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291.
Shuai Ma Shuhui Sun Jiaming Li Yanling Fan Jing Qu Liang Sun Si Wang Yiyuan Zhang Shanshan Yang Zunpeng Liu Zeming Wu Sheng Zhang Qiaoran Wang Aihua Zheng Shuguang Duo Yang Yu Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Moshi Song Weiqi Zhang Guang-Hui Liu 《Cell research》2021,(4):415-432
Aging is a major risk factor for many diseases,especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Diseas... 相似文献
292.
Bingqing Xia Xurui Shen Yang He Xiaoyan Pan Feng-Liang Liu Yi Wang Feipu Yang Sui Fang Yan Wu Zilei Duan Xiaoli Zuo Zhuqing Xie Xiangrui Jiang Ling Xu Hao Chi Shuangqu Li Qian Meng Hu Zhou Yubo Zhou Xi Cheng Xiaoming Xin Lin Jin Hai-Lin Zhang Dan-Dan Yu Ming-Hua Li Xiao-Li Feng Jiekai Chen Hualiang Jiang Gengfu Xiao Yong-Tang Zheng Lei-Ke Zhang Jingshan Shen Jia Li Zhaobing Gao 《Cell research》2021,31(8):847-860
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology 相似文献
293.
【目的】生物启发的细菌表面仿生矿化人造矿物壳被用于保护活细胞。【方法】将细菌限制在坚固而完整的矿物壳中,有限的物理空间和物质交换使其暂时进行休眠,降低长期保存期间的活力损失以及提高在各种极端环境中的生存能力,并且能够通过酸去除矿物壳而重新激活细菌。【结果】相较于未仿生矿化的细菌(EcN),矿化细菌(EcN@CaCO3)在32 d的储存实验中活力最高提升262倍;在pH 2.5的强酸环境中存活率提高837倍;在pH 12.0的强碱环境中存活率提高171倍;在80 ℃的高温条件下存活率提高59.1倍;甚至在抗生素溶液中,EcN@CaCO3中细菌的存活率是EcN的729.7倍。【结论】本研究利用仿生矿化提高了细菌的保存稳定性,使其能在酸刺激下去除涂层恢复活性,也能在极端环境下保留细菌的活力,为微生物在环境生态、食品制造和生物医药等领域的应用提供研究基础。 相似文献
294.
Qiang Lv Shuang Han Lei Wang Jinchan Xia Peng Li Ruoyang Hu Jinzheng Wang Lei Gao Yuli Chen Yu Wang Jing Du Fang Bao Yong Hu Xingzhi Xu Wei Xiao Yikun He 《Nucleic acids research》2022,50(12):6820
Nitric oxide (NO) is a key player in numerous physiological processes. Excessive NO induces DNA damage, but how plants respond to this damage remains unclear. We screened and identified an Arabidopsis NO hypersensitive mutant and found it to be allelic to TEBICHI/POLQ, encoding DNA polymerase θ. The teb mutant plants were preferentially sensitive to NO- and its derivative peroxynitrite-induced DNA damage and subsequent double-strand breaks (DSBs). Inactivation of TEB caused the accumulation of spontaneous DSBs largely attributed to endogenous NO and was synergistic to DSB repair pathway mutations with respect to growth. These effects were manifested in the presence of NO-inducing agents and relieved by NO scavengers. NO induced G2/M cell cycle arrest in the teb mutant, indicative of stalled replication forks. Genetic analyses indicate that Polθ is required for translesion DNA synthesis across NO-induced lesions, but not oxidation-induced lesions. Whole-genome sequencing revealed that Polθ bypasses NO-induced base adducts in an error-free manner and generates mutations characteristic of Polθ-mediated end joining. Our experimental data collectively suggests that Polθ plays dual roles in protecting plants from NO-induced DNA damage. Since Polθ is conserved in higher eukaryotes, mammalian Polθ may also be required for balancing NO physiological signaling and genotoxicity. 相似文献
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298.
Yu Shang Li Li Tengfei Zhang Qingping Luo Qingzhong Yu Zhe Zeng Lintao Li Miaomiao Jia Guoyi Tang Sanlin Fan Qin Lu Wenting Zhang Yuhan Xue Hongling Wang Wei Liu Hongcai Wang Rongrong Zhang Chan Ding Huabin Shao Guoyuan Wen 《PLoS pathogens》2022,18(6)
The development of thermostable vaccines can relieve the bottleneck of existing vaccines caused by thermal instability and subsequent poor efficacy, which is one of the predominant reasons for the millions of deaths caused by vaccine-preventable diseases. Research into the mechanism of viral thermostability may provide strategies for developing thermostable vaccines. Using Newcastle disease virus (NDV) as model, we identified the negative surface charge of attachment glycoprotein as a novel determinant of viral thermostability. It prevented the temperature-induced aggregation of glycoprotein and subsequent detachment from virion surface. Then structural stability of virion surface was improved and virus could bind to and infect cells efficiently after heat-treatment. Employing the approach of surface charge engineering, thermal stability of NDV and influenza A virus (IAV) vaccines was successfully improved. The increase in the level of vaccine thermal stability was determined by the value-added in the negative surface charge of the attachment glycoprotein. The engineered live and inactivated vaccines could be used efficiently after storage at 37°C for at least 10 and 60 days, respectively. Thus, our results revealed a novel surface-charge-mediated link between HN protein and NDV thermostability, which could be used to design thermal stable NDV and IAV vaccines rationally. 相似文献
299.
LRG‐1 promotes fat graft survival through the RAB31‐mediated inhibition of hypoxia‐induced apoptosis
Chiakang Ho Danning Zheng Jiaming Sun Dongsheng Wen Shan Wu Li Yu Ya Gao Yifan Zhang Qingfeng Li 《Journal of cellular and molecular medicine》2022,26(11):3153
Autologous adipose tissue is an ideal soft tissue filling material, and its biocompatibility is better than that of artificial tissue substitutes, foreign bodies and heterogeneous materials. Although autologous fat transplantation has many advantages, the low retention rate of adipose tissue limits its clinical application. Here, we identified a secretory glycoprotein, leucine‐rich‐alpha‐2‐glycoprotein 1 (LRG‐1), that could promote fat graft survival through RAB31‐mediated inhibition of hypoxia‐induced apoptosis. We showed that LRG‐1 injection significantly increased the maintenance of fat volume and weight compared with the control. In addition, higher fat integrity, more viable adipocytes and fewer apoptotic cells were observed in the LRG‐1‐treated groups. Furthermore, we discovered that LRG‐1 could reduce the ADSC apoptosis induced by hypoxic conditions. The mechanism underlying the LRG‐1‐mediated suppression of the ADSC apoptosis induced by hypoxia was mediated by the upregulation of RAB31 expression. Using LRG‐1 for fat grafts may prove to be clinically successful for increasing the retention rate of transplanted fat. 相似文献