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Dendritic nanomedicine enhances chemoimmunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3680-3696页

作者： Yunkun Li Xiaoding Shen Haitao Ding Yuxin Zhang Dayi Pan Liping Su Yahui Wu Zaixiang Fang jie zhoua Qiyong Gong Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune ***,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-231)*** cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen ***,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating *** a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

关键词： Dendritic prodrug Enhanced penetration Metabolic intervention Cancer-associated fibroblasts Immunogenic cell death Chemotherapy Immunotherapy Immune microenvironment reconstitution

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Crystal structure of a bacterial homolog to human lysosomal transporter,spinster

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Science Bulletin 2019年第18期64卷 1310-1317页

作者： Fu zhoua Deqiang Yao Bing Rao Li Zhang Wang Nie Yan Zou jie Zhao Yu Cao CAS Center for Excellence on Molecular Cell Science Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 201210China Institute of Precision Medicine The Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200125China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of Orthopaedics Shanghai Key Laboratory of Orthopaedic ImplantShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

Lysosomes break down various biomolecules and spinster is one of the major efflux carriers removing degradation products from lysosomal lumen to keep it in healthy size and proper *** it is well established that a dysfunctional spinster will cause enlarged lysosomes and in turn lead to developmental defects and abnormal behavior in animals,little was known about the transportation mechanism and substrate specificity of ***,we report a crystal structure of spinster homolog from Hyphomonas neptunium,HnSPNS,in its inward-facing conformation with and without substrate *** is crystallized in a monomer and a substrate-binding cavity was formed in the center of its transmembrane helices.A blob of electron density corresponding to its substrate was found in the cavity near a conserved residue,R42,which is locked in position by the interactions with conserved residues E129 and *** results suggest that human spinster serves as a transporter translocating negativelycharged lipophilic small molecules and E129 might serve as a switch to control the conformational change via its protonation-deprotonation cycle.

关键词： Major facilitator superfamily Transporter Spinster Membrane protein

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Taking the pulse of COVID-19:a spatiotemporal perspective

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International Journal of Digital Earth 2020年第10期13卷 1186-1211页

作者： Chaowei Yang Dexuan Sha Qian Liu Yun Li Hai Lan Weihe Wendy Guan Tao Hu Zhenlong Li Zhiran Zhang John Hoot Thompson Zifu Wang David Wong Shiyang Ruan Manzhu Yu Douglas Richardson Luyao Zhang Ruizhi Hou You zhoua Cheng Zhong Yifei Tian Fayez Beaini Kyla Carte Colin Flynn Wei Liu Dieter Pfoser Shuming Bao Mei Li Haoyuan Zhang Chunbo Liu jie Jiang Shihong Du Liang Zhao Mingyue Lu Lin Li Huan Zhou Andrew Ding NSF Spatiotemporal Innovation Center George Mason Univ.FairfaxVAUSA Department of Geography and GeoInformation Science George Mason Univ.FairfaxVAUSA Department of Geographical Sciences University of MarylandCollege ParkMDUSA Center for Geographic Analysis Harvard UniversityCambridgeMAUSA Geoinformation and Big Data Research Lab Department of GeographyUniversity of South CarolinaColumbiaSCUSA Chinese Academy of Surveying and Mapping BeijingPeople’s Republic of China School of Resource and Environmental Sciences Wuhan UniversityWuhanPeople’s Republic of China Cloud Computeand Storage OperationsInformation Technology ServicesGeorge Mason UniversityFairfaxVAUSA Department of Geography Pennsylvania State UniversityState CollegePAUSA School of Business Management East China Normal UniversityShanghaiPeople’s Republic of China School of Mathematical Sciences East China Normal UniversityShanghaiPeople’s Republic of China Department of Psychology George Mason UniversityFairfaxVAUSA mDepartment of Computer Science George Mason UniversityFairfaxVAUSA Department of Information Technology George Mason UniversityFairfaxVAUSA Department of Biology George Mason UniversityFairfaxVAUSA College of Land Science and Technology China Agricultural UniversityBeijingPeople’s Republic of China China Data Institute Ann ArborMIUSA Institute of Remote Sensing and GIS Peking UniversityBeijingPeople’s Republic of China Aerospace Information Research Institute Chinese Academy of SciencesBeijingPeople’s Republic of China School of Geomatics and Urban Spatial Informatics Beijing University of Civil Engineering and ArchitectureBeijingPeople’s Republic of China School of Geographical Sciences Nanjing University of Information Science&TechnologyNanjingPeople’s Republic of China School of Geodesy and Geomatics Wuhan UniversityWuhanPeople’s Republic of China wFaculty of Environment University of WaterlooWaterlooCanada

