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Idiopathic pulmonary fibrosis (IPF) is a paradigmatic aging-related lung disorder. In this retrospective cohort study, we evaluated 101 treatment-naïve patients at diagnosis (T0) and a subgroup (n = 31) after one year of antifibrotic therapy (T1). Analyses included leukocyte telomere length (LTL), DNA methylation age [DNAmAge assessed by Horvath, Levine (PhenoAge), Skin & Blood, Hannum, BLUP, Elastic Net (EN), and a 5-CpG panel], age acceleration (AgeAcc), and genetic susceptibility. At T1, LTL was independently predicted by baseline LTL (p = 0.0004) and treatment duration (p = 0.0056). Longitudinally, ΔLTL increased in nintedanib- versus pirfenidone-treated patients (p = 0.0402) and with treatment duration (p = 0.0233). DNAmAge modestly increased with chronological aging across all clocks, while AgeAcc remained stable, decreasing at follow-up (p = 0.0435) and higher in males (p = 0.0204). Genetic analyses on 17 IPF-associated SNPs confirmed enrichment of established risk variants, including MUC5B and DPP9, and identified an association between higher genetic burden and lower forced vital capacity (p = 0.0136). Extending this approach, genome-wide imputation enabled polygenic risk score (PRS) analysis, revealing significant case-control differences and discrimination (AUC up to 0.79), supporting a measurable polygenic contribution to disease susceptibility. These findings highlight the added value of integrating telomeric, epigenetic, and genome-wide genetic burden-captured through PRS-for improved risk stratification in IPF.

Gammaherpesviruses have been associated with granulomatous inflammation in the skin of various species. Equine sarcoidosis (idiopathic granulomatous disease) can cause granulomatous dermatitis, and its cause remains unknown. This retrospective study aimed to investigate the possible association between equine gammaherpesviruses-2 and -5 (EHV-2, -5) and cutaneous equine sarcoidosis (cES). Thirty client-owned equids. All animals had histologically and clinically confirmed cES. Signalment, geographical location and clinical features were recorded. Gram, Ziehl-Nielsen and Grocott-Gömöri methenamine silver histochemical stains, quantitative (q)PCR and in situ hybridisation were performed on formalin-fixed paraffin-embedded tissue samples. Quarter horses and thoroughbreds were overrepresented, and ages ranged from 10 months to 31 years old, with minimal difference in sex distribution. Localised, partially generalised, and generalised forms were noted in 13, 11 and six animals, respectively. The most common lesions were alopecia, crust and scale, and the limbs were the most affected site. Neither bacteria nor fungi were detected with histochemical stains. EHV-5 and -2 DNA were detected by qPCR in eight and four of 30 animals, respectively. Of those eight horses, EHV-5 hybridisation signals were found within skin lesions of five. ISH did not detect EHV-2 in any of the 29 animals tested. Although the exact cause of sarcoidosis remains uncertain, these findings suggest that EHV-5 may play some role in the pathogenesis of cES. This study also reports a single case of cES in a donkey.

To evaluate procedure- and operator-specific learning curves in Versius-assisted colorectal cancer surgery using risk-adjusted cumulative sum (RA-CUSUM) analysis in a real-world single-center setting. This retrospective study included consecutive adult patients with histologically confirmed colorectal cancer who underwent elective robotic surgery using the Versius system between December 2022 and August 2025. Right hemicolectomy (RHC), sigmoid resection (SR), and anterior rectal resection (AR) were analyzed. Learning curves were assessed using RA-CUSUM analysis of skin-to-skin operative time, adjusted for patient- and procedure-specific variables. Separate models were constructed for each procedure and operator. A total of 156 procedures were included: 79 AR, 51 RHC, and 26 SR. Median operative time was 215 min (IQR 185-255). Conversion to open surgery was low (3.2%), and major postoperative complications were infrequent. RA-CUSUM analysis demonstrated distinct procedure- and operator-specific learning patterns. RHC and SR reached earlier stabilization, whereas AR required a higher case volume to achieve consistent operative time reduction, with more prolonged variability in the learning phase. Oncological quality indicators were within accepted standards. Learning curves in Versius-assisted colorectal surgery are procedure- and operator-dependent. RA-CUSUM provides a structured method for monitoring trends in operative performance and may support structured training pathways and quality monitoring during implementation of robotic surgery programs.

