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A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy

药学学报:英文版 2023年第7期13卷 3027-3042页

作者： Luchen Sun nanfei yang Bing Chen Yuncheng Bei Zisheng Kang Can Zhang Nan Zhang Peipei Xu Wei yang Jia Wei Jiangqiong Ke Weijian Sun Xiaokun Li Pingping Shen The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 325027China School of Pharmaceutical Science Wenzhou Medical UniversityWenzhou 325035China Department of Urology Drum Tower HospitalMedical School of Nanjing UniversityInstitute of UrologyNanjing UniversityNanjing 210008China The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing 210008China Department of Hematology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210093China State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases Center of Drug DiscoveryChina Pharmaceutical UniversityNanjing 210009China Centre of Micro/Nano Manufacturing Technology(MNMT-Dublin) School of Mechanical&Materials EngineeringUniversity College DublinDublin 4Ireland Department of Surgery Division of Cancer Biology and TherapeuticsCedars-Sinai Medical CenterLos AngelesCA 90048USA Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)&School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhou 325035China Shenzhen Research Institute of Nanjing University Shenzhen 518000China

Currently the main treatment of acute myeloid leukemia(AML)is chemotherapy combining hematopoietic stem cell transplantation.However,the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice.Thus,there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects.Here,we revealed that umbilical cord-derived mesenchymal stem cells(UC-MSC)efficiently induced AML cell differentiation by shuttling the neutrophil elastase(NE)-packaged extracellular vesicles(EVs)into AML cells.Interestingly,the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor(VDR)activation in UC-MSC.Chemical activation of VDR by using its agonist 1a,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model.Based on these discoveries,to evade the risk of hypercalcemia,we synthetized and identified sw-22,a novel non-steroidal VDR agonist,which exerted a synergistic prodifferentiation function with UC-MSC on mitigating the progress of AML.Collectively,our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

关键词： Mesenchymal stem cell Acute myeloid leukemia Extracellular vesicles Nonsteroidal VDR modulators Combination therapy

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Crosstalk between IL-15Rα^(+)tumor-associated macrophages and breast cancer cells reduces CD8+T cell recruitment

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Cancer Communications 2022年第6期42卷 536-557页

作者： Wenlong Zhang Qing Zhang nanfei yang Qian Shi Huifang Su Tingsheng Lin Zhonglei He Wenxin Wang Hongqian Guo Pingping Shen State Key Laboratory of Pharmaceutical Biotechnology and Department of Urology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolSchool of Life SciencesNanjing UniversityNanjingJiangsu 210023P.R.China Department of Urology Drum Tower HospitalMedical School of Nanjing UniversityInstitute of UrologyNanjing UniversityNanjingJiangsu 210008P.R.China Shenzhen Research Institute of Nanjing University Shenzhen 518000China Department of Cellular and Integrative Physiology The University of Texas Health Science Center at San AntonioSan AntonioTexas 78229-3904USA Charles Institute of Dermatology School of MedicineUniversity College DublinDublin Eircode D04 V1W8Ireland

Background:Interleukin-15(IL-15)is a promising immunotherapeutic agent owing to its powerful immune-activating effects.However,the clinical benefits of these treatments are limited.Crosstalk between tumor cells and immune cells plays an important role in immune escape and immunotherapy drug resistance.Herein,this study aimed to obtain in-depth understanding of crosstalk in the tumor microenvironment for providing potential therapeutic strategies to prevent tumor progression.Methods:T-cell killing assays and co-culture models were developed to determine the role of crosstalk between macrophages and tumor cells in breast cancer resistant to IL-15.Western blotting,histological analysis,CRISPR-Cas9 knockout,multi-parameter flow cytometry,and tumor cell-macrophage co-injection mouse models were developed to examine the mechanism by which IL-15Rα^(+)tumor-associated macrophages(TAMs)regulate breast cancer cell resistance to IL-15.Results:We found thatmacrophages contributed to the resistance of tumor cells to IL-15,and tumor cells induced macrophages to express high levels of theαsubunit of the IL-15 receptor(IL-15Rα).Further investigation showed that IL-15Rα^(+)TAMs reduced the protein levels of chemokine CX3C chemokine ligand 1(CX3CL1)in tumor cells to inhibit the recruitment of CD8^(+)T cells by releasing the IL-15/IL-15Rαcomplex(IL-15Rc).Administration of an IL-15Rc blocking peptide markedly suppressed breast tumor growth and overcame the resistance of cancer cells to anti-programmed cell death protein 1(PD-1)antibody immunotherapy.Interestingly,Granulocyte-macrophage colony-stimulating factor(GMCSF)inducedγchain(γc)expression to promote tumor cell-macrophage crosstalk,which facilitated tumor resistance to IL-15.Additionally,we observed that the non-transcriptional regulatory function of hypoxia inducible factor-1alpha(HIF-1α)was essential for IL-15Rc to regulateCX3CL1 expression in tumor cells.Conclusions:The IL-15Rc-HIF-1α-CX3CL1 signaling pathway serves as a crosstalk between macrophages and tumor cells in the t

