This study aimed to investigate the relationship between total antioxidant capacity (TAC) and phenotypic age acceleration (PhenoAgeAccel), a measure of accelerated biological aging, using data from the National Health and Nutrition Examination Survey (NHANES). Data from the 2003–2010 NHANES surveys, encompassing 16,395 participants, were analyzed. Principal component analysis (PCA) was used to reduce data dimensionality. Multivariate logistic regression models were employed to evaluate the association between TAC and antioxidant vitamins (α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein-zeaxanthin, vitamin A, vitamin C, vitamin E) with PhenoAgeAccel, adjusting for demographic, lifestyle, and clinical factors. Smoothed curve fitting and threshold effects analysis were conducted to explore the nonlinear relationship between log-transformed TAC and PhenoAgeAccel. Subgroup analyses were performed to assess potential effect modifiers based on age, gender, race, education, smoking, alcohol use, diabetes, hypertension, and hyperlipidemia. The weak correlations between the original variables prevent PCA from effectively capturing the primary variability within the data. Higher TAC was significantly inversely associated with PhenoAgeAccel in both unadjusted and adjusted models. Participants in the second tertile (T2) of TAC exhibited 11% lower odds of PhenoAgeAccel compared to those in the first tertile (T1) (OR = 0.89, 95% CI: 0.81–0.98, P = 0.0176). Intake of several antioxidant vitamins, including α-carotene, β-carotene, lutein-zeaxanthin, vitamin A, vitamin C, and vitamin E, was also inversely associated with the odds of PhenoAgeAccel. A nonlinear relationship between log-transformed TAC and PhenoAgeAccel was observed, with a significant protective effect within a specific range of TAC. Subgroup analyses revealed no significant effect modification by most factors, except for gender, smoking, and alcohol consumption. TAC is closely associated with PhenoAgeAccel. A nonlinear relationship was observed, with higher TAC exhibiting significant protective effects within a specific range, particularly among males, smokers, and alcohol consumer. These findings underscore the potential value of TAC in mitigating the aging process.

To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial–mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response.

To comprehensively understand the disease burden of NASH-related liver cancer (NRLC) in China, we analyzed and evaluated the disease burden of NRLC in mainland China from 1990 to 2021 and predicted the trend in its health burden over the next 20 years. We characterized the burden of NRLC in China using the Global Burden of Disease (GBD) 2021 method and results based on incidence, prevalence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs). Joinpoint and age-period-cohort (APC) analysis methods were used to interpret the epidemiological characteristics and compare them with global prevalence trends. Moreover, the Bayesian age-period-cohort model was used to predict the incidence of mortality in different age groups over the next 20 years. From 1990 to 2021, the age-standardized incidence rates of males and females in China changed from 4.75 (95% confidence interval [CI]: 3.81–5.81) to 5.42 (95% CI: 4.18–6.85), and the mortality rate changed from 5.02 (95% CI: 4.01–6.14) to 5.06 (3.88, 6.42) per 100,000 people. The age-standardized DALY rate in China has decreased from 133.91 (95% CI: 107.69–163.99) per 100,000 people in 1990 to 122.20 (95% CI: 94.14–154.42) per 100,000 people in 2021. The average annual percentage changes (AAPCs) in the age-standardized incidence, prevalence, and mortality of NRLC in China were 0.44 (95% CI: 0.34–0.54), 1.00 (95% CI: 0.75–1.25), and 0.13 (95% CI: −0.36 to 0.61), respectively. Age, period, and cohort had different effects on the incidence and mortality. Personally, middle-aged and elderly men should pay more attention to the prevention of NRLC. Given the large population, growing SDI index, and aging trend in China, multiple prevention policies and popular education programs should be considered in the near future to minimize the burden of NRLC.