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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

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A Novel Scalable Fault-Tolerant Control Design for DC Microgrids With Nonuniform Faults

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IEEE/CAA Journal of Automatica Sinica 2024年第8期11卷 1886-1888页

作者： Aimin Wang Minrui Fei dajun Du yang Song the Shanghai Key Laboratory of Power Station Automation Technology the School of Mechatronic Engineering and Automation Shanghai University

Dear Editor,The existing control schemes for microgrids (MGs) face challenges in effectively addressing plugging in/out operations under uncertain power lines and faults. To tackle this issue, this letter proposes a novel scalable fault-tolerant control (FTC) strategy for DC MGs. By developing a structured Lyapunov matrix (SLM), a decoupled FTC method is introduced to mitigate the adverse effects of uncertain lines and nonuniform faults.

关键词： Linear matrix inequalities

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Integration of traditional,complementary,and alternative medicine with modern biomedicine:the scientization,evidence,and challenges for integration of traditional Chinese medicine

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Acupuncture and Herbal Medicine 2024年第1期4卷 68-78页

作者： Zihao Zhang Raorao Li Yu Chen Hui yang Martin Fitzgerald Qiaochu Wang Ziwen Xu Nanxi Huang dajun Lu Lu Luo Georgetown University Medical Center Washington DCUSA Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijingChina Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijingChina The First Clinical Medical College Guizhou University of Traditional Chinese MedicineGuiyangChina Ashdale Clinic Half Moon LaneSouth Douglas RoadCorkIreland

Traditional medicine has garnered significant global recognition,with an estimated 80%of the global population using ***,it is essential to fully understand the integration of traditional medicines into current healthcare *** review aims to provide a comprehensive overview of the standard process to modernize traditional medicine scientifically in the context of modern biomedicine,further termed here as“scientization”.Specifically,we aim to summarize the advancements made in understanding the efficacy,effectiveness,and underlying mechanisms of herbal *** also examined the transition from experience-to evidence-based medicine during ***,we explore the development of universal safety and quality control ***,we discuss international trade and export markets for Chinese medical *** development and integration of traditional medicine have allowed it to further improve human health,resulting in a more comprehensive health solution for the global population.

关键词： Acupuncture Conventional medicine Herbal medicine Modernization Scientization Traditional Chinese medicine

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Apogossypolone targets mitochondria and light enhances its anticancer activity by stimulating generation of singlet oxygen and reactive oxygen species

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Chinese Journal of Cancer 2011年第1期30卷 41-53页

作者： Zhe-Yu Hu Jing Wang Gang Cheng Xiao-Feng Zhu Peng Huang dajun yang Yi-Xin Zeng State Key Laboratory of Oncology in South China Guangzhou Guangdong 510060 P. R. China Department of Experimental Research Sun Yat-sen University Cancer Center Guangzhou Guangdong 510060 P. R. China Department of Molecular Pathology The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA Aseenta Therapeutics Incorporation Malvern Pennsylvania 19355 USA The First Hospital of Changsha City Changsha Hunan 410005 P. R. China.

Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC.

关键词：线粒体膜电位活性氧物种抗癌活性单线态氧细胞死亡细胞生长鼻咽癌光动力疗法

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双并列转子永磁直驱电机转子不平衡力分析与优化

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电工技术学报 2024年第10期39卷 2961-2973页

作者：陶大军陈阳李峥戈宝军大型电机电气与传热技术国家地方联合工程研究中心(哈尔滨理工大学) 哈尔滨150080

双并列转子永磁直驱电机受轴间距限制,设计时会切掉部分定子铁心和绕组,造成转子电磁力不平衡。为最大限度地抑制转子所受的不平衡电磁力,该文从双并列转子结构出发,分析了电机绕组电感参数不对称的原因,提出通过合理设计线圈跨距和分... 详细信息