Venous leg ulcers (VLUs) are prevalent hard-to-heal (chronic) wounds that decrease quality of life due to pain, reduced function and economic burden. One advanced therapy or cellular, acellular and matrix-like product (CAMP) which serves as a protective barrier for the management of acute and hard-to-heal wounds is a hypothermically stored amniotic membrane (HSAM). The objective of this study was to assess the clinical effectiveness and safety of HSAM plus standard of care (SoC) compared to SoC alone for the management of challenging and complex VLUs. This prospective, multicentre, randomised controlled trial (RCT) evaluated patients over 24 weeks after a four-week run-in period. Endpoints included: frequency of wound closure of cohorts stratified by wound duration (>6 and >24 months); and intent-to-treat (ITT) population wound improvements of >60% area, >50% depth and >75% volume reduction. The experimental cohort comprised 206 patients (randomised 1:1 to HSAM+SoC or SoC alone). Patient baseline demographics and wound characteristics were comparable between groups. The HSAM+SoC group demonstrated significantly higher rates of wound closure at weeks 12 and 16 (p<0.05) across both wound duration strata. In the ITT population, the HSAM+SoC group achieved significantly greater incidences of reduction in wound area (p=0.036), depth (p<0.001) and volume (p=0.034) compared to SoC alone. In this study, HSAM+SoC was shown to be effective in the most challenging and complex VLUs, with increased wound closure rates compared to SoC alone when stratified by wound duration. These findings, alongside diabetic foot ulcer RCT results, provide compelling evidence for the significant clinical benefit of HSAM for hard-to-heal wounds.

Cutaneous development is initiated by crosstalk between non-neural ectodermal epithelium and underlying mesenchymal cells. Recent studies have shown that some mesenchymal cells contribute to keratinocyte regeneration in injured skin. However, whether mesenchymal cells contribute to keratinocyte formation in physiologically normal skin remains unclear. Here we show, using lineage tracing, single-cell transcriptome and epigenome analyses of mouse skin, that the interfollicular epidermis consists largely of mesenchymal-lineage cells. Further lineage-tracing and live-imaging analysis of mouse embryos indicate that these mesenchymal-lineage epidermal progenitor cells arise from ectomesenchyme and contribute to the surface ectoderm through a mesenchymal-to-epithelial transition-like process between embryonic days 8.5 and 9.5. We also establish human induced pluripotent stem cell-derived ectomesenchyme and demonstrate that it generates p63-expressing keratinocytes. These data reveal a previously unappreciated contribution of ectomesenchyme to cutaneous development and provide insight into skin diseases involving epidermal mosaicism.

BACKGROUND Dermatomyositis is a rare autoimmune condition characterized primarily by proximal muscle weakness and cutaneous rashes, such as Gottron's papules and heliotrope rash, and is classified as a subtype of idiopathic inflammatory myopathies. While the clinical spectrum of dermatomyositis is broad, its initial onset as fulminant rhabdomyolysis (complicated by acute renal failure) is exceedingly rare. Such atypical presentations necessitate proactive clinical vigilance to ensure a prompt and accurate diagnosis. CASE REPORT Our patient was a 53-year-old woman who presented with progressive proximal muscle weakness, dysphagia, dysphonia, elevated creatinine kinase levels, hyperkalemia, and renal impairment. She was initially treated for rhabdomyolysis; however, due to increasing creatinine kinase levels and renal impairment, she required hemodialysis. During hospitalization she developed characteristic skin manifestations, including heliotrope rash and sleeve sign. Further investigation revealed pancreatic adenocarcinoma of the pancreatic head. CONCLUSIONS This report underscores the diagnostic difficulties in differentiating paraneoplastic-associated dermatomyositis from isolated primary rhabdomyolysis. It emphasizes the imperative of screening for occult malignancies in adult patients presenting with profound muscle necrosis and secondary kidney impairment. Identifying unusual clinical patterns of dermatomyositis early, combined with the rapid initiation of immunosuppressant and rigorous cancer surveillance, is essential for improving prognosis. This becomes paramount in scenarios in which the clinical presentation is suggestive of a paraneoplastic origin, notably pancreatic malignancy.

