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Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia

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Genes & Diseases 2024年第5期11卷 140-162页

作者： Xudong Li Wei Li Yanli Zhang Linping Xu yongping song Department of Hematology Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China

The advent of tyrosine kinase inhibitors(TKI)targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia(CML),greatly prolonged the life of CML patients,and improved their ***,TKI resistance is still a major problem with CML patients,reducing the efficacy of treatment and their quality of *** resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent ***,the main clinical strategy addressing TKI resistance is to switch to newly developed ***,data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance ***,finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system(UPS)has emerged as a *** UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological *** recent years,the study of UPS in hematological malignant tumors has resulted in effective treatments,such as bortezomib in the treatment of multiple myeloma and mantle cell *** CML,the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL,interfering with CML-related signaling pathways,and negatively or positively affecting leukemia stem *** of these molecules may help overcome TKI resistance and treat *** this review,the mechanism of TKI resistance is briefly described,the components of UPS are introduced,existing studies on UPS participating in TKI resistance are listed,and UPS as the therapeutic target and strategies are discussed.

关键词： Chronic myeloid leukemia Deubiquitinases E3 ligase PROTAC TKI resistance Ubiquitin-proteasome system

Chimeric antigen receptor-immune cells against solid tumors:Structures,mechanisms,recent advances,and future developments

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Chinese Medical Journal 2024年第11期137卷 1285-1302页

作者： Xudong Li Wei Li Linping Xu yongping song Department of Hematology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China

The advent of chimeric antigen receptor(CAR)-T cell immunotherapies has led to breakthroughs in the treatment of hematological ***,their success in treating solid tumors has been ***-natural killer(NK)cells have several advantages over CAR-T cells because NK cells can be made from pre-existing cell lines or allogeneic NK cells with a mismatched major histocompatibility complex(MHC),which means they are more likely to become an"off-the-shelf"***,they can kill cancer cells via CAR-dependent/independent pathways and have limited *** are the most malleable immune cells in the *** cells can efficiently infiltrate into tumors and are present in large numbers in tumor microenvironments(TMEs).Importantly,CAR-macrophages(CAR-Ms)have recently yielded exciting preclinical results in several solid ***,CAR-T,CAR-NK,and CAR-M all have their own advantages and *** this review,we systematically discuss the current status,progress,and the major hurdles of CAR-T cells,CAR-NK cells,and CAR-M as they relate to five aspects:CAR structure,therapeutic mechanisms,the latest research progress,current challenges and solutions,and comparison according to the existing research in order to provide a reasonable option for treating solid tumors in the future.

关键词： Immunotherapy Chimeric antigen receptor-T cells Chimeric antigen receptor-NK cells Chimeric antigen receptor-macrophage Solid tumors

Identification of potential immune-related mechanisms related to the development of multiple myeloma

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Chinese Medical Journal 2024年第13期137卷 1603-1613页

作者： Yaomei Wang Wenli Zhang Tiandong Li Mengmeng Liu Mengya Gao Xinqing Li Yufei Chen yongping song Wei Li Chunyan Du Fang Wang Lina Liu Department of Hematology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China The Academy of Medical Science College of MedicalZhengzhou UniversityZhengzhouHenan 450052China College of Public Health Zhengzhou UniversityZhengzhouHenan 450000China Department of Research and Foreign Affairs The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China Department of Clinical Medicine Zhengzhou UniversityZhengzhouHenan 450052China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Laboratory Animal Center School of Medical SciencesZhengzhou UniversityZhengzhouHenan 450052China

Background:Although significant advances have been made in the treatment of multiple myeloma(MM),leading to unprecedented response and survival rates among patients,the majority eventually relapse,and a cure remains *** situation is closely related to an incomplete understanding of the immune microenvironment,especially monocytes/macrophages in patients with treatment-naïve *** aim of this study was to provide insight into the immune microenvironment,especially monocytes/macrophages,in patients with treatment-naïve ***:This study used the single-cell RNA sequencing(scRNA-seq)data of both patients with MM and heathy donors to identify immune cells,including natural killer(NK)cells,T cells,dendritic cells(DCs),and monocytes/*** data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM ***:A significant difference was observed between the bone marrow(BM)immune cells of the healthy controls and treatment-naïve MM patients through *** is noteworthy that,through an scRNA-seq data analysis,this study found that interferon(IFN)-induced NK/T cells,terminally differentiated effector memory(TEMRA)cells,T-helper cells characterized by expression of IFN-stimulated genes(ISG^(+)Th cells),IFN-responding exhausted T cells,mannose receptor C-type 1(MRC1)^(+)DCs,IFN-responding DCs,MHCII^(+)DCs,and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve ***,transcriptomic data of monocytes/macrophages demonstrated that"don’t eat me"-related genes and IFN-induced genes increase in treatment-naïve MM ***,scRNA-seq,transcriptomic data,and flow cytometry also showed an increased proportion of CD16^(+)monocytes/macrophages and expression level of ***-cell communication analysis indicated that monocytes/macrophages,whose related important signaling pathways include migration i

