Wu Zhu

Background: Existing skin health assessments predominantly focus on single topics or diseases, making it difficult to cover the complete “Knowledge–Self-efficacy–Attitudes–Behaviors (KSAB)” continuum. Objective: To develop and validate a skin health knowledge, attitudes, and behaviors questionnaire for the general population. Methods: A cross-sectional online survey was conducted among the general population between October and November 2025. The questionnaire was developed based on a conceptual structure incorporating four dimensions: knowledge, self-efficacy, attitudes, and behaviors. Content validity was assessed by 13 experts, and the Item-level Content Validity Index (I _CVI ) and modified Kappa (K ^* ) were calculated. Construct validity was examined using confirmatory factor analysis (CFA). Item-level evaluation was performed using item response theory (IRT), including the two-parameter logistic (2PL) model for dichotomous items and the graded response model (GRM) for ordered items. Results: A total of 865 individuals were enrolled (men: women = 1.24:1). Content validity was good (I _CVI = 0.846–1.000, K* = 0.845–1.000). The five-factor model from CFA showed a good fit (CFI = 0.969, TLI = 0.960, RMSEA = 0.070, SRMR = 0.095). IRT analysis indicated that K1–K5 had acceptable discrimination ( a = 0.59–2.40) and difficulty parameters ranging from −3.63 to −1.33. However, items K6, K7 and S1 were excluded due to insufficient threshold coverage. The proportion of women reporting frequent sunscreen use was higher than that of men. Self-efficacy levels showed a decreasing trend with age. Furthermore, individuals in service/manual labor occupations exhibited lower proportions on certain items. Conclusion: This study developed and validated a KSAB questionnaire on skin health knowledge, attitudes, and behaviors, showing good validity and item-level performance. The findings support targeted health promotion for men, older adults, and service/manual workers.

Background: Immunosuppressive tumour‐associated macrophages (TAMs) represent a promising target for cancer immunotherapy; however, existing TAM‐directed therapies have shown limited clinical efficacy. C‐type lectin domain family 4 member E (CLEC4E), a pro‐inflammatory molecule expressed on macrophages, was recently found to be highly enriched in TAMs. This study aims to elucidate the role of CLEC4E in TAMs and identify potential therapeutic agents targeting CLEC4E, and to clarify the mechanism of Bromodomain and extraterminal domain (BET) inhibitor NHWD‐870 in downregulating CLEC4E. Methods: We first assessed the correlation between CLEC4E expression and survival in melanoma patients. Clec4e ^flox/flox Lyz2‐cre (knockout) and Clec4e ^flox/flox (control) mice were generated and implanted with melanoma or ovarian cancer models. Single‐cell RNA sequencing was performed to characterise macrophage phenotypic changes following CLEC4E knockout, with validation via RT‐PCR, flow cytometry and proteomic sequencing. A drug screen identified BET inhibitors targeting CLEC4E, and their mechanisms were further investigated using RNA silencing, Chromatin Immunoprecipitation (ChIP)‐seq and luciferase reporter assays. Results: In melanoma patients, high CLEC4E ⁺ TAM infiltration was associated with poor prognosis. CLEC4E knockout significantly suppressed tumour growth compared to control mice. TAMs from knockout mice exhibited downregulated proliferation markers and upregulated genes related to antigen presentation and pro‐inflammatory responses. Mechanistically, CLEC4E deletion inhibited TAM proliferation via the Erk signalling pathway, enhanced TAM‒T cell interactions, and increased granzyme B expression in T cells. The BET inhibitor NHWD‐870 was shown to disrupt BRD4‒CEBPβ interaction, leading to downregulation of CLEC4E expression. Conclusions: CLEC4E ⁺ TAMs promote an immunosuppressive microenvironment by enhancing their own proliferation and impairing anti‐tumour functions, thereby limiting T‐cell cytotoxicity. Targeting the BRD4/CEBPβ/CLEC4E axis with BET inhibitors represents a promising therapeutic strategy for reprogramming TAMs and enhancing anti‐tumour immunity.

