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Find video protocols related to scientific articles indexed in Pubmed.
Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection.
Gut
PUBLISHED: 11-16-2014
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To elucidate the association between antiviral therapy and extrahepatic outcomes in individuals infected with HCV.
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Intracellular osteopontin inhibits Toll-like receptor signaling and impedes liver carcinogenesis.
Cancer Res.
PUBLISHED: 11-16-2014
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Osteopontin (OPN) has been implicated widely in tumor growth and metastasis but the range of its contributions are not yet fully understood. In this study, we show that genetic ablation of OPN in the mouse sensitizes them to diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Opn deficient mice (Opn-/- mice) exhibited enhanced production of proinflammatory cytokines and compensatory proliferation. Administering OPN antibody or recombinant OPN protein to wild type (WT) or Opn-/- mice-derived macrophages, respectively, had little effect on cytokine production. In contrast, overexpression of intracellular Opn (iOpn) in Opn-deficient macrophages strongly suppressed production of proinflammatory cytokines. In addition, we found iOPN was able to interact with the pivotal Toll-like receptor (TLR) signaling protein MyD88 in macrophages after stimulation with cellular debris, thereby disrupting TLR signaling in macrophages. Our results indicated that iOPN was capable of functioning as an endogenous negative regulator of TLR-mediated immune responses, acting to ameliorate production of proinflammatory cytokines and curtail DEN-induced hepatocarcinogenesis. Together, our results expand the important role of OPN in inflammation-associated cancers and deepen its relevance for novel treatment strategies in liver cancer.
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Immunosuppressive treatment combined with nucleoside analog is superior to nucleoside analog only in the treatment of severe thrombocytopenia in patients with cirrhosis associated with hepatitis B in China: A multicenter, observational study.
Platelets
PUBLISHED: 11-15-2014
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Abstract No effective treatment has been identified for patients of liver cirrhosis (LC) associated with hepatitis B virus (HBV) and severe thrombocytopenia. We aimed to explore the effectiveness and safety of low-dose prednisone or cyclosporine A (CsA) combined with nucleoside analog (NA) in patients with severe thrombocytopenia associated with HBV-related LC. We included 145 consecutive compensated HBV-associated LC patients with severe thrombocytopenia between 1 January 2006 and 31 December 2013. We divided the patients into three groups by treatment strategy, including NA only (n?=?57), NA plus prednisone (n?=?46), and NA plus CsA (n?=?42). We analyzed the platelet counts, bleeding events, liver function, replication of HBV, and outcomes in each group. At all time points during this observation, the platelet counts in prednisone or CsA group were higher than those in the NA only group. There are significant differences in the cumulative rates of bleeding events among the three groups. The platelet counts and treatment were factors associated with bleeding events in multivariate analysis. The differences in HBV-DNA negative rates, HBV-DNA elevated rates, normal serum alanine transaminase rates, serum alanine transaminase elevated more than two times the baseline rates, and HBeAg seropositive conversion ratio among the groups did not reach statistical significance. The adverse events in our study were, in general, mild and balanced among the three treatment groups. Treatment with low-dose prednisone or CsA plus NA could elevate the platelet counts and reduce the risk of bleeding events in HBV LC with severe thrombocytopenia.
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Unusual role of epilayer-substrate interactions in determining orientational relations in van der Waals epitaxy.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-12-2014
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Using selected-area low-energy electron diffraction analysis, we showed strict orientational alignment of monolayer hexagonal boron nitride (h-BN) crystallites with Cu(100) surface lattices of Cu foil substrates during atmospheric pressure chemical vapor deposition. In sharp contrast, the graphene-Cu(100) system is well-known to assume a wide range of rotations despite graphene's crystallographic similarity to h-BN. Our density functional theory calculations uncovered the origin of this surprising difference: The crystallite orientation is determined during nucleation by interactions between the cluster's edges and the substrate. Unlike the weaker B- and N-Cu interactions, strong C-Cu interactions rearrange surface Cu atoms, resulting in the aligned geometry not being a distinct minimum in total energy. The discovery made in this specific case runs counter to the conventional wisdom that strong epilayer-substrate interactions enhance orientational alignment in epitaxy and sheds light on the factors that determine orientational relation in van der Waals epitaxy of 2D materials.
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Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses.
Mol Ther Methods Clin Dev
PUBLISHED: 11-11-2014
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Controlling the specificity of retroviral DNA integration could improve the safety of gene therapy vectors, and fusions of heterologous chromatin binding modules to the integrase-binding domain from the lentiviral integration host cofactor LEDGF/p75 are a promising retargeting strategy. We previously proposed the utility of integrase mutant lentiviral vectors that are selectively activated by complementary LEDGF/p75 variants, and our initial modifications in HIV-1 integrase and LEDGF/p75 supported about 13% of wild-type vector transduction activity. Here we describe the selection and characterization of the K42E gain-of-function mutation in HIV-1 integrase, which greatly improves the efficiency of this system. Both K42E and initial reverse-charge mutations in integrase negatively impacted reverse transcription and integration, yet when combined together boosted viral transduction efficiency to ~75% of the wild-type vector in a manner dependent on a complementary LEDGF/p75 variant. Although the K42E mutation conferred functional gains to integrase mutant viral reverse transcription and integration, only the integration boost depended on the engineered LEDGF/p75 mutant. We conclude that the specificity of lentiviral retargeting strategies based on heterologous LEDGF/p75 fusion proteins will benefit from our optimized system that utilizes the unique complementation properties of reverse-charge integrase mutant viral and LEDGF/p75 host proteins.
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Microscopic mechanism of electron transfer through the hydrogen bonds between carboxylated alkanethiol molecules connected to gold electrodes.
J Chem Phys
PUBLISHED: 11-10-2014
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The atomic structure and the electron transfer properties of hydrogen bonds formed between two carboxylated alkanethiol molecules connected to gold electrodes are investigated by employing the non-equilibrium Green's function formalism combined with density functional theory. Three types of molecular junctions are constructed, in which one carboxyl alkanethiol molecule contains two methylene, -CH2, groups and the other one is composed of one, two, or three -CH2 groups. Our calculations show that, similarly to the cases of isolated carboxylic acid dimers, in these molecular junctions the two carboxyl, -COOH, groups form two H-bonds resulting in a cyclic structure. When self-interaction corrections are explicitly considered, the calculated transmission coefficients of these three H-bonded molecular junctions at the Fermi level are in good agreement with the experimental values. The analysis of the projected density of states confirms that the covalent Au-S bonds localized at the molecule-electrode interfaces and the electronic coupling between -COOH and S dominate the low-bias junction conductance. Following the increase of the number of the -CH2 groups, the coupling between -COOH and S decreases deeply. As a result, the junction conductance decays rapidly as the length of the H-bonded molecules increases. These findings not only provide an explanation to the observed distance dependence of the electron transfer properties of H-bonds, but also help the design of molecular devices constructed through H-bonds.
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The influenza NA protein transmembrane and head domains have co-evolved.
J. Virol.
PUBLISHED: 11-08-2014
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Transmembrane domains (TMDs) from single-spanning membrane proteins are commonly viewed as membrane anchors for functional domains. Influenza virus neuraminidase (NA) exemplifies this concept as it retains enzymatic function upon proteolytic release from the membrane. However, the subtype 1 NA TMDs have become increasingly polar in human strains since 1918, which suggests that selection pressure exists on this domain. Here, we investigated the N1 TMD-head domain relationship by exchanging a prototypical 'old' TMD (1933) with a 'recent' (2009) more polar TMD and an engineered hydrophobic TMD. Each exchange altered the TMD association, decreased the NA folding efficiency, and significantly reduced viral budding and replication at 37°C compared to 33°C where NA folds more efficiently. Passaging the chimera viruses at 37°C restored the NA folding efficiency, viral budding and infectivity by selecting for NA TMD mutations that correspond with their polar or hydrophobic assembly properties. These results demonstrate that single-spanning membrane protein TMDs can influence distal domain folding, as well as membrane-related processes, and suggests the NA TMD in H1N1 viruses has become more polar to maintain compatibility with the evolving enzymatic head domain.
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PD-L1 expression in melanocytic lesions does not correlate with the BRAF V600E mutation.
