Background:Hyperuricemia induces endothelial dysfunction, oxidative stress and inflammation, increasing cardiovascular morbidities. It also raises the incidence of atrial fibrillation; however, ...underlying mechanisms are unknown.Methods and Results:The effects of urate on expression of Kv1.5 in cultured mouse atrial myocytes (HL-1 cells) using reverse transcriptase-PCR, immunoblots, flow cytometry and patch-clamp experiments were studied. Treatment with urate at 7 mg/dl for 24 h increased the Kv1.5 protein level, enhanced ultra-rapid delayed-rectifier K+channel currents and shortened action potential duration in HL-1 cells. HL-1 cells expressed the influx uric acid transporter (UAT), URATv1, and the efflux UATs, ABCG2 and MRP4. An inhibitor against URATv1, benzbromarone, abolished the urate effects, whereas an inhibitor against ABCG2, KO143, augmented them. Flow cytometry showed that urate induced an increase in reactive oxygen species, which was abolished by the antioxidant, N-acetylcysteine (NAC), and the NADPH-oxidase inhibitor, apocynin. Both NAC and apocynin abolished the enhancing effects of urate on Kv1.5 expression. A urate-induced increase in the Kv1.5 proteins was accompanied by phosphorylation of extracellular signal-regulated kinase (ERK), and was abolished by an ERK inhibitor, PD98059. NAC abolished phosphorylation of ERK by urate.Conclusions:Intracellular urate taken up by UATs enhanced Kv1.5 protein expression and function in HL-1 atrial myocytes, which could be attributable to ERK phosphorylation and oxidative stress derived from nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase. (Circ J 2015; 79: 2659–2668)
Cross-linked chitosan(CS), cross-linked chitosan/graphene(CS/RGO
10
) and cross-linked chitosan/graphene oxide(CS/GO
10
) were prepared as adsorbents for Cu(II). The effects of pH, contact time, ...adsorbent dosage and initial concentration of Cu(II) on the adsorbing abilities of CS,CS/RGO
10
and CS/GO
10
to Cu(II) were investigated. The results demonstrate that the adsorption capacities of CS/GO
10
and CS/RGO
10
are greater than that of CS, especially at pH 5.0 and the adsorption capacities are 202.5, 150 and 137.5 mg/g, respectively. Their behaviors obey the Freundlich isotherm model very well. Additionally, CS/GO
10
has the shortest time to achieve adsorption equilibrium among them and can be used as a perspective adsorbent for Cu(II).
The electro-polymerization behavior of aniline in reverse (W/O) microemulsion was investigated. The experiment results show that the cyclic voltammetry polymerization behavior of aniline in W/O ...microemulsion is different from that in aqueous solution remarkably. With the increase of scan cycle, the oxidation potential shifts positively and the reduction potential shifts negatively, i.e., the redox potential difference increases. H
+
apparent concentration affects the aniline polymerization evidently. When H
+
concentration is lower than 0.08 mol/L, the electro-polymerization of aniline is difficult. With the increase of H
+
concentration, the polymerization current of aniline increases gradually. Only when H
+
concentration is high enough (0.5 mol/L), aniline can be well electro-polymerized. Moreover, under the same condition, the aniline polymerization current in W/O microemulsion is higher than that in aqueous solution. The scanning electron microscopy image shows that the deposited polyaniline (PANI) has uniform fiber morphology with diameter of about 100 nm. Further study result suggests that the electrochemical activity of the PANI in HCl is similar to that of the PANI prepared in aqueous solution.
We determined the prevalence of hypertension, medication usage and attainment of blood pressure goals in older (≥65 to <80 years and ≥80 years) urban community-dwelling Chinese subjects. Data were ...obtained in 3950 subjects (mean age 72.0 years, 1745 male) including 609 subjects aged ≥80 years in the Shanghai Elderly Cardiovascular Health Study (SHECHS). Established cardiovascular disease was present in 7.7% of participants. The prevalence of hypertension was 74.8% overall and it was more than 80% in individuals considered to be in moderate and higher cardiovascular disease risk categories. In hypertensive subjects, 67.1% were on treatment and treatment was more frequent in high and very high cardiovascular risk individuals. Attainment of the systolic blood pressure goal <150 mmHg was 62.9% and was greater in the ≥65 to <80 years group than in the ≥80 years group. The most commonly used antihypertensive treatments were calcium channel blockers (54.2%), followed by angiotensin receptor blockers (43.1%). Diuretics were used in 2.6%. Fixed-dose combination antihypertensive tablets were used in some of the ≥65 to <80 years group (12.4%) and more of the ≥80 years group (18.2%) and 70.9% of the ≥65 to <80 years group and 80.2% of the ≥80 years group were on monotherapy. There were high prevalence and high treatment rates of hypertension, but poor attainment of the systolic blood pressure goal of <150 mmHg, especially in the ≥80 years group of community-dwelling Chinese. Considering that more intensive treatment of hypertension in older subjects may be warranted after recent studies, this might be achieved by more frequent use of combinations of effective therapies and diuretics.
In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients,
, the most common human fungal pathogen, may cause mucosal and even life-threatening ...systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with
or its degradation by
-secreted proteases that contribute to the fungi's resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living
cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications.
