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TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis

Chinese Medical Journal 2024年第13期137卷 1592-1602页

作者： Jingyi Han Xue Zhang menghua cai Feng Tian Yi Xu Hui Chen Wei He Jianmin Zhang Hui Tian Department of Thoracic Surgery Qilu Hospital of Shandong UniversityJinanShandong 250012China CAMS Key Laboratory of T Cell and Immunotherapy Department of ImmunologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeState Key Laboratory of Medical Molecular BiologyBeijing 100005China Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy ChangzhouJiangsu 213000China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

Background:Acute respiratory distress syndrome(ARDS)is a common cause of respiratory failure in many critically ill *** inflammasome activation plays an important role in the induction of acute lung injury(ALI)and ARDS,the regulatory mechanism of this process is still *** cells are stimulated by inflammation,the integrity and physiological function of mitochondria play a crucial part in ***,the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet ***,we identified the 18-kDa translocator protein(TSPO),a mitochondrial outer membrane protein,as an important mediator regulating nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome activation in macrophages during ***:TSPO gene knockout(KO)and lipopolysaccharide(LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of *** macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome *** of NLRP3 inflammasome was preformed through LPS+adenosine triphosphate(ATP)co-stimulation,followed by detection of mitochondrial membrane potential,reactive oxygen species(ROS)production,and cell death to evaluate the potential biological function of *** between two groups were performed with a two-sided unpaired ***:TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced *** deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway,promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue,including interleukin(IL)-1β,IL-18,and macrophage inflammatory protein(MIP)-*** in TSPO-KO macrophages tended to depolarize in response to cellular *** increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membr

关键词： Acute respiratory distress syndrome Acute lung injury 18-kDa translocator protein Macrophage NLRP3 inflammasome Inflammation

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Anti-PD-1 antibody armored γδ T cells enhance anti-tumor efficacy in ovarian cancer

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5470-5480页

作者： Yue Wang Jingyi Han Dongdong Wang menghua cai Yi Xu Yu Hu Hui Chen Wei He Jianmin Zhang Department of Immunology CAMS Key Laboratory of T-cell and ImmunotherapyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major DiseasesBeijing 1oooo5China Department of Thoracic Surgery Qilu Hospital of Shandong UniversityJinanShandong 250012China Haihe Laboratory of CellEcosystem Chinese Academy of Medical Sciences&Peking Union Medical College288 Nanjing RoadTianjin 300020China Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy Changzhou 213000China

γδ T cells have the unique ability to detect a wide range of tumors with low mutation burdens,making them attractive candidates for CAR-T-cell *** aβT cells and other immune cells,γδ T cells are superior in MHC non-restriction,selective cell recruitment,and rapid ***,clinical trials have shown limited clinical benefits,and the adoptive transplantation of γδ T cells has often fallen short of *** hypothesized that the limited effectiveness of γδ T cells in eradicating tumor cells may be attributed to the inhibitory tumor microenvironment induced by the suppressive PD-1/PD-L1 ***,we constructed novel armored γδ T cells capable of secreting humanized anti-PD-1 antibodies,referred to as"Lv-PD1-ys T ***-PD1-γδ T cells showed improved proliferation and enhanced cytotoxicity against tumor cells,resulting in augmented therapeutic effects and survival benefits in ovarian tumor-bearing *** engineered cells demonstrated a prolonged in vivo survival of more than 29 days,without any potential for tumorigenicity in immunodeficient NOD/SCID/null *** also found that Lv-PD1-γδ T cells exhibited excellent tolerance and safety in humanized NOD/SCID/null *** attenuated or eliminated immunosuppression and maximized cytotoxicity efficacy by the local secretion of anti-PD1 antibodies in tumors,Lv-PD1-γδ T cells can serve as a promising"off-the-shelf"cell therapy against cancers.

关键词： PD1 attractive sized

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过表达膜定位IL-3的293T细胞外泌体的纯化及体外功能验证

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基础医学与临床 2024年第7期44卷 947-953页

作者：高璐蔡孟华许依何维陈慧张建民中国医学科学院基础医学研究所北京协和医学院基础医学院免疫学系中国医学科学院T细胞与免疫治疗重点实验室重大疾病共性机制研究全国重点实验室北京100005 常州西太湖细胞治疗前沿技术研究院江苏常州213000

目的体外验证过表达膜定位IL-3的293T细胞外泌体的功能,为在阿尔茨海默病模型动物的体内功能验证奠定基础。方法利用本课题组的专利结构,构建能定位于外泌体膜上的重组IL-3慢病毒载体,包装病毒感染293T细胞,筛选稳定表达细胞株。用流式... 详细信息

