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Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer

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National Science Review 2024年第1期11卷 107-119页

作者： shuren Zhang Dongfan song Wenhao Yu Ji Li Xiaoyu Wang Yachao Li Zihan Zhao Qi Xue Jing Zhao Jie P.Li Zijian Guo State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center (ChemBIC) Nanjing University Department of Urology Afflliated Drum Tower HospitalMedical SchoolNanjing University Nanchuang (Jiangsu)Institute of Chemistry and Health

Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes(STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two PtIV-MSA-2 conjugates(Ⅰand Ⅱ) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immuneactivating STING agonist MSA-2; these conjugates showed great potential as multispecific small-molecule drugs against pancreatic cancer. Mechanistic studies revealed that conjugate Ⅰ upregulated the expression of transcripts associated with innate immunity and metabolism in cancer cells, significantly differing from cisplatin and MSA-2. An analysis of the tumor microenvironment demonstrated that conjugate I could enhance the infiltration of natural killer(NK) cells into tumors and promote the activation of T cells, NK cells and dendritic cells in tumor tissues. These findings indicated that conjugate I, which was created by incorporating a Pt chemotherapeutic drug and STING agonist into one molecule, is a promising and potent anticancer drug candidate, opening new avenues for small-molecule-based cancer metalloimmunotherapy.

关键词： platinum drug STING agonist single-molecule multitarget metalloimmunology

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收入分配格局变迁之阶层变动分析

现代经济探讨 2010年第9期 74-78页

作者：宋树仁南开大学经济学院经济研究所博士生天津300071

2010年,中国居民收入分配问题再次成为全社会关注的焦点。该文选择了20个社会群体,测度出中国阶层收入分配格局,通过对比中国居民收入分配格局和中国阶层收入分配格局,从阶层视角,剖析了中国居民收入分配格局两次变迁过程中,阶层的分化... 详细信息

2010年,中国居民收入分配问题再次成为全社会关注的焦点。该文选择了20个社会群体,测度出中国阶层收入分配格局,通过对比中国居民收入分配格局和中国阶层收入分配格局,从阶层视角,剖析了中国居民收入分配格局两次变迁过程中,阶层的分化、重组与变动,并估测出现阶段和未来中国下产阶层、中产阶层和上产阶层构成和发展趋势。

关键词：收入分配格局变迁阶层

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国际气候合作中的公平性问题研究评述

江西社会科学 2010年第3期30卷 77-84页

作者：钟茂初史亚东宋树仁南开大学经济研究所

哥本哈根气候大会之所以没有达成实质性的协议,其根本原因在于各国对于应对全球气候变化责任分担的公平性难以达成共识。本文系统梳理了气候合作中关于公平性问题的学术讨论和政策主张,发现影响合作的主要矛盾可归纳为两点:一是公平原... 详细信息

哥本哈根气候大会之所以没有达成实质性的协议,其根本原因在于各国对于应对全球气候变化责任分担的公平性难以达成共识。本文系统梳理了气候合作中关于公平性问题的学术讨论和政策主张,发现影响合作的主要矛盾可归纳为两点:一是公平原则的南北分歧,二是公平与效率的分歧。本文认为,在促进全球合作尽快形成的目标下,解决公平争论、提出可被广泛接受的公平原则将是解决目前困境的研究方向。

关键词：国际气候合作京都议定书公平原则责任分担碳排放

城镇居民收入差距变动轨迹的总体特征及分解分析:1988～2008

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经济与管理研究 2010年第9期31卷 10-18页

作者：马草原李运达宋树仁南开大学经济研究所

本文使用全国数据分析了改革以来中国城镇居民收入差距的总体特征,并基于天津市典型调查数据,应用基尼系数分解方法研究了近20年来城镇居民收入差距的变动轨迹及其影响因素。针对基尼系数的收入构成分解研究显示,工资性收入的分布状况... 详细信息

