SLCO3A1

A genomic study was conducted to identify the effects of urbanization and environmental contaminants with heavy metals on selection footprints in dairy cattle populations reared in the megacity of Bengaluru, South India. Dairy cattle reared along the rural-urban interface of Bengaluru with/without access to roughage from public lakeshores were selected. The genotyped animals were subjected to the cross-population-extended haplotype homozygosity (XP-EHH) methodology to infer selection sweeps caused by urbanization (rural, mixed, and urban) and environmental contamination with cadmium and lead. We postulated that social-ecological challenges contribute to mechanisms of natural selection. A number of selection sweeps were identified when comparing the genomes of cattle located in rural, mixed, or urban regions. The largest effects were identified on BTA21, displaying pronounced peaks for selection sweeps for all three urbanization levels (urban_vs_rural, urban_vs_mixed and rural_vs_mixed). Selection sweeps are located in chromosomal segments in close proximity to the genes lrand rab interactor 3 (RIN3), solute carrier family 24 member 4 (SLC24A4), tetraspanin 3 (TSPAN3), and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1). Functional enrichment analyses of the selection sweeps for all three comparisons revealed a number of gene ontology (GO) and KEGG terms, which were associated with reproduction, metabolism, and cell signaling-related functional mechanisms. Likewise, a number of the chromosomal segments under selection were observed when creating cattle groups according to cadmium and lead contaminations. Stronger and more intense positive selection sweeps were observed for the cadmium contaminated group, i.e., signals of selection on BTA 16 and BTA19 in close proximity to genes regulating the somatotropic axis (growth factor receptor bound protein 2 (GRB2) and cell ion exchange (chloride voltage-gated channel 6 (CLCN6)). A few novel, so far uncharacterized genes, mostly with effects on immune physiology, were identified. The lead contaminated group revealed sweeps which were annotated with genes involved in carcass traits (TNNC2, SLC12A5, and GABRA4), milk yield (HTR1D, SLCO3A1, TEK, and OPCML), reproduction (GABRA4), hypoxia/stress response (OPRD1 and KDR), cell adhesion (PCDHGC3), inflammatory response (ADORA2A), and immune defense mechanism (ALCAM). Thus, the findings from this study provide a deeper insight into the genomic regions under selection under the effects of urbanization and environmental contamination.

Gaining a deeper insight into the single-cell RNA sequencing (scRNA-seq) results of bladder cancer (BLCA) provides a transcriptomic profiling of individual cancer cells, which may disclose the molecular mechanisms involved in BLCA carcinogenesis.

scRNA data were obtained from GSE169379 dataset. We used the InferCNV software to determine the copy number variant (CNV) with normal epithelial cells serving as the reference, and performed the pseudo-timing analysis on subsets of epithelial cell using Monocle3 software. Transcription factor analysis was conducted using the Dorothea software. Intercellular communication analysis was performed using the Liana software. Cox analysis and LASSO regression were applied to establish a prognostic model.

We investigated the heterogeneity of tumors in four distinct cell types of BLCA cancer, namely immune cells, endothelial cells, epithelial cells, and fibroblasts. We evaluated the transcription factor activity of different immune cells in BLCA and identified significant enrichment of TCF7 and TBX21 in CD8+ T cells. Additionally, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs), namely iCAFs and myoCAFs, which exhibited distinct communication patterns. Using sub-cluster and cell trajectory analyses, we identified different states of normal-to-malignant cell transformation in epithelial cells. TF analysis further revealed high activation of MYC and SOX2 in tumor cells. Finally, we identified five model genes (SLCO3A1, ANXA1, TENM3, EHBP1, LSAMP) for the development of a prognostic model, which demonstrated high effectiveness in stratifying patients across seven different cohorts.

We have developed a prognostic model that has demonstrated significant efficacy in stratifying patients with BLCA.

Persistent organic pollutant perfluorooctane sulfonate (PFOS) is strongly associated with male reproductive disorders, but the related mechanisms are still not fully understood. In this study, we used in vivo and in vitro models to explore the role of organic anion transporting polypeptide 3a1 (Oatp3a1) on PFOS-induced male reproductive injury. Thirty male C57BL/6 (B6) mice were orally given PFOS (0-10 mg/kg/bw) for 28 days. Body weight, organ index, sperm count, histology, and blood-testis barrier (BTB) integrity were evaluated. Primary Sertoli cells were used to describe the related molecular mechanisms of male reproductive injury caused by PFOS. Our results showed that PFOS induced a decrease in sperm count, morphological damage to testicular Sertoli cells, and disruption of BTB. In the in vitro model, exposure to PFOS significantly increased Oatp3a1 mRNA and protein levels and decreased miR-23a-3p expression in Sertoli cells, accompanied by reduced trans-epithelial electrical resistance (TEER) value. By performing the ¹⁴C-PFOS uptake experiment, we showed that ¹⁴C-PFOS uptake in HEK293-Oatp3a1 cells was apparently higher than in HEK293-MOCK cells. Meanwhile, treating Sertoli cells with Oatp3a1 siRNA significantly decreased Oatp3a1 expression and rescued PFOS-induced decreases in TEER value. As such, the present study highlights that Oatp3a1 may play an important role in the toxic effect of PFOS on Sertoli cells, advancing our understanding of molecular mechanisms for PFOS-induced male reproductive disorders.