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Find video protocols related to scientific articles indexed in Pubmed.
A Chemical Tuned Strategy to Develop Novel Irreversible EGFR-TK Inhibitors with Improved Safety and Pharmacokinetic Profiles.
J. Med. Chem.
PUBLISHED: 11-20-2014
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Gatekeeper T790M mutation in EGFR is the most prevalent factor underlying acquired resistance. Acrylamide-bearing quinazoline derivatives are powerful irreversible inhibitors for overcoming resistance. Nevertheless, concerns about the risk of non-specific covalent modification have motivated the development of novel cysteine-targeting inhibitors. In this paper, we demonstrate that fluoro-substituted olefins can be tuned to alter Michael addition reactivity. Incorporation of these olefins into the quinazoline templates produced potent EGFR inhibitors with improved safety and pharmacokinetic properties. A lead compound 5a was validated against EGFRWT, EGFR T790M as well as A431 and H1975 cancer cell lines. Additionally, compound 5a displayed a weaker inhibition against the EGFR-independent cancer cell line SW620 when compared withafatinib. Oral administration of 5a at a dose of 30mg/kg induced tumor regression in a murine-EGFRL858R/T790M driven H1975 xenograft model. Also, 5a exhibited improved oral bioavailability and safety, as well as favorable tissue distribution properties and enhanced brain uptake. These findings provide the basis of a promising strategy toward the treatment of NSCLC patients with drug resistance.
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Discovery and Characterization of the Tuberculosis Drug Lead Ecumicin.
Org. Lett.
PUBLISHED: 11-20-2014
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The new tuberculosis (TB) lead ecumicin (1), a cyclic tridecapeptide, was isolated from Nonomuraea sp. MJM5123, following a high-throughput campaign for anti-TB activity. The large molecular weight of 1599 amu detected by LC-HR-MS precluded the initial inference of its molecular formula. The individual building blocks were identified by extensive NMR experiments. The resulting two possible planar structures were distinguished by LC-MS(2). Determination of absolute configuration and unambiguous structural confirmation were carried out by X-ray crystallography and Marfey's analysis.
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Synthesis and properties of greenish-blue-emitting iridium dendrimers with N-phenylcarbazole-based polyether dendrons by a post-dendronization route.
Dalton Trans
PUBLISHED: 11-20-2014
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A series of solution processible greenish-blue-emitting Ir dendrimers with polyether dendrons that consist of N-phenylcarbazole (NPC) are developed via a convenient post-dendronization method. It involves two steps: (i) the successful preparation of a reactive Ir core, namely m-HO-dfppyIr, only when the hydroxyl group is located at the meta position relative to the N atom in the C^N ligand so as to eliminate the possible resonance structure between enol and keto; and (ii) the subsequent functionalization with NPC-based polyether dendrons to afford the first, second and third generation Ir dendrimers (Ir-G1B, Ir-G2B and Ir-G3B) with ease and high yields over 60%. All these dendritic complexes possess good thermal stability with decomposition temperatures higher than 380 °C and glass transition temperatures higher than 200 °C. In addition, with the growing generation number, the intermolecular interactions between emissive Ir cores are expected to be effectively inhibited to avoid the luminescence quenching, which is confirmed from the blue-shifted emission peak and the enhanced lifetime of Ir-G3B in the solid state. As a result, on going from Ir-G1B to Ir-G3B, the maximum luminous efficiency rises upward from 4.7 to 9.2 cd A(-1) for nondoped electrophosphorescent devices. Further optimization by doping them into a dendritic H2 host leads to the improved luminous efficiencies as high as 20.0-25.2 cd A(-1).
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Plasma-induced grafting of polyacrylamide on graphene oxide nanosheets for simultaneous removal of radionuclides.
Phys Chem Chem Phys
PUBLISHED: 11-20-2014
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Polyacrylamide (PAM) grafted graphene oxide (denoted as PAM/GO) was synthesized by the plasma-induced polymerization technique and applied as an adsorbent for the simultaneous removal of radionuclides from radioactive wastewater. The interactions of PAM/GO with the radionuclides U(vi), Eu(iii) and Co(ii) were studied, along with their sorption kinetics. The results indicated that radionuclide sorption on PAM/GO was affected by the solution pH and ionic strength. The maximum sorption capacities of U(vi), Eu(iii) and Co(ii) on PAM/GO (0.698, 1.245 and 1.621 mmol g(-1), respectively) at pH = 5.0 ± 0.1 and T = 295 K were much higher than those of radionuclides on GO and other adsorbents. The thermodynamic data (?H(0), ?S(0) and ?G(0)) calculated from the temperature-dependent sorption isotherms suggested that the sorption of radionuclides on PAM/GO was a spontaneous and endothermic process. These results indicate that PAM/GO is a promising material for the control of radionuclide pollution.
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Field-Induced Slow Magnetic Relaxation in Cobalt(II) Compounds with Pentagonal Bipyramid Geometry.
Inorg Chem
PUBLISHED: 11-20-2014
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Field-induced slow magnetic relaxation was observed for air-stable mononuclear cobalt(II) compounds with pentagonal bipyramid geometry. These are the first examples of such behavior observed in the seven-coordinated mononuclear 3d metal compounds.
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Strong temperature-dependent crystallization, phase transition, optical and electrical characteristics of p-type CuAlO2 thin films.
Phys Chem Chem Phys
PUBLISHED: 11-20-2014
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We report here a reliable and reproducible single-step (without post-annealing) fabrication of phase-pure p-type rhombohedral CuAlO2 (r-CuAlO2) thin films by reactive magnetron sputtering. The dependence of crystallinity and phase compositions of the films on the growth temperature was investigated, revealing that highly-crystallized r-CuAlO2 thin films could be in situ grown in a narrow temperature window of ?940 °C. Optical and electrical property studies demonstrate that (i) the films are transparent in the visible light region, and the bandgaps of the films increased to ?3.86 eV with the improvement of crystallinity; (ii) the conductance increased by four orders of magnitude as the film was evolved from the amorphous-like to crystalline structure. The predominant role of crystallinity in determining CuAlO2 film properties was demonstrated to be due to the heavy anisotropic characteristics of the O 2p-Cu 3d hybridized valence orbitals.
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Structure, Bonding and Catalytic Activity of Monodisperse, Transition-Metal Substituted CeO2 Nanoparticles.
J. Am. Chem. Soc.
PUBLISHED: 11-19-2014
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We present a simple and generalizable synthetic route towards phase-pure, monodisperse transition-metal substituted ceria nanoparticles (M0.1Ce0.9O2-x, M = Mn, Fe, Co, Ni, Cu). The solution-based pyrolysis of a series of heterobimetallic Schiff base complexes ensures a rigorous control of the size, morphology and composition of 3 nm M0.1Ce0.9O2-x crystallites for CO oxidation catalysis and other applications. X-ray absorption spectroscopy confirms the dispersion of aliovalent (M(3+) and M(2+)) transition-metal ions into the ceria matrix without the formation of any bulk transition-metal oxide phases, while steady-state CO oxidation catalysis reveals an order of magnitude increase in catalytic activity with copper substitution. Density functional calculations of model slabs of these compounds confirm the stabilization of M(3+) and M(2+) in the lattice of CeO2. These results highlight the role of the host CeO2 lattice in stabilizing high oxidation states of aliovalent transition-metal dopants that ordinarily would be intractable, such as Cu(3+), as well as demonstrating a rational approach to catalyst design. The current work demonstrates, for the first time, a generalizable approach for the preparation of transition-metal substituted CeO2 for a broad range of transition-metals with unparalleled synthetic control and illustrates that Cu(3+) is implicated in the mechanism for CO oxidation on CuO-CeO2 catalysts.
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Identification of Potential Drugs for Parkinson's Disease Based on a Sub-Pathway Method.
Int. J. Neurosci.
PUBLISHED: 11-19-2014
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Abstract Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. Current therapeutic regimen suffers from general side effects and a poor efficiency for PD symptoms. The need for development new therapeutic agents for PD is urgent. Here, we aimed to explore the metabolic mechanism of PD and identified potential novel agents for PD by a sub-pathway based method. By using the GSE7621 microarray data from the GEO database, we first identified the 1,226 differentially expressed genes (DEGs) between PD and normal samples. Then we identified 19 significant enriched metabolic sub-pathways which may involve in development of PD. Finally, by an integrated analysis of PD-involved sub-pathways and drug-affected sub-pathways, we identified 49 novel small molecular drugs capable to target the PD-involved sub-pathways. Our method could not only identify existing drug (apomorphine) for PD, but also predict potentially novel agents (ketoconazole and astemizole) which might have therapeutic effects via targeting some key enzymes in arachidonic acid metabolism. These candidate agents identified by our approach may provide insights into a novel therapy approach for PD.
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Initial experience of thoracoscopic lobectomy with partial removal of the superior vena cava for lung cancers.
