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A prodrug nanoplatform via esterification of STING agonist and IDO inhibitor for synergistic cancer immunotherapy

Nano Research 2022年第10期15卷 9215-9222页

作者： Madiha Zahra Syeda Tu Hong Min Zhang Yanfei Han Xiaoling Zhu songmin ying Longguang Tang International Institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital Zhejiang University School of MedicineKey Laboratory of Respiratory Disease of Zhejiang ProvinceHangzhou 310009China

Cancer immunotherapy has made significant progress in the last few decades,revolutionizing ***,low patient response rates and potential immune-related adverse events continue to be major clinical *** nanomedicine,by virtue of its regulated delivery and modular flexibility,has shown the potential to strengthen antitumor immune responses and sensitize tumors to *** this study,we developed tumor microenvironment(TME)responsive nanomedicine to achieve specific and localized amplification of the immune response in tumor tissue in a safe and effective manner,while simultaneously reducing immune-related side *** synthesized the TME responsive prodrug by coupling MSA-2,a stimulator of interferon genes(STING)agonist,and NLG-919,an indoleamine 2,3 dioxygenase(IDO)*** prodrug was assembled into nanoparticles to enhance the solubility and *** synthesizing a TME responsive prodrug,we aim to explore the therapeutic efficacy of combined regimen(STING agonist and IDO inhibitor)for cancer,and reduce the unwanted side effects of STING agonism on normal *** prodrug and nanoparticles were characterized by mass spectrometry,dynamic light scattering(DLS),and transmission electron microscopy(TEM).Following that,we investigated the tumor accumulation,anti-tumor activity,and toxicity in vitro and in *** nanoparticles demonstrated the ability to inhibit the tumor growth and activate antitumor immune response by modulating immune cells populations in tumor *** TME responsive nanomedicine provided an effective tool for precise targeting,promoting antitumor immunity,and efficient tumor growth inhibition with *** of this study may have implications for future clinical trials.

关键词： prodrug esterase-responsive immunotherapy stimulator of interferon genes(STING) indoleamine 2 3 dioxygenase(IDO)

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LPS-induced mitochondrial DNA synthesis and release facilitate RAD50-dependent acute lung injury

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1104-1106页

作者： Xueqin Zhan Rui Cui Xinwei Geng Jiaqian Li Yunlian Zhou Lulu He Chao Cao Chao Zhang Zhimin Chen songmin ying Department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNational Children's Regional Medical CenterHangzhouZhejiangChina International Institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwuChina Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital Zhejiang University School of MedicineKey Laboratory of Respiratory Disease of Zhejiang ProvinceHangzhouZhejiangChina

Dear Editor,ATP-binding cassette(ABC)-ATPase(RAD50),together with meiotic recombination 11 homolog 1(MRE11)subunits,to form MRE11-RAD50 complex,plays important roles in recognition of double-stranded DNA(dsDNA)and initiation of consequent inflammatory *** lung injury(ALI)and acute respiratory destress syndrome(ARDS)are systemic uncontrolled inflammation and ***,the function of the DNA sensor in ALI/ARDS remains poorly *** we investigated functions of RAD50 using mouse primary macrophages and conditionally RAD50 knockout mice in vitro and in a lipopolysaccharide(LPS)-induced lung injury model.

关键词： RAD50 acute lung

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Eosinophil-derived chemokine(hCCL 15/23,mCCL6)interacts with CCR1 to promote eosinophilic airway inflammation

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Signal Transduction and Targeted Therapy 2021年第3期6卷 1046-1056页

作者： Xufei Du Fei Li Chao Zhang Na Li Huaqiong Huang Zhehua Shao Min Zhang Xueqin Zhan Yicheng He Zhenyu Ju Wen Li Zhihua Chen songmin ying Huahao Shen Key Laboratory of Respiratory Disease of Zhejiang Province Department of Respiratory and Critical Care Medicinethe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310009China Department of Anatomy Zhejiang University School of MedicineHangzhou 310058China Key Laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative MedicineJinan UniversityGuangzhouGuangdong 510632China International Institutes of Medicine Zhejiang University School of MedicineYiwu 322000China Department of Pharmacology Zhejiang University School of MedicineHangzhou 310058China State Key Lab of Respiratory Disease Guangzhou 510120China

