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Find video protocols related to scientific articles indexed in Pubmed.
Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B.
N. Engl. J. Med.
PUBLISHED: 11-20-2014
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Background In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity. Methods We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×10(12) vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. Results A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. Conclusions In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00979238 .).
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The small-molecule inhibitor selectivity between IKK? and IKK? kinases in NF-?B signaling pathway.
J. Recept. Signal Transduct. Res.
PUBLISHED: 11-12-2014
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Abstract The enzyme complex I?B kinase (IKK) is an essential activator of NF-?B signaling pathway involved in propagating the cellular response to inflammation. The complex contains two functional subunits IKK? and IKK?, which are structurally conserved kinases and selective inhibition of them would result in distinct biological effects. However, most existing IKK inhibitors show moderate or high promiscuity for the two homologous kinases. Understanding of the molecular mechanism and biological implication underlying the specific interactions in IKK-ligand recognition is thus fundamentally important for the rational design of selective IKK inhibitors. In the current work, we integrated molecular docking, quantum mechanics/molecular mechanics calculation and Poisson-Boltzmann/surface area analysis to investigate the structural basis and energetic property of the selective binding of small-molecule ligands to IKK? and IKK?. It was found that the selectivity is primarily determined by the size and topology difference in ATP-binding pocket of IKK? and IKK? kinase domains; bulky inhibitor molecules commonly have, respectively, low and appropriate affinities towards IKK? and IKK?, and thus exhibit relatively high selectivity for IKK? over IKK?, whereas small ligands can only bind weakly to both the two kinases with low selectivity. In addition, the conformation, arrangement and distribution of residues in IKK pockets are also responsible for constituting the exquisite specificity of ligand binding to KK? and IKK?. Next, a novel quantitative structure-selectivity relationship model was developed to characterize the relative contribution of each kinase residue to inhibitor selectivity and to predict the selectivity and specificity for a number of known IKK inhibitors. Results showed that the active-site residues contribute significantly to the selectivity by directly interacting with inhibitor ligands, while those protein portions far away from the kinase active sites may also play an important role in determining the selectivity through long-range non-bonded forces and indirect allosteric effect.
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Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism.
Biol Open
PUBLISHED: 10-19-2014
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The essential metabolic enzyme CTP synthase (CTPsyn) can be compartmentalised to form an evolutionarily-conserved intracellular structure termed the cytoophidium. Recently, it has been demonstrated that the enzymatic activity of CTPsyn is attenuated by incorporation into cytoophidia in bacteria and yeast cells. Here we demonstrate that CTPsyn is regulated in a similar manner in Drosophila tissues in vivo. We show that cytoophidium formation occurs during nutrient deprivation in cultured cells, as well as in quiescent and starved neuroblasts of the Drosophila larval central nervous system. We also show that cytoophidia formation is reversible during neurogenesis, indicating that filament formation regulates pyrimidine synthesis in a normal developmental context. Furthermore, our global metabolic profiling demonstrates that CTPsyn overexpression does not significantly alter CTPsyn-related enzymatic activity, suggesting that cytoophidium formation facilitates metabolic stabilisation. In addition, we show that overexpression of CTPsyn only results in moderate increase of CTP pool in human stable cell lines. Together, our study provides experimental evidence, and a mathematical model, for the hypothesis that inactive CTPsyn is incorporated into cytoophidia.
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Reconstruction of the gene regulatory network involved in the sonic hedgehog pathway with a potential role in early development of the mouse brain.
PLoS Comput. Biol.
PUBLISHED: 10-01-2014
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The Sonic hedgehog (Shh) signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1- and Shh-Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh-Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1- domain and down-regulates the genes characteristic of the Shh-Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain.
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The Duality of Fgl2 - Secreted Immune Checkpoint Regulator Versus Membrane-Associated Procoagulant: Therapeutic Potential and Implications.
Int. Rev. Immunol.