Aging profoundly remodels the immune system, impairing defense, repair and homeostatic function across tissues. Because the immune system operates in every organ, its deterioration has been proposed to drive or exacerbate systemic dysfunction and accelerate overall biological aging, making it an attractive biomarker and target for geroscience-guided trials. Despite this central role, there is no consensus on how to quantify immune aging, especially in clinical trials. Here, we establish a translational framework to identify immune aging biomarkers for this purpose. We define five evaluation criteria for immune aging biomarkers and apply these to candidate biomarkers, discussing their utility in the context of a major international healthspan competition, XPRIZE Healthspan. Metrics encapsulating multidimensional aspects of immune function, inflammaging scores and functional assays performed best against our selection criteria. Finally, we identify promising emerging measures, together with critical gaps that must be addressed to develop reliable, predictive biomarkers of human immune competence. Our framework provides a coherent path toward actionable and clinically meaningful immune aging biomarkers capable of quantifying immune fitness and resilience, and accelerating the clinical translation of geroscience-guided interventions.

Many users have now switched to using short video platforms as the main channel in their search for skin health information. With high internet penetration and a large market for the skincare industry, short video platforms play an important role in the "beauty discovery" process and purchase decisions. However, the increasing consumption of skin health content is also accompanied by the risk of misinformation, uneven content quality, and the dominance of creators who are not health professionals. Therefore, it is important to determine what factors affect the use of short video platforms in the search for skin health information. By adopting the stimulus-organism-response framework, health belief model, and media richness theory, this study aims to analyze the factors that influence the use of short video platforms in the search for skin health information. This study used a mixed methods approach by distributing an online survey to 603 respondents and conducting interviews with 30 interviewees. Survey data were analyzed using the covariance-based structural equation modeling method, and qualitative data were analyzed using the thematic analysis method. The results of this study found that perceived usefulness (P=.01), attitude (P=.02), perceived severity (P=.009), and perceived susceptibility (P=.02) directly affected the behavior of seeking skin health information on short video platforms. Health content expressiveness (P=.001) and personalized health insights (P<.001) directly affected perceived usefulness. These findings support the media richness theory, which shows that the expressiveness of health content and personalization can increase the perception of the usability of short video platforms. Perceived interactivity has an influence on attitude (P<.001), which then affects skin health information seeking on short video platforms (SHEs; P=.02). Upward skin comparison also had a direct influence on skin stigmatization (P<.001). Moreover, perceived severity (P=.009) and perceived susceptibility (P=.02) have an effect on SHEs. These findings confirm the health belief model's theory that perception of the severity of a skin problem and the perception of a person's likelihood of developing a skin problem can improve skin health seeking behavior. However, no effect of source credibility (P=.17) and skin stigmatization (P=.30) was found on SHEs. This is due to the user's willingness to exchange aspects of trust in information sources such as the functionality of the platform and familiarity with the platform or the existence of other internal cognitive or psychological aspects that can be investigated in the future. This study can provide guidance for the development of more effective health communication strategies in the digital era using short video platforms.

Atopic dermatitis (AD) is a complex inflammatory skin disorder. Rhodiola crenulata extract (RC) contains bioactive compounds with potential benefits for AD, but its mechanisms are not fully elucidated. A DNCB-induced AD mouse model and zebrafish models were used to evaluate efficacy and multi-dimensional activities. RC was separated into microfractions by preparative liquid chromatography. An OPLS-DA model, based on zebrafish bioactivity and LC-MS profiling, predicted active compounds, which were validated. Mechanisms were investigated via transcriptome sequencing, Western blot, qPCR, network pharmacology, and molecular docking. RC alleviated AD-like symptoms in mice, reducing epidermal thickening, mast cell infiltration, and splenomegaly. Four active monomers were identified, with kaempferol and naringenin showing the most prominent anti-inflammatory and analgesic effects, while salidroside exhibited strong antioxidant activity. RC and its active components primarily inhibited the NLRP3/Caspase-1/IL-1&#x3b2; axis, while also modulating oxidative stress (e.g., NOX2, PRDX2), cAMP/PKA signaling, and skin barrier-repair pathways. Network pharmacology and molecular docking confirmed efficient binding of four core compounds to NLRP3, CASP1, and IL-1B. This study demonstrates that RC alleviates AD by inhibiting the NLRP3 inflammasome pathway, identifying kaempferol, naringenin, salidroside and rhodiosin as key constituents, providing a foundation for developing RC as a natural AD therapeutic.

