Secular Trends of Clinical Characteristics and Survival of Hepatocellular Carcinoma in Taiwan from 2011 to 2019.

Hepatocellular carcinoma (HCC) is a major cause of cancer death in Taiwan, and in the past 30-40 years, Taiwan has been committed to its prevention and treatment. We aimed to investigate the secular trends of characteristics and the survival of HCC in recent decades after making increased efforts. Between 2011 and 2019, a total of 73,817 cases were enrolled from the TCR database. The overall male-to-female ratio was 7/3. The overall, male and female mean ages increased from 63.8 to 66.1 years, 62.0 to 64.3 years and 68.3 to 70.4 years, respectively. After dividing by viral etiologies and gender, the mean age showed increasing trends in all subgroups. The proportions of HBV-HCC, HCV-HCC, HBV+HCV-HCC and Non-HBV+non-HCV-HCC were 48.3%, 25.2%, 5.3% and 21.3% in males, compared with 25.5%, 48.6%, 5.3% and 20.5% in females, respectively. The 5-year survival rates of BCLC stages 0, A, B, C and D were 70%, 58%, 34%, 11% and 4%, respectively. The proportion of BCLC stage 0 increased from 6.2% to 11.3%. Multivariate analysis showed that being female, older age, diagnostic year, BCLC stages, hospital level, body mass index, smoking, alcohol consumption, AFP, Child-Pugh classification and HBV/HCV status were independent predictors for survival. In recent decades, the overall survival of HCC in Taiwan has been improving and might be partly associated with increased BCLC 0 and Child-Pugh A patients, while with the consequent age of patients increasing over time. The proportion of viral-related HCC is decreasing, while nonviral-related HCC is increasing.

Surface Structure Analysis of Initial High-Temperature Oxidation of SS441 Stainless Steel.

Chromia-forming ferritic stainless steel (FSS) is a highly promising interconnect material for application in solid oxide fuel cells. In this study, initial oxidation of chromium oxides was performed at 500-800 °C to understand the evolution of materials at an early stage. The structural variations in oxide scales were analyzed through scanning electron microscopy, energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), X-ray diffractometry (XRD), laser confocal microscopy (LSCM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Surface electrochemical properties were investigated through electrochemical impedance spectroscopy to understand how the heat treatment temperature affected surface impedance. Treatment temperatures higher than 700 °C facilitate the diffusion of Cr and Mn, thus allowing ferritic spinels to form on the surface and leading to high electrical conductivity.

Effects of oxygen functional groups on the enhancement of the hydrogen spillover of Pd-doped activated carbon.

The hydrogen storage performance of Pd-doped oxidized activated carbon (Pd/AC-ox) with various oxygen contents or functional groups was investigated. The surface chemistry of the Pd/AC-ox sample was modified by treatment with hydrogen gas. Temperature-programmed desorption was performed to characterize the oxygen functional groups in each sample. In this study, low- and high-pressure hydrogen adsorption isotherm experiments were conducted using a static volumetric measurement at room temperature (RT) and pressures of up to 8 MPa. The results showed that increasing the oxygen content and functional groups on the surface of the Pd/AC-ox significantly improved the reversible RT hydrogen storage capacity due to the spillover effect. The hydrogen spillover enhancement factors at 0.12 MPa were greater than 100% for all samples. The hydrogen uptake of Pd/AC-ox1 at RT and 8 MPa with an oxygen content of 8.94 wt.% was 0.37 wt.%, which was 48% greater than that of Pd-free AC-ox (0.25 wt.%). In addition, the hydrogen uptake of Pd/AC-ox3 with lower oxygen contents demonstrates that the hydrogen spillover enhancement gradually disappears when the pressure is increased to more than 2 MPa (i.e., a transition from spillover to physisorption). The surface diffusion, or reversible adsorption, of the spiltover H atoms, which is enhanced by oxygen functional groups, was affected by a threshold amount of oxygen groups (such as hydroxyl groups).

Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding.

