Concentration-dependent transcriptome of zebrafish larvae for environmental bisphenol S assessment.

The widespread use of bisphenol S (BPS) as an alternative to bisphenol A has captured attention due to its potential toxicity to aquatic organisms. In the present study, the zebrafish was used as a model to evaluate the toxicity of BPS and determine the underlying mechanisms. The environmental concentration-dependent (0, 0.1, 1, 10, 100, and 1000 µg/L BPS) transcriptome approach was employed in combination with toxicity assays to address the problem. Based on a weighted correlation network analysis, we speculated that excess reactive oxygen species (ROS) may initiate cellular events in BPS-exposed zebrafish, leading to multiple toxic effects. Furthermore, we used pathway enrichment analysis to identify key pathways (MAPK signalling pathway and metabolic pathways) that link the molecular mechanisms with different toxic effects. In addition, we performed protein-protein network and shortest path analyses to identify six hub genes (erbb2, rrm2, rps27a, his2h3c, cdk1, and mcm5) and their interactions. Moreover, we suggest that BPS may interact with erbb2 by molecular docking. Thus, the BPS-erbb2 interaction may activate the MAPK signalling and metabolic pathways, resulting in ROS production and then caused multiple toxic effects in zebrafish. This study provides information for characterising the mechanisms of BPS exposure in aquatic environments.

3D spheroid culture synchronizes heterogeneous MSCs into an immunomodulatory phenotype with enhanced anti-inflammatory effects.

Mesenchymal stem cells (MSCs) are heterogeneous in morphology and transcriptome, resulting in varying therapeutic outcomes. In this study, we found that 3D spheroid culture of heterogeneous MSCs, which have undergone conventional 2D monolayer culture for 5-6 passages, synchronized the cells into a uniform cell population with dramatically reduced cell size, and considerably increased levels of immunosuppressive genes and growth factors. Single-cell RNA sequencing (scRNA-seq) analysis of the cells revealed that 3D MSCs consisted of 2 major cell subpopulations and both expressed high levels of immunosuppressive factors, compared to 6 subpopulations in 2D MSCs. In addition, 3D MSCs showed a greater suppressive effect on T cells. Moreover, intravenous infusion of a large dose of 3D MSCs prior to imiquimod (IMQ) treatment significantly improved psoriatic lesion. Thus, our results indicate that 3D spheroid culture reprograms heterogeneous MSCs into a uniform immunosuppressive phenotype and promises a novel therapeutic potential for inflammatory diseases.

Identification of a Five-Gene Prognostic Model and Its Potential Drug Repurposing in Colorectal Cancer Based on TCGA, GTEx and GEO Databases.

Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Unfortunately, many CRC patients are still being diagnosed at an advanced stage of the cancer, and the 5-year survival rate is only ~30%. Effective prognostic markers of CRC are therefore urgently needed. To address this issue, we performed a detailed bioinformatics analysis based on the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases to identify prognostic biomarkers for CRC, which in turn help in exploring potential drug-repurposing. We identified five hub genes (PGM2, PODXL, RHNO1, SCD, and SEPHS1), which had good performance in survival prediction and might be involved in CRC through three key pathways ("Cell cycle," "Purine metabolism," and "Spliceosome" KEGG pathways) identified by a KEGG pathway enrichment analysis. What is more, we performed a co-expression analysis between five hub genes and transcription factors to explore the upstream regulatory region. Furthermore, we screened the potential drug-repurposing for the five hub genes in CRC according to the Binding DB and ZINC15 databases. Taking together, we constructed a five-gene signature to predict overall survival of CRC and found the potential drug-repurposing, which may improve the outcome of CRC in the future.

Metabolomics of Eothenomys miletus from five Hengduan Mountains locations in summer.

Climatic characteristics of Hengduan Mountains region were diverse, and Eothenomys miletus was a native species throughout this region. To investigate adaptive strategies of E. miletus to environmental factors in different locations in this region, five locations were selected, including Deqin (DQ), Xianggelila (XGLL), Lijiang (LJ), Jianchuan (JC) and Ailaoshan (ALS). Then, body mass, visceral organ masses, and serum and liver metabolomes of E. miletus from each location were examined. The results showed that body mass was significantly different among these five sites. Liver mass was lower in ALS than in other locations. PLS-DA analysis, metabolite tree maps and heat maps of serum and liver metabolites showed that samples from DQ and XGLL clustered together, as did the samples from LJ, JC and ALS. Serum concentrations of lipid and amino acid metabolites, concentrations of TCA cycle intermediates, lipid metabolites and amino acid metabolites in livers from DQ and XGLL were higher than those from other three regions. However, the concentrations of glycolytic metabolites were lower in DQ and XGLL. All these results indicated that E. miletus adapts to changes in environmental temperature and altitude of this region by adjusting body mass and serum and liver metabolite concentrations.