In 2026, the US Centers for Medicare & Medicaid Services implemented an update to the Physician Fee Schedule establishing a unified reimbursement rate for skin substitutes, also referred to as cellular, acellular and matrix-like products (CAMPs). This policy change introduced a fixed payment of [Formula: see text]127.14 per cm2, regardless of product type or regulatory classification. The aim of this work was to assess perceived impacts of the revised fee schedule that went into effect on 1 January 2026. The Wound and Hyperbaric Association conducted an online national survey of wound care practitioners and practices from 4 February 2026 to 14 April 2026. The Access Crisis Feedback Form consisted of 13 questions, including two open-ended items. Over the 69 days that the survey was open, 130 (~3%) responses were received from a comparative pool of 4551 National Provider Identifiers that had applied a CAMP in 2024. Collectively, respondents reported providing care to approximately 12,000 patients with wounds per week. Geographic representation included 36 of 50 (72%) states and Washington DC, and 8 of 12 (67%) Medicare Administrative Contractors. Most respondents (82%) practiced in non-facility settings; however, hospital-affiliated outpatient wound centres, and ambulatory surgery centres were also represented. The most severe concern identified was the 'Closure or planned closure of a wound care practice or service line', reported by just over 45% of responding settings. Only five (4%) respondents reported no significant impact, indicating that 96% perceived at least one operational impact following implementation of the revised payment policy. The most frequently cited concern (61%) was 'Authorisation delays for clinically eligible patients'. Analysis of the survey data suggests widespread impacts of the implemented CAMPs universal fee schedule across diverse wound care delivery settings in the US, including a substantial risk of service line closures. These findings raise concerns that a uniform CAMP product payment may not achieve site-of-care neutrality when hospital outpatient departments receive a separate application facility payment, while non-facility providers do not. Respondents reported that patients are already experiencing reduced access to advanced wound care, with associated complications such as: infection; sepsis; amputation; wound deterioration or enlargement; hospital readmission; the need for surgical debridement in the operating room setting; and flap- or graft-based salvage procedures. Responding wound care providers and practices, across diverse care settings and geographic regions, urge reevaluation of the current reimbursement framework to ensure the financial sustainability of wound care services, and to protect patient access and outcomes.

SERINC3, a member of the serine incorporator protein family, is known for its roles in viral resistance and tumorigenesis, however, its function in osteogenesis remains unexplored. Lentivirus infection, alkaline Phosphatase/Alizarin Red S Staining, and RT-qPCR were used to evaluate the osteogenic differentiation of mesenchymal stem cells mediated by SERINC3. MicroCT, H&E, and Masson staining were performed to investigate the bone formation and bone defect repair via Serinc3 knockout (KO) mice and nude mice. RNA sequencing, Co-IP, Western blotting, and Seahorse energy metabolism analysis were performed to elucidate the regulatory mechanism of SERINC3. Here, we identify SERINC3 as a critical regulator of osteogenic differentiation of bone marrow-derived stem cells (BMSCs) and bone regeneration. SERINC3 expression was significantly upregulated during osteogenic differentiation of BMSCs and stem cells from human exfoliated deciduous teeth (SHED). Functional assays revealed that SERINC3 overexpression enhanced osteogenic differentiation, proliferation, and migration of MSCs, while Serinc3-KO impaired these processes and led to osteopenia in mice. In a calvarial defect model, Serinc3-KO mice exhibited 42% less bone volume (BV/TV) and 35% lower bone mineral density (BMD), whereas SERINC3-overexpressing BMSCs significantly improved bone repair. Mechanistically, RNA sequencing and pathway analysis revealed that SERINC3 interacts with IL32 to activate the AMPK-ULK1-autophagy axis, thereby promoting osteogenesis. Additionally, SERINC3 enhanced mitochondrial energy metabolism by upregulating tricarboxylic acid cycle enzymes (ACO1, DLAT, SDHA) and increasing oxygen consumption rates. Rescue experiments confirmed that AMPK inhibition or autophagy blockade abolished SERINC3-mediated osteogenic effects, whereas mitochondrial electron transport chain activators restored osteogenesis in SERINC3-knockdown cells. In summary, this study identifies SERINC3 as a novel regulator of bone formation that orchestrates osteogenesis through IL32-AMPK-autophagy signaling axis and mitochondrial metabolism. These findings highlight SERINC3 as a potential therapeutic target for enhancing bone regeneration and treating skeletal defects.

