BackgroundAlthough fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated. FGF19, a member of the FGF family, has unique specificity for its receptor FGFR4. This study aimed to clarify the involvement of FGF19 in the development of HCC.MethodsWe investigated human FGF19 and FGFR4 expression in 40 hepatocellular carcinoma specimens using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Moreover, we examined the expression and the distribution of FGF19 and FGFR4 in 5 hepatocellular carcinoma cell lines (HepG2, HuH7, HLE, HLF, and JHH7) using RT-PCR and immunohistochemistry. To test the role of the FGF19/FGFR4 system in tumor progression, we used recombinant FGF19 protein and small interfering RNA (siRNA) of FGF19 and FGFR4 to regulate their concentrations.ResultsWe found that FGF19 was significantly overexpressed in HCCs as compared with corresponding noncancerous liver tissue (P < 0.05). Univariate and multivariate analyses revealed that the tumor FGF19 mRNA expression was an independent prognostic factor for overall and disease-free survival. Moreover, we found that the FGF19 recombinant protein could increase the proliferation (P < 0.01, n = 12) and invasion (P < 0.01, n = 6) capabilities of human hepatocellular carcinoma cell lines and inhibited their apoptosis (P < 0.01, n = 12). Inversely, decreasing FGF19 and FGFR4 expression by siRNA significantly inhibited proliferation and increased apoptosis in JHH7 cells (P < 0.01, n = 12). The postoperative serum FGF19 levels in HCC patients was significantly lower than the preoperative levels (P < 0.01, n = 29).ConclusionsFGF19 is critically involved in the development of HCCs. Targeting FGF19 inhibition is an attractive potential therapeutic strategy for HCC.

Clinicians need to understand the underlying principles and pathologic and pharmacokinetic backgrounds of contrast-enhanced CT and MRI to further improve diagnostic performance. With adjustments in image acquisition and postprocessing, contrast-enhanced CT and MRI, especially the dynamic versions, can have enhanced clinical application for pulmonary nodules and expanded clinical relevance for other thoracic diseases.

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Although not as eye‐catching as their business counterparts, many public and private institutions are currently experimenting with using platforms as a strategy of governance. Governance platforms are now being constructed by a wide array of actors at different geographical scales and across a wide range of issue areas. Although often enabled by digital technology, governance platforms fundamentally embody a new organizing logic to achieve distributed participation and mobilization. While private platforms are transforming the way that companies create and market their products or services and shifting the fundamental logic of how value is produced and appropriated, can this powerful organizing logic be harnessed for public as well as private purposes? We investigate how governance platforms generate powerful effects and survey the extant literature on governance platforms. We conclude that governance platforms do demonstrate promise, although they face a number of challenges.

Double proton transfer in the formic acid dimer has been investigated with Car-Parrinello ab initio molecular dynamics calculations. The electronic structure of the dimer has been obtained using gradient-corrected density functional theory based on the B-LYP ͑Becke exchange ͓Phys. Rev. A 38, 3098 ͑1988͔͒ and Lee-Yang-Parr correlation ͓Phys. Rev. B 37, 785 ͑1988͔͒ functional. The optimized equilibrium and saddle-point geometries, obtained by simulated annealing, are in good agreement with previous ab initio quantum chemical predictions and experiment. Thermal and quantum fluctuations of nuclei along the double proton transfer reaction path have also been investigated at Tϭ300 K. Thermal fluctuations give a broad distribution of nuclei around the minimum energy path on the potential energy surface. Quantum fluctuations, investigated using ab initio path integral molecular dynamics, make the distribution even broader around the equilibrium structure, and cause the distribution to deviate appreciably from the minimum energy path on approaching the reaction barrier. In particular, the system passes through higher energy regions than the geometrical saddle point by tunneling; an observation which is consistent with the conventional understanding of heavy-light-heavy mass combination reactions. While there is asynchronous movement of the two protons around the equilibrium structure, synchronous movement becomes relevant on approaching the reaction barrier.