The sudden outbreak of the Coronavirus disease(COVID-19)swept across the world in early 2020,triggering the lockdowns of several billion people across many countries,including China,Spain,India,the U.K.,Italy,France,Germany,Brazil,Russia,and the *** transmission of the virus accelerated rapidly with the most confirmed cases in the U.S.,India,Russia,and *** response to this national and global emergency,the NSF Spatiotemporal Innovation Center brought together a taskforce of international researchers and assembled implementation strategies to rapidly respond to this crisis,for supporting research,saving lives,and protecting the health of global *** perspective paper presents our collective view on the global health emergency and our effort in collecting,analyzing,and sharing relevant data on global policy and government responses,human mobility,environmental impact,socioeconomical impact;in developing research capabilities and mitigation measures with global scientists,promoting collaborative research on outbreak dynamics,and reflecting on the dynamic responses from human societies.

关键词： Big Data Earth system emergency geospatial sciences epidemics applications

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High performance liquid chromatographic separation of thirteen drugs collected in Chinese Pharmacopoeia 2010(Ch.P2010) on cellulose ramification chiral stationary phase

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Journal of Pharmaceutical Analysis 2012年第1期2卷 48-55页

作者： Ying zhoua,b, Chao Maa, Yan Wanga, Qi-Ming Zhangb, Yi-Ying Zhanga, jie Fua, Hong Gaoc, Li-Xun Zhaoc aState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China bNational Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China cInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China. National Institute for the Control of Pharmaceutical and Biological Products Beijing 100050 China. Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China.

The enantiomers separation of thirteen drugs collected in Ch.P2010 was performed on chiral stationary phase of cellulose ramification (chiralpak OD and chiralpak OJ) by high performance liquid chromatographic (HPLC) methods, which included ibuprofen (C1), ketoprofen (C2), nitrendipine (C3), nimodipine (C4), felodipine (C5), omeprazole (C6), praziquantel (C7), propranolol hydrochloride (C8), atenolol (C9), sulpiride (C10), clenbuterol hydrochloride (C11), verapamil hydrochloride (C12), and chlorphenamine maleate (C13). The mobile phase consisted of isopropanol and n-hexane. The detection wavelength was set at 254 nm and the fiow rate was 0.7 mL/min. The enantiomers separation of these thirteen racemates on chiralpak OD column and chiralpak OJ column was studied, while the effects of proportion of organic additives, alcohol displacer and temperature on the separation were studied. And the mechanism of some of racemates was discussed. The results indicated that thirteen chiral drugs could be separated onchiral stationary phase of cellulose ramification in normal phase chromatographic system. The chromatographic retention and resolution of enantiomers could be adjusted by factors including column temperature and the concentration of alcohol displacer and organic alkaline modifier in mobile phase. It was shown that the resolution was improved with reducing concentration of alcohol displacer. When concentration of organic alkaline modifier was 0.2% (v/v), the resolution and the peak shape were fairly good. Most racemates mentioned above had better resolution at column temperature of 25 1C. When racemates were separated, the temperature should be kept so as to obtain stable separation results.

关键词： HPLC Chiral stationary phase Optical enantiomers Cellulose ramification

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