Shionone-Targeted Pneumolysin to Ameliorate Acute Lung Injury Induced by Streptococcus pneumoniae In Vivo and In Vitro.

Streptococcus pneumoniae (S. pneumoniae), as a Gram-positive bacterium, can cause severe bacterial pneumonia, and result in high morbidity and mortality in infected people. Meanwhile, isolated drug-resistant S. pneumoniae is growing, which raises concerns about strategies for combatting S. pneumoniae infection. To disturb S. pneumoniae pathogenicity and its drug-resistance, developing novel anti-infective strategies or compounds is urgent. In this study, the anti-infective effect of shionone was explored. A minimum inhibitory concentration (MIC) assay and growth curve determination were performed to evaluate the effect of the tetracyclic triterpenoid compound shionone against S. pneumoniae. Hemolysis tests, western blotting, oligomerization inhibition assays, and molecular docking were carried out to explore the anti-infective mechanism of shionone. Moreover, the protective effect of shionone was also confirmed in a mousepneumonia model. The results showed that the excellent hemolytic inhibitory activity of shionone was observed at less than 8 µg/mL. Meanwhile, shionone could disturb the oligomerization of pneumolysin (PLY) but did not interfere with PLY expression at less than 4 µg/mL. Molecular docking suggested that shionone targeted the ASP-59, ILE-60, THR-57, PHE-344, and ASN-346 amino acid sites to reduce S. pneumoniae pathogenicity. Furthermore, shionone alleviated lung histopathologic injury and decreased lung bacterial colonization in vivo. The above results showed that shionone could bind to the PLY active pocket under the concentrations of 8 µg/mL and neutralize PLY hemolysis activity to reduce S. pneumoniae pathogenicity in vitro and in vivo.

Wish-making during the COVID-19 pandemic enhances positive appraisals and job satisfaction.

Guided by cognitive appraisal theory, we argue that wish-making is a conceptually distinct type of coping strategy and that wish-making during the COVID-19 pandemic has functional cognitive-affective consequences. Specifically, it facilitates positive appraisals of the pandemic, which then facilitate job satisfaction. Enhanced job satisfaction in turn reduces counterproductive work behavior during the pandemic. These arguments were tested via two empirical studies involving 546 Hong Kong employees surveyed on two consecutive working days during the pandemic. The individuals who made wishes during the pandemic reported more positive appraisals of the pandemic, which in turn promoted their job satisfaction and lowered their counterproductive work behavior. Crucially, wish-making had significant effects on positive appraisals above and beyond other coping strategies. Thus, we contribute to the employee coping literature by highlighting one relatively easy way for employees to combat the psychological effects of the pandemic (and other challenges in life) and regulate their affective well-being and behaviors at work. Namely, making wishes that envision a better future can enhance employees' job satisfaction, which in turn lowers counterproductive work behavior.