Hierarchical micro/mesoporous carbons were prepared using ZnO nanoparticles as hard templates and a petroleum industrial-residual pitch as the carbon source via a solvent-free process. The ZnO ...templates can be easily removed using HCl(aq), thereby avoiding limitations present in conventional porous silica templating approaches that require highly corrosive HF(aq) for template removal. Notably, the proposed solvent-free synthetic method from low-cost pitch to high-value porous carbons is a friendly process with respect to our overexploited environment. With the combination of ZnO nanoparticles and pitch, the surface area (76–548 m2 g–1) of the resultant mesoporous carbons increases with an increase in the weight ratios of ZnO to pitch. Furthermore, the hierarchical micro/mesoporous carbons with a large surface area (854–1979 m2 g–1) can be feasibly fabricated by only adding an appropriate amount of an activating agent. Meanwhile, N-doped hierarchical porous carbons can be achieved by carbonizing the blend of these materials with melamine. For supercapacitor application, the resultant carbons exhibit a high capacitance up to 200.5 F g–1 at 5 mV s–1 using LiClO4/PC as the electrolyte in a symmetrical two-electrode cell. More importantly, the coin-cell supercapacitor based on porous carbons achieved a capacitance of 94 F g–1 at 5 mV s–1 and 63% capacitance retention at 500 mV s–1, thereby holding the potential for commercialization.
A 12-week grazoprevir/elbasvir regimen is highly effective against hepatitis C virus genotype 1 (HCV-1) infection. The efficacy of an 8-week regimen for treatment-naive HCV-1-infected patients with ...mild fibrosis has not been determined.
Treatment-naive HCV-1b-infected patients with mild fibrosis were randomly assigned to receive 8 (n = 41) or 12 (n = 41) weeks of grazoprevir/elbasvir therapy. The primary end point was a sustained virologic response, defined as an HCV RNA level of < 12 IU/mL, at posttreatment week 12 (SVR12).
SVR12 was achieved by 87.8% of patients (36 of 41) in the 8-week arm and 100% (41 of 41) in the 8-week arm of the full-analysis population and by 90.0% (36 of 40) and 100% (41 of 41), respectively, in the per-protocol population (all P = .055). In the 8-week arm, a significantly lower SVR12 rate was observed among patients with a high HCV-1b load, defined as ≥1 500 000 IU/mL (79% vs 100%; P = .042), and among those with a baseline Y93H resistance-associated substitution (RAS) frequency of >15% in HCV nonstructural protein 5A (NS5A; 40.0% vs 97.1%; P = .004). Between-group analysis demonstrated that, among patient with a high HCV-1b load and a baseline Y93H RAS frequency of >15%, those in the 8-week arm had a substantially lower SVR12 rate than those in the 12-week arm (40.0% vs 100.0%). All 4 HCV-1b relapses had a Y93H RAS frequency of >99% at posttreatment week 12.
Twelve weeks of grazoprevir/elbasvir therapy is highly effective for treatment-naive patients with mild fibrosis. A truncated, 8-week grazoprevir/elbasvir regimen might be applied for those with low viral loads or without a significant NS5A RAS frequency.
NCT03186365.
Osteoarthritis (OA) is the most common degenerative joint disease that is involved in the degradation of articular cartilage. The exact etiology of OA is not completely understood. CCN4 is related to ...up-regulation in the cartilage of patients with osteoarthritis. Previous studies have shown that CCN4 might be associated with the pathogenesis of OA, but the exact signaling pathways in CCN4-mediated IL-6 expression in synovial fibroblasts (SF) are largely unknown. Therefore, we explored the intracellular signaling pathway involved in CCN4-induced IL-6 production in human synovial fibroblast cells.
CCN4-induced IL-6 production was assessed with quantitative real-time qPCR and ELISA. The mechanisms of action of CCN4 in different signaling pathways were studied by using Western blotting. Neutralizing antibodies of integrin were used to block the integrin signaling pathway. Luciferase assays were used to study IL-6 and NF-κB promoter activity. Immunocytochemistry was used to examine the translocation activity of p65.
Osteoarthritis synovial fibroblasts (OASFs) showed significant expression of CCN4 and the expression was higher than in normal SFs. OASF stimulation with CCN4 induced concentration- and time-dependent increases in IL-6 production. Pretreatment of OASFs with αvβ5 but not α5β1 and αvβ3 integrin antibodies reduced CCN4-induced IL-6 production. CCN4-mediated IL-6 production was attenuated by PI3K inhibitor (LY294002 and Wortmannin), Akt inhibitor (Akti), and NF-κB inhibitor (PDTC and TPCK). Stimulation of cells with CCN4 also increased PI3K, Akt, and NF-κB activation.
Our results suggest that CCN4 activates αvβ5 integrin, PI3K, Akt, and NF-κB pathways, leading to up-regulation of IL-6 production. According to our results, CCN4 may be an appropriate target for drug intervention in OA in the future.
Nanovesicles (NVs) conjugating ligands can deliver to the specific nidus. We designed a nanosystem targeting the injectable niosomes to liver for examining biodistribution.
Vitamin A and ...antiplatelet-derived growth factor receptor antibody were employed as the ligands to be taken by hepatic stellate cells. The biodistribution in rats was visualized by bioimaging.
