityChengdu 610041China Department of Geriatrics West China Hospital of Sichuan UniversityChengdu 610041China Department of Radiology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Clinical Laboratory Peking Union Medical College Hospital(PUMCH)Peking Union Medical CollegeChinese Academy of Medical Sciences(CAMS)Beijing 100730China Center for Primary Health Care Research Lund University and Region Skåne25002 MalmöSweden Emergency Center Zhongnan Hospital of Wuhan UniversityWuhan 403371China Department of Allergology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan UniversityWuhan 43071China Department of Critical Care Medicine Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Emergency Medicine and Chest Pain Center Qilu Hospital of Shandong UniversityJinan 250002China Department of Respiratory and Critical Care Medicine Suizhou Central HospitalHubei University of MedicineSuizhou 441300HubeiChina Department of Clinic Pharmacy Second People’s Hospital of Huaihua Ci

The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the *** and treatment guidelines for clinicians caring for patients are *** the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based *** formed a working group of clinical experts and *** steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge *** searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)*** were either strong or weak,or in the form of ungraded consensus-based ***,we issued 34 *** them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based *** covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung

关键词： COVID-19 SARS-CoV-2 Recommendation Chemoprophylaxis Diagnosis Treatment Discharge management Traditional Chinese medicine guideline

新型非环核苷膦酸L-氨基酸酯类化合物的设计、合成与抗乙型肝炎病毒活性

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药学学报 2008年第5期43卷 495-503页

作者：傅晓钟江赛红杨玉社嵇汝运贵阳医学院药学院贵州贵阳550004 中国科学院上海生命科学研究院上海药物研究所新药研究国家重点实验室上海201203

设计合成具有抗乙型肝炎病毒活性的非环核苷膦酸双L-氨基酸酯系列衍生物。以adefovir dipivoxil为先导化合物,根据核苷L-氨基酸酯前药提高生物利用度及抗病毒活性的研究结果对先导化合物进行结构优化,设计并合成一系列新型非环核苷膦酸... 详细信息

设计合成具有抗乙型肝炎病毒活性的非环核苷膦酸双L-氨基酸酯系列衍生物。以adefovir dipivoxil为先导化合物,根据核苷L-氨基酸酯前药提高生物利用度及抗病毒活性的研究结果对先导化合物进行结构优化,设计并合成一系列新型非环核苷膦酸双L-氨基酸类化合物,确定其结构,并通过测定其对HepG2 2.2.15细胞分泌的HBV-DNA的抑制作用评价其体外抗病毒活性。结果发现8个adefovir双L-氨基酸类化合物可显示不同程度活性,其中化合物11的抗病毒活性最强、选择性指数最高(EC500.095 2μmol.L-1,SI 69523)。以上研究提示L-氨基酸酯策略可适用于非环核苷膦酸的前药修饰,以期发现有效抗HBV药物。

关键词：非环核苷膦酸 L-氨基酸前药

Insulin-sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative in vitro

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Acta Pharmacologica Sinica 2007年第3期28卷 417-422页

作者： Hao-shu WU~(2,4) juan-hong yu~(3,4) Ying-yin LI~2 yu-she yang~3 Qiao-jun HE~2 Yi-jia LOU~(2,5) ru-yun ji~3 ~2Department of Pharmacology and Toxicology,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China ~3State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Shanghai Institutes for Biological Sciences,Graduate School of the Chinese Academy of Sciences,Shanghai 201203,China Department of Pharmacology and Toxicology College of Pharmaceutical Sciences Zhejiang University Hangzhou China Department of State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Graduate School of the Chinese Academy of Sciences Shanghai China

Aim:To examine the insulin sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative YY20 in insulin-sensitive cell ***:Theperoxisome proliferator-activated receptor γ（PPARγ）agonist bioactivities of YY20were detected by a preadipocyte differentiation ***-PCR and Westernblotting analysis were used to detect the expression of the target gene or *** effects of YY20 on insulin-mediated glucose consumption were determined inthe HepG2 human hepatocellular carcinoma ***:YY20 could enhancethe differentiation of preadipocytes to adipocytes and upregulate the gene ex-pression of PPARγ2,as well as the protein expression of insulin receptor sub-strate-1（IRS-1）,glucose transporter-4（GLUT4）,and adiponectin（ACRP30）.Theeffects on GLUT4 and ACRP30 could be reversed by the PPARγ inhibitor ***,YY20 efficiently reduced glucose consumptions in HepG2 cells after24 h culture,and the effects were related to insulin and YY20 ***:YY20,a potential insulin-sensitizing agent like rosiglitazone,couldenhance glucose consumption in HepG2 cells in a concentration-and insulin-dependent *** may improve the insulin resistance associated with type 2diabetes.

关键词： YY20 peroxisome proliferator-activated receptor y insulin sensitivity glucose consumption