Lactylation, a novel post-translational histone modification, has emerged as a critical regulatory mechanism in various metabolic disorders. However, its role in the pathogenesis of type 2 diabetes (T2D) remains poorly understood. This study aims to investigate the potential of lactylation-related genes as diagnostic biomarkers for T2D. Differential analysis and weighted gene co-expression network analysis (WGCNA) were performed on the GSE164416 dataset. Genes obtained from these analyses were intersected with the lactylation-related genes to screen candidate genes. The LASSO, SVM-RFE and random forest algorithms were applied to screen the characteristic genes, and their diagnostic efficacy was verified in the independent cohort. The functions and immune associations were analyzed by GSVA, ssGSEA, and TF-miRNA regulatory network analysis, and qRT-PCR, western blot and CCK-8 experiments were conducted in the T2D cell model for verification. Lactylation-related IKZF1, S100A4 and VIM were identified as potential diagnostic markers for T2D. These three genes were significantly upregulated in T2D samples and exhibited excellent diagnostic performance (AUC > 0.80) in both the training set and validation set. The GSVA analysis revealed that these three genes were involved in key biological processes such as immune regulation, transcriptional modification, metabolic homeostasis and cytoskeleton remodeling. Cell experiments demonstrated that the three genes were upregulated in T2D cell models and knockdown of their expression could promote cell viability. This study identified and validated three potential diagnostic markers related to lactylation for T2D, providing new molecular evidence for the early diagnosis and mechanism research of this disease.

The incidence of IgA vasculitis (IgAV) in children is relatively high. Cases with severe kidney involvement can lead to death. This study aimed to assess whether the ratio of triglyceride and cystatin C (TG/CysC) represented a risk factor for nephritis in children with IgAV. A total of 451 children were recruited in this ‍study, including 64 children with IgAV and 387 with IgAV with nephritis (IgAVN), according to renal puncture results. Triglycerides, creatinine, urea, uric acid, cystatin C, immuno­glob­ulin A, complement C3, and complement C4 were measured. Compared with the IgAV group, the children with IgAVN had higher triglycerides, creatinine, urea, uric acid and TG/CysC and lower cystatin C and complement C4 (p<0.05). Stepwise multiple logistic regression models showed that TG/CysC (odds ratio: OR = 3.246) was an independent indicator of the presence of nephritis in children with IgAV as well as age (OR = 1.233), creatinine (OR = 1.052), and complement C4 (OR = 0.007). Furthermore, after adjustment for confounding variables, the prevalence of nephritis in children with IgAV was significantly higher according to increased serum TG/CysC levels. The adjusted ORs for nephritis according to TG/CysC tertiles were 1.00 (as references), 2.202 (1.117–4.342), and 14.188 (4.576–43.992). When the TG/CysC ratio was set as 1.94, the diagnostic sensitivity was 53%, and the specificity was 90.6%. Our data suggested that high levels of TG/CysC in children with IgAV was an increased risk for developing nephritis.

Oxidative stress has long been implicated in the pathogenesis of a wide range of chronic diseases; however, systemic antioxidant therapies have yielded limited clinical benefits, partly due to their non-selective distribution and interference with physiological redox signaling. Increasing evidence suggests that the intestine plays a central role in amplifying systemic inflammation, yet the causal contribution of intestinal reactive oxygen species (ROS) has ‍remained unclear. In this review, we summarize a series of ‍studies demonstrating that selective scavenging of intestinal ROS, ‍achieved by orally administered, non-absorbable antioxidant nanoparticles, exerts profound effects on whole-body pathophysi­ology without systemic drug exposure. These gut-localized antioxidants remain confined to the intestinal lumen, effectively suppressing oxidative damage to the intestinal barrier while avoiding adverse effects associated with intracellular or mitochondrial ROS depletion. Experimental evidence across multiple disease models shows that attenuation of intestinal oxidative stress prevents systemic inflammation, reduces circulating pro-inflammatory cytokines such as interleukin-6, and improves diverse pathological outcomes, including exercise-induced organ damage, depression-like behaviors via the gut–brain axis, and muscle wasting in cancer cachexia. Collectively, these findings establish intestinal oxidative stress as an upstream driver of systemic disease progression and highlight gut-confined antioxidant intervention as a safe and mechanistically distinct therapeutic strategy. This concept provides a new framework for re-evaluating oral antioxidant therapy from the perspective of intestinal redox control and its clinical implications.