本文使用全国数据分析了改革以来中国城镇居民收入差距的总体特征,并基于天津市典型调查数据,应用基尼系数分解方法研究了近20年来城镇居民收入差距的变动轨迹及其影响因素。针对基尼系数的收入构成分解研究显示,工资性收入的分布状况基本上决定了城镇居民收入差距的变动趋势,财产性收入和经营性收入的分配状况趋于相对均等化,转移性收入对总收入差距的平抑作用被大大削弱,社会保障体系在覆盖面扩大的同时可能存在识别和瞄准上的方向性偏误;而从人口特征角度进行的基尼系数分解研究则显示,居民行业差别、就业性质以及受教育程度成为影响城镇居民收入差距最重要的三大因素。

关键词：城镇居民收入差距基尼系数分解收入构成人口特征

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大数据技术在引信性能评估中的应用

探测与控制学报 2024年第4期46卷 5-12页

作者：宋高敏王震马秋华和先孟张书任中国兵器工业集团第二一二研究所陕西西安710065

针对弹药引信在实战环境下考核数据缺失,现有数据平台无法满足引信评估数据分析需求,直接影响其考核评估的充分性和完备性,提出大数据技术在引信性能评估中的应用。将大数据技术应用于引信实战化考核评估领域,建立引信性能评估大数据分... 详细信息

针对弹药引信在实战环境下考核数据缺失,现有数据平台无法满足引信评估数据分析需求,直接影响其考核评估的充分性和完备性,提出大数据技术在引信性能评估中的应用。将大数据技术应用于引信实战化考核评估领域,建立引信性能评估大数据分析平台,对引信考核数据进行规范管理和统计模型构建,并采用智能算法,对获取的数据进行关联分析与模型验证,为未来数据的积累与价值挖掘提供先决条件,为引信性能评估试验检验系统的构建提供新的方向。

关键词：引信性能评估大数据技术

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2476-2486页

作者： Zhao-Dan Ye Li Zhuang Meng-Chen song Zhe Yang Wu Zhang Jing-Feng Zhang Guo-Hong Cao Department of Radiology Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical CollegeHangzhou 310022Zhejiang ProvinceChina Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical CollegeHangzhou 310022Zhejiang ProvinceChina Diagnostic and Therapeutic Center for Difficult Diseases Hwa Mei HospitalUniversity of Chinese Academy of SciencesNingbo 315010Zhejiang ProvinceChina

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic *** To determine whether DEB-TACE before LT is superior to LT for advanced-stage *** A total of 99 individuals diagnosed with advanced HCC were studied *** participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with *** control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with *** on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were *** overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier *** and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and *** The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization *** 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=

关键词： Hepatocellular carcinoma Liver transplantation Portal vein tumor thrombus Drug-eluting bead transarterial chemoembolization Neoadjuvant treatment

The induction of PANoptosis in KRAS-mutant pancreatic ductal adenocarcinoma cells by a multispecific platinum complex

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Science China Chemistry 2022年第10期65卷 1978-1984页

作者： Xin Yuan shuren Zhang Xuanmeng Zhong Hao Yuan Dongfan song Xiaoyu Wang Hanyang Yu Zijian Guo State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center(ChemBIC)Nanjing UniversityNanjing 210023China Department of Biomedical Engineering College of Engineering and Applied SciencesChemistry and Biomedicine Innovation Center(ChemBIC)Nanjing UniversityNanjing 210023China

Oncogenic KRAS reprograms pancreatic ductal adenocarcinoma(PDAC) cells to a state that is awfully resistant to *** alternative coping strategy is to trigger a nonapoptotic cell ***,a multi specific platinum complex SEP was constructed by conjugating a quinone derivative seratrodast to a prodrug of ***,SEP-treated KRAS-mutant PDAC cells showed the characteristics of pyroptosis,apoptosis and necroptosis,similar to PANoptosis(a newfound inflammatory cell death).Mechanistically,SEP could enter cancer cells effectively,then damage nuclear DNA,boost mitochondrial superoxide anion radicals and affect various signaling pathways related to redox homeostasis and tumor *** our best knowledge,SEP is the first metal complex,even small molecule,to elicit PANoptosis(pyroptosis,apoptosis and necroptosis) in cancer cells,providing a new strategy to overcome apoptotic resistance of KRAS-mutant PDAC.

