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Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Connexin is a transmembrane protein involved in gap junctions (GJs) formation. Our previous study found that connexin 37 (Cx37), encoded by gap junction protein alpha 4 (GJA4), expressed on fibroblasts acts as a promoter of CRC and is closely related to epithelial-mesenchymal transition (EMT) and tumor immune microenvironment. However, to date, the mechanism concerning the malignancy of GJA4 in tumor stroma has not been studied. Methods: Hematoxylin-eosin (HE) and immunohistochemical (IHC) staining were used to validate the expression and localization of GJA4. Using single-cell analysis, enrichment analysis, spatial transcriptomics, immunofluorescence staining (IF), Sirius red staining, wound healing and transwell assays, western blotting (WB), Cell Counting Kit-8 (CCK8) assay and in vivo experiments, we investigated the possible mechanisms of GJA4 in promoting CRC. Results: We discovered that in CRC, GJA4 on fibroblasts is involved in promoting fibroblast activation and promoting EMT through a fibroblast-dependent pathway. Furthermore, GJA4 may act synergistically with M2 macrophages to limit T cell infiltration by stimulating the formation of an immune-excluded desmoplasic barrier. Finally, we found a significantly correlation between GJA4 and pathological staging (P < 0.0001) or D2 dimer (R = 0.03, P < 0.05). Conclusion: We have identified GJA4 expressed on fibroblasts is actually a promoter of the tumor mesenchymal phenotype. Our findings suggest that the interaction between GJA4+ fibroblasts and M2 macrophages may be an effective target for enhancing tumor immunotherapy.

Cylas formicarius is one of the most important pests of sweet potato worldwide, causing considerable ecological and economic damage. This study improved the effect of comprehensive management and understanding of genetic mechanisms by examining the functional genomics of C. formicarius. Using Illumina and PacBio sequencing, this study obtained a chromosome-level genome assembly of adult weevils from lines inbred for 15 generations. The high-quality assembly obtained was 338.84 Mb, with contig and scaffold N50 values of 14.97 and 34.23 Mb, respectively. In total, 157.51 Mb of repeat sequences and 11 907 protein-coding genes were predicted. A total of 337.06 Mb of genomic sequences was located on the 11 chromosomes, accounting for 99.03% of the total length of the associated chromosome. Comparative genomic analysis showed that C. formicarius was sister to Dendroctonus ponderosae, and C. formicarius diverged from D. ponderosae approximately 138.89 million years ago (Mya). Many important gene families expanded in the C. formicarius genome were involved in the detoxification of pesticides, tolerance to cold stress and chemosensory system. To further study the role of odorant-binding proteins (OBPs) in olfactory recognition of C. formicarius, the binding assay results indicated that CforOBP4–6 had strong binding affinities for sex pheromones and other ligands. The high-quality C. formicarius genome provides a valuable resource to reveal the molecular ecological basis, genetic mechanism, and evolutionary process of major agricultural pests; it also offers new ideas and new technologies for ecologically sustainable pest control.