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Abstract The weight-adjusted waist index (WWI) has emerged as a reliable indicator of abdominal obesity. α-Klotho, a transmembrane protein, functions as a suppressor of aging. However, the relationship between these two factors remains underexplored. This study aims to investigate the association between WWI and serum α-Klotho levels in middle-aged and elderly Americans, with a focus on exploring the potential mediating role of the systemic immune inflammation index (SII). A cross-sectional study was conducted using data from 6997 middle-aged and elderly Americans participating in the National Health and Nutrition Examination Surveys (NHANES) between 2011 and 2016. Multiple linear regression analysis was employed to assess the relationship between WWI and serum α-Klotho concentrations. Additionally, mediation analysis was performed to investigate the mediating effect of SII on the relationships. Our analysis revealed a significant negative correlation between WWI and serum α-Klotho levels in the survey-weighted multiple linear regression models (adjusted percent change: -7.79; 95% CI: -10.15, -5.37). Mediation analysis demonstrated that the association between WWI and α-Klotho levels was partially mediated by SII (adjusted percent change: -0.88; 95% CI: -1.24, -0.45), with the proportion of mediation amounting to 11.6%. Further age-stratified results showed that the mediating role of SII was more pronounced among individuals aged ≥ 60 years, exhibiting a mediating effect of 26.3%, in contrast to 4.2% for those

Intrauterine growth restriction (IUGR) is an abnormal fetal growth pattern that can lead to neonatal morbidity and mortality. IUGR may be affected by prenatal exposure to environmental pollutants, including perfluoroalkyl substances (PFASs). However, research linking PFAS exposure to IUGR is limited, with inconsistent results. We aimed to investigate the association between PFAS exposure and IUGR by using nested casecontrol study based on Guangxi Zhuang Birth Cohort (GZBC), in Guangxi, China. A total of 200 IUGR cases and 600 controls were enrolled in this study. The maternal serum concentrations of nine PFASs were measured using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLCMS). The associations single and mixed effects of prenatal PFAS exposure on IUGR risk were assessed using conditional logistic regression (single-exposure), Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models. In the conditional logistic regression models, the log10-transformed concentrations of perfluoroheptanoic acid (PFHpA, adjusted OR: 4.41, 95% CI: 3.03–6.41), perfluorododecanoic acid (PFDoA, adjusted OR: 1.94, 95% CI: 1.14–3.32), and perfluorohexanesulfonate (PFHxS, adjusted OR: 1.83, 95% CI: 1.15–2.91) were positively associated with risk of IUGR. In the BKMR models, the combined effect of PFASs was positively associated with IUGR risk. In the qgcomp models, we also found an increased IUGR risk (OR=5.92, 95% CI: 2.33–15.06) when all nine PFASs increased by one tertile as a whole, and PFHpA (43.9%) contributed the largest positive weights. These findings suggested prenatal exposure to single and mixtures of PFASs may increase IUGR risk, with the effect being largely driven by the PFHpA concentration.