Cyclic GMP–AMP (cGAMP) is a second messenger that activates the stimulator of interferon genes (STING) innate immune pathway to induce the expression of type I interferons (IFNs) and other cytokines. Pharmacological activation of STING is considered a potent therapeutic strategy in cancer. In this study, we employed a cell-based phenotypic screen and identified podophyllotoxin (podofilox), a microtubule destabilizer, as a robust enhancer of the cGAMP–STING signaling pathway. We found that podofilox enhanced the cGAMP-mediated immune response by increasing STING-containing membrane puncta and the extent of STING oligomerization. Furthermore, podofilox changed the trafficking pattern of STING and delayed trafficking-mediated STING degradation. Importantly, the combination of cGAMP and podofilox had profound antitumor effects on mice by activating the immune response through host STING signaling. Together, these data provide insights into the regulation of cGAMP–STING pathway activation and demonstrate what we believe to be a novel approach for modulating this pathway and thereby promoting antitumor immunity.
Teaching for creativity (TfC) has received increasing attention as an important way to cultivate students’ creative thinking and behaviors. The purpose of this study is to examine the mediating role of teachers’ work engagement (WE) on the relationship between their emotional intelligence (EI) and teaching for creativity. The study is a cross-sectional design. The sample of the study is 3,307 secondary school English teachers working in Jilin Province, China. The findings show that the teachers’ perceptions of emotional intelligence, work engagement and teaching for creativity are relatively high. The findings confirm the hypotheses. The results of structural equation modeling and bootstrapping show that teachers’ emotional intelligence is positively correlated with work engagement and teaching for creativity, and teachers’ work engagement mediates the relationship between emotional intelligence and teaching for creativity.
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