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Global research trends and prospects of cellular metabolism in colorectal cancer

World Journal of Gastrointestinal Oncology 2024年第2期16卷 527-542页

作者： Yan-Chen Liu Zhi-Cheng Gong Chao-Qun Li Peng Teng Yan-Yan Chen Zhao-Hui Huang Wuxi Cancer institute Affiliated Hospital of Jiangnan UniversityWuxi 214122Jiangsu ProvinceChina Wuxi School of medicine Jiangnan UniversityWuxi 214122Jiangsu ProvinceChina Wuxi institute of integrated chinese and western medicine Affiliated Hospital of Jiangnan UniversityWuxi 214062Jiangsu ProvinceChina

BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

关键词： Cellular metabolism Colorectal cancer Glucose metabolism Amino acid metabolism Lipid metabolism Nucleotide metabolism

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IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

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Genes & Diseases 2024年第1期11卷 495-508页

作者： Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang Qingli Bie Rou Zhao Li Wei Baogui Zhang Bin Zhang Department of Laboratory medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China postdoctoral Mobile station of Shandong University of Traditional chinese medicine JinanShandong 250355China Department of Reproductive medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Department of Gastrointestinal Surgery Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China institute of Forensic medicine and Laboratory medicine Jining Medical UniversityJiningShandong 272067China

Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease progression.Targeting these rare cancer cells,however,remains challenging with respect to therapeutic benefit.Here,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid cells.The expression of IL-13RA2 was positively correlated with canonical stemness markers in CRC.We further demonstrated that the level of IL-13 was up-regulated in the serum of CRC patients.Biologically,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in vivo.This phenotype could be reversed by knocking down IL-13RA2.Mechanistically,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of IL-13.We further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of p53.In conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.

关键词： Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53

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Time-lagged Effects of the Spring Atmospheric Heat Source over the Tibetan Plateau on Summer Precipitation in Northeast China during 1961–2020:Role of Soil Moisture

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Advances in Atmospheric Sciences 2024年第8期41卷 1527-1538页

作者： Yizhe HAN Dabang JIANG Dong SI Yaoming MA Weiqiang MA institute of Atmospheric Physics Chinese Academy of Sciences State Key Laboratory of Tibetan Plateau Earth System Environment and Resources (TPESER)Institute of Tibetan Plateau Research Chinese Academy of Sciences National institute of Natural Hazards Ministry of Emergency Management of China University of chinese Academy of Sciences College of Atmospheric Sciences Lanzhou University National Observation and research station for Qomolongma Special Atmospheric Processes and Environmental Changes Kathmandu Center of research and Education Chinese Academy of Sciences China-Pakistan Joint research Center on Earth Sciences Chinese Academy of Sciences

The spring atmospheric heat source(AHS) over the Tibetan Plateau(TP) has been suggested to affect the Asian summer monsoon and summer precipitation over South China. However, its influence on the summer precipitation in Northeast China(NEC) remains unknown. The connection between spring TP AHS and subsequent summer precipitation over NEC from 1961 to 2020 is analyzed in this study. Results illustrate that stronger spring TP AHS can enhance subsequent summer NEC precipitation, and higher soil moisture in the Yellow River Valley-North China region(YRVNC)acts as a bridge. During spring, the strong TP AHS could strengthen the transportation of water vapor to East China and lead to excessive rainfall in the YRVNC. Thus, soil moisture increases, which regulates local thermal conditions by decreasing local surface skin temperature and sensible heat. Owing to the memory of soil moisture, the lower spring sensible heat over the YRVNC can last until mid-summer, decrease the land–sea thermal contrast, and weaken the southerly winds over the East Asia–western Pacific region and convective activities over the South China Sea and tropical western Pacific. This modulates the East Asia–Pacific teleconnection pattern, which leads to a cyclonic anomaly and excessive summer precipitation over NEC.

