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Nano Research 2022年第4期15卷 3367-3375页

作者： Xin Wang Lingxiao Li Danping Wang Shiyi Zuo Tian Liu fudan dong Xuanbo Zhang Zhonggui He Bingjun Sun Jin Sun Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Radiology Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Prodrug-based nanoassembly emerges as a hopeful way for the efficient delivery of antitumor drugs,with carrier-free structure and ultra-high drug loading.Carbon chains are widely used to design self-assembling prodrugs.The impacts of the length of carbon chains on the self-assembly stability,drug delivery efficiency and antitumor effect of prodrugs have not been fully elucidated.Here,three paclitaxel prodrugs were synthesized by conjugating paclitaxel with octanol(C_(8)),decanol(C_(10))or dodecanol(C_(12))through disulfide bond.The three prodrugs could form homogeneous nanoparticles,with over 50%drug loading and redox dual-responsivity.Interestingly,the length extension of carbon chains ameliorates the self-assembly and the colloidal stability of prodrugs,thus improving the drug delivery efficiency.The optimal paclitaxel-dodecanol prodrug nanoassemblies exhibit better antitumor efficacy than Taxol and Abraxane.These findings are meaningful for the rational design of advanced nanomedicines in cancer therapy.

关键词： prodrug self-assembly chain length paclitaxel redox responsive drug release

Synergetic lethal energy depletion initiated by cancer cell membrane camouflaged nano-inhibitor for cancer therapy

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Nano Research 2022年第4期15卷 3422-3433页

作者： fudan dong Qikun Jiang Lingxiao Li Tian Liu Shiyi Zuo Lin Gao Mengna Fang Yanlin Gao Bingjun Sun Cong Luo Zhonggui He Jin Sun Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Mitochondrial bioenergy plays a vital role in the occurrence and development of cancer.Although strategies to impede mitochondrial energy supply have been rapidly developed,the anticancer efficacy is still far from satisfactory,mainly attributed to the hybrid metabolic pathways of mitochondrial oxidative phosphorylation(OXPHOS)and glycolysis.Herein,we construct a cancer cell membrane camouflaged nano-inhibitor,mTPPa-Sy nanoparticle(NP),which co-encapsulates OXPHOS inhibitor(mitochondrial-targeting photosensitizers:TPPa)and glycolysis inhibitor(syrosingopine(Sy))for synergistically blocking the two different energy pathways.The mTPPa-Sy NPs exhibit precision tumor-targeting due to the high affinity between the biomimic membrane and the homotypic cancer cells.Under laser irradiation,the mitochondrial-targeting TPPa,which is synthesized by conjugating pyropheophorbide a(PPa)with triphenylphosphin,produces excessive reactive oxygen species(ROS)and further disrupts the OXPHOS.Interestingly,OXPHOS inhibition reduces O_(2) consumption and improves ROS production,further constructing a closed-loop OXPHOS inhibition system.Moreover,TPPa-initiated OXPHOS inhibition in combination with the Sytriggered glycolysis inhibition results in lethal energy depletion,significantly suppressing tumor growth even after a single treatment.Our findings highlight the necessity and effectiveness of synergetic lethal energy depletion,providing a prospective strategy for efficient cancer therapy.

关键词： synergetic lethality energy depletion mitochondria-targeting mitochondrial oxidative phosphorylation glycolysis

Studies on the alcohol exchange reactions of methoxide ditungsten [W(IV)] compound W_2Cl_4(OCH_3)_4(CH_3OH)_2, prepared from (n-Bu_4N)_3W_2Cl_9 HONG Bo;JIN, Song-Lin;Yih-Tong KU;(GU, Yi-dong), Department of Chemistry, fudan University, Shanghai 200433CHE

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Chinese Journal of Chemistry 1990年第6期8卷 520-528页

作者： HONG Bo JIN, Song-Lin Yih-Tong KU (GU, Yi-dong), Department of Chemistry, fudan University, Shanghai 200433 CHEN, Ming-QinCenter of Analyses and Measurements, fudan University, Shanghai 200433 Department of Chemistry Fudan University Shanghai 200433 Center of Analyses and Measurements Fudan University Shanghai 200433