Melatonin has been shown to be produced by nonpineal cells and possess anti-inflammatory actions in animal models. In the present study, we tested the hypothesis that melatonin suppresses the expression of proinflammatory genes such as cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (INOS) by a common transcriptional mechanism. Melatonin but not tryptophan or serotonin inhibited lipopolysaccharide (LPS)-induced COX-2 and iNOS protein levels and promoter activities in RAW 264.7 cells in a time- and concentration-dependent manner. LPS or LPS plus interferon-gamma (IFNgamma) increased binding of all 5 isoforms of NF-kappaB to COX-2 and iNOS promoters. Melatonin selectively inhibited p52 binding without affecting p100 expression, p52 generation from p100, or p52 nuclear translocation. p52 acetylation was enhanced by LPS, which was abrogated by melatonin. Melatonin inhibited p300 histone acetyltransferase (HAT) activity and abrogated p300-augmented COX-2 and iNOS expression. HAT inhibitors suppressed LPS-induced p52 binding and acetylation to an extent similar to melatonin, and melatonin did not potentiate the effect of HAT inhibitors. These results suggest that melatonin inhibits COX-2 and iNOS transcriptional activation by inhibiting p300 HAT activity, thereby suppressing p52 acetylation, binding, and transactivation.

Lipopolysaccharide-induced transcriptional activation of interleukin-10 is mediated by MAPK- and NF-kappaB-induced CCAAT/enhancer-binding protein delta in mouse macrophages.

We have previously revealed that LPS can activate transcription of the IL-10 gene promoter through transcription factors Sp1, C/EBPbeta and C/EBPdelta in mouse macrophages. In this study, we determined that NF-kappaB and MAPK signal pathways, including ERK, JNK, and p38, were all involved in LPS-induced IL-10 gene expression. Treatment of cells with the pharmacological inhibitors of ERK, JNK, p38 and NF-kappaB respectively inhibited LPS-induced IL-10 protein expression in a dose-dependent manner. These inhibitors also decreased the LPS-induced IL-10 mRNA expression at a high concentration used. With transient overexpression of the IkappaB expression plasmids, or the dominant negative plasmids of ERK2, JNK, p38 together with reporter vector containing IL-10 promoter region, all four expression plasmids inhibited LPS-induced IL-10 promoter activity individually. It is known that the increase in protein and DNA binding of C/EBPbeta and delta could activate IL-10 gene expression. In this study, we also identified that all four pharmacological inhibitors inhibited the protein expression of C/EBPdelta individually, but not C/EBPbeta. In the presence of all three MAPK inhibitors, or only NF-kappaB inhibitor, LPS-induced protein expression and DNA binding of C/EBPdelta were completely inhibited simultaneously, and LPS-induced expression of IL-10 protein and mRNA was also inhibited totally. Taken together, these results suggested that LPS-induced IL-10 expression was mediated at least through the pathway of NF-kappaB- and MAPK-induced protein expression and DNA binding of C/EBPdelta.

Functional cooperation of simian virus 40 promoter factor 1 and CCAAT/enhancer-binding protein beta and delta in lipopolysaccharide-induced gene activation of IL-10 in mouse macrophages.

Previous studies have revealed that LPS can activate transcription of the IL-10 gene promoter through an SV40 promoter factor 1 (Sp1) binding site in mouse macrophage RAW264.7. In this study, we determined that, in addition to Sp1, C/EBPbeta and delta were also involved in LPS-induced gene expression of IL-10. By transient transfection with 5'-deletion mutants of the IL-10 promoter, we found that there were two LPS-responsive elements in the promoter of the mouse IL-10 gene. Analysis of these two regions by gel shift assay suggested that Sp1 and C/EBPbeta and delta were bound to these two regions, respectively. By site-directed mutagenesis, we found that disruption at both the Sp1 and C/EBP binding sites almost completely blocked the LPS response. By gel shift assay and Western blotting, we found that the DNA binding complex and protein expression of C/EBPbeta and delta were increased by LPS treatment, but these results were not found for Sp1. Overexpression of C/EBPbeta or C/EBPdelta, respectively, activated the promoter of the IL-10 gene, and they were enhanced by LPS. Coimmunoprecipitation experiments in intact cells indicated that LPS stimulated interaction between Sp1 and C/EBPbeta and delta. These results suggested that the interaction between Sp1 and C/EBPbeta and delta induced by LPS cooperatively activated expression of the IL-10 gene. The increase of C/EBPbeta and delta proteins and the enhancement of transactivation activity of C/EBPbeta and delta by LPS treatment, at least in part, explain the activation of IL-10 gene expression.