Aging is a complex process influenced by various factors, including gut microbiota and food likings. Focusing on gut and dietary health is a crucial strategy for promoting long-term health and active aging. This study investigates the reciprocal causal relationships between gut microbiota, food likings and aging using Mendelian Randomization (MR) approaches. We leveraged the summary statistics of gut microbiota (n = 5,959), food likings (n = 161,625), and three aging phenotypes including telomere length (n = 472,174), facial aging (n = 423,999), and frailty index (n = 175,226). We performed bidirectional MR analyses to explore the causal effects of gut microbiota and food likings on aging, and mediation analyses to discover potential mediating gut microbiota and food likings. We discovered numerous correlations between gut microbiota, food likings, and aging. Notably, we identified that Lachnospira rogosae and CAG-83 sp000435555 influenced the frailty index through diet fizzy drinks liking, while UBA2922 sp900313925 had an effect through F-wine liking. Our findings provide insights into these complex interactions and offer a basis for personalized dietary interventions to slow aging and improve health, potentially informing new strategies for preventing age-related diseases.

Infected high-stage pressure injuries (IHPIs) in older, immobile patients lack validated biomarkers to distinguish infection-driven chronicity and guide therapy. We leveraged multi-omics integration to nominate biomarker candidates and mechanistic signatures of IHPI. An aged-rat IHPI model was established by combining deep-tissue magnetic compression with Staphylococcus aureus inoculation. Acute wounds (AW), non-infected high-stage pressure injuries (HPI), and IHPI were compared through laser-speckle perfusion imaging, in vivo bioluminescence for bacterial burden, histology, and immunohistochemistry. Serum IL-1β was measured by ELISA. Bulk RNA sequencing (AW n = 3, HPI n = 3, IHPI n = 5) and quantitative proteomics (AW n = 3, IHPI n = 5) were cross-layer integrated using network analysis. IHPI wounds exhibited delayed closure, purulent exudate, reduced angiogenesis, diminished collagen deposition, and elevated systemic inflammation. Transcriptomic data revealed activation of innate-immune, chemokine, and keratinization programs, while proteomics highlighted NF-κB, lysosomal, and extracellular-matrix (ECM) remodeling processes. Integration defined a translational immune biomarker panel-SELL (L-selectin)↑, ARG1↑, CD163↓, IL33↓-implicating sustained leukocyte recruitment and impaired resolution. Concurrently, MMP9-driven ECM degradation and enrichment of sarcomeric/calcium-handling proteins (Tnnt2, Casq2, Tnnc1, Myh8, Myl4) indicated deep-tissue and muscle-layer involvement. Multi-omics integration in an aged-rat IHPI model yields a translational immune biomarker panel (SELL↑/ARG1↑/CD163↓/IL33↓) for detection/stratification and a mechanistically coherent ECM-remodeling signature (MMP9↑) that explains tissue-level non-healing. Using accessible assays (IHC/ELISA), these candidates prioritize testable biomarkers for IHPI detection, stratification, and therapeutic targeting, while the model provides a translational platform for future validation.

"Suanrou", a characteristic moist fermented meat product indigenous to Southwest China, inspiring this study based on "analogical orientation" and "shape-based nourishment" concepts of traditional Chinese medicine. This study aimed to isolate lactic acid bacteria (LAB) with broad-spectrum antibacterial activity against common infectious bacteria in chronic diabetic wounds from Suanrou to promote chronic wound healing. 347 lactic acid bacteria strains were isolated from 6 types of Suanrou samples. After many screening, including antibacterial assay, hemolysis test, antibiotic susceptibility test, and aggregation assay, Lacticaseibacillus paracasei YL36 was identified as strain with optimal comprehensive performance. Subsequent analyses of whole-genome sequencing and metabolomics were conducted, along with further validation using cellular and animal models. L. paracasei YL36 exhibited inhibitory activity against five common pathogenic bacteria in chronic wounds, including Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Streptococcus haemolyticus. Genomic analysis revealed that strain harbors gene clusters responsible for synthesizing antimicrobial metabolites such as terpenoids and class II bacteriocins; its genome length was 3,029,192 bp, with a G + C content of 46.38 %. Additionally, L. paracasei YL36 possessed rich and diverse metabolic profile, with clear associations between its metabolic pathways, metabolites, and antibacterial activity. The strain displayed excellent adhesion and colonization capabilities, with no clinically relevant antibiotic resistance genes or virulence factor genes detected in its genome, and a hemolysis rate of <5 %. L. paracasei YL36 is a safe and functionally excellent probiotic candidate strain with potential application value in the field of chronic wound healing.

