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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

Pan-cancer immunogenic death analysis identifies key roles of CXCR3 and CCL18 in hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 568-570页

作者： Jia Guo Xin Sun Guowei Pan Ce Li Xin He Xiaofang Che Zan Teng Xiujuan Qu Yunpeng Liu Bowen Yang Department of Medical Oncology Provincial Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning ProvinceLiaoning Provincial Clinical Research Center for CancerClinical Cancer Research Center of ShenyangThe First Hospital of China Medical UniversityShenyangLiaoning 110001China research center for Universal Health School of Public HealthChina Medical UniversityShenyangLiaoning 110122China

Immunogenic death is a form of programmed cell death that is common in the development and progression of cancer.However,its impact on tumor progression differs depending on the location of the tumor.Meanwhile,it also plays an important role in antitumor immunity because the process of immunogenic death can release substances that activate immunity.1 Therefore,in this study,the key mechanism of mediating immunogenic death in hepatocellular carcinoma(HCC)was found from the excavation of the immunogenic death characteristics of pan-cancer and the in-depth investigation of its effects on different tumor types(Fig.1A).

关键词： death CXCR3 immunity

Organoid co-culture models of the tumor microenvironment promote precision medicine

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Cancer Innovation 2024年第1期3卷 79-103页

作者： Zhaoru Gu Quanyou Wu Bingqing Shang Kaitai Zhang Wen Zhang State Key Laboratory of Molecular Oncology Department of Etiology and CarcinogenesisNational Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of urology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Immunology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

In recent years,the three-dimensional(3D)culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue structure and molecular characteristics of solid tumors in vivo.This system offers several advantages,including high throughput,efficiency,and retention of tumor heterogeneity.Traditional Matrigel-submerged organoid cultures primarily support the long-term proliferation of epithelial cells.One solution for the exploration of the tumor microenvironment is a reconstitution approach involving the introduction of exogenous cell types,either in dual,triple or even multiple combinations.Another solution is a holistic approach including patient-derived tumor fragments,air-liquid interface,suspension 3D culture,and microfluidic tumor-on-chip models.Organoid co-culture models have also gained popularity for studying the tumor microenvironment,evaluating tumor immunotherapy,identifying predictive biomarkers,screening for effective drugs,and modeling infections.By leveraging these 3D culture systems,it is hoped to advance the clinical application of therapeutic approaches and improve patient outcomes.

关键词： air-liquid interface immunotherapy organoid tumor microenvironment tumor-on-chip

The evolution and functional divergence of 10 Apolipoprotein D-like genes in Nilaparvata lugens

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Insect Science 2024年第1期31卷 91-105页

作者： Jia-Bao Lu Peng-Peng Ren Qiao Li Fang He Zhong-Tian Xu Sai-Nan Wang Jian-Ping Chen Jun-Min Li Chuan-Xi Zhang Citrus research Institute Southwest University/Chinese Academy of Agricultural SciencesNational Engineering Research Center for CitrusChongqingChina Technology center of Wuhan Customs District HubeiChina Institute of Insect Science Zhejiang UniversityHangzhouChina

Apolipoprotein D(ApoD),a member of the lipocalin superfamily of proteins,is involved in lipid transport and stress resistance.Whereas only a single copy of the ApoD gene is found in humans and some other vertebrates,there are typically several ApoD-like genes in insects.To date,there have been relatively few studies that have examined the evolution and functional differentiation of ApoD-like genes in insects,particularly hemi-metabolous insects.In this study,we identified 10 ApoD-like genes(NlApoD1−10)with distinct spatiotemporal expression patterns in Nilaparvata lugens(BPH),which is an important pest of rice.NlApoD1−10 were found to be distributed on 3 chromosomes in a tandem array of NlApoD1/2,NlApoD3−5,and NlApoD7/8,and show sequence and gene structural divergence in the coding regions,indicating that multiple gene duplication events occurred during evolution.Phylogenetic analysis revealed that NlApoD1−10 can be clustered into 5 clades,with NlApoD3−5 and NlApoD7/8 potentially evolving exclusively in the Delphacidae family.Functional screening using an RNA interference approach revealed that only NlApoD2 was essential for BPH development and survival,whereas NlApoD4/5 are highly expressed in testes,and might play roles in reproduction.Moreover,stress response analysis revealed that NlApoD3−5/9,NlApoD3−5,and NlApoD9 were up-regulated after treatment with lipopolysaccharide,H2O2,and ultraviolet-C,respectively,indicating their potential roles in stress resistance.

