Daily Cosmetic Research Analysis

BACKGROUND: Tumor cell heterogeneity contributes to melanoma progression, therapeutic resistance, and clinical outcome variability. However, the identity and functional role of specific proliferative subpopulations remain incompletely understood. This study aims to characterize TYRP1-positive melanoma cells and elucidate their role in tumor proliferation, signaling regulation, and treatment response. METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data from primary and metastatic melanoma samples to identify transcriptionally distinct tumor cell subtypes. Functional validation of TYRP1-positive cells was performed using patient-derived organoids, TYRP1-overexpressing melanoma cell lines (A375, SK-MEL-28), and xenograft mouse models. The downstream molecular mechanisms were investigated through gene expression profiling, siRNA-mediated knockdown, recombinant protein treatment, and pathway inhibition assays. Therapeutic responses were assessed using dabrafenib and pembrolizumab treatments. RESULTS: TYRP1 marked a transcriptionally distinct melanoma subpopulation associated with poor patient survival. TYRP1-high organoids and cell lines exhibited significantly enhanced proliferation in vitro and accelerated tumor growth in vivo, without increased metastatic capacity. Mechanistically, TYRP1 induced expression of GPNMB, which activated Notch1 signaling and subsequently upregulated SOX10 and MITF. These transcription factors formed a positive feedback loop with TYRP1 that maintained the proliferative phenotype. GPNMB or Notch1 inhibition disrupted this loop and suppressed tumor growth. Importantly, TYRP1-overexpressing tumors demonstrated resistance to immune checkpoint blockade but increased sensitivity to dabrafenib, suggesting distinct therapeutic vulnerabilities. CONCLUSIONS: Our findings identify TYRP1 as a marker of a highly proliferative melanoma subpopulation that promotes tumor progression through the GPNMB-Notch1-SOX10/MITF axis. The TYRP1-SOX10-MITF feedback loop represents a key driver of melanoma proliferation and a potential biomarker for stratifying therapeutic response, offering a novel avenue for precision treatment in melanoma.

BACKGROUND: Robot-assisted mastectomy (RAM) is increasingly adopted in breast and plastic surgery with proposed benefits including improved cosmetic outcomes, surgical precision, and surgeon ergonomics. However, concerns remain regarding longer operative times. This systematic review and meta-analysis aimed to evaluate outcomes of RAM with immediate breast reconstruction (IBR) of any type compared with conventional mastectomy (CM). METHODS: The study was conducted according to PRISMA guidelines. Database searches were conducted (May 1, 2025) to identify studies assessing RAM with IBR. Studies were included if they reported at least 25 RAM procedures and at least one predefined outcome. Two meta-analyses were performed: A) a comparative meta-analysis including both RAM and CM cohorts, and B) a single-arm meta-analysis with RAM studies without a control group. Primary effect measures included odds ratios (ORs) and mean difference (MD). MAIN FINDINGS: Thirty studies comprising 3985 patients were included. Margin status was comparable between RAM and CM (OR: 1.04, 95% CI: 0.43 to 2.52, p = 0.93). RAM was associated with a significantly lower risk of overall complications (OR: 0.76, 95% CI: 0.63 to 0.92, p = 0.004), reduced intraoperative blood loss, and longer hospital stay. A non-significant trend towards improved BREAST-Q scores and reduced risk of individual complications was observed with RAM. Surgery duration was significantly longer in the RAM group, with an estimated learning curve of 17 procedures required to achieve a significant reduction in operative time. Substantial heterogeneity was observed across studies (I CONCLUSION: Current evidence suggests that RAM with IBR is a feasible alternative to CM in selected patients, with comparable margin status and similar overall complication rates. However, the evidence is limited by heterogeneity, potential selection bias, and lack of long-term oncologic data.

Infected chronic wounds are trapped in a vicious cycle of bacterial infection, oxidative stress, and inflammation. This dynamic and multifactorial pathology presents a formidable challenge that conventional dressings cannot adequately address. Herein, we report a microenvironment-adaptive dynamic hydrogel (BBR/CAT@Gel) engineered with hierarchical therapeutic functions to break this cascade. These functions consist of three integrated levels: contact killing, on-demand responsive release of antibacterial/antioxidant agents, and pro-regenerative microenvironment remodeling. To achieve these functions, the hydrogel is formed via dual dynamic covalent cross-linking through Schiff base and phenylboronate ester bonds between phenylboronic acid-grafted polylysine and chlorogenic acid-grafted oxidized hyaluronic acid, followed by encapsulation of berberine (BBR) and catalase (CAT). This reversible network endows the system with injectability, self-healing capacity, and tissue adhesion, enabling on-demand drug release in response to the acidic pH and reactive oxygen species (ROS) of the infected wound microenvironment. The hydrogel exerts multifaceted antibacterial effects through membrane disruption mediated by ε-polylysine and chlorogenic acid (CGA), as well as inhibition of bacterial protein synthesis induced by BBR. Concurrently, the released CAT and BBR provide ROS scavenging, while CGA contributes antioxidant activities, collectively alleviating oxidative stress, inhibiting macrophage M1 polarization, promoting cell migration, and facilitating angiogenesis. This hierarchical design achieves rapid bactericidal action alongside sustained microenvironment remodeling. Based on these merits, BBR/CAT@Gel rapidly cleared infection and achieved complete epidermal regeneration with well-organized collagen deposition in a mouse model of infected chronic wounds. This work establishes a rationally designed, microenvironment-adaptive hydrogel platform that integrates hierarchical therapeutic mechanisms, offering a compelling strategy for advanced chronic wound management.