ABSTRACT
Tuberculosis is the second leading cause of death by infectious disease worldwide after COVID-19. Mycobacterium tuberculosis, which causes tuberculosis, is showing alarming levels of resistance to first-line antibiotics, jeopardizing efforts to eradicate the disease. Research is underway to develop new, safer drugs to treat drug resistant tuberculosis. One of these breakthrough drugs is bedaquiline, which targets the mycobacterial ATP synthase, an essential enzyme in mycobacteria. The success of bedaquiline, which has become a cornerstone of treatment for multidrug-resistant and extensively drug-resistant tuberculosis, demonstrates the importance of the mycobacterial ATP synthase as a key drug target against M. tuberculosis. Since the discovery of bedaquiline in 2005, there has been a renewed interest in developing new and improved mycobacterial ATP synthase inhibitors. We have determined electron cryomicroscopy structures of M. smegmatis ATP synthase in complex with inhibitors. We provide detailed mechanistic and structural insights into the mode of action of these compounds, which will support medicinal chemistry efforts to design new tuberculosis drugs. Our work reveals new inhibitor binding sites in the enzyme, opening the route for development of new classes of compounds and improved inhibitors. Copyright © 2022
ABSTRACT
The COVID-19 outbreak has raised awareness of the importance of increased motivation and resilience in nurses. To explore the level of nurse Job involvement in Z hospital in Zhuhai city of China, and the influence of Organizational justice and Organizational identity, a total of 125 nurses in Z hospital in Zhuhai city, Guangdong province, were selected by convenient sampling method and investigated with general information questionnaire, Organizational justice, Organizational identity,and Job involvement Scale. There were 114 valid questionnaires returned;The scores of nurse's Organizational justice, Distributive justice, Procedural justice and Interactive justice, Organizational identity,and Job involvement were 3.532±0.581, 3.397±0.691, 3.487±0.729, 3.840±0.641 and 3.912±0.615 respectively. The score of organization justice positively correlated with the scores of Organizational identity (r=0.627, P<0.001), and positively correlated with the score of Job involvement (r=0.627,P<0.001). The scores of Organizational identity were positively correlated with the score of Job involvement (r=0.724,P<0.001). The results of regression analysis showed that Organizational justice, Organizational identity can positively affect nurses' Job involvement, and explained 59.9% of the cumulative variance. At the same time,Organization identity played a partial mediating role between Organizational justice, as well as its three sub-dimensions and Job involvement. The scores of Organizational justice and Job involvement in selected nurses in Zhuhai are only a little higher than the average levels, which needs to be improved. The perceived Interactive justice is high while the Distributive justice is low. Nurses' Job involvement and Organizational identity can be promoted directly by increasing Distributive justice, followed by Interactive justice and Procedural justice. © The Authors, published by EDP Sciences, 2021.