Neurofibromatosis type 1 (NF1) is associated with cognitive impairments affecting attention, executive function, memory, visuospatial abilities, and processing speed, which are well described in children and adolescents and may interfere with daily functioning. In contrast, cognitive functioning in adults with NF1 remains less clearly defined, particularly in individuals without previous neurological or psychological conditions affecting cognitive functioning that may confound neuropsychological performance. This cross-sectional study aimed to characterize cognitive performance across multiple domains in adults with NF1 and to examine the relationship between cognitive performance and psychological and clinical variables. Eighty-seven adults with NF1 and no intellectual disability or previously diagnosed cognitive or psychiatric disorders underwent standardized neuropsychological assessment across seven cognitive domains commonly reported as affected in NF1, particularly in pediatric populations: visual memory, verbal memory, executive function, attention, visuospatial ability, working memory, and visuomotor speed. Participants also completed questionnaires assessing sociodemographic and psychological variables. Cognitive performance was standardized using age-adjusted normative Z-scores. Adults with NF1 performed below the normative mean across several cognitive domains relative to age-adjusted Spanish reference data. Executive function showed clinically significant impairment (z&#x2009;=&#x2009;-2.267), whereas attention showed low-average performance (z&#x2009;=&#x2009;-1.171). Although attention was associated with skin severity and visuospatial ability with depressive symptoms (p&#x2009;<&#x2009;0.05), these associations were not significant after correction for multiple comparisons. These findings suggest a consistent pattern of cognitive underperformance in adults with NF1 without previous neurological or psychological conditions affecting cognitive functioning, supporting the presence of a specific cognitive vulnerability associated with the condition. Although some clinical factors showed associations with specific cognitive domains, these relations were small and did not remain significant after correction for multiple comparisons. These results highlight the importance of routine cognitive assessment and targeted cognitive and psychosocial support strategies, including their integration into genetic counseling, to improve clinical follow-up and patient care.

To describe the implementation of the Agency for Healthcare Research and Quality safety program for improving skin care and multidrug-resistant organism prevention in long-term care (LTC), a national program that emphasized skin care and bathing to prevent multidrug-resistant organism transmission in LTC facilities, which had a 97% (309/318 enrolled LTC facilities) retention rate. A quality improvement initiative that used a mixed-methods approach to assess process outcomes. Nursing leadership and direct-care staff at LTC facilities in the United States. The 18-month intervention (June 2023-November 2024) included educational webinars, office hours, and supporting materials. Implementation advisors (IAs) provided ongoing support to sites and assisted with data submission. Quantitative data on log-ins to webinars and office hours as well as resource downloads measured engagement. Qualitative analysis of reports and debriefing calls from the IAs provided perspective on implementation successes and challenges. Educational content comprised 19 webinars delivered over 18 months, office hours offered twice monthly, and supporting material that included 60 one-page "Teachable Moments" designed to promote practice change among direct-care staff. Although webinar log-ins and office hours decreased over time, participants claimed 1031 continuing education credits throughout the program. Of the 6104 downloads of supporting material, 4713 (77%) were for Teachable Moment documents. Qualitative analysis of the IA's reports and debriefing calls yielded 4 themes: program engagement, data collection and reporting, enhanced barrier precautions, and the role of IAs. The availability of continuing education credit, inclusion of flexible, high-interest educational content adaptable to each site's workflow, combined with robust implementation support, and low-burden data requirements likely contributed to sustaining high program retention. This approach can be adopted for future quality improvement programs, informing the strategy for public health agencies, quality improvement organizations, and LTC systems seeking to strengthen their infection prevention practices.

