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Science China Chemistry 2023年第6期66卷 1869-1876页

作者： Xuemei Dong lixin sun Ziwen Zhang Tianli Zhu Jie sun Jinzhu Gao Chengjun Dong Rongchen Wang Xianfeng Gu Chunchang Zhao Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center Institute of Fine ChemicalsSchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghai 200237China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China

Taking apart in numerous physiological and pathological activities,hydrogen sulfide(H_(2)S)has been selected as an excellent target spot for the early diagnosis of *** far,there are many mature probes that apply single optical imaging to monitor endogenous H_(2)***,a single modality is not an ideal method to afford accurate diagnostic information in comprehensive biological ***,we developed a dual-modal imaging probe *** designed probe showed a specific response to H_(2)S with both chemiluminescence and NIR fluorescence *** concurrence of fluorescence and chemiluminescence signal provided“double insurances”for highly accurate monitoring of H_(2)***,this dual-modal imaging probe performed precise visualization of endogenous H_(2)S in living cells and in *** envisaged that this chemiluminescence/fluorescence real-time dual-modality strategy for H_(2)S detection will expand and optimize the multimodal imaging methods for efficient diagnosis and treatment of cancer.

关键词： chemiluminescence fluorescence BODIPY dual-modal imaging H_(2)S

Discovery of carbonaceous compressions and their multicellular tissues from the Changzhougou Formation (1 800 Ma) in the Yanshan range, North China

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Chinese Science Bulletin 2000年第9期45卷 841-847页

作者： ZHU Shixing sun Shufen HUANG Xueguang HE Yuzhen ZHU Gengxin sun lixin ZHANG Kuan Tianjin Institute of Geology and Mineral Resources Chinese Academy of Geological SciencesTianjin 300170China Regional Geological Survey Institute Hebei Bureau of Geology and ExplorationLangfang 065001China

In 1997 and 1998, hundreds of specimens of megascopic carbonaceous compressions or algal fossils were found from - 1800-million-year old Changzhougou Formation, which is the lowermost unit of the latest Palaeoproterozoic Changcheng Group (~1 600-1 800 Ma) in the Xinglong-Kuancheng areas at the middle Yanshan Range, North China. They are discoid, ellipsoid and sausage-like, namely shaped like Chuaria Shouhsiennia (Ellipsophyta) and Tawuia. By adopting HF acid-resistant maceration coupled with scanning electron microscope and petrologic section, the authors made a preliminary research on the histology for some circular and ellipsoid carbonaceous compressions, namely Chuaria- and Shouhsienia-llke forms, in addition to their morphology. The following three types of multicellular tissues have been found in the fragments of them: colony-like, pseudoparenchyma-like and parenchyma-like. All of the new data about multicelluar tissues not only supply a very important basis in histology to determine the

关键词： multicellular tissues Carbonaceous compressions Changzhougou Formation Changcheng Group.

A multi-parameter-induced activation of gas therapeutic platform to remarkably amplify photodynamic therapy efficacy

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Science China Chemistry 2024年第7期67卷 2403-2411页

作者： Jie sun Ziwen Zhang Hongyu Wu Xuemei Dong Chengjun Dong lixin sun Zhiqian Guo Yingchao Liu Xianfeng Gu Chunchang Zhao Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center Institute of Fine ChemicalsSchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghai 200237China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China Shandong Provincial Hospital Affiliated to Shandong First Medical University Shandong First Medical University&Shandong Academy of Medical ScienceJinan 250021China

Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT *** uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological ***,we report a multifunction nanomedicine that enables precise gas therapy(including carbon monoxide(CO)release and H_(2)S depletion)using a multi-parameter-induced activation gas release strategy,enlarging the PDT *** nanomedicine uses a disulfide bond to covalently link a photosensitizer with the CO donor 3-hydroxyflavone(3-HF).The disulfide bond can be specifically consumed in H_(2)S-rich tumor areas,releasing the CO donor(3-HF),and also depleting H_(2)*** importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor *** H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT *** expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic *** multi-parameter-activated design strategy provides a new way to improve the precision and efficacy of multimodal synergistic therapy of tumors.

