Many attempts to modulate leukocyte-endothelial interaction to prevent or reduce excessive inflammatory reactions were made in the past. However, the basic regulatory principles of the endothelial inflammatory process remain unclear. It seems that the inhibition of individual components of the inflammatory cascade, for example, by a single antibody against an adhesion molecule, may not be enough to achieve a sustained effect on vascular inflammation.In the past years, microRNAs have been identified as important regulators of gene expression in a wide range of Molecular Medicine© 2017 American Heart Association, Inc. Rationale:The interaction of circulating cells within the vascular wall is a critical event in chronic inflammatory processes, such as atherosclerosis, but the control of the vascular inflammatory state is still largely unclear.Objective: This study was undertaken to characterize the function of the endothelial-enriched microRNA miR-100 during vascular inflammation and atherogenesis. Methods and Results:Based on a transcriptome analysis of endothelial cells after miR-100 overexpression, we identified miR-100 as a potent suppressor of endothelial adhesion molecule expression, resulting in attenuated leukocyte-endothelial interaction in vitro and in vivo as shown by flow cytometry and intravital imaging. Mechanistically, miR-100 directly repressed several components of mammalian target of rapamycin complex 1-signaling, including mammalian target of rapamycin and raptor, which resulted in a stimulation of endothelial autophagy and attenuated nuclear factor κB signaling in vitro and in vivo. In a low-density lipoprotein receptordeficient atherosclerotic mouse model, pharmacological inhibition of miR-100 resulted in enhanced plaque lesion formation and a higher macrophage content of the plaque, whereas a systemic miR-100 replacement therapy had protective effects and attenuated atherogenesis, resulting in a decrease of plaque area by 45%. Finally, analysis of miR-100 expression in >70 samples obtained during carotid endarterectomy revealed that local miR-100 expression was inversely correlated with inflammatory cell content in patients. Conclusions: In summary, we describe an anti-inflammatory function of miR-100 in the vascular response to injury and inflammation and identify an important novel modulator of mammalian target of rapamycin signaling and autophagy
State-of-the-art electrode materials for all-vanadium redox flow batteries are based on carbon. Unfortunately, the impact of the carbon structure, i.e., microstructure/crystallinity, surface functional groups, and porosity/morphology/surface area, on the electrochemical performance is still unclear. This is due to the fact that usually several structural characteristics are varied due to synthesis or post-treatment procedures at the same time. Therefore, this paper shows systematically how microstructure, porosity, and surface functional groups vary with carbonization and graphitization temperature (ranging from 700 to 1500 °C) for a mesoporous N-doped carbon (MPNC). Changes in the material’s structure (e.g., morphology, porosity, crystal structure, surface functionalization), determined by scanning and transmission electron microscopy, X-ray diffraction (pair distribution function analysis), X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy, and N2 sorption measurements, are correlated to changes in wettability, conductivity, and electrochemical kinetics, investigated by H2O sorption measurements, cyclic voltammetry, and electrochemical impedance spectroscopy in the VO2+ electrolyte, respectively. We found that the kinetics of the VO2+/VO2 + reaction increases with an increase in sp2-C content and therefore an increase in crystallite size and conductivity of the mesoporous N-doped carbon. Nevertheless, the largest current for the VO2+/VO2 + reaction for the same amount of carbon during cyclic voltammetry is observed for the MPNC carbonized at an intermediate temperature, 1000 °C, as a result of its larger wettability and thus available surface area compared to the MPNC carbonized at 1500 °C.
We demonstrate an electrodeposition process for the fabrication of highly porous PtCu alloy anodes. In the fabrication process, Pt and different amounts of a second noble metal (Pd, Ru, Au) are repeatedly co‐deposited with Cu from an aqueous electrolyte, followed by selective dealloying of Cu. In this way, highly porous PtCu alloys with roughness factors ranging from 400 to 4000 can be obtained. In all cases, both noble‐metal partners are present on the electrode surface, whereas the majority of copper is likely buried underneath. In addition, we can show that H desorption and CO stripping yield substantially different roughness factors, even when applied to PtCu anodes. Hence, when using or comparing results from different stripping methods, a calibration is required. Compared to PtCu anodes, small additions of Ru (ca. 3 at% Ru) lead to significantly enhanced catalytic activity for the electro‐oxidation of formic acid and methanol, whereas Au‐rich PtCu−Au alloys (ca. 75 at% Au) exhibit significantly improved electrocatalytic activity for glucose oxidation. In some cases, large variations impede the identification of significant differences in electrocatalytic activity. To reduce process variability and to increase the specific surface area, further optimization of the fabrication process is required. Similarly, the deposition of defined alloy compositions will require further investigation, as the composition of electrolyte and deposited alloy do not directly correspond.
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