Eur J Cardiothorac Surg
PUBLISHED: 11-19-2014
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The objectives of this study were to report the surgical techniques and clinical outcome of thoracoscopic lobectomy with partial removal of the superior vena cava for lung carcinomas.
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Synthesis and Biological Evaluation of Sophoridinol Derivatives as a Novel Family of Potential Anticancer Agents.
ACS Med Chem Lett
PUBLISHED: 11-13-2014
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New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 ?M. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentration-time curve (AUC) of 10.3 ?M·h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
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Mimicking the hierarchical functions of dentin collagen cross-links with plant derived phenols and phenolic acids.
Langmuir
PUBLISHED: 11-08-2014
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Proanthocyanidins (PACs) are secondary plant metabolites that mediate non-enzymatic collagen cross-linking and enhance the properties of collagen based tissue, such as dentin. The extent and nature of cross-linking is influenced by the composition and specific chemical structure of the bioactive compounds present in certain PAC-rich extracts. This study investigated the effect of the molecular weight and stereochemistry of polyphenol compounds on two important properties of dentin, biomechanics and biostability. For that, purified phenols, a phenolic acid and some of its derivatives were selected: PACs dimers (A1, A2, B1 and B2) and a trimer (C1), gallic acid (Ga), its esters methyl gallate (MGa) and propyl gallate (PGa), and a pentagalloyl ester of glucose (PGG). Synergism was assessed by combination of the most active PAC and gallic acid derivative. Mechanical properties of dentin organic matrix were determined by the modulus of elasticity obtained in a flexural test. Biostability was evaluated by resistance to collagenase degradation. PACs significantly enhanced dentin mechanical properties and decreased collagen digestion. Among the gallic acid derivatives, only PGG had a significant enhancing effect. The lack of observed C1:PGG synergy indicates that both compounds have similar mechanisms of interaction with the dentin matrix. These findings reveal that the molecular weight of polyphenols have a determinant effect on their interaction with type I collagen and modulate the mechanism of cross-linking at the molecular, inter-molecular, and inter-micro-fibrillar levels.
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Effect of Silicate on the Formation and Stability of Ni-Al LDH at the ?-Al2O3 Surface.
Environ. Sci. Technol.
PUBLISHED: 11-05-2014
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The formation of mixed metal precipitates has been identified as a significant mechanism for the immobilization and elimination of heavy metal ions. Silicate is present in natural systems ubiquitously, which may interfere with metal uptake on the mineral surface and thereby influences the solubility of the precipitate. Herein, kinetic sorption and dissolution experiments combined with extended X-ray absorption fine structure spectroscopy (EXAFS) were performed to elucidate the effect of silicate on the formation of Ni precipitates at the ?-Al2O3 surfaces. The uptake of Ni on ?-Al2O3 decreased with increasing amounts of silicate coated onto the ?-Al2O3 surface. Results of EXAFS analyses suggested the formation of Ni-Al layered double hydroxide (LDH) phases. The surface coating of silicate on ?-Al2O3 reduced Al release and finally resulted in a high Ni:Al ratio due to a lower extent of Al substitution into the precipitates. The presence of silicate prevented the growth of the precipitates and led to the formation of less stable Ni-Al LDH. The influence of silicate on the precipitate formation provided the evidence for the growth relationship between the precipitate and mineral substrate in the real environment. Increased rates of proton-promoted dissolution of Ni surface precipitates were mainly attributed to higher Ni:Al ratios in Ni-Al LDH precipitates formed in the presence of silicate.
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Importance of Purity Evaluation and the Potential of Quantitative (1)H NMR as a Purity Assay.
J. Med. Chem.
PUBLISHED: 10-09-2014
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In any biomedical and chemical context, a truthful description of chemical constitution requires coverage of both structure and purity. This qualification affects all drug molecules, regardless of development stage (early discovery to approved drug) and source (natural product or synthetic). Purity assessment is particularly critical in discovery programs and whenever chemistry is linked with biological and/or therapeutic outcome. Compared with chromatography and elemental analysis, quantitative NMR (qNMR) uses nearly universal detection and provides a versatile and orthogonal means of purity evaluation. Absolute qNMR with flexible calibration captures analytes that frequently escape detection (water, sorbents). Widely accepted structural NMR workflows require minimal or no adjustments to become practical (1)H qNMR (qHNMR) procedures with simultaneous qualitative and (absolute) quantitative capability. This study reviews underlying concepts, provides a framework for standard qHNMR purity assays, and shows how adequate accuracy and precision are achieved for the intended use of the material.
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Normal-pressure microwave rapid synthesis of hierarchical SnO2@rGO nanostructures with superhigh surface areas as high-quality gas-sensing and electrochemical active materials.
Nanoscale
PUBLISHED: 10-04-2014
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Hierarchical SnO2@rGO nanostructures with superhigh surface areas are synthesized via a simple redox reaction between Sn(2+) ions and graphene oxide (GO) nanosheets under microwave irradiation. XRD, SEM, TEM, XPS, TG-DTA and N2 adsorption-desorption are used to characterize the compositions and microstructures of the SnO2@rGO samples obtained. The SnO2@rGO nanostructures are used as gas-sensing and electroactive materials to evaluate their property-microstructure relationship. The results show that SnO2 nanoparticles (NPs) with particle sizes of 3-5 nm are uniformly anchored on the surfaces of reduced graphene oxide (rGO) nanosheets through a heteronucleation and growth process. The as-obtained SnO2@rGO sample with a hierarchically sesame cake-like microstructure and a superhigh specific surface area of 2110.9 m(2) g(-1) consists of 92 mass% SnO2 NPs and ?8 mass% rGO nanosheets. The sensitivity of the SnO2@rGO sensor upon exposure to 10 ppm H2S is up to 78 at the optimal operating temperature of 100 °C, and its response time is as short as 7 s. Compared with SnO2 nanocrystals (5-10 nm), the hierarchical SnO2@rGO nanostructures have enhanced gas-sensing behaviors (i.e., high sensitivity, rapid response and good selectivity). The SnO2@rGO nanostructures also show excellent electroactivity in detecting sunset yellow (SY) in 0.1 M phosphate buffer solution (pH = 2.0). The enhancement in gas-sensing and electroactive performance is mainly attributed to the unique hierarchical microstructure, high surface areas and the synergistic effect of SnO2 NPs and rGO nanosheets.
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Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway.
Int. J. Oncol.
PUBLISHED: 08-21-2014
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Macrophages are a major component of the leukocyte infiltrate of tumors and play a pivotal role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which macrophages promote HCC invasion are poorly understood. The present study was undertaken to investigate the relationship between macrophages and epithelial-mesenchymal transition (EMT) of HCC. Double-staining immunohistochemistry was used to observe the association between macrophages and EMT markers in clinical HCC samples and it showed that EMT primarily occurred at the edge of the tumor nest, in which infiltrating macrophages were always observed. This indicated that CD68 which is a marker of macrophages, was correlated with EMT marker levels. In addition, after being cultured with macrophages for 24 h, the ability of HCC cells to migrate and invade increased, Snail and N-Cadherin expression was upregulated, and E-Cadherin was downregulated. An antibody array assay was applied to analyze the supernatant of these cultures and it demonstrated IL-8 increased significantly in the macrophage co-culture system. Finally, the role of macrophage-derived IL-8 in the invasion of HCC cells was assayed, and downstream signaling pathways were also investigated. We found that IL-8: i) may induce EMT and promote HCC cell migration and invasion and ii) is associated with the JAK2/STAT3/Snail signaling pathway. Taking together, these findings revealed that macrophages that have infiltrated tumors may induce epithelial-mesenchymal transition of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway. Thus, this may offer a potential target for developing new HCC therapies.
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Non-intubated complete thoracoscopic bronchial sleeve resection for central lung cancer.
J Thorac Dis
PUBLISHED: 08-09-2014
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Bronchial sleeve resection has emerged as an effective thoracoscopic approach for central lung cancer with reduced operation mortality rates, optimal lung function and long-term survival. Endobronchial intubation is a commonly used method of anesthesia for such thoracoscopic procedures, but is associated with increased intubation-related and lung complications. Non-intubated epidural anesthesia represents an alternative approach which may avoid such difficulties, particularly in complicated sleeve resection situations. Here we have described a case of complete endoscopic bronchial sleeve resection of right lower lung cancer under non-intubated epidural anesthesia.
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Prognostic Significance of MicroRNA-375 Downregulation in Solid Tumors: A Meta-Analysis.
Dis. Markers
PUBLISHED: 08-07-2014
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Objective. Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. We performed a meta-analysis to evaluate the impact of miR-375 expression in solid tumors on patients' overall survival (OS). Methods. Studies were identified by searching PubMed, Embace, and Cochrane Library (last search update was in May 2014) and were assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and stratified analyses were calculated to investigate the association between miR-375 expression and cancer patients OS. Results. Our analysis results indicated that downregulation of miR-375 predicted poor OS (HR = 1.91, 95% CI 1.48-2.45, P < 0.001). Subgroup analyses showed that lower expression of miR-375 was significantly related with poor OS in patients with esophageal carcinoma (HR = 2.24, 95% CI 1.69-2.96, P < 0.001) and non-small-cell lung cancer (NSCLC) (HR = 1.71, 95% CI 1.31-2.24, P < 0.001). Conclusions. The findings from this meta-analysis suggest that miR-375 expression is associated with OS of patients with malignant tumors and could be a useful clinical prognostic biomarker.
