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Inhalable metal–organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2281-2297页

作者： Chongzheng Yan Ying Liu Guozhi Zhao Huatian Yang Huaiyou Lv Genju Li Yuhan Li Yaqing Fu fengqin Sun yafei feng Yizhe Li Zhongxi Zhao Department of Pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China Key University Laboratory of Pharmaceutics&Drug Delivery Systems of Shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Cuproptosis shows enormous application prospects in lung metastasis treatment.However,the glycolysis,Cu^(+)efflux mechanisms,and insufficient lung drug accumulation severely restrict cuproptosis efficacy.Herein,an inhalable poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)(OPDEA)-coated copper-based metal–organic framework encapsulating pyruvate dehydrogenase kinase 1 siRNA(siPDK)is constructed for mediating cuproptosis and subsequently promoting lung metastasis immunotherapy,namely OMP.After inhalation,OMP shows highly efficient lung accumulation and long-term retention,ascribing to the OPDEA-mediated pulmonary mucosa penetration.Within tumor cells,OMP is degraded to release Cu2+under acidic condition,which will be reduced to toxic Cu^(+)to induce cuproptosis under glutathione(GSH)regulation.Meanwhile,siPDK released from OMP inhibits intracellular glycolysis and adenosine-5ʹ-triphosphate(ATP)production,then blocking the Cu^(+)efflux protein ATP7B,thereby rendering tumor cells more sensitive to OMP-mediated cuproptosis.Moreover,OMP-mediated cuproptosis triggers immunogenic cell death(ICD)to promote dendritic cells(DCs)maturation and CD8^(+)T cells infiltration.Notably,OMP-induced cuproptosis up-regulates membrane-associated programmed cell death-ligand 1(PD-L1)expression and induces soluble PD-L1 secretion,and thus synergizes with anti-PD-L1 antibodies(aPD-L1)to reprogram immunosuppressive tumor microenvironment,finally yielding improved immunotherapy efficacy.Overall,OMP may serve as an efficient inhalable nanoplatform and afford preferable efficacy against lung metastasis through inducing cuproptosis and combining with aPD-L1.

关键词： Cuproptosis Immunogenic cell death PD-L1 checkpoint blockade Copper-based metal-organic framework Immunotherapy Tumor microenvironment Transmucosal deliveryLung metastasis

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Oxygen vacancy stabilized Bi_(2)O_(2)CO_(3)nanosheet for CO_(2)electroreduction at low overpotential enables energy efficient CO-production of formate

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InfoMat 2023年第3期5卷 21-32页

作者： Yangyang Zhang Yanxu Chen Rong Liu Xiaowen Wang Huanhuan Liu Yin Zhu Qizhu Qian yafei feng Mingyu Cheng Genqiang Zhang Hefei National Research Center for Physical Sciences at the Microscale CAS Key Laboratory of Materials for Energy ConversionDepartment of Materials Science and EngineeringUniversity of Science and Technology of ChinaHefeiAnhuithe People's Republic of China School of Materials Science and Engineering Hebei University of TechnologyTianjinthe People's Republic of China

Bismuth-based electrocatalysts are promising candidates for electrochemical CO_(2)reduction to formate attributing to the accelerated formation of*OCHO intermediate,while the high-energy consumption remains a major challenge for practicability.Herein,we present the ultrathin Bi_(2)O_(2)CO_(3)nanosheets with abundant oxygen vacancy(Vo-BOC-NS)reconstructed from S,N-co-doped bismuth oxides that can act as durable electrocatalyst for CO_(2)-to-formate conversion with faradic efficiency(FEformate)of>95%,partial current density of 286 mA cm^(-2) with energy efficiency of 73.8%at-0.62 V(vs.RHE)and low overpotential of 200 mV in a flow electrolyzer.The theoretical calculations decipher that the oxygen vacancy can optimize*OCOH adsorption/desorption for the accelerated conversion kinetics.The pair-electrosynthesis tactic of formate co-production can enable a superior FE_(formate) of>90%at wide cell voltage of 2–3.3 V and total yield rate of 3742μmol cm^(-2)h^(-1)at 3.3 V,suggesting great potential for future industrialization.