OBJECTIVE:To investigate the association between the Prognostic Nutritional Index (PNI) and mortality risk in intensive care unit (ICU) patients with pressure injuries (PIs) to provide a basis for early risk stratification and clinical decision-making. APPROACH:This retrospective cohort study used data from the Medical Information Mart for Intensive Care IV database, which included 972 ICU patients diagnosed with PI. Patients were stratified by median PNI levels, and Kaplan-Meier survival analysis, Cox regression, logistic regression, restricted cubic splines, and propensity score matching (PSM) were performed to assess the relationship between PNI and 28-day, 90-day, and ICU mortality. RESULTS:A higher PNI was significantly associated with lower 28-day (hazard ratio [HR] = 0.702, 95% confidence interval [CI] 0.551-0.895), 90-day (HR = 0.722, 95% CI: 0.576-0.905), and ICU mortality (odds ratio [OR] = 0.644, 95% CI: 0.474-0.872). An L-shaped relationship between the PNI and all-cause mortality was observed. This association remained robust after multivariate adjustment, subgroup analysis, and PSM. INNOVATION:This study is the first to evaluate the prognostic significance of the PNI in ICU patients with PIs, addressing the gap in current research by identifying a simple and accessible marker associated with mortality risk in this vulnerable population. CONCLUSION:PNI can be calculated from routine laboratory results and may guide early nutritional or wound care interventions in ICU patients with PI. A PNI value below 19.02 is associated with an increased risk of mortality (i.e., PNI <19.02 = high risk) and serves as a critical threshold for identifying patients at elevated risk.

The study of facial skin aging has attracted significant attention not only for its esthetic implications but also for its potential to shed light on the mechanisms underlying the development of age-related diseases. The purpose of this research was to systematically investigate potential drug targets for facial skin aging through multi-omics genetic methods. We utilized expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) as instruments to explore the therapeutic potential for facial skin aging. This was supplemented with transcriptome analysis and in vitro experiments, including siRNA knockdown in human HaCaT and NIH 3T3 cells, which confirmed the genetic results. Additionally, we conducted two-sample Mendelian randomization (MR) to investigate the causal effect of facial aging on skin neoplasms and performed metabolome-wide MR to screen for metabolic biomarkers associated with facial aging. Through integrated analysis of eQTLs and colocalization, five potential druggable genes were identified, including BRSK2, IL20RB, NEK10, RAB35, and SEMA7A. Of these, SEMA7A showed strong evidence with facial skin aging through subsequent pQTL and colocalization analysis. Additionally, genetically determined facial skin aging exhibited a significant causal effect on basal cell carcinoma (BCC) (OR = 3.973, 95

