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| 1 | Dark matter direct search sensitivity of the PandaX-4T experiment显示文摘The Panda X-4T experiment, a 4-ton scale dark matter direct detection experiment, is being planned at the China Jinping Underground Laboratory. In this paper we present a simulation study of the expected background in this experiment. In a 2.8-ton fiducial mass and the signal region between 1-10 keV electron equivalent energy, the total electron recoil background is found to be 4.9 × 10^(-5) kg^(-1) d^(-1) keV^(-1). The nuclear recoil background in the same region is 2.8 × 10^(-7) kg^(-1) d^(-1) keV^(-1). With an exposure of 5.6 ton-years, the sensitivity of Panda X-4 T could reach a minimum spin-independent dark matter-nucleon cross section of 6 × 10^(-48) cm^2 at a dark matter mass of 40 Ge V/c^2. | HongGuang Zhang Abdusalam Abdukerim Wei Chen Xun Chen YunHua Chen XiangYi Cui BinBin Dong DeQing Fang ChangBo Fu Karl Giboni Franco Giuliani LinHui Gu XuYuan Guo ZhiFan Guo Ke Han ChangDa He ShengMing He Di Huang XingTao Huang Zhou Huang Peng Ji XiangDong Ji YongLin Ju ShaoLi Li Yao Li Heng Lin HuaXuan Liu JiangLai Liu YuGang Ma YaJun Mao KaiXiang Ni JinHua Ning XiangXiang Ren Fang Shi AnDi Tan AnQing Wang Cheng Wang HongWei Wang Meng Wang QiuHong Wang SiGuang Wang XiuLi Wang XuMing Wang Zhou Wang MengMeng Wu ShiYong Wu JingKai Xia MengJiao Xiao PengWei Xie BinBin Yan JiJun Yang Yong Yang ChunXu Yu JuMin Yuan JianFeng Yue Dan Zhang Tao Zhang Li Zhao QiBin Zheng JiFang Zhou Ning Zhou XiaoPeng Zhou | 2019 | Science China(Physics,Mechanics & Astronomy)2019，62，3： | 6 |
| 2 | Analytical methods for investigating in vivo fate of nanoliposomes:A review显示文摘Nanoliposomes are considered to be the most successful nanoparticle drug delivery system, but their fate in vivo has not been fully understood due to lack of reliable bioanalytical methods, which seriously limits the development of liposomal drugs. Hence, an overview of currently used bioanalytical methods is imperative to lay the groundwork for the need of developing a bioanalytical method for liposome measurements in vivo. Currently, major analytical methods for nanoliposomes measurement in vivo include fluorescence labeling, radiolabeling, magnetic resonance imaging(MRI), mass spectrometry and computed tomography. In this review, these bioanalytical methods are summarized, and the advantages and disadvantages of each are discussed. We provide insights into the applicability and limitations of these analytical methods in the application of nanoliposomes measurement in vivo, and highlight the recent development of instrumental analysis techniques. The review is devoted to providing a comprehensive overview of the investigation of nanoliposomes design and associated fate in vivo, promoting the development of bioanalytical techniques for nanoliposomes measurement, and understanding the pharmacokinetic behavior, effectiveness and potential toxicity of nanoliposomes in vivo. | Chong Su Yingze Liu Yang He Jingkai Gu | 2018 | Journal of Pharmaceutical Analysis2018，8，4： | 5 |
| 3 | Synchrotron radiation-based Fourier-transform infrared spectromicroscopy for characterization of the protein/peptide distribution in single microspheres显示文摘The present study establishes a visualization method for the measurement of the distribution and localization of protein/peptide constituents within a single poly-lactide-co-glycolide(PLGA) microsphere using synchrotron radiation–based Fourier-transform infrared spectromicroscopy(SR-FTIR).The representative infrared wavenumbers specific for protein/peptide(Exenatide) and excipient(PLGA) were identified and chemical maps at the single microsphere level were generated by measuring and plotting the intensity of these specific bands.For quantitative