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The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies

Acta Pharmaceutica Sinica B 2024年第5期14卷 1951-1964页

作者： Longsheng Wang Jie Zhang Wenxin Zhang Mingming Zheng hongjie guo Xiaohui Pan Wen Li Bo Yang Ling Ding Zhejiang Province Key Laboratory of Anti-Cancer Drug Research Institute of Pharmacology and ToxicologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China The Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310018China Nanhu Brain-Computer Interface Institute Hangzhou 311100China

Adenosine(Ado)is significantly elevated in the tumor microenvironment(TME)compared to normal tissues.It binds to adenosine receptors(AdoRs),suppressing tumor antigen presentation and immune cell activation,thereby inhibiting tumor adaptive immunity.Ado downregulates major histocompatibility complex II(MHC II)and co-stimulatory factors on dendritic cells(DCs)and macrophages,inhibiting antigen presentation.It suppresses anti-tumor cytokine secretion and T cell activation by disrupting T cell receptor(TCR)binding and signal transduction.Ado also inhibits chemokine secretion and KCa3.1 channel activity,impeding effector T cell trafficking and infiltration into the tumor site.Furthermore,Ado diminishes T cell cytotoxicity against tumor cells by promoting immune-suppressive cytokine secretion,upregulating immune checkpoint proteins,and enhancing immune-suppressive cell activity.Reducing Ado production in the TME can significantly enhance anti-tumor immune responses and improve the efficacy of other immunotherapies.Preclinical and clinical development of inhibitors targeting Ado generation or AdoRs is underway.Therefore,this article will summarize and analyze the inhibitory effects and molecular mechanisms of Ado on tumor adaptive immunity,as well as provide an overview of the latest advancements in targeting Ado pathways in anti-tumor immune responses.

关键词： Adenosine Adenosine receptors Adenosine-generating enzymes Tumor microenvironment Immune suppression Immune escape Clinical treatment Targeting drugs

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MODELS: a six-step framework for developing an infectious disease model

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贫困所致传染病(英文) 2024年第2期13卷 1-11页

作者： Rui Jia Li Kangguo Wei hongjie guo Xiaohao Zhao Zeyu Wang Yao Song Wentao Abudunaibi Buasiyamu Chen Tianmu State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory School of Public Health Xiamen University Xiamen city China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Innovation Platform for Industry-Education Integration in Vaccine Research Xiamen University Xiamen City China

Since the COVID-19 pandemic began, a plethora of modeling studies relatedto COVID-19 have been released. While some models stand out due to their innovative approaches, others are flawed in their methodology. To assist novices, frontline healthcare workers, and public health policymakers in navigating the complex landscape of these models, we introduced a structured framework named MODELS. This framework is designed to detail the essential steps and considerations for creating a dependable epidemic model, offering direction to researchers engaged in epidemic modeling endeavors.

关键词： Epidemic models Model construction MODELS framework

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The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1761-1780页

作者： Tiecheng Zhong Wenxin Zhang hongjie guo Xiaohui Pan Xi Chen Qiaojun He Bo Yang Ling Ding Zhejiang Province Key Laboratory of Anti-Cancer Drug Research Institute of Pharmacology and ToxicologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China

Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.

关键词： TRP channels Cancer progression Tumor microenvironment Tumor-associated immunocytes Intracellular mechanism Programmed cancer cell death Targeted tumor therapy

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The impact of lipids on the cancer—immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1488-1497页

作者： Mingming Zheng Wenxin Zhang Xi Chen hongjie guo Honghai Wu Yanjun Xu Qiaojun He Ling Ding Bo Yang Zhejiang Province Key Laboratory of Anti-Cancer Drug Research Institute of Pharmacology and ToxicologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Medical Thoracic Oncology the Cancer Hospital of University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Chinese Academy of SciencesHangzhou 310022China The Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310018China Cancer Center of Zhejiang University Hangzhou 310058China

Lipids have been found to modulate tumor biology,including proliferation,survival,and metastasis.With the new understanding of tumor immune escape that has developed in recent years,the influence of lipids on the cancer—immunity cycle has also been gradually discovered.First,regarding antigen presentation,cholesterol prevents tumor antigens from being identified by antigen presenting cells.Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells,impairing antigen presentation to T cells.Prostaglandin E2(PGE2)reduce the accumulation of tumor-infiltrating dendritic cells.Regarding T-cell priming and activation,cholesterol destroys the structure of the T-cell receptor and reduces immunodetection.In contrast,cholesterol also promotes T-cell receptor clustering and relative signal transduction.PGE2 represses T-cell proliferation.Finally,regarding T-cell killing of cancer cells,PGE2 and cholesterol weaken granule-dependent cytotoxicity.Moreover,fatty acids,cholesterol,and PGE2 can improve the activity of immunosuppressive cells,increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines.Given the regulatory role of lipids in the cancer—immunity cycle,drugs that modulate fatty acids,cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy.These strategies have been studied in both preclinical and clinical studies.