Non-thermal plasma (NTP) is an ionized gas composed of electrons, ions, radicals, and UV. NTP-irradiated solutions induce reactive oxygen species (ROS)-dependent cell death. NTP irradiation of solutions containing methionine (Met) has been reported to enhance the cytotoxic effects of NTP; however, the exact mechanism by which NTP-irradiated Met solutions exhibit cytotoxicity is not fully understood. In this study, we aimed to elucidate the mechanism using the human breast cancer cell line MDA-MB-231 cells. NTP-irradiated Met-containing acetate Ringer’s solution (Met/PAA) potently induced cytotoxicity compared with NTP-irradiated acetate Ringer’s solution (PAA). Catalase-treated Met/PAA induced cytotoxicity to the same extent, suggesting that NTP irradiation might generate a novel cytotoxic substance distinct from ROS. Catalase-treated Met/PAA decreased intracellular glutathione (GSH) levels, increased ROS production, and caused mitochondrial dysfunction. When catalase-treated Met/PAA was pretreated with antioxidants, GSH and N-acetylcysteine, its cytotoxicity was suppressed. These phenomena indicate that oxidative stress is involved in cell death induced by catalase-treated Met/PAA. Dehydromethionine and methionine sulfoxide were identified as oxidation products of Met in the Met/PAA solution, but neither of the products exhibited cytotoxicity. Taken together, the irradiation of Met-containing solutions likely generates unidentified Met oxidation products other than ROS, resulting in cell death through oxidative stress-induced energy production failure.

Diet is a modifiable risk factor for chronic kidney disease (CKD). However, in China, the trend of changes in CKD burden caused by dietary risk has not been fully elucidated. The CKD burden in China and globally from 1990 to 2021 was analyzed, with the time-dependent trend in CKD burden detected through Joinpoint regression analysis. We also analyzed the trend of CKD burden with age and the contribution of specific dietary risk behaviors to the burden of CKD. From 1990 to 2021, the ASR of deaths and disability-adjusted life years (DALYs) caused by dietary risk factors showed a downward trend in China, decreasing by 31.82% and 33.38%, respectively, while exhibiting an upward trend at the global level, increasing by 18.44% and 11.18%, respectively. The analysis of specific dietary risk behaviors demonstrated that highly sweetened beverages had the largest contribution to the increase in age standardized mortality rate (ASMR) and age standardized DALY rate (ASDR) for CKD at both the Chinese and global levels. Our study revealed that the burden of CKD caused by dietary risk factors is decreasing in China, while it is increasing globally. This result provides a scientific reference for developing targeted dietary and public health strategies.

To analyze the relationship between serum Vitamin D (VD) and Vitamin C (VC) levels and melanoma risk in American adults using NHANES data. The exposure variables were serum VD and VC. The outcome variable was melanoma presence. Covariates included sex, age, race, BMI, poverty-income ratio, alcohol consumption, smoking, diabetes, hypertension, sunscreen use, and sunburn history. We use weighted logistic regression and restricted cubic spline (RCS) analyses to evaluate the relationship and ROC curve to assess the prediction performance. Data from 12,743 (VD) and 12,615 (VC) participants were included. Higher serum VD levels (≥75 nmol/L) and the highest VC quartile levels (OR = 1.91, 95% CI: 1.24–2.97) were associated with an increased melanoma risk. The ROC analysis indicated that the combination of VC or VD with covariates exhibited excellent predictive efficacy (VD and VC model 3: AUC = 0.863). RCS analysis revealed a non-linear correlation between VD and melanoma, and a significant non-linear dose-response relationship between serum VC levels and melanoma. Stratified analysis indicated the adverse effect of higher VD on melanoma was more pronounced in men (OR = 3.55, 95% CI: 1.99–6.33; P < 0.001), non-Hispanic white individuals (95% CI: 1.19–2.95; P = 0.009), and diabetic patients (OR = 18.81, 95% CI: 3.44–102.79; P = 0.002). Sensitivity analysis confirmed results stability. High serum VD and VC levels are associated with increased melanoma risk. Personalized prevention considering ultraviolet exposure and genetic factors are recommended to avoid excessive supplementation.

