Skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) is the most lethal skin cancer with increasing incidence. Regulated cell death plays an important role in tumorigenesis and serves as an important target for almost all treatment strategies. Cuproptosis is the most recently identified copper-dependent regulated cell death form that relies on mitochondria respiration. However, its role in tumorigenesis remains unknown. The correlation of cuproptosis-related genes with tumor prognosis is far to be understood, either. In the present study, we explored the correlation between cuproptosis-related genes with the prognosis of melanoma by accessing and analyzing a public database and found 11 out 12 genes were upregulated in melanoma tissues and three genes (LIPT1, PDHA1, and SLC31A1) have predictive value for the prognosis. The subgroup of melanoma patients with higher cuproptosis-related gene expression showed longer overall survival than those with lower gene expression. We chose LIPT1 for further exploration. LIPT1 expression was increased in melanoma biopsies and was an independent favorable prognostic indicator for melanoma patients. Moreover, LIPT1 expression was positively correlated with PD-L1 expression and negatively associated with Treg cell infiltration. The melanoma patients with higher LIPT1 expression showed longer overall survival than those with lower LIPT1 expression after receiving immunotherapy, indicating the prognostic predictive value of LIPT1. Finally, a pan-cancer analysis indicated that LIPT1 was differentially expressed in diverse cancers as compared to normal tissues and correlated with the expression of multiple immune checkpoints, especially PD-L1. It could serve as a favorable prognosis indicator in some cancer types. In conclusion, our study demonstrated the prognostic value of cuproptosis-related genes, especially LIPT1, in melanoma, and revealed the correlation between LIPT1 expression and immune infiltration in melanoma, thus providing new clues on the prognostic assessment of melanoma patients and providing a new target for the immunotherapy of melanoma.

Prototheca zopfii commonly exists in the environment, and causes invasive infections (protothecosis) in humans. The morbidity of protothecosis has increased rapidly in recent years, especially in systemic infections of patients with an impaired immune system. The infection in immunocompromised patients has a poor prognosis due to limited understanding of the pathogenesis of the disease, as most previous studies mainly focused on classification and recognition of pathogenic strains. In this study, we constructed the genome and transcriptome of two pathogenic strains and one environmental strain, by next generation sequencing methods. Based on our preliminary gene expression findings, genes in P. zopfii pathogenic strains are significantly up-regulated in metabolism in peroxisome, such as glyoxylate cycle, which may improve the organism’s resistance to the harsh environment in phagolysosome of macrophage and its ability to survive in an anaerobic environment. We also found some significant up-regulated genes, which are related to adherence and penetration in dermatophytes, and we speculate that this may enhance the virulence capacity of pathogenic strains. Finally, the genomes and transcriptomes of P. zopfii described here provide some base for further studies on the pathogenesis of this organism.

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Surgical interventions are mainstream therapies for refractory vitiligo that are resistant to conventional approaches. This clinical trial is a single center retrospective cohort study. 726 vitiligo patients treated with ACEG were collected from January 2015 to June 2019 in China. The patient characteristics such as gender, age, clinical type, lesion sites, course of the disease, and disease stable period were recorded. In 2118 pieces of skin lesions from 726 patients received ACEG, the total effective rate was 82.81% (1754/2118) ACEG can increase the number of melanocytes and KRT6C+ keratinocytes in skin lesions, thereby restoring a skin microenvironment suitable for melanocyte survival. ACEG is a promising therapeutic agent for refractory vitiligo. Age, clinical type, lesion site, and lesion stable period before surgery have significant impacts on repigmentation in ACEG. ACEG can increase the number of melanocytes, cytokine secretion keratinocyte and KRT6C+ keratinocytes in skin lesions, thereby restoring a skin microenvironment suitable for melanocyte survival.

Autologous cultured epithelium grafting (ACEG) is a promising treatment for refractory vitiligo. Concerns for infections or immunological reactions caused by serum and feeder used in culture medium may limit the use for surgical interventions. Here, we cultured autologous epithelium under serum- and feeder-free (SFF) conditions and compared its safety and efficacy with epithelium cultured under serum- and feeder-dependent (SFD) conditions in patients with stable vitiligo. Then, single-cell RNA transcriptomics of SFF and SFD cultured epithelium and healthy skin were conducted. There were no significant differences in repigmentation between the SFF and the SFD conditioned grafting. Increased LAMB3 + basal keratinocytes and ZNF90 + fibroblasts were found in the SFF epithelial sheets. The LAMB3 + basal keratinocytes had active cellular metabolism and participated in extracellular matrix homeostasis. The ZNF90 + fibroblasts were more differentiated and implicated in collagen formation for cell adhesion. Both the LAMB3 + basal keratinocytes and the ZNF90 + fibroblasts were more involved in the interactions with melanocytes in the SFF epithelial sheets compared to the SFD epithelial sheets. Our findings support the LAMB3 + basal keratinocytes and the ZNF90 + fibroblasts as key factors behind the repigmentation in ACEG under SFF conditions. The study provides translational insights into ACEG repigmentation and potential therapeutic targets for vitiligo.