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Synthesis and Anticholinesterase Activity of （-）-Physostigmine Analogues with Modifications at C3a and C5

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Chemical Research in Chinese Universities 2013年第5期29卷 888-893页

作者： wang Hui-jing ZHANG Dan wang fu-sheng WU Yi SONG Hao Innovative Drug Research Center Chongqing University Chongqing 401331 P. R. China Key Laboratory of Drug Targeting and Novel Delivery System of the Ministry of Education West China School of Pharmacy Sichuan University Chengdu 610041 P. R. China

A new series of physostigmine analogues 3a--3j with modifications at the C3a and C5 positions was de- signed and synthesized. Bioassay of the synthetic analogues 3a--3j, along with the previous synthesized C3a-ethyl-C5-triazole physostigmine analogues laJlg and 2a--2j was performed, which indicates that the replace- ment of the carbamoyl moiety of C3a-ethyl-C5-triazole analogues 1 and 2 with a triazole moiety decreased acetyl- cholinesterase（AchE） inhibitory activity, whereas the introduction of heterocycles into the triazole ring increased both AChE and butyrylcholinesterase（BchE） inhibitory activities. Structure-activity relationship（SAR） studies of C3a-methyl-C5-triazole analogues 3 reveal the C3a-methyl substituent is important for AChE and BChE inhibition and the introduction of a second ionizable N center improved the binding of the synthetic analogues to both AChE and BChE.

关键词： C3a-ethyl-C5-triazole physostigmine analogue C3a-methyl-C5-triazole physostigmine analogue Anti-cholinesterase activity Alzheimer's disease

The Mining of Citrus EST-SNP and Its Application in Cultivar Discrimination

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Agricultural Sciences in China 2010年第2期9卷 179-190页

作者： JIANG Dong YE Qing-liang wang fu-sheng CAO Li Citrus Research Institute Chinese Academy of Agricultural Sciences Chongqing 400712 P.R.China

Single nucleotide polymorphisms （SNPs） are the most abundant sequence variations found in plant genomes and are widely used as molecular genetic markers in cultivar identification and genetic diversity studies. The objective of this study was to identify SNP markers useful for discrimination of citrus cultivars, since large numbers of expressed sequence tags （ESTs） of sweet orange are available from the National Center for Biotechnology Information （NCBI）. We now have the opportunity to discover SNP markers suitable for determining the haplotypes with which to distinguish very closely related cultivars and to assess genetic diversity within or between related species of citrus. SNPs and small insertions/deletions （Indels） from ESTs of sweet orange and satsuma were identified by the in silico SNP discovery strategy. 55 296 EST sequences of sweet orange and 2 575 of satsuma retrieved from the NCBI repository were mined for potential SNPs. Cleaved amplified polymorphic sequences （CAPS） and sequencing approaches were used to validate putative SNPs in a sample of 30 citrus accessions. A total of 3 348 putative SNPs were identified based on the abundance of sequences and haplotype cosegregation. Of these 3 348 SNPs, the transitions, transversions and Indels ratios were 47.9, 36.1 and 16.0%, respectively. The SNPs occurred on average at a frequency of 1 per 164 bp in the coding region of citrus. 14 SNPs were randomly selected and genotyped according to 30 citrus accessions including 23 accessions of sweet orange; 11 SNPs displayed polymorphism with an average polymorphism information content （PIC） of 0.20 among 30 citrus accessions. The genetic diversity present in sweet orange was low, so the 14 SNP markers failed to discriminate different cultivars of sweet orange, but they did succeed in distinguishing accessions of inter-species of citrus. In this study, SNPs were mined from EST sequences of sweet orange and satsuma, which displayed potential capability as molecular ma

关键词： citrus single nucleotide polymorphisms (SNPs) EST-SNP cleaved amplified polymorphic sequences (CAPS)

In Situ Synthesis, Structural Characterization and Catalytic Properties of a 2D Cu(Ⅰ)-cyanide Coordination Polymer

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Chinese Journal of Structural Chemistry 2019年第5期38卷 811-818,671页

作者： YANG Ying-Jie wang fu-sheng DONG Gui-Ying College of Chemical Engineering North China University of Science and Technology Tangshan 063210 China College of Mining Engineering North China University of Science and Technology Tangshan 063210 China

A new Cu(Ⅰ) coordination polymer(CP) formulated as [Cu2(L)(CN)2]n(1, L =1,1′-bis(5,6-dimethylbenzimidazole)methane) was synthesized, in which the cyanide anions were generated in situ by the cleavage of C–C bond of acetonitrile under hydrothermal conditions. CP 1 was characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. It crystallizes in the orthorhombic system, Pccn space group, with a = 10.314(3), b = 20.966(7), c =9.432(3)?, V = 2039.5(11)?3, Z = 4, C21 H20 Cu2 N6, Mr = 483.51, Dc = 1.575 g×cm^-3,μ= 2.105 mm-1 and F(000)= 984, the final R = 0.0608 and wR = 0.1942 for 1226 observed reflections with Ⅰ> 2s(Ⅰ)for the CP 1. The CP 1 possesses a 2D {63} layer structure which is composed of Cu(Ⅰ) centers bridged by L and CN– ligands. The thermal stability and luminescence properties of CP 1 are discussed in detail. The complex also displays a remarkable activity for the degradation of methyl orange by hydrogen peroxide in a Fenton-like process.