To investigate associations of total dietary fiber intake (DFI) and fiber sources with all-cause and cardiovascular mortality in individuals with accelerated biological aging, and to assess inflammation's mediating role. This study included 9,322 adults with accelerated aging from National Health and Nutrition Examination Survey (NHANES) 1999–2018. Weighted Cox models examined associations between DFI and mortality. Restricted cubic spline, subgroup, and mediation analyses were applied. Compared to the lowest quartile, the highest DFI quartile had 35% lower all-cause mortality risk [hazard ratio (HR) = 0.65, 95% confidence interval (CI): 0.45–0.92] and 49% lower cardiovascular mortality risk (HR = 0.51, 95% CI: 0.30–0.87). Each 9.74 ‍‍g/day increase in DFI was associated with an 18% (HR = 0.82, 95% CI: 0.71–0.94) and 24% (HR = 0.76, 95% CI: 0.63–0.93) reduction in all-‍cause and cardiovascular mortality risk, respectively. Only grain-based fiber showed a significant inverse association with both outcomes. Mediation analysis indicated inflammation partially mediated the association, with the monocyte-to-lymphocyte ratio having the strongest effect. In adults with accelerated aging, higher DFI, particularly from grains, is inversely associated with all-cause and cardiovascular mortality, partly by attenuating systemic inflammation, suggesting a potential nutri­tional intervention to improve prognosis.

Heterogeneity of treatment effects is common in functional-food studies, particularly when baseline characteristics influence the magnitude of response. Change-point regression models (CPRM) are useful for identifying the baseline level at which an intervention effect begins to appear. However, conventional CPRM relies on ordinary least squares (OLS-CPRM) and is sensitive to outliers, which can lead to unstable estimation of the change point (τ). To address this issue, I developed a rank-based robust CPRM (RR-CPRM) and evaluated its utility using two clinical datasets. RR-CPRM produced estimates of τ consistent with those of the conventional model while providing narrower bootstrap confidence intervals, indicating improved stability and reduced sensitivity to outliers. In datasets with little to no influence from outliers, RR-CPRM yielded results comparable to OLS-CPRM, demonstrating that robustness is achieved without loss of performance. These findings suggest that RR-CPRM offers a reliable and flexible framework for evaluating baseline-dependent intervention effects in human functional-food trials and may contribute to more accurate interpretation of clinical outcomes.

To investigate the impact of serum vitamin {25-hydroxyvitamin D3 [25(OH)D3] and vitamin B12} and trace element [iron (Fe), zinc (Zn), and copper (Cu)] levels on major adverse cardiovascular events (MACE) and prognosis in patients with first-onset ST-segment elevation myocardial infarction (STEMI) after percuta­neous coronary intervention (PCI). A total of 202 first-onset STEMI patients undergoing emergency PCI were prospectively enrolled and divided into MACE (n = 72) and non-MACE (n = 130) groups according to 12-month postoperative MACE occurrence. Baseline characteristics, cardiac function parameters, and serum levels of 25(OH)D3, vitamin B12, Fe, Zn, and Cu were measured. Multi­variate logistic regression was performed to identify independent influencing factors. Receiver operating characteristic curves were used to evaluate predictive value for MACE. Kaplan–Meier analysis was conducted to assess associations with rehospitalization rates and quality of life (SF-36 scale). The MACE group exhibited significantly lower serum 25(OH)D3, vitamin B12, and Zn levels but higher Fe and Cu levels compared with the non-MACE group. Multivariate analysis identified 25(OH)D3, vitamin B12, and Zn were independently associated with a lower risk of MACE, while Fe and Cu were independently associated with a higher risk of MACE. The combined predictive AUC of 25(OH)D3 and vitamin B12 for MACE was 0.79, which was superior to individual indicators. Moreover, abnormal levels were associated with higher 12-month rehospitalization rates and lower SF-36 scores. Decreased serum 25(OH)D3, vitamin B12, and Zn levels and elevated Fe/Cu levels are significantly associated with MACE occurrence and poor prognosis in first-onset STEMI patients post-PCI.

Oxidative stress and vascular inflammation predominantly influence restenosis following angioplasty, causing neointimal hyperplasia. Conventional antioxidants are rapidly eliminated and inadequately localized to injured vessels. We evaluated nitroxide radical-containing nanoparticles (RNPs), polymeric micelles covalently conjugated with 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, in a rat carotid artery balloon injury model. Rhodamine-labeled RNPs selectively accumulated at the injured endothelium and penetrated into the neointima and media. RNPs significantly reduced intimal area, intima-to-media ratio, and preserved lumen patency compared with saline and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL). Mechanistic analyses revealed suppression of reactive oxygen species and oxidized low-density lipoprotein accumulation, LOX-1 expression attenuation, E-selectin–positive endothelial cell reduction, and decreased proinflammatory M1 macrophage infiltration. These findings demonstrate that RNPs effectively suppress angioplasty-induced neointimal hyperplasia through selective vascular accumulation and sustained radical scavenging. Therefore, antioxidant nanomedicine represents a promising therapeutic approach distinct from conventional antioxidants or drug-eluting stents, with translational potential for restenosis prevention.