Identifying of immune-associated genes for assessing the obesity-associated risk to the offspring in maternal obesity: A bioinformatics and machine learning.

BACKGROUND: Perinatal exposure to maternal obesity predisposes offspring to develop obesity later in life. Immune dysregulation in the hypothalamus, the brain center governing energy homeostasis, is pivotal in obesity development. This study aimed to identify key candidate genes associated with the risk of offspring obesity in maternal obesity. METHODS: We obtained obesity-related datasets from the Gene Expression Omnibus (GEO) database. GSE135830 comprises gene expression data from the hypothalamus of mouse offspring in a maternal obesity model induced by a high-fat diet model (maternal high-fat diet (mHFD) group and maternal chow (mChow) group), while GSE127056 consists of hypothalamus microarray data from young adult mice with obesity (high-fat diet (HFD) and Chow groups). We identified differentially expressed genes (DEGs) and module genes using Limma and weighted gene co-expression network analysis (WGCNA), conducted functional enrichment analysis, and employed a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to pinpoint candidate hub genes for diagnosing obesity-associated risk in offspring of maternal obesity. We constructed a nomogram receiver operating characteristic (ROC) curve to evaluate the diagnostic value. Additionally, we analyzed immune cell infiltration to investigate immune cell dysregulation in maternal obesity. Furthermore, we verified the expression of the candidate hub genes both in vivo and in vitro. RESULTS: The GSE135830 dataset revealed 2868 DEGs between the mHFD offspring and the mChow group and 2627 WGCNA module genes related to maternal obesity. The overlap of DEGs and module genes in the offspring with maternal obesity in GSE135830 primarily enriched in neurodevelopment and immune regulation. In the GSE127056 dataset, 133 DEGs were identified in the hypothalamus of HFD-induced adult obese individuals. A total of 13 genes intersected between the GSE127056 adult obesity DEGs and the GSE135830 maternal obesity module genes that were primarily enriched in neurodevelopment and the immune response. Following machine learning, two candidate hub genes were chosen for nomogram construction. Diagnostic value evaluation by ROC analysis determined Sytl4 and Kncn2 as hub genes for maternal obesity in the offspring. A gene regulatory network with transcription factor-miRNA interactions was established. Dysregulated immune cells were observed in the hypothalamus of offspring with maternal obesity. Expression of Sytl4 and Kncn2 was validated in a mouse model of hypothalamic inflammation and a palmitic acid-stimulated microglial inflammation model. CONCLUSION: Two candidate hub genes (Sytl4 and Kcnc2) were identified and a nomogram was developed to predict obesity risk in offspring with maternal obesity. These findings offer potential diagnostic candidate genes for identifying obesity-associated risks in the offspring of obese mothers.

[Effect of Sulfur to Quartz Sand Ratios on the Removal of High-Concentration Perchlorate in Packed-Bed Reactors].

Three autotrophic packed-bed reactors, each with a different sulfur/quartz sand ratio(R1, 2:1; R2, 1:1; R3, 1:2,)were used to remove high-concentration perchlorate from contaminated water. The perchlorate removal efficiency, kinetics, and biofilm of the reactors were studied using different perchlorate concentrations and hydraulic retention times (HRTs). The perchlorate removal efficiency decreased with higher perchlorate concentration and shorter HRT, and the removal efficiency of R1 was higher than of R2 and R3. The maximum removal loading of R1 was 2.18 kg·(m3·d)-1at an HRT of 3.2 h and perchlorate concentration of 300 mg·L-1. The half-order kinetics model fit the reactors' experimental data well; the reaction rate constants of R1, R2, and R3 were 8.036, 6.596, and 4.212 mg1/2·(L1/2·h)-1. The yield of SO42- was greater than the stoichiometric yield of sulfur autotrophic reduction owing to sulfur disproportionation. The disproportionation was inhibited with a higher perchlorate concentration or shorter HRT. Moreover, disproportionation of R3 was the weakest because the SO42- yield of R3 was lower than of R1 and R2. The pH and alkalinity of the effluent increased with lower perchlorate concentration and shorter HRT. The development of biofilm in R2 and R3 was better than in R1. The secretion of extracellular polymeric substances can promote the formation of biofilm.