Background-Myocardial ischemia provides a potent stimulus to angiogenesis, and the mobilization and differentiation of endothelial progenitor cells (EPCs) has been shown to be important in this process. An elevated level of C-reactive protein (CRP) has emerged as one of the most powerful predictors of cardiovascular disease. However, the impact of CRP on EPC biology is unknown. Methods and Results-EPCs were isolated from the peripheral venous blood of healthy male volunteers. Cells were cultured in endothelial cell basal medium-2 in the absence and presence of CRP (5 to 20 g/mL), rosiglitazone (1 mol/L), and/or vascular endothelial growth factor. EPC differentiation, survival, and function were assayed. CRP at concentrations Ն15 g/mL significantly reduced EPC cell number, inhibited the expression of the endothelial cell-specific markers Tie-2, EC-lectin, and VE-cadherin, significantly increased EPC apoptosis, and impaired EPC-induced angiogenesis. EPC-induced angiogenesis was dependent on the presence of nitric oxide, and CRP treatment caused a decrease in endothelial nitric oxide synthase mRNA expression by EPCs. However, all of these detrimental CRP-mediated effects on EPCs were attenuated by pretreatment with rosiglitazone, a peroxisome proliferator-activated receptor-␥ (PPAR␥) agonist. Conclusions-Human recombinant CRP, at concentrations known to predict adverse vascular outcomes, directly inhibits EPC differentiation, survival, and function, key components of angiogenesis and the response to chronic ischemia. This occurs in part via an effect of CRP to reduce EPC eNOS expression. The PPAR␥ agonist rosiglitazone inhibits the negative effects of CRP on EPC biology. The ability of CRP to inhibit EPC differentiation and survival may represent an important mechanism that further links inflammation to cardiovascular disease.

This study examines how green intellectual capital (GIC) affects economic and green performance through green innovation. We show ways in which a firm's performance is influenced by three dimensions of GIC, that is, green human capital (GHC), green relational capital (GRC), and green structural capital (GSC), and use the mediating role of green innovation to explain the relationships. The results of a survey conducted on 138 high-tech firms indicate that the three GIC constructs positively affect economic performance, green performance, and green innovation, respectively.Further analysis finds that green innovation fully mediates the linkage of GHCeconomic performance and GSC-green performance and partially mediates the linkage of GRC-economic performance and GRC-green performance. We find that green innovation does not mediate the linkage of GSC-economic performance and GHC-green performance, and this contributes towards business strategy and implementation of green innovation practices.green human capital, green innovation, green intellectual capital, green relational capital, green structural capital | INTRODUCTIONRecently, there has been increased academic debate and concern with environmental sustainability (Hsueh, 2019). More than a century of

Objective-Both matrix metalloproteinases (MMPs) and endothelial progenitor cells (EPCs) have been implicated in the process of neovascularization. Here we show that the impaired neovascularization in mice lacking MMP-9 is related to a defect in EPC functions in vasculogenesis. Methods and Results-Hindlimb ischemia surgery was conducted in MMP-9 Ϫ/Ϫ mice and wild-type (MMP-9 ϩ/ϩ ) mice. Blood flow recovery was markedly impaired in MMP-9 Ϫ/Ϫ mice when compared with that in wild-type mice as determined by laser Doppler imaging. Flow cytometry demonstrated that the number of EPC-like cells (Sca-1 ϩ /Flk-1 ϩ ) in peripheral blood increased in wild-type mice after hindlimb ischemia surgery and exogenous vascular endothelial growth factor stimulation, but not in MMP-9 Ϫ/Ϫ mice. Plasma levels and bone marrow concentrations of soluble Kit-ligand (sKitL) were significantly elevated in wild-type mice in response to tissue ischemia, but not in MMP-9 Ϫ/Ϫ mice. C-kit positive bone marrow cells of MMP-9 Ϫ/Ϫ mice have attenuated adhesion and migration than those isolated from wild-type mice. In in vitro studies, incubation with selective MMP-9 inhibitor suppressed the colony formation, migration, and tube formation capacities of EPC. Transplantation of bone marrow cells from wild-type mice restored collateral flow formation in MMP-9 Ϫ/Ϫ mice. Conclusions-These findings suggest that MMP-9 deficiency impairs ischemia-induced neovascularization, and these effects may occur through a reduction in releasing the stem cell-active cytokine, and EPC mobilization, migration, and vasculogenesis functions.