Cancer Immunol Res
PUBLISHED: 11-06-2014
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PD-L1 expression in melanoma correlates with response to PD-1 pathway blocking antibodies. Aberrant tumor cell PD-L1 expression may be oncogene-driven and/or induced by interferon-gamma (IFN-g). Melanomas express PD-L1 in association with tumor infiltrating lymphocytes (TILs), but the potential contribution of the BRAF V600E mutation (BRAFmut) to induced PD-L1 expression has not been determined. Fifty-two archival melanocytic lesions were simultaneously assessed for PD-L1 expression, TIL infiltration and BRAFmut. IFN-g-induced PD-L1 expression in cultured melanomas was also assessed according to BRAF status. Melanocyte PD-L1 expression was observed in 40% of specimens, and BRAFmut was observed in 42% of specimens, but there was no significant concordance between these variables. Almost all melanocytes displaying PD-L1 expression were observed adjacent to TILs, irrespective of BRAF status. TIL(-) lesions were not more likely to be associated with BRAFmut, compared to TIL(+) lesions. Baseline expression of PD-L1 by melanoma cell lines was virtually nil regardless of BRAFmut status, and the intensity of interferon-induced PD-L1 expression in melanoma cell lines likewise did not correlate with BRAF mutational status. PD-L1 expression in melanocytic lesions does not correlate with the BRAFmut. Thus, distinct populations of melanoma patients will likely benefit from BRAF inhibitors vs. PD-1 pathway blockade.
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Rapid Screening of Peptide Probes through In Situ Single-Bead Sequencing Microarray.
Anal. Chem.
PUBLISHED: 11-06-2014
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Peptide ligands as targeting probes for in vivo imaging and drug delivery have attracted great interest in the biomedical community. However, high affinity and specificity screening of large peptide libraries remains a tedious process. Here, we report a continuous-flow microfluidic method for one-bead-one-compound (OBOC) combinatorial peptide library screening. We screened a library with 2 × 10(5) peptide beads within 4 h and discovered 140 noncanonical peptide hits targeting the tumor marker, aminopeptidase N (APN). Using the Clustal algorithm, we identified the conserved sequence Tyr-XX-Tyr in the N terminal. We demonstrated that the novel sequence YVEYHLC peptides have both nanomolar affinity and high specificity for APN in ex vivo and in vivo models. We envision that the successful demonstration of this integrated novel nanotechnology for peptide screening and identification open a new avenue for rapid discovery of new peptide-based reagents for disease diagnostics and therapeutics.
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?-Glucosidase Involvement in the Bioactivation of Glycosyl Conjugates in Plants: Synthesis and Metabolism of Four Glycosidic Bond Conjugates in Vitro and in Vivo.
J. Agric. Food Chem.
PUBLISHED: 11-06-2014
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Mobile glucose-pesticide conjugates in the phloem are often restricted by decreases in biological activity. However, plants can bioactivate endogenous glucosides, which are assumed as able to bioactivate exogenous conjugates. In this study, four glycosidic bonds (O-, S-, N-, and C-glycosidic bonds) of glucose-pesticide conjugates were designed and synthesized, and then metabolism assays were carried out in vitro and in vivo. Results showed that ?-glucosidases played a role in the hydrolysis of O-glycosidic bond conjugates in Ricinus communis L. The liberated aglycons possessed insecticidal activities against Plutella xylostella L. and Spodoptera litura F. These results could help establish methods of circumventing the mutual exclusivity of phloem mobility and biological activity by hydrolyzing endogenous ?-glucosidases.
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Nano-Confined Squaraine Dye Assemblies: New Photoacoustic and Near-Infrared Fluorescence Dual-Modular Imaging Probes in Vivo.
Bioconjug. Chem.
PUBLISHED: 11-05-2014
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For the purpose of near-infrared (NIR) fluorescence and photoacoustic (PA) tomography dual-modular imaging, self-assembly of squaraine (SQ) dyes is constructed in the hydrophobic phospholipid bilayers of liposomes (SQ?L) with variable mixing ratios of SQ and phospholipids from 1:500 to 1:10 (w/w). When doping minimal amounts of SQ, molecularly dispersed SQ in bilayers shows remarkable fluorescence. Interesting, the PA signal is enhanced with increase of SQ in the nanoconfined bilayer region, which is attributed to the formation of SQ-based H-aggregates and enhanced thermal conversion efficiency (?). SQ?L shows satisfactory chemical and thermal stabilities and photobleaching resistance. SQ?L is well-distributed in the cytoplasm of MCF-7 cells and its fluorescence signal remains for 7 days without dramatic quenching owing to the good stability of SQ?L. Furthermore, SQ?L is subjected to in vivo NIR fluorescence imaging to evaluate the whole-body biodistribution in organ level. Particularly, PA imaging with deeper tissue penetration capability is utilized to investigate the heterogeneous distribution SQ?L inside solid tumor. The majority of SQ?L are enriched in the area where the blood vessels are generated, implying that the liposomal nanocarriers exhibit lower tumor tissue penetration capability after the vascular leakage. This result is validated by histological examination of tumor tissue in parallel.
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The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints.
Cancer Discov
PUBLISHED: 11-01-2014
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We examined the immune microenvironment of primary colorectal cancer (CRC) using immunohistochemistry, laser capture microdissection/qRT-PCR, flow cytometry and functional analysis of tumor infiltrating lymphocytes. A subset of CRC displayed high infiltration with activated CD8+ CTL as well as activated Th1 cells characterized by IFN-? production and the Th1 transcription factor Tbet. Parallel analysis of tumor genotypes revealed that virtually all of the tumors with this active Th1/CTL microenvironment had defects in mismatch repair, as evidenced by microsatellite instability (MSI). Counterbalancing this active Th1/CTL microenvironment, MSI tumors selectively demonstrated highly up-regulated expression of multiple immune checkpoints, including five - PD-1, PD-L1, CTLA-4, LAG-3 and IDO - currently being targeted clinically with inhibitors. These findings link tumor genotype with the immune microenvironment, and explain why MSI tumors are not naturally eliminated despite a hostile Th1/CTL microenvironment. They further suggest that blockade of specific checkpoints may be selectively efficacious in the MSI subset of CRC.
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In-situ TEM imaging of the anisotropic etching of graphene by metal nanoparticles.
Nanotechnology
PUBLISHED: 10-31-2014
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Few-layer graphene was successfully tailored with smooth edges along crystallographic directions by Joule heating-driven tungsten nanoparticles inside a transmission electron microscope. The dynamic process was monitored in real time at the atomic resolution level. These high-resolution in-situ observations show that the neighboring graphene layers joined together to form closed edges, which is in contrast to the supposed open edges formed with hydrogen passivation. The tungsten nanoparticles transformed to W2C in the intermediate stage of etching and to WC after etching, suggesting that carbon dissolution helped the continuous action of the metal nanoparticles in the catalytic anisotropic etching reaction.
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Trans-Golgi Network-Located AP1 Gamma Adaptins Mediate Dileucine Motif-Directed Vacuolar Targeting in Arabidopsis.
Plant Cell
PUBLISHED: 10-30-2014
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Membrane proteins on the tonoplast are indispensible for vacuolar functions in plants. However, how these proteins are transported to the vacuole and how they become separated from plasma membrane proteins remain largely unknown. In this study, we used Arabidopsis thaliana vacuolar ion transporter1 (VIT1) as a reporter to study the mechanisms of tonoplast targeting. We showed that VIT1 reached the tonoplast through a pathway involving the endoplasmic reticulum (ER), Golgi, trans-Golgi network (TGN), prevacuolar compartment, and tonoplast. VIT1 contains a putative N-terminal dihydrophobic type ER export signal, and its N terminus has a conserved dileucine motif (EKQTLL), which is responsible for tonoplast targeting. In vitro peptide binding assays with synthetic VIT1 N terminus identified adaptor protein complex-1 (AP1) subunits that interacted with the dileucine motif. A deficiency of AP1 gamma adaptins in Arabidopsis cells caused relocation of tonoplast proteins containing the dileucine motif, such as VIT1 and inositol transporter1, to the plasma membrane. The dileucine motif also effectively rerouted the plasma membrane protein SCAMP1 to the tonoplast. Together with subcellular localization studies showing that AP1 gamma adaptins localize to the TGN, we propose that the AP1 complex on the TGN mediates tonoplast targeting of membrane proteins with the dileucine motif.
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Isolation and Characterization of Sesquiterpenes from Celastrus orbiculatus and Their Antifungal Activities against Phytopathogenic Fungi.
J. Agric. Food Chem.
PUBLISHED: 10-29-2014
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Celastrus orbiculatus is an insecticidal plant belonging to the Celastraceae family. In this survey on the secondary metabolites of plants for obtaining bioactive substances to serve agriculture, the chemical constituents of the fruits of C. orbiculatus were investigated. This phytochemical investigation resulted in the isolation of nine new and one known sesquiterpene. Their structures, especially the complicated stereochemical features, were elucidated on the basis of extensive NMR spectroscopic data analyses, time-dependent density functional theory CD calculations, and the CD exciton chirality method. Biological screenings disclosed that these sesquiterpenes showed antifungal activities against six phytopathogenic fungi. The results of our phytochemical investigation further disclosed the chemical components of C. orbiculatus, and biological screening implied that it may be potentially useful to protect crops against phytopathogenic fungi and the bioactive compounds may be regarded as candidate agents of antifungal agrochemicals for crop protection products.