Eosinophils are terminally differentiated cells derived from hematopoietic stem cells(HSCs)in the bone *** studies have confirmed the effective roles of eosinophils in asthmatic airway ***,their regulatory functions have not been well ***,increased C-C chemokine ligand 6(CCL6)in asthmatic mice and the human orthologs CCL15 and CCL23 that are highly expressed in asthma patients are described,which are mainly derived from *** Cc/6 knockout mice,further studies revealed CCL6-dependent allergic airway inflammation and committed eosinophilia in the bone marrow following ovalbumin(OVA)challenge and identified a CCL6-CCR1 regulatory axis in hematopoietic stem cells(HSCs).Eosinophil differentiation and airway inflammation were remarkably decreased by the specific CCR1 antagonist ***,the study identifies that the CCL6-CCR1 axis is involved in the crosstalk between eosinophils and HSCs during the development of allergic airway inflammation,which also reveals a potential therapeutic strategy for targeting G protein-coupled receptors(GPCRs)for future clinical treatment of asthma.

关键词： CCR1 inflammation airway

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Activating transcription factor 3 represses cigarette smoke-induced IL-6 and IL-8 expression via suppressing NF-κB activation

Activating transcription factor 3 represses cigarette smoke-...

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2016（第三十八届）浙江省呼吸系病学术年会

作者： Wu Yanping Cao Chao ying songmin Chen Zhihua Shen Huahao Li Wen Department of Respiratory and Critical Care Medicine Second Affiliated HospitalSchool of MedicineZhejiang University

OBJECTIVE:Airway and lung inflammation is a primary feature of chronic obstructive pulmonary disease(COPD).As a transcriptional modulator,activating transcription factor 3(ATF3)negatively regulates lots of proinflammatory cytokines and *** this study,we investigated the effects of ATF3 on the inflammatory response of *** AND METHODS:Cigarette smoke(CS)-induced model and cigarette smoke extract(CSE)-

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Activating Transcription Factor 3 Is Essential for Cigarette Smoke-Induced Mucin Expression via Interaction with Activator Protein-1

Activating Transcription Factor 3 Is Essential for Cigarette...

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2016（第三十八届）浙江省呼吸系病学术年会

作者： Wu Yanping Wu Yinfang ying songmin Chen Zhihua Shen Huahao Li Wen Department of Respiratory and Critical Care Medicine Second Affiliated HospitalSchool of MedicineZhejiang University

OBJECTIVE:Our study investigated whether ATF3 is involved in the regulation of MUC5AC expression in COPD and explore the molecular *** AND METHODS:CS-induced ATF3 and MUC5AC expression levels were examined in HBE cells,human NCI-H292 cells and ***3 small interfering RNA(siRNA)and plasmid were used to investigate whether ATF3 is involved in CS-induced MUC5AC *** used quantitative real time PCR,Western Blot and immunofluorescence to assess whether the loss or gain of ATF3

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新版中国支气管哮喘防治指南与全球支气管哮喘防治创议的异同

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中华结核和呼吸杂志 2018年第3期41卷 166-168页

作者：沈华浩杜旭菲应颂敏浙江大学医学院附属第二医院呼吸与危重症医学科浙江省呼吸疾病诊治及研究重点实验室杭州310009

支气管哮喘（哮喘）防治指南（2016年版）（以下简称“新版指南”）总结了中国近年来哮喘研究发展和诊治现状，在2008年版哮喘指南。的基础上修订而成，新增哮喘流行病学、哮喘的评估、重症哮喘、特殊类型哮喘及哮喘的某些特殊问题等4... 详细信息

支气管哮喘（哮喘）防治指南（2016年版）（以下简称“新版指南”）总结了中国近年来哮喘研究发展和诊治现状，在2008年版哮喘指南。的基础上修订而成，新增哮喘流行病学、哮喘的评估、重症哮喘、特殊类型哮喘及哮喘的某些特殊问题等4块内容。全球哮喘防治创议（GINA）报告作为全球哮喘防治的风向标，是哮喘指南修订的重要参考。

关键词：全球哮喘防治创议支气管哮喘防治指南中国异同流行病学重症哮喘修订

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The Role of SETD8 in Genome Intergrity Maintenance and Tumoregenesis: Revelation from a Pair of Identical Twins

The Role of SETD8 in Genome Intergrity Maintenance and Tumor...