关键词： Cu(Ⅰ) coordination polymer crystal structure catalytic property in situ reaction luminescence property

Manipulating the 4-1BB Pathway to Cure HBV

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Infectious Diseases & Immunity 2024年第4期4卷 156-157页

作者： Zhang Chao wang fu-sheng Department of Infectious Diseases the Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China

Chronic Hepatitis B Virus(HBV)infection is a major global health issue leading to liver cirrhosis and hepatocellular *** available treatments have limited efficacy in completely eradicating the virus.

关键词： cirrhosis infection hepatocellular

Guidelines for the Diagnosis and Management of Herb-Induced Liver Injury

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Chinese Journal of Integrative Medicine 2018年第9期24卷 696-706页

作者： wang Jia-bo ZHU Yun BAI Zhao-fang wang fu-sheng LI Xiu-hui XIAO Xiao-he Integrative Medical Center 302 Military Hospital of China Research Center for Biological Therapy 302 Military Hospital of China Integrative Medical Center Beijing You An HospitalCapital Medical University

Herb-induced liver injury （HILl） is a type of adverse drug reactions related to using Chinese medicine （CM） or herbal medicine （HM）, and is now a growing segment of drug-induced liver injury （DILl） worldwide. Owing to the complicated compositions and miscellaneous risk factors associated with the clinical usage of CM or HM, it is more challenging to diagnose and manage HILl than DILl. In the present guideline issued by the China Association of Chinese Medicine （CACM）, the authors present an evidence chain-based workflow with 9 structured judgment criteria for diagnosing HILl. The 3 diagnostic ending points--suspected diagnosis, clinical diagnosis, and confirmed diagnosis--could be reached according to the length of the evidence chain acquired in the structured diagnostic workflow. Either identifying the species of CM or HM or excluding adulterations and toxin contaminants was strongly recommended to improve the level of evidence for a clinical diagnosis of HILl. In addition, the authors report that the improper use of CM, which violates the general law of CM theory, is one of the most important factors that contributes to HILl and should be avoided. By contrast, based on syndrome differentiation, some CM can also be used to treat HILl if used in accordance with the general law of CM theory. Therefore, 9 recommendations are put forward in this guideline.

关键词： herb-induced liver injury diagnosis treatment management Chinese medicine guideline

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1999年长江洪水及几点认识

人民长江 2001年第S1期32卷 45-49页

作者： wang sheng-fu Profesor Bureau of River Management Changjiang Water Resources Commissi on Senior Engineer Bureau of River Management Changjiang Water Resources C ommission

Following the basin wide heavy flood on Changjiang River in 1998, a si gnificant flood occurred in 1999. Comparative analysis of both floods in terms of flows and flooding situations shows that both floods had one common feature, that is, the flood stages were fairly high. But they differed greatly at the sa me time, that is, the 1998 flood was a basin wide heavy one while the 1999 flood was a significant local one. At Yichang station there occurred eight flood pea ks in 1998, while in 1999 only three peaks took place. The maximum peak dischar ge at this station in 1999 was 57 600 cubic meters per second, which was smaller than that in 1998. The maximum flood-volume in 30 d of the 1998 flood at this s t ation equaled that in 1954, when an extraordinary heavy flood happened on the River, while the maximum flood-volume in 30 d in 1999 was 25.8 billion cubic me t ers per second smaller than the 1998 one. It is seen that inflow floods from th e upstream Changjiang River (above Yichang) in 1999 were not so big. Comparison of flood volumes in longer period shows that the 1999 flood was relatively conc entrated while the 1998 one had lasted longer duration. Analysis shows that flo oding situations in both years differed significantly in terms of the flood volu mes diverted from river channels due to dyke breaches and collapses, the cases o f polder embankment collapses, the areas of inundated cultivated land and the nu mbers of dangerous events for hydraulic structures. These differences had been resulted from the different properties of both floods and the dyke strengthening efforts made after the 1998 flood. It is seen that flood control engineering c onstructions initiated in the days following the 1998 flood have played an impor tant role in fighting the 1999 flood.

