Silicosis is a lung inflammatory disease caused by chronic exposure to crystalline silica (CS). Leukotriene B (LTB) plays an important role in neutrophilic inflammation, which drives silicosis and promotes lung cancer. In this study, we examined the mechanisms involved in CS-induced inflammatory pathways. Phagocytosis of CS particles is essential for the production of LTB and IL-1β in mouse macrophages, mast cells, and neutrophils. Phagosomes enclosing CS particles trigger the assembly of lipidosome in the cytoplasm, which is likely the primary source of CS-induced LTB production. Activation of the JNK pathway is essential for both CS-induced LTB and IL-1β production. Studies with bafilomycin-A1- and NLRP3-deficient mice revealed that LTB synthesis in the lipidosome is independent of inflammasome activation. Small interfering RNA knockdown and confocal microscopy studies showed that GTPases Rab5c, Rab40c along with JNK1 are essential for lipidosome formation and LTB production. BI-78D3, a JNK inhibitor, abrogated CS-induced neutrophilic inflammation in vivo in an air pouch model. These results highlight an inflammasome-independent and JNK activation-dependent lipidosome pathway as a regulator of LTB synthesis and CS-induced sterile inflammation.

High aspect ratio zinc oxide nanowires (ZnONWs) have become one of the most important products in nanotechnology. The wide range applications of ZnONWs have heightened the need for evaluating the risks and biological consequences to these particles. In this study, we investigated inflammatory pathways activated by ZnONWs in cultured cells as well as the consequences of systemic exposure in mouse models. Confocal microscopy showed rapid phagocytic uptake of FITC-ZnONWs by macrophages. Exposure of macrophages or lung epithelial cells to ZnONWs induced the production of CCL2 and CCL11. Moreover, ZnONWs exposure induced both IL-6 and TNF-α production only in macrophages but not in LKR13 cells. Intratracheal instillation of ZnONWs in C57BL/6 mice induced a significant increase in the total numbers of immune cells in the broncho alveolar lavage fluid (BALFs) 2 days after instillation. Macrophages and eosinophils were the predominant cellular infiltrates of ZnONWs exposed mouse lungs. Similar cellular infiltrates were also observed in a mouse air-pouch model. Pro-inflammatory cytokines IL-6 and TNF-α as well as chemokines CCL11, and CCL2 were increased both in BALFs and air-pouch lavage fluids. These results suggest that exposure to ZnONWs may induce distinct inflammatory responses through phagocytic uptake and formation of soluble Zn2+ ions.

Palm kernel meal (PKM) has been shown to be a high‐quality protein source in ruminant feeds. This study focused on the effects of feed, supplemented with different amounts of PKM (ZL‐0 as blank group, and ZL‐15, ZL‐18, and ZL‐21 as treatment group), on the quality and flavor profile of Tibetan sheep meat. Furthermore, the deposition of beneficial metabolites in Tibetan sheep and the composition of rumen microorganisms on underlying regulatory mechanisms of meat quality were studied based on ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry as well as 16S rDNA sequencing. The results of the study showed that Tibetan sheep in the ZL‐18 group exhibited superior eating quality and flavor profile while depositing more protein and fat relative to the other groups. The ZL‐18 group also changed significantly in terms of the concentration and metabolic pathways of meat metabolites, as revealed by metabolomics. Metabolomics and correlation analyses finally showed that PKM feed mainly affected carbohydrate metabolism in muscle, which in turn affects meat pH, tenderness, and flavor. In addition, 18% of PKM increased the abundance of Christensenellaceae R‐7 group, Ruminococcaceae UCG‐013, Lachnospiraceae UCG‐002, and Family XIII AD3011 group in the rumen but decreased the abundance of Prevotella 1; the above bacteria groups regulate meat quality by regulating rumen metabolites (succinic acid, DL‐glutamic acid, etc.). Overall, the addition of PKM may improve the quality and flavor of the meat by affecting muscle metabolism and microorganisms in the rumen.