Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well known for its roles in regulation of energy homeostasis and glucose metabolism. We recently reported that TGR5 activation inhibits nuclear factor κB (NF-κB)-mediated inflammation. Here we show that TGR5 deficiency enhances chemically-induced liver carcinogenesis, and that TGR5 is a negative regulator of signal transducer and activator of transcription 3 (STAT3) signaling. Mice lacking TGR5 were much more susceptible to diethylnitrosamine (DEN)-induced acute liver injury and liver carcinogenesis than wild-type (WT) mice. Consistent with the increasing incidence of liver cancer in TGR5−/− mice, hepatocyte death, compensatory proliferation, and gene expression of certain inflammatory cytokines and matrix metalloproteinases were more sensitive to DEN induction in the absence of TGR5 signaling. In vitro, TGR5 activation greatly inhibited proliferation and migration of human liver cancer cells. We then found that TGR5 activation strongly suppressed STAT3 signaling in vitro and in vivo. Furthermore, we revealed that TGR5 antagonizes STAT3 pathway through suppressing STAT3 phosphorylation, its transcription activity and DNA binding activity, which suggests that TGR5 antagonizes liver tumorigenesis at least in part by inhibiting STAT3 signaling.
Conclusion
These findings identify TGR5 as a novel liver tumor suppressor that may serve as an attractive therapeutic tool for human liver cancer.
The truth that APA may have a chance to progress to carcinoma suggests that APA is at least an indicator lesion for the development of EEC, and highlights that clinicians should carefully monitor the patients, and a meticulous follow-up examination is mandatory.
Numerical simulation of Energetic materials combustion and Energetic materials burning rate determination is the key issues of Energetic materials combustion study. Material point method inherits the advantages of Lagrange and Euler, which have a great advantage when dealing with large deformation and multi-media coupling problem. On the basis of the material point method, research energetic materials combustion problems, establish energetic materials combustion model based on material point method, extend the material point method to the combustion numerical computing. With the numerical simulation of the closed bomb test, get the pressure-time curve, burning rate-pressure curve and others combustion characteristic curve of the measuring point in energetic materials, which were in good agreement compared with experimental data and burning rate-pressure formula. Numerical simulation of energetic materials burning based on material point method provides a new way to the energetic materials combustion simulation and provides the numerical method and an important reference to study the combustion characteristics of energetic materials..
Broadband absorbers with high absorption, ultrathin thickness, and lithography-free planar structure have a wide range of potential applications, such as clocking and solar energy harvesting. For plasmonic metal materials, achieving perfect ultra-broadband absorption remains a challenge owing to the intrinsically narrow bandwidth. In this study, wafer-scale Al-SiO2 stack metasurfaces were experimentally fabricated to realize perfect ultra-broadband absorption. The experimental results show that the absorption for Al-SiO2 stack metasurfaces can reach up to 98% for the wavelength range from the ultraviolet to the near-infrared (350–1400 nm). It was experimentally verified that the absorption performance of Al-SiO2 stack metasurfaces is dependent on the layer number and is superior to that of other metal-based stack metasurfaces. This study will pave the way for development of plasmonic metal-based ultra-broadband absorbers as in low cost and high performance robust solar energy devices.
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