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| 1 | SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation显示文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is the ongoing global pandemic that poses substantial challenges to public health worldwide.A subset of COVID-19 patients experience systemic inflammatory response,known as cytokine storm,which may lead to death.Receptor-interacting serine/threonine-protein kinase 1(RIPK1)is an important mediator of inflammation and cell death.Here,we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection.We found evidence of RIPK1 activation in human COVID-19 lung pathological samples,and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2.Inhibition of RIPK1 using multiple smallmolecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids.Furthermore,therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load,and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice.Mechanistically,we found that the RNA-dependent RNA polymerase of SARS-CoV-2,NSP12,a highly conserved central component of coronaviral replication and transcription machinery,promoted the activation of RIPK1.Furthermore,NSP12323L variant,encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy,Italy,that carries a Pro323Leu amino acid substitution in NSP12,showed increased ability to activate RIPK1.Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells.Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19. | Gang Xu Ying Li Shengyuan Zhang Haoran Peng Yunyun Wang Dekang Li Taijie Jin Zhuohao He Yilun Tong Chunting Qi Guowei Wu Kangyun Dong Jizhou Gou Yang Liu Tongyang Xiao Jing Qu Liang Li Liang Liu Ping Zhao Zheng Zhang Junying Yuan | 2021 | Cell Research2021，31，12： | 6 |
| 2 | Estrogen Receptor-A in Medial Preoptic Area Contributes to Sex Difference of Mice in Response to Sevoflurane Anesthesia显示文摘A growing number of studies have identified sex differences in response to general anesthesia;however,the underlying neural mechanisms are unclear.The medial preoptic area(MPA),an important sexually dimorphic structure and a critical hub for regulating consciousness transition,is enriched with estrogen receptor alpha(ERa),particularly in neuronal clusters that participate in regulating sleep.We found that male mice were more sensitive to sevoflurane.Pharmacological inhibition of ERαin the MPA abolished the sex differences in sevoflurane anesthesia,in particular by extending the induction time and facilitating emergence in males but not in females.Suppression of ERαin vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females.Furthermore,ERα.knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia.Collectively,MPA ERαpositively regulates the activity of MPA GABAergic neurons in males but not in females,which contributes to the sexdifference of mice in sevoflurane anesthesia. | Yunyun Zhang Huiming Li Xinxin Zhang Sa Wang Dan Wang Jiajia Wang Tingting Tong Zhen Zhang Qianzi Yang Hailong Dong | 2022 | Neuroscience Bulletin2022，38，7： | 1 |
| 3 | Analysis of risk factors of ST-segment elevation myocardial infarction in young patients显示文摘 | Yunyun W Tong L Yingwu L | 2014 | BMC Cardiovasc Disord2014，14，： | 1 |
| 4 | A single-cell transcriptome atlas of the aging human and macaque retina显示文摘The human retina is a complex neural tissue that detects light and sends visual information to the brain.However,the molecular and cellular processes that underlie aging primate retina remain unclear.Here,we provide a comprehensive transcriptomic atlas based on 119520 single cells of the foveal and peripheral retina of humans and macaques covering different ages.The molecular features of retinal cells differed between the two species,suggesting distinct regional and species specializations of the human and macaque retinae.In addition,human retinal aging occurred in a region-and cell-type-specific manner.Aging of human retina exhibited a foveal to peripheral gradient.MYO9A-rods and a horizontal cell subtype were greatly reduced in aging retina,indicating their vulnerability to aging.Moreover,we generated a dataset showing the cell-type-and region-specific gene expression associated with 55 types of human retinal disease,which provides a foundation to understanding of the molecular and cellular mechanisms underlying human retinal diseases.Such datasets are valuable to understanding of the molecular characteristics of primate retina,as well as molecular regulation of aging progression and related diseases. | Wenyang Yi Yufeng Lu Suijuan Zhong Mei Zhang Le Sun Hao Dong Mengdi Wang Min Wei Haohuan Xie Hongqiang Qu Rongmei Peng Jing Hong Ziqin Yao Yunyun Tong Wei Wang Qiang Ma Zeyuan Liu Yuqian Ma Shouzhen Li Chonghai Yin Jianwei Liu Chao Ma Xiaoqun Wang Qian Wu Tian Xue | 2021 | National Science Review2021，8，4： | 1 |
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