关键词： gas therapy precision gas release hydrogen sulfide depletion photodynamic therapy multimodal synergistic therapy

Aldehyde Dehydrogenase 1 making molecular inroads into the differential vulnerability of nigrostriatal dopaminergic neuron subtypes in Parkinson’s disease

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Translational Neurodegeneration 2014年第1期3卷 212-218页

作者： Huaibin Cai Guoxiang Liu lixin sun Jinhui Ding Transgenics Section Laboratory of NeurogeneticsNational Institute on AgingNational Institutes of HealthBethesdaMD 20892USA Computational Biology Core Laboratory of NeurogeneticsNational Institute on AgingNational Institutes of HealthBethesdaMD 20892USA

A preferential dysfunction/loss of dopaminergic(DA)neurons in the substantia nigra pars compacta(SNpc)accounts for the main motor symptoms of Parkinson’s disease(PD),the most common degenerative movement ***,the neuronal loss is not stochastic,but rather displays regionally selectivity,indicating the existence of different DA subpopulations in the *** identify the underlying molecular determinants is thereby instrumental in understanding the pathophysiological mechanisms of PD-related neuron dysfunction/loss and offering new therapeutic ***,we have demonstrated that aldehyde dehydrogenase 1(ALDH1A1)is one such molecular determinant that defines and protects an SNpc DA neuron subpopulation preferentially affected in *** this review,we provide further analysis and discussion on the roles of ALDH1A1 in the function and survival of SNpc DA neurons in both rodent and human *** also explore the feasibility of ALDH1A1 as a potential biomarker and therapeutic target for PD.

关键词： Parkinson’s disease Substantia nigra pars compacta Dopaminergic neuron Aldehyde dehydrogenase 1,α-synuclein Neurodegeneration Aging

Multi-dimensional visualization for the morphology of lubricant stearic acid particles and their distribution in tablets

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Asian Journal of Pharmaceutical Sciences 2020年第1期15卷 60-68页

作者： Liu Zhang Shailendra Shakya Li Wu Jiangtao Wang Guanghui Jin Huimin sun Xianzhen Yin lixin sun Jiwen Zhang School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Center for Drug Delivery Systems Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Weihai Disu Pharmaceutical Manufacturer Weihai 264200China National Institutes for Food and Drug Control Beijing 100050China

The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid(SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional(3 D) information of SA particles in tablets was detected by a quantitative and non-invasive 3 D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography(SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA(GUT), reprocessed SA(GRT), as well as reference listed drug(RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.

关键词： Stearic acid Morphology Spatial distribution SR-μCT Glipizide tablets

A new perspective of triptolide-associated hepatotoxicity:the relevance of NF-κB and NF-κB-mediated cellular FLICE-inhibitory protein

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Acta Pharmaceutica Sinica B 2020年第5期10卷 861-877页

作者： Ziqiao Yuan Zihang Yuan Muhammad Hasnat Haoran Zhang Peishi Liang lixin sun Zhenzhou Jiang Luyong Zhang Jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China Center for Drug Research and Development Guangdong Pharmaceutical UniversityGuangzhou 510006China Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Quality Control and Pharmacovigilance(China Pharmaceutical University) Ministry of EducationNanjing 210009China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Institute of Pharmaceutical Sciences University of Veterinary and Animal SciencesLahore 54000Pakistan College of Traditional Chinese Medicine Guangdong Pharmaceutical UniversityGuangzhou 510006China