双并列转子永磁直驱电机受轴间距限制,设计时会切掉部分定子铁心和绕组,造成转子电磁力不平衡。为最大限度地抑制转子所受的不平衡电磁力,该文从双并列转子结构出发,分析了电机绕组电感参数不对称的原因,提出通过合理设计线圈跨距和分布平衡三相电感。在此基础上,构建转子所受总电磁力的数学模型,理论分析各个分力的来源及影响因素,研究各个分力对转子所受总电磁力的影响,提出了优化占空角、优化耦合间距、采用定子端部不对称结构、采用转子偏心结构和切除部分单元电机五种优化方法,实现对转子所受电磁力的优化,探讨了不同方法的优化效果,以及其对转矩脉动的影响,总结了不同优化方法的优缺点。

关键词：双并列转子永磁直驱电机电磁力优化方法

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黏土地层泥水劈裂伸展压力及路径试验研究

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隧道建设（中英文） 2024年第4期44卷 698-704页

作者：杨公标袁大军陈健王滕韩冰宇中铁十四局集团有限公司山东济南250014 中国铁建水下隧道工程实验室山东济南250014 北京交通大学土木建筑工程学院北京100044

为解决水下盾构隧道修建过程中由于泥水支护压力过大导致的掌子面前方地层劈裂,以及劈裂发生后如何防止裂缝伸展至水底地表等难题,采用大型三轴劈裂试验平台进行泥水劈裂伸展试验,测得裂缝伸展过程中的泥水压力及裂缝伸展路径,并研究泥... 详细信息

为解决水下盾构隧道修建过程中由于泥水支护压力过大导致的掌子面前方地层劈裂,以及劈裂发生后如何防止裂缝伸展至水底地表等难题,采用大型三轴劈裂试验平台进行泥水劈裂伸展试验,测得裂缝伸展过程中的泥水压力及裂缝伸展路径,并研究泥水黏度及应力状态对伸展压力及路径的影响。结果表明:1)泥水黏度较小时,裂缝伸展过程中劈裂压力基本不变;泥水黏度较大时,裂缝伸展过程中劈裂压力逐渐增大。2)启裂压力和伸展压力均随着泥水黏度的增大而逐渐增大,但增大速度逐渐减小;伸展压力随围压线性增大,但增大速率略小于启裂压力。3)通过对比不同工况下盲孔试样的裂缝倾角可知,裂缝倾角仅与轴压和围压的压差相关。4)实际施工中建议泥水黏度大于21 Pa·s。5)当隧道埋深变化较大时,应实时调整泥水压力。6)当初始劈裂发生后,泥水支护压力会骤降,此时不应过快地补充泥水压力,而应采取加快掘进速度的方法快速通过。

关键词：水下隧道泥水盾构劈裂试验泥水黏度伸展压力裂缝形态

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Direct Observation on H-Elimination Enhancement from C_(2)H_(4) through Non-Adiabatic Process by Femtosecond Laser Induced Coulomb Explosion

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Chinese Physics Letters 2024年第5期41卷 17-22页

作者：金无维王春成赵晓戈杨译章任殿相刘泽槿李孝开罗嗣佐丁大军 Institute of Atomic and Molecular Physics Jilin UniversityChangchun 130012China Jilin Provincial Key Laboratory of Applied Atomic and Molecular Spectroscopy Jilin UniversityChangchun 130012China

Ethylene, the simplest model of a carbon-carbon double bond system, is pivotal in numerous chemical and biological processes. By employing intense infrared laser pump-probe techniques alongside coincidence measurements, we investigate the ultrafast non-adiabatic dynamics involved in the breakage of carbon-carbon double bonds and hydrogen elimination in dissociation of ethylene. Our study entails analyzing the dynamic kinetic energy release spectra to assess three bond-breaking scenarios, movements of nuclei, and structural changes around the carbon atoms. This allows us to evaluate the relaxation dynamics and characteristics of various dissociative states. Notably, we observe a significant rise in the yield of fragments resulting from C–H bond breakage with the delay time extended, suggesting non-adiabatic coupling through conical intersections from C–C bond breakage as a probable cause.