PUBLISHED: 09-27-2014
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Fibrinogen-like protein 2 (Fgl2), a member of the fibrinogen family, can be expressed as a membrane-associated protein with coagulation activity or in a secreted form possessing unique immune suppressive functions. The biological importance of Fgl2 is evident within viral-induced fibrin depositing inflammatory diseases and malignancies and provides a compelling rationale for Fgl2 expression to not only be considered as a disease biomarker but also as a therapeutic target. This article will provide a comprehensive review of the currently known biological properties of Fgl2 and clarifies future scientific directives.
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Predictive value of indocyanine green retention rate with respect to complications of radiofrequency ablation in 878 patients with hepatocellular carcinoma.
Int J Hyperthermia
PUBLISHED: 09-27-2014
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Radiofrequency ablation (RFA) is a minimally invasive technique used for the treatment of hepatocellular carcinoma (HCC). It may produce complications. The indocyanine green (ICG) retention rate at 15?min (ICGR15) has been used to predict complications after hepatectomy. In this study, the prediction of the value of ICGR15 for complications of RFA to the patients with HCC was evaluated.
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Expression and purification of the trypsin inhibitor from tartary buckwheat in Pichia pastoris and its novel toxic effect on Mamestra brassicae larvae.
Mol. Biol. Rep.
PUBLISHED: 09-16-2014
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The gene of the trypsin inhibitor of tartary buckwheat (Fagopyrum tataricum) was successfully cloned, expressed in Pichia pastoris and tested for regulatory effects on insect growth. The three significant factors were optimized by single-factor experiments and central composite design in response surface methodology. Proteins were efficiently expressed at levels of 489.6-527.4 U/mg in shaken flasks. The trypsin inhibitor from tartary buckwheat (FtTI) was purified by affinity chromatography and centrifugal ultrafiltration. The purified FtTI efficiently inhibited trypsin protease activity by competitive inhibition with a Ki value 1.5 nM. The molecular mass of the purified protein was approximately 13.8 kDa. FtTI had a higher toxic killing effect on Mamestra brassicae larvae. The median lethal concentration for the larvae was 15 ?g/mL.
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Targeted Noninvasive Imaging of EGFR-Expressing Orthotopic Pancreatic Cancer Using Multispectral Optoacoustic Tomography.
Cancer Res.
PUBLISHED: 09-12-2014
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Detection of orthotopic xenograft tumors is difficult due to poor spatial resolution and reduced image fidelity with traditional optical imaging modalities. In particular, light scattering and attenuation in tissue at depths beyond subcutaneous implantation hinder adequate visualization. We evaluate the use of multispectral optoacoustic tomography (MSOT) to detect upregulated epidermal growth factor (EGF) receptor in orthotopic pancreatic xenografts using a near-infrared EGF-conjugated CF-750 fluorescent probe. MSOT is based on the photoacoustic effect and thus not limited by photon scattering, resulting in high-resolution tomographic images. Pancreatic tumor-bearing mice with luciferase-transduced S2VP10L tumors were intravenously injected with EGF-750 probe before MSOT imaging. We characterized probe specificity and bioactivity via immunoblotting, immunocytochemistry, and flow cytometric analysis. In vitro data along with optical bioluminescence/fluorescence imaging were used to validate acquired MSOT in vivo images of probe biodistribution. Indocyanine green dye was used as a nonspecific control to define specificity of EGF-probe accumulation. Maximum accumulation occurred at 6 hours postinjection, demonstrating specific intratumoral probe uptake and minimal liver and kidney off-target accumulation. Optical bioluminescence and fluorescence imaging confirmed tumor-specific probe accumulation consistent with MSOT images. These studies demonstrate the utility of MSOT to obtain volumetric images of ligand probe biodistribution in vivo to detect orthotopic pancreatic tumor lesions through active targeting of the EGF receptor. Cancer Res; 74(21); 6271-9. ©2014 AACR.
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Preparation of multi-shelled conductive polymer hollow microspheres by using Fe?O? hollow spheres as sacrificial templates.
Chem. Commun. (Camb.)