BACKGROUND:Impaired healing of diabetic foot ulcers (DFU) is a major clinical challenge. This condition is driven by unresolved inflammation and cellular dysfunction. However, the specific role of macrophage ferroptosis in this process remains poorly defined. PURPOSE:This study aimed to investigate the contribution of macrophage ferroptosis to DFU pathogenesis. We also evaluated the therapeutic effect and underlying mechanism of the Ruan Jian Qing Mai formula (RJQM). Our investigation focused on the NINJ1-ferroptosis-inflammation axis and its role in intercellular communication. METHODS:We combined single-cell RNA sequencing of human wound tissues with a streptozotocin-induced diabetic mouse model. The chemical composition of RJQM was characterized by HPLC-MS. For in vitro experiments, we used macrophages stimulated with high glucose and LPS to model diabetic conditions. Key markers for ferroptosis, inflammation, and signaling pathways were assessed using Western blot, qPCR, and flow cytometry. Finally, endothelial cell behavior was evaluated through migration and tube formation assays. RESULTS:Our analysis revealed that macrophages exhibited the highest ferroptosis activity in diabetic wounds. In diabetic mice, RJQM treatment accelerated wound healing in a ferroptosis-dependent manner. We identified 87 compounds in RJQM. These compounds effectively suppressed ferroptosis by enhancing GPX4/xCT expression while reducing lipid peroxidation and iron overload. Mechanistically, RJQM inhibited a positive feedback loop involving NINJ1 and ferroptosis, and also suppressed downstream STAT3 activation. Furthermore, conditioned media from RJQM-treated macrophages promoted endothelial migration and tube formation. This pro-angiogenic effect was reversed by NINJ1 overexpression, confirming its critical role. CONCLUSION:RJQM promotes diabetic wound repair by targeting the NINJ1-STAT3-ferroptosis pathway in macrophages. This action reduces inflammation and restores the cells' pro-angiogenic functions. Our findings support RJQM as a promising therapeutic strategy for DFU.

Background Autologous diced costal cartilage is widely used in rhinoplasty and auricular reconstruction; however, long-term graft survival is often compromised by oxidative stress, inflammation, and insufficient vascularization after transplantation. Emerging evidence suggests that NLRP3/Caspase-1/GSDMD-mediated pyroptosis and impaired autophagy contribute to chondrocyte injury and cartilage degeneration. This study investigated whether adipose-derived stem cell (ADSC) sheets could improve diced cartilage graft survival by regulating the autophagy–pyroptosis axis. Methods A rabbit ectopic transplantation model was established to evaluate the effects of ADSC sheet wrapping on diced cartilage grafts in vivo. Histological staining, TUNEL assay, immunohistochemistry, and immunofluorescence were performed to assess graft morphology, apoptosis, oxidative stress, pyroptosis, and autophagy. In vitro, human chondrocytes were exposed to H₂O₂-induced oxidative stress and co-cultured with ADSCs. Cell viability, reactive oxygen species (ROS), migration, inflammatory cytokines, and related molecular markers were analyzed by CCK-8, flow cytometry, RT-qPCR, western blotting, ELISA, and transmission electron microscopy. Autophagy was modulated using rapamycin and bafilomycin A1. Statistical analyses were performed using Student’s t-test or one-way ANOVA. Results ADSC sheet-wrapped grafts showed improved cartilage architecture, increased retention of chondrocyte lacunae, reduced apoptosis and nuclear loss, and enhanced type II collagen deposition compared with control and autologous perichondrium groups. ADSC sheets significantly suppressed NLRP3, Caspase-1, GSDMD, and NOX4 expression, while increasing SOD1, LC3, and Beclin-1 and decreasing P62, indicating reduced oxidative stress, inhibited pyroptosis, and enhanced autophagy. In vitro, ADSCs attenuated H₂O₂-induced oxidative stress, reduced ROS accumulation and inflammatory cytokine secretion, restored autophagic flux, and suppressed pyroptosis in chondrocytes. Rapamycin further enhanced these protective effects, whereas bafilomycin A1 partially reversed them. Transcriptomic analysis further confirmed coordinated regulation of autophagy-, inflammation-, and metabolism-related pathways. Conclusions ADSC sheets function as a biomimetic regenerative niche that improves the transplantation microenvironment and enhances diced cartilage graft survival by promoting autophagy and suppressing NLRP3/Caspase-1/GSDMD-mediated pyroptosis. This strategy provides a promising stem cell-based approach for improving long-term cartilage graft stability in reconstructive surgery.