Patients with chronic kidney disease have an increased prevalence of peripheral arterial disease. Endothelial progenitor cells (EPC) are pivotal in neovascularization, but their role in mediating peripheral arterial disease in chronic kidney disease is not fully known. Here we studied the impact of indoxyl sulfate, a protein-bound uremic toxin, on EPC function in response to tissue ischemia or cell hypoxia in mice that underwent subtotal nephrectomy or sham operation. At 16 weeks, unilateral hindlimb ischemia was induced in all. Four weeks later, subtotal nephrectomy mice had significantly increased plasma levels of indoxyl sulfate, reduced reperfusion, decreased EPC mobilization, and impaired neovascularization in ischemic hindlimbs compared with control mice. Treatment with AST-120, an oral adsorbent of uremic toxins, reversed these changes. Ischemia-induced protein expression including phospho-eNOS, phospho-STAT3, interleukin-10, and VEGF were significantly decreased in ischemic hindlimbs of subtotal nephrectomy mice versus control mice; all effects were reversed by AST-120. Subtotal nephrectomy mice fed a diet with indole for 12 weeks resulted in impaired neovascularization in ischemic hindlimbs; also reversed by AST-120. In cultured human EPCs, VEGF expression was increased in hypoxia through HIF-1α and interleukin-10/STAT3 signaling; effects suppressed by pretreatment with indoxyl sulfate. Moreover, indoxyl sulfate markedly attenuated hypoxia-induced EPC migration and tube formation. Thus, indoxyl sulfate may be a therapeutic target for EPC-rescue of impaired neovascularization in patients with chronic kidney disease and peripheral arterial disease.

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light, these piezoelectric charges have been utilized to enhance the conversion effi ciency of light-emitting diodes [ 10 ] and solar cells [ 11 ] in addition to the sensitivity of photodetectors [ 12 ] and active imaging pressure sensors [ 13 ] via the piezo-phototronic effect. The piezotronic and piezo-phototronic effects expand the applications of piezoelectric semiconductor materials.For developing high-output-power NGs, the geometrical design and inner resistance of semiconductor nanomaterials have been shown to be paramount, both in experiments [ 14,15 ] and calculations. [16][17][18][19] The room-temperature carrier concentration in semiconductors is often overlooked in the design of NGs, even though it is one of the most fundamental characteristics and can be easily tuned through doping and photoexcitation. For instance, it has been demonstrated that the output performance of n-type ZnO-based NGs can be enhanced by p-type doping, [ 20 ] but decreased with higher hole concentration achieved with antimony (Sb). [ 21 ] Surface passivation improves the output voltage of NGs under UV illumination because the carrier screening effect is minimized. [ 22 ] This implies that the doping concentration greatly affects NG performance and should thus be studied in depth. However, its effect has rarely been studied due to the lack of an effi cient method of controlling the defect levels inside intrinsic ZnO.GaN, which has a low intrinsic electron concentration and is insensitive to the ambient, is an ideal model material for the investigation of the carrier concentration effect on the output performance of NGs. In this work, a series of Si-doped GaN nanowire (NW) arrays was employed to study the carrier screening effect on piezopotential, and thus the output power of NGs.The basic semiconductor and crystal properties of the GaN NW arrays synthesized by plasma-assisted molecular beam epitaxial (PA-MBE) system were investigated since they enormously infl uence the power generation and the mechanisms of electricity generation of NGs. The typical diameter and density of the as-grown vertically aligned n-GaN NW arrays are ≈50 nm and 7.95 × 10 10 cm −2 , respectively, as shown in Figure 1 a, while the length is ≈500 nm after 2 h growth. Figure 1 b shows a typical high-resolution TEM (HR-TEM) image of a NW. The GaN NWs exhibit high crystallinity without noticeable linear or planar defects. Moreover, the spacing of the lattice fringes is measured to be ≈0.251 nm, which corresponds to the c -plane interplanar distance of a GaN crystal. The polarity of the GaN NWs was found to be -c polar with respect to the growth direction. A detailed crystal polarity characterization is presented in the Supporting Information.As fossil fuels are consumed at an extremely fast rate, various types of renewable energy technologies have been developed to either replace or work with traditional energy power plants. Recently, piezoelectric nanogenerators (NGs) have been proposed for scavenging mechanical energy from movements or vibrations. Both dire...

Though there has been much research into green performance, few studies have analyzed whether a green market orientation (GMO) is important. In this study, we propose and test a model that links three subconstructs of GMO (i.e., green customer orientation, green interfunctional orientation, and green competitor orientation) and green performance. The mediating role of green innovation and if there is a missing link between these relationships is also tested. By decomposing the components of GMO and introducing green innovation as a mediator, the results contribute to a more nuanced understanding of how and why green innovation is important in the linkage between GMO and green innovation. Using a survey of 248 high-tech firms in Taiwan, the results highlight three subconstructs of GMO in facilitating green innovation and green performance. Green innovation fully mediates the association between green interfunctional orientation and green performance. However, green innovation only partially mediates the effects of green customer orientation and green competitor orientation on green performance.

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