Diabetic wound therapy faces significant challenges due to the complexity of the wound microenvironment, especially dysregulated immune cell responses and persistent pro-inflammatory sate. Targeting immune cells to reverse pathological wound conditions has increasingly become a promising strategy to promote diabetic wound healing. It has been reported that prolonged memory to acute inflammation sensitizes epidermal stem cells (EpSCs) to tissue damage. The increasing importance of interactions between immune cells and tissue stem cells has raised interest in the potential of EpSCs to induce inflammatory adaptations in diabetic wounds, and meanwhile, the inflammation memory patterns also provide new insight in EpSCs for tissue repair. Here, bioinspired cell-derived mimetic nanovesicles (MNVs) were obtained from inflammation memory-activated EpSCs. LPS treatment could trigger acute inflammation response and activate inflammation memory. MNVs derived from LPS-pretreated EpSCs (LEM) can effectively promote diabetic wound healing by manipulating crucial neutrophil regulatory mechanisms. The in vitro and in vivo studies demonstrated that LEM could stimulate neutrophil mitochondrial metabolic reprogramming, overcome phenotypic switching deficiency of neutrophils, and skew neutrophils toward N2 anti-inflammatory phenotype via regulating miR-193a-5p/TLR4/ JNK/P38 MAPK pathways in diabetic models. Our findings highlighted the great potential of inflammation memory in EpSCs, and also provided an alternative for diabetic wound treatment.

Background: Invasive Trichosporon asahii ( T. asahii ) infection frequently occurs with a high mortality in immunodeficient hosts, but the pathogenesis of T. asahii infection remains elusive. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that participate in various disease processes. However, the mechanism of circRNAs in T. asahii infection remains completely unknown. Methods: RNA sequencing (RNA-seq) was performed to analyze the expression profiles of circRNAs, microRNAs (miRNAs), and mRNAs in THP-1 cells infected with T. asahii or uninfected samples. Some of the RNA-seq results were verified by RT-qPCR. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed mRNAs. A circRNA-miRNA-mRNA network was constructed and verified by dual-luciferase reporter assay and overexpression experiments. Results: A total of 46 circRNAs, 412 mRNAs and 47 miRNAs were differentially expressed at 12 h after T. asahii infection. GO and KEGG analyses showed that the differentially expressed mRNAs were primarily linked to the leukocyte migration involved in the inflammatory response, the Toll-like receptor signaling pathway, and the TNF signaling pathway. A competing endogenous RNA (ceRNA) network was constructed with 5 differentially expressed circRNAs, 5 differentially expressed miRNAs and 42 differentially expressed mRNAs. Among them, hsa_circ_0065336 was found to indirectly regulate PTPN11 expression by sponging miR-505-3p. Conclusions: These data revealed a comprehensive circRNA-associated ceRNA network during T. asahii infection, thus providing new insights into the pathogenesis of the T. asahii -host interactions.

Trichosporon asahiiis the major pathogen causing invasive trichosporonosis. Conventional methods of its detection are time-consuming or costly and often require complex DNA extraction and purification steps, which hinders rapid clinical diagnosis. In this study, we evaluated colony PCR, which directly uses colonies or trace clinical samples as the template for amplification, for rapid detection ofT. asahiiinfection. Four methods, namely, direct colony, freeze-thaw, glass beads, and enzymolysis, were compared to select the best DNA extraction strategy. We subsequently designed and screened species-specific primers targeting the intergenic spacer 1 (IGS1) of the ribosomal DNA ofT. asahiiand used them to detect mock infection clinical samples. The species-specific colony PCR based on glass beads proved advantageous, with short procedure time (154.8 ± 0.6 min), good sensitivity (detection limit, 10²CFU/mL), and specificity forT. asahii, indicating that this method can be used for the rapid and simple identification of clinical samples ofT. asahiiinfection.