Improved performance of polymer light-emitting diodes with nanocomposites

The characteristics of a hybrid polymer light-emitting diode (HPLED) with an active layer of poly [2-methoxy,5-(2-ethylhexoxy)-1,4-phenylenevinylene] blended with Au-capped TiO(2) nanocomposites are reported. Both the increased current in the active layer and low turn-on voltage were attributed to incorporation of Au-capped TiO(2) in the electroluminescent polymer. The maximal brightness of 11 630 cd/m(2) was observed in HPLED with a 1:1 ratio of Au-capped TiO(2). The enhanced performance was attributed to the roughness assisted charge transport induced by the Au-capped TiO(2) nanocomposites in the active polymer.open111

Role of Rho-kinase in regulation of insulin action and glucose homeostasis

SummaryAccumulating evidence indicates an important role for serine phosphorylation of IRS-1 in the regulation of insulin action. Recent studies suggest that Rho-kinase (ROK) is a mediator of insulin signaling, via interaction with IRS-1. Here we show that insulin stimulation of glucose transport is impaired when ROK is chemically or biologically inhibited in cultured adipocytes and myotubes and in isolated soleus muscle ex vivo. Inactivation of ROK also reduces insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activity. Moreover, inhibition of ROK activity in mice causes insulin resistance by reducing insulin-stimulated glucose uptake in skeletal muscle in vivo. Mass spectrometry analysis identifies IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites inhibits insulin signaling. These results strongly suggest that ROK regulates insulin-stimulated glucose transport in vitro and in vivo. Thus, ROK is an important regulator of insulin signaling and glucose metabolism

Molecular characterization of partial-open reading frames 1a and 2 of the human astroviruses in South Korea

Human astroviruses (HAstVs) are among the major causes of gastroenteritis in South Korea. In this study, the partial regions of the open reading frame (ORF) 1a and ORF2 genes of HAstVs from gastroenteritis patients in nine hospitals were sequenced, and the molecular characterization of the viruses was revealed. 89 partial nucleotide sequences of ORF1a and 88 partial nucleotide sequences of ORF2 were amplified from 120 stool specimens. Phylogenetic analysis showed that most of the nucleotide sequences of ORF1a and ORF2 were grouped with HAstV type 1 but had evolutionary genetic distance compared with the reference sequences, such as the HAstV-1 prototype, Dresden strain, and Oxford strain. According to the phylogenetic analysis, some nucleotide sequences including SE0506041, SE0506043, and SE0506058, showed the discrepancy of the genotypes, but there was no proof of recombination among the HAstV types. In conclusion, this study showed that the dominant HAstV isolated from the Seoul metropolitan area in 2004-2005 was HAstV type 1, and that Korean HAstV-1 had the genetic distance in evolution compared with the reference sequences of HAstVs. Lots of nucleotide sequences of the ORF1a and ORF2 genes of HAstV will be useful for studying for the control and prevention of HAstV gastroenteritis in South Korea

Chemoenzymatic Synthesis of Glycosylated Macrolactam Analogues of the Macrolide Antibiotic YC‐17

YC‐17 is a 12‐membered ring macrolide antibiotic produced from Streptomyces venezuelae ATCC 15439 and is composed of the polyketide macrolactone 10‐deoxymethynolide appended with D‐desosamine. In order to develop structurally diverse macrolactam analogues of YC‐17 with improved therapeutic potential, a combined approach involving chemical synthesis and engineered cell‐based biotransformation was employed. Eight new antibacterial macrolactam analogues of YC‐17 were generated by supplying a novel chemically synthesized macrolactam aglycone to S. venezuelae mutants harboring plasmids capable of synthesizing several unnatural sugars for subsequent glycosylation. Some YC‐17 macrolactam analogues were active against erythromycin‐resistant bacterial pathogens and displayed improved metabolic stability in vitro. The enhanced therapeutic potential demonstrated by these glycosylated macrolactam analogues reveals the unique potential of chemoenzymatic synthesis in antibiotic drug discovery and development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113147/1/adsc_201500250_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113147/2/2697_ftp.pd

Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 1: Glucocorticoid-Associated Osteonecrosis.

