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Simultaneous quantification of chlorogenic acid and taurocholic acid in human plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Shuanghua Baihe tablets

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Chinese Journal of Natural Medicines 2016年第4期14卷 313-320页

作者： GU Pan LIU Rui-Juan CHENG Min-lu WU Yao zheng lu LIU Yu-Jie MA Peng-Cheng ding Li Department of Pharmaceutical Analysis China Pharmaceutical UniversityNanjing 210009China Nanjing Clinical Tech laboratories Inc. Nanjing 211000China Yangtze River Pharmaceutical Group Taizhou 225321China Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical CollegeNanjing 210042China

An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid(CGA) and taurocholic acid(TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatographic separation was achieved on a Hedera ODS-2 column with a gradient elution using 10 mmol·L^(-1) of ammonium acetate buffer solution containing 0.5% of formic acid- acetonitrile as mobile phase at a flow rate of 300 μL·min-1. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration ranges of 0.1–10 ng·m L^(-1) for CGA and 2–150 ng·m L^(-1) for TCA. It was successfully applied to a pharmacokinetic study of CGA and TCA in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets(SBTs). In the single-dose study, the maximum plasma concentration(C_(max)), time to reach C_(max)(T_(max)) and elimination half-life(t_(1/2)) of CGA were(0.763 8 ± 0.542 0) ng·m L^(-1),(1.0 ± 0.5) h, and(1.3 ± 0.6) h, respectively. In the multiple-dose study, the C_(max), T_(max) and t_(1/2) of CGA were(0.663 7 ± 0.583 3) ng·m L^(-1),(1.1 ± 0.5) h, and(1.4 ± 0.7) h, respectively. For TCA, no significant characteristic increasing plasma TCA concentration-time curve was found in the volunteers after oral administration of SBTs, indicating its complicated process in vivo as an endogenous ingredient.

关键词： Chlorogenic acid Taurocholic acid Shuanghua Baihe tablets Pharmacokinetics LC-MS/MS

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Self-immolative micellar drug delivery:The linker matters

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Nano Research 2018年第12期11卷 6177-6189页

作者： Xuan Meng Min Gao Jian Deng Di lu Aiping Fan Dan ding Deling Kong zheng Wang Yanjun Zhao School of Pharmaceutical Science &Technology Tianjin Key Laboratory for Modem Drug Delivery &High Efficiency and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin)Tianjin UniversityTianjin 300072China State Key Laboratory of Medicinal Chemical Biology (Nankai University) Tianjin 300071China Key Laboratory of Bioactive Materials Ministry of EducationCollege of Life Sciences and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin)Nankai UniversityTianjin 300071China

Redox-responsive polymer-drug conjugate micelles are excellent nanoscale vehicles for self-immolative intracellular drug delivery. To covalently connect the polymer and drug, disulfide-bearing linkers, such as 3,3’-dithiodipropionic acid (DDPA) and 4,4’-dithiodibutyric acid (DDBA), are used. In this paper, we report the influence of linker length on the therapeutic outcome of redox-sensitive conjugate micelles. Curcumin was selected as the model drug and it was conjugated to a multivalent methoxy poly(ethylene glycol)-polylysine copolymer with DDPA or DDBA as the linker. The obtained two polymer-curcumin conjugates were amphiphilic and could self-assemble into micelles that have a hydrodynamic diameter less than 100 nm. The loading of curcumin in both micelles was above 20% (w/w). Irrespective of the linker type, micelle disassembly was observed due to the collapse of the disulfide bond in a reducing environment. However, the rate of curcumin release was much faster with the DDBA linker than with the DDPA linker as the side product was a 5-membered ring with a low ring strain. The linker length-induced variation of curcumin release kinetics caused a significant difference in the intracellular drug concentration and a higher cytotoxicity was witnessed in three model cell lines (HeLa, PC3, and 4T1) for the micelles with a DDBA linker compared to those containing a DDPA linker. As expected, this phenomenon was also observed in HeLa tumor-bearing nude mice in vivo. The current work highlights the significance of linker length in engineering redox-responsive on-demand delivery systems.