关键词： Bi_(2)O_(2)CO_(3) CO_(2)reduction electrocatalysis oxygen vacancy pair-electrosynthesis

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Magic hybrid structure as multifunctional electrocatalyst surpassing benchmark Pt/C enables practical hydrazine fuel cell integrated with energy-saving H_(2)production

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eScience 2022年第4期2卷 416-427页

作者： Ziyun Li Wentao Wang Qizhu Qian Yin Zhu yafei feng Yangyang Zhang Huaikun Zhang Mingyu Cheng Genqiang Zhang Hefei National Research Center for Physical Sciences at the Microscale CAS Key Laboratory of Materials for Energy ConversionDepartment of Materials Science and EngineeringUniversity of Science and Technology of ChinaHefeiAnhui230026China Guizhou Provincial Key Laboratory of Computational Nano-Material Science Guizhou Education UniversityGuiyangGuizhou550018China

A hybrid catalyst structure can provide abundant active sites and tailored electronic properties,but the major challenge lies in achieving delicate control over its composition and architecture to improve the catalytic activity toward different electrochemical reactions simultaneously.Herein,we present the rational design of a magic hybrid structure with low Pt loading(5.90 wt%),composed of CoPt_(3)and CoPt nanoparticles supported on N-doped carbon(CoPt_(3)/CoPt⊂PLNC).Importantly,it shows superior multifunctional catalytic activity in alkaline conditions,requiring a low overpotential of 341 and 20 mV to achieve 10 mA cm^(−2)for the hydrazine oxidation reaction(HzOR)/hydrogen evolution reaction(HER),respectively,and it delivers a half-wave potential of 0.847 V for the oxygen reduction reaction(ORR).Theoretical calculations reveal that the metal-carbon hybrid modulates kinetic behavior and induces electron redistribution,achieving the energetic requirements for multiple electrocatalysis.We demonstrate sustainable H_(2)production utilizing solely the CoPt_(3)/CoPt⊂PLNC catalyst,without external electric power input,suggesting its inspiring practical utility.

关键词： Electrocatalysis Hybrid structure Fuel cell Hydrazine oxidation H_(2)production

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分阶段管理在动静脉内瘘血液透析患者护理不良事件管控中的应用价值

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临床医学研究与实践 2024年第19期9卷 183-186页

作者：冯娅飞华琳安康市中心医院陕西安康725000

目的探讨分阶段管理在动静脉内瘘血液透析患者护理不良事件管控中的应用价值。方法选取2020年6月至2022年6月我院收治的140例动静脉内瘘血液透析患者为研究对象,根据随机数字表法将其分为对照组(n=70,常规护理管理)和研究组(n=70,分阶... 详细信息

目的探讨分阶段管理在动静脉内瘘血液透析患者护理不良事件管控中的应用价值。方法选取2020年6月至2022年6月我院收治的140例动静脉内瘘血液透析患者为研究对象,根据随机数字表法将其分为对照组(n=70,常规护理管理)和研究组(n=70,分阶段管理)。比较两组的干预效果。结果干预后,研究组的自我概念、自我责任感、自我护理技术及健康知识掌握评分高于对照组(P<0.05)。干预后,研究组的D-二聚体(D-D)、凝血酶原时间(PT)、纤维蛋白原(FIB)、头静脉内径、头静脉血流量优于对照组(P<0.05)。研究组的不良事件总发生率低于对照组,内瘘通畅率高于对照组(P<0.05)。结论分阶段管理在动静脉内瘘血液透析患者中的应用效果显著,能有效控制不良事件发生风险。

关键词：动静脉内瘘血液透析分阶段管理不良事件

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基于沟通达标理论的护理干预结合同伴教育对尿毒症维持性血液透析患者疾病进展恐惧感及日常生活自我管理能力的影响

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临床医学研究与实践 2024年第16期9卷 174-177页

作者：华琳冯娅飞石娟黄朝琴邓婷安康市中心医院陕西安康725000 延安大学咸阳医院陕西咸阳712000

目的探讨基于沟通达标理论的护理干预结合同伴教育在尿毒症维持性血液透析患者中的应用效果。方法选取2019年5月至2022年5月收治的100例尿毒症维持性血液透析患者为研究对象,随机将其分为对照组和观察组,各50例。对照组予以常规护理,观... 详细信息

目的探讨基于沟通达标理论的护理干预结合同伴教育在尿毒症维持性血液透析患者中的应用效果。方法选取2019年5月至2022年5月收治的100例尿毒症维持性血液透析患者为研究对象,随机将其分为对照组和观察组,各50例。对照组予以常规护理,观察组予以基于沟通达标理论的护理干预结合同伴教育。比较两组的干预效果。结果干预后,观察组的疾病进展恐惧简化量表(FoP-Q-SF)各维度评分低于对照组,血液透析患者自我管理量表各维度评分高于对照组(P<0.05)。干预后,观察组的认知、透析依从性评分高于对照组(P<0.05)。观察组的并发症总发生率低于对照组(P<0.05)。结论基于沟通达标理论的护理干预结合同伴教育可减轻尿毒症维持性血液透析患者的疾病进展恐惧感,提高其日常生活自我管理能力,改善其认知和透析依从性,降低并发症发生率。