The rapid expansion of social media has significantly altered the landscape of patient communication, professional branding, and ethical practice in plastic surgery. In China, where the aesthetic medicine market is growing rapidly, surgeons increasingly rely on platforms such as Xiaohongshu and Douyin to engage with patients. However, the implications of this digital transformation for clinical practice remain insufficiently explored. A national cross-sectional survey of 800 licensed plastic surgeons was conducted from December 2024 to March 2025. The questionnaire assessed platform usage, perceived benefits, patient interactions, and ethical concerns. Data were analyzed using descriptive statistics and correlation analysis. WeChat Video (62.75 www.springer.com/00266 .

Diabetic implant failure is primarily driven by hyperglycemia-induced inflammation and reduced nitric oxide (NO) bioavailability, both of which impair angiogenesis. Conventional Ti6Al4V lacks bioactivity and risks cytotoxicity from aluminum or vanadium ion release; moreover, titanium alloys produced by existing laser powder bed fusion (LPBF) intrinsically retain high residual oxygen (>= 0.24 wt%), leading to oxygen-dominated interstitial strengthening that triggers excessive oxidative stress. To address this, we developed a retrofitted LPBF platform incorporating a jet pump evacuation module, which reduces residual oxygen to below 0.04 vol% during building, thereby enabling an ultra-low-oxygen, nitrogen-dominated strengthening mechanism. The resulting Ti-N-LOC alloy (0.085 wt% O, 0.536 wt% N) provides sustained release of trace NO, effectively suppressing inflammation and promoting osseointegration. Compared to Ti6Al4V, Ti-N-LOC exhibits superior mechanical properties (83% higher elongation) and enhanced biocompatibility. Mechanistically, the sustained release of trace NO activates the NO-PPAR gamma-PI3K/AKT-VEGF axis and inhibits the ROS-MAPK pathway, thereby promoting M2 macrophage polarization and enhancing bone integration. By decoupling nitrogen strengthening from oxygen-induced oxidative stress, Ti-N-LOC offers a clinically translatable strategy for patient-specific implants in diabetic populations and establishes a viable framework for the biomedical application of interstitially strengthened alloys.

Circular RNAs (circRNAs) contribute to gene expression regulation by interacting with splicing factors, a process that is often disrupted in cancers such as cutaneous melanoma (CM). A circRNA microarray analysis was performed to identify differentially expressed circRNAs. qRT‒PCR was conducted to confirm the expression of circROR1. CCK-8, colony formation, wound healing, and transwell assays were used to analyze proliferation, metastasis and apoptosis in CM cells. Xenograft models and IHC experiments were established to confirm the effects of circROR1 on tumor growth and metastasis in vivo. RNA sequencing and pull-down–MS experiments were performed to identify the mechanisms downstream of circROR1. Nuclear and cytoplasmic fractionation, along with FISH experiments, were conducted to determine the cellular localization of circROR1. To target circROR1 for CM treatment, we used a microfluidic strategy to develop FA-PEG(si-circ) nanoparticles for efficient siRNA delivery. In CM samples, circROR1 levels were positively correlated with HNRNPL levels and tumor metastasis but negatively correlated with FOXO4 protein levels. CircROR1 was prevalent in CM, and its upregulation increased the levels of factors involved in epithelial–mesenchymal transition, cell migration, and invasion. CircROR1 overexpression conferred resistance to PD-L1-antibody therapy in CM cells by downregulating PD-L1 expression. CircROR1 recruited HNRNPL, influencing its nuclear translocation, and further prevented intron retention in FOXO4 mRNA. In HNRNPL-overexpressing CM cells, circROR1 upregulation inhibited FOXO4α expression and promoted FOXO4ζ expression. Increased FOXO4α expression counteracted circROR1’s effects and suppressed metastatic behaviors. FA-PEG(si-circ) enhanced siRNA stability and efficiency, reducing CM cell lung colonization in vivo. This study identified circROR1 as an oncogenic circular RNA that plays a crucial role in tumor progression and metastasis. CircROR1-targeted nanotherapy is a promising option for the treatment of metastatic cancer.