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Restoration of Autophagy Alleviates Hepatic ER stress and Impaired Insulin Signalling Transduction in High Fructose-Fed Male Mice.
Endocrinology
PUBLISHED: 10-25-2014
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High carbohydrate (mainly fructose) consumption is a major dietary factor for hepatic insulin resistance, involving endoplasmic reticulum (ER) stress and lipid accumulation. As autophagy has been implicated in ER stress, the present study investigated the role of autophagy in high-fructose (HFru) diet induced hepatic ER stress and insulin resistance in male C57BL/6J mice. The results show that chronic HFru feeding induced glucose intolerance and impaired insulin signalling transduction in the liver, associated with ER stress and accumulation of lipids. Intriguingly, hepatic autophagy was suppressed as a result of activation of mammalian target of rapamycin (mTOR). The suppressed autophagy was detected within 6 hours after HFru feeding along with activation of both inositol-requiring enzyme 1 (IRE1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathways. These events occurred prior to lipid accumulation or lipogenesis and were sufficient to blunt insulin signalling transduction with activation of c-Jun N-terminal kinase (JNK)/I?B kinase (IKK) and serine-phosphorylation of insulin receptor substrate 1 (IRS1). Stimulation of autophagy attenuated ER stress and JNK/IKK associated impairment in insulin signalling transduction in an mTOR-independent manner. Taken together, our data suggest that restoration of autophagy functions disrupted by fructose is able to alleviate ER stress and improve insulin signalling transduction.
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Convex Nanobending at a Moving Contact Line: The Missing Mesoscopic Link in Dynamic Wetting.
ACS Nano
PUBLISHED: 10-23-2014
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The morphological information on the very front of a spreading liquid is fundamental to our understanding of dynamic wetting. Debate has lasted for years concerning the nanoscopic local angles and the transition from them to the macroscopic counterpart, ?D. This study of nonvolatile liquids analyzes the interface profile near the advancing contact line using an advanced atomic force microscopy. The interface is found following the macroscopic profile until bending in a convex profile around 20 nm from the substrate. This shoe-tip-like feature is common in partially wetting while absent for completely wetting, and its curvature varies with advancing speed. The observation ends the long-standing debate about the nanoscopic contact angles and their speed dependency. The convex nanobending provides a mesoscopic link and effectively complicates the dynamic wetting behaviors.
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[Neurotrophins up-express in peripheral blood of allergic rhinitis patients and related to Th2 hypothesis].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 10-22-2014
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To detect the expression of NGF, BDNF, NT-3 mRNA in the peripheral blood of patients with allergic rhinitis (AR). And to analyze the correlation between NGF, BDNF, NT-3 mRNA expression and the epidsode of rhinitis through Th-2 Hypothesis.
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Feedback activation of STAT3 mediates trastuzumab resistance via upregulation of MUC1 and MUC4 expression.
Oncotarget
PUBLISHED: 10-21-2014
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Although HER2-targeting antibody trastuzumab confers a substantial benefit for patients with HER2-overexpressing breast and gastric cancer, overcoming trastuzumab resistance remains a large unmet need. In this study, we revealed a STAT3-centered positive feedback loop that mediates the resistance of trastuzumab. Mechanistically, chronic exposure of trastuzumab causes the upregulation of fibronection (FN), EGF and IL-6 in parental trastuzumab-sensitive breast and gastric cells and convergently leads to STAT3 hyperactivation. Activated STAT3 enhances the expression of FN, EGF and IL-6, thus constituting a positive feedback loop which amplifies and maintains the STAT3 signal; furthermore, hyperactivated STAT3 signal promotes the expression of MUC1 and MUC4, consequently mediating trastuzumab resistance via maintenance of persistent HER2 activation and masking of trastuzumab binding to HER2 respectively. Genetic or pharmacological inhibition of STAT3 disrupted STAT3-dependent positive feedback loop and recovered the trastuzumab sensitivity partially due to increased apoptosis induction. Combined trastuzumab with STAT3 inhibition synergistically suppressed the growth of the trastuzumab-resistant tumor xenografts in vivo. Taken together, our results suggest that feedback activation of STAT3 constitutes a key node mediating trastuzumab resistance. Combinatorial targeting on both HER2 and STAT3 may enhance the efficacy of trastuzumab or other HER2-targeting agents in HER2-positive breast and gastric cancer.
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Image quality enhancement and computation acceleration of 3D holographic display using a symmetrical 3D GS algorithm.
Appl Opt
PUBLISHED: 10-17-2014
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The 3D Gerchberg-Saxton (GS) algorithm can be used to compute a computer-generated hologram (CGH) to produce a 3D holographic display. But, using the 3D GS method, there exists a serious distortion in reconstructions of binary input images. We have eliminated the distortion and improved the image quality of the reconstructions by a maximum of 486%, using a symmetrical 3D GS algorithm that is developed based on a traditional 3D GS algorithm. In addition, the hologram computation speed has been accelerated by 9.28 times, which is significant for real-time holographic displays.
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A Randomized, Three-arm Study to Optimize Lamivudine Efficacy in HBeAg Positive Chronic Hepatitis B Patients.
J. Gastroenterol. Hepatol.
PUBLISHED: 10-14-2014
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To compare the efficacy at week 104 of lamivudine monotherapy (MONO), lamivudine plus adefovir dipivoxil (ADV) combination therapy (COMBO), and lamivudine optimization strategy (OPTIMIZE).
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[Survival rate and risk factors of mortality among first-ever stroke patients].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 10-09-2014
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To describe the survival status and to analyze the factors associated with mortality on first-ever stroke patients.
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Morphologically Controlled Synthesis of Porous Spherical and Cubic LaMnO3 with High Activity for the Catalytic Removal of Toluene.
ACS Appl Mater Interfaces
PUBLISHED: 10-07-2014
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A morphology-controlled molten salt route was developed to synthesize porous spherical LaMnO3 and cubic LaMnO3 nanoparticles using the as-prepared porous Mn2O3 spheres as template. The porous LaMnO3 spheres with an average pore size of about 34.7 nm and the cubic LaMnO3 nanoparticles with a good dispersion were confirmed by scanning electron microscope, transmission electron microscope, and N2 adsorption-desorption measurements. The mechanism of morphological transformation from the porous spherical structure to the cubic particle in the molten salt was proposed. The porous spherical LaMnO3 and cubic LaMnO3 catalysts exhibited high catalytic performance for the combustion of toluene, and the latter performed better than the former. Under the conditions of toluene/oxygen molar ratio = 1/400 and space velocity = 20?000 h(-1), the temperature required for 10, 50, and 90% toluene conversion was 110, 170, and 220 °C over the cubic LaMnO3 catalyst, respectively. Based on the results of X-ray photoelectron spectroscopic and hydrogen temperature-programmed reduction characterization, we deduce that the higher surface Mn(4+)/Mn(3+) molar ratio and better low-temperature reducibility enhanced the catalytic performance of cubic LaMnO3. Taking the facile morphology-controlled synthesis and excellent catalytic performance into consideration, we believe that the well-defined morphological LaMnO3 samples are good candidate catalytic materials for the oxidative removal of toluene.
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Stereoselective Synthesis of ?-Linked 2-Deoxy Glycosides Enabled by Visible-Light-Mediated Reductive Deiodination.
Chemistry
PUBLISHED: 10-03-2014
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2-Deoxy sugars and their derivatives occur abundantly in many pharmaceutically important natural products. However, the construction of specific 2-deoxy-glycosidic bonds remains as a challenge. Herein, we report an efficient way to prepare 2-deoxy-?-glycosides by glycosylation of 2-iodo-glycosyl acetate and subsequent visible-light-mediated tin-free reductive deiodination. We have successfully applied the postglycosylational-deiodination strategy in the synthesis of more than 30 mono-, di-, tri-, tetra- and pentadeoxysaccharides with excellent stereoselectivity and efficiency. This method has also been applied to the synthesis of a 2-deoxy-tetrasaccharide containing four ?-linkages.
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Ruthenium-catalyzed double-fold C-H tertiary alkoxycarbonylation of arenes using di-tert-butyl dicarbonate.
Chem. Commun. (Camb.)
PUBLISHED: 10-03-2014
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An efficient ruthenium-catalyzed double-fold C-H alkoxycarbonylation of arenes was developed using di-tert-butyl dicarbonate as the tertiary esterification reagent, which leads to a direct route to valuable 2,6-dicarboxylated products.
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[Application of cervical triangulating stapled anastomosis in minimally invasive esophagectomy].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 10-03-2014
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To explore the safety and feasibility of cervical triangulating stapled anastomosis(TSA) for esophagogastric anastomosis(EGA) after minimally invasive esophagectomy (MIE).
