Abstract Objective: Diabetic wound healing is frequently impaired by excessive oxidative stress, persistent inflammation, and insufficient tissue regeneration. The aim of this study was to develop a multifunctional cerium-based nanozyme capable of regulating the oxidative and inflammatory microenvironments to promote diabetic wound repair. Methods: A tannic acid–functionalized cerium-based nanocomposite (Ce@BSA-TA) was constructed via bovine serum albumin (BSA)-mediated biomineralization followed by tannic acid (TA) modification. The physicochemical properties and enzyme-mimetic activity of Ce@BSA-TA were characterized, and its ability to scavenge reactive oxygen species (ROS) was evaluated. Cytoprotective and pro-migratory effects were investigated in vitro under high-glucose–associated oxidative stress. A diabetic mouse model with full-thickness skin wounds was used to evaluate wound healing, inflammatory regulation, angiogenesis, and collagen deposition. Results: Benefiting from the Ce 3+ /Ce 4+ redox cycle, Ce@BSA-TA exhibited superoxide dismutase (SOD)- and catalase (CAT)-mimetic activities and effectively scavenged superoxide anions (O 2 •− ) and hydrogen peroxide (H 2 O 2 ). Ce@BSA-TA alleviated intracellular oxidative stress, protected cells from oxidative damage, and promoted fibroblast migration in vitro . In diabetic wounds, Ce@BSA-TA reduced oxidative stress and pro-inflammatory cytokine expression, promoted macrophage polarization toward the M2 phenotype, and enhanced angiogenesis and collagen deposition, which collectively accelerated wound closure. Conclusion: Ce@BSA-TA integrates ROS scavenging and immunomodulatory activities to improve the hostile microenvironment of diabetic wounds and promote tissue repair. Our study findings support the potential of multifunctional cerium-based nanozymes as a therapeutic strategy for the management of chronic diabetic wounds.
Ovarian cancer cells exploit the lipid-rich peritoneal microenvironment to sustain survival and dissemination. An increase in fatty acid uptake enriches the microenvironment in oxidizable membrane phospholipids and raises the risk of lipid peroxidation (LP)-driven ferroptosis. We argue that ovarian cancers exposed to chronic oxidative stress may acquire an enhanced dependence on ferroptosis defense pathways, particularly the solute carrier family 7 member 11 (SLC7A11)–glutathione (GSH)–glutathione peroxidase 4 (GPX4) axis, the ferroptosis suppressor protein 1 (FSP1)–coenzyme Q10 (CoQ10) system, and nuclear factor erythroid 2–related factor 2 (NRF2)-regulated antioxidant programs. Consequently, ferroptosis-targeted therapy should not be applied indiscriminately. Patient stratification is needed to identify tumors with a demonstrable dependence on anti-LP defenses. Lipidomic profiling, functional ferroptosis assays, and paired analyses of primary tumors, ascites, and metastatic lesions will be essential for identification of the patients who are most likely to benefit. This commentary proposes a biomarker-guided translational framework that integrates peroxidizable lipid burden, ongoing LP pressure, and functional defense dependence to guide patient selection and advance precision therapy in ovarian cancer.
Background: Prediabetes has a high prevalence worldwide; however, the prevalence of mental health conditions within the population with prediabetes is not well understood. This study was aimed at determining the prevalence and incidence of insomnia, fatigue, anxiety, and depression among a large, real-world cohort of adults with prediabetes, and examining demographic patterns by age and sex. Methods: This retrospective cohort analysis used data from 578,972 individuals with laboratory-confirmed prediabetes (HbA1c 5.7%–6.4%) in the TriNetX Global Collaborative Network. Outcomes were identified with ICD-10-CM codes. Prevalence was assessed over a 25-year period (2000–2025). Cumulative incidence required a 90-day washout after prediabetes diagnosis and excluded patients with prior diagnoses. Incidence rates per 1,000 person-years with 95% confidence intervals (CIs) were calculated. Analyses were stratified by age (19–39 vs. 40–65 years) and sex. Results: Anxiety, depression, fatigue, and insomnia were assessed among 578,972 participants with prediabetes (mean age 53 ± 11 years; 56.2% female). The overall prevalence of these conditions was 37.8% (95% CI: 37.78–37.82), 26.0% (95% CI: 25.98–26.02), 23.9% (95% CI: 23.88–23.92), and 15.7% (95% CI: 15.67–15.73), respectively. During a median follow-up of 628 days (IQR: 1,134 days), the cumulative incidence of these new-onset conditions (≥90 days after diagnosis, excluding prior cases) was 8.6% (95% CI: 8.53–8.67), 4.8% (95% CI: 4.74–4.86), 5.7% (95% CI: 5.64–5.76), and 4.0% (95% CI: 3.95–4.05), respectively. The incidence rates per 1,000 person-years were 34.9 (95% CI: 34.54–35.26), 22.6 (95% CI: 22.31–22.89), 20.5 (95% CI: 20.26–20.74), and 12.9 (95% CI: 12.73–13.07), respectively. In stratified analyses, middle-aged adults (40–65 years) had substantially higher incidence of all outcomes than younger adults (19–39 years) (risk ratios: 0.263–0.298; all P < 0.001). Women had consistently higher incidence than men (risk ratios: 0.593–0.754; all P < 0.001). A secondary race-stratified prevalence analysis indicated that the prevalence was highest in White individuals and lowest in Asian individuals. Conclusion: Mental health conditions affected more than one-third of patients with prediabetes. Middle-aged adults and women had the highest observed incidence. Routine mental health screening in prediabetes care is warranted, particularly among these high-risk demographic subgroups.
