This study uses hybrid functional calculations to investigate the effects of various crystal facet combinations in BiOCl and BiOI on the photocatalytic activity of the BiOCl/BiOI heterostructure. The results show that the separation efficiencies of photo-generated electron-hole pairs in BiOCl(010)/BiOI(001) and BiOCl(010)/BiOI(010) are constrained by type I band alignments in principle. In contrast, BiOCl(001)/BiOI(001) and BiOCl(001)/BiOI(010) heterostructures, which operate under the direct Z-scheme type, exhibit an enhanced photo-generated charge separation efficiency, superior redox capacity, and enhanced visible light absorption. Specifically, BiOCl(001)/BiOI(010) exhibits a more remarkable reduction ability that can reduce O2 to ˙O2-. Furthermore, our investigations demonstrate that targeted I element doping in BiOCl(001)/BiOI(010) can reduce the band gap of the BiOCl(001) sheet, enhance visible light absorption, and maintain the direct Z-scheme characteristics, thereby further improving the photocatalytic performance. Additionally, we discovered that I doping can transform the BiOCl(010)/BiOI(001) heterostructure from type I into a direct Z-scheme heterostructure, resulting in a substantial enhancement in the separation efficiency and reduction ability of photo-generated carriers as well as visible light absorption with increasing I doping concentration. Considering the excellent charge injection efficiency observed in experiments with the BiOCl(010)/BiOI(001) heterostructure, I-BiOCl(010)/BiOI(001) may represent a superior photocatalyst. Thus, this study highlights the crucial and substantial roles of engineering specific crystal facet combinations and I doping in enhancing the photocatalytic performance of the BiOCl/BiOI heterostructure. This theoretical study contributes to the comprehension of related experimental findings and offers valuable insights for the development of novel BiOCl/BiOI heterostructures with superior photocatalytic activity.
The role of intestine‐derived factors in promoting liver regeneration after partial hepatectomy (PHx) are not entirely known, but bile acids (BAs) and fibroblast growth factor 15 (Fgf15) that is highly expressed in the mouse ileum could promote hepatocyte proliferation. Fgf15 strongly suppresses the synthesis of BAs, and emerging evidence indicates that Fgf15 is important for liver regeneration. The mechanisms by which Fgf15 promotes liver regeneration are unclear, but Fgf15 may do so indirectly by reducing BA levels and/or directly by promoting cell proliferation. However, it remains undetermined whether these two mechanisms are independent or integrated. In this study, we aimed to clarify these relationships by generating Fgf15 Tet‐Off, transgenic mice ( Fgf15 Tg) that had very low BA levels as a result from overexpressed Fgf15‐mediated suppression of BA synthesis. Compared with wild‐type mice, the Fgf15 Tg mice showed increased hepatocyte proliferation even without surgery, and a further induction of the genes in cell‐cycle progression after PHx. Moreover, overexpression of Fgf15 by adeno‐associated virus (AAV)‐ Fgf15 transduction or treatment with the recombinant Fgf15 protein led to increased cell proliferation in vivo . Furthermore, Fgf15 Tg mice exhibited an earlier and greater activation of mitogen‐activated protein kinase, signal transducer and activator of transcription 3, and NF‐κB signaling pathways in the priming stage, and a disruption of the hippo signaling pathway in the termination stage of liver regeneration. Conclusion: Direct in vivo evidence demonstrates that Fgf15 is critical in stimulating the phases of priming and termination of liver regeneration that are critical for cell survival and liver‐size determination, independent of BA levels. (H epatology 2018; 00:000‐000).
