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The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype,promoting a favorable response to anti-PD-1 therapy via NLRP3 activation

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Cellular & Molecular Immunology 2024年第1期21卷 60-79页

作者： Fan Luo Han Li Wenjuan Ma Jiaxin Cao Qun Chen Feiteng Lu Miaozhen qiu Penghui Zhou Zengfei xia Kangmei Zeng Jianhua Zhan Ting Zhou qiuyun Luo Wentao Pan Lin Zhang Chaozhuo Lin Yan Huang Li Zhang Dajun Yang Hongyun Zhao State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina Ascentage Pharma(Suzhou)Co Ltd 218 Xinghu StreetSuzhouJiangsu ProvinceChina

The main challenges in the use of immune checkpoint inhibitors(ICIs)are ascribed to the immunosuppressive tumor microenvironment and the lack of sufficient infiltration of activated CD8+T *** the tumor microenvironment(TME)from“cold”to“hot”and thus more likely to potentiate the effects of ICIs is a promising strategy for cancer *** found that the selective BCL-2 inhibitor APG-2575 can enhance the antitumor efficacy of anti-PD-1 therapy in syngeneic and humanized CD34+mouse *** single-cell RNA sequencing,we found that APG-2575 polarized M2-like immunosuppressive macrophages toward the M1-like immunostimulatory phenotype with increased CCL5 and CXCL10 secretion,restoring T-cell function and promoting a favorable immunotherapy ***,we demonstrated that APG-2575 directly binds to NF-κB p65 to activate NLRP3 signaling,thereby mediating macrophage repolarization and the activation of proinflammatory caspases and subsequently increasing CCL5 and CXCL10 chemokine *** a result,APG-2575-induced macrophage repolarization could remodel the tumor immune microenvironment,thus improving tumor immunosuppression and further enhancing antitumor T-cell *** immunohistochemistry confirmed that patients with better immunotherapeutic efficacy had higher CD86,p-NF-κB p65 and NLRP3 levels,accompanied by lower CD206 expression on ***,these data provide evidence that further study on APG-2575 in combination with immunotherapy for tumor treatment is required.

关键词： BCL-2 APG-2575 ICIs Macrophages NLRP3

Experimental investigation of closed-loop active control to modulate coherent structures by mu-level method

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Chinese Physics B 2024年第7期33卷 408-417页

作者：白建侠范子椰姜楠李秋营郑小波 Department of Mathematics Tianjin Renai CollegeTianjin 301636China Institute of Mechanics Department of MechanicsSchool of Mechanical EngineeringTianjin UniversityTianjin 300354China College of Energy and Power Engineering Lanzhou University of TechnologyLanzhou 730050China Tianjin Key Laboratory of Modern Engineering Mechanics Tianjin 300354China

The experimental research on zero-net-mass-flux jet closed-loop active control was conducted in the wind *** mu-level method successfully detected burst events of the coherent structures. The streamwise velocity signals in the turbulent boundary layer were measured by HWA. The drag reduction rate of 16.7% is obtained comparable to that of the open-loop control and saves 75% of the input energy at the asynchronous 100 V/160 Hz control case, which reflects the advantages of the closed-loop control. The experimental findings indicate that the intensity increases in the near-wall *** perturbation of the PZT vibrators on the skewness factor is concentrated in the region y+ying scales are observed. The correlation coefficient exhibits a strong positive correlation, which indicates that the large-scale structures produce modulation effect on small-scale *** occurrence of burst events is effectively suppressed. The disturbance has the characteristics of stable periodicity,positive and negative symmetry, low intermittency, and high pulsation strength. The conditional phase waveform shows that the fluctuation amplitude increases, indicating amplitude modulation effects on coherent structures.

关键词： turbulent boundary layer(TBL) burst event coherent structures mu-level method

血清CEA、CA19-9和CA72-4检测在胃癌机会性筛查中应用价值的荟萃分析

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中华健康管理学杂志 2024年第4期18卷 271-278页

作者：阴建邱思睿张凯国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院北京协和医学院肿瘤医院流行病学研究室北京100021 国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院北京协和医学院肿瘤医院防癌科北京100021

目的基于荟萃分析评价血清癌胚抗原(CEA)、糖类抗原(CA)19-9、CA72-4检测在胃癌机会性筛查中的应用价值。方法从中国知网、万方、重庆维普、PubMed、Cochrane和Embase数据库进行电子检索,文献发表时间为建库到2023年5月,收集CEA、CA19-9... 详细信息