关键词：长江洪水 Changjiang River flood control engineering cultivated land

Characteristics of HIV-1-specific CD8 T-cell responses and their role in loss of viremia in children chronically infected with HIV-1 undergoing highly active antiretroviral therapy

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Chinese Medical Journal 2006年第23期119卷 1949-1957页

作者： ZHANG Zheng ZHAO Qing-xia fu Jun-liang YAO Jin-xia HE Yun JIN Lei wang fu-sheng Research Center of Biological Therapy PLA 302 Hospital Beijing100039 China Department of Infectious Diseases Zhengzhou Sixth HospitalZhengzhou 450054 China

Background Few studies have examined the properties of human immunodeficiency virus type 1 （HIV-1） epitope-specific cytotoxic T lymphocyte （CTL） responses in children. To address this issue, we characterized epitope-specific CTL responses and analyzed the determinants that may affect CTL responses before and after highly active antiretroviral therapy （HAART） in children with HIV-1 infection. Methods A total of 22 HIV-1-infected children and 23 uninfected healthy children as control were enrolled in the study. Circulating CD4 T cells and HIV-1 RNA load in plasma were routinely measured. Peripheral HIV-l-specific CTL frequency and HIV-1 epitope-specific, interferon-y （IFN-y）-producing T lymphocytes were measured using tetramer staining and enzyme-linked immunospot （ELISPOT） assay, respectively. Circulating dendritic cell （DC） subsets were monitored with FACS analysis. Results More than 80% of the children with HIV-1 infection exhibited a positive HIV-1-epitope-specific CTL response at baseline, but HIV-specific CTLs and IFN-y-producing lymphocytes decreased in patients who responded to HAART in comparison with non-responders and HAART-naive children. The duration of virus suppression resulted from HAART was inversely correlated with CTL frequency. While in HAART-naive children, HIV-l-specific CTL frequency was positively correlated with myeloid DC （mDC） frequency, although the cause and effect relationship between the DCs and CTLs remains unknown. Conclusions HIV-l-epitope-specific CTL responses are dependent on antigenic stimulation. The impaired DC subsets in blood might result in a defect in DC-mediated T cell responses. These findings may provide insight into understanding the factors and related mechanisms that influence the outcome of HIV-1 carriers to HAART or future antiviral therapies.

关键词： cytotoxic T lymphocyte dendritic cells human immunodeficiency virus child

Multiresolution for Closed Curves and Surfaces Using Wavelets

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Computer Aided Drafting,Design and Manufacturing 2005年第2期15卷 1-13页

作者： ZHAO Gang BAI Jie wang Chao YAO fu-sheng School of Mechanical Engineering and Automation Beijing University of Aeronautics ＆ Astronautics Beijing 100083 China

Multiresolution modeling is becoming a powerful tool for fast display, and geometric data compression and transmission of complex shapes. Most of the existing literatures investigating the multiresolution for B-spline curves and surfaces are concentrated on open ones. In this paper, we focus on the multiresolution representations and editing of closed B-spline curves and surfaces using wavelets. A repetition approach is adopted for the multiresolution analysis of closed B-spline curves and surfaces. Since the closed curve or surface itself is periodic, it can overcome the drawback brought by the repetition method, i.e. introducing the discontinuities at the boundaries. Based on the models at different multiresolution levels, the multiresolution editing methods of closed curves and surfaces are introduced. Users can edit the overall shape of a closed one while preserving its details, or change its details without affecting its overall shape.

关键词： closed B-spline curves closed B-spline surfaces wavelets multiresolution representation analysis multiresolution representation multiresolution editing

天然免疫应答清除HBV的作用及其临床免疫治疗的前景

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中华医学杂志 2005年第17期85卷 1158-1159页

作者：王福生解放军第三○二医院生物治疗研究中心全军艾滋病和病毒性肝炎重点实验室北京100039

人体抗感染的免疫应答不仅能够控制病毒的复制和清除病毒颗粒、使机体产生保护性的免疫应答和临床恢复,而且还会导致肝脏的慢性炎症和坏死,甚至发生肝硬化等一系列病变,因此抗病毒的免疫应答参与了乙型肝炎的致病过程,因而对乙型肝炎的... 详细信息

人体抗感染的免疫应答不仅能够控制病毒的复制和清除病毒颗粒、使机体产生保护性的免疫应答和临床恢复,而且还会导致肝脏的慢性炎症和坏死,甚至发生肝硬化等一系列病变,因此抗病毒的免疫应答参与了乙型肝炎的致病过程,因而对乙型肝炎的临床进展和预后产生了重要的影响[1].人体抗肝炎病毒的免疫应答包括天然免疫(innate immunity)和特异性免疫应答(adaptive immunity)两个部分.天然免疫应答主要包括NK/NKT细胞亚群、巨噬细胞、树突状细胞(dendritic cells, DC)亚群;特异性免疫应答主要包括各种T淋巴细胞和B淋巴细胞亚群等.上述免疫细胞中DC细胞可能发挥联络的桥梁的作用,NK/NKT、各种T淋巴细胞和B淋巴细胞发挥具体的抗病毒效应[1].本文简述本实验室和国际上其他实验室近年来在乙型肝炎天然免疫(pDC)方面的研究进展。

关键词：临床免疫治疗天然免疫应答清除 HBV 特异性免疫应答乙型肝炎抗肝炎病毒病毒颗粒临床恢复慢性炎症致病过程临床进展抗感染保护性肝硬化抗病毒