关键词：沟通达标理论同伴教育尿毒症维持性血液透析疾病进展恐惧感自我管理能力

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Analysis of Geographical Distribution of Missing Children Based on the Missing Children Mobile GIS Mutual Assistance System of China

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Journal of Geoscience and Environment Protection 2017年第12期5卷 117-134页

作者： Xiaodong Gong Hao Cheng Lu Yang Yueming Duan Yuan Yao yafei feng Le Fu Jianhua Liu Mingyi Du Key Laboratory for Urban Geomatics of National Administration of Surveying Mapping and Geoinformation Beijing China College of Surveying and Mapping Engineering Beijing University of Civil Engineering and Architecture Beijing China

The Missing Children Mobile GIS Mutual Assistance System of China (MCMAS) is a mobile service software based on mobile GIS platform software, and it is committed to providing the most convenient and efficient system of personally mutual tracing services for missing children family and society. Relying on collaborative utilization of location-based service technology, face image intelligent recognition technology, cloud computing technology, public big data sharing technology, and mobile GIS technology, the MCMAS has achieved prominent application effects since it was deployed. At present, the MCMAS is running soundly, and it has received and released the information about 1011 missing children from May 25, 2016 to May 25, 2017. In order to explore the geographical distribution features and the influencing factors of missing children, the data of missing children are used for spatial and visual analysis by the data mining and GIS technologies. At the same time, we have built the spatial thermodynamic diagram of the big data of China missing children. By comparing provinces and cities with a higher proportion of missing children, the results showed that: 1) The high proportion of missing children spatially concentrated in the eastern part of the China. 2) The number of missing children was significantly correlated with the population density and economic status of the city. Furthermore, the paper macro-levelly presents a basic basis for rescuing the missing children from two aspects: regionally spatial characteristics and influencing factors.

关键词： Missing Children Mobile GIS Location Based Service Spatiotemporal Big Data Mining

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二甲双胍对2型糖尿病患者脊柱内固定手术后远期功能的影响:一项回顾性研究

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空军军医大学学报 2024年第4期45卷 440-445,449页

作者：郝凯利王天吉马田成张扬赵雄吴子祥冯亚非雷伟空军军医大学西京医院骨科陕西西安710032

目的探讨二甲双胍对2型糖尿病(T2DM)患者脊柱内固定手术后远期功能的影响。方法选取2011年1月至2022年1月在空军军医大学西京医院骨科行脊柱内固定手术的T2DM患者,根据降糖药物的不同,将患者分为二甲双胍组和胰岛素组。收集患者的病... 详细信息

目的探讨二甲双胍对2型糖尿病(T2DM)患者脊柱内固定手术后远期功能的影响。方法选取2011年1月至2022年1月在空军军医大学西京医院骨科行脊柱内固定手术的T2DM患者,根据降糖药物的不同,将患者分为二甲双胍组和胰岛素组。收集患者的病历资料和生活质量、脊柱功能及疼痛的评估资料,采用t检验、单因素方差分析、Mann-Whitney U检验、Kruskal-Wallis H检验、χ^(2)检验和多元线性回归分析进行数据比较和分析。结果共纳入患者204例,其中二甲双胍组108例(52.94%),胰岛素组96例(47.06%)。术后远期功能评估,相对于胰岛素,二甲双胍的使用可显著提高患者健康调查简表生理机能维度评分(75.14分vs 65.36分,P<0.05)和一般健康状况维度评分(58.02分vs 48.08分,P<0.05),同时显著降低颈椎功能障碍指数或Oswestry功能障碍指数(15.93 vs 23.16,P<0.05)。此外,空腹血糖或餐后血糖越高、手术节段越多和体质量指数越大是影响患者术后远期功能的危险因素(P<0.05);在手术方式方面,相对于颈前路椎间盘切除融合术,腰椎后路椎间融合术是影响患者术后远期功能的危险因素(P<0.05)。结论相对于胰岛素,二甲双胍的使用可有效改善T2DM患者脊柱内固定手术后的远期功能。

关键词：二甲双胍 2型糖尿病脊柱内固定手术术后远期功能

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不同来源外泌体对股骨头坏死的治疗作用研究进展

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空军军医大学学报 2024年第5期45卷 578-581页

