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| 1 | Exosomes secreted from cardiomyocytes suppress the sensitivity of tumor ferroptosis in ischemic heart failure显示文摘Heart failure(HF)patients in general have a higher risk of developing cancer.Several animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression,highlighting a cause-and-effect relationship between these two disease entities.Targeting ferroptosis,a prevailing form of non-apoptotic cell death,has been considered a promising therapeutic strategy for human cancers.Exosomes critically contribute to proximal and distant organ-organ communications and play crucial roles in regulating diseases in a paracrine manner.However,whether exosomes control the sensitivity of cancer to ferroptosis via regulating the cardiomyocyte-tumor cell crosstalk in ischemic HF has not yet been explored.Here,we demonstrate that myocardial infarction(MI)decreased the sensitivity of cancer cells to the canonical ferroptosis activator erastin or imidazole ketone erastin in a mouse model of xenograft tumor.Post-MI plasma exosomes potently blunted the sensitivity of tumor cells to ferroptosis inducers both in vitro in mouse Lewis lung carcinoma cell line LLC and osteosarcoma cell line K7M2 and in vivo with xenograft tumorigenesis model.The expression of miR-22-3p in cardiomyocytes and plasma-exosomes was significantly upregulated in the failing hearts of mice with chronic MI and of HF patients as well.Incubation of tumor cells with the exosomes isolated from post-MI mouse plasma or overexpression of miR-22-3p alone abrogated erastin-induced ferroptotic cell death in vitro.Cardiomyocyte-enriched miR-22-3p was packaged in exosomes and transferred into tumor cells.Inhibition of cardiomyocyte-specific miR-22-3p by AAV9 sponge increased the sensitivity of cancer cells to ferroptosis.ACSL4,a pro-ferroptotic gene,was experimentally established as a target of miR-22-3p in tumor cells.Taken together,our findings uncovered for the first time that MI suppresses erastin-induced ferroptosis through releasing miR-22-3p-enriched exosomes derived from cardiomyocytes.Therefore,targeting exosome-mediated cardiomyocyte/tumor pathological communication may offer a novel approach for the ferroptosis-based antitumor therapy. | Ye Yuan Zhongting Mei Zhezhe Qu Guanghui Li Shuting Yu Yingqi Liu Kuiwu Liu Zhihua Shen Jiaying Pu Yanquan Wang Changhao Wang Zhiyong Sun Qian Liu Xiaochen Pang Ao Wang Zijing Ren Tong Wang Ying Liu Jinhuan Hong Jiajie Xie Xin Li Zhonghua Wang Weijie Du Baofeng Yang | 2023 | Signal Transduction and Targeted Therapy2023，8，4： | 2 |
| 2 | Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein显示文摘Background:The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome-related coronavirus-2(SARS-CoV-2)is pandemic.However,the origins and global transmission pattern of SARS-CoV-2 remain largely unknown.We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics.Methods:Using the full-length sequences of SARS-CoV-2 with intact geographic,demographic,and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020,we constructed the transmission tree to depict the evolutionary process by the R package'outbreaker'.The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2(ACE2)was predicted using mCSM-PPI2 software.Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test.Results:From 26 December 2019 to 8 March 2020,early stage of the COVID-19 pandemic,SARS-CoV-2 strains identified worldwide were mainly composed of three clusters:the Europe-based cluster including two USA-based subclusters;the Asia-based cluster including isolates in China,Japan,the USA,Singapore,Australia,Malaysia,and Italy;and the USA-based cluster.The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade.After 8 March 2020,the clusters of SARS-CoV-2 strains tended to be independent and became'pure'in each of the major countries.Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2.Of all predicted mutants,the number of E484K was the largest one with 86585 sequences,followed by S477N with 55442 sequences worldwide.In more than ten countries,the frequencies of the isolates with E484K and S477N increased significantly.V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses(P<0.001).SARS-CoV-2 with V367F was more sensitive to the S1-targeting neutralizing antibody than the wild-type counterpart(P<0.001).Conclusions:SARS-CoV-2 strains might have originated in several countries simultaneously under certain evolutionary pressure.Travel restrictions might cause location-specific SARS-CoV-2 clustering.The SARS-CoV-2 evolution appears to facilitate its transmission via altering the affinity to ACE2 or immune evasion. | Jiluo Liu Xi Chen Yan Liu Jiansheng Lin Jiaying Shen Hongwei Zhang Jianhua Yin Rui Pu Yibo Ding Guangwen Cao | 2021 | Infectious Diseases of Poverty2021，10，4： | 2 |
| 3 | On Shanghai-style Flower Arrangement Art显示文摘Origin of Shanghai-style culture and its features were introduced, and characteristics of Shanghai-style flower arrangement were analyzed. It was proposed that Shanghai-style flower arrangement put human needs on the top priority, highlighted regional cultures, and inherited essence of traditional Chinese flower arrangement art. It absorbed alien cultures selectively, integrated western floriculture and local concept, humanistic environment and natural environment. In addition, Shanghai-style flower arrangement art pursued natural styles, was particular about lines and artistic ambience. It was an inclusive style because essence of many other flower arrangement styles was absorbed, and was characterized by strong commercial atmosphere and appealed to both refined and popular taste. Shanghai-style flower arrangement showed the spirits of 'open and innovative', and focused on publicity and cultivation of talents. | Chen Jiaying CHEN Xuan PU Yan | 2012 | Journal of Landscape Research2012，4，12： | 0 |
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