analysis of the distribution within microspheres,Matlab software was used to transform the map file into a 3D matrix and the matrix values specific for the drug and excipient were extracted.Comparison of the normalized SR-FTIR maps of PLGA and Exenatide indicated that PLGA was uniformly distributed,while Exenatide was relatively non-uniformly distributed in the microspheres.In conclusion,SR-FTIR is a rapid,nondestructive and sensitive detection technology to provide the distribution of chemical constituents and functional groups in microparticles and microspheres. | Manli Wang Xiaolong Lu Xianzhen Yin Yajun Tong Weiwei Peng Li Wu Haiyan Li Yan Yang Jingkai Gu Tiqiao Xiao Min Chen Jiwen Zhang | 2015 | Acta Pharmaceutica Sinica B2015，5，3： | 5 |
| 4 | Separation and simultaneous quantitation of PGF2α and its epimer 8-iso-PGF2α using modifier-assisted differential mobility spectrometry tandem mass spectrometry显示文摘Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of-principle report of a novel DMS–MS/MS method to separate and simultaneously quantify epimers, taking PGF2α and its 8-epimer, 8-iso-PGF2α, as an example. Good accuracy and precision were achieved in the range of 10–500 ng/m L with a run time of only 1.5 min. Isopropanol as organic modifier facilitated a good combination of sensitivity and separation. The method is the first example of the quantitation of epimers without chromatographic separation. | Chunsu Liang Hui Sun Xiangjun Meng Lei Yina J.Paul Fawcett Huaidong Yu Ting Liu Jingkai Gu | 2018 | Acta Pharmaceutica Sinica B2018，8，2： | 3 |
| 5 | Current status of in vivo bioanalysis of nano drug delivery systems显示文摘The development of nano drug delivery systems(NDDSs)provides new approaches to fighting against diseases.The NDDSs are specially designed to serve as carriers for the delivery of active pharmaceutical ingredients(APIs)to their target sites,which would certainly extend the benefit of their unique physicochemical characteristics,such as prolonged circulation time,improved targeting and avoiding of drugresistance.Despite the remarkable progress achieved over the last three decades,the understanding of the relationships between the in vivo pharmacokinetics of NDDSs and their safety profiles is insufficient.Analysis of NDDSs is far more complicated than the monitoring of small molecular drugs in terms of structure,composition and aggregation state,whereby almost all of the conventional techniques are inadequate for accurate profiling their pharmacokinetic behavior in vivo.Herein,the advanced bioanalysis for tracing the in vivo fate of NDDSs is summarized,including liquid chromatography tandemmass spectrometry(LC-MS/MS),Forster resonance energy transfer(FRET),aggregation-caused quenching(ACQ)fluorophore,aggregation-induced emission(AIE)fluorophores,enzyme-linked immunosorbent assay(ELISA),magnetic resonance imaging(MRI),radiolabeling,fluorescence spectroscopy,laser ablation inductively coupled plasma MS(LA-ICP-MS),and size-exclusion chromatography(SEC).Based on these technologies,a comprehensive survey of monitoring the dynamic changes of NDDSs in structure,composition and existing form in system(i.e.carrier polymers,released and encapsulated drug)with recent progress is provided.We hope that this review will be helpful in appropriate application methodology for investigating the pharmacokinetics and evaluating the efficacy and safety profiles of NDDSs. | Tingting Wang Di Zhang Dong Sun Jingkai Gu | 2020 | Journal of Pharmaceutical Analysis2020，10，3： | 3 |
