The NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) inflammasome senses pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), and activates caspase-1, which provokes release of proinflammatory cytokines such as interleukin-1β (IL-1β) and IL-18 as well as pyroptosis to engage in innate immune defense. The endoplasmic reticulum (ER) is a large and dynamic endomembrane compartment, critical to cellular function of organelle networks. Recent studies have unveiled the pivotal roles of the ER in NLRP3 inflammasome activation. ER–mitochondria contact sites provide a location for NLRP3 activation, its association with ligands released from or residing in mitochondria, and rapid Ca²⁺ mobilization from ER stores to mitochondria. ER-stress signaling plays a critical role in NLRP3 inflammasome activation. Lipid perturbation and cholesterol trafficking to the ER activate the NLRP3 inflammasome. These findings emphasize the importance of the ER in initiation and regulation of the NLRP3 inflammasome.

Studies have shown that there are differences between the sexes regarding to the occurrence and development of liver diseases, which may be associated with sex hormones. However, the mechanisms behind it are largely unknown. In this study, we first investigated the differences of liver injury between male and female mice, using the CCl₄-induced liver injury mouse model. It showed that the liver damage of male mice was much more severe than that of female mice. Both the acute injury and fibrosis of the liver were reduced when androgens were depleted by castration of male mice. The vulnerability of male liver was associated with testis endocrine and excessive activation of inflammatory response in the liver. Castrated male mice with testosterone supplementation showed aggravated liver inflammatory response and fibrosis. The activity of NOD-like receptor protein 3 (NLRP3) inflammasome was increased when testosterone supplementation was provided. However, the enhanced inflammatory response and fibrosis due to testosterone supplementation were negated by inhibiting the activation of NLRP3 using the specific small molecule inhibitor MCC950. It suggests that testosterone is a key factor that influences liver injury by regulating the NLRP3 inflammasome activation-mediated inflammatory response.

Green pesticides are highly desirable, as they are environmentally friendly and efficient. In this study, the antifungal peptide P852 was employed to suppress Fusarium wilt in the Faba bean. The disease index and a range of physiological and metabolomic analyses were performed to explore the interactions between P852 and the fungal disease. The incidence and disease index of Fusarium wilt were substantially decreased in diseased Faba beans that were treated with two different concentrations of P852 in both the climate chamber and field trial. For the first time, P852 exhibited potent antifungal effects on Fusarium in an open field condition. To explore the mechanisms that underlie P852′s antifungal effects, P852 treatment was found to significantly enhance antioxidant enzyme capacities including guaiacol peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and the activities of antifungal enzymes including chitinase and β-1,3-glucanase, as well as plant dry and fresh weights, and chlorophyll content compared to the control group (p ≤ 0.05). Metabolomics analysis of the diseased Faba bean treated with P852 showed changes in the TCA cycle, biological pathways, and many primary and secondary metabolites. The Faba bean treated with a low concentration of P852 (1 μg/mL, IC₅₀) led to upregulated arginine and isoquinoline alkaloid biosynthesis, whereas those treated with a high concentration of P852 (10 μg/mL, MFC) exhibited enhanced betaine and arginine accumulation. Taken together, these findings suggest that P852 induces plant tolerance under Fusarium attack by enhancing the activities of antioxidant and antifungal enzymes, and restoring plant growth and development.

Type I interferon (IFN) induction is a critical component of innate immune response to viral and bacterial infection, including S. aureus, but whether it activates the signaling in macrophages and the regulation mechanisms is less well understood. Here we show that S. aureus infection promoted the IFN-β mRNA expression and stimulator of IFN genes (STING)/TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)-dependent production of IFN-β. Infection with S. aureus induced caspase recruitment domain and membrane-associated guanylate kinase-like domain protein 3 (CARMA3) expression at both the mRNA and protein levels. The heat-killed bacteria failed to trigger IRF3 phosphorylation and upregulation of CARMA3 expression. However, overexpression of CARMA3 did not affect phosphorylation of TBK1 or IRF3 in RAW264.7 cells, J774A.1 macrophages, and mouse embryonic fibroblast (MEF) cells. In conclusion, S. aureus infection induces STING/TBK1/IRF3-mediated IFN-β production in a CARMA3-independent manner.

Epithelial morphogenesis is a common feature in various organs and contributes to functional formation. However, the molecular mechanisms behind epithelial morphogenesis remain largely unknown. Mammary gland is an excellent model system to investigate the molecular mechanisms of epithelial morphogenesis. In this study, we found that cysteine dioxygenase (CDO), a key enzyme in cysteine oxidative metabolism, was involved in mammary epithelial morphogenesis. CDO knockout (KO) females exhibited severe defects in mammary branching morphogenesis and ductal elongation, resulting in poor lactation. CDO contributes to the luminal epithelial cell differentiation, proliferation, and apoptosis mainly through its downstream product cysteine sulfinic acid (CSA). Exogenous supplementation of CSA not only rescued the defects in CDO KO mouse but also enhanced ductal growth in wild-type mouse. It suggests that CDO regulates luminal epithelial differentiation and regeneration via CSA and consequently contributes to mammary development, which raises important implications for epithelial morphogenesis and pathogenesis of breast cancer.