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In alignment with the global movement toward reducing animal testing, several reconstructed human epidermis (RHE) models have been created for conducting skin irritation tests. These models have undergone development, verification, validation, and integration into OECD TG 439. Our team has introduced a novel in-house RHE named GB-RHE, and we adhere to OECD TG 439 to pre-validate the model and test its potential employment for nanoparticle irritation studies. GB-RHE exhibits morphological, biochemical, and physiological attributes equivalent to the human epidermis, featuring well-differentiated multilayered viable keratinocytes with a robust barrier function. The performance of the GB-RHE model was evaluated using ten reference chemicals, following the performance standard of OECD TG 439. The results demonstrated commendable predictive capacity and showed that titanium dioxide nanoparticles (TiO 2 NPs) are 'non-irritant' to the human epidermis following the globally harmonized classification system. However, although the histological analysis did not show morphological changes, transmission electron micrographs demonstrated that TiO 2 NPs can be internalized, reaching the external viable layers of the epidermis. This study demonstrates that in addition to the potential of the GB-RHE model to evaluate skin irritation, this model also has the potential to evaluate the skin toxicity of NPs and carry out cell internalization studies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Leishmania presents a complex life cycle that involves both invertebrate and vertebrate hosts. By regulating gene expression, protein synthesis, and metabolism, the parasite can adapt to various environmental conditions. This regulation occurs mainly at the post-transcriptional level and may involve epitranscriptomic modifications of RNAs. Recent studies have shown that mRNAs in humans undergo a modification known as N4-acetylcytidine (ac4C) catalyzed by the enzyme N-acetyltransferase (NAT10), impacting mRNAs stability and translation. Here, we characterized the NAT10 homologue of L. mexicana, finding that the enzyme exhibits all the conserved acetyltransferase domains although failed to functionally complement the Kre33 mutant in Saccharomyces cerevisiae. We also discovered that LmexNAT10 is nuclear, and seems essential, as evidenced by unsuccessful attempts to obtain null mutant parasites. Phenotypic characterization of single-knockout parasites revealed that LmexNAT10 affects the multiplication of procyclic forms and the promastigote-amastigote differentiation. Additionally, in vivo infection studies using the invertebrate vector Lutzomyia longipalpis showed a delay in the parasite differentiation into metacyclics. Finally, we observed changes in the cell cycle progression and protein synthesis in the mutant parasites. Together, these results suggest that LmexNAT10 might be important for parasite differentiation, potentially by regulating ac4C levels., (© 2025 John Wiley & Sons Ltd.)