关键词： breast cancer CD8^(+)T-cell crosstalk IL-15Rα immunotherapy tumor microenvironment tumor-associated macrophages

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Intervening pyruvate carboxylase stunts tumor growth by strengthening anti-tumor actions of tumor-associated macrophages

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Signal Transduction and Targeted Therapy 2022年第3期7卷 607-609页

作者： Yuxin Shu nanfei yang Nan Cheng Zhengyun Zou\Wenlong Zhang Yuncheng Bei Qian Shi Menghao Qin Wei-Guo Zhu Pingping Shen State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer Center Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolSchool of Life SciencesNanjing UniversityNanjing 210023PR Chino Guangdong Key Laboratory of Genome Instability and Human Disease Shenzhen University International Cancer CenterDepartment of Biochemistry and Molecular BiologyShenzhen UniversityShenzhen 518060PR China Department of Cellular and Integrative Physiology The University of Texas Health Science Center at San Antonio7703 Floyd Curl DriveSan AntonioTX 78229-3904USA

Dear Editor,Tumor-associated macrophages(TAMs)are critical pro-tumor immunocytes and depletion of TAMs has been exploited for cancer therapy.1 However,the phenotypes and functions of TAMs are plastic,TAMs can also be effector cells by engulfing tumor cells and recruiting cytotoxic T cells,thus shaping the actions of TAMs is more scientific rational than depleting them indiscriminately.2 To promote the entry of reorienting TAMs into the clinical treatments of tumors,it is essential to explore the underline mechanisms controlling the anti-and pro-tumor activities of TAMs.

关键词： strengthening clinical rational

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Solar adaptive optics systems for the New Vacuum Solar Telescope at the Fuxian Lake Solar Observatory

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Astronomical Techniques and Instruments 2024年第2期1卷 95-104页

作者： Lanqiang Zhang Xuejun Rao Hua Bao Youming Guo Jinsheng yang nanfei Yan Xian Ran Dingkang Tong Xinlong Fan Zhongyi Feng Changhui Rao National Laboratory on Adaptive Optics Chengdu 610209China The Laboratory on Adaptive Optics Institute of Optics and ElectronicsChinese Academy of SciencesChengdu 610209China University of Chinese Academy of Sciences Beijing 100049China

Adaptive optics(AO)is essential for high-quality ground-based observations with large telescopes because it counters the impact of wavefront aberrations caused by atmospheric turbulence.The new vacuum solar telescope(NVST)is one of the most important high-resolution solar observation instruments in the world.Three sets of solar adaptive optics systems have been developed and installed on this telescope:conventional adaptive optics,ground layer adaptive optics,and multi-conjugate adaptive optics.These have been in operation from 2018 to 2023.This paper details the development and application of solar adaptive optics on the NVST and discusses the newest instrumentation.

关键词： Solar observation Adaptive optics Multi-conjugate adaptive optics

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象征与本质:论数码电影中的框架装置与图像空间构成的关系

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电影评介 2024年第1期 57-62页

作者：陈南飞中央戏剧学院表演系

无论是在影像世界还是现实空间,我们的感知都受到物理定律的规范,可见,物理规律会对虚拟空间与物质实物的视听感知产生一样的作用。在目前的空间图像表达形式中,线性透视法是最为完备和简明易懂的空间法则。但在数码电影中,动画化的虚... 详细信息

无论是在影像世界还是现实空间,我们的感知都受到物理定律的规范,可见,物理规律会对虚拟空间与物质实物的视听感知产生一样的作用。在目前的空间图像表达形式中,线性透视法是最为完备和简明易懂的空间法则。但在数码电影中,动画化的虚拟制图方式却不一定遵循现实中的透视法则,甚至可以通过透视法的颠倒描绘大小异常的物象、改变人眼的视觉习惯、建构异质性的电影空间等。

关键词：物理定律物理规律视觉习惯空间图像现实空间影像世界图像空间电影空间

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从气血同治探讨慢性气道疾病的异病同治

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世界中医药 2024年第9期19卷 1293-1296页

作者：赵卫华刘南飞李尤佳邵良碧天津中医药大学第二附属医院天津300250 浙江康德药业集团股份有限公司衢州324000

支气管哮喘和慢性阻塞性肺疾病(简称慢阻肺)同属慢性气道炎症疾病,在病机和治法上有一定的相似性,其都可通过调节气血以恢复肺气宣肃,行使正常生理功能。针对肺的生理功能和气血的关系,探讨支气管哮喘和慢阻肺的共同病机:支气管哮喘的... 详细信息

支气管哮喘和慢性阻塞性肺疾病(简称慢阻肺)同属慢性气道炎症疾病,在病机和治法上有一定的相似性,其都可通过调节气血以恢复肺气宣肃,行使正常生理功能。针对肺的生理功能和气血的关系,探讨支气管哮喘和慢阻肺的共同病机:支气管哮喘的基本病机是痰伏于肺,外邪引动,痰气互结,肺失宣降,并可兼有瘀血阻络之象;慢阻肺的病机以久病肺虚为本,加之痰浊、水饮、瘀血等病理产物,使得肺失宣降,本虚标实的病机随病程持续进展;进而从气血同治角度探讨支气管哮喘和慢阻肺2种慢性气道疾病的异病同治,得出“气血同治,畅通气道”的治疗理念。结合成药的应用,分析以此病机为指导的丹龙口服液组方特点和功效主治,为丹龙口服液异病同治2种气道疾病提供理论依据。

