Atherosclerosis is a common and deadly cardiovascular disease with extremely high prevalence. Areas of the vasculature exposed to oscillatory shear stress (OSS) or disturbed blood flow are particularly prone to the development of atherosclerotic lesions. In part, various mechanosensitive receptors on the surface of endothelial cells play a role in regulating the ability of the vasculature to cope with variations in blood flow patterns. However, the exact mechanisms behind flow-mediated endothelial responses remain poorly understood. Along with the development of highly specific receptor agonists, the class of G coupled-protein receptors has been receiving increasing attention as potential therapeutic targets. G coupled-protein receptor 81 (GPR81), also known as hydroxycarboxylic acid receptor 1 (HCA 1 ), is activated by lactate, its endogenous ligand. In the present study, we show for the first time that expression of GPR81 is significantly downregulated in response to OSS in endothelial cells and that activation of GPR81 using physiologically relevant doses of lactate can rescue OSS-induced reduced GPR81 expression. Importantly, our findings demonstrate that activation of GPR81 can exert valuable atheroprotective effects in endothelial cells exposed to OSS by reducing oxidative stress and significantly downregulating the expression of inflammatory cytokines including interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and high mobility group box 1 (HMGB1). We also show that activation of GPR81 can potentially prevent the attachment of monocytes to the endothelium by suppressing OSS-induced secretion of vascular cellular adhesion molecule (VCAM)-1 and endothelial-selectin (E-selectin). Finally, we show that activation of GPR81 can rescue OSS-induced reduced expression of the key atheroprotective transcription factor Kruppel-like factor 2 (KLF2), which is mediated through the extracellularregulated kinase 5 (ERK5) pathway. These findings demonstrate a potential Abbreviations: ECL, electrochemiluminescence; E-selectin, endothelial-selectin; ELISA, Enzyme-linked immunosorbent assay; ERK5, extracellularregulated kinase 5; FBS, fetal bovine serum; GPR81, G coupled-protein receptor 81; GPCRs, G protein-coupled receptors; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HMGB1, high mobility group box 1; HSS, high shear stress; HUVECs, human umbilical vascular endothelial cells; HCA 1 , hydroxycarboxylic acid receptor 1; IL-6, interleukin; KLF2, Kruppel-like factor 2; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein; OSS, oscillatory shear stress; PAK1, p21-activated kinase 1; PVDF, polyvinylidene fluoride; ROS, reactive oxygen species; RT-PCR, reverse transcription PCR; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; VCAM-1, vascular cellular adhesion molecule.

BackgroundApatinib, a novel small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, have shown remarkable efficacy in many solid cancers. But evidence of antitumor activity in patients with lymphoma is still limited. We conducted an open-label, single-armed, exploratory study in relapse or refractory non-Hodgkin lymphoma patients for the efficacy and safety of apatinib.Experimental designPatients with relapse or refractory non-Hodgkin patients meet the criteria were eligible for enrollment. Treatment comprised of oral apatinib 500 mg once daily with 21 days as a treatment cycle. The primary end point was response rate. Secondary end points included progression-free survival (PFS) and overall survival (OS).ResultsBetween February 2016 and December 2016, 21 patients were enrolled. The ORR (CR plus PR) was 47.6% (10 of 21 patients) included 9.5% CRs and 38.1% PRs. 23.8% patients achieved stable disease made the DCR 71.4% (15/21). The median OS was 7.3 months (95% CI, 7.1 to 7.9) and the median PFS was 7.1 months (95% CI, 4.2 to 7.3). Most patients suffered from grade 1 to grade 2 treatment-related adverse events and the most common nonhematologic adverse events were proteinuria (47.6%), hypertension (42.9%) and hand-foot syndrome (33.3%), respectively.ConclusionsIn our study, the results we presented showed apatinib might have a rapid, safe and high efficacy on relapsed or refractory non-Hodgkin lymphoma patients. Based on the data more clinic trials are expected to be taken to identification the efficacy of apatinib on lymphoma further.

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Exploring efficient and inexpensive oxygen evolution reaction (OER) electrocatalysts is essential for clean renewable energy systems. Ni-based nanomaterials have been intensively pursued for NiOOH can play a key role in OER processes in alkaline electrolytes. In this work, Ni nanoparticles (NPs) absorbed onto commercial carbon black and nitrogen-doped reduced graphene oxide as electrochemical catalysts activities in OER have been explored. The study found that the current density and Tafel slope of Ni/C nanocomposite in OER were affected obviously by different carbon supporter and the surface properties of Ni NPs. The work revealed that the Ni NPs electrical contact with supporter and surface hydrophilism of catalytically active species is more important than the size and loaded amount. The awareness of the catalytic kinetics difference deepened their comprehension of the structure-property relationship of the electrocatalyst, which would contribute to the rational design of excellent OER catalysts.