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Psoriasis (PsO) is a chronic inflammatory skin disease with both local and systemic components. PsO-associated arthritis, known as psoriatic arthritis (PsA), develops in approximately 13%-25% of PsO patients. Various factors associated with both PsO and PsA indicate that these conditions are part of a single disease. Identification of novel targets for the development of drugs to treat both PsO and PsA is desirable to provide more patient-friendly treatment regimens. Such targets will likely represent 'common checkpoints' of inflammation, for example key components or transduction cascades of the signalling pathways involved. Emerging evidence supports involvement of the non-canonical Wnt signalling pathways in the development of both PsO and PsA, especially the Wnt5a-activated signalling cascades. These, together with interlinked factors, are crucial in the interactions among keratinocytes, immune cells and inflammatory factors in PsO, as well as among chondrocytes, osteoblasts and osteoclasts that trigger both subchondral bone remodelling and cartilage catabolism in PsA. This review focuses on the pathological role of Wnt5a signalling and its interaction with other interlinked pathways in both PsO and PsA, and also on the main challenges for future research, particularly with respect to molecules targeting Wnt signalling pathways for the treatment of PsO and PsA.

Aqueous emulsion polymerization is a robust technique for preparing nanoparticles of block copolymers; however, it typically yields spherical nanoassemblies. The scale preparation of nanoassemblies with nonspherical high‐order morphologies is a challenge, particularly 2D core–shell nanosheets. In this study, the polymerization‐induced self‐assembly (PISA) and crystallization‐driven self‐assembly (CDSA) are combined to demonstrate the preparation of 2D nanosheets and their aggregates via aqueous reversible addition‐fragmentation chain transfer (RAFT) emulsion polymerization. First, the crucial crystallizable component for CDSA, hydroxyethyl methacrylate polycaprolactone (HPCL) macromonomer is synthesized by ring opening polymerization (ROP). Subsequently, the RAFT emulsion polymerization of HPCL is conducted to generate crystallizable nanomicelles by a grafting‐through approach. This PISA process simultaneously prepared spherical latices and bottlebrush block copolymers comprising poly(N′,N′‐dimethylacrylamide)‐block‐poly(hydroxyethyl methacrylate polycaprolactone) (PDMA‐b‐PHPCL). The latexes are now served as seeds for inducing the formation of 2D hexagonal nanosheets, bundle‐shaped and flower‐like aggregation via the CDSA of PHPCL segments and unreacted HPCL during cooling. Electron microscope analysis trace the morphology evolution of these 2D nanoparticles and reveal that an appropriate crystallized component of PHPCL blocks play a pivotal role in forming a hierarchical structure. This work demonstrates significant potential for large‐scale production of 2D nanoassemblies through RAFT emulsion polymerization. [ABSTRACT FROM AUTHOR]

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]

BackgroundSensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin.ObjectiveTo assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin.MethodsFollowing topical applications of individual vehicle or skin care product to C57BL/6J mice twice daily for 4 days, transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration and skin surface pH were measured on treated versus untreated mouse skin with an MPA5 device and pH 900 pH meter.ResultsOur results show that all tested products induced abnormalities in epidermal functions of varying severity, including elevations in TEWL and skin surface pH, and reduced SC hydration.ConclusionsOur results suggest that mice can serve as a predictive model that could be used to evaluate the potential safety of skin care products in humans with sensitive skin.

A 65-year-old man presented with a slowly enlarging, hyperplastic cutaneous nodule on the abdomen that developed over a period of 20 years. Based on the clinical manifestation and typical histopathology, the patient received a diagnosis of giant basal cell carcinoma.

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]