(n-Bu_4N)_3W_2Cl_9, prepared from K_3W_2Cl_9, can be readily converted to a series of [W(IV)]cluster compounds,W_3Cl_4(μ-OR)_2(OR')_2(R'OH)_2, including seven known compounds and two newcompounds with R=Me, R＇=i-Pr ... 详细信息

关键词： CI prepared from HONG Bo JIN Song-Lin Yih-Tong KU Studies on the alcohol exchange reactions of methoxide ditungsten Yi-dong compound W2Cl4 n-Bu4N CH3OH fudan University GU Cl IV

Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

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Zoological Research 2024年第3期45卷 506-517页

作者： Xilei Peng Haonan dong Lixing Zhang Suling Liu fudan University Shanghai Cancer Center&Institutes of Biomedical Sciences/State Key Laboratory of Genetic Engineering/Cancer Institutes/Department of Oncology/Key Laboratory of Breast Cancer in Shanghai/Shanghai Key Laboratory of Medical Epigenetics/Shanghai Key Laboratory of Radiation Oncology/International Co-laboratory of Medical Epigenetics and Metabolism Ministry of Science and Technology/Shanghai Medical College/Fudan UniversityShanghai 200032China

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

关键词： Breast cancer Metastasis Cancer stem cell Ecosystem Tumor microenvironment Mouse model

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 efficacy.The uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological application.Herein,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 efficacy.This 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)S.More importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor location.Such H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT efficiency.As expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic effect.This 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

The top-order energy of quasilinear wave equations in two space dimensions is uniformly bounded

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Fundamental Research 2024年第2期4卷 270-283页

作者： Shijie dong Philippe G.LeFloch Zhen Lei Southern University of Science and Technology SUSTech International Center for Mathematicsand Department of MathematicsShenzhen 518055China fudan University School of Mathematical Sciences220 Handan RoadShanghai 200433China Laboratoire Jacques-Louis Lions and Centre National de la Recherche Scientifique Sorbonne Université4 Place JussieuParis 75252France Shanghai Center for Mathematical Sciences Shanghai 200433China

Alinhac solved a long-standing open problem in 2001 and established that quasilinear wave equations in two space dimensions with quadratic null nonlinearities admit global-in-time solutions,provided that the initial data are compactly supported and sufficiently small in Sobolev norm.In this work,Alinhac obtained an upper bound with polynomial growth in time for the top-order energy of the solutions.A natural question then arises whether the time-growth is a true phenomenon,despite the possible conservation of basic energy.In the present paper,we establish that the top-order energy of the solutions in Alinhac theorem remains globally bounded in time.

关键词： Quasilinear wave equation Global-in-time solution Uniform energy bounds Quadratic null nonlinearity Hyperboloidal foliation method Vector field method

Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation

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World Journal of Emergency Medicine 2024年第3期15卷 190-196页

作者： Huixin Zhao Yiming dong Sijia Wang Jiayuan Shen Zhenju Song Mingming Xue Mian Shao Department of Emergency Medicine Zhongshan HospitalFudan UniversityShanghai 200032China

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and preDIC status in sepsis patients.METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation.RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7%,22.0%and 31.5%,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P3 had a significantly higher sensitivity(72.00%)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00%,SAC status 52.00%;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P<0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95%confidence interval[95%CI]:0.060–0.783,P=0.018)and SAC(adjusted HR=0.146,95%CI:0.041–0.513,P=0.003).CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

关键词： Sepsis Disseminated intravascular coagulation Sepsis-induced coagulopathy Sepsis-associated coagulopathy

Diverse functions of sox9 in liver development and homeostasis and hepatobiliary diseases

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Genes & Diseases 2024年第4期11卷 170-187页

作者： Taiyu Shang Tianyi Jiang Xiaowen Cui Yufei Pan Xiaofan Feng Liwei dong Hongyang Wang School of Life Sciences Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China National Center for Liver Cancer The Naval Medical UniversityShanghai 201805China International Cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteThe Second Military Medical UniversityShanghai 200438China Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer Second Military Medical University&Ministryof EducationShanghai 200438China

The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative capacities.The hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events of cell proliferation,migration,and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription factors.Studies on liver development and diseases have revealed that SRY-related high-mobility group box 9(SOx9)plays an important role in liver embryogenesis and the progression of hepatobiliary diseases.sox9 is not only a master regulator of cell fate determination and tissue morphogenesis,but also regulates various biological features of cancer,including cancer stemness,invasion,and drug resistance,making Sox9 a potential biomarker for tumor prognosis and progression.This review systematically summarizes the latest findings of sox9 in hepatobiliary development,homeostasis,and disease.We also highlight the value of sox9 as a novel biomarker and potential target for the clinical treatment of major liverdiseases.