Background: Myocardial infarction (MI) is characterized by extensive immune activation and dynamic remodeling of the cardiac microenvironment, in which myeloid cells play critical roles in regulating inflammation and tissue repair. However, the cellular heterogeneity, developmental trajectories, and intercellular communication networks of myeloid cell subtypes during MI remain incompletely understood. Methods: Single-cell RNA sequencing (scRNA-seq) data from MI tissues were integrated to construct a comprehensive immune atlas. Cell clustering, differential expression, cell cycle, and functional enrichment analyses were performed to characterize cellular composition and biological functions. CytoTRACE, Monocle2, and Slingshot were applied to investigate macrophage differentiation trajectories, whereas transcriptional regulatory network analysis and CellChat were used to identify regulatory modules and intercellular communication pathways. Results: A total of 44,574 high-quality cells comprising 24 cell types were identified, which revealed prominent myeloid cell accumulation and enhanced immune activation in infarcted tissues. Macrophages were enriched in infarcted regions and exhibited increased proliferative activity and immune-related pathway activation. Four transcriptionally distinct macrophage subtypes were identified (C0 GPNMB +, C1 S100A4 +, C2 IL1B +, and C3 EGR1 +), among which C 1 S100A4 + macrophages predominated, displayed the strongest proliferative ability, and expressed high levels of inflammatory mediators, including IL1B, CCL3, and CXCL8. Trajectory and regulatory analyses revealed dynamic macrophage differentiation and subtype-specific transcriptional programs. Cell-cell communication analysis identified C1 S100A4 + macrophages as a central signaling hub interacting with endothelial cells, fibroblasts, and immune cells through CXCL, MHC-II, and TNF pathways, thereby suggesting their critical role in post-MI inflammatory remodeling. Conclusion: This study provided a comprehensive single-cell immune atlas of MI and systematically elucidated the heterogeneity, developmental dynamics, transcriptional regulation, metabolic reprogramming, and intercellular communication of macrophage subtypes. C1 S100A4 + macrophages were identified as a key inflammatory population orchestrating immune remodeling after MI. Our findings provide insights into the cellular mechanisms underlying cardiac injury that may offer potential therapeutic targets for precision immunomodulation in MI.
Objective: This study was aimed at evaluating the feasibility of using non-invasive urinary metabolomics to track individual training responses in Sanda athletes, as well as exploring characteristic metabolic signatures in a top-tier performer. Methods: Ten longitudinal biological urine samples collected across separate training days from a single international champion (n = 1) were compared against an 11-participant collegiate cohort (n = 11) as a benchmark reference. Pre- and post-exercise urine samples were collected after a standardized high-intensity sparring session and analyzed with UPLC-Q Exactive Plus LC-MS/MS. Results: Post-exercise metabolic variations in the non-elite cohort clustered primarily within core energy pathways, including the tricarboxylic acid cycle and arginine/proline turnover. In contrast, the longitudinal profiles of the elite champion revealed a distinct, signal-dominant phenotype, with nominal enrichment (p < 0.05) in retrograde endocannabinoid signaling and GABAergic synapse pathways. Supervised multivariate filtering identified specific structural phospholipids, such as phosphatidylcholine (PC) (16:0/18:2), phosphatidylethanolamine (PE) (18:0/22:6), and PC (15:0/P-18:1), as key candidate features demonstrating clear mathematical separation within this dataset. Conclusion: Given the single-case experimental design and inherent training age imbalances, the identified nominal variations offer hypothesis-generating clues potentially associated with chronic physiological adaptation, rather than providing validated selection criteria. This study therefore reframes individual metabolomics as a discovery tool to capture individual homeostatic states and identified peripheral lipid regulation networks warranting future validation in larger independent cohorts.
