Low oxygen or hypoxia can be observed in the central region of solid tumors. Hypoxia is a strong stimulus for new blood vessel formation or angiogenesis, which is essential for tumor growth and progression. Fibroblast growth factor 11 (FGF11) is an intracellular non-secretory FGF whose function has not yet been fully characterized. In the present study, we demonstrated that FGF11 expression is upregulated under hypoxic conditions in human umbilical vein endothelial cells (HUVECs). FGF11 overexpression stimulated capillary-like tube formation, yet did not affect cell migration. Notably, FGF11 markedly increased the levels of tight junction proteins including occludin, zonula occludens-1 (ZO-1) and claudin-5 in HUVECs. The FGF11 promoter contains hypoxia response elements (HREs), and hypoxia-inducible factor-1 (HIF-1) binds to HREs to activate hypoxia-related genes. We demonstrated that hypoxia or HIF-1 expression under normoxic conditions increased the luciferase activity driven by the FGF11 promoter. However, deletion of the HREs from the FGF11 promoter rendered reporter gene activity unresponsive to hypoxia or HIF-1. Taken together, we propose that FGF11 may be involved in the stabilization of capillary-like tube structures associated with angiogenesis and may act as a modulator of hypoxia-induced pathological processes such as tumorigenesis.
Graphene/Si quantum dot (QD) heterojunction diodes are reported for the first time. The photoresponse, very sensitive to variations in the size of the QDs as well as in the doping concentration of graphene and consistent with the quantum-confinement effect, is remarkably enhanced in the near-ultraviolet range compared to commercially available bulk-Si photodetectors. The photoresponse proves to be dominated by the carriertunneling mechanism.
Cetacean body structure and physiology exhibit dramatic adaptations to their aquatic environment. Fibroblast growth factors (FGFs) are a family of essential factors that regulate animal development and physiology; however, their role in cetacean evolution is not clearly understood. Here, we sequenced the fin whale genome and analysed FGFs from 8 cetaceans. FGF22, a hair follicle-enriched gene, exhibited pseudogenization, indicating that the function of this gene is no longer necessary in cetaceans that have lost most of their body hair. An evolutionary analysis revealed signatures of positive selection for FGF3 and FGF11, genes related to ear and tooth development and hypoxia, respectively. We found a D203G substitution in cetacean FGF9, which was predicted to affect FGF9 homodimerization, suggesting that this gene plays a role in the acquisition of rigid flippers for efficient manoeuvring. Cetaceans utilize low bone density as a buoyancy control mechanism, but the underlying genes are not known. We found that the expression of FGF23, a gene associated with reduced bone density, is greatly increased in the cetacean liver under hypoxic conditions, thus implicating FGF23 in low bone density in cetaceans. Altogether, our results provide novel insights into the roles of FGFs in cetacean adaptation to the aquatic environment.
Fibroblast growth factor 11 (FGF11) is an intracellular FGF. Although induction of FGF11 by hypoxia has been observed in several cell types, the molecular function of FGF11 is not clearly understood yet. Here, we investigated the role of FGF11 under hypoxia. We identified hypoxia-inducible factor-1α (HIF-1α) as an interacting protein of FGF11 using immunoprecipitation and mass spectrometry. FGF11 knockdown decreased HIF-1α protein, while FGF11 overexpression increased it, without affecting HIF-1α mRNA. Protein stability test and ubiquitination assay showed that FGF11 increased HIF-1α stability by acting upstream of proteasomal degradation. Altogether, these results suggest a cross-regulation between HIF-1α and FGF11, through which hypoxia-induced FGF11 reinforces hypoxia responses by enhancing the stability of HIF-1α.
Single-layer graphene sheets have been synthesized by using chemical vapor deposition, and subsequently doped with AgNO₃ at various doping concentrations (n(D)) from 5 to 50 mM. Atomic force microscopy and field emission scanning electron microscopy images reveal the formation of ∼10-100 nm Ag particles on the graphene surface after doping. The type of n doping is confirmed by analyzing the n(D)-dependent behaviors of Raman scattering and the work function of the doped graphene films. The sheet resistance monotonically decreases to ∼173 Ω/sq with the increase of n(D) to 50 mM, and the transmittance is reduced by only about 3% for the highest n(D). At n(D) = 10 mM optimized doped graphene layers with a sheet resistance of 202 Ω/sq and a transmittance of 96% are obtained, resulting in a maximum DC conductivity/optical conductivity ratio (σ(DC)/σ(OP)) of ∼45.5, much larger than the minimum industry standard (σ(DC)/σ(OP) = ∼35) for transparent conductive electrodes.
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