BACKGROUND:Driven by advancements in deep learning, surgical robots, and predictive modeling technologies, the integration of artificial intelligence (AI) and plastic surgery has expanded rapidly. Although AI shows the potential to enhance precision and efficiency, its clinical integration faces challenges, including ethical concerns and interdisciplinary complexity, which require a systematic analysis of research trends. METHODS:The CiteSpace and VOSviewer software were used to conduct a quantitative analysis of 235 documents in the core collection of Web of Science from 2016 to 2024. Co-citation networks, keyword co-occurrence, burst detection, and cluster analysis were employed to map the research trajectories. The inclusion criteria gave priority to studies that explicitly incorporated artificial intelligence into surgical designs or outcomes. The contributions of countries, institutions, and authors were evaluated through centrality indicators. RESULT:Publications related to artificial intelligence have grown exponentially, with the USA, Germany, and Canada leading research output. Harvard and Stanford Universities dominate in terms of institutional contributions, but cross-institutional collaboration remains limited. The keyword cluster highlights the innovations of artificial intelligence in breast reconstruction, facial analysis, and automated grading systems. Burst terms such as "deep learning," "risk assessment," and "attractiveness" underscore AI's role in optimizing surgical outcomes, but they also expose biases against Western-centric beauty standards. Ethical concerns, dataset diversity gaps, and overreliance on AI-driven decisions have become key obstacles. CONCLUSION:The integration of artificial intelligence in plastic surgery goes beyond the utility based on tools and into data-informed surgical engineering. The persistent gap in collaboration and dataset diversity highlights the need for global, interdisciplinary efforts to address technical and ethical challenges while advancing AI's clinical utility. Future research must prioritize transparency, inclusivity, and collaborative innovation to realize AI's transformative potential while mitigating risks. LEVEL OF EVIDENCE IV:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

OBJECTIVES:Sodium hydroxide (NaOH) is known to cause severe injuries through lipid saponification; however, the mechanisms underlying NaOH-induced skin injuries, particularly their effects on lipid metabolism and ferroptosis, are unclear. Here, we aimed to elucidate these mechanisms based on lipid profile evaluations and ferroptosis occurrence. METHODS:We used experimental rat models of NaOH-induced skin burns (skin exposed to 0.05% NaOH for 90 or 180 s) alongside a sham-treated control group. Skin morphology and integrity were assessed. Differentially expressed lipid profiles were monitored via untargeted lipidomics. Oxidative stress, lipid peroxidation, and iron metabolism were also assessed. The expression of ferroptosis-associated genes, including acyl-CoA synthetase long-chain family member 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and glutathione peroxidase 4 (GPX4), was analysed using immunohistochemical and quantitative reverse transcription-polymerase chain reaction analyses. RESULTS:NaOH exposure for 90 and 180 s caused second- and third-degree burns, respectively, leading to elevated and reduced levels of polyunsaturated and monosaturated fatty acid phospholipids, respectively. Both groups showed significant increases in reactive oxygen species, ferrous iron, and malondialdehyde levels and significant decreases in glutathione levels. ACSL4 and LPCAT3 expression increased, and GPX4 expression decreased. CONCLUSION:NaOH-induced skin burns disrupt skin appendages, resulting in lipid metabolism alterations and ferroptosis induction. These findings could provide valuable insights for elucidating the precise mechanisms underlying ferroptosis in the context of NaOH burns and for identifying potential therapeutic strategies.