关键词： Apolipoprotein D BPH evolution functional divergence gene duplication NIApoD

Operando investigation of particle re-entrainment mechanism in electrostatic capture process on the lab-on-a-chip

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Journal of Environmental Sciences 2024年第2期136卷 337-347页

作者： Yong Zhu Yikun Zhang Xiaoyong Yang Shanlong Tao Mingxia Chen Wenfeng Shangguan research center for Combustion and Environmental Technology School of Mechanical EngineeringShanghai Jiao Tong UniversityShanghai 200240China

Inhalable particle is a harmful air pollutant that causes a significant threat to people's health and ecological environments,which should be removed to purify air,but there exists limited removal efficiency due to particle re-entrainment.Here,Operando observation system based on microscopic visualization method is developed to make in situ test of particle migration,deposition and re-entrainment characteristics on a lab-on-a-chip to achieve the investigation in micro-level scale.The deposition evolution of charged particles is recorded in electric field region intuitively,which confirms the fracture of particle chain occurs during the growth process of deposited particles.It captures the instantaneous process that a larger particle with micron size due to the coagulation of submicron particles fractures from main body of the particle chain for the first time.The analysis of migration behavior of a single submicron particle near electrode surface demonstrates the direct influence of drag force on the fracture of particle chain.This work is the first-time visualization of dynamic process and mechanism elucidation of particle re-entrainment at the micron level,and the findings will provide the theory support for the particle re-entrainment mechanism and bring inspires of enhancing capture efficiency of inhalable particle.

关键词： Inhalable particle Re-entrainment mechanism Operando observation Lab-on-a-chip Capture efficiency

Proactive Resilience Enhancement of Power Systems with Link Transmission Model-based Dynamic Traffic Assignment Among Electric Vehicles

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CSEE Journal of Power and Energy Systems 2024年第3期10卷 1320-1330页

作者： Haoyuan Yan Tianyang Zhao Zhanglei Guan Energy Electricity research center Jinan UniversityGuangzhou 510632China Energy research Institute Nanyang Technological UniversitySingapore IEEE

The rapid development of electric vehicles(EVs)is strengthening the bi-directional interactions between electric power networks(EPNs)and transportation networks(TNs)while providing opportunities to enhance the resilience of power systems towards extreme events.To quantify the temporal and spatial flexibility of EVs for charging and discharging,a novel dynamic traffic assignment(DTA)problem is proposed.The DTA problem is based on a link transmission model(LTM)with extended charging links,depicting the interaction between EVs and power systems.It models the charging rates as continuous variables by an energy boundary model.To consider the evacuation requirements of TNs and the uncertainties of traffic conditions,the DTA problem is extended to a two-stage distributionally robust version.It is further incorporated into a two-stage distributionally robust unit commitment problem to balance the enhancement of EPNs and the performance of TNs.The problem is reformulated into a mixed-integer linear programming problem and solved by off-the-shelf commercial solvers.Case studies are performed on two test networks.The effectiveness is verified by the numerical results,e.g.,reducing the load shedding amount without increasing the unmet traffic demand.

关键词： Coupled transportation and power network link transmission model resilience enhancement

Suppression of Co(Ⅱ)ion deposition and hazards:Regulation of SEI film composition and structure

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Journal of Energy Chemistry 2024年第2期89卷 259-265,I0007页

作者： Jiaqi Zhan Mingzhu Liu Yutian Xie Jiarong He Hebing Zhou Lidan Xing Weishan Li National and Local Joint Engineering research center of MPTES in High Energy and Safety LIBs Engineering Research Center of MTEES(Ministry of Education)Research Center of BMET(Guangdong Province)Key Lab.of ETESPG(GHEI)Innovative Platform for ITBMD(Guangzhou Municipality)School of ChemistrySouth China Normal UniversityGuangzhou 510006GuangdongChina

