Tumor necrosis factor-like cytokine 1A plays a role in inflammatory bowel disease pathogenesis.

The binding of tumor necrosis factor-like cytokine 1A (TL1A) to death receptor 3 (DR3) plays an important role in the interaction between dendritic cells (DCs) and T cells and contributes to intestinal inflammation development. However, the mechanism by which DCs expressing TL1A mediate helper T (Th) cell differentiation in the intestinal lamina propria (LP) during the pathogenesis of inflammatory bowel disease remains unclear. In this study, we found that TL1A/DR3 promoted Th1 and Th17 cell differentiation in T-T and DC-T cell interaction-dependent manners. TL1A-deficient CD4+ T cells failed to polarize into Th1/Th17 cells and did not cause colonic inflammation in a T cell transfer colitis model. Notably, TL1A was located in the cytoplasm and nuclei of DCs, positively regulated the DC-specific ICAM-grabbing nonintegrin/RAF1/nuclear factor κB signaling pathway, enhanced the antigen uptake ability of DCs, and promoted TLR4-mediated DC activation, inducing naive CD4+ T cell differentiation into Th1 and Th17 cells. Our work reveals that TL1A plays a regulatory role in inflammatory bowel disease pathogenesis.

Metabolome and transcriptome profiling in different bagging pear fruit reveals that PbKCS10 affects the occurrence of superficial scald via regulating the wax formation.

Superficial scald is a physiological disorder of fruit, which is easy to occur during long-term cold storage after harvest. Different preharvest bagging treatments (no bagging, polyethylene bagging and non-woven fabric bagging) were used to explore the occurrence mechanism of superficial scald. UHPLC-MS analysis, GC-MS analysis and RNA-seq revealed the influence of the wax of 'Chili' on the occurrence of superficial scald. The wax content and wax components (Lupeol, lup-20(29)-en-3-one, heptacosane, 9-octadecenoic acid, eicosanoic acid, cis-11-eicosenoic acid) were significantly higher in the fruit bagged with non-woven fabric (NWF, with low incidence of superficial scald) than that in fruit bagged with polyethylene (PE, high incidence of superficial scald). Transcriptomics and qRT-PCR data identified a wax synthesis gene, PbKCS10, which exhibited high expression levels in fruit with low of superficial scald. The results of gene function showed that PbKCS10 reduced the occurrence of superficial scald by increasing the wax formation.

Study of Carbon Matrix Composite as Wear-Resistant Plate Material on Improving Wear Resistance and Mixing Effect in Mixing Process.

Silica and carbon black are the most important reinforcing systems in rubber formula. In the process of continuous optimization of the formula, silica gradually replaces carbon black by its characteristics. In view of the wear problem of the components of the mixer chamber caused by the increase in the proportion of silica in the formula, this research applied carbon matrix composite (CMC) materials to wear-resistant plate materials, and compared them with common wear-resistant (CWR) plate materials to explore the impact of replacing CWR plate with CMC on improving wear resistance and mixing effect. The results showed that compared with the CWR plate, CMC wear-resistant plate showed characteristics of a high friction coefficient and low wear rate (reduced by about 23%) in the mixing process of silica compound. However, the friction behavior of carbon black compound and carbon matrix composite wear-resistant plate showed an opposite trend, where the friction coefficient and wear rate increased simultaneously, especially the wear rate that increased by about 35%. The main reasons for the experimental results were related to the characteristics, elemental composition and surface morphology of carbon matrix composite, silica and carbon black. The experimental results also indicated that the carbon matrix composite wear-resistant plate is more suitable for a silica mixing process, and the increasing friction coefficient with decreasing wear rate of wear-resistant plate can further improve the importance of effective friction in mixing and prolonging the service life of wear-resistant plate.

CD30L is involved in the regulation of the inflammatory response through inducing homing and differentiation of monocytes via CCL2/CCR2 axis and NF-κB pathway in mice with colitis.

The pathogenesis of inflammatory bowel diseases (IBD) is complex, and dysregulated immune responses play a pivotal role in its occurrence and development. Our previous studies indicated that CD30L may participate in monocyte-mediated inflammation in patients with UC through the activation of circulating monocytes. However, it remains unclear how CD30L participates in monocyte-mediated inflammation in IBD by activation of circulating monocytes. In this study, we observed an increase in the expression of CD30L and chemokine receptor type 2 (CCR2) on circulating monocytes and pro-inflammatory monocytes in the colon lamina propria in mice with dextran sulfate sodium salt (DSS)-induced colitis. Moreover, there was a positive correlation between the expression levels of CCR2 and CD30L (r = 0.8817, p = 0.0480) in monocytes. In Cd30l-/- mice with DSS-induced colitis, the percentage and absolute number of circulating monocytes and pro-inflammatory monocytes decreased with the downregulation of CCR2. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed the expression of pNF-κB p65, pIκBα, p65 and CCR2 and up-regulated the expression of IκBα in the sorted pro-inflammatory monocytes in Cd30l-/- mice with DSS-induced colitis. The mRNA levels of Ccr2 in the sorted pro-inflammatory monocytes were significantly down-regulated with the presence of immobilized RM153 and inhibitors of NF-κB (BAY 11-7082) in WT mice with DSS-induced colitis. Our results suggested that CD30L could promote the inflammatory response by inducing the homing and differentiation of monocytes via the chemokine ligand 2 (CCL2)/CCR2 axis and NF-κB signaling pathway in mice with colitis. These findings provide a novel target for monocyte-based immunotherapy against IBD.

Aucuboside Inhibits the Generation of Th17 Cells in Mice Colitis.

Aucuboside is an iridoid glycoside extracted from traditional Chinese medicine such as Rehmannia glutinosa, possessing a wide range of biological activities, including antioxidant, anti-aging, anti-inflammatory, and anti-fibrotic effects. The effects of aucuboside on inflammatory bowel disease (IBD) have not been studied. Therefore, the effects of aucuboside on the generation of Foxp3+ regulatory T (Treg) cells and IL-17-producing T helper (Th17) cells in colitis were studied. A mouse colitis model was established by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to mimic human IBD. The generation of Treg and Th17 cells was evaluated by flow cytometry. Aucuboside significantly alleviated colitis symptoms, including weight loss, high disease activity index, and inflammatory responses. The generation of Th17 cells in colitis was significantly inhibited by aucuboside and accompanied by the suppression of IL-17 expression. In Raw264.7 cells, the LPS-induced increase in IL-17 expression was also suppressed by aucuboside, which was significantly blocked by the RORγt inhibitor sr2211. In addition, the decrease in the proportion of Treg cells was also partially reversed by aucuboside, which may reflect the aucuboside-induced inhibition of Th17 cells. This previously unrecognized immunoregulatory function of aucuboside may have clinical applications in IBD.