关键词： Lipids Fatty acids Cholesterol Prostaglandin E2 Tumor immune escape Cancer—immunity cycle Immunotherapy Combination therapy

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Research progress of integrated optical gyroscope

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Chinese Optics Letters 2024年第3期22卷 42-49页

作者：郭宏杰刘海锋雷明谭满清宋志刚 Institute of Semiconductors Chinese Academy of SciencesBeijing 100083China College of Materials Science and Opto-electronics Technology University of Chinese Academy of SciencesBeijing 100049China Beijing Huairou Instruments and Sensors Co. Ltd.Beijing 101400China Beijing Institute of Automation and Control Equipment Key Laboratory of National Defense Science and Technology of Inertial TechnologyBeijing 100074China

Integrated optical gyroscopes(IOGs)have been an efficient tool for numerous applications in various fields,including inertial navigation,flight control,and earthquake monitoring.Here,we review the progress of integrated optical gyroscopes based on two categories of integrated interferometric optical gyroscopes(IIOGs)and integrated resonant optical gyroscopes(IROGs).

关键词： integrated optical gyroscopes interferometric optical gyroscopes integrated resonant optical gyroscopes

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Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA

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药学学报:英文版 2023年第6期13卷 2585-2600页

作者： Wenxin Zhang Xiaohui Pan Yanjun Xu hongjie guo Mingming Zheng Xi Chen Honghai Wu Fengming Luan Qiaojun He Ling Ding Bo Yang Zhejiang Province Key Laboratory of Anti-Cancer Drug Research Institute of Pharmacology and ToxicologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Medical Thoracic Oncology the Cancer Hospital of University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Chinese Academy of SciencesHangzhou 310022China Department of Gastrointestinal Surgery Second Affiliated Hospital of Zhejiang UniversitySchool of MedicineHangzhou 310009China The Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310018China Cancer Center of Zhejiang University Hangzhou 310058China

Mevalonate metabolism plays an important role in regulating tumor growth and progression;however,its role in immune evasion and immune checkpoint modulation remains unclear.Here,we found that non-small cell lung cancer(NSCLC)patients with higher plasma mevalonate response better to antiPD-(L)1 therapy,as indicated by prolonged progression-free survival and overall survival.Plasma mevalonate levels were positively correlated with programmed death ligand-1(PD-L1)expression in tumor tissues.In NSCLC cell lines and patient-derived cells,supplementation of mevalonate significantly upregulated the expression of PD-L1,whereas deprivation of mevalonate reduced PD-L1 expression.Mevalonate increased CD274 mRNA level but did not affect CD274 transcription.Further,we confirmed that mevalonate improved CD274 mRNA stability.Mevalonate promoted the affinity of the AU-rich elementbinding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA.By in vivo study,we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1,increased the infiltration of CD8^(+)T cells,and improved cytotoxic function of T cells.Collectively,our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody,and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

关键词： Metabolites Mevalonate PD-L1 mRNA stability HuR NSCLC Immune checkpoint blockade

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调制光学参量放大器对双机械振子量子纠缠与压缩的影响

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天津师范大学学报（自然科学版） 2024年第1期44卷 42-48页

作者：杜宏杰郭金良天津师范大学物理与材料科学学院天津300387

为了研究包含调制光参量放大器(optical parametric amplifier,OPA)的双机械振子腔光力系统中的量子纠缠和机械压缩,通过数值求解和解析求解,讨论了系统的有关参数,如OPA相位、调制频率、热声子数和相位增益量在腔光力系统中对量子纠缠... 详细信息

为了研究包含调制光参量放大器(optical parametric amplifier,OPA)的双机械振子腔光力系统中的量子纠缠和机械压缩,通过数值求解和解析求解,讨论了系统的有关参数,如OPA相位、调制频率、热声子数和相位增益量在腔光力系统中对量子纠缠和机械压缩的影响,重点分析了调制OPA对产生力学纠缠和机械压缩的作用.结果表明:本光学腔不需要额外的压缩光来驱动,并在较易实现的参数条件下通过调制OPA增强了2个机械振子间的纠缠.当系统处于稳定状态时,在边带可分辩和不可分辨条件下均可产生机械压缩,并可通过调制OPA在边带可分辨条件下实现强机械压缩.此外,在调制OPA的辅助下,机械振子间的纠缠和机械压缩对环境温度具有很强的鲁棒性.

