Amplification and/or activation of the c-Myc protooncogene is one of the leading genetic events along hepatocarcinogenesis. The oncogenic potential of c-Myc has been proven experimentally by the finding that its overexpression in the mouse liver triggers tumor formation. However, the molecular mechanism whereby c-Myc exerts its oncogenic activity in the liver remains poorly understood. Here, we demonstrate that the mammalian target of rapamycin complex 1 (mTORC1) cascade is activated and necessary for c-Myc dependent hepatocarcinogenesis. Specifically, we found that ablation of Raptor, the unique member of the mTORC1 complex, strongly inhibits c-Myc liver tumor formation. Also, p70S6K/ribosomal protein S6 (RPS6) and eukaryotic translation initiation factor 4E-binding protein 1/eukaryotic translation initiation factor 4E (4EBP1/eIF4E) signaling cascades downstream of mTORC1 are required for c-Myc-driven tumorigenesis. Intriguingly, microarray expression analysis revealed the upregulation of multiple amino acid transporters, including SLC1A5 and SLC7A6, leading to robust uptake of amino acids, including glutamine, into c-Myc tumor cells. Subsequent functional studies showed that amino acids are critical for activation of mTORC1, as their inhibition suppressed mTORC1 in c-Myc tumor cells. In human HCC specimens, levels of c-Myc directly correlate with those of mTORC1 activation as well as of SLC1A5 and SLC7A6. Conclusion Our current study indicates that an intact mTORC1 axis is required for c-Myc-driven hepatocarcinogenesis. Thus, targeting mTOR pathway or amino acid transporters may be an effective and novel therapeutic option for the treatment of HCC with activated c-Myc signaling.

This paper describes the fabrication of two different 3D mesoporous TiO2 microspheres via one-step solvothermal process without templates using different titanium sources. The resulting materials were characterized by XRD, FESEM, TEM, and nitrogen adsorption techniques. Their photodegradation of bisphenol A [2,2-bis(4-hydroxyphenyl)propane, BPA] in aqueous suspension was investigated under UV irradiation. The experimental results revealed that the photocatalytic effect of the two 3D mesoporous TiO2 microspheres was superior to the commercial P25 TiO2, and as-prepared samples as catalysts demonstrated that the smaller pore size it is, the higher the effective degradation for BPA is. Particular attention was paid to the identification of intermediates and analysis of photocatalytic degradation mechanism of BPA by HPLC-MS and HPLC-MS-MS. Five main intermediates were formed during photocatalytic degradation, and their evolution was discussed. On the basis of the evidence of oxidative intermediate formation, a detailed degradation pathway of BPA degradation by two mesoporous TiO2 microspheres photocatalysts are proposed.

Sunlight-induced photodegradation of rhodamine B over Ag3PO4 has been observed. Nanosized Ag3PO4 was synthesized by a facile ion-exchange route. X-ray powder diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, the Brunauer–Emmett–Teller surface area, UV–vis diffuse reflectance spectroscopy and photoluminescence spectra were employed to investigate the phase structure, morphology and optical property of the Ag3PO4 product. Nearly 100% of rhodamine B was degraded after a very short irradiation time using simulated sunlight in Ag3PO4 suspension, and the total organic carbon measurement revealed that a high degree of mineralization was achieved in the present photocatalytic system. Ag3PO4 catalyst has an excellent photocatalytic performance due to the high separation efficiency of electron and hole pairs. In the neutral pH solution, Ag3PO4 catalyst exhibited the best photoactivity under simulated sunlight. The photoinduced holes were considered to be the dominant active species in the photodegradation process.

Two-dimensional (2D) nanosheets directly grew into three-dimensional (3D) microspheres through a one-step solvothermal route under controlled conditions; during this procedure the decomposition of hexamethylenetetramine at temperatures higher than 120 °C provided OH− at the rate of good diffusion, and surfactants were used as templates to provide the growth sites and control the crystalline growth direction. By means of the Ostwald ripening process, precursor microspheres formed with narrowly distributed diameters, and then NiO 3D microspheres were obtained with further calcination at 300 °C for 2 h. NiO microspheres presented a high initial discharge capacity as anode materials in Li ion batteries, but degraded quickly during subsequent cycles, and further improvement in cyclic stability is still needed for practical application in Li ion batteries.

