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| 1 | Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics显示文摘Colorectal cancer(CRC), a malignant tumor worldwide consists of microsatellite instability(MSI) and stable(MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing wasperformed to explore the role of SHP2 in all cell types of tumor microenvironment(TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68;macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively,our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy. | Jian Gao Zhigui Wu Mingxia Zhao Rui Zhang Manru Li Dongdong Sun Haibo Cheng Xianjia Qi Yuxian Shen Qiang Xu Hongqi Chen Dijun Chen Yang Sun | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 5 |
| 2 | Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis显示文摘Impairment of glucose(Glu)uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases.Heterogeneous nuclear ribonucleoprotein A1(hnRNP Al)is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions.The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis.Our results showed that conditional deletion of hnRNP Al in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet(HFD).Conditional knockout mice fed a HFD showed exacerbated obesity,insulin resistance,and hepatic steatosis.In vitro interference of hnRNP Al in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake,whereas hnRNP Al overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin.The expression and stability of glycogen synthase(gysl)mRNA were also decreased in the absence of hnRNP A l.Mechanistically,hnRNP Al interacted with gys l and stabilized its mRNA,thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue.Taken together,our findings are the first to show that reduced expression of hnRNP Al in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis. | Mingxia Zhao Lihong Shen Zijun Ouyang Manru Li Guoliang Deng Chenxi Yang Wei Zheng Lingdong Kong Xuefeng Wu Xudong Wu Wenjie Guo Ye Yin Qiang Xu Yang Sun | 2020 | Journal of Molecular Cell Biology2020，12，4： | 2 |
| 3 | Restoration processes of pollution zones in Hanjiang River显示文摘RestorationprocessesofpollutionzonesinHanjiangRiver￥ShenYunfen;TanYuyun;FengWeisong;GuManru(InstituteofHydrobiology,ChineseAc... | Shen Yunfen Tan Yuyun Feng Weisong Gu Manru (Institute of Hydrobiology, Chinese Academy of Sciences, Wuchang 430072, China) He Chengying (Environmental Protection Station of Xiantao City ,China) Li Aiguo (Environmental Protection Station of Xiangfan Ci | 1996 | Journal of Environmental Sciences1996，8，2： | 2 |
| 4 | Parasite-host network analysis provides insights into the evolution of two mistletoe lineages(Loranthaceae and Santalaceae)显示文摘Mistletoes are ecologically important parasitic plants,with> 1600 species from five lineages worldwide.Mistletoe lineages exhibit distinct patterns of species diversification and host specificity,however,the mechanisms underlying these differences are poorly understood.In this study,we analysed a comprehensive parasite-host network,including 280 host species from 60 families and 22 mistletoe species from two lineages(Santalaceae and Loranthaceae) in Xishuangbanna,located in a biodiversity hotspot of tropical Asia.We identified the factors that predict the infection strength of mistletoes.We also detected host specificity and the phylogenetic signal of mistletoes and their hosts.We found that this interaction network could be largely explained by a model based on the relative abundance of species.Host infection was positively correlated with diameter at breast height and tree coverage,but negatively correlated with wood density.Overall,closely related mistletoe species tend to interact more often with similar hosts.However,the two lineages showed a significantly different network pattern.Rates of host generality were higher in Loranthaceae than in Santalaceae,although neither lineage showed phylogenetic signal for host generality.This study demonstrates that the neutral interaction hypothesis provides suitable predictions of the mistletoe-host interaction network,and mistletoe species show significant phylogenetic signals for their hosts.Our findings also indicate that high species diversification in Loranthaceae may be explained by high rates of host generality and the evolutionary history shared by Loranthaceae species with diverse host plants in the tropics. | Jin Zhao Yuanjie Li Xuanni Wang Manru Li Wenbin Yu Jin Chen Ling Zhang | 2023 | Plant Diversity2023，45，6： | 0 |
| 5 | 一种泛性桑寄生植物繁殖物候异步性的寄主介导效应显示文摘寄主介导效应被认为会导致半寄生性的桑寄生植物的繁殖物候异步性,并由此为与桑寄生植物互惠共生的传粉者和种子散布者提供更长时间的食物资源供应,但目前关于此方面的研究还缺乏相关的实证数据。本研究以广泛分布于中国西南西双版纳地区的一种泛性桑寄生科植物五蕊寄生(Dendrophthoe pentandra)为材料,每周监测其开花、结果物候,检测了其开花和结果物候是否呈季节性格局,量化了五蕊寄生繁殖物候的异步程度,并检测了影响该植物始花期早晚的因素。最后,本研究还检验了五蕊寄生繁殖物候的异步性随寄主种类数量变化的效应。研究结果表明:(i)在连续两年的物候观测中五蕊寄生的花期和果期都呈单峰分布格局;(ii)始花期显著受到植物大小和光照强度的影响,即冠幅越大和受光程度越高的植物个体有更早的始花期和更长的花期和果期;(iii)不同的寄主种类对五蕊寄生的繁殖物候有显著的影响,但与假设相反的是,随着寄主种类数量的增加,五蕊寄生繁殖物候的异步性没有显著提高。这项研究表明,在解释泛性桑寄生植物的繁殖物候异步性及寄主种类的数量对其影响的生态学意义还需进行更深入的探究。 | Manru Li Jin Chen Ling Zhang | 2022 | Journal of Plant Ecology2022，15，2： | 0 |
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