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Genetic variation in the tissue factor gene is associated with clinical outcome in severe sepsis patients.
Crit Care
PUBLISHED: 08-03-2014
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IntroductionActivation of inflammation and coagulation was closely related and mutually interdependent in sepsis. Tissue factor (TF) and its endogenous inhibitor, tissue factor pathway inhibitor (TFPI) was the main regulators of the initiation of coagulation process. Altered plasma levels of TF and TFPI have been related to worse outcome in sepsis. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the TF and TFPI genes were associated with risk and outcome for patients with severe sepsis.MethodsSeventeen SNPs in TF and TFPI were genotyped in samples of sepsis (n =577) and severe sepsis patients (n =476), and tested for association in this case¿control collection. We then investigated correlation between the associated SNPs and the mRNA expression, and protein level of the corresponding gene. The mRNA levels of TF were determined using real-time quantitative reverse transcription-polymerase chain reaction and the soluble plasma levels of TF were measured using enzyme linked immunosorbent assay (ELISA) method.ResultsAssociation analysis revealed that three TF SNPs in perfect linkage disequilibrium, rs1361600, rs3917615 and rs958587, were significantly associated with outcome of severe sepsis. G allele frequency of rs1361600 in survivor patients was significantly higher than that in nonsurvivor severe sepsis patients (P =4.91¿×¿10¿5, odds ratio (OR) =0.48, 95% confidence interval (CI) 0.33 to 0.69). The association remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons. Lipopolysaccharide-induced TF-mRNA expression levels in peripheral blood mononuclear cells from subjects carrying rs1361600 AG and GG genotypes, were significantly lower than those subjects carrying AA genotype (P =0.0012). Moreover, severe sepsis patients of GG and GA genotypes showed lower serum levels of TF than patients with AA genotype (P adj =0.02). The plasma levels of TF were also associated with outcome of severe sepsis patients (P adj =0.01). However, genotype and allele analyses did not show any significant difference between sepsis and severe sepsis patients.ConclusionsOur findings indicate that common genetic variation in TF was significantly associated with outcome of severe sepsis in Chinese Han population.
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M13 virus-directed synthesis of nanostructured metal oxides for lithium-oxygen batteries.
Nano Lett.
PUBLISHED: 07-28-2014
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Transition metal oxides are promising electrocatalysts for both water oxidations and metal-air batteries. Here, we report the virus-mediated synthesis of cobalt manganese oxide nanowires (NWs) to fabricate high capacity Li-O2 battery electrodes. Furthermore, we hybridized Ni nanoparticles (NPs) on bio Co3O4 NWs to improve the round trip efficiency as well as the cycle life of Li-O2 batteries. This biomolecular directed synthesis method is expected to provide a selection platform for future energy storage electrocatalysts.
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Impact of EGFR mutation status on tumor response and progression free survival after first-line chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis.
J Thorac Dis
PUBLISHED: 07-17-2014
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Non-small-cell lung cancer (NSCLC) patients harboring sensitive epidermal growth factor receptor (EGFR) mutations derive greater benefits from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) than those with wild type tumors. However, whether EGFR mutation status is associated with the efficacy of cytotoxic chemotherapy or prognosis in advanced NSCLC patients remained controversial. Thus, we sought to conduct a meta-analysis to answer this question.
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Separation mechanisms for palonosetron stereoisomers at different chiral selector concentrations in MEKC.
Electrophoresis
PUBLISHED: 07-16-2014
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The separation mechanisms for palonosetron (PALO) stereoisomers in MEKC using sodium cholate (SC) as surfactant and chiral selector have been studied, in a wide range of concentrations below and above the CMC. It was found that SC micelles only provide chirally selective recognition for 3a carbon chiral center in PALO molecules. The resolution of the configurations of 2 carbon chiral center is achieved by the difference of mobility in continuous phase. A schematic diagram depicting the separation mechanisms and the corresponding migration orders among all of four stereoisomers was proposed based on the measured separation parameters. A MEKC method to achieve the complete separation of four stereoisomers in very short time using a very low chiral selector concentration, instead of high concentrations generally considered, was developed based on the understanding of the mechanisms. This article is protected by copyright. All rights reserved.
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Safety and feasibility of video-assisted thoracoscopic surgery for stage IIIA lung cancer.
Chin. J. Cancer Res.
PUBLISHED: 07-05-2014
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The current study was prospectively designed to explore the application of video-assisted thoracoscopic surgery (VATS) radical treatment for patients with stage IIIA lung cancer, with the primary endpoints being the safety and feasibility of this operation and the second endpoints being the survival and complications after the surgery.
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Deciphering the heterogeneity in DNA methylation patterns during stem cell differentiation and reprogramming.
BMC Genomics
PUBLISHED: 06-30-2014
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Human induced pluripotent stem cells (iPSCs) have a wide range of applications throughout the fields of basic research, disease modeling and drug screening. Epigenetic instable iPSCs with aberrant DNA methylation may divide and differentiate into cancer cells. Unfortunately, little effort has been taken to compare the epigenetic variation in iPSCs with that in differentiated cells. Here, we developed an analytical procedure to decipher the DNA methylation heterogeneity of mixed cells and further exploited it to quantitatively assess the DNA methylation variation in the methylomes of adipose-derived stem cells (ADS), mature adipocytes differentiated from ADS cells (ADS-adipose) and iPSCs reprogrammed from ADS cells (ADS-iPSCs).
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Resveratrol attenuates inflammation in the rat heart subjected to ischemia-reperfusion: Role of the TLR4/NF-?B signaling pathway.
Mol Med Rep
PUBLISHED: 06-24-2014
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It has been previously reported that Toll?like receptor 4 (TLR4)/NF??B signaling mediates early inflammation during myocardial ischemia and reperfusion. It has additionally been suggested that resveratrol produces cardioprotective and anti?inflammatory effects. The aim of the present study was to investigate whether resveratrol could modulate TLR4/NF??B signaling, reduce neutrophil accumulation and TNF?? induction in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to a sham operation, myocardial ischemia and reperfusion (MI/R), MI/R + resveratrol or MI/R + resveratrol + L?NAME. The data showed that following MI/R, the expression of myocardial TLR4 and NF??B increased significantly in the area of induced ischemia. As compared with MI/R, resveratrol significantly attenuated the expression of TLR4 and NF??B and reduced the levels of myeloperoxidase, serum and myocardial TNF?? production, myocardial infarct size and myocardial apoptosis induced by MI/R. All the effects of resveratrol were abolished upon application of L?NAME, a nitric oxide (NO) synthase inhibitor. These data provide evidence that resveratrol inhibits TLR4/NF??B signaling in the rat heart subjected to MI/R, and the anti?inflammatory effect of resveratrol is associated with NO production.
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Long-term survival outcomes of video-assisted thoracic surgery for patients with non-small cell lung cancer.
Chin. J. Cancer Res.
PUBLISHED: 06-10-2014
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Video-assisted thoracic surgery (VATS) has been shown to be a safe alternative to conventional thoracotomy for patients with non-small cell lung cancer (NSCLC). However, popularization of this relatively novel technique has been slow, partly due to concerns about its long-term outcomes. The present study aimed to evaluate the long-term survival outcomes of patients with NSCLC after VATS, and to determine the significant prognostic factors on overall survival.
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Essential parameters for structural analysis and dereplication by (1)H NMR spectroscopy.
J. Nat. Prod.
PUBLISHED: 06-04-2014
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The present study demonstrates the importance of adequate precision when reporting the ? and J parameters of frequency domain (1)H NMR (HNMR) data. Using a variety of structural classes (terpenoids, phenolics, alkaloids) from different taxa (plants, cyanobacteria), this study develops rationales that explain the importance of enhanced precision in NMR spectroscopic analysis and rationalizes the need for reporting ?? and ?J values at the 0.1-1 ppb and 10 mHz level, respectively. Spectral simulations paired with iteration are shown to be essential tools for complete spectral interpretation, adequate precision, and unambiguous HNMR-driven dereplication and metabolomic analysis. The broader applicability of the recommendation relates to the physicochemical properties of hydrogen ((1)H) and its ubiquity in organic molecules, making HNMR spectra an integral component of structure elucidation and verification. Regardless of origin or molecular weight, the HNMR spectrum of a compound can be very complex and encode a wealth of structural information that is often obscured by limited spectral dispersion and the occurrence of higher order effects. This altogether limits spectral interpretation, confines decoding of the underlying spin parameters, and explains the major challenge associated with the translation of HNMR spectra into tabulated information. On the other hand, the reproducibility of the spectral data set of any (new) chemical entity is essential for its structure elucidation and subsequent dereplication. Handling and documenting HNMR data with adequate precision is critical for establishing unequivocal links between chemical structure, analytical data, metabolomes, and biological activity. Using the full potential of HNMR spectra will facilitate the general reproducibility for future studies of bioactive chemicals, especially of compounds obtained from the diversity of terrestrial and marine organisms.