关键词： atmospheric heat source Northeast China soil moisture summer precipitation Tibetan Plateau

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Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

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Journal of Pharmaceutical Analysis 2024年第3期14卷 348-370页

作者： Binbin Zhao Dongfeng Wei Qinghua Long Qingjie Chen Fushun Wang Linlin Chen Zefei Li Tong Li Tao Ma Wei Liu Linshuang Wang Caishui Yang Xiaxia Zhang Ping Wang Zhanjun Zhang State Key Laboratory of Cognitive Neuroscience and Learning&IDG/McGovern institute for Brain research Beijing Normal UniversityBeijing100875China institute of Gerontology Hubei University of Chinese MedicineWuhan430065China institute of Basic research in Clinical medicine China Academy of Chinese Medical SciencesBeijing100700China Medical School Hubei Minzu UniversityEnshiHubei445000China HuBei University of Science and Technology XianningHubei437100China institute of Brain and Psychological Science Sichuan Normal UniversityChengdu610066China Key Laboratory of Traditional chinese medicine Resource and Compound Prescription Ministry of EducationHubei University of Chinese MedicineWuhan430065China Dongfang Hospital Beijing University of Chinese MedicineBeijing100078China Beijing Key Laboratory of Traditional chinese medicine Basic research on Prevention and Treatment for Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing100700China School of Systems Science Beijing Normal UniversityBeijing100875China BABRI Centre Beijing Normal UniversityBeijing100875China

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

关键词： Alzheimer's disease Synaptic currents Mitophagy Mitochondrial fusion and fission Dengzhan Shengmai capsules

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METTL1 promotes colorectal cancer cell proliferation by attenuating CHEK2-induced G1/S phase arrest

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Genes & Diseases 2024年第2期11卷 579-581页

作者： Houxiang Jiang Ying Liu Huibin Song Jinquan Xia Ying Tian Luolin Wang Mingwei Li Zhenyu Xu Zhenglei Xu Chang Zou Department of Gastrointestinal Surgery The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College)WuhuAnhui 241001China Anhui Province Clinical research Center for Critical Respiratory medicine WuhuAnhui 241001China Department of Clinical Medical research Center The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan UniversityThe First Affiliated Hospital of Southern University of Science and TechnologyShenzhenGuangdong 518020China integrated chinese and western medicine postdoctoral research station Jinan UniversityGuangzhouGuangdong 510632China School of Pharmacy Southwest Medical UniversityLuzhouSichuan 646000China Department of Gastroenterology Shenzhen People's Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China Precision medicine Center The First Affiliated Hospital of Wannan Medical College(Yijishan Hospital of Wannan Medical College)WuhuAnhui 241001China School of medicine Life and Health SciencesThe Chinese University of Hong KongShenzhenGuangdong 518172China

Colorectal carcinoma(CRC),the third most commonly diagnosed cancer,accounts for 9.7%of all newly diagnosed cancer cases and 9.4%of cancer-related deaths globally.1 Recent studies have demonstrated that post-transcriptional RNA modifications,such as N^(6)-methyladenosine,N^(5)-methylcytosine,and N^(7)-methylguanosine,play critical roles in the regulation of mRNA stability and translation,primary microRNA processing,and lncRNA-protein complex that contributes to the progression of human cancer.

关键词： cancer colorectal globally

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Analyzing the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells

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Clinical research Communications 2024年第1期7卷 3-10页

作者： Rui-Xue Chen Jing Li Guo-Zhen Dong Sheng-Yan Qiao Xiao Hu Li-Guo Chen School of integrated chinese and western medicine Jining Medical UniversityJining 272067China institute of Integration of Traditional chinese and western medicine the Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China School of chinese medicine Jinan UniversityGuangzhou 510632China

Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.

关键词： Xuefu Zhuyu decoction hypertension vascular endothelial cells pharmacological substances and targets

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Megafossils of Betulaceae from the Oligocene of Qaidam Basin and their paleoenvironmental and phytogeographic implications

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Plant Diversity 2024年第1期46卷 101-115页

作者： Tao Yang Jia-Hao Cai Yan-Zhi Dai Hong-Yu Chen Lei Han Li Zhang Wei-Yu Liang Xu-Jun Li Wen-Jia Li Jing-Yu Wu San-Ping Xie De-Fei Yan School of Earth Sciences and Key Laboratory of Mineral Resources in western China(Gansu Province) Lanzhou UniversityLanzhou 730000China Key Laboratory of Vertebrate Evolution and Human Origins of chinese Academy of Sciences Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China State Key Laboratory of Palaeobiology and Stratigraphy Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and PaleoenvironmentChinese Academy of SciencesNanjing 210008China Center for research and Education on Biological Evolution and Environments School of Earth Sciences and EngineeringNanjing UniversityNanjing 210023China