目的体外验证过表达膜定位IL-3的293T细胞外泌体的功能,为在阿尔茨海默病模型动物的体内功能验证奠定基础。方法利用本课题组的专利结构,构建能定位于外泌体膜上的重组IL-3慢病毒载体,包装病毒感染293T细胞,筛选稳定表达细胞株。用流式细胞测量术和免疫荧光技术对IL-3的膜定位进行验证;超滤离心纯化IL-3外泌体,透射电镜观察外泌体形态;纳米流式测量术检测外泌体粒径分布及浓度;Western blot检测IL-3及外泌体相关标志蛋白质表达;免疫荧光技术检测其对小胶质细胞系BV-2吞噬Aβ淀粉样蛋白能力的影响。结果经过载体构建、病毒感染、嘌呤霉素筛选和验证,得到稳定过表达膜定位IL-3的293T细胞株;收集纯化外泌体,在透射电镜下可见直径50~100 nm的双层膜囊泡结构;免疫印迹结果显示CD63、ALIX、TSG101等多种外泌体标志蛋白质检测阳性,且与对照相比富含IL-3,提示IL-3外泌体纯化成功;免疫荧光技术检测结果显示IL-3外泌体能在体外促进BV-2细胞对Aβ淀粉样蛋白的吞噬作用。结论过表达膜定位IL-3的基因修饰293T细胞外泌体在体外兼具IL-3和外泌体的作用,能够促进小胶质细胞的吞噬作用,为阿尔茨海默病的临床治疗提供新的思路。

关键词：白细胞介素3(IL-3) 外泌体小鼠脑小胶质细胞系(BV-2) 阿尔茨海默病

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Construction and Characterization of ATAD1 Interacting Network

Construction and Characterization of ATAD1 Interacting Netwo...

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第十届全国免疫学学术大会

作者： menghua cai Yu Zhou Huaishan Wang Yu Hu Jianmin Zhang Department of Immunology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and School of Basic Medicine Peking Union Medical College

Purpose:ATAD1 belongs to an AAA+ATPase family which frequently performs chaperone-like functions,including membrane dynamics,protein transport,and assembly or disassembly of protein complexes without unfolding or destroying their target *** aim is to illustrate functions of ATAD1 in neurodegenerations,such as Alzheimer disease and Parkinsons ***:We expressed and purified ATAD1 and mutant ones in Escherichia *** CHIP(17k)was used to explore ATAD1 interacting *** down our interest targets,we constructed several EGFP-tag vectors and transfected ATAD1 with potent partners in HEK293T cells followed by co-immunoprecipitation(co-IP)as well as microscale thermophoresis(MST)***:As a bait protein,ATAD1 binding to 375 proteins was detected by protein CHIP 17k ***-IP and MST indicated that ATAD1 specifically interacted with 14 proteins which were involved in functions of mitochondria and cell ***:Our findings have provided further insight into understanding the function of ATAD1,which may facilitate the development of therapeutic strategies for targeting ATAD1 from basic to clinics in future.

关键词： ATAD1 Protein CHIP Co-immunoprecipitation Mitochondria Apoptosis

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基于全生命周期评价的中国制氨路线碳排放、能源效率研究及展望

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中国科学：技术科学 2024年第7期54卷 1329-1346页

作者：刘梦华黄逍李爽史翊翔喻朝庆蔡宁生清华大学能源与动力工程系北京100084 海南大学生态与环境学院海口570228 清华大学山西清洁能源研究院太原030032

我国实现双碳目标的核心在于能源系统的低碳化和清洁化.未来风电、光伏电等一次能源大比例接入电网,其波动性、间歇性等特点使得可跨季广域消纳储能技术的发展成为刚需.氨的稳定性、易存储、输储设施完善等特性使其成为极具竞争力的化... 详细信息

我国实现双碳目标的核心在于能源系统的低碳化和清洁化.未来风电、光伏电等一次能源大比例接入电网,其波动性、间歇性等特点使得可跨季广域消纳储能技术的发展成为刚需.氨的稳定性、易存储、输储设施完善等特性使其成为极具竞争力的化学储能介质,有望破解当前氢储运难题,助力实现“碳中和、碳达峰”目标.目前面向我国规模化应用的中国制氨路线生命周期评估工作较少,缺乏考虑细分环节的合成氨路线的全生命周期碳排放及能效等指标的评估与分析.针对上述氨储能技术发展存在的机遇和挑战,本文建立各主要阶段的合成氨全生命周期评估(life cycle assessment,LCA)集成模型,结合低碳排技术对不同制氨路线生命周期间的一次能源投入及碳排放进行评估与分析.通过核算煤制氨(R1)、天然气制氨(R2)、市电制氨(R3)及可再生电力制氢合成氨(R4)四种技术路线的碳排放及能源效率,并对关键参数进行敏感度分析,确定造成碳排放的关键环节和关键因素,提出减少碳排放的技术改进建议.研究表明,未采用碳捕获与封存技术(carbon capture and storage,CCS)的煤制氨(R1-w/o CCS)与天然气制氨路线(R2-w/o CCS)碳排放则分别高达4.190和2.356 kg CO_(2)/kg NH_(3),R3路线碳排放高达6.384 kg CO_(2)/kg NH_(3),分别以光伏电站(R4-PV)和风力发电站(R4-Wind)为电力输入的可再生电力制氢合成氨路线碳排放分别为0.569和0.335 kg CO_(2)/kg NH_(3).结合CCS技术后,R1-w/CCS和R2-w/CCS路线碳排放可分别降低61.8%和55.4%,但因CO_(2)捕获、运输和封存带来的额外能耗使每功能单位氨生产的化石能源消耗量相应增长4.2%和5.8%,生命周期能源效率分别降低1.6%和2.5%.本文从全生命周期的碳排放和能效角度出发,通过定义统一系统边界提高模型的精准度与可对比度,为不同制氨路线的工艺改进情景提供了可靠的分析.