| 6 | Protein target discovery of drug and its reactive intermediate metabolite by using proteomic strategy显示文摘Identifying protein targets of bioactive compounds is an effective approach to discover unknown protein functions,identify molecular mechanisms of drug action,and obtain information for optimization of lead compounds.At the same time,metabolic activation of a drug can lead to cytotoxicities.Therefore,it is very important to systemically characterize the drug and its reactive intermediate.Mass spectrometry-based proteomic approach has emerged as the most efficient to study protein functions and modifications.This review will discuss method development for the drug target discovery and the application in different fields including the drug toxicity mechanism caused by reactive metabolites. | Lianghai Hu John Paul Fawcett Jingkai Gu | 2012 | Acta Pharmaceutica Sinica B2012，2，2： | 2 |
| 7 | Liquid chromatography–tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma显示文摘A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasma using liquid chromatography–tandem mass spectrometry. Probenecid was used as internal standard and solid-phase extraction was selected for sample preparation. A chromatographic separation was performed on an Agilent Poroshell SB-C_(18) column(50 mm*4.6 mm i.d., 2.7 μm) by an optimized gradient elution at a flow rate of 0.9 mL/min. The total run time was 7 min. Electrospray ionization was used in negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 143.0→143.0 for valproic acid, m/z 140.9→140.9 for 2-enevalproic acid and 4-enevalproic acid for their poor fragments, and m/z 283.9→239.9 for probenecid. The results showed good linearity of valproic acid, 2-enevalproic acid and 4-enevalproic acid in their respective linear ranges.The correlation coef fi cients were more than 0.998. The intra- and inter-day precision of the assay was less than 11.0% and the accuracy ranged from 2% to 12%. This analytical method was successfully applied to assay plasma concentrations of valproic acid and its two ene-metabolites in epilepsy patient plasma and used for therapeutic drug monitoring. | Huan Lu Chong Su Lei Yin Liqiang Gu Jingkai Gu Xiaohui Chen | 2016 | Journal of Pharmaceutical Analysis2016，6，2： | 2 |
| 8 | Determination of telmisartan in human plasma by liquid chromatography–tandem mass spectrometry显示文摘 | Pengfei Li Yingwu Wang Yan Wang Yunbiao Tang J. Paul Fawcett Yimin Cui Jingkai Gu | 2005 | Journal of Chromatography B2005，，1： | 1 |
| 9 | Simultaneous nonchiral determination of artemisinin and arteannuin B in artemisia annua using circular dichroism detection 显示文摘 | Chen J Gu Jingkai Zhao Rui | 2009 | Chromatographia2009，69，： | 1 |
| 10 | Disposition and fate of polyoxyethylene glycerol ricinoleate as determined by LC-Q-TOF MS coupled with MS^(ALL),SWATH and HR MS/MS techniques显示文摘Polyoxyethylene glycerol ricinoleate(PGR) serves as a solubilizer/emulsifier that is commonly used in pharmaceutical formulations despite being associated with severe anaphylactoid hypersensitivity reactions.Cremophor EL?(CrEL) is the most representative PGR produced from reacting ethylene oxide with castor oil.To help clarify the cause of side effects and potentially improve the safety of PGR-based drug delivery vehicle,we have developed separate but related analytical methods for the quantitation of CrEL and its main metabolites,glycerol ethoxylate(GE) and ricinoleic acid(RA).Since CrEL and GE are highly disperse mixtures of polymers that are not amenable to analysis by conventional liquid chromatographytandem mass spectrometry(LC-MS/MS),we used liquid chromatography-triple-quadrupole-time-of-flight mass spectrometry(LC-Q-TOF MS) combined with product ion data acquisition by MSALLand sequential window acquisition of all theoretical fragments mass spectrometry(SWATH MS),respectively to perform the analysis.In contrast,RA is a single molecular entity that could be readily analyzed using conventional LC-HR MS/MS.Selection of specific fragment ions for CrEL,GE,RA and their internal standards enabled a precise