Psoriasis represents a prevalent long-term inflammatory skin condition marked by the dysregulation of immune responses. T cells are integral to the pathogenesis of psoriasis. This study conducted a comprehensive analysis to recognize biomarkers associated with T cell infiltration in psoriasis and to elucidate their underlying molecular mechanisms. Three biomarkers (AKR1B10, C10orf99, and CKS2) demonstrated high sensitivity and specificity in receiver operating characteristic (ROC) curve, and the reliability of the developed nomogram diagnostic model was observed. In addition, gene set enrichment analysis (GSEA) revealed notable enrichment of the biomarkers in the NOD-like receptor signaling pathway and focal adhesion. Immune infiltration analysis indicated elevated levels of activated B cells and CD8 T cells in psoriasis samples, with the biomarkers showing meaningful correlations with the majority of immune cell infiltration statuses. Importantly, preliminary reverse transcription quantitative PCR (RT-qPCR) validation showed increased expression of AKR1B10, C10orf99, and CKS2 in psoriasis tissues, confirmed higher expression of AKR1B10, C10orf99, and CKS2 in psoriasis patients. AKR1B10, C10orf99, and CKS2 may serve as candidate molecules for future mechanistic studies and provide potential diagnostic biomarkers for further investigation of psoriasis-related immune regulation.

C5a, the most potent anaphylatoxin in the complement system, exerts its effects through the canonical G protein-coupled receptor C5aR1 and the arrestin-coupled receptor C5aR2. Despite the critical role of C5aR2 in immunomodulation, the molecular mechanisms underlying its biased signaling, ligand recognition, and associated pathophysiology remain poorly understood. Here, we report cryo-electron microscopy structures of &#x3b2;-arrestin 1-bound C5aR2 and C5aR1 stimulated by C5a or its metabolite C5adesArg. By combining structural analysis with functional assays, we identified the key structural determinants that prevent G protein coupling and confer intrinsic bias toward &#x3b2;-arrestins. Comparative analysis elucidated the distinct ligand recognition mechanism of C5aR2 and explained the retained affinity of C5adesArg for C5aR2. These findings guided the rational design of ZQ105, a highly selective C5aR2 agonist. Leveraging ZQ105 as a chemical probe, functional studies revealed that selective C5aR2 activation induces distinct pro-inflammatory responses and receptor internalization in neutrophils. This study provides novel structural insights into transducer engagement and ligand recognition by C5aR2, yielding a valuable pharmacological tool for exploring C5aR2-related pathophysiological processes.

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Allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, and food allergies, are characterized by immune dysregulation, epithelial barrier dysfunction, and exaggerated type 2 inflammation. Although current therapeutic strategies have improved disease management, many treatments remain symptomatic, costly, and insufficiently effective in a substantial proportion of patients. Increasing recognition of the gut-immune axis has shifted attention toward microbiome-derived therapeutic approaches. However, safety concerns and inconsistent clinical outcomes associated with live probiotics have accelerated interest in postbiotics, defined as preparations of inanimate microorganisms and/or their bioactive components that confer health benefits to the host.&#xa0;This comprehensive review summarizes current mechanistic, translational, and clinical evidence regarding the role of postbiotics in allergic diseases. Particular emphasis is placed on immunological checkpoints targeted by postbiotic-derived bioactive molecules, including modulation of Th1/Th2 balance, induction of regulatory T cells, restoration of epithelial barrier integrity, regulation of innate lymphoid cells, and systemic immune signaling through the gut-lung and gut-skin axes.&#xa0;Accumulating evidence indicates that postbiotics-including short-chain fatty acids, cell wall components, extracellular vesicles, exopolysaccharides, and microbial metabolites-can modulate immune responses independently of microbial viability. Preclinical studies consistently demonstrate that postbiotics restore immune tolerance, attenuate allergic inflammation, and improve epithelial barrier function. Clinical studies, particularly in atopic dermatitis, have shown promising but heterogeneous outcomes, highlighting the need for standardized formulations and biomarker-guided patient stratification.&#xa0;Postbiotics represent a mechanistically distinct and potentially safer microbiome-based therapeutic strategy for allergic diseases. Nevertheless, important challenges remain regarding standardization, regulatory harmonization, mechanistic characterization, and long-term clinical validation. Future progress will depend on rigorously designed longitudinal studies, multi-omics integration, and precision medicine approaches to determine whether postbiotics can evolve from adjunctive therapies into disease-modifying interventions.

