Anemia, a global health concern, significantly impacts children and adolescents, impairing their physical and cognitive development. While nutritional deficiencies are primary contributors, oxidative stress has emerged as a key factor in anemia pathogenesis. Flavonoids, known for their antioxidant properties, may play a protective role, but their relationship with anemia in pediatric populations remains underexplored. Using data from the National Health and Nutrition Examination Survey (NHANES) cycles (2007–2008, 2009–2010, and 2017–2018), we analyzed 6815 participants aged ≤20 years to investigate the association between dietary flavonoid intake and anemia risk. Flavonoid intake was assessed via two 24 h dietary recalls, and anemia was defined using WHO hemoglobin thresholds. Multivariable logistic regression and restricted cubic spline (RCS) models were employed, adjusting for sociodemographic, dietary, and lifestyle factors. The results showed that lower dietary flavonoid intake was significantly associated with increased anemia risk. High-intake groups of total flavonoids and flavan-3-ols were linked to a reduced anemia prevalence compared to low-intake groups, with odds ratios (ORs) of OR = 0.641 (95% CI: 0.439, 0.935) and 0.612 (95% CI: 0.406, 0.921), respectively. This study highlights the potential protective role of dietary flavonoids, particularly flavan-3-ols, in reducing the anemia risk among children and adolescents, underscoring the importance of flavonoid-rich diets in anemia prevention.

Metabolic disorders mediated chimeric antigen receptor - T cell (CAR-T) exhaustion impaired cancer immunotherapy. Endogenous sulfur dioxide (SO₂) derived from L-cysteine catalysis regulated immune cell functions. However, its role in CAR-T cell exhaustion remained unknown. In this study, we identified that SO₂ accumulated in the bone marrow microenvironment of relapsed multiple myeloma patients inhibited CD8⁺ T cell and CAR-T cell infiltration and promoted a transcriptional profile consistent with functional exhaustion, leading to impaired antitumor immunity. Tumor cell derived SO₂ altered mitochondrial morphology and disrupted mitochondrial membrane potential in CAR-T cells, accompanied by impaired cytokine secretion and loss of cytotoxic function. Mechanistically, SO₂ enhanced interaction of dynamin-related protein 1 (DRP1) and voltage-dependent anion channel 1 and mitochondrial fission via DRP1 sulphenylation at cysteine 607 (Cys607), with abnormal increases in DRP1 GTPase activity, disrupting mitochondrial integrity. Site mutation of Cys607 in CAR-T cells abrogated DRP1 sulphenylation and restored mitochondrial structure and improves antitumor immunity. These findings define a novel redox-mediated mechanism of mitochondrial dysfunction in CAR-T cells exhaustion and identify the SO₂-DRP1 axis as a potential therapeutic target to overcome metabolic exhaustion in CAR-T cell therapy.