quantitation of such a complex analytes system in rat plasma after a single and simple sample preparation method.Assay validation indicated linearity for CrEL,GE and RA over the concentration ranges 0.2~20.0 μg/mL,0.1~10.0 μg/mL and 0.1~20.0 μg/m L,respectively with satisfactory results for other validation parameters.A subsequent pharmacokinetic study involving single intravenous 200 mg/kg injections of CrEL to rats showed the methods enable comprehensive and high throughput quantitation of CrEL and its metabolites in a biological matrix.Our combination of assays provides effective application in investigating the cause of the hypersensitivity reaction of PGR and potentially to improve its safety for using as a vehicle in drug formulations. | Ruifeng Bai Dong Sun Yuqin Shan Zhiqiong Guo Dafeng Chu John Paul Fawcett Jingkai Gu | 2021 | Chinese Chemical Letters2021，32，10： | 1 |
| 11 | The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)in rat显示文摘Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)(PEG-PLA)is a typical amphiphilic di-block copolymer widely used as a nanoparticle carrier(nanocarrier)in drug delivery.Understanding the in vivo fate of PEG-PLA is required to evaluate its overall safety and promote the development of PEG-PLA-based nanocarrier drug delivery systems.However,acquiring such understanding is limited by the lack of a suitable analytical method for the bioassay of PEG-PLA.In this study,the pharmacokinetics,biodistribution,metabolism and excretion of PEG-PLA were investigated in rat after intravenous administration.The results show that unchanged PEG-PLA is mainly distributed to spleen,liver,and kidney before being eliminated in urine over 48 h mainly(>80%)in the form of its PEG metabolite.Our study provides a clear and comprehensive picture of the in vivo fate of PEG-PLA which we anticipate will facilitate the scientifc design and safety evaluation of PEG-PLA-based nanocarrier drug delivery systems and thereby enhance their clinical development. | Xiangjun Meng Zhi Zhang Jin Tong Hui Sun John Paul Fawcett Jingkai Gu | 2021 | Acta Pharmaceutica Sinica B2021，11，4： | 1 |
| 12 | Ternary system of dihydroartemisinin with hydroxypropyl-β-cyclodextrin and ledthin;simultaneous enhancement of drug solubility and stability in aqueous solutions显示文摘 | Dan Wang Haiyan Lia Jingkai Gu | | 0，，： | 1 |
| 13 | Ternary system of dihydroartemisinin with hydroxypropy1-13-cyclodextrin and lecithin :simultaneous enhancement of drug solubility and stability in aqueous solutions 显示文摘 | Wang Dan Li Haiyan Gu Jingkai | 2013 | Journal of Pharma- ceutical and Biomedical Analysis2013，83，： | 1 |
| 14 | Simultaneous nonchiral determination of artemisinin and arteannuin B in Artemisia an- nua using circular dichroism detection 显示文摘 | Chen Jing Gu Jingkai Zhao Rui | 2009 | Chromatographia2009，69，： | 1 |
| 15 | An improved evaluation of the neutron background in the PandaX-Ⅱ experiment显示文摘In dark matter direct detection experiments,neutron is a serious source of background,which can mimic the dark matter-nucleus scattering signals.In this paper,we present an improved evaluation of the neutron background in the PandaX-II dark matter experiment by a novel approach.Instead of fully relying on the Monte Carlo simulation,the overall neutron background is determined from the neutron-induced high energy signals in the data.In addition,the probability of producing a dark-matter-like background per neutron is evaluated with a complete Monte Carlo generator,where the correlated emission of neutron(s)andγ(s)in the(α,n)reactions and spontaneous fissions is taken into consideration.With this method,the neutron backgrounds in the Run 9(26-ton-day)and Run 10(28-ton-day)data sets of PandaX-II are estimated to be(0.66±0.24)and(0.47±0.25)events,respectively. | QiuHong