Chrysanthemum-analogous Bi 2 O 3 -Bi 2 WO 6 composite microspheres, assembled by nanosheets, were synthesized through a one-step hydrothermal route with the aid of surfactant templates. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were employed to clarify the structure and morphology of the Bi 2 O 3 -Bi 2 WO 6 microspheres. Nitrogen adsorption and desorption isotherms were conducted to examine the specific surface area and the pore nature of the as-prepared microspheres. The photocatalytic activity of the Bi 2 O 3 -Bi 2 WO 6 composite microspheres was evaluated by using rhodamine B as a model contaminant, and over 99% of rhodamine B was degraded within 10 min under the exposure of sunlight. The Bi 2 O 3 -Bi 2 WO 6 composite microspheres presented enhanced photocatalytic performances compared with separate Bi 2 O 3 , Bi 2 WO 6 , and conventional P25.

Cytochrome P450s metabolize the naturally occurring nephrotoxin aristolochic acid. Using liver-specific cytochrome P450 reductase-null mice we found that a low but lethal dose of aristolochic acid I was ineffective in wild-type mice. Induction of hepatic CYP1A by 3-methylcholanthrene pretreatment markedly increased the survival rate of wild type mice given higher doses and these mice were protected from aristolochic acid I-induced renal injury. Clearance of aristolochic acid I in null mice was slower compared to control and the 3-methylcholanthrene-pretreated wild type mice. The levels of aristolochic acid I in the kidney and liver were much higher in null mice but much lower in 3-methylcholanthrene-treated compared to control wild type mice. Hepatic microsomes from 3-methylcholanthrene-treated wild type mice had greater activity compared to untreated mice. Finally, aristolochic acid I was more cytotoxic than its major metabolite aristolactam I and this cytotoxicity was decreased in human renal tubular epithelial HK2 cells in the presence of a reconstituted hepatic microsome-cytosol (S9) system. These results indicate that hepatic P450s play an important role in metabolizing aristolochic acid I into less toxic metabolites and thus have a detoxification role in aristolochic acid I-induced kidney injury.

Nanostructured TiO2 with different hierarchical morphologies were synthesized via a warmly hydrothermal route. The properties of the products were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, N2 adsorption, UV-vis spectroscopy, etc. Two of the products, TiO2 1D nanorods (one-dimensional rutile TiO2 nanorods) and TiO2 3D0D microspheres (three-dimensional anatase TiO2 nanoparticle-assembled microspheres) exhibited superior photocatalytic effects on phenol degradation under UV illumination, compared with TiO2 3D1D microspheres (three-dimensional rutile TiO2 nanorods-assembled microspheres). Moreover, TiO2 3D0D was superior to TiO2 1D, as indicated by a 30% higher mineralization of dissolved phenol. Dihydroxybenze, 4,4'-dihydroxybiphenyl, benzoquinone, maleic anhydride, etc. were identified as the degradation intermediates. The excellent catalytic effect was attributed to the structural features of TiO2 1D nanorods and TiO2 3D0D microspheres, that is, a larger amount of surface active sites and a higher band gap energy resulted in more efficient decomposition of organic contaminants.

Lead (Pb) exposure has been implicated in the impairment of synaptic plasticity in the developing hippocampus, but the mechanism remains unclear. Here, we investigated whether developmental lead exposure affects the dendritic spine formation through Wnt signaling pathway in vivo and in vitro. Sprague–Dawley rats were exposed to lead throughout the lactation period and Golgi-Cox staining method was used to examine the spine density of pyramidal neurons in the hippocampal CA1 area of rats. We found that lead exposure significantly decreased the spine density in both 14 and 21 days-old pups, accompanied by a significant age-dependent decline of the Wnt7a expression and stability of its downstream protein (β-catenin). Furthermore, in cultured hippocampal neurons, lead (0.1 and 1 µM lead acetate) significantly decreased the spine density in a dose-dependent manner. Exogenous Wnt7a application attenuated the decrease of spine density and increased the stability of the downstream molecules in Wnt signaling pathway. Together, our results suggest that lead has a negative impact on spine outgrowth in the developing hippocampus through altering the canonical Wnt pathway.