PtCoFe nanowires with different alloying compositions are chemically prepared and acted as counter electrodes (CEs) in dye‐sensitized solar cells (DSSCs) with Ru(II)‐based dyes. Due to their superior ...I3− reduction activity, PtCoFe nanowires with rich (111) facets enhance the performance of DSSCs. Hence, N719 DSSCs with PtCoFe nanowires, respectively, produce better power conversion efficiency (PCE) of 8.10% for Pt33Co24Fe43 nanowire, 8.33% for Pt74Co12Fe14 nanowire, and 9.26% for Pt49Co23Fe28 nanowire in comparison to the PCE of Pt CE (7.32%). Further, the PRT‐22 DSSC with Pt49Co23Fe28 nanowire exhibits a maximum PCE of 12.29% with a certificated value of 12.0%, which surpass the previous PCE record of the DSSCs with Ru(II)‐based dyes. The photovoltaic and electrochemical results reveal the composition‐dependent activity along with a volcano‐shaped trend in the I−/I3− redox reaction. Theoretical work on the adsorption energies of I2, the desorption energies of I−, and the corresponding absolute energy demonstrates that the I3− reduction activity followed in the order of Pt49Co23Fe28(111) plane > Pt74Co12Fe14(111) plane > Pt33Co24Fe43(111) plane, proving Pt49Co23Fe28 nanowire to be a superior cathode material for DSSCs.
PtCoFe nanowires with rich (111) planes are chemically prepared and act as the counter electrodes of dye‐sensitized solar cells (DSSCs). Evidently, Pt49Co23Fe28 nanowires demonstrate the superior catalytic properties with respect to the I−/I3− redox reactions. Thus, PRT‐22 DSSC based on Pt49Co23Fe28 nanowire produces an impressive power conversion efficiency of 12.29%.
The effect of hydrogen diffusion in the bilayer bottom gate insulator (BGI) in dual-gate InGaZnO (IGZO) thin-film transistors (TFT) is investigated. It is discovered that hydrogen diffuses from the ...first deposited GI, migrates toward the second one, and forms a weak chemical bond with a dangling bond at the interface between the GI and the active layer. The stress condition with a positive gate bias at various temperatures makes the weakly bonded hydrogen break, thereby forming defects that can induce electron trapping in the interface and bulk, causing the threshold voltage to increase. With the rising temperature of positive bias temperature stress (PBTS), more broken bonds appear at the interface, which results in more trapped electrons. Through a charge trapping model and data fitting, the parameter that indicates the quality of the film can be extracted and compared. The trend of degradation between threshold voltage, bond breaking, and defect generation is examined.
Fall is a major threat to stroke survivors with the problems of gait and balance disorders in the rehabilitation phase following severe consequences on quality of life and a heavy burden to their ...families. Many solutions have been proposed to assess fall risk for elders based on inertial sensor‐based signals, however, there still exists a great challenge of transferring them from elderly populations to the stroke‐survivors populations as gait disorder patterns are significant difference between elders and stroke survivors. In this study, we conduct a pilot study to collect inertial sensor‐based signals from stroke survivors when they performed the timed up and go test, and build an automatic fall risk assessment model with the architecture of Siamese network, with a merit of mitigating the problem of small sample size. Specifically, the proposed automatic fall risk assessment model consists of two parallel convolutional neural networks, each of which is composed of three convolutional layers, two max‐pooling layers, and three fully connected layers. To utilize the space relation among accelerator‐based and gyroscope‐based signals, two‐dimensional discrete wavelet transform extracts image‐like features, wavelet coefficients, from inertial sensor‐based signals as the input. Experimental results show that the proposed fall risk assessment model has achieved a promising results, which outperform cutting‐edge methods with a big margin. The proposed fall risk assessment model with low computational complexity and limited memory consuming can be deployed on an embedded system to provide fall risk assessment service for stroke survivors in point‐of‐care environments or community settings.
The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related ...adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed.
The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells' membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies.
The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to strengthen immune activation than LPPC/MP, and that LPPC/MP/CTLA4 could abolish the LPPC/MP complex-mediated gene expression back to un-treatment.
Overall, we proved a convenient and flexible immunotherapy platform for developing personalized cancer therapy.
We aimed to identify novel molecular associations between chronic intermittent hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea (OSA). We analyzed gene expression ...profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients on long-term continuous positive airway pressure treatment (VSOC). Comparisons of the microarray gene expression data identified eight genes up-regulated with OSA and down-regulated with CPAP treatment, and five genes down-regulated with OSA and up-regulated with CPAP treatment. Protein expression levels of two genes related to endothelial tight junction (AMOT P130, and PLEKHH3), and three genes related to anti-or pro-apoptosis (BIRC3, ADAR1 P150, and LGALS3) were all increased in the VSO group, while AMOT P130 was further increased, and PLEKHH3, BIRC3, and ADAR1 P150 were all decreased in the VSOC group. Subgroup analyses revealed that AMOT P130 protein expression was increased in OSA patients with excessive daytime sleepiness, BIRC3 protein expression was decreased in OSA patients with hypertension, and LGALS3 protein expression was increased in OSA patients with chronic kidney disease. In vitro short-term intermittent hypoxia with re-oxygenation experiment showed immediate over-expression of ADAR1 P150. In conclusion, we identified a novel association between AMOT/PLEKHH3/BIRC3/ADAR1/LGALS3 over-expressions and high severity index in OSA patients. AMOT and GALIG may constitute an important determinant for the development of hypersomnia and kidney injury, respectively, while BIRC3 may play a protective role in the development of hypertension.
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