关键词： pump Femto adiabatic

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定理证明辅助工具PVS剖析

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计算机工程 2000年第9期26卷 140-142页

作者：廖宇杨大军南京大学计算机科学与技术系南京210093

ＰＶＳ是斯坦福研究机构开发的强大的规约、验证系统，它的适用领域广泛。在概要介绍ＰＶＳ的构成、功能后，着重分析了ＰＶＳ的规约语言、验证系统的特点，以及使得ＰＶＳ灵活、强大的设计决策和内在机制．

关键词：规约语言定理证明器 PVS

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Effect of cutterhead configuration on tunnel face stability during shield machine maintenance outages

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Frontiers of Structural and Civil Engineering 2023年第4期17卷 522-532页

作者： Yinzun yang dajun YUAN Dalong JIN Key Laboratory of the Ministry of Education for Urban Underground Engineering Beijing Jiaotong UniversityBeijing 100044China School of Civil Engineering Beijing Jiaotong UniversityBeijing 100044China

Owing to long-distance advancement or obstacles,shield tunneling machines are typically shut down for *** safety during maintenance outages is determined by the stability of the tunnel *** maintenance openings are typically used under complicated hydrogeological *** tunnel face is supported by a medium at the bottom of the excavation chamber and compressed air at the *** to the high risk of face failure,the necessity of support pressure when cutterhead support is implemented and a method for determining the value of compressed air pressure using different support ratios must to be *** this study,a non-fully chamber supported rotational failure model considering cutterhead support is developed based on the upper-bound theorem of limit *** simulation is conducted to verify the accuracy of the proposed *** results indicate that appropriately increasing the specific gravity of the supporting medium can reduce the risk of *** required compressed air pressure increases significantly as the support ratio *** the supporting effect of the cutterhead will result in a tunnel face with underestimated *** satisfy the requirement of chamber openings at atmospheric pressure,the stratum reinforcement strength and range at the shield end are provided based on different cutterhead aperture ratios.

关键词： tunnel face stability cutterhead configuration aperture ratio pressure gradient support ratio

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GI.5和GII.4诺如病毒P蛋白的克隆表达及与长牡蛎类HBGAs的结合特性

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食品科学 2024年第2期45卷 113-119页

作者：佟利惠杨敏王珊珊王大军王明丽周德庆中国水产科学研究院黄海水产研究所青岛海洋科学与技术试点国家实验室海洋药物与生物制品功能实验室山东青岛266071 青岛滨海学院山东青岛266555 烟台海裕食品有限公司山东烟台264000 蓬莱汇洋食品有限公司山东烟台264000

为明确人诺如病毒(human norovirus,HuNoV)与长牡蛎类组织血型抗原(histo-blood group antigens,HBGAs)的结合特性,本实验运用大肠杆菌表达系统,克隆表达了基因簇I.5(genogroup I.5,GI.5)和GII.4 HuNoV P蛋白,采用酶联免疫吸附测定研究HuNoV P蛋白与唾液HBGAs和长牡蛎类HBGAs的结合特性。结果表明,GII.4 HuNoV与唾液A型、B型、AB型和O型HBGAs均有较好的结合,而GI.5 HuNoV与B型HBGAs结合较弱,与O型HBGAs具有明显的结合优势。GI.5和GII.4 HuNoV在长牡蛎鳃、消化腺和外套膜中均可富集,其中在消化腺中富集最多,二者主要与类A型和H1型HBGAs结合,GII.4HuNoV与类Lea型、Leb型、Lex型和Ley型HBGAs有不同程度的结合,而GI.5 HuNoV与类Leb型HBGAs仅微弱结合,与类H1型HBGAs具有明显结合优势。综上,不同型别HuNoV与HBGAs的结合特性不尽相同,GII.4HuNoV具有广谱结合特性,GI.5HuNoV具有选择结合特性。

关键词：人诺如病毒 P蛋白长牡蛎组织血型抗原结合特性

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