目的基于荟萃分析评价血清癌胚抗原(CEA)、糖类抗原(CA)19-9、CA72-4检测在胃癌机会性筛查中的应用价值。方法从中国知网、万方、重庆维普、PubMed、Cochrane和Embase数据库进行电子检索,文献发表时间为建库到2023年5月,收集CEA、CA19-9和CA72-4筛查及诊断胃癌的文献。采用诊断准确性研究的质量评价工具(QUADAS-2)和Stata17.0软件对文献进行质量评价和荟萃分析。结果共23篇文献入选,其中胃癌患者组5287例,对照组6129例。CEA、CA19-9、CA72-4在胃癌诊断(筛查)中合并灵敏度和特异度分别为0.42、0.45、0.53和0.94、0.91、0.95。综合受试者工作特征(sROC)曲线下面积(area under curve,AUC)分别为0.82、0.77、0.87。3种标志物联合(并联)灵敏度升高为0.66(95%CI:0.54~0.76),特异度下降为0.85(95%CI:0.81~0.89),AUC基本不变为0.86(95%CI:0.83~0.89)。结论血清CEA、CA19-9和CA72-4作为胃癌筛查及健康体检的生物标志物,其灵敏度都比较低,应用效果有限。

关键词：癌胚抗原糖类抗原19-9 糖类抗原72-4 胃癌体格检查

The activation of adenosine monophosphate–activated protein kinase inhibits the migration of tongue squamous cell carcinoma cells by targeting Claudin-1 via epithelial–mesenchymal transition

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Animal Models and Experimental Medicine 2024年第5期 606-616页

作者： Xin-Yue Zhou qiu-Ming Liu Zhuang Li xia-Yang Liu Qi-Wei Zhao Yu Wang Feng-Hua Wu Gang Zhao Rui Sun xiao-Hong Guo Department of Basic Medicine Hubei University of Chinese Medicine Hubei Shizhen Laboratory Sino-German Biomedical Center Hubei University of Technology Center of Applied Biotechnology Wuhan Institute of Bioengineering Department of Stomatology Shanxi Bethune Hospital Shanxi Academy of Medical Sciences Tongji Shanxi Hospital Third Hospital of Shanxi Medical University Department of Oral and Maxillofacial Surgery Shanxi Provincial People's Hospital

Background: The role of Claudin-1 in tongue squamous cell carcinoma(TSCC) metastasis needs further clarification, particularly its impact on cell migration. Herein, our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying ***: 36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1. Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells. Claudin-1 knockdown cell lines were established using short hairpin RNA transfection. Migration effects were assessed through wound healing assays. Furthermore, the expression of EMTassociated molecules was measured via western ***: Claudin-1 expression decreased as TSCC malignancy increased. Adenosine monophosphate–activated protein kinase(AMPK) activation led to increased Claudin-1 expression and membrane translocation, inhibiting TSCC cell migration and epithelial–mesenchymal transition(EMT). Conversely, Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK ***: Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.

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High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

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Science China(Life Sciences) 2024年第8期67卷 1635-1647页

作者： Feng-Qi Liu Qing-Yuan Qu ying Lei Qi Chen Yu-Xiu Chen Meng-Lin Li Xue-Yan Sun Ye-Jun Wu qiu-Sha Huang Hai-xia Fu Yuan Kong Yue-ying Li Qian-Fei Wang xiao-Jun Huang xiao-Hui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044China National Clinical Research Center for Hematologic Disease Beijing 100044China Collaborative Innovation Centre of Hematology Peking UniversityBeijing 100044China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100074China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the *** soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP *** the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T *** contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell *** a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune ***-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of *** conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of *** may offer novel targets to develop personalized immunotherapies.

关键词： immune thrombocytopenia autoimmune diseases co-stimulatory co-inhibitory immune checkpoint CTLA4 Cytometry by Time of Flight bone marrow

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应用于低速冲击的新型力学超材料

包装工程 2024年第19期45卷 115-124页

作者：谭路遥邱利彬尹霞盛俊杰中国工程物理研究院总体工程研究所四川绵阳621900

目的针对低速碰撞场景下的吸能缓冲需求,设计一种具有准零刚度特性的新型力学超材料。方法首先对力学超材料的几何结构进行参数化建模,超材料主要组成包括薄壁结构与格栅结构。薄壁结构为正弦构型的曲梁,格栅结构由圆杆组成,将薄壁曲梁... 详细信息

目的针对低速碰撞场景下的吸能缓冲需求,设计一种具有准零刚度特性的新型力学超材料。方法首先对力学超材料的几何结构进行参数化建模,超材料主要组成包括薄壁结构与格栅结构。薄壁结构为正弦构型的曲梁,格栅结构由圆杆组成,将薄壁曲梁连接成整体。为了缩短不同应用场景下缓冲结构的设计周期,提出了一种结构力学响应的计算方法。首先建立基于欧拉-伯努利梁原理的薄壁结构运动微分方程,随后提出了一种基于四阶龙格库塔法以及打靶法的数值求解方法,最后基于叠加原理,提出了缓冲结构的力学响应预测方法并进行了相应的线性补偿。结果提出的数值算法可以准确地计算大柔度薄壁结构的力学响应,从而减少设计迭代的次数,大幅缩短设计周期。结论准静态试验结果表明,提出的超材料构型具有准零刚度的特点,并且压缩率超过70%。落锤冲击场景下缓冲结构无明显的初始峰值,响应载荷得到抑制。这说明这种超材料在缓冲领域具有很大的应用潜力,尤其适用于体积受限场景下的冲击防护。

