Immune checkpoint inhibitors (ICIs) have made breakthrough progress in the treatment of various malignant tumors. However, only some patients receiving ICIs obtain long-lasting clinical effects, and some patients still do not achieve remission. Improving the treatment benefits of this part of the population has become a concern of clinicians. IL-1 signaling plays an important role in the tumor microenvironment (TME). However, the relationship between the IL-1 signaling mutation status and the prognosis of colon adenocarcinoma (COAD) patients receiving ICIs has not been reported. We downloaded the data of a COAD cohort receiving ICIs, including prognostic data and mutation data. Additionally, we downloaded the data of a COAD cohort from The Cancer Genome Atlas (TCGA) database, including clinical data, expression data and mutation data. Gene set enrichment analysis (GSEA) was used to assess differences in the activity of some key physiological pathways between the IL-1 signaling mutated-type (IL-1-MT) and IL-1 signaling wild-type (IL-1-WT) groups. The CIBERSORT algorithm was used to evaluate the contents of immune cells in the TME of COAD patients. The multivariate Cox regression model results suggested that IL-1-MT can be used as an independent predictor of a better prognosis in COAD patients receiving ICIs (P = 0.03, HR = 0.269, 95% CI: 0.082-0.883). Additionally, IL-1-MT COAD patients had significantly longer overall survival (OS) (log-rank P = 0.015). CIBERSORT analysis showed that the IL-1-MT group had high infiltration levels of activated dendritic cells (DCs), M1 macrophages, neutrophils, activated natural killer (NK) cells, activated CD4+ memory T cells and CD8+ T cells. Similarly, the IL-1-MT group had significantly upregulated immunogenicity, including in terms of the tumor mutation burden (TMB), neoantigen load (NAL) and number of mutations in DNA damage repair (DDR) signaling. GSEA showed that the IL-1-MT group was highly enriched in the immune response and proinflammatory mediators. Additionally, the expression levels of immune-related genes, immune checkpoint molecules and immune-related signatures were significantly higher in the IL-1-MT group than in the IL-1-WT group. IL-1-MT may be an independent predictor of a good prognosis in COAD patients receiving ICIs, with significantly longer OS in IL-1-MT COAD patients. Additionally, IL-1-MT was associated with significantly increased immunogenicity, activated immune cell and inflammatory mediator levels and immune response-related scores.
Electrical synaptic transmission is an essential form of interneuronal communication which is mediated by gap junctions that permit ion flow. Three gene families (connexins, innexins, and pannexins) have evolved to form gap junctional channels. Each gap junctional channel is formed by the docking of the hemichannel of one cell with the corresponding hemichannel of an adjacent cell. To date, there has been a lack of study models to describe this structure in detail. In this study, we demonstrate that numerical simulations suggest that the passive transmembrane ion transport model, based on the generality of ion channels, also applies to hemichannels in non-junctional plasma membranes. On this basis, we established a gap junctional channel model, which describes hemichannels' docking. We simulated homotypic and heterotypic gap junctions formed by connexins, innexins, and pannexins. Based on the numerical results and our theoretical model, we discussed the physiology of hemichannels and gap junctions, including ion blockage of hemichannels, voltage gating of gap junctions, and asymmetry and delay of electrical synaptic transmission, for which the numerical simulations are first comprehensively realized.
After the reform and opening up, China's wooden furniture industry has made great progress. The production of wooden furniture has continued to grow, and the total amount of exports is also steadily increasing. Wooden furniture is also an integral part of our daily life. As China's economy continues to develop, the demand for wooden furniture is increasing and the proportion of its exports is rising year on year. Since China's accession to the WTO, China's exports of wooden furniture have gradually expanded and China's influence and competitiveness in the international market has increased. However, there are still many problems in China's wooden furniture export trade, including the export market being too congregated and facing trade barriers; facing competitive pressure from the markets of emerging countries, led by Vietnam; increasing export costs and low added value of products; and a single product structure and weak brand awareness. The main reason for these problems is that the export value of Chinese wooden furniture products is small, the export scale is not large, and the export scale fluctuates; the export product structure is simple, of which bedroom wooden furniture occupies a large proportion; the export market structure is too aggregated, mainly in the United States. Therefore, China's wooden furniture industry should continue to optimize the market structure of products, and actively respond to trade barriers; actively respond to the challenges from the international market, to strengthen international competitiveness; constantly adjust the product structure, establish and strengthen brand awareness, to create high-quality, high value-added wooden furniture products, in order to promote the development of wooden furniture export trade.
Electrical synaptic transmission is an essential form of interneuronal communication, mediated by gap junctions that permit ion flow. Three gene families (connexins, innexins, and pannexins) have evolved to form gap junctional channels. Each gap junctional channel is formed by the docking of the hemichannel of one cell with the corresponding hemichannel of an adjacent cell. To date, there is a lack of models describing this structure in detail. In this study, we demonstrate that numerical simulations suggest that the passive transmembrane ion transport model, based on the generality of ion channels, also applies to hemichannels in non-junctional plasma membranes. On this basis, we established a gap junctional channel model, which describes hemichannels' docking. We simulated homotypic and heterotypic gap junctions formed by connexins, innexins, and pannexins. Based on the numerical results and our theoretical model, we discussed the physiology of hemichannels and gap junctions, including ion blockage of hemichannels, voltage gating of gap junctions, and asymmetry and delay of electrical synaptic transmission, for which the numerical simulations are first comprehensively realized.
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