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The dynamics of DNA methylation fidelity during mouse embryonic stem cell self-renewal and differentiation.
Genome Res.
PUBLISHED: 05-16-2014
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The faithful transmission of DNA methylation patterns through cell divisions is essential for the daughter cells to retain a proper cell identity. To achieve a comprehensive assessment of methylation fidelity, we implemented a genome-scale hairpin bisulfite sequencing approach to generate methylation data for DNA double strands simultaneously. We show here that methylation fidelity increases globally during differentiation of mouse embryonic stem cells (mESCs), and is particularly high in the promoter regions of actively expressed genes and positively correlated with active histone modification marks and binding of transcription factors. The majority of intermediately (40%-60%) methylated CpG dinucleotides are hemi-methylated and have low methylation fidelity, particularly in the differentiating mESCs. While 5-hmC and 5-mC tend to coexist, there is no significant correlation between 5-hmC levels and methylation fidelity. Our findings may shed new light on our understanding of the origins of methylation variations and the mechanisms underlying DNA methylation transmission.
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Nonintubated Video-Assisted Thoracoscopic Surgery Under Epidural Anesthesia Compared With Conventional Anesthetic Option: A Randomized Control Study.
Surg Innov
PUBLISHED: 05-14-2014
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Objective. The purposes of this study were to evaluate the feasibility, safety, and advantages of nonintubated video-assisted thoracoscopic surgery (VATS) under epidural anesthesia, by comparing with the performance of conventional approaches. Patients and methods. A total of 354 patients (245 men and 109 women) were recruited in this study. The surgical procedures included bullae resection, pulmonary wedge resection, and lobectomy. The anesthetic technique (epidural vs general) was selected randomly. Patients who underwent nonintubated VATS under epidural anesthesia comprised the intervention group, and patients who received VATS under general anesthesia with double lumen tube comprised the control group. Results. In total, 167 patients were included in the intervention group, and 180 patients were included in the control group. The 2 treatment groups of bullae resection showed significant differences in postoperative fasting time, duration of postoperative antibiotic use depending on the time when the white blood cells decreased to normal levels, and duration of postoperative hospital stay (P < .05). Nonintubated VATS is associated with a decreased level of inflammatory cytokines (P < .05). Conclusion. VATS under anesthesia with nontracheal intubation is safe and feasible, and has demonstrated advantages, including shorter postoperative fasting time, shorter duration of antibiotic use, and shorter hospital stay, compared with VATS under general anesthesia with double lumen tube.
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Melatonin prevents neonatal dexamethasone induced programmed hypertension: Histone deacetylase inhibition.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 05-11-2014
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Adulthood hypertension can be programmed by corticosteroid exposure in early life. Oxidative stress, epigenetic regulation by histone deacetylases (HDACs), and alterations of renin-angiotensin system (RAS) are involved in the developmental programming of hypertension. We examined whether melatonin prevented neonatal dexamethasone (DEX)-induced programmed hypertension and how melatonin prevented these processes. We also examined whether HDAC inhibition by trichostatin A (TSA, a HDAC inhibitor) had similar effects. Male offspring were assigned to 5 groups (n=6/group): control, DEX, melatonin, DEX+melatonin, and DEX+TSA. Male rat pups were injected i.p. with DEX on day 1 (0.5mg/kg BW), day 2 (0.3mg/kg BW), and day 3 (0.1mg/kg BW) after birth. Melatonin was administered in drinking water at the dose of 0.01% during the lactation period. The DEX+TSA group received DEX and 0.5mg/kg TSA subcutaneous injection once daily for 1 week. All rats were killed at 16 weeks of age. Neonatal DEX exposure induced hypertension in male offspring at 16 weeks of age, which melatonin prevented. Neonatal DEX exposure decreased gene expression related to apoptosis, nephrogenesis, RAS, and sodium transporters. Yet DEX treatment increased protein levels of HDAC-1, -2, and -3 in the kidney. Melatonin therapy preserved the decreases of gene expression and decreased HDACs. Similarly, HDAC inhibition prevented DEX-induced programmed hypertension. In conclusion, melatonin therapy exerts a long-term protection against neonatal DEX-induced programmed hypertension. Its beneficial effects include alterations of RAS components and inhibition of class I HDACs. Given that the similar protective effects of melatonin and TSA, melatonin might inhibit HDACs to epigenetic regulation of hypertension-related genes to prevent programmed hypertension.
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Impact of Al2O3 on the aggregation and deposition of graphene oxide.
Environ. Sci. Technol.
PUBLISHED: 04-30-2014
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To assess the environmental behavior and impact of graphene oxide (GO) on living organisms more accurately, the aggregation of GO and its deposition on Al2O3 particles were systematically investigated using batch experiments across a wide range of solution chemistries. The results indicated that the aggregation of GO and its deposition on Al2O3 depended on the solution pH and the types and concentrations of electrolytes. MgCl2 and CaCl2 destabilized GO because of their effective charge screening and neutralization, and the presence of NaH2PO4 and poly(acrylic acid) (PAA) improved the stability of GO with the increase in pH values as a result of electrostatic interactions and steric repulsion. Specifically, the dissolution of Al2O3 contributed to GO aggregation at relatively low pH or high pH values. Results from this study provide critical information for predicting the fate of GO in aquatic-terrestrial transition zones, where aluminum (hydro)oxides are present.
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Association between Glutathione S-Transferase T1, M1, and P1 Genotypes and the Risk of Colorectal Cancer.
J. Korean Med. Sci.
PUBLISHED: 04-24-2014
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Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 null genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P heterozygous=0.790 or P variant=0.261). Furthermore, individuals who simultaneously carried the null genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.
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Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops.
Mol Nutr Food Res
PUBLISHED: 04-09-2014
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Women seeking alternatives to hormone-replacement therapy for menopausal symptoms often try botanical dietary supplements containing extracts of hops (Humulus lupulus L.). Hops contain 8-prenylnaringenin (8-PN), a potent phytoestrogen, the related flavanones 6-prenylnaringenin and isoxanthohumol (IX), and the prenylated chalcone xanthohumol (XN).
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A novel reduction approach to fabricate quantum-sized SnO?-conjugated reduced graphene oxide nanocomposites as non-enzymatic glucose sensors.
Phys Chem Chem Phys
PUBLISHED: 04-05-2014
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Quantum-sized SnO2 nanocrystals can be well dispersed on reduced graphene oxide (rGO) nanosheets through a convenient one-pot in situ reduction route without using any other chemical reagent or source. Highly reactive metastable tin oxide (SnO(x)) nanoparticles (NPs) were used as reducing agents and composite precursors derived by the laser ablation in liquid (LAL) technique. Moreover, the growth and phase transition of LAL-induced SnO(x) NPs and graphene oxide (GO) were examined by optical absorption, X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy and high-resolution transmission electron microscopy. Highly dispersed SnO(x) NPs can also prevent rGO from being restacked into a multilayer structure during GO reduction. Given the good electron transfer ability and unsaturated dangling bonds of rGO, as well as the ample electrocatalytic active sites of quantum-sized SnO2 NPs on unfolded rGO sheets, the fabricated SnO2-rGO nanocomposite exhibited excellent performance in the non-enzymatic electrochemical detection of glucose molecules. The use of LAL-induced reactive NPs for in situ GO reduction is also expected to be a universal and environmentally friendly approach for the formation of various rGO-based nanocomposites.
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Soft-template-carbonization route to highly textured mesoporous carbon-TiO? inverse opals for efficient photocatalytic and photoelectrochemical applications.
Phys Chem Chem Phys
PUBLISHED: 04-04-2014
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Hierarchically organized mesoporous carbon-TiO2 inverse opal nanostructures were synthesized by complementary colloid and block copolymer (BCP) self-assembly, where the triblock copolymer P123 acts simultaneously as the template and the carbon source. Highly ordered mesoporous inverse opal nanostructures with a nano-textured surface morphology and multiple-length scale nanopores provide increased light-activated surface area and scattering effects, leading to enhanced photoabsorption efficiency and the transport of matter. UV-vis absorption, X-ray photoelectron spectroscopy and Mott-Schottky measurement studies show that incorporation of carbon moieties into TiO2via direct conversion of BCPs creates a new energy level above the valence band of TiO2, resulting in an effective decrease in the band gap. A significantly enhanced visible light photocatalytic activity was demonstrated for the mesoporous carbon-TiO2 inverse opals in terms of the degradation of p-nitrophenol (~79%) and photoelectrochemical water splitting (~0.087%).