关键词： drug delivery micelles redox-responsive curcumin polymer-drug conjugate

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De novo mutation of NAXE(APOAIBP)-related early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1:A case report

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World Journal of Clinical Cases 2023年第14期11卷 3340-3350页

作者： Le ding Ting-Ting Huang guo-Huan Ying Shang-Yu Wang Hai-Feng Xu Hao Qian Faiza Rahman Xiao-Peng lu Hu guo guo zheng Gang Zhang Department of Neurology Children’s Hospital of Nanjing Medical UniversityNanjing 210008Jiangsu ProvinceChina Rehman Medical Institute Peshawar Peshawar 39250Pakistan

BACKGROUND Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1(PEBEL1)is a rare autosomal recessive severe neurometabolic *** aim of this study was to investigate the clinical characteristics and genetic pathogenicity of PEBEL1 caused by rare NAXE(or APOA1BP)-related *** SUMMARY The patient was a girl aged 2 years and 10 *** was hospitalized due to walking disorder for>40 *** clinical manifestations were ataxia,motor function regression,hypotonia,and eyelid *** 1 mo of hospitalization,she developed sigh breathing,respiratory failure,cerebellar edema and brain hernia,and finally she *** were found in cranial imaging,including cerebellar edema accompanied by symmetrical *** whole exome sequencing,we detected NAXE compound heterozygous variation(NM 144772.3)c.733A>C(***245Gln,dbSNP:rs770023429)and novel variation c.370G>T(***124Cys)in the germline *** clinical features and core phenotypes of this case were consistent with 18 previously reported cases of *** This is the first case of NAXE-related PEBEL1 with severe clinical phenotype in China' *** ***124Cys mutation discovered in this case has enriched the pathogenic variation spectrum of NAXE.

关键词： Encephalopathy Respiratory insufficiency Cerebral edema NAXE gene APOAIBP gene Novel variation Case report

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Petrogenesis and tectonic implications of Indosinian granitoids from Western Qinling Orogen,China:Products of magma-mixing and fractionation

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Geoscience Frontiers 2020年第4期11卷 1305-1321页

作者： Xiao Xiong Laimin Zhu guowei Zhang M.Santosh Hang Jiang Jun zheng Anlin guo Lele ding State Key Laboratory of Continental Dynamics Department of GeologyNorthwest UniversityXi’an 710069China School of Earth Sciences and Resources China University of Geosciences Beijing29 Xueyuan RoadBeijing 100083China Department of Earth Sciences University of AdelaideAdelaideSA5005Australia

The Western Qinling Orogen(WQO) is characterized by voluminous distribution of Indosinian granitoids,the formation of which provides an important window to unravel the geochemical and geodynamic evolution and associated *** we investigate a group of intrusions termed "Five Golden Flowers" based on petrological,geochemical,zircon U-Pb geochronological and lu-Hf isotopic studies on the granitoids and their mafic microgranular enclaves(MMEs).Our results show that these intrusions are genetically divided into two types,namely,magma-mixing and highly *** Jiaochangba,lujing,Zhongchuan,and luchuba granitoids are biotite monzogranites(220±0.8 Ma to 217±2.6 Ma) with abundant coeval MMEs(220±.1 Ma to 217±2.7 Ma).The rocks contain moderate to high SiO2,high MgO,Rb,Sr,Ba,and Th contents,but low TiO2,P2 O5,and Sc values,A/CNK of lues of-11.7 to +2.23 with corresponding TDM2values of 1967-1228 *** MMEs possess K-feldspar megacrysts,abundant acicular apatites,and show lopsided *** have lower SiO2,Al2 O3,and Th contents,but higher MgO,TiO2,and Sc,with εHf(t) values of-18.0 to +3.18 and TDM1 of 849-720 *** data indicate that the MMEs were derived from a magma sourced from the enriched lithospheric *** suggest that these host granitoids were produced by partial melting of latePaleoproterozoic to early-Mesoproterozoic lower crust with the involvement of Neoproterozoic SCLM-derived mafic *** Baijiazhuang pluton is dominantly composed of leucogranite(muscovite granite and twomica monzogranite,216±1.5 Ma) without *** rocks are peraluminous with high A/CNK(1.06-1.27).Compared with the other four granitoids,the Baijiazhuang leucogranite shows higher SiO2 content,markedly lower concentrations of TiO2,MgO,Al2 O3,CaO,and Fe2 O3T,and lower LREE/HREE and(La/Yb)N *** leucogranites are also rich in Rb,Th,and U,and display marked depletions in Ba,Sr,Ti,and Eu,indicating that they experienced significa

关键词： Granitoids Western qinling orogen MMEs Magma mixing Fractionation Syn-to post-collisional transition

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Hierarchical Manganese Oxide/Carbon Nanocomposites for Supercapacitor Electrodes

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Nano Research 2011年第2期4卷 216-225页

作者： Yiting Peng zheng Chen Jing Wen Qiangfeng Xiao ding Weng Shiyu He Hongbin Geng Yunfeng lu Department of Materials Science and Engineering Harbin Institute of Technology Harbin 150001 China Department of Chemical and Biomolecular Engineering University of California. Los Angeles CA 90095. USA