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2018年（第四十届）浙江省医学会呼吸系病学术年会

作者： Miao Li Hongwei Liao Chen Zhu Yanping Wu Yinfang Wu Xinwei Geng Zhihua Chen Huahao Shen songmin ying Wen Li Department of Respiratory and Critical Care Medicine Second Affiliated Hospital Institute of Respiratory Diseases Zhejiang University School of Medicine Department of Pharmacology Zhejiang University School of Medicine

Objective :Pulmonary sarcomatous neoplasms are a rare group of tumors occur in the lung[1]. We received a pair of monozygotic twins discordant for sarcomatoid neoplasms of the right principal bronchus in their early age. Identical twins were grown in the same environment and the genetic similarity was highly consistent, so we thought the very small number of genetic differences between the sisters may be involved in the occurrence of the disaster. As we all know, most human pathogenic genes are caused by mutations in exons. In order to find out novel genes related to the patient’s tumor, exome sequencing which has unique advantages in identifying the causative genes of rare diseases was *** : Exome sequencing was used in the twins mentioned above. Through comparison analysis among the twins and the general population, 11 genes were first screened out. After further siRNA screening of these genes, we identified H4K20-specific histone methyltransferase SETD8 as the most possible participant in tumor occurrence. Two individual siRNAs of SETD8 were used in U2OS and human bronchial epithelium(HBE) cells, cell proliferation, apoptosis, ageing, cell cycle were analyzed. To determine the effect of single nucleotide variation(SNV, T904C) in patient’s setd8, we overexpressed wildtype and mutant SETD8 respectively in cells, immunoprecipitation and mass spectrometry were followed to analysis the differences in interaction with other proteins, we also amplified wildtype and mutant SETD8 protein in vitro to assess their methyltransferase *** : : The silencing of SETD8 inhibited cell proliferation and increased apoptosis in both two cell lines. Cell cycle arrest and DNA damage also occurred without setd8. DNA fiber assay showed that compared with control, cells transfected with setd8 siRNA exhibited slower replication fork speed. Overexpress exogenous wildtype and mutant SETD8, protein interaction analysis revealed that the mutant SETD8 enhanced histone H4

关键词： Exome Sequencing SETD8 Genome Intergrity Methyltransferase TumourgenesisREFERENCE

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New progresses of fine-grained sediment gravity-flow deposits and their importance for unconventional shale oil and gas plays

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Petroleum Science 2025年第1期22卷 1-15页

作者： Tian Yang ying-Lin Liu State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation (Chengdu University of Technology) Institute of Sedimentary Geology Key Laboratory of Deep-time Geography and Environment Reconstruction and Applications of Ministry of Natural Resources Chengdu University of Technology

Fine-grained sediments are widely distributed and constitute the most abundant component in sedimentary systems, thus the research on their genesis and distribution is of great significance. In recent years, fine-grained sediment gravity-flows(FGSGF) have been recognized as an important transportation and depositional mechanism for accumulating thick successions of fine-grained sediments. Through a comprehensive review and synthesis of global research on FGSGF deposition, the characteristics,depositional mechanisms, and distribution patterns of fine-grained sediment gravity-flow deposits(FGSGFD) are discussed, and future research prospects are clarified. In addition to the traditionally recognized low-density turbidity current and muddy debris flow, wave-enhanced gravity flow, lowdensity muddy hyperpycnal flow, and hypopycnal plumes can all form widely distributed FGSGFD. At the same time, the evolution of FGSGF during transportation can result in transitional and hybrid gravityflow deposits. The combination of multiple triggering mechanisms promotes the widespread development of FGSGFD, without temporal and spatial limitations. Different types and concentrations of clay minerals, organic matters, and organo-clay complexes are the keys to controlling the flow transformation of FGSGF from low-concentration turbidity currents to high-concentration muddy debris flows. Further study is needed on the interaction mechanism of FGSGF caused by different initiations, the evolution of FGSGF with the effect of organic-inorganic synergy, and the controlling factors of the distribution patterns of FGSGFD. The study of FGSGFD can shed some new light on the formation of widely developed thin-bedded siltstones within shales. At the same time, these insights may broaden the exploration scope of shale oil and gas, which have important geological significances for unconventional shale oil and gas.

