Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein. 相似文献
Silicon - Following our interest in exotic silylenes, here we compare and contrast 20 novel five-membered cyclic silylenes, including saturated (sila)0–4 cyclopentasilylenes (1–10) and... 相似文献
We focus on the quantitative and local topological properties of range images. We consider the spaces Mm of m × m high-contrast patches of range images for m=?3, 5, 7, 9, 11. Using computational topological tools to analyze range image patches, we detect that M3 (M9, M11) has core subsets with the topology of a circle, M3, M5, M7, M9 and that M11 have some subspaces with the topology of a Klein bottle. We also discover that the largest subspace with the Klein bottle’s topology decreases as the measurements of patches increase, which generalizes the results in the paper of H. Adams and G. Carlsson, and demonstrates properties among optical images and range image patches, which are more similar than those established by Lee et al.
Reflective judgement is crucial for medical-related practitioners in dealing with controversial issues. However, the conformity phenomenon is likely to occur and interfere with reflective judgement learning during interactive activities. Effective strategies are required to moderate the conformity behaviour tendency (CBT) and improve reflective judgement performance (RJP). This study demonstrates two significant results: (a) Compared with the guided self-reflection learning strategy, the online collective reflection (OCR) learning strategy effectively weakened the learners' general CBT while dealing with professional controversial issues; and (b) a significantly negative correlation between the RJP achieved and the change of CBT in online environment was detected in the OCR group. The implications and potential applications in higher education were discussed. Further studies are needed to confirm the long-term effects and the extending application to other professional studies. 相似文献
Based on the potential therapeutic value in targeting mitochondria and the fluorophore tracing ability, a fluorescent mitochondria-targeted organic arsenical PDT-PAO-F16 was fabricated, which not only visualized the cellular distribution, but also exerted anti-cancer activity in vitro and in vivo via targeting pyruvate dehydrogenase complex (PDHC) and respiratory chain complexes in mitochondria. In details, PDT-PAO-F16 mainly accumulated into mitochondria within hours and suppressed the activity of PDHC resulting in the inhibition of ATP synthesis and thermogenesis disorder. Moreover, the suppression of respiratory chain complex I and IV accelerated the mitochondrial dysfunction leading to caspase family-dependent apoptosis. In vivo, the acute promyelocytic leukemia was greatly alleviated in the PDT-PAO-F16 treated group in APL mice model. Our results demonstrated the organic arsenical precursor with fluorescence imaging and target-anticancer efficacy is a promising anticancer drug. 相似文献