The ongoing outbreak of COVID-19 has been a serious threat to human health worldwide. The virus SARS-CoV-2 initiates its infection to the human body via the interaction of its spike (S) protein with the human Angiotensin-Converting Enzyme 2 (ACE2) of the host cells. Therefore, understanding the fundamental mechanisms of how SARS-CoV-2 S protein receptor binding domain (RBD) binds to ACE2 is highly demanded for developing treatments for COVID-19. Here we implemented multi-scale computational approaches to study the binding mechanisms of human ACE2 and S proteins of both SARS-CoV and SARS-CoV-2. Electrostatic features, including electrostatic potential, electric field lines, and electrostatic forces of SARS-CoV and SARS-CoV-2 were calculated and compared in detail. The results demonstrate that SARS-CoV and SARS-CoV-2 S proteins are both attractive to ACE2 by electrostatic forces even at different distances. However, the residues contributing to the electrostatic features are quite different due to the mutations between SARS-CoV S protein and SARS-CoV-2 S protein. Such differences are analyzed comprehensively. Compared to SARS-CoV, the SARS-CoV-2 binds with ACE2 using a more robust strategy: The electric field line related residues are distributed quite differently, which results in a more robust binding strategy of SARS-CoV-2. Also, SARS-CoV-2 has a higher electric field line density than that of SARS-CoV, which indicates stronger interaction between SARS-CoV-2 and ACE2, compared to that of SARS-CoV. Key residues involved in salt bridges and hydrogen bonds are identified in this study, which may help the future drug design against COVID-19.
Cervical cancer (CC) is the second most common malignant cancer in women. CC is difficult to diagnose, has a high recurrence rate, and is resistant to systemic therapies; as a result, CC patients have a relatively poor prognosis. One potential link to CC is the Wnt signaling pathway and its downstream effectors, which regulate cell differentiation, proliferation, migration, and fate. The aberrant activation of Wnt signaling is associated with various cancers, including CC. Recent studies have shown that activating or inhibiting the intracellular signal transduction in this pathway can regulate cancer cell growth and viability. This review will summarize the experimental evidence supporting the significance of the Wnt signaling pathway in CC, and will also discuss the current clinical role of Wnt signaling in CC diagnosis, therapy, and prognosis.
Aim:To investigate the mechanism leading to in vivo carbapenem resistance development in Klebsiella pneumoniae. Methods: Carbapenemase was detected using the modified carbapenem inactivation method. β-lactamases resistant genes were identified by PCR and sequencing. Clonal relatedness was evaluated by random amplified polymorphic DNA and multiple locus sequence typing. The relationship between sequence typing and resistant genes was analyzed by using the chi-squared test. Results: All ST37 carbapenem-resistant isolates were bla OXA-1 positive and all ST37 carbapenem-sensitive isolates were bla OXA-1 negative at Stage I. A significant relationship between carbapenem resistance and bla OXA-1 was observed. The bla OXA-1 -positive rate was significantly higher in ST37 K. pneumoniae than others. Conclusion: This is the first study about the development of carbapenem resistance in vivo potentially mediated by bla OXA-1 in ST37 K. pneumoniae among neonates.
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