The original data of GO and KEGG analysis.

Background
Volatile organic compounds (VOCs) are ubiquitous in our environment, and their associations with sarcopenia are unknown. The aim of this study is to evaluate the association between VOCs exposure and sarcopenia.
Methods
Data from 2429 U.S. adults (aged ≥ 20 years) were extracted from the NHANES (2011–2018). Logistic regression, LASSO, Weighted Quantile Sum (WQS) and Bayesian Kernel Machine regression (BKMR) analyses were used to assess the associations between VOCs and sarcopenia. Mediation analysis tested roles of inflammation and oxidative stress in this association. The underlying mechanisms were further investigated through database enrichment analysis, molecular docking, and molecular dynamics simulations.
Results
Among the 2429 adults included, 1213 (49.9%) were male, 1216 (50.1%) were female, and the median age was 39 years (interquartile range, 29–49 years), with a prevalence of sarcopenia of 8.03%. According to the logistic analysis, nine mVOCs were significantly associated with sarcopenia, with N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA) identified as a potential independent risk factor (odds ratio [OR], 4.51 [95% CI: 1.7–12.1]). WQS analysis revealed a positive association between LASSO-selected 12 mVOCs and sarcopenia (OR 1.39 [95% CI: 1.17–1.90]). BKMR analysis further confirmed this association, with DHBMA showing a significant contribution. Mediation analysis confirmed that inflammation and oxidative stress exert mediating effects. GO and KEGG enrichment analyses indicated that its effects are exerted through the TNF and PI3K–Akt signaling pathways, and that DHBMA binds stably to AKT1.
Conclusion
This nationally representative cross-sectional study revealed a positive correlation between exposure to mVOCs and sarcopenia via TNF and PI3K–Akt signaling pathways. DHBMA plays a potentially pivotal role in this association.

背景
挥发性有机化合物（Volatile Organic Compounds, VOCs）广泛存在于人类生存环境中，目前其与少肌症（Sarcopenia）的关联尚未明确。本研究旨在评估挥发性有机化合物暴露与少肌症之间的关联。

方法
本研究从2011-2018年美国国家健康与营养调查（National Health and Nutrition Examination Survey, NHANES）中提取了2429名年龄≥20岁的美国成年人群数据。采用logistic回归、套索回归（Least Absolute Shrinkage and Selection Operator, LASSO）、加权分位数和（Weighted Quantile Sum, WQS）以及贝叶斯核机器回归（Bayesian Kernel Machine Regression, BKMR）分析，以评估挥发性有机化合物暴露与少肌症的关联。通过中介分析检验炎症与氧化应激在该关联中的介导作用，并借助数据库富集分析、分子对接及分子动力学模拟进一步探究其潜在作用机制。

结果
在纳入的2429名成年人群中，男性1213例（占比49.9%），女性1216例（占比50.1%），中位年龄为39岁（四分位数间距（Interquartile Range, IQR）：29~49岁），少肌症患病率为8.03%。经logistic回归分析，9种挥发性有机化合物代谢物（mVOCs）与少肌症存在显著关联，其中N-乙酰-S-(3,4-二羟丁基)-L-半胱氨酸（N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine, DHBMA）被鉴定为潜在独立危险因素（比值比（Odds Ratio, OR）=4.51，95%置信区间（95% Confidence Interval, 95% CI）：1.7~12.1）。加权分位数和分析显示，经套索回归筛选出的12种挥发性有机化合物代谢物与少肌症呈正相关（OR=1.39，95%置信区间（95% Confidence Interval, 95% CI）：1.17~1.90）。贝叶斯核机器回归分析进一步验证了该关联，且DHBMA展现出显著贡献度。中介分析证实，炎症与氧化应激发挥了介导作用。基因本体（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析结果表明，其作用通过肿瘤坏死因子（Tumor Necrosis Factor, TNF）及磷脂酰肌醇3-激酶-蛋白激酶B（Phosphatidylinositol 3-Kinase-Protein Kinase B, PI3K-Akt）信号通路实现，且DHBMA可与AKT1（AKT丝氨酸/苏氨酸激酶1）稳定结合。

结论
本项具有全国代表性的横断面研究表明，挥发性有机化合物代谢物暴露与少肌症之间呈正相关，该关联通过TNF及PI3K-Akt信号通路介导。DHBMA在该关联中发挥潜在关键作用。