Ciclopirox

Ciclopirox (CPX) is an FDA approved, broad-spectrum antifungal agent. The prodrug of CPX, fosciclopirox, was evaluated for safety and preliminary efficacy in patients with advanced solid tumors, including bladder cancer, and was found to inhibit cell proliferation, the γ-secretase complex, and Notch signaling. However, the effects of CPX on human T cell function have remained undefined. In this study, we investigated the impact of CPX on primary human T cell activation and their effector responses. CPX enhanced early activation markers and IL-2 production; yet, suppressed activation-driven expansion, altered cell cycle progression, and reduced effector functions, including IFN-γ production and cytotoxic granule expression, in vitro. Mechanistically, CPX modulates Notch1 activation temporally and reprograms T cell metabolism by limiting glycolysis, both of which impact proliferative and effector responses in activated T cells. Together, these findings identify CPX as a modulator of T cell immunity, highlighting the broader immunologic implications for its therapeutic application.

Dermatophytosis caused by the Trichophyton mentagrophytes/T. interdigitale species complex (TMTISC) has attracted global attention, with increasing reports of terbinafine‐resistant T. indotineae in China.

This study aims to evaluate the epidemiological features of antifungal‐resistant TMTISC in China and monitor the prevalence of T. indotineae .

A total of 230 TMTISC strains were isolated from nine tertiary hospitals across three economic regions of China. These isolates were identified through molecular sequencing and phylogenetic analysis. Additionally, in vitro antifungal susceptibility testing (AFST) was performed for eight drugs, following the EUCAST 11.0 protocol. Mutations in the squalene epoxidase ( SQLE ) gene were detected.

The phylogenetic tree revealed that 120 strains (52.17%) were T. mentagrophytes , 92 (40.0%) were T. interdigitale , and 18 (7.83%) were T. indotineae . Eight different genotypes were identified, including TM‐IX, which was predominant in China, along with two newly discovered genotypes, TM‐XXX and TM‐XXXI. Among T. mentagrophytes isolates, tinea faciei (44.17%) was the common clinical type, primarily isolated from the central region. T. interdigitale isolates were mainly found in onychomycosis (36.96%), T. indotineae was commonly isolated from tinea corporis (94.44%) and tinea cruris (55.56%). AFST showed that all isolates of T. interdigitale and T. mentagrophytes were susceptible to terbinafine [minimum inhibitory concentrations (MICs) < 0.125 mg/L] and voriconazole (MICs < 0.5 mg/L). All isolates of T. indotineae were resistant to terbinafine (0.25 to >4.0 mg/L), exhibiting a single amino acid substitution in SQLE (Phe397Leu, Leu393Ser or Phe415Cys). Additionally, elevated MICs were observed in TMTISC for itraconazole, miconazole, ciclopirox (1–2 mg/L) and griseofulvin (1–64 mg/L).

The TMTISC was predominantly composed of T. mentagrophytes , followed by T. interdigitale and T. indotineae . A rising trend of reduced azoles susceptibility in TMTISC and multi‐drug resistance among T. indotineae isolates has been observed in China.