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2D NMR barcoding and differential analysis of complex mixtures for chemical identification: the Actaea triterpenes.
Anal. Chem.
PUBLISHED: 03-27-2014
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The interpretation of NMR spectroscopic information for structure elucidation involves decoding of complex resonance patterns that contain valuable molecular information (? and J), which is not readily accessible otherwise. We introduce a new concept of 2D-NMR barcoding that uses clusters of fingerprint signals and their spatial relationships in the ?-? coordinate space to facilitate the chemical identification of complex mixtures. Similar to widely used general barcoding technology, the structural information of individual compounds is encoded as a specifics pattern of their C,H correlation signals. Software-based recognition of these patterns enables the structural identification of the compounds and their discrimination in mixtures. Using the triterpenes from various Actaea (syn. Cimicifuga) species as a test case, heteronuclear multiple-bond correlation (HMBC) barcodes were generated on the basis of their structural subtypes from a statistical investigation of their ?H and ?C data in the literature. These reference barcodes allowed in silico identification of known triterpenes in enriched fractions obtained from an extract of A. racemosa (black cohosh). After dereplication, a differential analysis of heteronuclear single-quantum correlation (HSQC) spectra even allowed for the discovery of a new triterpene. The 2D barcoding concept has potential application in a natural product discovery project, allowing for the rapid dereplication of known compounds and as a tool in the search for structural novelty within compound classes with established barcodes.
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La(0.8)Sr(0.2)MnO(3-?) decorated with Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-?): a bifunctional surface for oxygen electrocatalysis with enhanced stability and activity.
J. Am. Chem. Soc.
PUBLISHED: 03-25-2014
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Developing highly active and stable catalysts based on earth-abundant elements for oxygen electrocatalysis is critical to enable efficient energy storage and conversion. In this work, we took advantage of the high intrinsic oxygen reduction reaction (ORR) activity of La(0.8)Sr(0.2)MnO(3-?) (LSMO) and the high intrinsic oxygen evolution reaction (OER) activity of Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-?) (BSCF) to develop a novel bifunctional catalyst. We used pulsed laser deposition to fabricate well-defined surfaces composed of BSCF on thin-film LSMO grown on (001)-oriented Nb-doped SrTiO3. These surfaces exhibit bifunctionality for oxygen electrocatalysis with enhanced activities and stability for both the ORR and OER that rival the state-of-the-art single- and multicomponent catalysts in the literature.
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HNRNPAB induces epithelial-mesenchymal transition and promotes metastasis of hepatocellular carcinoma by transcriptionally activating SNAIL.
Cancer Res.
PUBLISHED: 03-17-2014
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Expression of heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) has been reported to be dysregulated in tumors, but its specific contributions to tumor formation and progression are not fully understood. Here, we demonstrate that HNRNPAB is overexpressed in highly metastatic cells and tumor tissues from patients with hepatocellular carcinoma (HCC) with recurrence. We found that HNRNPAB overexpression promoted epithelial-mesenchymal transition (EMT) in a manner associated with HCC metastasis in vitro and in vivo. RNA interference-mediated silencing of the EMT factor SNAIL attenuated HNRNPAB-enhanced cell invasion in vitro and lung metastasis in vivo. Mechanistically, HNRNPAB acted to transactivate SNAIL1 transcription, which in turn inhibited transcription of the pivotal SNAIL target gene E-cadherin. Overexpression of HNRNPAB in HCC samples correlated with higher SNAIL levels, shorter overall survival, and higher tumor recurrence. HNRNPAB overexpression, alone or in combination with SNAIL, was found to be a significant independent risk factor for recurrence and survival after curative resection. In conclusion, our findings define HNRNPAB as an activator of EMT and metastasis in HCC that predicts poor clinical outcomes.
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Common carotid artery intima-media thickness is useful for diagnosis of the acute stage of Kawasaki disease.
BMC Pediatr
PUBLISHED: 03-13-2014
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This study aimed to investigate intima-media thickness (IMT) of the common carotid arteries in children with acute Kawasaki disease (KD).
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Effect of low concentration sodium dodecyl sulfate on the electromigration of palonosetron hydrochloride stereoisomers in micellar electrokinetic chromatography.
J Chromatogr A
PUBLISHED: 03-06-2014
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The effect of low concentrations of sodium dodecyl sulfate (SDS) on the separation of palonosetron hydrochloride (PALO) stereoisomers by micellar electrokinetic chromatography (MEKC) has been investigated. It was found that the addition of SDS prolongs the migration time and the migration order of four stereoisomers changes regularly with the SDS concentration. Good separations for all the four stereoisomers were achieved at appropriate SDS concentration. The effect of SDS on the electromigration (mobilities) of PALO stereoisomers has been studied, in order to explain its effect on the separation by MEKC. It was found that low concentrations of SDS added into the separation media forms negatively charged complexes with PALO stereoisomers and hence reverses their electromigration direction. Furthermore, the migration order between two enantiomeric pairs is also reversed because the enantiomeric pair with a bigger positive mobility than that of another pair turns to have a bigger negative mobility when bound with SDS. Based on these results, the effect of SDS on the MEKC separation of PALO stereoisomers was elucidated reasonably. The performance of the developed chiral MEKC method was validated by the analysis of a real sample.
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Fabrication of predominantly Mn4+ -doped TiO2 nanoparticles under equilibrium conditions and their application as visible-light photocatalyts.
Chem Asian J
PUBLISHED: 02-25-2014
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The chemical state of a transition-metal dopant in TiO(2) can intrinsically determine the performance of the doped material in applications such as photocatalysis and photovoltaics. In this study, manganese-doped TiO2 is fabricated by a near-equilibrium process, in which the TiO(2) precursor powder precipitates from a hydrothermally obtained transparent mother solution. The doping level and subsequent thermal treatment influence the morphology and crystallization of the TiO(2) samples. FTIR spectroscopy and X-ray photoelectron spectroscopy analyses indicate that the manganese dopant is substitutionally incorporated by replacing Ti(4+) cations. The absorption band edge can be gradually shifted to 1.8?eV by increasing the nominal manganese content to 10?at?%. Manganese atoms doped into the titanium lattice are associated with the dominant 4+ valence oxidation state, which introduces two curved, intermediate bands within the band gap and results in a significant enhancement in photoabsorption and the quantity of photogenerated hydroxyl radicals. Additionally, the high photocatalytic performance of manganese-doped TiO(2) is also attributed to the low oxygen content, owing to the equilibrium fabrication conditions. This work provides an important strategy to control the chemical and defect states of dopants by using an equilibrium fabrication process.
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Capn4 contributes to tumour growth and metastasis of hepatocellular carcinoma by activation of the FAK-Src signalling pathways.
J. Pathol.
PUBLISHED: 02-17-2014
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Calpain small subunit 1 (Capn4) has been identified as a major gene that promotes metastasis of hepatocellular carcinoma (HCC). However, the mechanism by which Capn4 promotes progression of HCC is not understood. In this study, we found that Capn4 expression was increased in highly metastatic HCC cell lines and in tumour tissue from HCC patients compared to healthy patient tissue. Over-expression of Capn4 in HCC cells enhanced tumour cell growth in vitro and increased invasiveness, tumourigenicity and lung metastasis in vivo. Protein microarray analyses showed that expression of multiple proteins was regulated by Capn4. Interestingly, Capn4 was found to physically associate with FAK and promoted hyperactivity of the FAK-Src signalling pathway via increased phosphorylation of specific tyrosine residues of FAK, Src and p130Cas. Knock-down of Capn4 expression suppressed the malignant behaviour of HCC cells and inhibited the FAK-Src signalling pathway. Furthermore, Capn4-mediated invasion and metastasis of HCC cells required up-regulation of matrix metalloproteinase-2 (MMP2) through activation of this signalling pathway. Our clinical data revealed that Capn4 expression correlated well with the levels of phospho-FAK, and over-expression of both Capn4 and phospho-FAK correlates with the poorest survival outcomes in HCC. In conclusion, our data showed that Capn4 can contribute to HCC growth and metastasis via activation of the FAK-Src signalling pathway and MMP2. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Src mediates extracellular signal-regulated kinase 1/2 activation and autophagic cell death induced by cardiac glycosides in human non-small cell lung cancer cell lines.
Mol. Carcinog.