关键词：合成氨生命周期评价能效分析能源消耗碳排放

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Modeling of Packed Bed Methanol Steam Reformer Integrated with Tubular High Temperature Proton Exchange Membrane Fuel Cell

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Journal of Thermal Science 2023年第1期32卷 81-92页

作者： LIU menghua SHI Yixiang cai Ningsheng Key Laboratory for Thermal Science and Power Engineering of Ministry of Education Department of Energy and Power EngineeringTsinghua UniversityBeijing 100084China

This work proposes a novel tubular structure of high-temperature proton exchange membrane fuel cell(PEMFC)integrated with a built-in packed-bed methanol steam reformer to provide hydrogen for power output.A two-dimensional axisymmetric non-isothermal model was developed in COMSOL Multiphysics 5.4 to simulate the performance of a tubular high temperature proton membrane fuel cell and a packed bed methanol *** model considers the coupling multi-physical processes,including methanol reforming reaction,water gas shift reaction,methanol cracking reaction as well as the heat,mass and momentum transport *** sub-model of the tubular packed-bed methanol reformer is validated between 433 K and 493 K with the experimental data reported in the *** sub-model of the high temperature proton exchange fuel cell is validated between 393 K and 433 K with the published *** results show that power output and temperature distribution of the integrated unit depend on methanol flow rates and working *** was suggested that stable power generation performance of 0.14 W/cm_(2)and temperature drop in methanol steam reformer of≤10 K could be achieved by controlling the methanol space-time ratio of≥250 kg·s/mol with working voltage at 0.6 V,even in the absence of an external heat source.

关键词： high temperature proton exchange membrane fuel cell methanol steam reformer tubular PEMFC hydrogen production Multiphysics modeling

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回火温度对高强钢板硬度的影响

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机电工程技术 2020年第1期49卷 132-133,185页

作者：蔡梦华陈海彬徐进李阳嘉东莞理工学院

研究了回火温度对QP980、MS1180、DP980及780TR 4种高强钢硬度的影响,并预测了实验钢其他力学性能的变化。实验前用HD-1000TM显微硬度计分别测量4组试样的初始硬度,后使用电炉对实验钢进行回火处理,期间用热像仪检测实验温度,水冷后再... 详细信息

研究了回火温度对QP980、MS1180、DP980及780TR 4种高强钢硬度的影响,并预测了实验钢其他力学性能的变化。实验前用HD-1000TM显微硬度计分别测量4组试样的初始硬度,后使用电炉对实验钢进行回火处理,期间用热像仪检测实验温度,水冷后再次用显微硬度计测量实验钢的硬度,分析实验前后的数据。结果表明:在300~500℃之间,随着回火温度的升高,实验钢的硬度逐渐减小,而初始硬度越高的试验钢,在同一温度区间内的硬度变化越大。并且相同条件下,温度升高也会导致抗拉强度和疲劳极限下降。

关键词：高强钢热处理机械性能硬度

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Using Imbalanced Triangle Synthetic Data for Machine Learning Anomaly Detection

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Computers, Materials & Continua 2019年第1期58卷 15-26页

作者： menghua Luo Ke Wang Zhiping cai Anfeng Liu Yangyang Li Chak Fong Cheang College of Computer National University of Defense TechnologyChangsha410073China Normal College of Jishou University Jishou416000China School of Information Science and Engineering Central South UniversityChangsha410083China Innovation Center China Academy of Electronics and Information TechnologyBeijing100041China Faculty of Information Technology Macao University of Science and Technology519020Macao

The extreme imbalanced data problem is the core issue in anomaly *** amount of abnormal data is so small that we cannot get adequate information to analyze *** mainstream methods focus on taking fully advantages of the normal data,of which the discrimination method is that the data not belonging to normal data distribution is the *** the view of data science,we concentrate on the abnormal data and generate artificial abnormal samples by machine learning *** this kind of technologies,Synthetic Minority Over-sampling Technique and its improved algorithms are representative milestones,which generate synthetic examples randomly in selected line *** our work,we break the limitation of line segment and propose an Imbalanced Triangle Synthetic Data *** theory,our method covers a wider *** experiment with real world data,our method performs better than the SMOTE and its meliorations.