Introduction: Secondary hyperparathyroidism (SHPT) remains a major complication of chronic kidney disease (CKD), characterized by parathyroid hyperplasia, inflammation, and parathyroid hormone (PTH) excessive secretion, affecting millions of patients worldwide. Current treatments can temporarily restore calcium–phosphate balance while failing to provide lasting relief due to unchecked parathyroid cell proliferation, which mechanisms remained unknown. Signal transducer and activator of transcription 3 (STAT3) has been implicated in the autophagic process and diverse cellular processes, including cell growth and apoptosis. Objectives: Present study seeks to uncover roles of STAT3 pathway-regulated autophagy and macrophage-mediated inflammation in SHPT progression. Building upon sequencing and pathology results, we propose a potential therapeutic approach for SHPT utilizing macrophage-derived exosomes loaded with a STAT3 inhibitor. Methods: RNA-seq and tissue-molecular examination were applied to identify the role of STAT3 and macrophage in SHPT. This study fabricates engineered M2 macrophage-derived exosomes loading with STAT3 inhibitor Stattic (M2-E@St) by a dual physics encapsulation. Results: Suppressing STAT3 phosphorylation through inhibitor, Stattic (St), SHPT primary cell autophagy blockage relieved shown as p62 and p53 reduced, LC3B II v.s. I elevated with cell proliferation suppression. Based on dual SHPT drivers, an M2 macrophage-derived exosomes-camouflaged nanomedicine, M2-E@St, was developed that can reprogram macrophages anti-inflammation and alleviate STAT3-mediated autophagy inhibition, reducing parathyroid cell proliferation in the parathyroid gland. M2-E@St efficacy on SHPT was evaluated at a comprehensive level, including in vitro SHPT primary cells and macrophages co-culture system, SHPT mouse model, human SHPT primary cells, and macrophage organoids. Once uptake by parathyroid cells and macrophages, M2-E@St blocks STAT3/mTOR signaling pathway and promotes downstream autophagy, while M2-E induces macrophage M2 polarization. Results show M2-E@St significantly reduced STAT3 phosphorylation, resumed autophagy, curbed cell proliferation, alleviated inflammation, and lowered PTH secretion in vitro and in vivo. Conclusion: Results suggest exosome-based Stattic delivery may serve as a promising therapy for SHPT.

Melanoma, a highly malignant skin cancer, has seen a rising incidence and death toll. MRGPRF is a novel melanoma suppressor that inhibits the PI3K/AKT pathway. However, the regulation of MRGPRF in melanoma remains unclear. Here, 40 ubiquitin-specific proteases (USPs) are screened and USP45 is identified as a significant stabilizer of MRGPRF. Immunohistochemistry on melanoma patient biopsies demonstrates that USP45 expression is markedly reduced in melanoma tissues compared to adjacent noncancerous epidermis. Bioinformatic analyses corroborate that USP45 mRNA levels are downregulated in melanoma, and low USP45 expression is associated with poor patient prognosis. Functional assays demonstrate that USP45 overexpression inhibits melanoma cell malignancy, whereas USP45 knockdown promotes it. Mechanistically, USP45's catalytic domain directly binds to the N-terminal of MRGPRF and stabilizes MRGPRF, likely by removing its K63-linked ubiquitination in melanoma cells. The antimelanoma effects of USP45 are mitigated by MRGPRF depletion, while MRGPRF overexpression rescues the enhanced malignant phenotype induced by USP45 deficiency. In vivo, a melanoma xenograft mouse model shows that USP45 overexpression significantly impairs melanoma progression. These findings establish USP45 as a melanoma suppressor, at least partially through its stabilization of MRGPRF, highlighting a novel mechanism in melanoma pathogenesis and suggesting that USP45 agonists may serve as potential therapeutic agents.