Understanding the paleoenvironment and phytogeographical history of the Tibetan Plateau,China relies on discovering new plant fossils.The Qaidam Basin has long been regarded as an ideal‘field laboratory’to investigate the paleoclimate and paleobiological evolution of the northern Tibetan Plateau.However,fossil angiosperms from the Qaidam Basin are rare,and our knowledge of its paleovegetation is poor.Here,we report fossil leaves and fruits of Betulaceae found from the Oligocene Shangganchaigou Formation of northwestern Qaidam Basin(Huatugou area).Comparative morphological analysis led us to assign the fruits to the Betula subgenus Betula and the leaves to Carpinus grandis.These findings,together with other reported fossil plants from the same locality,reveal a close floristic linkage between the Qaidam Basin and Europe during the Oligocene.The northern pathway of this floristic exchange may have crossed through the Qaidam Basin during the late Paleogene.This floristic linkage may have been facilitated by the continuous narrowing of the Turgai Strait and stronger westerlies,which transported moisture and provided favorable climatic conditions.Indeed,fossil plants collected from the Qaidam Basin suggest that during the Oligocene this region had warm and humid deciduous broad-leaf forest,which differs from the region’s modern vegetation and indicates that the Qaidam Basin may have been a suitable region for these plants to flourish and spread during the Oligocene.

关键词： Paleoenvironment Biogeography Betulaceous fossil Qaidam basin Tibetan Plateau Oligocene

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Status and trends in the stability of the three largest ice shelves in Antarctica

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Science China Earth Sciences 2024年第8期67卷 2615-2632页

作者： Rongxing LI Guojun LI Lu AN Menglian XIA Da LV Yuan CHENG Aiguo ZHAO Tian CHANG Xiangbin CUI Shengkai ZHANG Shijie LIU Yixiang TIAN Weian WANG Center for Spatial Information Science and Sustainable Development Applications Tongji University College of Surveying and Geo-informatics Tongji University postdoctoral research station of Shanghai Surveying and Mapping institute Key Laboratory of Spatial-temporal Big Data Analysis and Application of Natural Resources in Megacities institute for Conservation of Cultural Heritage School of Cultural Heritage and Information Management Shanghai University Polar research institute of China chinese Antarctic Center of Surveying and Mapping Wuhan University

The Ross, Filchner-Ronne, and Amery ice shelves are the three largest ice shelves in Antarctica, playing a crucial role in supporting the Antarctic ice sheet. However, current studies on the stability of the three largest ice shelves primarily focus on singular or limited factors, lacking a comprehensive assessment of multiple parameters. To systematically and in-depth study the stability and trend of the three largest ice shelves, we comprehensively collected and analyzed key parameters, including elevation changes, basal melting, surface meltwater, major rifts propagation rate, suture zones, ice front area change rate,grounding lines, ice velocity, and mass balance. Additionally, we selected the collapsed Larsen B Ice Shelf(LBIS), the rapidly changing and structurally weakened Pine Island Ice Shelf(PIIS), and the accelerating Totten Ice Shelf(TIS) as reference ice shelves. By comparing and analyzing the key parameters between these reference ice shelves and the three largest ice shelves, we find the status and trends in the stability of the latter. Our findings reveal that most key parameters of the three largest ice shelves present relatively minor variations compared to those of the reference ice shelves. Specifically, 50% of the parameters are smaller than those of the accelerating TIS, 88% are smaller than those of the rapidly changing PIIS, and all parameters are smaller than those of the collapsed LBIS. Furthermore, after analyzing parameters that are not smaller than those of the TIS, it is observed that they remain in a stable state. Hence, the three largest ice shelves are currently undergoing natural changes that do not threaten their stability in the short term. Nevertheless, the evolution of the ice shelves under global climate change remains uncertain,making long-term observation and monitoring essential to assess their impact on sea level rise.

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Three dimensional velocity model and its tectonic implications at China Seismic Experimental Site,eastern margin of the Tibetan Plateau

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Science China Earth Sciences 2024年第7期67卷 2268-2290页

作者： Jianping WU Yan CAI Wei WANG Weilai WANG Changzai WANG Lihua FANG Yaning LIU Jing LIU institute of Geophysics China Earthquake AdministrationBeijing 100081China Beijing Bajatuan Earth Science National Observation and research station Beijing 1095China Beijing Earthquake Agency Beijing 100080China