Previously,we proposed a new perspective of triptolide(TP)-associated hepatotoxicity:liver hypersensitivity upon lipopolysaccharide(LPS)***,the mechanisms for TP/LPSinduced hepatotoxicity remained *** present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS ***-αinhibitor,etanercept,was injected intraperitoneally into mice to investigate whether induction of TNF-αby LPS participated in the liver injury induced by TP/LPS *** and hepatocytes pretreated with TP were stimulated with recombinant TNF-αto assess the function of TNF-αin TP/LPS ***,time-dependent MF-κB activation and NF-κB-mediated pro-survival signals were measured in vivo and in ***,overexpression of cellular FLICEinhibitory protein(FLIP),the most potent NF-κB-mediated pro-survival protein,was measured in vivo and in vitro to assess its function in TP/LPS-induced *** counteracted the toxic reactions induced by TP/***-treatment sensitized mice and hepatocytes to TNF-α,revealing the role of TNF-αin TP/LPS-induced *** studies revealed that TP inhibited NF-κB dependent pro-survival signals,especially FLIP,induced by LPS/TNF-α.Moreover,overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity in vivo and TP/TNF-α-induced apoptosis in *** and hepatocytes treated with TP were sensitive to TNF-α,which was released from LPS-stimulated immune *** and other results show that the TP-induced inhibition of NF-κB-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

关键词： Triptolide LPS TNF-x NF-KB FLIP

Deformation-induced interfacial-twin-boundary ω-phase in an Fe_(48)Mn_(37)Al_(15) body-centered cubic metastable alloy

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Journal of Materials Science & Technology 2023年第15期146卷 252-258页

作者： Huabei Peng Xiao Yang lixin sun Liqiu Yong Jiazhen Yan Jinyong Zhang Bingnan Qian Yuhua Wen School of Mechanical Engineering Sichuan UniversityChengdu 610065China School of Mechanical Engineering Hebei University of TechnologyTianjin 300401China State Key Laboratory of Materials Processing and Die and Mould Technology School of Materials Science and EngineeringHuazhong University of Science and TechnologyWuhan 430074China School of Materials and Physics China University of Mining and TechnologyXuzhou 221116China State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an 710072China Innovation Center NPU ChongqingChongqing 401135China Department of Mechanical and Energy Engineering Southern University of Science and TechnologyShenzhen 518055China

Omega(ω)phase has a trigonal or hexagonal crystal structure and was first discovered inβ-type Ti-Cr alloys[1].Since then,theω-phase has been widely reported in numerous group IV transition metal(Ti,Ta,Hf,and Zr)based alloys[2–9].The morphologies ofω-phase could be particle-like(athermalω-phase)[10],ellipsoidal or cuboidal after aging(isothermalω-phase)[11],and plate-like after deformation(stress-relatedω-phase)[12].Amongst,the stressrelatedω-phase is usually located at the twinning boundary,thus also called interfacial-twin-boundary-ω(ITB-ω)*** formation of the ITB-ωphase is considered to be related to the formation of{112}bccmechanical twin(i.e.,{112}bcc twin)in bodycentered cubic(BCC)metals and alloys[13].

关键词： alloys alloy deformation

Population Viability Analysis of Gloydius shedaoensis from Northeastern China:A Contribution to the Assessment of the Conservation and Management Status of an Endangered Species

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Asian Herpetological Research 2010年第1期1卷 48-56页

作者： LIU Peng sun lixin LI Jianli WANG Li ZHAO Wenge JIA Jingbo College of Life Sciences and Technology Harbin Normal University Administrative Office of Snake Island and Laotie Mountain Nature Reserve College of Wildlife Resources Northeast Forestry University

Shedao pit-vipers(Gloydius shedaoensis) on Snake Island in the Liaoning Province, China, are among the most imperiled species in China. The isolated and unique populations are crucial in the recovery of this endangered species by providing a way for conservation and management. Research based on the ecological simulation tools can evaluate alternative mitigation strategies in terms of their benefits to the populations, which are vital for informed decision-making. In this paper, using the program VORTEX 9.42, we developed a population viability analysis(PVA) for the Shedao pit-viper to:(1) address the extinction likelihood of the population;(2) simulate population dynamics under various environment events, and(3) evaluate the efficacy of current protection and management strategies. Overall, we found the population to be susceptible to the factors of catastrophic events, mortality and environment capacity. The population is recovering slowly at present on account of improvement of habitat and greater food availability. Under the current conditions, the probability of extinction in 100 years is approximately zero. These data coincide with the evidence that the wild population may be arriving at K. Our results strengthen the view that protection and management can create a pronounced effect on populations of this endangered species.

