Qinghai Zeng

Repair strategies predicated on controlled micro-injury are widely applied in dermatology; however, the distinct molecular cascades initiated by different injury modalities remain incompletely characterized. To systematically delineate and compare the acute transcriptomic landscapes of mouse skin following fire filiform needling (FFN), ablative fractional CO ₂ laser (AFCO ₂ L), and conventional filiform needling (FN), we performed high-throughput RNA sequencing on dorsal skin samples harvested from C57BL/6J mice one day after treatment with FFN (combining thermal and mechanical stimuli), AFCO ₂ L (purely thermal), or FN (purely mechanical). All three interventions disrupted skin barrier integrity and activated canonical injury and repair transcriptional programs. Notably, the two modalities involving thermal stimulation (FFN and AFCO ₂ L) elicited a more robust and expansive transcriptomic response than purely mechanical FN, including immune activation, cell proliferation, differentiation, cell migration, metabolic reprogramming, and neurovascular remodeling. Although FFN and AFCO ₂ L exhibited broadly convergent transcriptional signatures, key distinctions emerged: FFN was preferentially associated with tissue remodeling, vascular processes, and neural regulation, whereas AFCO ₂ L displayed stronger enrichment for immune activation and cell migration. This study provides a comprehensive transcriptomic atlas of acute skin responses to distinct micro-injury modalities and underscores the potent role of thermal stimulation in amplifying dermal repair and remodeling. Our findings establish a systematic framework for understanding the mechanistic underpinnings of micro-injury therapies and for refining their clinical application.

As the impact of global warming continues to intensify, the effects of heat stress on the skin are becoming increasingly evident. Growing clinical evidence suggests that heat stress can induce cutaneous hyperpigmentation. However, the underlying mechanisms remain incompletely understood. In this study, we demonstrate that heat stress promotes repigmentation in vitiligo lesions and induces melanogenesis in depigmented mouse skin. Mechanistically, we reveal that heat stress upregulates WNT5A expression and paracrine secretion in dermal fibroblasts (FB) through METTL3‐mediated N ⁶ ‐methyladenosine (m ⁶ A) modification. The stability of WNT5A mRNA is regulated through a YTHDC1‐dependent pathway. Treatment with recombinant WNT5A protein significantly increases melanin content in melanocytes (MC), MNT1 cells, and human skin explants. Furthermore, WNT5A induces the expression of both β‐catenin and its receptor FZD10 in MC. Functional rescue experiments confirm that FZD10 knockdown abolishes WNT5A‐ and heat stress‐induced β‐catenin activation, thereby attenuating melanogenesis. Collectively, our findings elucidate a novel mechanism whereby heat stress triggers fibroblast‐derived WNT5A secretion via METTL3/YTHDC1‐dependent m ⁶ A methylation to promote melanogenesis. This study provides novel insights into the pathogenesis of heat‐induced skin pigmentation disorders, and reveals the potential of thermotherapy as a promising avenue for treating hypopigmentary diseases.

This study aimed to systematically evaluate cutaneous adverse events (AEs) associated with Rybrevant (amivantamab), the first bispecific antibody targeting EGFR and MET, using the FDA Adverse Event Reporting System (FAERS) database. Using data from the FAERS between Q2 2021 and Q4 2024, we conducted a comprehensive evaluation of AEs related to Rybrevant. After data cleaning, 1,372 unique cases were identified where Rybrevant was designated as the primary suspect drug. Among these, 483 cutaneous AEs were included for further analysis. At the Preferred Term (PT) level, paronychia, dermatitis acneiform, and skin toxicity showed the highest signal intensities. Sex disparities revealed folliculitis as more prevalent in males. The median time-to-onset (TTO) of cutaneous AEs was 11 days (range: 0–139 days), with rash occurring earliest (median TTO less than 1 days) and skin toxicity latest (median: 139 days). Besides other events, hospitalization events were the most common clinical outcome of cutaneous AEs. Rybrevant-associated cutaneous AEs are significant and heterogeneous in real-world settings, with paronychia and dermatitis acneiform representing critical risks. Early monitoring and tailored management are essential, particularly for long-term users.

Pigmented diseases can significantly impact people's quality of life, with melanogenesis playing a key role. In this study, we first analysed the relationship between peroxisomes, peroxisomal biogenesis factor 16 (PEX16), and melanin synthesis using omics data and clinical samples. Our results showed that peroxisome function and PEX16 expression were negatively associated with melanogenesis. Overexpression of PEX16 in the melanin‐producing MNT1 cell line resulted in an increase in peroxisome production and the inhibition of key genes related to melanogenesis, such as microphthalmia‐associated transcription factor (MITF), tyrosinase (TYR), tyrosinase‐related protein 1 (TYRP1), and dopachrome tautomerase (DCT). Consistently, when PEX16 was overexpressed in melanocytes, there was a significant reduction in melanin content. The expression of PEX16 was detected in skin tissues. We found that PEX16 expression was higher in the areas with relatively lower pigmentation and decreased following ultraviolet B (UVB) irradiation. Furthermore, our findings suggest that PEX16 can inhibit melanogenesis by suppressing the Wnt/β‐catenin signalling pathway. In conclusion, PEX16 can inhibit the Wnt/β‐catenin signalling pathway, thereby reducing melanogenesis. Our research provides new insights for the clinical diagnosis and treatment of skin pigmentation disorders.