关键词： Multiple myeloma Monocytes/macrophages Single-cell RNA sequencing Immune cell Microenvironment Bone marrow Molecular characterization

RIS-4D生物雷达多人体定位与生命体征监测

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信号处理 2024年第2期40卷 225-235页

作者：金添李志戴永鹏宋勇平国防科技大学电子科学学院陆军工程大学通信士官学校

非接触式生命体征监测是一种可以被广泛用于健康医疗、辅助生活、汽车交通、搜索救援和公共安全的新兴技术。在本文工作中，我们开发了RIS-4D生物雷达用于非接触式生命体征监测，提出了同时定位多个人体目标以及监测对应的呼吸和心跳微... 详细信息

非接触式生命体征监测是一种可以被广泛用于健康医疗、辅助生活、汽车交通、搜索救援和公共安全的新兴技术。在本文工作中，我们开发了RIS-4D生物雷达用于非接触式生命体征监测，提出了同时定位多个人体目标以及监测对应的呼吸和心跳微动信号的方法，具有低成本、低能耗、可编程、易部署的优势。该系统利用可重构智能表面（Reconfigurable Intelligent Surface,RIS）天线动态操纵电磁波进行波束形成和三维雷达成像，从而实现对多个人体目标的三维空间定位，然后从时间维度上的连续回波中提取呼吸和心跳信号。“三维空间”+“一维时间”形成的四维时空高分辨率信息使得该RIS-4D生物雷达能够多维度感知目标和环境。空间波束形成使得电磁波能量聚焦在人体胸腔位置，有助于减少杂波（四肢以及环境多径等杂波）造成的干扰和失真，从而提高生物雷达的探测性能。在真实室内办公环境中的实测数据对该系统和所提出方法进行了验证，实验结果表明，利用该系统可以准确地定位并监测多个受试者的呼吸和心跳微动信号，对瞬时心率和心变异率的监测结果进一步验证了该系统的有效性。所提出的RIS-4D生物雷达为非接触生理信号采集提供了一种多目标、多功能、高精度的实现方式。

关键词：生命体征生物雷达四维可重构智能表面定位

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Ferroptosis in acute leukemia

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Chinese Medical Journal 2023年第8期136卷 886-898页

作者： Tianxin Lyu Xudong Li yongping song Department of Hematology The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China

Ferroptosis is an iron-dependent cell death pathway that is different from apoptosis,pyroptosis,and *** main characteristics of ferroptosis are the Fenton reaction mediated by intracellular free divalent iron ions,lipid peroxidation of cell membrane lipids,and inhibition of the anti-lipid peroxidation activity of intracellular glutathione peroxidase 4(GPX4).Recent studies have shown that ferroptosis can be involved in the pathological processes of many disorders,such as ischemia-reperfusion injury,nervous system diseases,and blood ***,the specific mechanisms by which ferroptosis participates in the occurrence and development of acute leukemia still need to be more fully and deeply *** article reviews the characteristics of ferroptosis and the regulatory mechanisms promoting or inhibiting *** importantly,it further discusses the role of ferroptosis in acute leukemia and predicts a change in treatment strategy brought about by increased knowledge of the role of ferroptosis in acute leukemia.

关键词： Acute lymphoblastic leukemia Acute myeloid leukemia Ferroptosis Oxidative damage Antioxidant defense Lipid peroxidation

Surface engineering of 1D nanocatalysts for value-added selective electrooxidation of organic chemicals

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Nano Research 2024年第3期17卷 1327-1336页

作者： yongping Yang Chuhao Liu Tinglu song Mufan Li Zipeng Zhao Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications Experimental Center of Advanced MaterialsSchool of Materials Science and EngineeringBeijing Institute of TechnologyBeijing 100081China Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

Electrolytic water splitting by renewable energy is a technology with great potential for producing hydrogen(H_(2))without carbon emission,but this technical route is hindered by its huge energy(electricity)cost,which is mainly wasted by the anode oxygen evolution reaction(OER)while the value of the anode product(oxygen)is very *** the high-energy-cost OER with a selective organic compound electrooxidation carried out at a relatively lower potential can reduce the electricity cost while producing value-added ***,H_(2) generation coupled with synthesis of value-added organic compounds faces the challenge of low selectivity and slow generation rate of the anodic ***-dimensional(1D)nanocatalysts with a unique morphology,well-defined active sites,and good electron conductivity have shown excellent performance in many electrocatalytic *** rational design and regulation of 1D nanocatalysts through surface engineering can optimize the adsorption energy of intermediate molecules and improve the selectivity of organic electrooxidation ***,we summarized the recent research progress of 1D nanocatalysts applied in different organic electrooxidation reactions and introduced several different fabrication strategies for surface engineering of 1D ***,we focused on the relationship between surface engineering and the selectivity of organic electrooxidation reaction ***,future challenges and development prospects of 1D nanocatalysts in the coupled system consisting of organic electrooxidation and hydrogen evolution reactions are briefly outlined.