关键词： Gloydius shedaoensis VORTEX simulation model sensitivity analysis model veracity test species conservation

On-the-fly active learning of interpretable Bayesian force fields for atomistic rare events

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npj Computational Materials 2020年第1期6卷 1502-1512页

作者： Jonathan Vandermause Steven B.Torrisi Simon Batzner Yu Xie lixin sun Alexie M.Kolpak Boris Kozinsky Department of Physics Harvard UniversityCambridgeMA 02138USA John A.Paulson School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA Center for Computational Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA Department of Mechanical Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA Bosch Research CambridgeMA 02139USA

Machine learned force fields typically require manual construction of training sets consisting of thousands of first principles calculations,which can result in low training efficiency and unpredictable errors when applied to structures not represented in the training set of the *** severely limits the practical application of these models in systems with dynamics governed by important rare events,such as chemical reactions and *** present an adaptive Bayesian inference method for automating the training of interpretable,low-dimensional,and multi-element interatomic force fields using structures drawn on the fly from molecular dynamics *** an active learning framework,the internal uncertainty of a Gaussian process regression model is used to decide whether to accept the model prediction or to perform a first principles calculation to augment the training set of the *** method is applied to a range of single-and multi-element systems and shown to achieve a favorable balance of accuracy and computational efficiency,while requiring a minimal amount of ab initio training *** provide a fully opensource implementation of our method,as well as a procedure to map trained models to computationally efficient tabulated force fields.

关键词： fields element typically

Targeted metabolic analysis of nucleotides and identification of biomarkers associated with cancer in cultured cell models

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Acta Pharmaceutica Sinica B 2013年第4期3卷 254-262页

作者： Chenchen Zhang Zheng Liu Xi Liu Lan Wei Yanjie Liu Jing Yu lixin sun School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Bio-pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China School of Medical Devices Shenyang Pharmaceutical UniversityShenyang 110016China

Cancer,like other diseases accompanied by metabolic changes,shows characteristic DNA/RNA modifications and activities of modifying enzymes,resulting in fluctuations in nucleoside *** this study,we undertook targeted metabolomic analyses of nucleotides in different cancer cell culture models using a sensitive and reproducible ion-pair HPLC *** experimental data were analyzed by principal component analysis(PCA)to identify potential biomarkers in cancer cells,and statistical significance was determined by one-way analysis of *** a result,a clear differentiation of normal and tumor cells into two clusters was shown,indicating abnormal metabolism of nucleotides in tumor *** variables(AMP,UDP,CTP levels with a significance of Po0.05;ATP,UTP and GMP levels with a significance of Po0.01)were considered as potential biomarkers;the content of AMP,UTP,GMP and ATP was significantly higher in cancer *** receiver operating characteristic(ROC)curve analysis allowed us to discriminate normal cells from tumor cells based on area under the curve(AUC).The sequence of their AUC values were:ATP(0.979)4UTP(0.938)4CTP¼GMP(0.896)4AMP(0.812)4UDP(0.792),so we conclude that ATP and UTP are the best potential biomarkers in tumor *** study may provide a valuable tool for studying minute alterations of intracellular nucleotide pools induced by anticancer/antiviral drugs,diseases or environmental factors.

关键词： Ion-pair HPLC Tumor cells Nucleotides Targeted metabolomics analysis PCA