作者：贾鸿陈永锋贾竟孙强冯亚非张大伟朱庆生空军军医大学西京医院骨科陕西西安710032 郑州大学基础医学院河南郑州450001

股骨头坏死(ONFH)是骨科的常见病和多发病,发病率逐渐增加,发病机制主要为骨内血流破坏导致骨坏死,治疗方法众多,但结果往往不尽如人意,严重影响患者的生活质量。而外泌体作为一种细胞分泌的囊泡,富含多种生物活性成分,通过侵袭、细胞... 详细信息

股骨头坏死(ONFH)是骨科的常见病和多发病,发病率逐渐增加,发病机制主要为骨内血流破坏导致骨坏死,治疗方法众多,但结果往往不尽如人意,严重影响患者的生活质量。而外泌体作为一种细胞分泌的囊泡,富含多种生物活性成分,通过侵袭、细胞分化、免疫调节等多种方式在组织修复、血管形成等方面存在重要的作用。研究者们发现不同来源外泌体在抑制骨细胞凋亡、促进血管生成方面起到一定的作用。本文将外泌体与ONFH的相关研究做进一步综述,以期为ONFH的可逆性治疗提供参考和依据。

关键词：股骨头坏死外泌体骨细胞血管再生

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Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes

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Science China(Life Sciences) 2024年第2期67卷 301-319页

作者： Xiaoli Tang Hong Liu Rongjia Rao yafei Huang Mengqi Dong Miaomiao Xu Shanshan feng Xun Shi Li Wang Zengwu Wang Bingying Zhou State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China Department of Epidemiology Cardiovascular Institute and Fuwai HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100037China Shenzhen Key Laboratory of Cardiovascular Disease Fuwai Hospital Chinese Academy of Medical SciencesShenzhenShenzhen 518020China

Mitochondrial toxicity induced by therapeutic drugs is a major contributor for cardiotoxicity,posing a serious threat to pharmaceutical industries and patients’lives.However,mitochondrial toxicity testing is not incorporated into routine cardiac safety screening procedures.To accurately model native human cardiomyocytes,we comprehensively evaluated mitochondrial responses of adult human primary cardiomyocytes(h PCMs)to a nucleoside analog,remdesivir(RDV).Comparison of their response to human pluripotent stem cell-derived cardiomyocytes revealed that the latter utilized a mitophagy-based mitochondrial recovery response that was absent in h PCMs.Accordingly,action potential duration was elongated in h PCMs,reflecting clinical incidences of RDV-induced QT prolongation.In a screen for mitochondrial protectants,we identified mitochondrial ROS as a primary mediator of RDV-induced cardiotoxicity.Our study demonstrates the utility of h PCMs in the detection of clinically relevant cardiac toxicities,and offers a framework for h PCM-based high-throughput screening of cardioprotective agents.

关键词： remdesivir mitochondrial toxicity cardiotoxicity human primary cardiomyocytes high-throughput screening

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Thermal safety boundary of lithium-ion battery at different state of charge

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Journal of Energy Chemistry 2024年第4期91卷 59-72页

作者： Hang Wu Siqi Chen Yan Hong Chengshan Xu Yuejiu Zheng Changyong Jin Kaixin Chen yafei He Xuning feng Xuezhe Wei Haifeng Dai Clean Energy Automotive Engineering Center Tongji UniversityShanghai 201804China College of Mechanical Engineering University of Shanghai for Science and TechnologyShanghai 200093China State Key Laboratory of Automotive Safety and Energy Tsinghua UniversityBeijing 100084China

Thermal runaway(TR)is a critical issue hindering the large-scale application of lithium-ion batteries(LIBs).Understanding the thermal safety behavior of LIBs at the cell and module level under different state of charges(SOCs)has significant implications for reinforcing the thermal safety design of the lithium-ion battery module.This study first investigates the thermal safety boundary(TSB)correspondence at the cells and modules level under the guidance of a newly proposed concept,safe electric quantity boundary(SEQB).A reasonable thermal runaway propagation(TRP)judgment indicator,peak heat transfer power(PHTP),is proposed to predict whether TRP occurs.Moreover,a validated 3D model is used to quantitatively clarify the TSB at different SOCs from the perspective of PHTP,TR trigger temperature,SOC,and the full cycle life.Besides,three different TRP transfer modes are discovered.The interconversion relationship of three different TRP modes is investigated from the perspective of PHTP.This paper explores the TSB of LIBs under different SOCs at both cell and module levels for the first time,which has great significance in guiding the thermal safety design of battery systems.

关键词： Lithium-ion battery Battery safety Thermal runaway State of charge Numerical analysis

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