The hallmark of enzymes from secondary metabolic pathways is the pairing of powerful reactivity with exquisite site selectivity. The application of these biocatalytic tools in organic synthesis, however, remains under-utilized due to limitations in substrate scope and scalability. Here we report the reactivity of a monooxygenase (PikC) from the pikromycin pathway is modified through computationally-guided protein and substrate engineering, and applied to the oxidation of unactivated methylene C-H bonds. Molecular dynamics and quantum mechanical calculations were employed to develop a predictive model for substrate scope, site selectivity, and stereoselectivity of PikC mediated C-H oxidation. A suite of menthol derivatives was screened computationally and evaluated through in vitro reactions where each substrate adhered to the predicted models for selectivity and conversion to product. This platform was also expanded beyond menthol-based substrates to the selective hydroxylation of a variety of substrate cores ranging from cyclic to fused bicyclic and bridged bicyclic compounds.
Purpose To investigate the anxiety and depression levels of frontline clinical nurses working in 14 hospitals in Gansu Province, China, during this period. Design A cross‐sectional survey was conducted online between February 7 and 10, 2020, with a convenience sample of 22,034 nurses working in 14 prefecture and city hospitals in Gansu Province, located in northwest China. Methods A self‐reported questionnaire with four parts (demographic characteristics, general questions related to novel coronavirus‐infected pneumonia, self‐rating anxiety scale, and self‐rating depression scale) was administered. Descriptive statistics including frequencies, means, and SDs were computed. The associations between anxiety and depression with sociodemographic characteristics, work‐related concerns, and impacts were analyzed, followed by multiple stepwise linear regression to identify factors that best predicted the nurses’ anxiety and depression levels. Findings A total of 21,199 questionnaires were checked to be valid, with an effective recovery rate of 96.21%. The mean ± SD age of the respondents was 31.89 ± 7.084 years, and the mean ± SD length of service was 9.40 ± 7.638 years. The majority of the respondents were female (98.6%) and married (73.1%). Some demographic characteristics, related concerns, and impacts of COVID‐19 were found to be significantly associated with both anxiety (p < .001) and depression (p < .001). Nurses who needed to take care of children or elderly relatives, took leave from work because they were worried about COVID‐19, avoided contact with family and friends, and wanted to obtain more COVID‐19‐related knowledge had higher levels of both anxiety and depression. Conclusions Results show that nurses faced with the COVID‐19 outbreak are at risk for experiencing anxiety and depression. Demographic background, psychosocial factors, and work‐related factors predicted the psychological responses. The family responsibilities and burdens of women may explain the higher levels of anxiety and depression among nurses with these obligations as compared to those without. On the other hand, nurses who chose not to take leave from work or who did not avoid going to work during this period were less anxious and depressed. Clinical Relevance Professional commitment might be a protective factor for adverse psychological responses. It is pertinent to provide emotional support for nurses and recognize their professional commitment in providing service to people in need.
Understanding the key factors that influence the preferences of residue-nucleotide interactions in specific protein-RNA interactions has remained a research focus. We propose an effective approach to derive residue-nucleotide propensity potentials through considering both the types of residues and nucleotides, and secondary structure information of proteins and RNAs from the currently largest nonredundant and nonribosomal protein-RNA interaction database. To test the validity of the potentials, we used them to select near-native structures from protein-RNA docking poses. The results show that considering secondary structure information, especially for RNAs, greatly improves the predictive power of pair potentials. The success rate is raised from 50.7 to 65.5% for the top 2000 structures, and the number of cases in which a near-native structure is ranked in top 50 is increased from 7 to 13 out of 17 cases. Furthermore, the exclusion of ribosomes from the database contributes 8.3% to the success rate. In addition, some very interesting findings follow: (i) the protein secondary structure element π-helix is strongly associated with RNA-binding sites; (ii) the nucleotide uracil occurs frequently in the most preferred pairs in which the unpaired and non-Watson-Crick paired uracils are predominant, which is probably significant in evolution. The new residue-nucleotide potentials can be helpful for the progress of protein-RNA docking methods, and for understanding the mechanisms of protein-RNA interactions.
A method for calculating the interaction between a superconductor and a permanent magnet for various initial cooling conditions is proposed. The exact solutions are obtained for the point magnetic dipole over a flat nonideal type-II superconductor. The distinction of the method from the frozen-image method is in the using of the vertical and horizontal movement images that create the same magnetic field distribution outside the superconductor as the trapped fluxes do when the permanent magnet moves vertically and horizontally, respectively. The vertical and lateral forces that are obtained by the method agree with the previous measurements qualitatively. Comparing with the frozen-image method, the method can give the lateral force in zero field cooling and the hysteresis in the vertical and lateral forces. The two characteristics cannot be obtained by the frozen-image method. In this case, the vertical stiffness during vertical traverses and the lateral and cross stiffnesses during lateral traverses are obtained by the analytic expressions of vertical and lateral forces. Those stiffness expressions can reflect the effect of cooling conditions and movement history.
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