关键词： Biliary system Cancer Homeostasis Liver diseases SOX9

Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies

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Asian Journal of Pharmaceutical Sciences 2021年第3期16卷 337-349页

作者： Lingxiao Li Shiyi Zuo fudan dong Tian Liu Yanlin Gao Yinxian Yang Xin Wang Jin Sun Bingjun Sun Zhonggui He Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China

Homodimeric prodrug-based self-assembled nanoparticles,with carrier-free structure and ultrahigh drug loading,is drawing more and more attentions.Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage.The influence of the linkages on the self-assembly,in vivo fate and antitumor activity of homodimeric prodrugs is the focus of research.Herein,three docetaxel(DTX)homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages.Interestingly,compared with the other two linkages,the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs,thus improving the stability,circulation time and tumor targeting of prodrug nanoassemblies.Besides,the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells.Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells,their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells,which finally“turned the table”.Our study illustrates the crucial role of linkages in homodimeric prodrugs,and gives valuable proposal for the development of advanced nano-DDS for cancer treatment.

关键词： Diselenide bond Homodimeric prodrug Docetaxel Self-assembly Redox responsive

Angiosperm-wide analysis of fruit and ovary evolution aided by a new nuclear phylogeny supports association of the same ovary type with both dry and fleshy fruits

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Journal of Integrative Plant Biology 2024年第2期66卷 228-251页

作者： Yezi Xiang Taikui Zhang Yiyong Zhao Hongjin dong Hongyi Chen Yi Hu Chien-Hsun Huang Jun Xiang Hong Ma State Key Laboratory of Genetic Engineering Ministry of Education Key Laboratory of Biodiversity and Ecological EngineeringInstitute of Plant BiologyCenter of Evolutionary BiologySchool of Life SciencesFudan UniversityShanghai 200438China Department of Biology Howard Hughes Medical InstituteDuke UniversityDurhamNC 27708USA Department of Biology the Eberly College of Scienceand the Huck Institutes of the Life Sciencesthe Pennsylvania State UniversityUniversity ParkPA 16802USA Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization College of Biology and Agricultural ResourcesHuanggang Normal UniversityHuanggang 438000China

Fruit functions in seed protection and dispersal and belongs to many dry and fleshy types,yet their evolutionary pattern remains unclear in part due to uncertainties in the phylogenetic relationships among several orders and families.Thus we used nuclear genes of 502 angiosperm species representing 231 families to reconstruct a well supported phylogeny,with resolved relationships for orders and families with previously uncertain placements.Using this phylogeny as a framework,molecular dating supports a Triassic origin of the crown angiosperms,followed by the emergence of most orders in the Jurassic and Cretaceous and their rise to ecological dominance during the Cretaceous Terrestrial Revolution.The robust phylogeny allowed an examination of the evolutionary pattern of fruit and ovary types,revealing a trend of parallel carpel fusions during early diversifications in eudicots,monocots,and magnoliids.Moreover,taxa in the same order or family with the same ovary type can develop either dry or fleshy fruits with strong correlations between specific types of dry and fleshy fruits;such associations of ovary,dry and fleshy fruits define several ovaryfruit"modules"each found in multiple families.One of the frequent modules has an ovary containing multiple ovules,capsules and berries,and another with an ovary having one or two ovules,achenes(or other single-seeded dry fruits)and drupes.This new perspective of relationships among fruit types highlights the closeness of specific dry and fleshy fruit types,such as capsule and berry,that develop from the same ovary type and belong to the same module relative to dry and fleshy fruits of other modules(such as achenes and drupes).Further analyses of gene families containing known genes for ovary and fruit development identified phylogenetic nodes with multiple gene duplications,supporting a possible role of whole-genome duplications,in combination with climate changes and animal behaviors,in angiosperm fruit and ovary diversification.

关键词： angiosperm fruit evolution MADS-box molecular clock nuclear phylogeny ovary and fruit developmental genes