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Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies

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Cancer Communications 2024年第3期44卷 408-432页

作者： Lu Tang Huan Zhang Fen Zhou Qiuzhe Wei Mengyi Du jianghua Wu Chenggong Li Wenjing Luo jie Zhou Xindi Wang Zhaozhao Chen Yinqiang Zhang Zhongpei Huang Zhuolin Wu Yuxi Wen Huiwen Jiang Danying Liao Haiming Kou Wei Xiong Heng Mei Yu Hu Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei Clinical Medical Center of Cell Therapy For Neoplastic Disease WuhanHubeiP.R.China Key Laboratory of Biological Targeted Therapy the Ministry of EducationWuhanHubeiP.R.China Department of Thoracic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Pediatrics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei Key Laboratory of Biological Targeted Therapy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China

Background:Chimeric antigen receptor T(CAR-T)therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignan-cies,but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully *** study aims to explore the molecular deter-minants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical ***:The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated *** in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR-T *** addition,the specific mechanisms influencing CAR-T cell-mediated cancer clearance were elucidated in mouse and cellular ***:The CRISPR/Cas9-based knockout screening showed that the enrich-ment of autophagy-related genes(ATG3,BECN1,and RB1CC1)provided protec-tion of cancer cells from CD19 CAR-T cell-mediated *** findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of ***,higher expression of the three autophagy-related proteins in tumor samples was correlated with poorer respon-siveness and worse survival in patients with relapsed/refractory B-cell lymphoma after CD19 CAR-T *** RNA sequencing analysis of bone marrow samples from B-cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR-T cell *** inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR-T cell-mediated killing in mouse models of both B-cell leukemia and ***,our study revealed that cancer-intrinsic

关键词： CAR-T resistance Autophagy Immune evasion Apoptosis Chemotaxis

航改燃机多点喷射贫预混燃烧室燃料分级实验研究

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推进技术 2024年第3期45卷 184-193页

作者：孙付军潘江华郭璐华李洁马宏宇索建秦西北工业大学动力与能源学院陕西西安710072 中国航发湖南动力机械研究所湖南株洲412002 中国航发沈阳发动机研究所辽宁沈阳110015

为保证多点喷射贫预混燃烧室在50%~100%载荷工况范围的NO_(x)和CO排放量满足排放标准,本文实验研究了燃料分级数及不同工况、进口压力、进口温度下燃料分级比例对七喷嘴燃烧室NO_(x)和CO排放的影响规律。结果表明:主模燃料不分级方案,50... 详细信息

为保证多点喷射贫预混燃烧室在50%~100%载荷工况范围的NO_(x)和CO排放量满足排放标准,本文实验研究了燃料分级数及不同工况、进口压力、进口温度下燃料分级比例对七喷嘴燃烧室NO_(x)和CO排放的影响规律。结果表明:主模燃料不分级方案,50%~60%载荷工况CO排放量较高而不满足排放标准;主模燃料分两级方案,50%~100%载荷工况范围内NO_(x)和CO排放量均满足f_(NOx)≤25×10^(-6),fCO≤50×10^(-6)(@15%O_(2))的排放标准,且70%工况是打开主模第二级燃料的过渡工况点。另外随着进口压力和温度升高,能同时满足NO_(x)和CO排放标准的R_(pilot)(副模燃料质量流量与总燃料质量流量之比)范围逐渐缩小,且NO_(x)排放量与进口压力关系为F_(NOx)∝p30.44。因此采用主模燃料两级分级方案且适当调节R_(pilot),本文多点喷射贫预混燃烧室NO_(x)和CO能满足目前航改地面燃机燃烧室排放要求。

关键词：航改燃机多点喷射贫预混燃烧低污染燃料分级

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烤烟苗期施用腐殖酸肥对低温胁迫的响应

云南农业大学学报（自然科学版） 2024年第3期39卷 72-78页

作者：旷子扬秦凌金江华张赛李旭黄杰夏冰邓小华湖南农业大学农学院湖南长沙410128 湖南省烟草公司永州市公司湖南永州425000 吉林烟草工业有限责任公司吉林延吉133000 湖南省烟草公司郴州市公司湖南郴州423000

