Although the activation of Ras pathway is frequently observed in human hepatocellular carcinoma (HCC), the in vivo role of Ras activation in HCC initiation and progression is underdetermined. To test the consequence of Kras activation in hepatocyte, we generated a hepatocyte-specific Kras(G12D) transgenic mouse strain and observed spontaneous development of HCC in these mice. Remarkably, HBV X protein (HBx) expression significantly promotes the formation and malignant progression of Kras(G12D)-driven HCC as shown with the accelerated tumor onset, the increased tumor burden and the more poorly differentiated lesions. At the cellular level, concomitant expression of Kras(G12D) and HBx results in a robust increase in hepatocellular proliferation. We reveal that the Akt, MAPK, p53 and TGF-β pathways are deregulated in the Kras(G12D)-driven HCCs. Also, the dysregulation is more pronounced in the HCCs developed in Kras(G12D) and HBx double transgenic mice. In addition, the altered expressions of β-catenin, CD44 and E-cadherin are only observed in the Kras(G12D) and HBx double transgenic mice. These results demonstrate a crucial role of Ras activation in hepatocellular carcinogenesis and the functional synergy between Kras(G12D) and HBx in HCC initiation and progression. The novel genetic mouse models that closely recapitulate the histopathologic progression and molecular alterations of human HCC may potentially facilitate the future therapeutic studies.
High quality InGaAsP/InGaAsP multiple quantum wells (MQWs) have been selectively grown by ultra-low-pressure (22 mbar) metal-organic chemical vapor deposition. A large bandgap energy shift of 46 nm and photoluminescence with FWHM less than 30 meV were obtained with a rather small mask width variation (15—30 μm). In order to study the uniformity of the MQWs grown in the selective area, novel tapered masks were employed, and the transition effect of the tapered region was also studied. The energy detuning of the tapered region was observed to be saturated at larger ratios of the mask width to the tapered region length.
The in situ crystallization of small-grain NaY in the presence of lauryl sodium sulfate was investigated. The product containing small-grain NaY was used as a matrix to prepare REUSY catalyst via ammonium ion exchange and rare earth ion exchange. X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray fluorescence (XRF), and N 2 physical adsorption-desorption were used to characterize the samples, while the catalytic performance of prepared catalysts was evaluated by micro-activity evaluation device and advanced catalytic evaluation (ACE). It is indicated that the addition of lauryl sodium sulfate (5% of Kaolin microsphere mass) to in situ crystallization system can decrease the average grain size of the zeolite from 540 to 250 nm. Relative to the conventional in situ crystallization fluid catalytic cracking (FCC) catalysts, the catalyst prepared from in situ crystallization product containing small-grain NaY exhibits improved performance in the conversion rate of feedstock, the selectivity of the cracking product, and the resistance to carbon deposition.
ObjectivesTo investigate the role of HIF-1α and NF-κB in intermittent hypoxia (IH) induced atherosclerosis in rabbits.MethodsNew-Zealand White rabbits were exposed to IH for 12 weeks (intermittent hypoxia of 21% O2 for 30 s and 8% O2 for 30 s, cyclically repeated for 8 h/day). We randomly assigned 48 male rabbits to groups of normoxia (RA) or IH. The rabbits in the RA group were continuously exposed to room air. After intervention of 4, 8, and 12 weeks, serum and aortic arch tissues were subjected to Elisa and immunohistochemical staining analyses respectively. The formation of atherosclerosis in the aortic arch was observed by HE.ResultsThe formation of atherosclerosis in aortic tissue was observed by HE staining after IH. Compared with the RA rats, the level of HIF-1α and NF-κB in the serum of IH rats started to increase 4, 8, and 12 weeks after the beginning of the experiment (p<0.05). The level of HIF-1α in IH rats was highest at 4 w, and there was no change between 8 w and 12 w (p>0.05). NF-κB protein expression was significantly increased after IH (p<0.05). HIF-1α and NF-κB positive cells in aortic tissue from IH rabbits were induced to a much higher level compared with normal controls (p<0.05). Compared with IH rabbits after 4 w, the positive cells of HIF-1α and NF-κB were higher at 8 w and 12 w after IH (p<0.05).ConclusionsIH may, through increased HIF-1α and NF-κB in rabbits, lead to lipid deposition, which leads to the formation of atherosclerosis and the occurrence of cardiovascular and cerebrovascular diseases.
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