Purpose: X protein (HBx), a product of hepatitis B virus, has been closely associated with the development of hepatocellular carcinoma (HCC). Based on observations that the COOH-terminal truncated HBx was frequently detected in HCC, the aim of this study is to evaluate the function of COOH-terminal truncated HBx in hepatocarcinogenesis. Experimental Design: Expression pattern of HBx was analyzed by immunohistochemistry on tissue microarray containing 194 pairs of HCCs and their matched nontumor liver tissues. MIHA and HepG2 cells transfected with full-length (X2) and COOH-terminal truncated HBx (X1) were tested for their ability to grow in soft agar and form tumors in vivo. Proliferation and apoptosis were assessed using 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assays, respectively. To gain additional insight, the expression profile of HepG2-X2 and HepG2-X1were compared using cDNA microarray. Results: COOH-terminal truncated HBx was frequently detected in HCCs (79.3%, n = 111), and our in vitro and in vivo studies showed that the truncated rather than the full-length HBx could effectively transform immortalized liver cell line MIHA. Interestingly, expression profiling revealed differential expression of key genes implicated in the control of cell cycle and apoptosis. Conclusions: These findings strongly suggest that the COOH-terminal truncated HBx plays a critical role in the HCC carcinogenesis via the activation of cell proliferation.Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third cause of cancer death in the world (1). The prognosis of HCC is very poor and the overall 5-year survival rate worldwide is estimated only f3%, mainly because of late diagnosis (2). Although the molecular pathogenesis of HCC remains elusive, the etiologic association between hepatitis B virus (HBV) infection and hepatocarcinogenesis has been established (3). Epidemiologic studies have shown that the relative risk of HCC among HBV carrier is 10-fold higher compared to noncarrier (4). Among the four proteins translated by HBV, the X-gene product (HBx) has been closely associated with the HCC carcinogenesis (5).HBx is a small protein with 154 amino acids, which is required for the establishment of viral infection. The correlation between HBx and HCC development has been extensively studied and oncogenic roles of HBx include the following: (a) the activation of a variety of transcription factors such as nuclear factor-nB (6), activator protein (7), and cAMPresponsive element binding protein/activating transcription factor 2 (8); (b) the interaction with cellular oncogenes such as Ras (9), Src (10), c-jun (11); and (c) the stimulation of cytoplasmic signal transduction pathways such as Ras-Rafmitogen-activated protein kinase pathway (7, 9), and cell stress -induced MEKK1-p38-cJNK pathway (12). One important question that needs to be answered is why HCC occurred only in a small percent...

To facilitate profiling mitochondrial transcriptomes, we developed a third-generation human mitochondria-focused cDNA microarray (hMitChip3) and its bioinformatic tools. hMitChip3 consists of the 37 mitochondrial DNA-encoded genes, 1098 nuclear DNA-encoded and mitochondria-related genes, and 225 controls, each in triplicate. The bioinformatic tools included data analysis procedures and customized database for interpretation of results. The database associated 645 molecular functions with 946 hMitChip3 genes, 612 biological processes with 930 genes, 172 cellular components with 869 genes, 107 biological chemistry pathways with 476 genes, 23 reactome events with 227 genes, 320 genetic disorders with 237 genes, and 87 drugs targets with 55 genes. To test these tools, hMitChip3 was used to compare expression profiles between human melanoma cell lines UACC903 (rapidly dividing) and UACC903(+6) (slowly dividing). Our results demonstrated internal gene-set consistency (correlation R > or = 0.980 +/- 0.005) and interexperimental reproducibility (R > or = 0.931 +/- 0.013). Expression patterns of 16 genes, involved in DNA, RNA, or protein biosyntheses in mitochondrial and other organelles, were consistent with the proliferation rates of both cell lines, and the patterns of 6 tested genes were verified by quantitative reverse transcription PCR (RT-PCR). Thus, hMitChip3 and its bioinformatics software provide an integrated tool for profiling mitochondria-focused gene expression.

Driven by huge demand for flexible optoelectronic devices, high-performance flexible transparent electrodes are continuously sought. In this work, a flexible multilayer transparent electrode with the structure of ZnO/Ag/CuSCN (ZAC) is engineered, featuring inorganic solution-processed cuprous thiocyanate (CuSCN) as a hole-transport antireflection coating. The ZAC electrode exhibits an average transmittance of 94% (discounting the substrate) in the visible range, a sheet resistance ( R) of 9.7 Ω/sq, a high mechanical flexibility without R variation after bending 10 000 times, a long-term stability of 400 days in ambient environment, and a scalable fabrication process. Moreover, spontaneously formed nanobulges are integrated into ZAC electrode, and light outcoupling is significantly improved. As a result, when applied into super yellow-based flexible organic light-emitting diode, the ZAC electrode provides a high-current efficiency of 23.4 cd/A and excellent device flexibility. These results suggest that multilayer thin films with ingenious material design and engineering can serve as a promising flexible transparent electrode for optoelectronic applications.

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