【目的】为应对湘南稻作烟区烤烟移栽期低温阴雨天气,促进烤烟早生快发。【方法】采用盆栽试验,研究腐殖酸肥(全能有机碳肥)在低温胁迫下对烟苗地上部分生长、根系生长、干物质积累与分配、叶片SPAD值、硝酸还原酶(NR)活性、丙二醛含量... 详细信息

【目的】为应对湘南稻作烟区烤烟移栽期低温阴雨天气,促进烤烟早生快发。【方法】采用盆栽试验,研究腐殖酸肥(全能有机碳肥)在低温胁迫下对烟苗地上部分生长、根系生长、干物质积累与分配、叶片SPAD值、硝酸还原酶(NR)活性、丙二醛含量和抗氧化酶活性的影响。【结果】腐殖酸肥质量浓度对低温胁迫下烤烟生长发育具有双重效果,表现为低质量浓度促进、高质量浓度抑制。适量施用腐殖酸肥(单株417~833 mg)可减缓低温胁迫对烟苗的损伤,促进其根系和地上部生长、干物质积累以及烟苗根系活力,叶片SPAD值提高4.64%~5.80%,超氧化物歧化酶(SOD)活性提升23.20%~50.26%,过氧化氢酶(CAT)活性提升5.39%~9.54%,过氧化物酶(POD)活性提升137.29%~151.43%;还可提高低温胁迫后烟苗的恢复生长能力,叶片SPAD值提高7.87%~10.64%,NR活性提升30.30%~42.42%,CAT活性提升0.89%~26.72%,POD活性提升90.91%~145.45%。【结论】施用腐殖酸肥可提高烟苗抗寒能力和恢复生长能力,有利于南方稻茬烟区烟苗早生快发。

关键词：低温胁迫腐殖酸肥烟苗生长烟叶生理生化指标

A-DA’D-A Type Pentacyclic Small Molecule Acceptors to Exceed 16.5%Efficiency by Heteroatom Effect at the Outer Side Chain

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Chinese Journal of Chemistry 2023年第15期41卷 1815-1822页

作者： Shaofeng Zhu Changzhou Shi Qingya Wei Can Zhu jie Ren jianghua Li Lei Meng Yongfang Li Jun Yuan Yingping Zou State Key Laboratory of Powder Metallurgy College of Chemistry and Chemical EngineeringCentral South UniversityChangshaHunan 410083China Beiing National Laboratory for Molecular Sciences CAS Key Laboratory of Organic SolidsInstitute of ChemistryChinese Academy of SciencesBeijing 100190China. MOE Key Laboratory of Macromolecular Synthesis and Functionalization International Research Center for X PolymersDepartment of Polymer Science and EngineeringZhejiang UniversityHangzhouZhejiang 310027China

Comprehensive Summary In this work,we adopt a“heteroatom side-chains”modification strategy to modify the thiophene units in A-DA'D-A(acceptor-donor-acceptor’-donor-acceptor)type pentacyclic SMAs(small molecule acceptors),that is,introducing branched alkyl chain at theβ-position of thiophene instead of straight alkyl chain,and then introducing oxygen atom at the third-position on the basis of branched *** new pentacyclic SMAs(BZ4F-EH and BZ4F-OEH)were synthesized,and the influence of the heteroatom side-chains on photoelectric properties of A-DA'D-A type pentacyclic SMAs was systematically *** with our previously reported BZ4F(Y26),BZ4F-EH shows slightly blue-shifted absorption,while BZ4F-OEH has obvious red-shifted *** a result,BZ4F-OEH-based binary device achieved a high power conversion efficiency(PCE)of 16.56%with a fill factor(FF)of 79.3%,which is the highest efficiency of pentacyclic SMAs to date.

