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Most recent studies on the coronavirus disease 2019 (COVID‐19) pandemic and cutaneous melanoma (CM) focused more on delayed diagnosis or advanced presentation. We aimed to ascertain mortality trends of CM between 2012 and 2022, focusing on the effects of the COVID‐19 pandemic. In this serial population‐based study, the National Vital Statistics System dataset was queried for mortality data. Excess CM‐related mortality rates were estimated by calculating the difference between observed and projected mortality rates during the pandemic. Totally there were 108,853 CM‐associated deaths in 2012–2022. CM‐associated mortality saw a declining trend from 2012 to 2019 overall. However, it increased sharply in 2020 (ASMR 3.73 per 100,000 persons, 5.95% excess mortality), and remained high in 2021 and 2022, with the ASMRs of 3.82 and 3.81, corresponding to 11.17% and 13.20% excess mortality, respectively. The nonmetro areas had the most pronounced rise in mortality with 12.20% excess death in 2020, 15.33% in 2021 and 20.52% in 2022, corresponding to a 4–6 times excess mortality risk compared to large metro areas during the pandemic. The elderly had the most pronounced rise in mortality, but the mortality in the younger population was reduced. [ABSTRACT FROM AUTHOR]

Background: Serine metabolism is crucial for tumour oncogenesis and immune responses. S‐adenosyl methionine (SAM), a methyl donor, is typically derived from serine‐driven one‐carbon metabolism. However, the involvement of serine metabolism in psoriatic skin inflammation remains unclear. Objectives: To investigate the association between serine metabolism and psoriatic skin inflammation. Methods: Clinical samples were collected from patients with psoriasis and the expression of serine biosynthesis enzymes was evaluated. The HaCaT human keratinocyte cell line was transfected with small interfering RNA (siRNA) of key enzyme or treated with inhibitors. RNA sequencing and DNA methylation assays were performed to elucidate the mechanisms underlying serine metabolism‐regulated psoriatic keratinocyte inflammation. An imiquimod (IMQ)‐induced psoriasis mouse model was established to determine the effect of the SAM administration on psoriatic skin inflammation. Results: The expression of serine synthesis pathway enzymes, including the first rate‐limiting enzyme in serine biosynthesis, phosphoglycerate dehydrogenase (PHGDH), was downregulated in the epidermal lesions of patients with psoriasis compared with that in healthy controls. Suppressing PHGDH in keratinocytes promoted the production of proinflammatory cytokines and enrichment of psoriatic‐related signalling pathways, including the tumour necrosis factor‐alpha (TNF‐α) signalling pathway, interleukin (IL)‐17 signalling pathway and NF‐κB signalling pathway. In particular, PHGDH inhibition markedly promoted the secretion of IL‐6 in keratinocytes with or without IL‐17A, IL‐22, IL‐1α, oncostatin M and TNF‐α (mix) stimulation. Mechanistically, PHGDH inhibition upregulated the expression of IL‐6 by inhibiting SAM‐dependent DNA methylation at the promoter and increasing the binding of myocyte enhancer factor 2A. Furthermore, PHGDH inhibition increased the secretion of IL‐6 by increasing the activation of NF‐κB via SAM inhibition. SAM treatment effectively alleviated IMQ‐induced psoriasis‐like skin inflammation in mice. Conclusions: Our study revealed the crucial role of PHGDH in antagonising psoriatic skin inflammation and indicated that targeting serine metabolism may represent a novel therapeutic strategy for treating psoriasis. [ABSTRACT FROM AUTHOR]