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Optical absorption enhancement in a Si nanohole structure with hexagonal unit cell for solar cell application.
Nanotechnology
PUBLISHED: 09-27-2014
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Periodic hexagonal unit cell silicon nanohole (SiNH) structures with different structural dimensions have been fabricated using polystyrene spheres and investigated in terms of their microstructures and optical reflectance. Compared with a planar Si wafer, such structures exhibit much lower reflectance due to the enhanced scattering introduced by the SiNHs. Optical simulation using the finite element method has also been carried out in order to optimize the structural periodicity and hole diameter for maximum light absorption. The optimum structure is found to have a periodicity of 693 nm and hole diameter of 560 nm, and it yields the highest ultimate efficiency of 28.8%.
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In Vivo Monitoring of Parathyroid Hormone Treatment after Myocardial Infarction in Mice with [68Ga]Annexin A5 and [18F]Fluorodeoxyglucose Positron Emission Tomography.
Mol Imaging
PUBLISHED: 09-25-2014
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Abstract[68Ga]Annexin A5 positron emission tomography (PET) reveals the externalization of phosphatidylserine as a surrogate marker for apoptosis. We tested this technique for therapy monitoring in a murine model of myocardial infarction (MI) including parathyroid hormone (PTH) treatment. MI was induced in mice, and they were assigned to the saline or the PTH group. On day 2, they received [68Ga]annexin A5 PET or histofluorescence TUNEL staining. Mice had 2-deoxy-2-[18F]fluoro-d-glucose (FDG)-PET examinations on days 6 and 30 for calculation of the left ventricular ejection fraction and infarct area. [68Ga]Annexin A5 uptake was 7.4 ± 1.3 %ID/g within the infarction for the controls and 4.5 ± 1.9 %ID/g for the PTH group (p ?=? .013). TUNEL staining revealed significantly more apoptotic cells in the infarct area on day 2 in the controls (64 ± 9%) compared to the treatment group (52 ± 4%; p ?=? .045). FDG-PET revealed a significant decrease in infarct size in the treatment group and an increase in the controls. Examinations of left ventricular ejection fraction on days 6 and 30 did not reveal treatment effects. [68Ga]Annexin A5 PET can detect the effects of PTH treatment as a marker of apoptosis 2 days after MI; ex vivo examination confirmed significant rescue of myocardiocytes. FDG-PET showed a small but significant reduction in infarct size but no functional improvement.
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Synthesis and molecular recognition studies on small-molecule inhibitors for thioredoxin reductase.
J. Med. Chem.
PUBLISHED: 09-24-2014
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Thioredoxin reductase (TrxR), which is overexpressed in many aggressive cancers, plays a crucial role in redox balance and antioxidant function, including defense of oxidative stress, control of cell proliferation, and regulation of cell apoptosis. Deactivation of TrxR can destroy the homeostasis of the cancer cells, inducing elevation of reactive oxygen species (ROS) levels and the oxidation of enzymatic substrates. Here, we synthesized and identified a new gold(I) small molecule (D9) that possesses two strong electron-donating moieties, i.e., 4-methylphenyl alkynyl and thionyldiphenyl phosphine, exhibiting an enhanced p-? conjunction effect. The resulting compound shows the increased soft Lewis acids and the stability of gold(I). And we demonstrated that D9 could efficiently and specifically inhibit the activity of TrxR in vitro and in vivo, and it could effectively avoid the ligand exchange with albumin that was one of the most abundant proteins in blood. We believe that these comprehensive studies on the relationship between the structure and performance will provide inspiring information on the precise synthesis and design of new compounds for targeting TrxR.
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Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock.
J Trauma Acute Care Surg
PUBLISHED: 09-24-2014
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Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss.
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Piecewise cause-specific association analyses of multivariate untied or tied competing risks data.
Int J Biostat
PUBLISHED: 09-23-2014
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Abstract In this paper we extend the bivariate hazard ratio to multivariate competing risks data and show that it is equivalent to the cause-specific cross hazard ratio. Two approaches are proposed to estimate these two equivalent association measures. One extends the plug-in estimator, and the other adapts the pseudo-likelihood estimator for bivariate survival data to multivariate competing risks data. The asymptotic properties of the extended estimators are established by using empirical processes techniques. The extended plug-in and pseudo-likelihood estimators have comparable performance with the existing U-statistic when the data have no tied events. However, in many applications, there are tied events in which all the three estimators are found to produce biased results. To our best knowledge, we are not aware of any association analysis for multivariate competing risks data that has considered tied events. Hence we propose a modified U-statistic to specifically handle tied observations. The modified U-statistic clearly outperforms the other estimators when there are rounding errors. All methods are applied to the Cache County Study to examine mother-child and sibship associations in dementia among this aging population, where the event times are rounded to the nearest integers. The modified U performs consistently with our simulation results and provides more reliable results in the presence of tied events.
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Mn(ii)/O2-promoted oxidative annulation of vinyl isocyanides with boronic acids: synthesis of multi-substituted isoquinolines.
Chem. Commun. (Camb.)
PUBLISHED: 09-20-2014
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An efficient manganese(ii)/O2-promoted oxidative radical cascade reaction was developed for the modular synthesis of multi-substituted isoquinolines from easily accessible vinyl isocyanides and boronic acids.
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[Comparison of 3-hour and 30-minute infusion regimens for meropenem in patients with hospital acquired pneumonia in intensive care unit: a randomized controlled clinical trial].
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
PUBLISHED: 09-19-2014
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To Compare the clinical efficacy and safety of meropenem with a 3-hour extended infusion or conventional 30-minute infusion regimen in treatment of hospital acquired pneumonia (HAP) in intensive care unit (ICU) patients.
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Protective factors in diabetic retinopathy: focus on blood-retinal barrier.
Discov Med
PUBLISHED: 09-18-2014
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The earliest and most significant change in diabetic retinopathy (DR) is blood-retinal barrier (BRB) dysfunction, followed by two main pathologies that may cause severe visual impairment: Diabetic Macular Edema (DME) and Proliferative Diabetic Retinopathy (PDR). The pathological hallmarks of BRB dysfunction include loss of tight junction integrity, VEGF- and AGE-induced damage, oxidative stress, and inflammatory changes. Recently, several BRB protective factors have been reported. Our aim is to give a review of those protective factors and discuss new potential therapeutic targets for DR.
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Morphology variability of radial pulse wave during exercise.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Pulse wave contains much information on a cardiovascular system. Pulse wave variability during exercise is of great significance as it reflects more information combining with pulse wave under stationary state. This paper studied the morphology variability of radial pulse wave during exercise. Radial pulse waves were collected from 30 subjects with two pressure pulse sensors worn at the wrists of the right and left hands, respectively. Electrocardiography (ECG) was also detected synchronously. After data preprocessing and feature point extraction, the variability of several parameters of pulse wave and ECG were analyzed. It is notable that pulse rate (PR) and heart rate (HR) change synchronously. During the exercise period, both systolic phase and diastolic phase of a radial pulse shorten but the latter is more obvious. The amplitude of the dicrotic notch decreases and even turns negative. Aligning the radial pulse waveforms together, the radial pulse waveforms prior to, during and after exercise coincide with each other except for some details like the tidal wave which fades away during exercise.
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A pressure-tolerant polymer microfluidic device fabricated by the simultaneous solidification-bonding method and flash chemistry application.
Lab Chip
PUBLISHED: 09-12-2014
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Pressure-tolerant polymer-glass microfluidic reactors with excellent bonding strength have been fabricated by the simultaneous solidification-bonding (SSB) method, in which a viscous and reactive matrix polymer was cast on the glass substrate with pre-patterned wax as a sacrificial template. Elaborate interfacial chemistry between the matrix polymer and the functionalized glass surface was designed to achieve simultaneous solidification and chemical bonding under UV or/and mild thermal conditions (<200 °C with no pressure). Highly pressure-tolerant microchannels were obtained by complete removal of the liquid wax template at 80 °C. Versatility was demonstrated by fabricating microreactors from various polymers with different interfacial chemistry, which were all stable at 1000 psi with the highest burst pressure of 2000 psi. In particular, the fluoropolymer-glass microreactor can withstand a burst pressure that is two orders of magnitude higher than that of the microchannel made by the conventional method. Finally, the polymer-glass microfluidic device was used for the synthesis of a natural product, tryptanthrin, by flash chemistry under high pressure induced conditions (synthetic yield: 90%, flow rate: 10.5 mL min(-1), reaction time: 14 ms). The transparent microfluidic device can be used as a useful platform for miniaturizing spectroscopic tools for chemical analysis studies under high pressure conditions.