关键词：低速冲击准零刚度多孔结构力学超材料落锤试验

“数智”还是“数滞”:数字化转型与非农就业

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经济学动态 2024年第2期 32-51页

作者：尹志超仇化首都经济贸易大学金融学院 100070

数字乡村建设是推动乡村振兴的重要举措和新动能。基于人口流动理论和中国家庭金融调查数据,本文度量微观层面的数字化水平,分析并检验数字化转型对非农就业的影响。研究发现,数字化转型是农户参与非农就业的有效动力,能显著提高就业质... 详细信息

数字乡村建设是推动乡村振兴的重要举措和新动能。基于人口流动理论和中国家庭金融调查数据,本文度量微观层面的数字化水平,分析并检验数字化转型对非农就业的影响。研究发现,数字化转型是农户参与非农就业的有效动力,能显著提高就业质量,促进农户收入与消费增加。机制分析表明,数字化转型主要通过提高农地转出率与农业机械使用率,拓宽社交网络促进非农就业。在经济发展较为落后、社区网络基础设施差的地区,数字化转型的积极作用更大。对于户主受教育水平较低、有老年人、无未成年子女的家庭,数字化转型对非农就业的影响更大。农户是数字乡村建设和乡村振兴的微观基础,本研究能为数字乡村建设提供有益借鉴和依据。

关键词：数字化转型非农就业乡村振兴共同富裕

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游戏化视角下博物馆重构观众关系的路径研究

东南文化 2024年第4期 140-147页

作者：邓又溪柴秋霞复旦大学文物与博物馆学系上海200433

在数字时代,注意力资源走向短缺,博物馆与观众的关系已经超越了“以观众为中心”的指涉,需要重新定位与再组织。当前观众具有主动性更强、情绪需求更高和深度注意下降的特点,博物馆需借助游戏元素与激励机制,激发观众的主动参与意识,从... 详细信息

在数字时代,注意力资源走向短缺,博物馆与观众的关系已经超越了“以观众为中心”的指涉,需要重新定位与再组织。当前观众具有主动性更强、情绪需求更高和深度注意下降的特点,博物馆需借助游戏元素与激励机制,激发观众的主动参与意识,从吸引观众注意迈向引导观众自发求知。博物馆首先应明确以创造观众与观众、观众与空间的情感联结为游戏化目标,向知识守门者的实践角色演进,要加强把关和引导观众主动反馈,以多主体协作来进行游戏化实践。

关键词：博物馆数字时代观众注意力游戏化激励机制

慢性淋巴细胞白血病中B细胞受体同型模式的生物学特征和临床意义

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中华血液学杂志 2024年第2期45卷 197-202页

作者：邱彤璐李建勇夏奕南京医科大学第一附属医院江苏省人民医院血液科南京医科大学血液研究重点实验室江苏省肿瘤个体化医学协同创新中心南京210029

慢性淋巴细胞白血病(CLL)是西方成人最常见的白血病,尽管CLL在亚洲人种中发病率偏低,但随着人口老龄化,CLL发病率在我国呈上升趋势。CLL细胞与微环境的交互中,B细胞受体免疫球蛋白(B-cell receptor immunoglobulin,BCR IG)对抗原的识别... 详细信息

慢性淋巴细胞白血病(CLL)是西方成人最常见的白血病,尽管CLL在亚洲人种中发病率偏低,但随着人口老龄化,CLL发病率在我国呈上升趋势。CLL细胞与微环境的交互中,B细胞受体免疫球蛋白(B-cell receptor immunoglobulin,BCR IG)对抗原的识别起重要作用,免疫球蛋白重链可变区(IG heavy variable region,IGHV)的突变状态更是判断CLL预后的经典标志物。超过40%的CLL患者间存在IGHV的偏向性使用和高度相似的重链可变区互补决定区3(heavy complementarity-determining region 3,HCDR3)氨基酸片段,此现象称为同型模式BCR。不同亚群的同型模式BCR存在独特的生物学和临床特征。其中IGHV有突变但预后差的#2亚群和发生Richter转化风险高的#8亚群被欧洲CLL研究启动组推荐纳入IGHV突变状态的临床报告之中。本文综述CLL中同型模式BCR的定义、分布、生物学特征和临床意义。

关键词：慢性淋巴细胞白血病 B细胞受体互补决定区3 Richter 免疫球蛋白偏向性重链可变区临床报告