PUBLISHED: 02-04-2014
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Aberrant Na(+) /K(+) -ATPases (NKA) expression is closely related to the incidence and development of cancer, making NKA targeted cancer therapy more intriguing. Cardiac glycosides (CGs) belong to NKA inhibitors and possess potent anti-cancer properties in many cancers. Our previous work demonstrates that CGs family member digoxin or ouabain induces autophagic cell death in human non-small cell lung cancer (NSCLC) cell lines through regulation of both mammalian target of rapamycin and extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. However, what acts as an upstream regulator of ERK1/2 activation during autophagy induction remains obscure. In the present study, the role of Src in the ERK1/2 signaling pathway as well as autophagic cell death induced by either digoxin or ouabain was examined in A549 and H460 cells. Src is significantly activated simultaneously with mitogen-activated protein kinase kinase 1/2 (MEK1/2) and ERK1/2 activation upon the drug treatment. Moreover, Src inhibitor PP2 could block either drug induced MEK1/2 and ERK1/2 phosphorylation, together with autophagic phenotypes in the cells. Knockdown of Src with siRNA causes the similar effect as PP2, both of which markedly alleviate the drugs' cytotoxicity. In addition, increased levels of intracellular reactive oxygen species (ROS) are found to be involved in Src mediated autophagy. Together, this work provides evidences showing that Src mediates MEK1/2 and ERK1/2 pathway as well as ROS generation, and regulates autophagic cell death induced by the cardiac glycosides. These observations may further help understand the molecular mechanisms of autophagy induced by NKA inhibitors in NSCLC cells. © 2014 Wiley Periodicals, Inc.
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Universal quantitative NMR analysis of complex natural samples.
Curr. Opin. Biotechnol.
PUBLISHED: 02-04-2014
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Nuclear Magnetic Resonance (NMR) is a universal and quantitative analytical technique. Being a unique structural tool, NMR also competes with metrological techniques for purity determination and reference material analysis. In pharmaceutical research, applications of quantitative NMR (qNMR) cover mostly the identification and quantification of drug and biological metabolites. Offering an unbiased view of the sample composition, and the possibility to simultaneously quantify multiple compounds, qNMR has become the method of choice for metabolomic studies and quality control of complex natural samples such as foods, plants or herbal remedies, and biofluids. In this regard, NMR-based metabolomic studies, dedicated to both the characterization of herbal remedies and clinical diagnosis, have increased considerably.
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Transarterial chemoembolization combined with sorafenib for advanced hepatocellular carcinoma.
Oncol Lett
PUBLISHED: 01-19-2014
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Sorafenib has been demonstrated to improve survival rate in patients with advanced hepatocellular carcinoma (HCC); however, the survival benefit remains modest and the response rates remain poor. Transarterial chemoembolization (TACE) may be used for the treatment of advanced HCC with well-preserved liver function and has a high local tumor control rate. We hypothesized that patients with advanced HCC may benefit from the combination of sorafenib with TACE. A retrospective study was conducted involving patients with advanced HCC, who had received at least one TACE session. Patients subsequently received 400 mg sorafenib twice per day and were monitored monthly. A dose reduction from 400 to 200 mg of sorafenib twice per day was permitted. The overall survival and side effects were subsequently followed up. In total, 38 patients were included from April 1st, 2009 to March 31st, 2012. All patients were treated with sorafenib after TACE was performed. As of March 31st, 2013, seven patients remained on sorafenib, and were censored at that time point. The median overall survival time was 12 months (95% confidence interval, 6.3-17.7 months). The sorafenib dose was reduced temporarily in 32 patients (84.2%). The most common toxicities were dermatological adverse effects (94.7%), diarrhea (63.2%) and alopecia (26.3%). The survival benefit of sorafenib combined with TACE for advanced HCC is promising, with no intolerable adverse events, provided that dose adjustment is permitted.
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Quantification of a botanical negative marker without an identical standard: ginkgotoxin in Ginkgo biloba.
J. Nat. Prod.
PUBLISHED: 01-16-2014
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A new strategy for the analysis of natural products uses a combination of quantitative (1)H NMR (qHNMR) and adsorbent-free countercurrent separation (CS) methodology to establish a quantification method for ginkgotoxin (4'-O-methylpyridoxine) in Ginkgo biloba preparations. The target analyte was concentrated in a one-step CS process using the ChMWat +2 solvent system (CHCl3-MeOH-H2O, 10:5:5) and subsequently assayed by qHNMR. While commercial G. biloba seeds contained 59 ?g of ginkgotoxin per seed, the compound was below the limit of detection (9 ppm) in a typical leaf extract. Due to the enrichment potential and loss-free operation of CS, the combination of CS and qHNMR is a generally suitable approach for threshold assays aimed at quantifying target compounds such as botanical negative markers at the low ppm level. As the proof of principle is demonstrated for relatively small CS capacities (20 mL, 1:40 loading) and modest NMR sensitivity (n = 16, 400 MHz, 5 mm RT probe), the approach can be adapted to quantification at the ppb level. The procedure enables the quantification of a botanical negative marker in the absence of identical reference material, which otherwise is a prerequisite for LC-based assays.
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Galloyl moieties enhance the dentin biomodification potential of plant-derived catechins.
Acta Biomater
PUBLISHED: 01-10-2014
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Proanthocyanidin-rich plant-derived agents have been shown to enhance dentin biomechanical properties and resistance to collagenase degradation. This study systematically investigated the interaction of chemically well-defined monomeric catechins with dentin extracellular matrix components by evaluating dentin mechanical properties as well as activities of matrix metalloproteinases (MMPs) and cysteine-cathepsins (CTs). Demineralized dentin beams (n=15) were incubated for 1h with 0.65% (+)-catechin (C), (-)-catechin gallate (CG), (-)-gallocatechin gallate (GCG), (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG). The modulus of elasticity (E) and the fold increase in E were determined by comparing specimens at baseline and after treatment. Biodegradation rates were assessed by differences in percentage of dry mass before and after incubation with bacterial collagenase. The inhibition of MMP-9 and CT-B by 0.65, 0.065 and 0.0065% of each catechin was determined using fluorimetric proteolytic assay kits. All monomeric catechins led to a significant increase in E. EGCG showed the highest fold increase in E, followed by ECG, CG and GCG. EGCG, ECG, GCG and CG significantly lowered biodegradation rates and inhibited both MMP-9 and CT-B at a concentration of 0.65%. Overall, the 3-O-galloylated monomeric catechins are clearly more potent than their non-galloylated analogues in improving dentin mechanical properties, stabilizing collagen against proteolytic degradation, and inhibiting the activity of MMPs and CTs. The results indicate that galloylation is a key pharmacophore in the monomeric and likely also in the oligomeric proanthocyanidins that exhibit high cross-linking potential for dentin extracellular matrix.
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Comparative study of systematic thoracoscopic lymphadenectomy and conventional thoracotomy in resectable non-small cell lung cancer.
J Thorac Dis
PUBLISHED: 01-03-2014
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To assess the feasibility and safety of the video-assisted thoracoscopy surgery (VATS) systematic lymph node dissection in resectable non-small cell lung cancer (NSCLC).
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Differential Regulation of Human Aortic Smooth Muscle Cell Proliferation by Monocyte-Derived Macrophages from Diabetic Patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Macrophage accumulation in the arterial wall and smooth muscle cell (SMC) proliferation are features of type 2 diabetes mellitus (DM) and its vascular complications. However, the effects of diabetic monocyte-derived macrophages on vascular SMC proliferation are not clearly understood. In the present study, we investigated the pro-proliferative effect of macrophages isolated from DM patients on vascular SMCs. Macrophage-conditioned media (MCM) were prepared from macrophages isolated from DM patients. DM-MCM treatment induced HASMC proliferation, decreased p21Cip1 and p27Kip1 expressions, and increased microRNA (miR)-17-5p and miR-221 expressions. Inhibition of either miR-17-5p or miR-221 inhibited DM-MCM-induced cell proliferation. Inhibition of miR-17-5p abolished DM-MCM-induced p21Cip1 down-regulation; and inhibition of miR-221 attenuated the DM-MCM-induced p27Kip1 down-regulation. Furthermore, blocking assays demonstrated that PDGF-CC in DM-MCM is the major mediators of cell proliferation in SMCs. In conclusion, our present data support the hypothesis that SMC proliferation stimulated by macrophages may play critical roles in vascular complications in DM patients and suggest a new mechanism by which arterial disease is accelerated in diabetes.
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Analysis of feasibility and safety of complete video-assisted thoracoscopic resection of anatomic pulmonary segments under non-intubated anesthesia.
J Thorac Dis
PUBLISHED: 01-01-2014
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To explore the feasibility and safety of complete video-assisted thoracoscopic surgery (C-VATS) under non-intubated anesthesia for the resection of anatomic pulmonary segments in the treatment of early lung cancer (T1N0M0), benign lung diseases and lung metastases.
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Two new compounds from the flowers of Rhododendron molle.
Chin J Nat Med
PUBLISHED: 12-24-2013
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To study the chemical constituents of the flowers of Rhododendron molle.
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CXCL5 contributes to tumour metastasis and recurrence of intrahepatic cholangiocarcinoma by recruiting infiltrative intratumoural neutrophils.