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Association of echocardiographic left ventricular structure and -344C/T aldosterone synthase gene variant: A meta-analysis.
J Renin Angiotensin Aldosterone Syst
PUBLISHED: 09-12-2014
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Aldosterone synthase (CYP11B2) is one of the most studied candidate genes related to essential hypertension (EH) and left ventricular hypertrophy (LVH). Some studies have focused on the relationship between -344C/T polymorphism (rs1799998) in the CYP11B2 gene and LVH, but the results are controversial. This meta-analysis is purposed to reveal the relationship between the -344C/T and the left ventricular structure and function, including left ventricular end diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular mass/left ventricular mass index (LVM/LVMI), left ventricular posterior wall thickness (LVPWT), and interventricular septal wall thickness (IVS).
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Characterization and NO inhibitory activities of chemical constituents from an edible plant Petasites tatewakianus.
J. Agric. Food Chem.
PUBLISHED: 09-12-2014
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Petasites tatewakianus is an edible plant belonging to the family Compositae. In our continuous search for NO inhibitors, which may be useful for the development of anti-inflammatory agents, the chemical constituents of the leaves of the edible plant P. tatewakianus were investigated. This phytochemical investigation led to the isolation of 3 new (1-3) and 10 known (4-13) sesquiterpenes and 2 other types of known compounds (14 and 15). Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses, and the absolute configurations of compounds 1 and 3 were confirmed by comparing their experimental CD spectra with those calculated by the time-dependent density functional theory (TDDFT) method. The following biological studies disclosed that these isolated compounds showed inhibitory activities on LPS-induced NO production in murine microglial BV-2 cells. The results of our phytochemical investigation, including two new bakkenolide sesquiterpenes (1 and 2), one new sesquiterpene with an unusual carbon skeleton (3), and the first report of compounds 5-7 and 10-15 from this species, further revealed the chemical composition of P. tatewakianus as an edible plant, and the biological studies implied that P. tatewakianus, containing bioactive substances with the inhibitory activities of NO production, was potentially beneficial to human health.
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[Expression of indoleamine 2, 3-dioxygenase modulates macrophage polarization in THP-1 cells].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 09-10-2014
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Objective To investigate whether indoleamine 2, 3-dioxygenase (IDO) has an effect on macrophage polarization of differentiated THP-1 (dTHP-1) cells. Methods The macrophage model was established through incubating the human monocyte line (THP-1 cells) with phorbol-12-myristate 13-acetate (PMA) (10 ng/mL) for 48 hours. To generate M1/M2-polarized macrophages, dTHP-1 cells were cultured with IFN-? (100 U/mL) and M-CSF (100 ng/mL), respectively. The expressions of molecular markers of macrophages (including HLA-DR, CCR7, IL-12p35, IL-10, CXCR4) and IDO were examined by real-time quantitative PCR (qRT-PCR), flow cytometry, and Western blotting. To investigate the role of IDO in the dTHP-1 cell polarization, the plasmid pEGFP-N1-IDO and siRNA-IDO were respectively transfected into cells. The mRNA levels of molecular markers of macrophages were examined by qRT-PCR. Results IFN-? could induce the differentiation of THP-1 cells into M1 phenotype and up-regulate the IDO expression. Interestingly, our results also indicated that the ectopic IDO could trigger the transformation of dTHP-1 cells to M2 phenotype. In contrast, the knockdown of IDO expression in dTHP-1 cells resulted in increased M1 markers and lower M2 markers. Conclusion The expression intensity of IDO could modulate macrophage polarization in THP-1 cells.
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Microwave-assisted polyol synthesis of gadolinium-doped green luminescent carbon dots as a bimodal nanoprobe.
Langmuir
PUBLISHED: 09-07-2014
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The development of multimodal nanoprobes is highly desired in medical imaging because it integrates the advantages of multiple imaging modes. In this study, the gadolinium-doped green luminescent carbon dots (Gd-CDs) were prepared by the simple one-step microwave-assisted polyol method. The obtained Gd-CDs emitted a unique green photoluminescence with a quantum yield of 5.4%. The Gd-CDs exhibited a low cytotoxicity and could optically label the C6 glioma cells. Meanwhile, the r1 relaxivity of Gd-CDs was measured to be 11.356 mM(-1) s(-1). This high r1 value together with the r2/r1 ratio close to 1 nominates Gd-CDs as an excellent T1 contrast agent for magnetic resonance imaging. These Gd-CDs combining two complementary imaging modalities are therefore a promising bimodal nanoprobe in medical imaging for a better diagnosis.
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Catalytic, enantioselective sulfenylation of ketone-derived enoxysilanes.
J. Am. Chem. Soc.
PUBLISHED: 09-05-2014
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A catalytic, enantioselective, Lewis base-catalyzed ?-sulfenylation of silyl enol ethers has been developed. To avoid acidic hydrolysis of the silyl enol ether substrates, a sulfenylating agent that did not require additional Brønsted acid activation, namely N-phenylthiosaccharin, was developed. Three classes of Lewis bases-tertiary amines, sulfides, and selenophosphoramides-were identified as active catalysts for the ?-sulfenylation reaction. Among a wide variety of chiral Lewis bases in all three classes, only chiral selenophosphoramides afforded ?-phenylthio ketones in generally high yield and with good enantioselectivity. The selectivity of the reaction does not depend on the size of the silyl group but is highly sensitive to the double bond geometry and the bulk of the substituents on the double bond. The most selective substrates are those containing a geminal bulky substituent on the enoxysilane. Computational analysis revealed that the enantioselectivity arises from an intriguing interplay among sterically guided approach, distortion energy, and orbital interactions.
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In-vivo monitoring of erythropoietin treatment after myocardial infarction in mice with [(68)Ga]Annexin A5 and [ (18)F]FDG PET.
J Nucl Cardiol
PUBLISHED: 09-05-2014
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Several studies substantiate the cardioprotective effects of erythropoietin (EPO). Our goal was to quantify the effects of EPO treatment on the early expression of the apoptosis marker phosphatidylserine as well as on the left ventricular volumes and function by means of small animal PET.
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[Increase expression of neurotrophins mRNA in peripheral blood of patients with allergic rhinitis].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-05-2014
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To assess the expression of NGF, BDNF, NT-3 mRNA in the peripheral blood of patients with allergic rhinitis (AR). Meanwhile, to analysis whether the expression of NGF, BDNF, NT-3 mRNA correlate with the severity of rhinitis.
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Forty years of the war against Ebola.
J Zhejiang Univ Sci B
PUBLISHED: 09-04-2014
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Humans have been fighting against the Ebola virus disease (EVD) since its first outbreak in 1976 in southern Sudan and Yambuku in Zaire which lies on the Ebola River. According to the data from the World Health Organization (WHO, 2014b), the first outbreak claimed 431 lives in 1976, and the disease awoke transiently in Sudan three years later and then disappeared for 15 years afterwards. Following that, large outbreaks appeared in 1995 in Zaire with 250 deaths of people, 2001-2002 in Uganda with 224 deaths, 2002-2003 in Congo with 128 deaths, and 2007 in Congo with 187 deaths. In 2014, the most severe and complicated outbreak swept through the West African countries having already taken 1069 lives, with the situation seeming to be out of control. To date, there have been 15 outbreaks in Africa, which have caused 4362 infected cases and claimed 2659 lives. The pandemics of Ebola show obvious independence from any season. Humans are generally susceptible to the Ebola virus without gender or age variation. The natural reservoir of the Ebola virus still remains unclear. During the past 40 years or so, the EVD disappeared after an outbreak in one region and erupted in another region without any warning. The difficulty in understanding the spreading pattern of Ebola was compared to that of the wave-particle duality of light.
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AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.
N. Engl. J. Med.
PUBLISHED: 09-03-2014
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The androgen-receptor isoform encoded by splice variant 7 lacks the ligand-binding domain, which is the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of androgen-receptor splice variant 7 messenger RNA (AR-V7) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone.
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Acetylcholine Promotes ROS Detoxification Against Hypoxia/reoxygenation-Induced Oxidative Stress Through FoxO3a/PGC-1? Dependent Superoxide Dismutase.
Cell. Physiol. Biochem.