A significant liver accumulation was detected for antibody-embedded NVs at 2 h after dosing. The vitamin A embedded NVs exhibited a delayed targeting to the liver (5 h). The spleen, intestine and kidneys were the nontargeted organs where the vitamin A loaded niosomes largely accumulated. The antibody-loaded NVs could deliver to the spleen, kidneys and lungs. The antibody-loaded nanocarriers increased silibinin uptake to lungs by fourfold than the plain NVs.
The results have practical application for better designing of active targeting nanocarriers.
Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9) induced migration of human aortic smooth muscle cells (HASMCs) is the most common and ...basic pathological feature. Carbon monoxide (CO), a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47
, Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R) and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47
translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed.
The enhancement of output intensity, the generation of polarized output, and the reduction of the efficiency droop effect in a surface plasmon (SP) coupled vertical light-emitting diode (LED) with an ...Ag nano-grating structure located between the p-GaN layer and the wafer bonding metal for inducing SP coupling with the InGaN/GaN quantum wells (QWs) are demonstrated. In fabricating the vertical LED, the patterned sapphire substrate is removed with a photoelectrochemical liftoff technique. Based on the reflection measurement from the metal grating structure and the numerical simulation result, it is found that the localized surface plasmon (LSP) resonance induced around the metal grating crest plays the major role in the SP-QW coupling process although a hybrid mode of LSP and surface plasmon polariton can be generated in the coupling process. By adding a surface grating structure to the SP-coupled vertical LED on the n-GaN side, the output intensity is further enhanced, the output polarization ratio is further increased, and the efficiency droop effect is further suppressed.
Magnetic and electric properties are investigated for the nanosized YMnO
3
samples with different grain sizes (25 nm to 200 nm) synthesized by a modified Pechini method. It shows that magnetic and ...electric properties are strongly dependent on the grain size. The magnetic characterization indicates that with increasing grain size, the antiferromagnetic (AFM) transition temperature increases from 52 to 74 K. A corresponding shift of the dielectric anomaly is observed, indicating a strong correlation between the electric polarization and the magnetic ordering. Further analysis suggests that the rising of AFM transition temperature with increasing grain size should be from the structural origin, in which the strength of AFM interaction as well as the electrical polarization is dependent on the in-plane lattice parameters. Furthermore, among all samples, the sample with grain size of 95 nm is found to have the smallest leakage current density (< 1 μA/cm
2
).
PACS: 75.50.Tt, 75.50.Ee, 75.85.+t, 77.84.-s
An extremely durable and highly active Pt catalyst has been successfully prepared by embedding Pt0 nanoparticles inside the pores of the nitrogen-dotted porous carbon layer surrounding carbon ...nanotubes (Pt@NC−CNT). The Pt@NC−CNT catalyst has a high BET surface area of 271 m2 g−1 (62 m2 g−1 for Pt/XC-72) and comparably high electrochemically active surface area of 64.3 m2 g−1 (68.2 m2 g−1 for Pt/XC-72). The prepared Pt nanoparticles are small in size (2.8 ± 1.3 nm) and have a strong interaction of nitrogen to platinum, as evidenced by the binding energy observed at 399.5 eV. The maximum current densities (I f) during methanol oxidation observed for Pt@NC−CNT (13.2 mA cm−1) is 1.2 times higher than that of Pt/XC-72 (10.8 mA cm−1) catalysts. Remarkably, in the long term durability test, the I f after 1000 cycles for Pt@NC−CNT decreased to 10.6 mA cm−1 compared with Pt/XC-72, which decreased to 2.6 mA cm−2. This means that the Pt@NC−CNT catalyst has a tremendously stable electrocatalytic activity for MOR because of the unique structure of Pt@NC−CNT formed in this novel synthesis technique.
NVP-BEZ235 is a dual phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor. A dual approach targeting more than one downstream effector is a promising strategy for treating ...cancers. The aim of this study was to evaluate the effect of NVP-BEZ235 in treating FaDu hypopharyngeal squamous cell carcinoma (HSCC), either alone or in combination with cisplatin. We found
expression was higher in patients with HSCC. In the in vitro study, treatment with NVP-BEZ235 alone attenuated cell proliferation and suppressed p-p70S6K and p-4E-BP1 expression in FaDu cells. When NVP-BEZ235 was combined with Cisplatin, apoptosis was induced more effectively than with either drug alone. In mice with a FaDu xenograft, cotreatment with NVP-BEZ235 and Cisplatin engendered synergistic effects and produced a greater antitumor response than did treatment with either drug alone. Resected tumor samples also showed decreased p-p70S6K expression. Collectively, these data demonstrate that NVP-BEZ235 inhibits HSCC growth through phospho-p70S6K suppression and has a synergistic effect with Cisplatin in treating HSCC. The data also provide a strategy for more effective HSCC treatment.
DNA mimic proteins have DNA-like negative surface charge distributions, and they function by occupying the DNA binding sites of DNA binding proteins to prevent these sites from being accessed by DNA. ...DNA mimic proteins control the activities of a variety of DNA binding proteins and are involved in a wide range of cellular mechanisms such as chromatin assembly, DNA repair, transcription regulation, and gene recombination. However, the sequences and structures of DNA mimic proteins are diverse, making them difficult to predict by bioinformatic search. To date, only a few DNA mimic proteins have been reported. These DNA mimics were not found by searching for functional motifs in their sequences but were revealed only by structural analysis of their charge distribution. This review highlights the biological roles and structures of 16 reported DNA mimic proteins. We also discuss approaches that might be used to discover new DNA mimic proteins.
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