关键词： Anomaly detection imbalanced data synthetic data machine learning

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Effects of rural domestic sewage reclaimed irrigation and regulation on heavy metals,PPCPs,water and nitrogen utilization,and microbial diversity in paddy field

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International Journal of Agricultural and Biological Engineering 2023年第4期16卷 245-256页

作者： Shizong Zheng menghua Xiao Lei Wang Yuanyuan Li Wanchuan Xiao Dan Xu Jiafang cai Rural Water Conservancy Research Institute Zhejiang Institute of Hydraulics and EstuaryHangzhou 310020China Zhejiang Institute of Marine Planning and Design Hangzhou 310020China School of Water Conservancy North China University of Water Resource and Electric PowerZhengzhou 450045China

Rural domestic reclaimed water(RDRW)is rural domestic sewage that being safely treated,the irrigation and reuse of RDRW are an effective way to alleviate the contradiction between supply and demand of water resources in South *** this study,four kinds of irrigation water sources(primary and secondary treated water R1 and R2,purified water R3 and river water CK)and three kinds of water level regulations(low,medium,and high field water level control of W1,W2 and W3)were set to study the impact of RDRW on soil and crop safety,water and nitrogen utilization and biodiversity for establishing the regulation mechanism of RDRW irrigation with field experiment,and monitoring was carried out in RDRW irrigation demonstration area to assess the effectiveness of *** results showed that,under RDRW irrigation,the contents of Cd and Pb increased slightly,while the contents of Cr,Cu and Zn decreased in paddy *** heavy metals content decreased along the direction of stem,leaf and grain in rice plants,but did not increase significantly in rice *** the increase of field water level,pharmaceutical and personal care products(PPCPs)content in 60-80 cm soil layer was accumulated,and the PPCPs content in rice husks was higher than that in grains,but it was at a very low *** to CK,RDRW irrigation can effectively increase rice yield,rainwater use efficiency(RUE)and nitrogen use efficiency(NUE)by 5.4%-7.6%,6.7%-9.4%and 21.7%-24.2%,respectively,and the species diversity,community diversity and richness in rice fields were ***,water level regulation of W3 with R2 water resource irrigation was conducive to the exertion of comprehensive *** monitoring of demonstration area showed that the consumption of fresh water was reduced by 530 mm,yield was increased by 9.6%,and the soil and crop were both ***-term irrigation of RDRW did not cause soil and crops pollution,however,it is still necessary to track and monitor the effect of the

关键词： reclaimed water irrigation heavy metals pharmaceutical and personal care products water and nitrogen use efficiency soil microbial diversity technique for order preference by similarity to an ideal solution

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LD泵浦的kHz,Er^(3+),Yb^(3+):glass被动调Q微片激光器

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红外与激光工程 2018年第10期47卷 90-94页

作者：郭娜惠勇凌蔡瑾鹭姜梦华雷訇李强北京工业大学激光工程研究院北京100124

目前1.5μmLD泵浦铒玻璃被动调Q微型激光器是军事激光测距的研究热点,获得较高的激光重复频率和单脉冲能量尤为重要。文中主要报道了一种应用于激光测距领域的铒镱共掺磷酸盐玻璃被动调Q微片激光器。激光器采用中心波长为940 nm的单管... 详细信息

目前1.5μmLD泵浦铒玻璃被动调Q微型激光器是军事激光测距的研究热点,获得较高的激光重复频率和单脉冲能量尤为重要。文中主要报道了一种应用于激光测距领域的铒镱共掺磷酸盐玻璃被动调Q微片激光器。激光器采用中心波长为940 nm的单管二极管为泵浦源,铒镱共掺磷酸盐玻璃(Er^(3+),Yb^(3+):glass)作为增益介质,CO_^(2+):MgAl_2O_4(CO:MALO)作为可饱和吸收体。通过分析泵浦光斑半径对模式匹配影响,优化泵浦光斑半径,实验分析可饱和吸收体初始透过率T0和输出镜反射率R对输出激光参数影响,优化T0和R值。最终实验中采用增益预泵浦方式,实现重频1 k Hz,单脉冲能量40μJ,脉宽5.09 ns,峰值功率7.85 k W,光束质量M2=1.4,波长1 535 nm的稳定激光输出。

关键词：微片激光器被动调Q 模式匹配

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