Carcinogenesis
PUBLISHED: 11-30-2013
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CXCL5 is a member of the CXC-type chemokine family that may play a role in carcinogenesis and cancer progression. This study investigates the biological function and clinical significance of CXCL5 in intrahepatic cholangiocarcinoma (ICC). We demonstrated that CXCL5 was overexpressed in ICC cell lines and tumour samples compared with paired normal tissues. CXCL5 had a direct chemoattractant effect on neutrophils in vitro through PI3K-Akt and ERK1/2 signalling pathways. In animal studies, CXCL5 promoted tumour growth and metastasis without altering in vitro proliferative and invasive ability of ICC cells, and this effect was mediated by the recruitment of intratumoural infiltrative neutrophils by tumour-derived CXCL5. Immunohistochemical analysis of ICC samples showed that overexpression of CXCL5 correlated strongly with intratumoural neutrophil infiltration, shorter overall survival, and high tumour recurrence. Multivariate analysis revealed that CXCL5 overexpression alone, or combined with the presence of intratumoural neutrophils, was an independent prognostic indicator for ICC. In conclusion, our data showed that CXCL5 promotes ICC growth and metastasis by recruiting intratumoural neutrophils. CXCL5 alone or combined with intratumoural neutrophils is a novel prognostic predictor for ICC patients and a potential therapeutic target.
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Thoracoscopic Half Carina Resection and Bronchial Sleeve Resection for Central Lung Cancer.
Surg Innov
PUBLISHED: 11-29-2013
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Background. The objectives of this study were to report the surgical techniques and clinical outcome of thoracoscopic half carina resection and thoracoscopic bronchial sleeve resection for central lung cancer. Methods. Between January 2011 and November 2012, 675 patients with lung cancer underwent radical surgery by thoracoscopy, and 49 (7.3%) underwent bronchial sleeve resection. Among 49 patients, 20 (41%) received thoracoscopic bronchial sleeve lobectomy. Perioperative variables and postoperative outcomes of these cases were analyzed to evaluate the technical feasibility and safety of this operation. Results. In one patient, right upper lung sleeve resection was combined with half-carinal resection and reconstruction. In another, right medial lung sleeve resection was combined with lower right dorsal segment resection. The average time of surgery was 239 ± 51 minutes (range = 142-330 minutes), and the average time of airway reconstruction was 44 ± 17 minutes (range = 22-75 minutes). The intraoperative blood loss averaged 207 ± 96 mL (range = 80-550 mL). The median postoperative hospital stay was 10 days (interquartile range = 8-12 days). Postoperatively, extubation was achieved in the recovery room without further need for mechanical ventilation. None of the patients developed anastomotic leak. Perioperative mortality was not observed. Conclusion. Thoracoscopic bronchial sleeve resection can be considered a feasible and safe operation for selected patients with central lung cancer. The complicated anastomosis technique of half carina resection was feasible.
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One-Pot Three-Component Approach to the Synthesis of Polyfunctional Pyrazoles.
Org. Lett.
PUBLISHED: 11-20-2013
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A simple, multicomponent, and straightforward reaction of vinyl azide, aldehyde, and tosylhydrazine affords the construction of 3,4,5-trisubstituted 1H-pyrazoles regioselectively in the presence of base with moderate to excellent yields. A range of functionality could be tolerated in this methodology, and a possible mechanism is proposed.
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Cation-Dependent Magnetic Ordering and Room-Temperature Bistability in Azido-Bridged Perovskite-Type Compounds.
J. Am. Chem. Soc.
PUBLISHED: 10-21-2013
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A series of end-to-end azido-bridged perovskite-type compounds [(CH3)nNH4-n][Mn(N3)3] (n = 1-4) were synthesized and characterized. Structural phase transitions indicating the general lattice flexibility were observed and confirmed by the crystal structures of different phases. These materials show cation-dependent magnetic ordering at up to 92 K and magnetic bistability near room temperature.
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Reactivity of carbon in lithium-oxygen battery positive electrodes.
Nano Lett.
PUBLISHED: 09-10-2013
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Unfortunately, the practical applications of Li-O2 batteries are impeded by poor rechargeability. Here, for the first time we show that superoxide radicals generated at the cathode during discharge react with carbon that contains activated double bonds or aromatics to form epoxy groups and carbonates, which limits the rechargeability of Li-O2 cells. Carbon materials with a low amount of functional groups and defects demonstrate better stability thus keeping the carbon will-o-the-wisp lit for lithium-air batteries.
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Proton fingerprints portray molecular structures: enhanced description of the 1H NMR spectra of small molecules.
J. Org. Chem.
PUBLISHED: 09-06-2013
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The characteristic signals observed in NMR spectra encode essential information on the structure of small molecules. However, extracting all of this information from complex signal patterns is not trivial. This report demonstrates how computer-aided spectral analysis enables the complete interpretation of 1D (1)H NMR data. The effectiveness of this approach is illustrated with a set of organic molecules, for which replicas of their (1)H NMR spectra were generated. The potential impact of this methodology on organic chemistry research is discussed.
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Synthesis of highly stable sub-8 nm TiO2 nanoparticles and their multilayer electrodes of TiO2/MWNT for electrochemical applications.
Nano Lett.
PUBLISHED: 09-04-2013
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Next-generation electrochemical energy storage for integrated microsystems and consumer electronic devices requires novel electrode materials with engineered architectures to meet the requirements of high performance, low cost, and robustness. However, conventional electrode fabrication processes such as doctor blading afford limited control over the electrode thickness and structure at the nanoscale and require the incorporation of insulating binder and other additives, which can promote agglomeration and reduce active surface area, limiting the inherent advantages attainable from nanoscale materials. We have engineered a route for the synthesis of highly stable, sub-8 nm TiO2 nanoparticles and their subsequent incorporation with acid-functionalized multiwalled carbon nanotubes (MWNTs) into nanostructured electrodes using aqueous-based layer-by-layer electrostatic self-assembly. Using this approach, binder-free thin film electrodes with highly controllable thicknesses up to the micrometer scale were developed with well-dispersed, nonagglomerated TiO2 nanoparticles on MWNTs. Upon testing in an Li electrochemical half-cell, these electrodes demonstrate high capacity (>150 mAh/gel(ectrode) at 0.1 A/gel(ectrode)), good rate capability (>100 mAh/gel(ectrode) up to 1 A/g(electrode)) and nearly no capacity loss up to 200 cycles for electrodes with thicknesses up to 1480 nm, indicating their promise as thin-film negative electrodes for future Li storage applications.
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Highly efficient enrichment of radionuclides on graphene oxide-supported polyaniline.
Environ. Sci. Technol.
PUBLISHED: 08-16-2013
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Graphene oxide-supported polyaniline (PANI@GO) composites were synthesized by chemical oxidation and were characterized by SEM, Raman and FT-IR spectroscopy, TGA, potentiometric titrations, and XPS. The characterization indicated that PANI can be grafted onto the surface of GO nanosheets successfully. The sorption of U(VI), Eu(III), Sr(II), and Cs(I) from aqueous solutions as a function of pH and initial concentration on the PANI@GO composites was investigated. The maximum sorption capacities of U(VI), Eu(III), Sr(II), and Cs(I) on the PANI@GO composites at pH 3.0 and T = 298 K calculated from the Langmuir model were 1.03, 1.65, 1.68, and 1.39 mmol·g(-1), respectively. According to the XPS analysis of the PANI@GO composites before and after Eu(III) desorption, nitrogen- and oxygen-containing functional groups on the surface of PANI@GO composites were responsible for radionuclide sorption, and that radionuclides can hardly be extracted from the nitrogen-containing functional groups. Therefore, the chemical affinity of radionuclides for nitrogen-containing functional groups is stronger than that for oxygen-containing functional groups. This paper focused on the application of PANI@GO composites as suitable materials for the preconcentration and removal of lanthanides and actinides from aqueous solutions in environmental pollution management in a wide range of acidic to alkaline conditions.
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Video-assisted thoracic surgery versus open thoracotomy for non-small-cell lung cancer: a propensity score analysis based on a multi-institutional registry.
Eur J Cardiothorac Surg
PUBLISHED: 08-15-2013
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Comparative long-term survival and oncological outcomes for patients with non-small-cell lung cancer (NSCLC) who undergo video-assisted thoracic surgery (VATS) or conventional open lobectomy remain uncertain. We conducted a multi-institutional propensity-matched study to stratify potential differences in these outcomes.
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Inhibition of human cytochrome P450 enzymes by hops (Humulus lupulus) and hop prenylphenols.
