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Constitutive activation of Hedgehog (Hh) signaling has been implicated in many cancers including hepatocellular carcinoma (HCC). Among them, the terminal glioma-associated oncogene homolog 1 (Gli1) regulates the expression of critical genes in the Hh pathway. The current study aims to evaluate the anti-HCC effect of the Gli1 inhibitor, GANT61. In vitro analysis including cell counting kit-8 (CCK-8) assay, flow cytometry, and migration and invasion assay were adopted to evaluate the effect of GANT61 on HCC cell lines. In vivo, xenograft studies were also performed to verify the effect of GANT61 on HCC. By CCK-8 assay, we found that GANT61 could significantly reduce the growth of HCC cell lines Huh7 and hemophagocytic lymphohistiocytosis (HLE), and their IC50 concentrations were 4.481 and 6.734 μM, respectively. Flow cytometry shows that GANT61 induced cell cycle arrest in the G2/M phase and accelerated apoptosis of both HLE and Huh7 cells. While migration and invasion assay shows that GANT61 weakens cells' migration and invasion ability. Besides that, GANT61 inhibits the expression of Gli1, FoxM1, CyclinD1, and Bcl-2, upregulates the level of Bax protein, and also reverses the epithelial–mesenchymal transition program by downregulating the expression of Vimentin and N-Cadherin and upregulating the expression of epithelial E-Cadherin expression. Furthermore, GANT61 inhibits the growth of subcutaneous xenografts of Huh7 cells in nude mice. Overall, this study suggests that Gli1 is a potential target for therapy and GANT61 shows promising therapeutic potential for future treatment in HCC. [ABSTRACT FROM AUTHOR]

An iterative method is used to find the values of the Hamiltonian parameters for Yb3+ in a given low-symmetry crystalline site. Samples of Yb3+:RETaO4 (RE = Gd, Y, and Sc) were prepared and their structures were determined. Based on the obtained structural data, their orbital-spin parameters and crystal field parameters were fitted by the superposition model (SM). Using the crystal field parameters obtained by the SM fitting as the initial parameters, the Hamiltonian parameters were fitted iteratively. The calculated and experimental energy levels for Yb3+:RETaO4 are consistent, and the maximal mean-root-square deviation is only 2.84 cm-1, indicating that the method is effective to determine the Hamiltonian parameters of Yb3+ in low-symmetry crystalline sites. [ABSTRACT FROM AUTHOR]

The theory model of current RC section non-linear analysis is studied to clarify the data demand, algorithm characteristics and data processing pattern. Parametric object-oriented modeling method is adopted to express the data demand of RC section non-linear analysis and the corresponding building information model (BIM) is developed. The BIM is used to fit the constitutive relationship of concrete according to environmental condition, loads and internal factors. Furthermore, Non-Linear Analysis System is developed based on the BIM to automate the analyzing process of deterioration laws of RC section under conditions of environment, loads and internal acts. A case study is elaborated to demonstrate how the system is capable of conducting the RC section non-linear analysis and the results fit well with the data from detection on spot. [ABSTRACT FROM AUTHOR]

Constitutive activation of Hedgehog (Hh) signaling has been implicated in many cancers including hepatocellular carcinoma (HCC). Among them, the terminal glioma-associated oncogene homolog 1 (Gli1) regulates the expression of critical genes in the Hh pathway. The current study aims to evaluate the anti-HCC effect of the Gli1 inhibitor, GANT61. In vitro analysis including cell counting kit-8 (CCK-8) assay, flow cytometry, and migration and invasion assay were adopted to evaluate the effect of GANT61 on HCC cell lines. In vivo, xenograft studies were also performed to verify the effect of GANT61 on HCC. By CCK-8 assay, we found that GANT61 could significantly reduce the growth of HCC cell lines Huh7 and hemophagocytic lymphohistiocytosis (HLE), and their IC 50 concentrations were 4.481 and 6.734 μM, respectively. Flow cytometry shows that GANT61 induced cell cycle arrest in the G2/M phase and accelerated apoptosis of both HLE and Huh7 cells. While migration and invasion assay shows that GANT61 weakens cells' migration and invasion ability. Besides that, GANT61 inhibits the expression of Gli1, FoxM1, CyclinD1, and Bcl-2, upregulates the level of Bax protein, and also reverses the epithelial-mesenchymal transition program by downregulating the expression of Vimentin and N-Cadherin and upregulating the expression of epithelial E-Cadherin expression. Furthermore, GANT61 inhibits the growth of subcutaneous xenografts of Huh7 cells in nude mice. Overall, this study suggests that Gli1 is a potential target for therapy and GANT61 shows promising therapeutic potential for future treatment in HCC., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.