BACKGROUND: Glucocorticoid usage, a leading cause of osteonecrosis of the femoral head (ONFH), and its prevalence was reported in 25%-50% of non-traumatic ONFH patients. Nevertheless, there have been no unified criteria to classify glucocorticoid-associated ONFH (GA-ONFH). In 2015, the Association Research Circulation Osseous addressed the issue of developing a classification scheme. METHODS: In June 2017, a task force was set up to conduct a Delphi survey concerning ONFH. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey consists of questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, the panel reached a consensus on the classification criteria. The response rates were 100% (Round 1), 96% (Round 2), and 100% (Round 3), respectively. RESULTS: The consensus on the classification criteria of GA-ONFH included the following: (1) patients should have a history of glucocorticoid use >2 g of prednisolone or its equivalent within a 3-month period; (2) osteonecrosis should be diagnosed within 2 years after glucocorticoid usage, and (3) patients should not have other risk factor(s) besides glucocorticoids. CONCLUSION: Association Research Circulation Osseous established classification criteria to standardize clinical studies concerning GA-ONFH

FE65 as a link between VLDLR and APP to regulate their trafficking and processing

<p>Abstract</p> <p>Background</p> <p>Several studies found that FE65, a cytoplasmic adaptor protein, interacts with APP and LRP1, altering the trafficking and processing of APP. We have previously shown that FE65 interacts with the ApoE receptor, ApoER2, altering its trafficking and processing. Interestingly, it has been shown that FE65 can act as a linker between APP and LRP1 or ApoER2. In the present study, we tested whether FE65 can interact with another ApoE receptor, VLDLR, thereby altering its trafficking and processing, and whether FE65 can serve as a linker between APP and VLDLR.</p> <p>Results</p> <p>We found that FE65 interacted with VLDLR using GST pull-down and co-immunoprecipitation assays in COS7 cells and in brain lysates. This interaction occurs via the PTB1 domain of FE65. Co-transfection with FE65 and full length VLDLR increased secreted VLDLR (sVLDLR); however, the levels of VLDLR C-terminal fragment (CTF) were undetectable as a result of proteasomal degradation. Additionally, FE65 increased cell surface levels of VLDLR. Moreover, we identified a novel complex between VLDLR and APP, which altered trafficking and processing of both proteins. Furthermore, immunoprecipitation results demonstrated that the presence of FE65 increased the interaction between APP and VLDLR <it>in vitro </it>and <it>in vivo</it>.</p> <p>Conclusions</p> <p>These data suggest that FE65 can regulate VLDLR trafficking and processing. Additionally, the interaction between VLDLR and APP altered both protein's trafficking and processing. Finally, our data suggest that FE65 serves as a link between VLDLR and APP. This novel interaction adds to a growing body of literature indicating trimeric complexes with various ApoE Receptors and APP.</p

Early statin use in ischemic stroke patients treated with recanalization therapy: retrospective observational study

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background We aimed to determine whether early statin use following recanalization therapy improves the functional outcome of ischemic stroke. Methods Using a prospective stroke registry database, we identified a consecutive 337 patients within 6 h of onset who had symptomatic stenosis or occlusion of major cerebral arteries and received recanalization therapy. Based on commencement of statin therapy, patients were categorized into administration on the first (D1, 13.4 %), second (D2, 20.8 %) and third day or later (D ≥ 3, 15.4 %) after recanalization therapy, and no use (NU, 50.4 %). The primary efficacy outcome was a 3-month modified Rankin Scale score of 0–1, and the secondary outcomes were neurologic improvement, neurologic deterioration and symptomatic hemorrhagic transformation during hospitalization. Results Earlier use of statin was associated with a better primary outcome in a dose-response relationship (P for trend = 0.01) independent of premorbid statin use, stroke history, atrial fibrillation, stroke subtype, calendar year, and methods of recanalization therapy. The odds of a better primary outcome increased in D1 compared to NU (adjusted odds ratio, 2.96; 95 % confidence interval, 1.19–7.37). Earlier statin use was significantly associated with less neurologic deterioration and symptomatic hemorrhagic transformation in bivariate analyses but not in multivariable analyses. Interaction analysis revealed that the effect of early statin use was not altered by stroke subtype and recanalization modality (P for interaction = 0.97 and 0.26, respectively). Conclusion Early statin use after recanalization therapy in ischemic stroke may improve the likelihood of a better functional outcome without increasing the risk of intracranial hemorrhage