Wang Abdusalam Abdukerim Wei Chen Xun Chen YunHua Chen XiangYi Cui YingJie Fan DeQing Fang ChangBo Fu LiSheng Geng Karl Giboni Franco Giuliani LinHui Gu XuYuan Guo Ke Han ChangDa He Di Huang Yan Huang YanLin Huang Zhou Huang Peng Ji XiangDong Ji YongLin Ju YiHui Lai Kun Liang HuaXuan Liu JiangLai Liu WenBo Ma YuGang Ma YaJun Mao Yue Meng Parinya Namwongsa KaiXiang Ni JinHua Ning XuYang Ning XiangXiang Ren ChangSong Shang Lin Si AnDi Tan AnQing Wang HongWei Wang Meng Wang SiGuang Wang XiuLi Wang Zhou Wang MengMeng Wu ShiYong Wu JingKai Xia MengJiao Xiao PengWei Xie BinBin Yan JiJun Yang Yong Yang ChunXu Yu Jumin Yuan Dan Zhang HongGuang Zhang Tao Zhang Li Zhao QiBin Zheng JiFang Zhou Ning Zhou XiaoPeng Zhou | 2020 | Science China(Physics,Mechanics & Astronomy)2020，63，3： | 0 |
| 16 | Constraining self-interacting dark matter with the full dataset of PandaX-II显示文摘Self-interacting dark matter(SIDM)is a leading candidate proposed to solve discrepancies between predictions of the prevailing cold dark matter theory and observations of galaxies.Many SIDM models predict the existence of a light force carrier that mediates strong dark matter self-interactions.If the mediator couples to the standard model particles,it could produce characteristic signals in dark matter direct detection experiments.We report searches for signals of SIDM models with a light mediator using the full dataset of the PandaX-II experiment,basing on a total exposure of 132 tonne-days.No significant excess over background is found,and our likelihood analysis leads to a strong upper limit on the dark matter-nucleon coupling strength.We further combine the PandaX-II constraints and those from observations of the light element abundances in the early universe,and show that direct detection and cosmological probes can provide complementary constraints on dark matter models with a light mediator. | Jijun Yang Abdusalam Abdukerim Wei Chen Xun Chen Yunhua Chen Chen Cheng Xiangyi Cui Yingjie Fan Deqing Fang Changbo Fu Mengting Fu Lisheng Geng Karl Giboni Linhui Gu Xuyuan Guo Ke Han Changda He Shengming He Di Huang Yan Huang Ran Huo Yanlin Huang Zhou Huang Xiangdong Ji Yonglin Ju Shuaijie Li Qing Lin Huaxuan Liu Jianglai Liu Xiaoying Lu Wenbo Ma Yugang Ma Yajun Mao Yue Meng Nasir Shaheed Kaixiang Ni Jinhua Ning Xuyang Ning Xiangxiang Ren Changsong Shang Guofang Shen Lin Si Andi Tan Anqing Wang Hongwei Wang Meng Wang QiuHong Wang Siguang Wang Wei Wang Xiuli Wang Zhou Wang Mengmeng Wu Shiyong Wu Weihao Wu Jingkai Xia Mengjiao Xiao Xiang Xiao Pengwei Xie Binbin Yan Yong Yang Chunxu Yu Hai-Bo Yu Jumin Yuan Ying Yuan Xinning Zeng Dan Zhang Tao Zhang Li Zhao Qibin Zheng Jifang Zhou Ning Zhou Xiaopeng Zhou | 2021 | Science China(Physics,Mechanics & Astronomy)2021，64，11： | 0 |
| 17 | Biological fate and interaction with cytochromes P450 of the nanocarrier material,D-α-tocopheryl polyethylene glycol 1000 succinate显示文摘D-a-Tocopheryl polyethylene glycol 1000 succinate(TPGS,also known as vitamin E-TPGS)is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol(PEG)1000.It is approved by the US Food and Drug Administration(FDA)and has found wide application in nanocarrier drug delivery systems(NDDS).Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS.However,to date,a bioassay for the simultaneous quantitation of TPGS and its metabolite,PEG1000,has not been reported.In the present study,we developed such an innovative bioassay and used it to investigate the pharmacokinetics,tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing.In addition,we evaluated the interaction of TPGS with cytochromes P450(CYP450s)in human liver microsomes.The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that,after intravenous administration,TPGS and PEG1000 are mainly distributed to the spleen,liver,lung and kidney before both being slowly eliminated in urine and feces as PEG1000.In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4.Overall,our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development. | Tianming Ren Runzhi Li Liqiang Zhao J.Paul Fawcett Dong Sun Jingkai Gu | 2022 | Acta Pharmaceutica Sinica B2022，12，7： | 0 |
| 18 | Determination of Double Beta Decay Half-Life of 136Xe with the PandaX-4T Natural Xenon Detector显示文摘Precise measurement of two-neutrino double beta decay(DBD)half-life is an important step for the searches of Majorana neutrinos with neutrinoless double beta decay.We report the measurement of DBD half-life of 136xe using the Pandax-4T dual-phase Time Projection Chamber(TPC)with 3.7-tonne natural xenon and the first 94.9-day physics data release. | Lin Si Zhaokan Cheng Abdusalam Abdukerim Zihao Bo Wei Chen Xun Chen Yunhua Chen Chen Cheng Yunshan Cheng Xiangyi Cui Yingjie Fan Deqing Fang Changbo Fu Mengting Fu Lisheng Geng Karl Giboni Linhui Gu Xuyuan Guo Ke Han Changda He Jinrong He Di Huang Yanlin Huang Zhou Huang Ruquan Hou Xiangdong Ji Yonglin Ju Chenxiang Li Jiafu Li Mingchuan Li Shu Li Shuaijie Li Qing Lin Jianglai Liu Xiaoying Lu Lingyin Luo Yunyang Luo Wenbo Ma Yugang Ma Yujun Mao Yue Meng Nasir Shaheed Xiaofeng Shang Xuyang Ning Ningchun Qi Zhicheng Qian Xiangxiang Ren Changsong Shang Guofang Shen Wenliang Sun Andi Tan Yi Tao Anqing Wang Meng Wang Qiuhong Wang Shaobo Wang Siguang Wang Wei Wang Xiuli Wang Zhou Wang Yuehuan Wei Mengmeng Wu Weihao Wu Jingkai Xia Mengjiao Xiao Xiang Xiao Pengwei Xie Binbin Yan Xiyu Yan Yong Yang Chunxu Yu Jumin Yuan Ying Yuan Zhe Yuan Dan Zhang Minzhen Zhang Peng Zhang Shibo Zhang Shu Zhang Tao Zhang Li Zhao Qibin Zheng Jifang Zhou Ning Zhou Xiaopeng Zhou Yong Zhou | 2023 | Research2023，，2： | 0 |
| 19 | Full-profile pharmacokinetics, anticancer activity and toxicity of an extended release trivalent PEGylated irinotecan prodrug显示文摘Irinotecan is an anticancer topoisomerase I inhibitor that acts as a prodrug of the active metabolite,SN-38.Unfortunately,the limited utility of irinotecan is attributed to its pH-dependent stability,short half-life and dose-limiting toxicity.To address this problem,a novel trivalent PEGylated prodrug(PEG-[Irinotecan]3)has been synthesized and its full-profile pharmacokinetics,antitumor activity and toxicity compared with those of irinotecan.The results show that after intravenous administration to rats,PEG-[Irinotecan]3 undergoes stepwise loss of irinotecan to form PEG-[Irinotecan]3-x(x=1,2)and PEG-[linker]during which time the released irinotecan undergoes conversion to SN-38.As compared with conventional irinotecan,PEG-[Irinotecan]3 displays extended release of irinotecan and efficient formation of SN-38 with significantly improved AUC and half-life.In a colorectal cancer-bearing model in nude mice,the tumor concentrations of irinotecan and SN-38 produced by PEG-[Irinotecan]3 were respectively 86.2 and 2293 times higher at 48 h than produced by irinotecan.In summary,PEG-[Irinotecan]3 displays superior pharmacokinetic characteristics and antitumor activity with lower toxicity than irinotecan.This supports the view that PEG-[Irinotecan]3 is a superior anticancer drug to irinotecan and it has entered the phaseⅡtrial stage. | Shiwen Song Dong Sun Hong Wang Jinliang Wang Huijing Yan Xuan Zhao John Paul Fawcett Xin Xu Deqi Cai Jingkai Gu | 2023 | Acta Pharmaceutica Sinica B2023，13，8： | 0 |
| 20 | LC-MS/MS Method for the Quantitation of Cefotetan in Human Plasma and Its Application to Pharmacokinetic Study显示文摘 | SHI Meiyun YIN Lei CAI Lanlan WANG Can LIU Xidong ZHAO Sen SUN Yantong FAWCETT J. Paul ZHAO Limei YANG Yan GU Jingkai | 2014 | Chemical Research in Chinese Universities2014，30，6： | 0 |
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