Introduction: Vitiligo is an autoimmune disease characterized by skin depigmentation, affecting approximately 1% of the global population. Reflectance confocal microscopy (RCM) enables high‐resolution visualization of pigmentary changes; however, accurate and efficient identification remains challenging due to blurred boundaries, variable brightness, and low contrast. Method: We retrospectively analyzed RCM images from 105 vitiligo patients. The proposed pipeline incorporated brightness equalization, segmentation using a U‐KAN network with reverse learning, and multichannel feature fusion of grayscale, histogram of oriented gradients (HOGs), and L‐luminance channels to capture both morphological and luminance‐based features. Pigment ring subtypes were classified using a Data‐efficient image Transformer (DeiT) transformer model, and concept relevance propagation (CRP) was applied to interpret model attention. Results: Feature enhancement through HOG and L‐channel fusion improved image contrast and detail visibility, yielding classification accuracy between 90% and 97%. The U‐KAN network achieved precise cell segmentation with an Intersection‐over‐Union (IoU) of 78 ± 2%. The DeiT model outperformed junior dermatologists and matched senior dermatologists in accuracy, precision, and specificity. Ablation studies showed the highest performance in the complete and incomplete categories, with recall reaching 100% for complete pigment rings. CRP maps indicated that contextual background information enhanced classification performance. Conclusion: This study presents an innovative RCM processing pipeline integrating reverse learning and multichannel fusion, achieving dermatologist‐level performance in pigment ring classification. The approach demonstrates strong potential as an automated diagnostic tool for vitiligo, with future work aimed at improving generalization and clinical applicability.

Ambient air pollutants are hazardous materials posing significant risks to global public health. While their impacts on respiratory and cardiovascular systems are well-established, their role in triggering specific autoimmune skin diseases remains under-explored. This study investigates the temporally resolved public health response to air pollutant exposure, using the autoimmune condition vitiligo as a sensitive health endpoint. We aimed to evaluate the differential public health responses to six major air pollutants by analyzing their lagged effects on vitiligo-related online search behavior, using the Baidu Search Index (BSI) as a novel proxy for public concern and health-seeking activity. In this ecological time-series study, we applied a Distributed Lag Non-linear Model (DLNM) to daily data on BSI, air pollutants, and meteorological factors in Changsha, China (2019–2021). The findings reveal distinct, pollutant-specific temporal patterns of public response, suggesting different toxicological pathways. Exposure to industrial pollutants like sulfur dioxide (SO₂) prompted an immediate, acute increase in search behavior. In contrast, traffic-related pollutants such as carbon monoxide (CO) were associated with a more persistent, long-term response. These associations remained robust in two-pollutant models. Short-term exposure to hazardous air pollutants is associated with significant changes in public health-seeking behavior. The study highlights the value of infodemiology as a near real-time surveillance tool for monitoring population-level responses to environmental hazards and provides new evidence on the differential health impacts of specific pollutants on autoimmune skin conditions.

The skin's unique thermosensitivity renders it exceptionally responsive to thermal perturbations, wherein heat stress exposure disrupts cutaneous homeostasis and activates pigmentary pathways. While clinical observations consistently link heat stress to hyperpigmentation disorders, the precise molecular mechanism for heat‐induced melanogenesis‐particularly the epigenetic‐immune crosstalk mediating this process‐constitutes an unmet research challenge. Transcriptomic analysis of melasma reveals a significant positive correlation between CX3CL1 and melanogenesis. Consistently, CX3CL1 significantly enhances melanogenesis in both cultured skin tissues and melanocytes. Mechanistically, CX3CL1 increases melanogenesis through CX3CR1‐dependent activation of JNK signaling pathway. Notably, heat stress triggers recruitment of WDR5, a core subunit of the H3K4me3 methyltransferase, to the CX3CL1 promoter. At this site, WDR5 catalyzes H3K4me3 modification, thereby driving the transcription of CX3CL1. Inhibition of WDR5 expression can reverse the heat stress‐induced upregulation of H3K4me3 enrichment level in the CX3CL1 promoter region, thereby suppressing CX3CL1 expression and subsequently reducing melanogenesis. Further investigation reveals that the recruitment of WDR5 to the CX3CL1 promoter is MYC‐dependent. In conclusions, heat stress promotes melanogenesis by upregulating CX3CL1 through the MYC‐WDR5‐H3K4me3 axis, thereby activating the CX3CL1/CX3CR1‐JNK signaling pathway. This study elucidates the mechanism by which heat stress regulates skin pigmentation and reveals novel targets with therapeutic potential for pigmentary skin disorders.