MnO2/carbon nanocomposites with hierarchical pore structure and controllable MnO2 loading have been synthesized using a self-limiting growth method. This was achieved by the redox reactions of KMnO4 with sacrificed carbon substrates that contain hierarchical pores. The unique pore structure allows the synthesis of nanocomposites with tunable MnO2 loading up to 83 wt.%. The specific capacitance of the nanocomposites increased with the MnO2 loading; the conductivity measured by electrochemical impedance spectroscopy, on the other hand, decreased with increasing MnO2 loading. Optimization of the MnO2 loading resulted in nanocomposites with high specific capacitance and excellent rate capability. This work provides important fundamental understanding which will facilitate the design and fabrication of high-performance supercapacitor materials for a large variety of applications.

关键词： Hierarchically porous carbon MnO2/carbon nanocomposite supercapacitor

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Synthesis, Biological Activity and 3D-QSAR Study of Novel Pyrrolidine-2,4-dione Derivatives Containing N-Substituted Phenylhydrazine Moiety

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Chemical Research in Chinese Universities 2015年第2期31卷 228-234页

作者： ZHANG Lizhi REN zhengjiao lu Aimin ZHAO zheng XU Wenqin BAO Qianqian ding Weijie YANG Chunlong Jiangsu Key Laboratory of Pesticide Science Key Laboratory of Monitoring and Management of Crop Diseases and Pest lnsects Ministry of Agriculture College of Science Nanjing Agricultural University Nanjing 210095 P R. China

Twenty-seven novel pyrrolidine-2,4-dione derivatives containing N-substituted phenylhydrazine moiety were synthesized. Their structures were confirmed by IH NMR, 13C NMR and MS. The half effective concentration （ECs0） values of the title compounds against the phytopathogenic fungi Rhizoctonia cerealis were evaluated. Com- pounds 61 and 6q displayed good bioactivity with EC50 values of 1.626 and 2.043 μg/mL, respectively. The 3D quantitative structure activity relationship（3D-QSAR） model of CoMFA was established with reliable cross-validated correlation coefficient q2 value of 0.585 and Noncross-validated correlation coefficient r2 value of 0.971. This model provided a tool for guiding further design and synthesis of novel pyrrolidine-2,4-dione derivatives with high fungicidal activity.

关键词： Pyrrolidine-2,4-dione N-Substituted phenylhydrazine Antifungal activity 3D quantitative structure activity relationship(3 D-QSAR)

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皖南伏岭A型花岗岩的成因——地球化学、锆石U-Pb年龄及lu—Hf同位素特征

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地质论评 2024年第1期70卷 189-206页

作者：郑伟陈天虎杜建国陈芳丁宁张舒合肥工业大学资源与环境工程学院合肥230009 安徽省地质调查院(安徽省地质科学研究所) 合肥230001 自然资源部覆盖区深部资源勘查工程技术创新中心合肥230001

伏岭花岗岩体,位于江南造山带东段的皖浙相邻区,岩浆岩沿着近北东向的宁国—绩溪深大断裂断分布。笔者等对伏岭岩体鱼龙川(γ_(5)^(3-2))单元花岗岩开展了系统的全岩岩石地球化学、LA-ICPMS锆石U-Pb同位素年龄和锆石原位lu—Hf同位素地... 详细信息

伏岭花岗岩体,位于江南造山带东段的皖浙相邻区,岩浆岩沿着近北东向的宁国—绩溪深大断裂断分布。笔者等对伏岭岩体鱼龙川(γ_(5)^(3-2))单元花岗岩开展了系统的全岩岩石地球化学、LA-ICPMS锆石U-Pb同位素年龄和锆石原位lu—Hf同位素地球化学研究,结果表明,花岗岩的侵位年龄为131.8±0.9 Ma,富硅、富碱、贫钙、贫铁,具有较高的Rb、Th、U、Ga、Zr和Y含量,较低的Sr、Ba和Nb含量,稀土配分曲线呈现典型的“海鸥式”分布特征,显示强烈的负Eu异常;微量元素原始地幔标准化蛛网图显示明显的Ba、Sr、Nb的负异常。其高SiO_(2)含量和Rb/Sr值、低Ba、Sr含量具备江南造山带东段皖南地区A型花岗岩的典型特征。岩体具有同源岩浆演化特征,源区可能存在磷灰石、钛铁矿的分离结晶作用,而辉石类的分离较少。伏岭岩体主要来源于地壳中镁铁质岩石的部分熔融,其地球化学特征继承于源岩。锆石ε_(Hf)(t)变化范围较小,均在-7.0~-4.6之间,二阶段模式年龄(TDM2)为1478~1630 Ma,伏岭花岗岩可能由中元古代古老下地壳部分熔融形成。伏岭岩体的形成可能受到碰撞作用的影响,岩体形成于后碰撞期,中元古代的基底岩石被大范围的熔融,从而产生了伏岭A型花岗岩。

