The outbreak of Coronavirus Disease 2019 (COVID-19) posed a powerful threat to human life. The preventive behaviors of individuals (e.g., home quarantine, disinfection, and wearing masks) play a key role in preserving and controlling the disease. In this case, as a motivational psychological system oriented toward avoiding infection, the behavioral immune system (BIS) may be activated and link to preventive behaviors. This study investigated the mechanisms through which emotional and cognitive processes resulted by BIS have promoted preventive behaviors in relation to COVID-19. We collected data on 22,005 active Sina Weibo users from 31 December 2019 to 8 February 2020 to measure their emotions (including disgust, happiness, and fear), cultural values (individualism and collectivism), moral concern (including purity vice, fairness vice, and authority virtue), and behavioral intentions (including isolation intention, protection intention, and aid intention) using Text Mind software and related dictionaries. Multiple regression and mediation analyses were performed to explore the relationships among variables. The results showed seven complete mediation paths (such as disgust–purity vice–protection intention). Each of these paths describes the effects of cognitive processes caused by BIS on preventive behaviors. We inferred that there may be path mechanisms such as disgust–cognitive processes–preventive behaviors. Using these results, policy makers can take appropriate measures to intervene in preventive behaviors (e.g., by posting disgusting images on social media to evoke disgust). The results can be used to explain differences in preventive behaviors among populations even in the face of similar thread levels. Furthermore, our research provides empirical evidence for the hypothesis of pathogen prevalence.

Pharmacological vitamin C (VC) is a potential natural compound for cancer treatment. However, the mechanism underlying its antitumor effects remains unclear. In this study, we found that pharmacological VC significantly inhibits the mTOR (including mTORC1 and mTORC2) pathway activation and promotes GSK3-FBXW7-mediated Rictor ubiquitination and degradation by increasing the cellular ROS. Moreover, we identified that HMOX1 is a checkpoint for pharmacological-VC-mediated mTOR inactivation, and the deletion of FBXW7 or HMOX1 suppresses the regulation of pharmacological VC on mTOR activation, cell size, cell viability, and autophagy. More importantly, it was observed that the inhibition of mTOR by pharmacological VC supplementation in vivo produces positive therapeutic responses in tumor growth, while HMOX1 deficiency rescues the inhibitory effect of pharmacological VC on tumor growth. These results demonstrate that VC influences cellular activities and tumor growth by inhibiting the mTOR pathway through Rictor and HMOX1, which may have therapeutic potential for cancer treatment.

Evidence shows that short-chain fatty acids (SCFAs) play an important role in health maintenance and disease development. In particular, butyrate is known to induce apoptosis and autophagy. However, it remains largely unclear whether butyrate can regulate cell ferroptosis, and the mechanism by which has not been studied. In this study, we found that RAS-selective lethal compound 3 (RSL3)- and erastin-induced cell ferroptosis were enhanced by sodium butyrate (NaB). With regard to the underlying mechanism, our results showed that NaB promoted ferroptosis by inducing lipid ROS production via downregulating the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Moreover, the FFAR2-AKT-NRF2 axis and FFAR2-mTORC1 axis accounts for the NaB-mediated downregulation of SLC7A11 and GPX4, respectively, in a cAMP-PKA-dependent manner. Functionally, we found that NaB can inhibit tumor growth and the inhibitory effect could be eliminated by administrating MHY1485 (mTORC1 activator) and Ferr-1 (ferroptosis inhibitor). Altogether, in vivo results suggest that NaB treatment is correlated to the mTOR-dependent ferroptosis and consequent tumor growth through xenografts and colitis-associated colorectal tumorigenesis, implicating the potential clinical applications of NaB for future colorectal cancer treatments. Based on all these findings, we have proposed a regulatory mechanism via which butyrate inhibits the mTOR pathway to control ferroptosis and consequent tumorigenesis.

No abstract

The amino acid-stimulated Rag GTPase pathway is one of the main pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation and function, but little is known about the effects of growth factors on Rag GTPase-mediated mTORC1 activation. Here, a highly conserved insulin-responsive phosphorylation site on folliculin (FLCN), Ser62, that is phosphorylates by AKT1 is identified and characterized. mTORC2-AKT1 is localized on lysosomes, and RagD-specific recruitment of mTORC2-AKT1 on lysosomes is identified as an essential step in insulin-AKT1-mediated FLCN phosphorylation. Additionally, FLCN phosphorylation inhibits the activity of RagC GTPase and is essential for insulin-induced mTORC1 activation. Functionally, phosphorylated FLCN promotes cell viability and induces autophagy, and also regulates in vivo tumor growth in an mTORC1-dependent manner. Its expression is also positively correlated with mTORC1 activity in colon cancer, clear cell renal cell carcinoma, and chordoma. These results indicate that FLCN is an important intermediate for cross-talk between the amino acid and growth factor pathways. Further, FLCN phosphorylation may be a promising therapeutic target for diseases characterized by mTORC1 dysregulation.