PUBLISHED: 09-02-2014
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Background/Aims: Acetylcholine (ACh) is known to modulate the cardiac redox environment and thereby suppress reactive oxygen species (ROS) generation during oxidative stress. However, there is little information about its regulation on ROS clearance. Here we investigate the beneficial effects of ACh on superoxide dismutase (SOD) as key ROS-detoxifying enzyme system in cultured rat cardiomyoblasts. Methods: H9c2 cells were subjected to hypoxia/reoxygenation (H/R) to mimic oxidative stress. Western blot was used to detect the expression of SOD and related signaling molecules. Specific protein knockdown was performed with siRNA transfection. Results: ACh treatment on the beginning of reoxygenation decreased ROS and apoptosis. ACh increased ATP synthesis and mitochondrial DNA. Furthermore, ACh significantly reversed H/R-induced reduction in protein expressions and activities of SOD. ACh stimulated peroxisome proliferator activated receptor ? co-activator 1? (PGC-1?) and decreased forkhead box subfamily O3a (FoxO3a) phosphorylation. Atropine (muscarinic receptor antagonist) abolished the cytoprotection afforded by ACh. PGC-1? siRNA blocked ACh-induced invigorating effects on SOD2, whereas it did not alter SOD1 and FoxO3a phosphorylation. FoxOSa siRNA drastically decreased the expressions of SOD2 and PGC-1?, while it did not affect SOD1. Conclusion: ACh activates SOD2 within mitochondria through FoxO3a/PGC-1? pathway and up-regulates SOD1 in the cytoplasm, thus protecting against oxidative injury induced by H/R. Our findings provide new insights into mechanisms underlying the cardioprotection of ACh on ROS detoxifying. © 2014 S. Karger AG, Basel.
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[A meta-analysis on the outcomes and potential benefits of hybrid robotic technique in rectal cancer surgery].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 08-29-2014
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To assess the efficacy and potential benefits of hybrid robotic technique in rectal cancer surgery.
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Type II transmembrane domain hydrophobicity dictates the cotranslational dependence for inversion.
Mol. Biol. Cell
PUBLISHED: 08-27-2014
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Membrane insertion by the Sec61 translocon in the endoplasmic reticulum (ER) is highly dependent on hydrophobicity. This places stringent hydrophobicity requirements on transmembrane domains (TMDs) from single-spanning membrane proteins. On examining the single-spanning influenza A membrane proteins, we found that the strict hydrophobicity requirement applies to the Nout-Cin HA and M2 TMDs but not the Nin-Cout TMDs from the type II membrane protein neuraminidase (NA). To investigate this discrepancy, we analyzed NA TMDs of varying hydrophobicity, followed by increasing polypeptide lengths, in mammalian cells and ER microsomes. Our results show that the marginally hydrophobic NA TMDs (?Gapp > 0 kcal/mol) require the cotranslational insertion process for facilitating their inversion during translocation and a positively charged N-terminal flanking residue and that NA inversion enhances its plasma membrane localization. Overall the cotranslational inversion of marginally hydrophobic NA TMDs initiates once ?70 amino acids past the TMD are synthesized, and the efficiency reaches 50% by ?100 amino acids, consistent with the positioning of this TMD class in type II human membrane proteins. Inversion of the M2 TMD, achieved by elongating its C-terminus, underscores the contribution of cotranslational synthesis to TMD inversion.
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Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts.
Chin J Nat Med
PUBLISHED: 08-27-2014
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The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of the total flavonoid C-glycosides isolated from Abrus mollis extracts (AME). In the anti-inflammatory tests, xylene-induced ear edema model in mice and carrageenan-induced paw edema model in rats were applied. The hepatoprotective effects of AME were evaluated with various in vivo models of acute and chronic liver injury, including carbon tetrachloride (CCl4)-induced hepatitis in mice, D-galactosamine (D-GalN)-induced hepatitis in rats, as well as CCl4-induced hepatic fibrosis in rats. In the acute inflammation experiment, AME significantly suppressed xylene-induced ear edema and carrageenan-induced paw edema, respectively. In the acute hepatitis tests, AME significantly attenuated the excessive release of ALT and AST induced by CCl4 and D-GalN. In CCl4-induced hepatic fibrosis model, AME alleviated liver injury induced by CCl4 shown by histopathological sections of livers and improved liver function as indicated by decreased liver index, serum ALT, AST, TBIL, and ALP levels and hydroxyproline contents in liver tissues, and increased serum ALB and GLU levels. These results indicated that AME possesses potent anti-inflammatory activity in acute inflammation models and hepatoprotective activity in both acute and chronic liver injury models. In conclusion, AME is a potential anti-inflammatory and hepatoprotective agent and a viable candidate for treating inflammation, hepatitis, and hepatic fibrosis.
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Dysbindin-1C Is Required for the Survival of Hilar Mossy Cells and the Maturation of Adult Newborn Neurons in Dentate Gyrus.
J. Biol. Chem.
PUBLISHED: 08-25-2014
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DTNBP1 (dystrobrevin-binding protein 1), which encodes dysbindin-1, is one of the leading susceptibility genes for schizophrenia. Both dysbindin-1B and -1C isoforms are decreased, but the dysbindin-1A isoform is unchanged in schizophrenic hippocampal formation, suggesting dysbindin-1 isoforms may have distinct roles in schizophrenia. We found that mouse dysbindin-1C, but not dysbindin-1A, is localized in the hilar glutamatergic mossy cells of the dentate gyrus. The maturation rate of newborn neurons in sandy (sdy) mice, in which both dysbindin-1A and -1C are deleted, is significantly delayed when compared with that in wild-type mice or with that in muted (mu) mice in which dysbindin-1A is destabilized but dysbindin-1C is unaltered. Dysbindin-1C deficiency leads to a decrease in mossy cells, which causes the delayed maturation of newborn neurons. This suggests that dysbindin-1C, rather than dysbindin-1A, regulates adult hippocampal neurogenesis in a non-cell autonomous manner.
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Prevalence, incidence, and comorbidity of clinically diagnosed obsessive-compulsive disorder in Taiwan: A national population-based study.
Psychiatry Res
PUBLISHED: 08-15-2014
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Obsessive-compulsive disorder (OCD) is a chronic debilitating anxiety disorder significant in intrusive thoughts and compensation repetitive behaviors. Few studies have reported on this condition Asia. This study estimated the prevalence, incidence and psychiatric comorbidities of OCD in Taiwan. We identified study subjects for 2000-2008 with a principal diagnosis of OCD according to the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic criteria by using National Health Research Institute database. These patients received either outpatient or inpatient care for their condition. Rates were directly age- and sex-adjusted to the 2004 Taiwan population distribution. The estimated mean annual incidence was 27.57 per 10(5) inhabitants and the one year prevalence was 65.05 per 10(5) inhabitants. Incidence and prevalence increased with age, peaking at age 18-24 years in males and at 35-44 years in females. About 53% of adults (?18 years) and 48% of child and adolescent patients (6-17 years) had one or more comorbid psychiatric conditions. The most common comorbid diagnosis was depressive disorders for both adult and child-adolescent patients. We found a lower prevalence and incidence of clinically diagnosed OCD than that of community studies. Many Asian patients with OCD also had various psychiatric comorbidities, a clinically relevant finding.
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New guaiane sesquiterpenes from Artemisia rupestris and their inhibitory effects on nitric oxide production.
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-08-2014
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Phytochemical investigation of the ethanol extract of the aerial parts of Artemisia rupestris resulted in the isolation of three new guaiane sesquiterpenes, (1R,7R,10S)-1-hydroxy-3-oxoguaia-4,11(13)-dien-12-oic acid (1), (1R,7R,10S)-10-hydroxy-3-oxoguaia-4,11(13)-dien-12-oic acid (2), pechueloic acid 12-O-?-d-glucopyranoside (3), together with 12 known compounds (4-15). The structures of these new compounds were established on the basis of extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation. All isolates were evaluated for their in vitro inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages cells, and the structure-activity relationships were also discussed.
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Sleep Apnea and the Risk of Chronic Kidney Disease: A Nationwide Population-Based Cohort Study.
Sleep
PUBLISHED: 08-06-2014
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Sleep apnea (SA) is characterized by apnea during sleep and is associated with cardiovascular diseases and an increase in all-cause mortality. Chronic kidney disease (CKD) is a global health problem that has placed a substantial burden on healthcare resources. However, the relationship between SA and the incidence of CKD is not clear. This study aimed to determine whether SA is an independent risk factor for the development of CKD.
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The inaccuracy of determining overcrowding status by using the National ED Overcrowding Study Tool.
Am J Emerg Med
PUBLISHED: 08-02-2014
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Emergency department (ED) crowding has become more common, and perceptions of crowding vary among different health care providers. The National Emergency Department Overcrowding Study (NEDOCS) tool is the most commonly used tool to estimate ED crowding but still uncertain of its reliability in different ED settings.
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Storage of Gold Nanoclusters in Muscle Leads to their Biphasic in Vivo Clearance.