关键词： Fine-grained sediment gravity-flow Depositional mechanism Transportation and evolution Distribution pattern Shale oil and gas

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Tuning the ion-dipole interactions between fluoro and carbonyl(EC)by electrolyte design for stable lithium metal batteries

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Chinese Chemical Letters 2025年第1期36卷 579-584页

作者： Guihuang Fang ying Liu Yangyang Feng ying Pan Hongwei Yang Yongchuan Liu Maoxiang Wu Faculty of Metallurgy and Energy Engineering Kunming University of Science and TechnologyKunming 650093China Key Laboratory of Optoelectronic Materials Chemistry and Physics Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China

Ethylene carbonate(EC)is the conventional and promising solvent to achieve high energy lithium metal ***,the innate low energy level of lowest unoccupied molecular orbital(LUMO)in EC makes it incompatible with lithium metal,causing uncontrolled lithium growth and low Coulombic efficiency(CE).Herein,we introduced bis(2,2,2-trifluoroethyl)carbonate(TFEC),a carbonate with a strong electron-withdrawing effect(-CF_(3)),which enhances the stability of EC at electrode interface by reducing ion-dipole interactions between Li^(+)and *** the interaction between Li and EC weakens,TFEC and more PF_(6)^(-)anions coordinate with Li^(+),promoting the formation of contact ion pairs(CIPs)and aggregates(AGGs),thereby increasing the inorganic composition within the solid electrolyte ***,the distinct solvated sheath structure favors the decomposition of fluorinated solvents and PF_(6)^(-)anions,forming inorganic-rich electrode-electrolyte interfaces(SEI and CEI),thereby ensuring high stability for both the Li anode and high-voltage ***,when applied in the full-cell Li||LiMn_(0.8)Fe_(0.2)PO_(4),it displays consistent cycling performance,exhibiting minimal capacity decay with a retention rate of 62.5%after800 cycles,substantially surpassing that of cells using base electrolytes(29.8%).

关键词： Lithium-ion batteries LiMn_(0.8)Fe_(0.2)PO_(4) High-voltage Solvation structure Ethylene carbonate Bis(2,2,2-trifluoroethyl)carbonate

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Quantile-based optimization under uncertainties for complex engineering structures using an active learning basis-adaptive PC-Kriging model

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Chinese Journal of Aeronautics 2025年第1期38卷 340-352页

作者： Yulian GONG Jianguo ZHANG Dan XU ying HUANG School of Reliability and Systems Engineering Beihang UniversityBeijing 100191China

The Reliability-Based Design Optimization(RBDO)of complex engineering structures considering uncertainties has problems of being high-dimensional,highly nonlinear,and timeconsuming,which requires a significant amount of sampling simulation *** this paper,a basis-adaptive Polynomial Chaos(PC)-Kriging surrogate model is proposed,in order to relieve the computational burden and enhance the predictive accuracy of a *** active learning basis-adaptive PC-Kriging model is combined with a quantile-based RBDO ***,five engineering cases have been implemented,including a benchmark RBDO problem,three high-dimensional explicit problems,and a high-dimensional implicit *** with Support Vector Regression(SVR),Kriging,and polynomial chaos expansion models,results show that the proposed basis-adaptive PC-Kriging model is more accurate and efficient for RBDO problems of complex engineering structures.

关键词： Reliability-based design optimization Quantile-based Basis-adaptive PC-Kriging Complex engineering structures Active learning Uncertainty

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