The skin serves as the body's primary defense barrier, crucial for protection against external aggressors and maintaining stable body temperature. Diabetic patients, due to vascular and neuropathic damage induced by hyperglycemia, experience significantly impaired healing capacity, rendering them vulnerable to chronic wounds and infections, which may necessitate amputations. Therefore, investigating effective treatments that expedite wound healing in diabetic patients is of considerable clinical importance. This study evaluates the efficacy of Dextran-Gelatin-Gellan Gum composite microspheres (DGGcm) loaded with Lactobacillus rhamnosus (LGG) in the repair of full-thickness skin defects and infected wounds in diabetic rats. Uniformly shaped DGGcm were prepared using a combination of emulsification and microfluidic technology. After LGG loading, in vitro experiments-including cell live/dead staining, CCK-8 proliferation assays, migration and tubule formation evaluations, and antibacterial testing-were performed to assess the effects of DGGcm combined with LGG on cell proliferation, migration, angiogenesis, and antibacterial efficacy. Subsequently, a diabetic rat model with full-thickness skin defects and infections was established to compare the therapeutic effects of DGGcm combined with LGG against other treatment groups. Histological analysis, qRT-PCR, and Western Blot (WB) assays were utilized to evaluate tissue repair, collagen deposition, and cytokine expression. The study demonstrated that DGGcm possesses excellent biocompatibility and degradability, with LGG incorporation facilitating sustained release. In vitro experiments revealed that DGGcm combined with LGG significantly enhanced cell proliferation, migration, tubule formation, and antibacterial properties. In vivo results indicated that this combination markedly accelerated wound healing in diabetic rats. Histological analysis revealed that the DGGcm-LGG formulation closely resembled normal skin architecture, exhibiting effective tissue restoration, fiber alignment, and collagen deposition. Molecular biology analyses indicated that DGGcm combined with LGG significantly suppressed the expression of the pro-inflammatory cytokine IL-6, elevated the expression of the anti-inflammatory cytokine IL-10, and promoted the expression of critical wound healing proteins, including CD31, KI-67, MMP-2, TGF-β, VEGF, and α-SMA. This study successfully developed DGGcm with exceptional biocompatibility and degradability, effectively loading LGG to achieve sustained release. The DGGcm-LGG combination significantly enhances cell proliferation, migration, tubule formation, and antibacterial efficacy, thereby promoting the healing of infected wounds in diabetic rats. These findings propose a novel therapeutic strategy with substantial clinical application potential for wound repair in diabetic patients.

BACKGROUND:Melanoma is highly aggressive, metastatic with a poor prognosis. Despite significant advances in targeted therapies and immunotherapies, their efficiency limited by drug resistance. Tanshinone IIA (Tan IIA), a bioactive compound derived from Traditional Chinese plant, exhibits significant anticancer potential, which still needs more research in its complex regulatory mechanisms. PURPOSE:This study aimed to elucidate the putative targets and regulatory mechanisms of Tan IIA in anti-melanoma, with a focus on its role in inducing ferroptosis. STUDY DESIGN:We designed the experiment to explore the effects of Tan IIA on melanoma through both in vitro and in vivo experiments and to investigate the underlying mechanisms through transcriptomics combining network pharmacology analysis. METHOD:Ferroptosis monitored by Malondialdehyde (MDA), Fe2+, reactive oxygen species (ROS) and glutathione (GSH) in vivo and in vitro. RNA sequence was performed to explore the key regulatory pathways involved in Tan IIA-induced ferroptosis. Chromatin immunoprecipitation (ChIP) and Luciferase assays were used to validate transcription factor responsible for prostaglandin-endoperoxide synthase 2 (PTGS2) regulation. Additionally, RT-qPCR, western blot, IF, IHC were aimed to evaluate the expression of target gene. RESULT:Tan IIA markedly suppresses melanoma growth in a xenograft model. The same effect performed on inhibition melanoma cells and promotion to ferroptosis with accumulation of ROS, MDA, and Fe²⁺levels and GSH consumption. RNA sequencing and public database analysis revealed that Tan IIA regulates PTGS2, the critical marker of ferroptosis, and PTGS2-knockdown attenuates Tan IIA -induced ferroptosis in melanoma cells. Furthermore, we identified that Tan IIA stimulate signal transducer and activator of transcription 1 (STAT1), a transcription factor, promoting PTGS2 expression and localized in the cell cytoplasm. Moreover, downregulation of the transcription factor STAT1 lead to PTGS2 downregulation and also inhibit ferroptosis in melanoma. CONCLUSION:This study, the first to link Tan IIA-induced ferroptosis to the STAT1/PTGS2 axis in melanoma, identifies STAT1 and PTGS2 as novel therapeutic targets for melanoma, which demonstrates the potential of natural compounds Tan IIA in overcoming drug resistance and integrates traditional medicine with advanced molecular techniques for mechanistic exploration.

