Trichophyton species, the leading cause of dermatophytosis globally, are increasingly resistant to antifungal treatments, concerns about effective management strategies. In light of the absence of established resistance criteria for terbinafine and azoles, coupled with a dearth of research on resistance mechanisms in Trichophyton, antifungal susceptibility and drug resistance gene diversity were analyzed across 64 T. mentagrophytes, 65 T. interdigitale, and 2 T. indotineae isolates collected in China between 1999 and 2024 and 101 published T. indotineae strains. Analyses of the minimum inhibitory concentrations (MICs) of terbinafine, itraconazole, voriconazole, posaconazole, and isavuconazole revealed a concerning increase in T. indotineae with terbinafine resistance, including two novel isolates from China. Compared with T. interdigitale, T. mentagrophytes presented higher terbinafine MICs but similar azole susceptibility. Notably, 27 T. interdigitale isolates were classified as non-wild-type for terbinafine. Genetic diversity was analyzed for the SQLE, CYP51A and CYP51B gene. Specifically, T. indotineae isolates presented SQLE protein changes linked to terbinafine resistance. SQLE diversity was linked to terbinafine sensitivity, whereas alterations in CYP51A were associated with itraconazole sensitivity, with notable statistical significance evident across various protein isoforms. The relationship between protein diversity and drug sensitivity is presented in detail. Together, these findings highlight a growing prevalence of antibiotic resistance among Trichophyton and identify potential target genes for new therapies, underscoring the need for ongoing monitoring and offering directions for novel therapeutics.
Background: Thyroxine is important to maintain the normal operation of the body. Both clinical and experimental results show thyroxine is closely related to hair growth, the mechanism of which is not fully understood. Purpose: Investigate the effect of thyroxine receptor agonist, TDM10842, for dorsal hair growth in C3H mice and explore its underlying mechanism. Methods: Depilated mice were applied with the TDM10842, vehicle of this drug and without any materials on dorsal skin. RNA‐sequencing (RNA‐seq) was employed to identify the change in gene expression of skin tissues. Quantitative real-time PCR (rt-PCR) and immunoblotting were conducted to validate key differentially expressed genes (DEGs) between different groups. Results: The TDM group showed early induction of anagen. 857, 782, and 276 differentially expressed genes were identified between 3 groups. As a critical DEG in group TDM, Pclaf was positively related to the motivation of Wnt/beta-catenin and Hedgehog signaling pathways, with a high expression of Ki67 and cyclinD1. Conclusion: TDM10842 accelerates the anagen entrance and the potential mechanism might be the activation of Wnt/beta-catenin and Hedgehog pathways. Pclaf serves as a critical molecule involved in pathway activation, and cyclinD1 is an important effector protein downstream of the pathways.