Despite the presence of Li F components in the solid electrolyte interphase(SEI)formed on the graphite anode surface by conventional electrolyte,these Li F components primarily exist in an amorphous state,rendering them incapable of effectively inhibiting the exchange reaction between lithium ions and transition metal ions in the electrolyte.Consequently,nearly all lithium ions within the SEI film are replaced by transition metal ions,resulting in an increase in interphacial impedance and a decrease in stability.Herein,we demonstrate that the SEI film,constructed by fluoroethylene carbonate(FEC)additive rich in crystalline Li F,effectively inhibits the undesired Li^(+)/Co^(2+)ion exchange reaction,thereby suppressing the deposition of cobalt compounds and metallic cobalt.Furthermore,the deposited cobalt compounds exhibit enhanced structural stability and reduced catalytic activity with minimal impact on the interphacial stability of the graphite anode.Our findings reveal the crucial influence of SEI film composition and structure on the deposition and hazards associated with transition metal ions,providing valuable guidance for designing next-generation electrolytes.

关键词： Lithium-ion batteries Transition metal ions SEI film Composition and structure

Numerical study of flow and thermal characteristics of pulsed impinging jet on a dimpled surface

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Theoretical & Applied Mechanics Letters 2024年第2期14卷 106-117页

作者： Amin Bagheri Kazem Esmailpour Morteza Heydari Renewable Energy research center Damavand BranchIslamic Azad UniversityDamavandIran

This research comprehensively investigates the flow and thermal characteristics of a pulsating impinging jet over a dimpled surface.It analyzes the impact of key parameters(e.g.,inlet velocity pulsation functions,pulsation frequency,amplitude,dimple pitch,dimple depth,Reynolds number)on flow patterns and heat transfer.Validated computational fluid dynamics and the Re-normalization group turbulence model are employed to accurately simulate complex turbulent flow behavior.Local and average heat transfer coefficients are calculated and compared to steady impingement cases,revealing the potential benefits of pulsation for heat transfer enhancement.The study also examines how pulsation-induced flow modulation and thermal mixing affect heat transfer mechanisms.Results indicate that combining fluctuating flow with a dimpled surface can improve heat transfer rates.In summary,increasing pulsation amplitude consistently enhances heat transfer,while the effect of frequency varies between impinging and wall jet zones.

关键词： Pulsating impinging jet Dimpled surface Heat transfer enhancement Pulsation frequency and amplitude Coherent structures

Incidence and Mortality of Cancers in Female Genital Organs—China,2022

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China CDC weekly 2024年第10期6卷 195-202,I0003,I0004页

作者： Kexin Sun Bingfeng Han Hongmei Zeng Shaoming Wang Li Li Ru Chen Rongshou Zheng Wenqiang Wei National Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Introduction:This study presented the incidence and mortality rates of cancers affecting the female genital organs in China,along with their trends spanning from 2010 to 2018.Methods:700 population-based cancer registries provided relevant cancer incidence and mortality data for the year 2018.Among these,106 registries had continuous monitoring data suitable for trend analysis from 2010 to 2018.We focused specifically on cancers affecting female genital organs(ICD10=C51-C54,C56)and projected their incidences and mortalities in China for 2022 based on data from 2018 and the trends observed from 2010 to 2018.Age-standardized incidence rate(ASIR)and mortality rate(ASMR)were calculated using Segi’s world standard population.Results:In 2022,there were an estimated 296,300 new cases and 104,900 deaths from female cancers in China.ASIRs for vulva(C51),vagina(C52),cervix uteri(C53),corpus uteri(C54),and ovary(C56)were 0.32,0.23,13.83,6.84,and 5.68 per 100,000 population.ASIRs for corpus uteri and ovary cancers were higher in urban areas.ASMRs for vulva,vagina,cervix,corpus uteri,and ovary cancers were 0.14,0.08,4.54,1.05,and 2.64 per 100,000 population,respectively.ASMR for ovarian cancer was higher in urban areas.ASIRs and ASMRs for most female genital organ cancers increased from 2010 to 2018,although the rate of increase for vulvar and cervical cancers in rural areas has slowed recently.Conclusions:Tailored cancer prevention and control programs specific to each region are necessary to address the growing disease burden.

关键词： ICD10 mortality organs