EC-18, a Synthetic Monoacetyldiacylglyceride, Inhibits Hematogenous Metastasis of KIGB-5 Biliary Cancer Cell in Hamster Model

EC-18 (monoacetyldiacylglyceride) stimulates T cell production of IL-2, IL-4, IL-12, IFN-γ, and GM-CSF in vitro. To study the effects of these cytokines stimulated by EC-18 on cancer cells, we applied hamster biliary cancer model, a difficult cancer to treat. Cancer (KIGB-5) cells were given intravenously to produce hematogenous metastatic lung lesions which were treated with EC-18 at 10, 25, and 50 mg/kg/day respectively. The fourth group was untreated control. At 4th, 8th, and 12th week the lungs were examined. EC-18 treated groups showed only a few microscopic lung lesions and no evidence of metastatic lesion with highest dose whereas widespread gross lung lesions were observed in untreated control. To investigate whether the anti-tumor effect of EC-18 is associated with suppression of tumor cell Toll-like receptor 4 (TLR-4) expression in addition to stimulation of the immune cells, KIGB-5 cells were exposed to LPS with or without EC-18. TLR-4 mRNA and protein expression, measured by reverse transcriptase PCR (RT-PCR), real-time quantitative PCR and western blot analysis, showed suppression of TLR-4 expression in KIGB-5 cells treated with EC-18 compared with control. In conclusion, EC-18 has a significant anti-tumor effect in this experimental model of biliary cancer suggesting potential for clinical application to this difficult cancer

Expression of TLR2, TLR4, and TLR9 in dermatomyositis and polymyositis

The aim of this study was to investigate the expressions of Toll-like receptor (TLR) 2, TLR4, TLR9, and their correlations with the expression of cytokines that are associated with activation of CD4+ T cells and inflammation including interferon γ (IFNγ), interleukin 4 (IL4), interleukin 17 (IL17), and tumor necrosis factor α (TNFα) in muscle tissues of patients with dermatomyositis (DM) and polymyositis (PM). The expressions of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were measured by real-time reverse transcription–polymerase chain reaction in muscle tissues from 14 patients with DM and PM (nine patients with DM, five patients with PM) and three controls. The expressions of TLR2, TLR4, and TLR9 were also localized with immunohistochemistry. The expression levels of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were significantly high in patients with DM and PM compared with those in the controls, and the expression levels of TLR4 and TLR9 had significant positive correlations with the expressions of IFNγ, IL4, IL17, and TNFα. Immunohistochemistry showed that TLR2, TLR4, and TLR9 were expressed by infiltrating cells of perimysium in DM, whereas they were expressed by infiltrating cells of endomysium in PM. These results suggest that the involvement of TLR4 and TLR9 in immunopathogenesis of DM and PM might be connected with activation of CD4+ T cells

Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists

Aims Oral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, is a prodrug converted to a selective and reversible direct thrombin inhibitor (AR-H067637). We report from a Phase II randomized, dose-guiding study (NCT00684307) to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of extended-release AZD0837 in patients with AF. Methods and results Atrial fibrillation patients (n = 955) with >= 1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2-3, target 2.5) for 3-9 months. Approximately 30% of patients were naive to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3-14.7%, mean exposure 138-145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). D-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naive subjects with treatment, whereas in VKA pre-treated patients, D-dinner levels started tow and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by similar to 10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase >= 3 x upper limit of normal was similar for AZD0837 and VKA. Conclusion AZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA