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Targeting carnitine palmitoyl transferase 1A(CPT1A)induces ferroptosis and synergizes with immunotherapy in lungg cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1675-1689页

作者： Lei Ma Chong Chen Chunxing Zhao Tong Li Lingyu Ma Jiayu Jiang Zhaojun Duan Qin Si Sung-Hsien Chuang Rong Xiang Yunping Luo Department of mmunology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBejing 100005China Collaborative Innovation Center for Biotherapy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Department of Lung Cancer Surgery Tianjin Medical University General HospitalTianjin 300052China Immunology Research Center National Health Research InstitutesZhunanMiaoliTaiwanROC Department of Immunology Nankai UniversityTianjin 300071China

Despite the successful application of immune checkpoint therapy,no response or recurrence is typical in lung cancer.Cancer stem cells(CSCs)have been identified as a crucial player in immunotherapy-related resistance.Ferroptosis,a form of cell death driven by iron-dependent lipid peroxidation,is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with immunotherapy.Metabolic adaption of CsCs drives tumor resistance,yet the mechanisms of their ferroptosis defense in tumor immune evasion remain elusive.Here,through metabolomics,transcriptomics,a lung epithelialspecific Cptla-knockout mouse model,and clinical analysis,we demonstrate that CPT1A,a key rate-limiting enzyme of fatty acid oxidation,acts with L-carnitine,derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8^(+)T cells inactivation in lung cancer.Mechanistically,CPT1A restrains ubiquitination and degradation of c-Myc,while c-Myc transcriptionally activates CPT1A expression.The CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating,thereby suppressing ferroptosis in CSCs.Significantly,targeting CPT1A enhances immune checkpoint blockadeinduced anti-tumor immunity and tumoral ferroptosis in tumor-bearing mice.The results illustrate the potential of a mechanismguided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CsCs to improve the efficacy of lung cancer immunotherapy.

关键词： immunotherapy metabolism peroxidation

Comparison of surgical indications for hysterectomy by age and approach in 4653 Chinese women

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Frontiers of Medicine 2014年第4期8卷 464-470页

作者： Jingjing Jiang Ting Ding Aiyue luo yunping Lu Ding Ma Shixuan Wang Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Approximately one million hysterectomies are performed each year in China. However, national data regarding the indications and the surgical approaches for hysterectomy are lacking. The aim of this study was to examine the surgical indications for hysterectomy in different age groups and the relative merits of different surgical approaches for hysterectomy in Chinese women. Clinical data from 4653 cases of hysterectomy performed in Tongji Hospital from 2004 to 2009 were analysed. Hysterectomy was most commonly performed among women aged 40-49 years （2299; 49.4%）. Overall, colporrhagia and abdominal pain were the two most common indications for hysterectomy. The most common indications by age groups were as follows： malignant ovarian tumour, 〈 20 years; malignant uterine tumour, 20-29 and 30-39 years; uterine myoma, 40-49 and 50-59 years; and uterine prolapse, 60-69 and 〉 70 years. The proportion of malignant aetiology also varied by age, being the highest in women aged 〈 20 years （75.0%） and the lowest in those aged 40-49 years （19.9%）. Approximately 35% women who had hysterectomies also had concomitant bilateral oophorectomy. The lowest rate of oophorectomy occurred in women aged 30-39years （15.8%）, whereas the highest rate was in those aged 50-59years （75.9%）. The abdominal surgical approach was used in 84% of all hysterectomies. Surgeries using the vaginal approach required a significantly shorter operating time （118 min average） than all other approaches （P 〈 0.05）. Both the amount of bleeding and the blood transfusion volume required were smaller in vaginal approaches, with no significant differences between the others. The surgical approaches used were also related to the scope of surgery. Both the surgical indications and the rates of bilateral oophorectomy varied by age. In terms of both operating time and the amount of bleeding and blood transfusion volume required, the vaginal approach was superior to all other surgical approaches.

关键词： hysterectomy surgical indications surgical approach bilateral oophorectomy

Fluorination-mitigated high-current degradation of amorphous InGaZnO thin-film transistors

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半导体学报:英文版 2023年第9期44卷 57-61页

作者： Yanxin Wang Jiye Li Fayang Liu Dongxiang luo yunping Wang Shengdong Zhang Lei Lu School of Electronic and Computer Engineering Peking University Shenzhen Graduate SchoolShenzhen 518055China Huangpu Hydrogen Innovation Center/Guangzhou Key Laboratory for Clean Energy and Materials School of Chemistry and Chemical EngineeringGuangzhou UniversityGuangzhou 510006China Institute of Microelectronics Peking UniversityBeijing 100871China

As growing applications demand higher driving currents of oxide semiconductor thin-film transistors(TFTs),severe instabilities and even hard breakdown under high-current stress(HCS)become critical challenges.In this work,the triggering voltage of HCS-induced self-heating(SH)degradation is defined in the output characteristics of amorphous indium-galliumzinc oxide(a-IGZO)TFTs,and used to quantitatively evaluate the thermal generation process of channel donor defects.The fluorinated a-IGZO(a-IGZO:F)was adopted to effectively retard the triggering of the self-heating(SH)effect,and was supposed to originate from the less population of initial deep-state defects and a slower rate of thermal defect transition in a-IGZO:F.The proposed scheme noticeably enhances the high-current applications of oxide TFTs.

关键词： amorphous indium-gallium-zinc oxide(a-IGZO) thin-film transistors(TFTs) current stress self-heating(SH) fluorination

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分享经济:大学生就业创业的新领域

昆明学院学报 2017年第4期39卷 115-120页

作者：罗云苹昆明学院社会管理学院云南昆明650214

分享经济通过对个体拥有的闲置资源的交换和分享,降低资源使用边际成本,并在移动互联网技术支撑下实现产消者一对一、点对点的交换与合作。这种商业模式使个体经济或小微企业发展得到广阔空间,让就业形式多样化和微型化,并有利于克服大... 详细信息

分享经济通过对个体拥有的闲置资源的交换和分享,降低资源使用边际成本,并在移动互联网技术支撑下实现产消者一对一、点对点的交换与合作。这种商业模式使个体经济或小微企业发展得到广阔空间,让就业形式多样化和微型化,并有利于克服大学生就业创业中存在的机会、资金、工作经验等不足的制约,为其提供新的机会。当代大学生在就业创业理念、方式、手段等方面与分享经济有许多契合点,能够在分享经济就业中占据优势地位。

关键词：大学生就业大学生创业分享经济个人就业创业就业

TIFA suppresses hepatocellular carcinoma progression via MALT1-dependent and-independent signaling pathways

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Signal Transduction and Targeted Therapy 2016年第1期1卷 81-90页

作者： Wenzhi Shen Renle Du Jun Li Xiaohe luo Shuangtao Zhao Antao Chang Wei Zhou Ruifang Gao Dehong luo Juan Wang Na Hao Yanhua Liu Yanan Chen Yunping Luo Peiqing Sun Shengyong Yang Na luo Rong Xiang Department of Immunology School of MedicineNankai UniversityTianjinChina International Joint Center for Biomedical Research of the Ministry of Education TianjinChina Department of Immunology Institute of Basic Medical ScienceChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina Department of Cancer Biology and Comprehensive Cancer Center Wake Forest University Medical CenterWinston-SalemNorth CarolinaUSA West China Hospital Molecular Medicine Research CentreState Key Lab BiotherapySichuan UniversityChengduChina

TIFA,also called T2BP,was first identified using yeast two-hybrid screening.Our previous work showed that TIFA suppresses hepatocellular carcinoma(HCC)progression via apoptosis and cell cycle arrest.However,the mechanism by which this TIFA suppression occurs remains unclear.Here we demonstrated that TIFA-induced apoptosis demonstrates two distinct time patterns(i.e.,at 48 h and 47 days)when TIFA reconstitution occurs.Moreover,we found that MALT1(a competitor of TIFA)plays a crucial role in short-duration TIFA reconstitution.In this regard,MALT1 silencing with shRNA markedly enhances TIFA-induced apoptosis in vitro and in vivo.In addition,TIFA overexpression triggers JNK and p38 activation in long-duration TIFA reconstitution through TRAF6 binding.In particular,JNK activation leads to TIFA-induced apoptosis while p38 activation governs TIFA-induced cell cycle arrest by p53-p21 signaling in vitro and in vivo.Our data suggest a novel mechanism by which TIFA suppresses HCC progression via both MALT1-dependent and MALT1-independent signaling pathways.This may provide insights into a novel targets where HCC progression may be vulnerable to clinical treatment.

关键词： MALT1 markedly hepatocellular

神经节苷脂GD2可作为肺癌干细胞一个潜在的候选标志物

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基础医学与临床 2023年第5期43卷 777-784页

作者：李珍段昭君罗云萍中国医学科学院基础医学研究所、北京协和医学院基础学院免疫学系北京100005

目的探索神经节苷脂GD2作为肺癌干细胞(LCSCs)标志物的可行性。方法用成球培养的方式在体外富集肺癌细胞系的肿瘤干细胞(CSCs);用实时定量PCR和蛋白质免疫印迹法检测LCSCs中干性相关基因以及GD3合成酶(GD3S)的表达;用流式细胞测量术检... 详细信息

目的探索神经节苷脂GD2作为肺癌干细胞(LCSCs)标志物的可行性。方法用成球培养的方式在体外富集肺癌细胞系的肿瘤干细胞(CSCs);用实时定量PCR和蛋白质免疫印迹法检测LCSCs中干性相关基因以及GD3合成酶(GD3S)的表达;用流式细胞测量术检测肺腺癌细胞系A549中GD2及其他干性表型的表达;用CCK8法检测细胞增殖;用Transwell小室法和细胞划痕愈合实验检测细胞的体外侵袭和迁移;用肺癌移植瘤模型比较细胞系A549中不同亚群的致瘤性。结果体外成球培养能够成功富集到A549细胞的肿瘤干细胞,贴壁培养时,GD2+细胞的比例为0.57%,成球培养后GD2+细胞比例能够上升至20.4%。与GD2-A549细胞相比,GD2+A549细胞的体外增殖(P<0.05)、侵袭(P<0.05)和迁移能力(P<0.01)均显著提高。GD2与另外两种肺癌干细胞表型之间有密切联系,其表达水平与CD44(P<0.01)及EpCAM(P<0.001)的表达呈正相关。体内的结果表明,相比于GD2-A549细胞,接种GD2+A549细胞后肿瘤生长更快(P<0.001),恶性程度更高(P<0.01)。结论神经节苷脂GD2可作为LCSCs的潜在标志物以识别肿瘤干细胞,将GD2作为肺癌免疫治疗的靶点提供了新的思路。

关键词：肺癌干细胞神经节苷脂GD2 肿瘤相关抗原免疫治疗

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领导干部行政美德的概念梳理与意义阐释

古田干部学院学报 2021年第4期1卷 32-37页

作者：王云萍罗美厦门大学公共事务学院政治学系

“领导”一词总是与决策、权力、价值相联系,因此承载着厚重的伦理和美德期望。美德作为人的一种卓越品质和人的功能的出色发挥,是一个人稳定而深沉的、值得赞赏的内在特质,因此,必然会对履行职责产生自我驱动力。行政美德有助于行政领... 详细信息

“领导”一词总是与决策、权力、价值相联系,因此承载着厚重的伦理和美德期望。美德作为人的一种卓越品质和人的功能的出色发挥,是一个人稳定而深沉的、值得赞赏的内在特质,因此,必然会对履行职责产生自我驱动力。行政美德有助于行政领域的权力控制和政策的有效执行,更能够提供行政活动的复杂性所需要的充满智虑和灵性的“实践智慧”和成熟的内在心灵状态。领导干部的行政美德对其所在组织目标的实现,乃至于对整个社会都起着巨大的引领和示范作用。引述行政实践中的具体案例也会证明,领导干部的行政美德对于整个社会的信任度、凝聚力和民众的实际获得感都会产生直接、实际而深远的影响。

关键词：美德行政美德领导干部

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教师工作投入研究动态与未来展望

现代教育管理 2018年第4期 61-66页

作者：陈运平李婷罗序斌江西师范大学江西南昌330022

积极投入工作的教师是保障和提高教育教学质量的重要前提。当前我国教师工作投入的研究更多侧重在其内涵、测量、影响因素以及与工作绩效等方面。未来在教师工作投入的分析领域或单元、教师工作投入的理论内涵、主客观相结合的教师工作... 详细信息

积极投入工作的教师是保障和提高教育教学质量的重要前提。当前我国教师工作投入的研究更多侧重在其内涵、测量、影响因素以及与工作绩效等方面。未来在教师工作投入的分析领域或单元、教师工作投入的理论内涵、主客观相结合的教师工作投入评价体系、教师工作投入影响因素的作用机理,以及教师工作投入与教师工作绩效之间的互动反馈机制等方面有待拓展和深入。

关键词：工作投入教师工作工作绩效研究展望

开挖孔径对隧道围岩卸载变形及破坏特性的影响

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石家庄铁道大学学报(自然科学版) 2022年第3期35卷 79-84页

作者：周建伟姬云平罗刚川藏铁路有限公司中铁第一勘察设计院集团有限公司西南交通大学地球科学与环境工程学院

隧道围岩开挖卸载效应等问题的研究仍存在不足，导致工程灾害频发。针对此问题，基于三轴试验系统(LDCTTS),通过对不同内径的围岩试样进行开挖卸载模拟试验，研究隧道开挖内径对围岩变形规律及破坏特性的影响，同时利用有限元软件开展... 详细信息

隧道围岩开挖卸载效应等问题的研究仍存在不足，导致工程灾害频发。针对此问题，基于三轴试验系统(LDCTTS),通过对不同内径的围岩试样进行开挖卸载模拟试验，研究隧道开挖内径对围岩变形规律及破坏特性的影响，同时利用有限元软件开展相同条件下的数值模拟，将试验结果与数值结果进行对比分析。结果表明，瞬态和缓慢卸载下围岩变形规律一致，且围岩变形随开挖内径的增大而增大；围岩试样破坏时呈现明显脆性特征，沿径向发生明显膨胀，沿卸载方向鼓起并掉块。

关键词：三轴试验系统开挖孔径变形规律破坏特征