The trend of homemade sunscreen recipes has rapidly gained popularity over the last decade, being largely fueled by social media influencers, natural health blogs, and the growing mistrust of large health organizations like the US Food and Drug Administration (FDA). Consumers are increasingly drawn to products labeled "natural," "organic," "vegan," and "cruelty-free," often conflating these terms with safety and effectiveness. However, when applied to sun protection, these assumptions can be dangerously misleading. According to the FDA, there is no verified mathematical formula that can be used to determine an accurate sun protection factor (SPF) rating for the amount of zinc oxide used in many of the recipes found online. The objective of this review is to examine the rising popularity and efficacy of homemade sunscreens compared to commercial sunscreens and highlight the potential public health implications of skin cancer risk related to homemade sunscreen use. Multiple databases were searched to find current and relevant literature analyzing the social media impact relating to homemade sunscreens and the efficacy of homemade sunscreens compared to commercially available products. Digital content that included or discussed homemade sunscreen recipes was included as well to provide examples of information trending online. One study analyzing social media trends found that many strong, unverified claims relating to homemade sunscreen versus commercial sunscreen use are being presented in the media, potentially influencing public knowledge. Additional studies analyzing the components of homemade sunscreen recipes compared to components in commercially available products found that homemade sunscreens offer little to no sun protection, therefore increasing the risk of UV damage for individuals using homemade products. Based on the presented evidence, the adoption of unregulated homemade sunscreens presents a substantial threat to public health. Misinformation spread through social media and influencer culture may unintentionally contribute to an increase in UV-related skin cancers. Greater efforts are needed from health care professionals, regulatory bodies, and online platforms to educate the public and promote the use of scientifically validated sun protection methods.

Diabetic ulcers (DUs) are characterized by delayed repair, persistent inflammation, and impaired angiogenesis, and effective topical treatments remain limited. To investigate the therapeutic effects and mechanisms of Germacrone in DU healing. Network pharmacology and molecular docking were utilized to predict therapeutic targets. In vitro assays evaluated Germacrone's biological effects and pathway dependence. The effects of Germacrone on diabetic wound healing were assessed in a streptozotocin (STZ)-induced diabetic mouse model. Network pharmacology analysis identified angiogenesis-related Hedgehog signaling as a potential pathway mediating the effects of Germacrone in DUs. Molecular docking showed favorable binding between Germacrone and the Hedgehog-related regulatory molecule GSK3B, with a predicted binding energy of -7.3&#xa0;kcal/mol, and CETSA further supported intracellular target engagement between Germacrone and GSK3B. In vitro experiments showed that Germacrone suppressed GSK3B kinase activity, as indicated by increased inhibitory phosphorylation of GSK3B at Ser9 and reduced phosphorylation of &#x3b2;-catenin. Moreover, Germacrone promoted HUVEC proliferation, reduced IL-1&#x3b2; and IL-6 mRNA expression, increased Hedgehog-related protein expression, and enhanced HUVEC migration and tube formation. Importantly, Hedgehog pathway inhibition with GANT61 attenuated the promotive effects of Germacrone on HUVEC migration and tube formation, suggesting dependence on Hedgehog signaling. In STZ-induced diabetic mice, Germacrone markedly accelerated wound closure, enhanced Hedgehog signaling and angiogenesis, suppressed inflammatory activation, and improved re-epithelialization. Germacrone effectively promotes DU healing by activating the Hedgehog signaling pathway, enhancing angiogenesis, and reducing inflammation. This study highlights Germacrone as a promising therapeutic candidate for DUs.