关键词：伏岭 A型花岗岩岩石地球化学锆石U-Pb年龄 lu—Hf同位素构造环境江南造山带皖南

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The Interoperability of Distributed DBMSs in a CORBA-Based Multidatabase System

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Wuhan University Journal of Natural Sciences 2002年第4期7卷 408-414页

作者： Sarem Mudar Li Rui-xuan Xiao Wei-jun lu zheng-ding Chen Chuan-bo Sch. of Comp. Sci. and Technol. Huazhong Univ. of Sci. and Technol. Wuhan 430074 China

One way of achieving interoperability among heterogeneous, distributed DBMSs is through a multidatabase system. Recently, there is an increasing use of CORBA implementation in developing multidatabase systems. Panorama is a multidatabase system that has been implemented on the top of CORBA compliant namely VisiBroker. It aims to achieve interoperability among Oracle, Sybase and other different DBMSs through the registration of these DBMSs to Panorama and through the single global query language PanoSQL designed for this system. In this paper, we first introduce CORBA for the interoperability in multidatabase systems. Then, a general view for our designed multidatabase system, Panorama, has been given. In section four, we introduce the global query language PanoSQL designed to achieve interoperability among the different DBMSs implemented in Panorama. Then, as an example, we present the registration of Oracle to Panorama in order to achieve interoperability in this system. And finally, a conclusion and the future work for this system have been given.

关键词： interoperability heterogeneity CORBA global query language multidatabase systems

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Reprogrammed astrocytes display higher neurogenic competence, migration ability and cell death resistance than reprogrammed fibroblasts

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Translational Neurodegeneration 2020年第1期9卷 55-65页

作者： Xiaohuan Xia Chunhong Li Yi Wang Xiaobei Deng Yizhao Ma lu ding Jialin zheng Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineShanghai 200072China Collaborative Innovation Center for Brain Science Tongji UniversityShanghai 200092China Departments of Pharmacology and Experimental Neuroscience University of Nebraska Medical CenterOmahaNE 68198-5930USA Department of Pathology and Microbiology University of Nebraska Medical CenterOmahaNE 68198-5930USA

The direct reprogramming of somatic cells into induced neural progenitor cells(iNPCs)has been envisioned as a promising approach to overcome ethical and clinical issues of pluripotent stem cell *** previously reported that astrocyte-derived induced pluripotent stem cells(iPSCs)have more tendencies for neuronal differentiation than fibroblast-derived ***,the differences of neurogenic potential between astrocytederived iNPCs(AiNPCs)and iNPCs from non-neural origins,such as fibroblast-derived iNPCs(FiNPCs),and the underlying mechanisms remain *** results suggested that AiNPCs exhibited higher differentiation efficiency,mobility and survival capacities,compared to *** whole transcriptome analysis revealed higher activities of TGFβsignaling in AiNPCs,versus FiNPCs,following a similar trend between astrocytes and *** higher neurogenic competence,migration ability,and cell death resistance of AiNPCs could be abrogated using TGFβ signaling inhibitor ***,our study demonstrates the difference between iNPCs generated from neural and non-neural cells,together with the underlying mechanisms,which,provides valuable information for donor cell selection in the reprogramming approach.

关键词： Reprogramming Astrocyte Fibroblast Induced neural progenitor cells TGFβsignaling Neurogenesis Proliferation Migration Survival

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流数据密度估计

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计算机科学 2006年第12期33卷 94-96页

作者：聂国梁卢正鼎华中科技大学计算机科学与技术学院武汉430074

密度估计在许多流数据决策系统中都有重要的意义。本文考虑了最近数据的重要性,利用核心密度估计方法,提出了一种适合流数据特点的密度估计算法。该算法利用远远小于数据长度的内存,通过对流数据进行窗口划分,为单个窗口保留少量的分布... 详细信息

密度估计在许多流数据决策系统中都有重要的意义。本文考虑了最近数据的重要性,利用核心密度估计方法,提出了一种适合流数据特点的密度估计算法。该算法利用远远小于数据长度的内存,通过对流数据进行窗口划分,为单个窗口保留少量的分布信息,再综合这些窗口信息,从而实时评估流数据的密度分布。理论和实验证明,该算法是快速有效的。

关键词：流数据密度估计流数据统计近似算法

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