Small
PUBLISHED: 07-25-2014
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Ultrasmall gold nanoclusters (Au NCs) show great potential in biomedical applications. Long-term biodistribution, retention, toxicity, and pharmacokinetics profiles are pre-requisites in their potential clinical applications. Here, the biodistribution, clearance, and toxicity of one widely used Au NC species-glutathione-protected Au NCs or GSH-Au NCs-are systematically investigated over a relatively long period of 90 days in mice. Most of the Au NCs are cleared at 30 days post injection (p.i.) with a major accumulation in liver and kidney. However, it is surprising that an abnormal increase of the Au amount in the heart, liver, spleen, lung, and testis is observed at 60 and 90 days p.i., indicating that the injected Au NCs form a V-shaped time-dependent distribution profile in various organs. Further investigations reveal that Au NCs are steadily accumulating in the muscle in the first 30 days p.i., and the as-stored Au NCs gradually release into the blood in 30-90 days p.i., which induces a re-distribution and re-accumulation of Au NCs in all blood-rich organs. Further hematology and biochemistry studies show that the re-accumulation of Au NCs still causes some liver toxicity at 30 days p.i. The muscle storage and subsequent release may give rise to the potential accumulation and toxicity risk of functional nanomaterials over long periods of time.
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Heat shock proteins at the crossroads between cancer and Alzheimer's disease.
Biomed Res Int
PUBLISHED: 07-24-2014
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Heat shock proteins 70 and heat shock proteins 90 (Hsp70/90) have been implicated in many crucial steps of carcinogenesis: stabilizing oncogenic proteins, inhibiting programmed cell death and replicative senescence, induction of tumor angiogenesis, and activation of the invasion and metastasis. Plenty of cancer related proteins have the ability of regulating the expression of Hsp70/90 through heat shock factor 1. Cancer and Alzheimer's disease (AD) have plenty of overlapping regions in molecular genetics and cell biology associated with Hsp70/90. The Hsp70, as a protein stabilizer, has a cellular protection against neurodegeneration of the central nervous system, while Hsp90 promote neurodegenerative disorders indirectly through regulating the expression of Hsp70 and other chaperones. All these make existing anticancer drugs target Hsp70/90 which might be used in AD therapy.
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Research on multirobot pursuit task allocation algorithm based on emotional cooperation factor.
ScientificWorldJournal
PUBLISHED: 07-23-2014
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Multirobot task allocation is a hot issue in the field of robot research. A new emotional model is used with the self-interested robot, which gives a new way to measure self-interested robots' individual cooperative willingness in the problem of multirobot task allocation. Emotional cooperation factor is introduced into self-interested robot; it is updated based on emotional attenuation and external stimuli. Then a multirobot pursuit task allocation algorithm is proposed, which is based on emotional cooperation factor. Combined with the two-step auction algorithm recruiting team leaders and team collaborators, set up pursuit teams, and finally use certain strategies to complete the pursuit task. In order to verify the effectiveness of this algorithm, some comparing experiments have been done with the instantaneous greedy optimal auction algorithm; the results of experiments show that the total pursuit time and total team revenue can be optimized by using this algorithm.
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Effects of gastrokine?2 expression on gastric cancer cell apoptosis by activation of extrinsic apoptotic pathways.
Mol Med Rep
PUBLISHED: 07-21-2014
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Gastrokine?2 is a putative gastric cancer?specific tumor suppressor gene, the loss of which is known to be involved in the development and progression of gastric cancer, and restoration of gastrokine?2 expression inhibits growth of gastric cancer cells in vitro. However, the underlying mechanism of these effects requires elucidation. In the present study, expression patterns of gastrokine?2 protein were examined in gastric cancer tissues and cell lines. Expression of gastrokine?2 was restored in gastric cancer cells in order to assess its effect on cell viability, apoptosis and gene expression. A total of 76 gastric cancer tissues with corresponding normal mucosae samples, and two gastric cancer cell lines (SGC?7901 and AGS) were subjected to western blot analysis of gastrokine?2 expression. SGC?7901 cells were transiently transfected with gastrokine?2 cDNA and then treated with anti?CD95 and/or anti?Fas antibodies prior to analysis of cell viability, apoptosis and gene expression levels. Expression of gastrokine?2 protein was reduced or absent in gastric cancer tissues and gastric cancer cell lines. Following restoration of gastrokine?2 expression, the protein expression level of Fas was significantly increased, but no marked change was observed in the levels of bcl?2 and Bax proteins. Expression of gastrokine?2 protein reduced gastric cancer cell viability and induced apoptosis. Activity of caspase?3 and caspase?8 was increased, but caspase?9 activity remained unchanged in the SGC?7901 cells. Reduction or knockout of gastrokine?2 protein expression may contribute to gastric cancer development or progression, as the current study demonstrated that restoration of gastrokine?2 expression induces apoptosis of gastric cancer cells through the extrinsic apoptosis pathway.
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Pressure overload-induced cardiac hypertrophy response requires janus kinase 2-histone deacetylase 2 signaling.
Int J Mol Sci
PUBLISHED: 07-10-2014
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Pressure overload induces cardiac hypertrophy through activation of Janus kinase 2 (Jak2), however, the underlying mechanisms remain largely unknown. In the current study, we tested whether histone deacetylase 2 (HDAC2) was involved in the process. We found that angiotensin II (Ang-II)-induced re-expression of fetal genes (Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) in cultured cardiomyocytes was prevented by the Jak2 inhibitor AG-490 and HDAC2 inhibitor Trichostatin-A (TSA), or by Jak2/HDAC2 siRNA knockdown. On the other hand, myocardial cells with Jak2 or HDAC2 over-expression were hyper-sensitive to Ang-II. In vivo, pressure overload by transverse aorta binding (AB) induced a significant cardiac hypertrophic response as well as re-expression of ANP and BNP in mice heart, which were markedly reduced by AG-490 and TSA. Significantly, AG-490, the Jak2 inhibitor, largely suppressed pressure overload-/Ang-II-induced HDAC2 nuclear exportation in vivo and in vitro. Meanwhile, TSA or HDAC2 siRNA knockdown reduced Ang-II-induced ANP/BNP expression in Jak2 over-expressed H9c2 cardiomyocytes. Together, these results suggest that HDAC2 might be a downstream effector of Jak2 to mediate cardiac hypertrophic response by pressure overload or Ang-II.
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Infusion of Mesenchymal Stem Cells Protects Lung Transplants from Cold Ischemia-Reperfusion Injury in Mice.
Lung
PUBLISHED: 07-09-2014
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Cold ischemia-reperfusion injury (IRI) is a major cause of graft failure in lung transplantation. Despite therapeutic benefits of mesenchymal stem cells (MSCs) in attenuating acute lung injury, their protection of lung transplants from cold IRI remains elusive. The present study was to test the efficacy of MSCs in the prevention of cold IRI using a novel murine model of orthotopic lung transplantation.
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Characterization of myeloid-specific peroxidase, keratin 8, and dual specificity phosphatase 1 as innate immune genes involved in theresistance of crucian carp (Carassius auratus gibelio) to Cyprinid herpesvirus 2 infection.
Fish Shellfish Immunol.
PUBLISHED: 07-07-2014
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Myeloid-specific peroxidase (MPO), keratin 8 (KRT-8), and dual specificity phosphatase 1 (DUSP-1) are believed to play essential roles in innate immunity. Through suppression subtractive hybridization (SSH) analysis, we previously identified MPO, KRT-8, and DUSP-1 as the three genes that were the most significantly upregulated in crucian carp (Carassius auratus gibelio) that survived Cyprinid herpesvirus 2 (CyHV-2) infection. Here, we have further characterized these three genes and their response to pathogen challenge. The open reading frames (ORF) of MPO, KRT-8, and DUSP-1 were cloned by RACE technique and sequenced. The full-length cDNAs of the three genes contained ORFs of 2,289, 1,575 and 1,083 bp respectively. The polypeptides from each ORF were projected to contain 762 (MPO), 524 (KRT-8), and 360 (DUSP-1) amino acids. Phylogenetic analysis showed that the three genes were most closely related to zebrafish. We found that MPO, KRT-8, and DUSP-1 were expressed at low levels in all of the tissues examined in healthy crucian carp. Quantitative real-time RT-PCR analysis indicated that MPO, KRT-8, and DUSP-1 mRNA expression was significantly upregulated within 72 hours of CyHV-2 infection compared to mock infected controls. Maximum expression of MPO was detected at 24 hpi (2.71-fold, P < 0.05). While, 12 hpi (3.80-fold, P < 0.01) and 6 hpi (8.70-fold, P < 0.01) were the highest expression time points for KRT-8 and DUSP-1, respectively. In contrast, after A. hydrophila challenge, the transcripts of these three genes remained unchanged or slightly down-regulated. For the fish survived from viral infection, expression levels of MPO and KRT-8 were 2.72 fold and 2.47 fold higher than those of fish died from acute infection, and similar level of DUSP-1 was observed in samples of survived fish. These data suggested MPO, KRT-8 and DUSP-1 might be involved in the antiviral, but not antibacterial innate immune response in crucian carp. These findings also support the use of MPO and KRT-8 as immunological markers for a response to viral infection in crucian carp.