关键词： hydrogen generation organic compound electrooxidation one-dimensional(1D)nanocatalysts surface engineering selectivity

A Novel Dominant Allele from 93-11, ES(4), Represses Reactive Oxygen Species Scavenging and Leads to Early-Senescence in Rice

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Phyton-International Journal of Experimental Botany 2023年第3期92卷 665-677页

作者： Zhishu Jiang Cong Gan Yulian Liu Xiaoli Lin Limei Peng yongping song Xiaowei Luo Jie Xu Key Laboratory of Crop Physiology Ecology and Genetic BreedingMinistry of EducationJiangxi Agricultural UniversityNanchang330045China

Senescence is the last developmental process in plant,which has an important impact on crop yield and *** this study,a stable hereditary early-senescence line BC64 was isolated from the high-generation recombinant inbred lines of 93-11 and Wuyunjing7(W7).Genetic analysis showed that the premature aging phenotype was controlled by a dominant gene derived from *** linkage analysis,the gene was primarily mapped in the region between marker B4 and B5 near the centromere of chromosome 4,described as ES(4).Through multiple backcrossing with W7,the near-isogenic line of ES(4)(NIL-ES(4))was *** with wild-type W7,NIL-ES(4)plants showed more sever senescence phenotype in both nature and dark *** NIL plants,leaves turned yellow at the fully tillering stage;photosynthetic rate,pollen fertility and seed setting rate were ***,the malondialdehyde,proline content and relative conductivity in NIL-ES(4)were significantly higher than those in W7;both transcript level and activities of reactive oxygen species scavenging enzymes were repressed;H2O2 and O^(2−)were significantly *** study provides a basis for further cloning and function identification of ES(4).

关键词： Rice early-senescence gene mapping chlorophyll degradation reactive oxygen species scavenging

Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

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Frontiers of Medicine 2016年第4期10卷 383-388页

作者： Shuhang Wang yongping song Feifei Yan Delong Liu The Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital Beijing 100142 China Henan Cancer Hospital and the Affiliated Cancer Hospital of Zhengzhou University Zhengzhou 450008 China

The tyrosine kinase inhibitors （TKI） of the epidermal growth factor receptor （EGFR） are becoming the first line of therapy for advanced non-small cell lung cancer （NSCLC）. Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 （osimertinib; Tagrisso） is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9-13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.

关键词： EGFR tyrosine kinase inhibitor AZD9291 EAI045

Characterization of a Novel Weak Allele of RGA1/D1 and Its Potential Application in Rice Breeding

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Rice science 2022年第6期29卷 522-534,I0021,I0022页

作者： LIU Yantong LI Ting JIANG Zhishu ZENG Chuihai HE Rong QIU Jiao LIN Xiaoli PENG Limei song yongping ZHOU Dahu CAI Yicong ZHU Changlan FU Junru HE Haohua XU Jie Key Laboratory of Crop Physiology Ecology and Genetic BreedingMinistry of Education/College of AgronomyJiangxi Agricultural UniversityNanchang 330045China

Semi-dwarfing improves the lodging resistance and yield of rice,and the vast majority of modern rice varieties harbor the sd1 allele to decrease plant height,resulting in reduced genetic diversity and negative agronomic ***,exploring alternative sources of dwarfism is imperative for rice ***,we identified a novel RGA1 allele,d1-w,from a local indica variety Xiaolixiang(XLX)using a map-based cloning *** with other rice varieties,RGA1 in XLX contained a unique single nucleotide polymorphism that resulted in an additional transcript and reduced functional RGA1 transcript *** RGA1 from Nipponbare was introduced into XLX to estimate the value of d1-w in rice *** with transgenic XLX plants(XLX^(D1)),XLX exhibited reduced plant height,increased stem strength,lower reactive oxygen species accumulation,delayed senescence,stronger photosynthesis,higher grain yield and quality(including external,milling and nutritional qualities),and enhanced resistance to drought and Rhizoctonia ***,we proposed that the d1-w allele has potential as an excellent dwarfism resource for rice breeding.

关键词： rice weak allele RGA1 dwarf germplasm resource yield grain quality drought resistance sheath blight