The China Seismic Experimental Site(CSES)is located at the intersection of the Tibetan Plateau,South China Block,and Indian Plate and has complex geological settings and intense crustal deformation,making it one of the most seismically active areas in chinese mainland.A high-resolution,three-dimensional(3D)crust-mantle velocity structure is crucial for understanding seismotectonic environments,lithospheric deformation mechanisms,and deep dynamic processes.We first constructed a high-vertical-resolution 3D initial velocity model using the joint inversion of receiver functions and surface waves and then obtained a 3D P-and S-wave velocity model(CSES-VM1.0)with the highest lateral resolution of 0.25°for the CSES using double-difference tomography.Owing to the limitations of the Sn observation data,the resolution of the S-wave velocity model in the lower crust and upper mantle was reduced,making it closer to the initial model provided by joint inversion.A comparison with explosive-source seismic data showed that the synthetic P-wave first-arrival travel times of the new model were closer to the observations than those of the previous velocity models.The velocity cross-sections across the source areas of the 2022 Lushan MS6.1 and Ludian MS6.8 earthquakes reveal that the former earthquake occurred near a weak contact zone between the Tibetan Plateau and Sichuan Basin,and the rupture of the latter earthquake occurred in a granitic area,with the northern end blocked by rigid high-velocity bodies.A clear high-velocity anomaly zone is distributed along the western margin of the Yangtze Block,revealing the spatial distribution of Neoproterozoic intermediate-basic intrusions.This high-velocity zone significantly controls the morphology of fault zones and influences the rupture processes of major earthquakes.Two northeast-southwest and north-south trending high-velocity anomalies were found near Panzhihua,potentially related to Neoproterozoic and Middle-Late Permian intermediate-basic intrusions.The imaging results revealed t

关键词： Eastern Tibetan Plateau China Seismic Experimental Site Yangtze Block Velocity model Double-difference tomography

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心肌缺血再灌注损伤中心肌免疫细胞单细胞图谱绘制及具有心肌保护效应的Ym-1hi中性粒细胞的鉴定

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Science Bulletin 2024年第7期69卷 949-967页

作者：董亚兰康真玉张子力张永强周海锋刘艳飞帅欣欣李君仪殷梁青青王埙埙马彦范恒 Feng Jiang 林志豪丁从珠金渊真 Alexey Sarapultsev 李芳菲张戈谢天尹长军程翔罗珊珊刘玥胡德胜 Department of integrated Traditional chinese and western medicine Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Key Laboratory of Biological Targeted Therapy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing 210008China National Clinical research Center for chinese medicine Cardiology Xiyuan HospitalChinese Academy of Chinese Medical SciencesBeijing 100091China Department of Cardiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of International Education Tianjin University of Traditional Chinese MedicineTianjin 300193China institute of Neuroscience School of MedicineXiamen UniversityXiamen 361102China School of Traditional chinese medicine Xiamen University MalaysiaSepang 43900Malaysia School of Medical Biology South Ural State UniversityChelyabinsk 620049Russia Shum Yiu Foon Sum Bik Chuen Memorial Centre for Cancer and Inflammation research(CCIR) School of Chinese MedicineHong Kong Baptist UniversityHong Kong 999077China institute of integrated Bioinfomedicine and Translational Science School of Chinese MedicineHong Kong Baptist UniversityHong Kong 999077China Division of Vascular Surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China institute of Precision medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China institute for Cardiovascular Prevention(IPEK) Ludwig-Maximilians-UniversityMunich 80336Germany institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China China-Russia Medical research Center for Stress Immunology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Myocardial ischemia–reperfusion injury(MIRI)is a major hindrance to the success of cardiac reperfusion therapy.Although increased neutrophil infiltration is a hallmark of MIRI,the subtypes and alterations of neutrophils in this process remain unclear.Here,we performed single-cell sequencing of cardiac CD45^(+)cells isolated from the murine myocardium subjected to MIRI at six-time points.We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI.Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations,including Ccl3^(hi)Neu and Ym-1^(hi)Neu,which were increased at 6 h and 1 d after reperfusion,respectively.Ym-1^(hi)Neu selectively expressed genes with protective effects and was,therefore,identified as a novel specific type of cardiac cell in the injured heart.Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues,especially instructing the response of macrophages.The abundance of Ym-1^(hi)Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D(Ly6G)or anti-Intercellular cell adhesion molecule-1(ICAM-1)neutralizing antibodies.In addition,a neutrophil subtype with the same phenotype as Ym-1^(hi)Neu was detected in clinical samples and correlated with prognosis.Ym-1 inhibition exacerbated myocardial injury,whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice,which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue.Overall,our findings reveal the antiinflammatory phenotype of Ym-1^(hi)Neu and highlight its critical role in myocardial protection during the early stages of MIRI.

关键词： Myocardial ischemia-reperfusion injury Neutrophil Ym-1 Cardiac immune response Single-cell sequencing

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