Healing of diabetic wounds is significantly impeded by a complex environment comprising biofilm formation, excessive inflammation, and compromised angiogenic capacity, leading to a disordered physiological healing process. Restoration and maintenance of a normal and orderly healing process in diabetic wounds remain unmet therapeutic objectives. Herein, an innovative bimetal-phenolic network hydrogel system is designed with a concentric circular structure, enabling dual-drug delivery with differentiated release kinetics. The outer layer, Cu@TA (tannic acid)-loaded ε-PL (poly-l-lysine)-SilMA (methacrylated silk), is engineered for an initial release to scavenge reactive oxygen species and exert antibacterial and anti-inflammatory effects. The inner layer, Zn@TA-loaded ε-PL-SilMA, is designed for sustained release to promote cell migration, modulate the immune microenvironment, and induce angiogenesis. By incorporating a polyphenolic-metal network, the Cu@TA/Zn@TA/ε-PL-SilMA hydrogel can alter its degradation rate, enabling the sequential release of Cu@TA and Zn@TA. An in vivo diabetic rat wound model, transcriptomic sequencing, and histological staining analyses revealed that the Cu@TA/Zn@TA/ε-PL-SilMA hydrogel effectively activates the Wnt/β-catenin signaling pathway, synergistically promoting wound healing by accelerating angiogenesis, effectively reducing inflammation, and promoting collagen deposition. This innovative hydrogel, with sequential degradation and release properties, is broadly applicable, ensures orderly wound healing, and holds promise for accelerating diabetic wound repair.

Infection, sustained inflammation, and angiogenesis disorders delay skin wound healing. Consequently, there is a substantial demand for bioactive wound dressings that exhibit antibacterial properties, modulate inflammation, and facilitate wound healing. In this study, we developed a double-layer bioactive Janus electrospun nanofiber (ESF) dressing endowed with antibacterial and anti-inflammatory capabilities. The beaded hydrophobic outer layer acts as a physical barrier, preventing external fluids from contaminating the dressing and discouraging microbial attachment and growth. In contrast, the coaxial hydrophilic inner layer supports cell adhesion and migration. The results of the CCK-8 test and in vitro scratch wound healing assay of fibroblasts and endothelial cells demonstrated that the polycaprolactone/phycocyanin/chitosan/poly(ethylene oxide)/ε-poly-l-lysine Janus ESF dressing increased cell viability and migration. The RAW264.7 macrophage phenotypic switching assay results indicated the anti-inflammatory effects of the dressing. The dressing also exhibited a satisfactory antibacterial effect. Herein, the bioactive Janus ESF dressing hold considerable promise for wound healing.

This study introduces an innovative design and application of a nitrogen-interstitially strengthened Cu-Fe-Zn alloy bioactive dressing, which combines intrinsic bioactivity with electromagnetic stimulation to significantly accelerate wound healing. Interstitial nitrogen solid-solution Cu-Fe-Zn alloys were fabricated by integrating a low-oxygen controlled powder sintering process (N2(10%)/Ar (90%) atmosphere). Subsequent cold drawing generated ultrafine alloy wires (0.04 ± 0.005 mm) with a tensile strength of 1120 MPa, representing a 20.37% enhancement compared with conventional approaches. Utilizing an intelligent jacquard textile system, these Cu-Fe-Zn alloy wires and cotton yarn were woven into coaxial circular dressings tailored to wound morphology, allowing controlled directional current flow while exhibiting excellent biocompatibility and antibacterial properties. A customized electromagnetic coupling system, consisting of an electromagnetic field generator and Helmholtz coils, was developed. Integration with bioactive dressings resulted in a precise, multifunctional therapeutic platform. Electromagnetic stimulation achieved dual therapeutic outcomes: (1) activating the VEGF/p38-HSP27 signaling pathway, significantly enhancing angiogenesis (2.1-fold compared with controls) and promoting M2 macrophage polarization (+25.6%), thereby accelerating tissue regeneration; and (2) inhibiting the IL-17/NF-κB signaling axis, reducing TNF-α expression by 68%, thus effectively suppressing inflammation. This study offers essential technical insights for developing next-generation intelligent electromagnetic wound healing systems with substantial clinical potential.