关键词：腔光力系统量子纠缠机械压缩 Langevin方程调制光参量放大器

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Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses

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Acta Pharmaceutica Sinica B 2020年第5期10卷 723-733页

作者： Xi Chen Xiaohui Pan Wenxin Zhang hongjie guo Shuyuan Cheng Qiaojun He Bo Yang Ling Ding Zhejiang Province Key Laboratory of Anti-Cancer Drug Research Institute of Pharmacology and ToxicologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China

Immunotherapy strategies targeting the programmed cell death ligand 1(PD-L1)/programmed cell death 1(PD-1)pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer.However,owing to the heterogeneity of tumors and individual immune systems,PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients.Accumulating evidence has shown that an effective response to anti-PD-Ll/anti-PD-1 therapy requires establishing an integrated immune cycle.Damage in any step of the immune cycle is one of the most important causes of immunotherapy failure.Impairments in the immune cycle can be restored by epigenetic modification,including reprogramming the environment of tumor-associated immunity,eliciting an immune response by increasing the presentation of tumor antigens,and by regulating T cell trafficking and reactivation.Thus,a rational combination of PD-L1/PD-1 blockade and epigenetic agents may offer great potential to retrain the immune system and to improve clinical outcomes of checkpoint blockade therapy.

关键词： Epigenetic regulation Immune cycle PD-L1PD-1 blockade Cancer Immunotherapy

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柑橘采后青霉菌的侵染及产毒机制的研究进展

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食品工业科技 2024年第6期45卷 389-395页

作者：黄欣娅郭婷戴宏杰张宇昊马良西南大学食品科学学院重庆400715 川渝共建特色食品重庆市重点实验室重庆400715 农业农村部柑橘类果品质量安全重点实验室重庆400715 发光分析和分子传感教育部重点实验室重庆400715

柑橘是中国的第一大水果作物,柑橘采后青霉病是影响柑橘品质安全的重大病害之一,还会造成果品霉菌毒素污染的风险。目前研究主要集中于P.digitatum的侵染机制,而重点青霉菌对柑橘的感染和产毒机制有着密切的联系,产生的真菌毒素会对食... 详细信息

柑橘是中国的第一大水果作物,柑橘采后青霉病是影响柑橘品质安全的重大病害之一,还会造成果品霉菌毒素污染的风险。目前研究主要集中于P.digitatum的侵染机制,而重点青霉菌对柑橘的感染和产毒机制有着密切的联系,产生的真菌毒素会对食品安全造成严重威胁,基于此,本文针对柑橘采后主要青霉菌,综述其侵染和致病机制、产毒机制,分析目前柑橘产业采后青霉病的研究趋势和方向,以期降低真菌毒素污染风险,推动柑橘产业“提质增效”,为柑橘品质提升和产业发展提供研究新思路。

关键词：青霉病柑橘 P.digitatum 真菌毒素

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煤矿在用安全设备检测检验的现状及策略分析

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当代化工研究 2024年第6期 21-23页

作者：郭洪杰山东立安工矿技术检测有限公司山东271219

煤矿开采作为人类社会的重要能源来源,一直以来都伴随着巨大的安全风险,如何规避煤矿开采不良风险已然成为煤矿行业的关键一环。基于此,本文旨在探讨煤矿在用安全设备检测检验情况,结合煤矿在用安全设备检测检验的必要性,阐述了煤矿在... 详细信息

煤矿开采作为人类社会的重要能源来源,一直以来都伴随着巨大的安全风险,如何规避煤矿开采不良风险已然成为煤矿行业的关键一环。基于此,本文旨在探讨煤矿在用安全设备检测检验情况,结合煤矿在用安全设备检测检验的必要性,阐述了煤矿在用设备检测的几种常见技术,分析了检验现状及存在问题,提出了针对性的改进策略,以期为该领域的研究提供一些参考。

关键词：煤矿行业安全设备检测检验

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