Phosphatidylcholines (PC) and S-adenosylmethionine (SAM) are critical determinants of hepatic lipid levels, but how their levels are regulated is unclear. Here, we show that Pemt and Gnmt, key one-carbon cycle genes regulating PC/SAM levels, are downregulated after feeding, leading to decreased PC and increased SAM levels, but these effects are blunted in small heterodimer partner (SHP)-null or FGF15-null mice. Further, aryl hydrocarbon receptor (AhR) is translocated into the nucleus by insulin/PKB signaling in the early fed state and induces Pemt and Gnmt expression. This induction is blocked by FGF15 signaling-activated SHP in the late fed state. Adenoviral-mediated expression of AhR in obese mice increases PC levels and exacerbates steatosis, effects that are blunted by SHP co-expression or Pemt downregulation. PEMT, AHR, and PC levels are elevated in simple steatosis patients, but PC levels are robustly reduced in steatohepatitis-fibrosis patients. This study identifies AhR and SHP as new physiological regulators of PC/SAM levels.
Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is essential in maintaining bile acid (BA) homeostasis, and FXR(-/-) mice develop cholestasis, inflammation, and spontaneous liver tumors. The signal transducer and activator of transcription 3 (STAT3) is well known to regulate liver growth, and STAT3 is feedback inhibited by its target gene, the suppressor of cytokine signaling 3 (SOCS3). Strong activation of STAT3 was detected in FXR(-/-) mouse livers. However, the mechanism of STAT3 activation with FXR deficiency remains elusive. Wild-type (WT) and FXR(-/-) mice were used to detect STAT3 pathway activation in the liver. In vivo BA feeding or deprivation was used to determine the role of BAs in STAT3 activation, and in vitro molecular approaches were used to determine the direct transcriptional regulation of SOCS3 by FXR. STAT3 was activated in FXR(-/-) but not WT mice. BA feeding increased, but deprivation by cholestyramine reduced, serum inflammatory markers and STAT3 activation. Furthermore, the Socs3 gene was determined as a direct FXR target gene. The elevated BAs and inflammation, along with reduced SOCS3, collectively contribute to the activation of the STAT3 signaling pathway in the liver of FXR(-/-) mice. This study suggests that the constitutive activation of STAT3 may be a mechanism of liver carcinogenesis in FXR(-/-) mice.
Farnesoid X receptor (FXR) is a ligand‐activated nuclear receptor and a transcription factor, regulating bile acid synthesis and transport. FXR is highly expressed in the liver, and more recently FXR has been shown to play a key role in modulating inflammation. Studies have shown that FXR, when activated, acts as a protective agent against liver inflammation and potentially liver diseases such as nonalcoholic steatohepatitis, a part of fatty liver disease. Furthermore, FXR may regulate acute phase proteins, which are secreted as a result of acute phase response (APR)—a systemic reaction that is important for innate immunity and is caused by infection, trauma, or tissue injury. However, the exact mechanism is not well‐established. Thus, the purpose of this study was to investigate the role of FXR in the regulation of the hepatic APR using a bacterial infection model. To understand the mechanism and the effects, hepatocyte‐specific FXR knockout mice (FXR hep −/− ) and wild‐type control mice (WT) were injected with Escherichia coli ( E. coli ) intraperitoneally. Serum, liver, and spleen were isolated 24 hrs following bacterial exposure, and in vivo bacterial counts were determined in whole blood, liver, and spleen. Gene expression of inflammatory cytokines (Tnfα, Il‐1β, Il‐6,) and acute phase proteins (LCN2, Mcp‐1, and Saa3) were measured using quantitative PCR (qPCR) in both liver and spleen. Compared to WT mice, FXR hep −/− mice had significantly increased bacterial load in the liver and spleen following the E.coli treatment, suggesting that they were more susceptible to bacterial infection; however, there was no significant increase in bacterial load in the blood. Serum activities of ALT and AST in FXR hep −/− mice were also elevated, indicating increased liver damage after E.coli treatment. In addition, following the E.coli treatment, gene expression showed a diminished induction of acute phase proteins, Mcp‐1 and Saa3, along with cytokines IL‐1β, IL‐6, and Tnfα in FXR hep −/− mice compared to WT mice. Furthermore, this infection resulted in high levels of LCN2 induction for both the WT and FXR hep −/− mice. In conclusion, the study demonstrates that FXR might be a putative regulator of hepatic acute phase proteins. Support or Funding Information R25ES020721, R01GM104037 and ASPET SURF Intern Program This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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