关键词： metallodrug pancreatic ductal adenocarcinoma PANoptosis cell death platinum prodrug

Temperature and Tumor Microenvironment Dual Responsive Mesoporous Magnetic Nanospheres for Magnetothermal Effect-Induced Cancer Theranostics

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CCS Chemistry 2023年第2期5卷 469-485页

作者： Zhiyi Wang shuren Wang Xiaoguang Zhang Ziyuan Li Zeeshan Ali Donghai Yu Hongtao Zhang Fugeng Sheng song Gao Yanglong Hou Beijing Key Laboratory for Magnetoelectric Materials and Devices School of Materials Science and EngineeringPeking UniversityBeijing 100871 Institute of Spin-X Science and Technology South China University of TechnologyGuangzhou 510641 School of Chemical and Materials Engineering National University of Sciences&TechnologyIslamabad 44000 Key Laboratory of Organofluorine Chemistry Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200032 Fifth Medical Center of Chinese PLA General Hospital Beijing 100071

The development of smart drug delivery systems(SDDSs)based on engineered nanomaterials is important for clinical ***,controllable administration of chemotherapeutic drugs for deep tumors and the avoidance of side effects caused by off-targeting during delivery remain a great ***,a stimulus-responsive system of mesoporous nanospheres(composed of Cu@Fe_(2)C@mSiO_(2))with good magnetothermal effect is introduced into the tumor *** system plays an important role in image-guided controllable targeted drug delivery that is independent of tumor ***-induced emission luminogen-based fluorescence imaging and magnetic resonance imaging were utilized since these techniques visualize the delivery process in real *** addition,the degraded nanocarriers showed high catalytic activity for Fenton and Fenton-like reactions,upregulating the level of hydroxyl radicals(•OH)in cancer cells to realize chemodynamic *** induced•OH led to the overexpression of pho-STAT3,activating the STAT3 signaling pathway,eventually inducing cancer cell *** metabolic monitoring,this SDDS is removed from the body after its degradation in *** synergistically enhanced therapeutic effect was obtained in the chemo-chemodynamic therapy of 4T1 tumor-bearing mice,offering a platform for efficient cancer therapy with a personalized theranostic strategy.

关键词： smart drug delivery systems magnetothermal effect stimulus-responsive system tumor microenvironment chemo-chemodynamic therapy

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分布式装配置换流水车间调度问题研究综述

计算机工程与应用 2024年第6期60卷 1-9页

作者：张静宋洪波林剑浙江警察学院计算机与信息安全系杭州310051 浙江树人学院信息科技学院杭州310015 浙江财经大学人工智能系杭州310018

近几十年来,现代制造业发展迅速,一种趋势是在分布式生产工厂进行工件的加工,待完成后到装配工厂集中装配成最终产品。该模式在带来诸多好处的同时,对资源调度提出了新的挑战。针对分布式装配置换流水车间调度问题(distributed assembly... 详细信息

近几十年来,现代制造业发展迅速,一种趋势是在分布式生产工厂进行工件的加工,待完成后到装配工厂集中装配成最终产品。该模式在带来诸多好处的同时,对资源调度提出了新的挑战。针对分布式装配置换流水车间调度问题(distributed assembly permutation flowshop scheduling problem,DAPFSP),介绍了DAPFSP的背景和存在的主要困难,进而对以最小化最大完工时间为优化目标的DAPFSP,从数学模型、编解码策略、全局和局部搜索算法角度进行探讨,分别综述了以最小化总流程时间等为优化目标,具有零等待等约束,以及考虑准备时间等因素的DAPFSP研究成果。最后,对有待进一步开展的研究工作进行展望。

关键词：分布式装配置换流水车间资源调度搜索算法