Eur J Pharm Sci
PUBLISHED: 07-24-2013
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As hops (Humulus lupulus L.) are used in the brewing of beer and by menopausal women as estrogenic dietary supplements, the potential for hop extracts and hop constituents to cause drug-botanical interactions by inhibiting human cytochrome P450 enzymes was investigated. Inhibition of major human cytochrome P450 enzymes by a standardized hop extract and isolated hop prenylated phenols was evaluated using a fast and efficient assay based on ultrahigh pressure liquid chromatography-tandem mass spectrometry. The hop extract at 5?g/mL inhibited CYP2C8 (93%), CYP2C9 (88%), CYP2C19 (70%), and CYP1A2 (27%) with IC50 values of 0.8, 0.9, 3.3, and 9.4?g/mL, respectively, but time-dependent inactivation was observed only for CYP1A2. Isoxanthohumol from hops was the most potent inhibitor of CYP2C8 with an IC50 of 0.2?M, whereas 8-prenylnaringenin was the most potent inhibitor of CYP1A2, CYP2C9 and CYP2C19 with IC50 values of 1.1?M, 1.1?M and 0.4?M, respectively. Extracts of hops contain prenylated compounds such as the flavanones isoxanthohumol and 8-prenylnaringenin and the chalcone xanthohumol that can inhibit CYP450s, especially the CYP2C family, which may affect the efficacy and safety of some CYP2C substrate drugs when co-administered.
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Feasibility of complete video-assisted thoracoscopic surgery following neoadjuvant therapy for locally advanced non-small cell lung cancer.
J Thorac Dis
PUBLISHED: 07-10-2013
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To explore the feasibility of complete video-assisted thoracoscopic surgery (c-VATS) following neoadjuvant therapy (chemotherapy, targeted therapy and radiotherapy, either alone or in combination) for the treatment of patients with non-small cell lung cancer (NSCLC).
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Video-assisted thoracoscopic lobectomy for non-small cell lung cancer in patients with severe chronic obstructive pulmonary disease.
J Thorac Dis
PUBLISHED: 07-08-2013
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To assess the feasibility, safety and long-term outcomes of video-assisted thoracic surgery (VATS) lobectomy for the treatment of non-small cell lung cancer (NSCLC) in patients with severe chronic obstructive pulmonary disease (COPD).
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Thoracoscopic minimally invasive surgery for non-small cell lung cancer in patients with chronic obstructive pulmonary disease.
J Thorac Dis
PUBLISHED: 07-07-2013
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To determine the incidence of peri-operative complications in non-small cell lung cancer (NSCLC) patients with co-existent chronic obstructive pulmonary disease (COPD) who undergo lung resection via traditional and minimally invasive techniques.
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RNA silencing targeting PIN (protein inhibitor of neuronal nitric oxide synthase) attenuates the development of hypertension in young spontaneously hypertensive rats.
J Am Soc Hypertens
PUBLISHED: 07-01-2013
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Nitric oxide (NO) deficiency contributes to hypertension. We previously showed that neuronal nitric oxide synthase (nNOS) was involved in hypertension and kidney damage in spontaneously hypertensive rats (SHRs). The protein inhibitor of nNOS (PIN) has been reported to inhibit activity of nNOS.Thus, we tested whether increased PIN in the kidney results in hypertension and whether small interfering RNA (siRNA) targeting PIN attenuates hypertension in SHRs. Four-week-old male SHRs were assigned into three groups (n = 6-7/group): SHR; SHR + PIN, SHR that received siRNA targeting PIN; and SHR + NC, SHR treated with random negative control siRNA. Rats were sacrificed at 12 weeks of age. PIN protein expression was inhibited considerably when PIN siRNA was transfected into NRK52E cells (90% siRNA at 1 nM). The increases of BP were attenuated by siRNA targeting PIN in12-week-old SHRs. Immunostaining of nNOS-? and total nNOS was greater in SHR + PIN group than SHR. Moreover, renal superoxide production and 8-hydroxydeoxyguanosine (8-OHdG) staining were more decreased in the SHR + PIN group than SHRs. We conclude that PIN siRNA reduced PIN expression in vitro and in vivo. PIN siRNA therapy attenuates hypertension in SHRs at 12 weeks of age. Our results suggest that PIN is involved in the development of hypertension.
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Prediction of posttranslational modification sites from amino acid sequences with kernel methods.
J. Theor. Biol.
PUBLISHED: 06-28-2013
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Post-translational modification (PTM) is the chemical modification of a protein after its translation and one of the later steps in protein biosynthesis for many proteins. It plays an important role which modifies the end product of gene expression and contributes to biological processes and diseased conditions. However, the experimental methods for identifying PTM sites are both costly and time-consuming. Hence computational methods are highly desired. In this work, a novel encoding method PSPM (position-specific propensity matrices) is developed. Then a support vector machine (SVM) with the kernel matrix computed by PSPM is applied to predict the PTM sites. The experimental results indicate that the performance of new method is better or comparable with the existing methods. Therefore, the new method is a useful computational resource for the identification of PTM sites. A unified standalone software PTMPred is developed. It can be used to predict all types of PTM sites if the user provides the training datasets. The software can be freely downloaded from http://www.aporc.org/doc/wiki/PTMPred.
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Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: l-citrulline and nitrate.
Transl Res
PUBLISHED: 06-27-2013
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Nitric oxide (NO) deficiency mediates oxidative stress in the kidney and is involved in the development of hypertension. NO synthesis occurs via 2 pathways: nitric oxide synthase (NOS) dependent and NOS-independent. We tested whether the development of hypertension is prevented by restoration of NO by dietary l-citrulline or nitrate supplementation in young spontaneously hypertensive rats (SHRs). Male SHRs and normotensive Wistar Kyoto control rats (WKYs)s age 4 weeks were assigned to 4 groups: untreated SHRs and WKYs, and SHRs and WKYs that received 0.25% l-citrulline for 8 weeks. In our second series of studies, we replaced l-citrulline with 1 mmol/kg/d sodium nitrate. All rats were sacrificed at age 12 weeks. We found an increase in the blood pressure of SHRs was prevented by dietary supplementation of l-citrulline or nitrate. Both treatments restored NO bioavailability and reduced oxidative stress in SHR kidneys. l-Citrulline therapy reduced levels of l-arginine and asymmetric dimethylarginine (ADMA)-an endogenous inhibitor of NOS-and increased the l-arginine-to-ADMA ratio in SHR kidneys. Nitrate treatment reduced plasma levels of l-arginine and ADMA concurrently in SHRs. Our findings suggest that both NOS-dependent and -independent approaches in the prehypertensive stage toward augmentation of NO can prevent the development of hypertension in young SHRs.
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Site-selective deposition of twinned platinum nanoparticles on TiSi2 nanonets by atomic layer deposition and their oxygen reduction activities.
ACS Nano
PUBLISHED: 06-27-2013
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For many electrochemical reactions such as oxygen reduction, catalysts are of critical importance, as they are often necessary to reduce reaction overpotentials. To fulfill the promises held by catalysts, a well-defined charge transport pathway is indispensable. Presently, porous carbon is most commonly used for this purpose, the application of which has been recently recognized to be a potential source of concern. To meet this challenge, here we present the development of a catalyst system without the need for carbon. Instead, we focused on a conductive, two-dimensional material of a TiSi2 nanonet, which is also of high surface area. As a proof-of-concept, we grew Pt nanoparticles onto TiSi2 by atomic layer deposition. Surprisingly, the growth exhibited a unique selectivity, with Pt deposited only on the top/bottom surfaces of the nanonets at the nanoscale without mask or patterning. Pt {111} surfaces are preferably exposed as a result of a multiple-twinning effect. The materials showed great promise in catalyzing oxygen reduction reactions, which is one of the key challenges in both fuel cells and metal air batteries.
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Dentin biomodification: strategies, renewable resources and clinical applications.
Dent Mater
PUBLISHED: 06-26-2013
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The biomodification of dentin is a biomimetic approach, mediated by bioactive agents, to enhance and reinforce the dentin by locally altering the biochemistry and biomechanical properties. This review provides an overview of key dentin matrix components, targeting effects of biomodification strategies, the chemistry of renewable natural sources, and current research on their potential clinical applications.
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Hybrid Video-Assisted Thoracic Surgery With Segmental-Main Bronchial Sleeve Resection for Non-Small Cell Lung Cancer.
Surg Innov
PUBLISHED: 06-21-2013
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Background. The purpose of the current study is to present the clinical and surgical results in patients who underwent hybrid video-assisted thoracic surgery with segmental-main bronchial sleeve resection. Methods. Thirty-one patients, 27 men and 4 women, underwent segmental-main bronchial sleeve anastomoses for non-small cell lung cancer between May 2004 and May 2011. Results. Twenty-six (83.9%) patients had squamous cell carcinoma, and 5 patients had adenocarcinoma. Six patients were at stage IIB, 24 patients at stage IIIA, and 1 patient at stage IIIB. Secondary sleeve anastomosis was performed in 18 patients, and Y-shaped multiple sleeve anastomosis was performed in 8 patients. Single segmental bronchiole anastomosis was performed in 5 cases. The average time for chest tube removal was 5.6 days. The average length of hospital stay was 11.8 days. No anastomosis fistula developed in any of the patients. The 1-, 2-, and 3-year survival rates were 83.9%, 71.0%, and 41.9%, respectively. Conclusion. Hybrid video-assisted thoracic surgery with segmental-main bronchial sleeve resection is a complex technique that requires training and experience, but it is an effective and safe operation for selected patients.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.