关键词： Organic solar cells Small molecule acceptors A-DA'D-A type structure Heteroatom side chains Substituent effects

Low BMI patients with advanced EGFR mutation-positive NSCLC can get a better outcome from metformin plus EGFR-TKI as first-line therapy:A secondary analysis of a phase 2 randomized clinical trial

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2023年第2期1卷 119-124页

作者： Rui Han jianghua Li Yubo Wang Tingting He jie Zheng Yong He Department of Respiratory Disease Daping HospitalArmy Medical UniversityChongqing 400042China

Background:The synergistic association between metformin and epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)has been confirmed in in vitro *** is still controversial which patients can benefit from metformin plus EGFR-TKIs *** mass index(BMI)was proved to be independently associated with prolonged progression-free survival(PFS)and overall survival(OS).This study aimed to in-vestigate whether BMI is associated with the synergistic effect of metformin and EGFR-TKIs in advanced EGFR mutation(EGFR m)-positive non-small cell lung cancer(NSCLC)among nondiabetic Asian ***:We performed a post hoc analysis of a prospective,double-blind phase II randomized clinical trial(COAST,NCT01864681),which enrolled 224 patients without diabetes with treatment-naïve stage IIIB-IV EGFR m *** stratified patients into those with a high BMI(≥24 kg/m^(2))and those with a low BMI(<24 kg/m^(2))to allow an analysis of the difference in PFS and OS between the two *** PFS and OS were analyzed using Kaplan-Meier curves,and the differences between groups were compared using log-rank ***:In the univariate analysis,patients who had a high BMI(n=56)in the gefitinib+metformin group(n=28)did not have a better PFS(8.84 months vs.11.67 months;P=0.351)or OS(15.58 months vs.24.36 months;P=0.095)than those in the gefitinib+placebo group(n=28).Similar results were also observed in the low-BMI ***,in the metformin plus gefitinib group,patients who had low BMI(n=69)showed significantly better OS than those with high BMI(24.89 months[95%CI,20.68 months-not reached]vs.15.58 months[95%CI,13.78-31.53 months];P=0.007),but this difference was not observed in PFS(10.78 months vs.8.84 months;P=0.285).Conclusions:Our study showed that nondiabetic Asian advanced NSCLC patients with EGFR mutations who have low BMI seem to get better OS from metformin plus EGFR-TKI treatment.

关键词： Non-small cell lung cancer Metformin Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs) Body mass index Gefitinib

肾组织石蜡切片Ⅳ型胶原α链免疫组织化学染色在诊断Alport综合征中的应用

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现代医药卫生 2024年第10期40卷 1660-1664页

作者：张能擘赵杰王美芳王慧萍周芹毕艳陈江华浙江大学医学院附属第一医院肾脏病中心/浙江省肾脏病防治技术研究重点实验室/国家临床重点专科/浙江大学肾脏病研究所/浙江省肾脏与泌尿系统疾病临床医学研究中心浙江杭州310000

目的对Alport综合征(AS)患者肾脏穿刺组织进行石蜡切片Ⅳ型胶原α链免疫组织化学检测,探讨其临床应用价值。方法选取2018年11月至2022年7月浙江大学医学院附属第一医院肾脏病中心确诊的10例AS患者(AS病例组)、10例心脏死亡器官捐献者(D... 详细信息

目的对Alport综合征(AS)患者肾脏穿刺组织进行石蜡切片Ⅳ型胶原α链免疫组织化学检测,探讨其临床应用价值。方法选取2018年11月至2022年7月浙江大学医学院附属第一医院肾脏病中心确诊的10例AS患者(AS病例组)、10例心脏死亡器官捐献者(DCD)供肾及10例确诊为免疫球蛋白A肾病患者(对照组)的肾组织进行石蜡切片Ⅳ型胶原α1、α3、α5链全自动免疫组织化学染色,将其与冰冻切片免疫荧光染色结果进行比较。将对照组肾组织石蜡切片分别采用多种方法进行抗原修复,比较修复效果。结果对照组肾组织2种染色方法Ⅳ型胶原α1、α3、α5链染色在肾小球基底膜(GBM)中均为连续线状阳性表达。AS病例组肾组织2种染色方法Ⅳ型胶原α1链染色在GBM均呈连续线状阳性表达,α3、α5链染色在GBM为阴性或节段弱阳性表达。2种染色方法染色结果具有较高的一致性(Kappa=0.615,P=0.035)。结论石蜡切片全自动免疫组织化学检测Ⅳ型胶原α1、α3和α5能较好地用于AS的诊断,为AS的诊断和研究提供了一种可靠的技术手段。

