The widespread use of food additives, such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and tert-butylhydroquinone (TBHQ), has raised concerns about their potential toxicity, especially their hepatotoxicity, nephrotoxicity, and neurotoxicity. This study explores the targets and mechanisms of food additive-induced toxicity using network toxicology. Toxicity predictions of BHA, BHT, and TBHQ were performed using the ProTox-3.0, ADMETlab 3.0, and Xundrug databases, and potential targets were identified using the SwissTargetPrediction, Batman-TCM, SuperPred, and SEA databases. These were integrated with GeneCards—The Human Gene Database (GeneCards) and the Online Mendelian Inheritance in Man (OMIM) database to extract toxicity-related targets for subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Core-acting genes were further screened through protein–protein interactions (PPIs), and molecular docking was performed to verify the binding free energy between BHA, BHT, and TBHQ and their core targets. Additionally, the mRNA-miRNA-lnRNA interaction regulatory networks of the core targets and potential carcinogenic mechanisms were analyzed. The targets of BHA, BHT, and TBHQ were as follows: ACE, HIF1A, NR1H4, NFKB1, TNF, IL6, IFNG, IL1B, and ESR1 for hepatotoxicity; APP, NFKB1, ACE, FOS, IL10, IL1B, IL6, TNF, and ALB for nephrotoxicity; and GRIN2B, IL1B, and TNF for neurotoxicity. These interactions primarily involved pathways such as interleukin-17 (IL-17) and Janus kinase-signal transducer and activator of transcription (JAK-STAT), as well as various pathways related to non-alcoholic fatty liver disease (NAFLD). This study highlights the potential toxicity of BHA, BHT, and TBHQ to the liver, kidneys, and nerves, providing insights for better safety evaluations.

Parabens (PBs) are associated with an increased risk of breast cancer, yet their underlying molecular mechanisms remain poorly understood. This study aimed

Schizophrenia (SCZ) and major depressive disorder (MDD) are severe psychiatric disorders with substantial shared genetic liability and frequent clinical co-occurrence, yet their shared cell type-specific genetic mechanisms remain unclear. We integrated single-cell expression quantitative trait locus (sc-eQTL) data from eight major brain cell types with large-scale genome-wide association study (GWAS) summary statistics for SCZ and MDD. Cell type-specific genetically regulated gene expression was evaluated using Mendelian randomization (MR) and Bayesian colocalization analyses, followed by validation in independent single-cell RNA sequencing datasets and functional characterization using virtual gene knockout and phenome-wide association study (PheWAS) analyses. Integrative analyses prioritized three shared candidate genes, ZSCAN31, BTN3A2, and YLPM1, all showing strong colocalization support (PP·H4 > 0.8). Single-cell transcriptomic validation supported distinct cell type-specific patterns, with ZSCAN31 enriched in astrocytes and endothelial cells, BTN3A2 in microglia, and YLPM1 in oligodendrocytes. Virtual knockout of YLPM1 suggested perturbation of neurodevelopment-related pathways in SCZ and synaptic signaling pathways in MDD. These findings provide a cell type-resolved view of shared genetic architecture between SCZ and MDD and highlight candidate genes for further mechanistic and translational investigation.