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Intercrossed Carbon Nanorings with Pure Surface States as Low-Cost and Environment-Friendly Phosphors for White-Light-Emitting Diodes.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-03-2014
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As an important energy-saving technique, white-light-emitting diodes (W-LEDs) have been seeking for low-cost and environment-friendly substitutes for rare-earth-based expensive phosphors or Pd(2+) /Cd(2+) -based toxic quantum dots (QDs). In this work, precursors and chemical processes were elaborately designed to synthesize intercrossed carbon nanorings (IC-CNRs) with relatively pure hydroxy surface states for the first time, which enable them to overcome the aggregation-induced quenching (AIQ) effect, and to emit stable yellow-orange luminescence in both colloidal and solid states. As a direct benefit of such scarce solid luminescence from carbon nanomaterials, W-LEDs with color coordinate at (0.28, 0.27), which is close to pure white light (0.33, 0.33), were achieved through using these low-temperature-synthesized and toxic ion-free IC-CNRs as solid phosphors on blue LED chips. This work demonstrates that the design of surface states plays a crucial role in exploring new functions of fluorescent carbon nanomaterials.
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TERS Detection of ?V ?3 Integrins in Intact Cell Membranes.
Chemphyschem
PUBLISHED: 07-01-2014
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Integrins are important membrane receptors that form focal adhesions with the extracellular matrix and are transmembrane signaling proteins. We demonstrate that nanoparticles functionalized with c-RGDfC ligands bind to intact cell membranes and selectively enhance the amino acid signals of the integrin receptor when coupled with tip-enhanced Raman scattering (TERS) detection. Controlling the plasmonic interaction between the functionalized nanoparticle and the TERS tip provides a clear Raman signal from ?V ?3 integrins in the cell membrane that matches the signal of the purified integrin receptor. Random aggregation of nanoparticles on the cell does not provide the same spectral information. Chemical characterization of membrane receptors in intact cellular membranes is important for understanding membrane signaling and drug targeting. These results provide a new method to investigate the chemical interactions associated with ligand binding to membrane receptors in cells.
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UFLC/MS-IT-TOF guided isolation of anti-HBV active chlorogenic acid analogues from Artemisia capillaris as a traditional Chinese herb for the treatment of hepatitis.
J Ethnopharmacol
PUBLISHED: 06-10-2014
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Hepatitis B induced by HBV is a serious health problem. Artemisia capillaris (Yin-Chen) has long been used to treat hepatitis in traditional Chinese medicine. Coumarins, flavonoids and organic acids were revealed as its hepatoprotective and choleretic components, but its anti-HBV active components remain unknown. This current study focused on its anti-HBV active constituents by various chromatographic methods.
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Rationally Designed Axially Chiral Diarylethene Switches with High Helical Twisting Power.
Chemistry
PUBLISHED: 05-27-2014
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Three rationally designed axially chiral diarylethene switches were synthesized and their application as chiral dopants for phototunable cholesteric liquid crystal devices was investigated. Design of these molecules was based on the combination of photochromic dithienylcyclopentene core with bridged binaphthyl units as chiral precursors. Aromatic groups were introduced to the molecules at 6,6'-positions of binaphthyls through a Suzuki-Miyaura coupling reaction. Their helical twisting powers (HTPs) are significantly higher than those of the known chiral diarylethenes reported as chiral dopants so far. Photocyclization of these molecules upon light irradiation brought out dramatic variation in HTPs between different states. The primary colors, red, green, and blue, were obtained in reflection on light irradiation and with thermal stability. Moreover, a multi-switchable photodisplay was demonstrated using one of these chiral molecular switches.
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Increased risk of hip fractures in patients with dementia: a nationwide population-based study.
BMC Neurol
PUBLISHED: 05-26-2014
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BackgroundDementia has been associated with an increased risk of hip fracture. However, little research has been conducted on the impact of dementia on wrist or vertebral fracture development. The aim of this study was to investigate whether dementia is a risk factor for different types of fracture in Taiwan.MethodsThe study sample was drawn from Taiwan¿s National Health Insurance Research Database of reimbursement claims, and comprised 1408 patients who visited ambulatory care centers or were hospitalized with a diagnosis of dementia. The comparison group consisted of 7040 randomly selected individuals. Cox proportional hazard regression model was used to examine associations between dementia and the risk of different types of fracture.ResultsDuring a 3-year follow-up period, 264 patients with dementia (18.75%) and 1098 patients without dementia (15.60%) developed fractures. Dementia was independently associated with increased risk of hip fracture [adjusted hazard ratio (HR) 1.92, 95% CI 1.48¿2.49]. Patients with dementia and osteoporosis had the highest risk of developing hip fracture (adjusted HR 2.27, 95% CI 1.28¿4.01). Dementia did not increase wrist fracture or vertebral fracture risk when compared to the control group, even in patients with osteoporosis.ConclusionsIndividuals with dementia are at greater risk of developing hip fracture, particularly if they also have osteoporosis. Early mental screening programs and health education should be initiated to decrease disability and dependence in patients with dementia.
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Drought analysis of the Haihe river basin based on GRACE terrestrial water storage.
ScientificWorldJournal
PUBLISHED: 04-24-2014
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The Haihe river basin (HRB) in the North China has been experiencing prolonged, severe droughts in recent years that are accompanied by precipitation deficits and vegetation wilting. This paper analyzed the water deficits related to spatiotemporal variability of three variables of the gravity recovery and climate experiment (GRACE) derived terrestrial water storage (TWS) data, precipitation, and EVI in the HRB from January 2003 to January 2013. The corresponding drought indices of TWS anomaly index (TWSI), precipitation anomaly index (PAI), and vegetation anomaly index (AVI) were also compared for drought analysis. Our observations showed that the GRACE-TWS was more suitable for detecting prolonged and severe droughts in the HRB because it can represent loss of deep soil water and ground water. The multiyear droughts, of which the HRB has sustained for more than 5 years, began in mid-2007. Extreme drought events were detected in four periods at the end of 2007, the end of 2009, the end of 2010, and in the middle of 2012. Spatial analysis of drought risk from the end of 2011 to the beginning of 2012 showed that human activities played an important role in the extent of drought hazards in the HRB.
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Bioinspired materials: from low to high dimensional structure.
Adv. Mater. Weinheim
PUBLISHED: 04-15-2014
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The surprising properties of biomaterials are the results of billions of years of evolution. Generally, biomaterials are assembled under mild conditions with very limited supply of constituents available for living organism, and their amazing properties largely result from the sophisticated hierarchical structures. Following the biomimetic principles to prepare manmade materials has drawn great research interests in materials science and engineering. In this review, we summarize the recent progress in fabricating bioinspired materials with the emphasis on mimicking the structure from one to three dimensions. Selected examples are described with a focus on the relationship between the structural characters and the corresponding functions. For one-dimensional materials, spider fibers, polar bear hair, multichannel plant roots and so on have been involved. Natural structure color and color shifting surfaces, and the antifouling, antireflective coatings of biomaterials are chosen as the typical examples of the two-dimensional biomimicking. The outstanding protection performance, and the stimuli responsive and self-healing functions of biomaterials based on the sophisticated hierarchical bulk structures are the emphases of the three-dimensional mimicking. Finally, a summary and outlook are given.
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Memantine Alleviates Brain Injury and Neurobehavioral Deficits after Experimental Subarachnoid Hemorrhage.
Mol. Neurobiol.
PUBLISHED: 04-15-2014
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Subarachnoid hemorrhage (SAH) causes brain injury via glutamate excitotoxicity, which leads to an excessive Ca(2+) influx and this starts an apoptotic cascade. Memantine has been proven to reduce brain injury in several types of brain insults. This study investigated the neuro-protective potential of memantine after SAH and explored the underlying mechanisms. An endovascular perforation rat model of SAH was used and Sprague-Dawley rats were randomized into sham surgery, SAH?+?vehicle, and SAH?+?memantine groups. The effects of memantine on SAH were evaluated by assessing the neuro-behavioral functions, blood-brain barrier (BBB) permeability and neuronal cell preservation. The mechanisms of action of memantine, with its N-methyl-D-aspartate (NMDA) antagonistic characteristics on nitric oxide synthase (NOS) expression and peroxynitrite formation, were also investigated. The apoptotic cascade after SAH was suppressed by memantine. Neuronal NOS (nNOS) expression, peroxynitrite formation, and subsequent oxidative/nitrosative stress were also reduced. Memantine effectively preserved BBB integrity, rescued neuronal injury, and improved neurological outcome in experimental SAH. Memantine has neuro-protective potential in experimental SAH and may help combat SAH-induced brain damage in the future.
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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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