关键词： Alport综合征诊断 Ⅳ型胶原α链免疫组织化学间接荧光抗体技术

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淀粉糊化度检测方法及在白酒应用中研究进展

酿酒 2024年第2期51卷 24-29页

作者：赵荣寿赵江华高占争黄荣杨果赵玲陶洪驰杨柳李捷四川郎酒股份有限公司四川泸州646523 四川省古蔺郎酒厂(泸州)有限公司四川泸州646601

淀粉糊化度是食品行业中重要控制指标,其测定方法主要有酶水解法,粘度检测法、脉冲核磁法、差示扫描量热法、累计光密度法、聚焦光束反射分析法,每种方法各有优缺点。白酒酿造中对粮食糊化有一定要求,通过测定糊化度可以了解蒸粮情况,... 详细信息

淀粉糊化度是食品行业中重要控制指标,其测定方法主要有酶水解法,粘度检测法、脉冲核磁法、差示扫描量热法、累计光密度法、聚焦光束反射分析法,每种方法各有优缺点。白酒酿造中对粮食糊化有一定要求,通过测定糊化度可以了解蒸粮情况,有利于优化白酒酿造工艺,以及白酒品质的提升。白酒酿造过程中糟醅糊化度检测方法不统一,还未形成相关标准,需进一步研究更加适合白酒酿造的糊化度检测方法,促进白酒酿造过程中糊化度的快速准确检测。

关键词：白酒淀粉糊化度检测方法研究进展

hSHIP induces S-phase arrest and growth inhibition in cervical cancer HeLa cells

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Journal of Genetics and Genomics 2010年第4期37卷 249-255页

作者： Kangxia He jie He Shengyu Wang jianghua Yan Cancer Research Center Medical College Xiamen University 422 Siming South Road Xiamen 361005 China School of Life Science Xiamen University 422 Siming South Road Xiamen 361005 China

hSHIP, a human SH2-containing inositol-5-phosphatase, acts as a negative regulator of proliferation and survival in hematopoietic cells. Therefore, hSHIP may play a crucial role in suppression of cervical cancer HeLa cells. In this study, pcDNA3.1-hSHIP-GFP plas- mid was constructed and transfected into HeLa cells with Lipofectamine2000, stably transfected HeLa cells were established and their responses were investigated by Flow cytometry, MTT, tumorigenicity in nude mice, RT-PCR and ELISA assays. The results showed that the expression of hSHIP significantly induced S-phase arrest, cell growth inhibition, and down-regulation of Aktl/2 mRNA and p-Akt in HeLa cells. Our study supports an important role for hSHIP in suppression of cervical cancer HeLa cells, which may prove to be a novel therapeutic option for non-hematopoietic cancers.

关键词： SH2-containing inositol-5-phosphatase (SHIP) cell cycle cell growth PI3K/Akt HeLa cells

Ultrafast all-optical switching of dual-band plasmon-induced transparency in terahertz metamaterials

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Chinese Optics Letters 2022年第1期20卷 174-179页

作者：孙豪张江华唐玉华刘衡竹杨杰郑鑫 College of Computer National University of Defense TechnologyChangsha 410073China National Innovation Institute of Defense Technology Beijing 100010China

An active ultrafast formation and modulation of dual-band plasmon-induced transparency(PIT) effect is theoretically and experimentally studied in a novel metaphotonic device operating in the terahertz regime,for the first time,to the best of our ***,we designed and fabricated a triatomic metamaterial hybridized with silicon islands following a newly proposed modulating *** this mechanism,a localized surface plasmon resonance is induced by the broken symmetry of a C_(2)structure,acting as the quasi-dark *** by exterior laser pumps,the photo-induced carriers in silicon promote the quasi-dark mode,which shields the near-field coupling between the dark mode and bright mode supported by the triatomic metamaterial,leading to the dynamical modulation of terahertz waves from individual-band into dual-band PIT effects,with a decay constant of 493 ***,a remarkable slow light effect occurs in the modulating process,accompanied by the dual-transparent *** dynamical switching technique of the dual-band PIT effect introduced in this work highlights the potential usefulness of this metaphotonic device in optical information processing and communication,including multi-frequency filtering,tunable sensors,and optical storage.

关键词： all-optical switching terahertz metamaterials dual-band plasmon-induced transparency ultrafast modulation