Indoor airborne carcinogen synergy in children: systematic interdisciplinary approach to PM2.5-nicotine driven lung tumorigenesis and targeted intervention

The indoor air environment has become an essential environmental factor affecting children's health and safety, among which nicotine and PM2.5, two common combined factors, have become pathogenic factors in indoor area that induce lung cancer in children. In order to reveal the specific mechanism of that, we developed the model of Systematic Environmental Information Medicine Engineering (SEIME), which combines environmental engineering, bioinformatics, and computational biology multidisciplinary approaches. We initially developed a comprehensive computational fluid dynamics (CFD) model, which was subsequently integrated with data from the GEO database, TCGA database, single-cell online databases, and molecular docking analyses to enhance our research framework. CFD results revealed that indoor concentrations of PM2.5 and nicotine were significantly higher than the recommended values of 15 µg/m³ and 1 µg/m³ in the WHO Global Air Quality Guidelines. Meanwhile, bioinformatics results indicated that MAPK and PI3K-Akt were important signaling pathways for inducing non-small cell lung cancer (NSCLC) in children. In addition, GADD45A and NPAS2, as key targets affecting children's NSCLC, were identified. Subsequently, drug repositioning and molecular docking assays were conducted, and more importantly, related small molecule targeted drugs were screened. Therefore, this study has set up a new interdisciplinary analysis model-SEIME, using environmental information medicine engineering to solve environmental disease models under the influence of multiple factors, and providing theoretical basis for molecular target screening and disease treatment.