关键词：异病同治慢性气道疾病支气管哮喘慢性阻塞性肺疾病气血同治丹龙口服液肺朝百脉瘀血

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杭州保俶塔1933年兴修计划及现存形制初探

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古建园林技术 2024年第3期 20-27页

作者：刘洁沈楠菲张玉瑜杭州西湖风景名胜区岳庙管理处【连横纪念馆】浙江大学建筑设计研究院有限公司浙江大学建筑工程学院

本文基于1929-1938年保俶塔兴修工程相关文献、雷达探测波谱两者的关联整合研究,初步探索保俶塔1933年兴修后封闭塔体的内部结构与形制。经由文献研究,梳理民国时期兴修保俶塔计划图说、筹款过程、施工情况,通过雷达探测波谱分析,验证... 详细信息

本文基于1929-1938年保俶塔兴修工程相关文献、雷达探测波谱两者的关联整合研究,初步探索保俶塔1933年兴修后封闭塔体的内部结构与形制。经由文献研究,梳理民国时期兴修保俶塔计划图说、筹款过程、施工情况,通过雷达探测波谱分析,验证了此次兴修工程后塔身一至五层、六至七层及顶层可能的内部结构情况,为西湖文化遗产的保护管理提供有益的学术研究依据。

关键词：杭州保俶塔雷达探测兴修保俶塔计划图说古塔形制演化

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绘本在幼小衔接过程中对幼儿品质培养的应用

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基础教育研究 2024年第5期 97-99页

作者：任南飞孙竟文刘莞重庆市立信职业教育中心重庆400036 重庆市巴蜀小学校重庆400013 重庆市渝北区空港佳园小学校重庆401120

幼小衔接阶段是幼儿升入小学前的准备阶段,若在该阶段正确、有效地开展各类教育活动,对幼儿的未来发展能起到正向的作用。绘本作为当下广受幼儿喜欢的读物,往往能激发起幼儿较强的阅读兴趣,推动幼儿各项品质及综合能力的发展。在此背景... 详细信息

幼小衔接阶段是幼儿升入小学前的准备阶段,若在该阶段正确、有效地开展各类教育活动,对幼儿的未来发展能起到正向的作用。绘本作为当下广受幼儿喜欢的读物,往往能激发起幼儿较强的阅读兴趣,推动幼儿各项品质及综合能力的发展。在此背景下,文章以绘本课堂为主环境,构建从认知达成到情感共鸣再到行为强化的分级策略,通过绘本培养幼儿的良好品质。

关键词：幼小衔接绘本教学幼儿品质

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扩频分组无线数据网的计算机辅助分析

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通信技术 1997年第2期30卷 37-41页

作者：杨南飞查光明电子科技大学通信学院成都610054

探讨了扩频分组无线数据网的计算机模型的建立方法，提出了区别于以往的分组无线网，衡量数据分组成功与否的标准，并探讨了在非理想ACK信道的无线网络中的应用以及非理想ACK信道的扩频分组无线网的网络性能。

关键词：分组无线数据网网络容量扩频通信

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Ground-layer adaptive optics for the New Vacuum Solar Telescope:Instrument description and first results

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Science China(Physics,Mechanics & Astronomy) 2023年第6期66卷 200-210页

作者： Lanqiang Zhang Hua Bao Xuejun Rao Youming Guo Libo Zhong Xian Ran nanfei Yan Jinsheng yang Cheng Wang Jiahui Zhou Ying yang Yunyao Long Xinlong Fan Zhongyi Feng Donghong Chen Changhui Rao The Key Laboratory on Adaptive Optics Chinese Academy of SciencesChengdu 610209China The Laboratryon Adaptive Optics Institute of Optics and ElectronicsChinese Academyof SciencesChengdu 629China University of Chinese Academy of Sciences Beijing 100049China

Ground-layer adaptive optics(GLAO)has shown its potential for use in solar observation owing to its wide field-of-view(FOV)correction.A high-order GLAO system that consists of a multiple direction Shack-Hartmann wavefront sensor(WFS),a realtime controller with a multi-CPU processor,and a 151-element deformable mirror was developed for the 1-m New Vacuum Solar Telescope at Yunnan Observatories,Chinese Academy of Sciences.A hexagonal microlens with 9×8 subapertures is employed in the WFS.The detection FOV is 42′′×37′′,in which 9(3×3)guide regions are extracted for multiple direction wavefront sensing with a frame rate of up to 2200 Hz.To our knowledge,this is the first professional solar GLAO system used as a regularly operating instrument for scientific observations.Its installation and adjustment were performed in the summer of 2021.In this article,a detailed account of the GLAO system and its first light results and a comprehensive analysis of the performance of the GLAO system are provided.The results show that this system can effectively improve the imaging quality after compensating for the wavefront aberration due to ground-layer turbulence.

关键词： adaptive and segmented optics solar instruments astronomical observations

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