Evolutionary analysis of SLC10 family members and insights into function and expression regulation of lamprey NTCP.

The Na ( +)-taurocholate cotransporting polypeptide (NTCP) is a member of the solute carrier family 10 (SLC10), which consists of 7 members (SLC10a1-SLC10a7). NTCP is a transporter localized to the basolateral membrane of hepatocytes and is primarily responsible for the absorption of bile acids. Although mammalian NTCP has been extensively studied, little is known about the lamprey NTCP (L-NTCP). Here we show that L-NTCP follows the biological evolutionary history of vertebrates, with conserved domain, motif, and similar tertiary structure to higher vertebrates. L-NTCP is localized to the cell surface of lamprey primary hepatocytes by immunofluorescence analysis. HepG2 cells overexpressing L-NTCP also showed the distribution of L-NTCP on the cell surface. The expression profile of L-NTCP showed that the expression of NTCP is highest in lamprey liver tissue. L-NTCP also has the ability to transport bile acids, consistent with its higher vertebrate orthologs. Finally, using a farnesoid X receptor (FXR) antagonist, RT-qPCR and flow cytometry results showed that L-NTCP is negatively regulated by the nuclear receptor FXR. This study is important for understanding the adaptive mechanisms of bile acid metabolism after lamprey biliary atresia based on understanding the origin, evolution, expression profile, biological function, and expression regulation of L-NTCP.

The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis.

Lamprey underwent biliary atresia (BA) at its metamorphosis stage. In contrast to patients with BA who develop progressive disease, lamprey can grow and develop normally, suggesting that lamprey has several adaptations for BA. Here we show that adaptive changes in bile acid and cholesterol metabolism are produced after lamprey BA. Among 1102 differentially expressed genes (DGEs) after BA in lamprey, many are enriched in gene ontology (GO) terms and pathways related to steroid metabolism. We find that among the DGEs related to bile acids and cholesterol metabolism, the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), sodium-dependent taurine cotransport polypeptide (NTCP) are significantly downregulated, whereas nuclear receptor farnesoid X receptor (FXR), multidrug resistance-associated protein 3 (MRP3), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), sterol O-acyltransferase 1 (SOAT1), and ATP binding cassette subfamily A member 1 (ABCA1) are remarkably upregulated. The changes in expression level are also validated by RT-qPCR. Furthermore, the level of high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in juvenile serum is higher compared to larvae. Taken together, the findings collectively indicate that after BA, lamprey may maintain bile acids and cholesterol homeostasis in liver tissue by inhibiting bile acids synthesis and uptake, promoting its efflux back to circulation, and enhancing cholesterol esterification for storage as lipid droplets and its egress to form nascent HDL (nHDL). Understanding the possible molecular mechanisms of lamprey metabolic adaptation sheds new light on the understanding of the development and treatment of diseases caused by abnormal bile acid and cholesterol metabolism in humans.

Environmental Safety Analysis of Red Mud-Based Cemented Backfill on Groundwater.

As one of the main industrial solid wastes, there are a large number of free alkaloids, chemically bound alkaloids, fluoride, and heavy metal ions in Bayer process red mud (BRM), which are difficult to remove and easily pollute groundwater as a result of open storage. In order to realize the large-scale industrial application of BRM as a backfilling aggregate for underground mining and simultaneously avoid polluting groundwater, the material characteristics of BRM were analyzed through physical, mechanical, and chemical composition tests. The optimum cement-sand ratio and solid mass concentration of the backfilling were obtained based on several mixture proportion tests. According to the results of bleeding, soaking, and toxic leaching experiments, the fuzzy comprehensive evaluation method was used to evaluate the environmental impact of BRM on groundwater. The results show that chemically bound alkaloids that remained in BRM reacted with Ca2+ in PO 42.5 cement, slowed down the solidification speed, and reduced the early strength of red mud-based cemented backfill (RMCB). The hydration products in RMCB, such as AFT and C-S-H gel, had significant encapsulation, solidification, and precipitation inhibition effects on contaminants, which could reduce the contents of inorganic contaminants in soaking water by 26.8% to 93.8% and the leaching of toxic heavy metal ions by 57.1% to 73.3%. As shown by the results of the fuzzy comprehensive evaluation, the degree of pollution of the RMCB in bleeding water belonged to a medium grade Ⅲ, while that in the soaking water belonged to a low grade II. The bleeding water was diluted by 50-100 times to reach grade I after flowing into the water sump and could be totally recycled for drilling and backfilling, thus causing negligible effects on the groundwater environment.