Background: Psoriasis, an inflammatory skin disorder, involves pyroptosis—a pro-inflammatory cell death process. However, cell-specific pyroptosis dynamics and immune microenvironment interactions remain unclear. Objective: To investigate cell-type-specific pyroptosis patterns in psoriasis and their immunoregulatory mechanisms. Methods: We integrated 21 transcriptomic datasets (from 2007 to 2020) obtained from the GEO database and two single-cell RNA sequencing datasets to quantify pyroptotic activity using Gene Set Variation Analysis and AUCell algorithms. Immune cell infiltration profiles were evaluated via CIBERSORT, while cell-cell communication networks were analyzed by CellChat. In vitro and in vivo experiments were performed to validate key findings. Results: Our analysis revealed that psoriasis patients exhibited significantly elevated levels of pyroptosis compared to healthy controls, with pyroptotic activity reflecting treatment responses. Notably, monocyte-derived macrophages (MDMs) in psoriatic lesions displayed markedly heightened pyroptotic activity. In vitro experiments confirmed that MDMs derived from psoriasis patients overexpressed pyroptosis-related molecules (Caspase 1 and Caspase 4) as well as pro-inflammatory cytokines (TNFα, IL6, IL1β) when compared to healthy controls. Furthermore, these cells showed increased expression of CXCL16, which might potentially activate Th17 cells through CXCR6 signaling, thereby driving skin inflammation. Inhibition of monocyte migration in an imiquimod-induced psoriasiform dermatitis model significantly alleviated skin inflammation and reduced the proportion of M1 macrophages and Th17 cells in lesional skin. Conclusions: This study revealed that MDMs in psoriatic lesions exhibited a hyperactive pyroptotic state, which contributed to disease progression through CXCL16-mediated remodeling of the immune microenvironment. These findings highlight pyroptosis as a potential therapeutic target for psoriasis.

Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis. An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways. IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder. TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.

Psoriasis is a chronic inflammatory skin disease often accompanied by comorbidities such as hyperglycemia, insulin resistance, and obesity. Acitretin, as a second-generation retinoid, is used in the treatment of psoriasis. This study aims to explore the role of acitretin on glucose and lipid metabolism in psoriasis. HepG2 cells were treated with acitretin under high- or low-glucose conditions. mRNA and protein expression levels of glucose transport-related genes were evaluated using real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Glucose uptake was analyzed by flow cytometry, and intracellular lipid droplet formation was assessed via Oil Red O staining. Healthy adult female BALB/C mice were randomly divided into 3 groups: a control group, an imiquimod (IMQ)-induced psoriasis model group (IMQ group), and an acitretin treatment group. Skin lesions and inflammatory markers were examined, along with changes in body weight, plasma glucose/lipid levels, and transcription of metabolic genes. Islets were isolated from normal and psoriasis-induced mice, and the effect of acitretin on insulin secretion was evaluated in vitro. Acitretin treatment increased glucose uptake and lipid droplet synthesis of HepG2 in high-glucose environment, with elevated transcription levels of glucose transport-related genes GLUT1 and GLUT4. Transcription of gluconeogenesis-related gene G6pase decreased, while transcription levels of glycogen synthesis-related genes AKT1 and GSY2 increased (all PPPDX-1 expression, while upregulating glucose homeostasis gene SIRT1 and insulin sensitivity gene PPARγ (all P<0.05). These findings suggest that acitretin plays a critical role in improving islet function and restoring islet homeostasis. Acitretin helps maintain the balance between hepatic glycogenesis and gluconeogenesis, enhances insulin sensitivity, and improves pancreatic islet function, thereby promoting systemic and cellular glucose homeostasis.

Dihydromyricetin (DMY), a flavonoid, belongs to a class of natural compounds and possesses anti-inflammatory properties. The objective of this research is to investigate the effects and mechanism of DMY in mice induced by imiquimod (IMQ). Here, DMY ointment was topically applied to evaluate the effect of DMY on psoriasis, while the results showed DMY improved clinical phenotype of IMQ-induced psoriasiform dermatitis. Histological evaluation revealed decreases in keratinocyte hyperplasia and immune cell infiltration in mice after DMY administration. Besides, DMY treatment could attenuate psoriasiform inflammation as showed in the decreased expression of inflammation mediators such as IL-17a, IL-23a, TNF-α, IL-6, IL-1β, IL-12a, CXCL2, and S100A8 in the skin of mice. Mechanistically, DMY reduced the polarization of macrophages towards the pro-inflammatory M1 phenotype by inhibiting the TLR4/NF-κB pathway, importantly, which subsequently regulated the differentiation of T helper (Th) 1 and Th17 cell subsets, leading to the relief of immune inflammatory response in psoriasis. In conclusion, the research reveals that DMY markedly attenuated IMQ-induced psoriasis in mice and provides that DMY have great potential for treatment of psoriasis.