PUBLISHED: 09-06-2014
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Multi-shelled conductive polymer hollow microspheres were successfully generated by using Fe3O4 hollow microspheres as sacrificial templates via a programmed reaction-temperature process. Moreover, the multi-shelled PEDOT microspheres exhibited superb microwave absorption performance.
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Microfluidic platform for the quantitative analysis of leukocyte migration signatures.
Nat Commun
PUBLISHED: 09-03-2014
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Leukocyte migration into tissues is characteristic of inflammation. It is usually measured in vitro as the average displacement of populations of cells towards a chemokine gradient, not acknowledging other patterns of cell migration. Here, we designed and validated a microfluidic migration platform to simultaneously analyse four qualitative migration patterns: chemoattraction, -repulsion, -kinesis and -inhibition, using single-cell quantitative metrics of direction, speed, persistence and fraction of cells responding. We find that established chemokines, complement component 5a and IL-8 induce chemoattraction and repulsion in equal proportions, resulting in the dispersal of cells. These migration signatures are characterized by high persistence and speed and are independent of the chemokine dose or receptor expression. Furthermore, we find that twice as many T lymphocytes migrate away than towards stromal cell-derived factor 1 and their directional migration patterns are not persistent. Overall, our platform helps discover migratory signature responses and uncovers an avenue for precise characterization of leukocyte migration and therapeutic modulators.
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The results of a two-stage double switch operation for congenital corrected transposition of the great arteries with a deconditioned morphologically left ventricle.
Interact Cardiovasc Thorac Surg
PUBLISHED: 08-30-2014
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The purpose of this retrospective study was to evaluate a two-stage double switch operation, morphological left ventricular (mLV) retraining followed by an atrial-arterial switch operation, in the management of patients with congenitally corrected transposition of the great arteries (CCTGA) and a deconditioned mLV.
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CD4(+)Foxp3(+) Tregs protect against innate immune cell-mediated fulminant hepatitis in mice.
Mol. Immunol.
PUBLISHED: 08-25-2014
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Foxp3(+) Tregs play important roles in maintaining homeostasis by suppressing excessive immune responses that result in serious tissue damage; yet, it is largely unknown about the impact of Tregs on innate immune cells in hepatitis models in vivo. In this study, we examined the effect of hepatic Tregs on innate immune-mediated liver injury by using the murine model of polyI:C and d-galactosamine (d-GalN)-induced hepatitis. Administration of polyI:C/d-GalN increased the number of CD4(+)Foxp3(+) Tregs in the liver. Depletion of Tregs leaded to higher levels of proinflammatory cytokine expression and severer liver injury, whereas adoptive transfer of Foxp3(+) Tregs attenuated liver injury in polyI:C/d-GalN-treated mice. In addition, depletion of Tregs leaded to a reduction in TGF-? and IL-10 expression in polyI:C/d-GalN-treated mice. Both of these cytokines were important for suppression of polyI:C/d-GalN-induced liver injury. TGF-? was derived from Tregs. IL-10 was derived from active Kupffer cells, and coincubation of Kupffer cells with Tregs increased IL-10 secretion. Furthermore, TGF-? blockade abrogated Treg-mediated suppression of proinflammatory cytokine production by innate immune cell in vitro.
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RNAi-directed downregulation of betaine aldehyde dehydrogenase 1 (OsBADH1) results in decreased stress tolerance and increased oxidative markers without affecting glycine betaine biosynthesis in rice (Oryza sativa).
Plant Mol. Biol.
PUBLISHED: 08-24-2014
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As an important osmoprotectant, glycine betaine (GB) plays an essential role in resistance to abiotic stress in a variety of organisms, including rice (Oryza sativa L.). However, GB content is too low to be detectable in rice, although rice genome possesses several orthologs coding for betaine aldehyde dehydrogenase (BADH) involved in plant GB biosynthesis. Rice BADH1 (OsBADH1) has been shown to be targeted to peroxisome and its overexpression resulted in increased GB biosynthesis and tolerance to abiotic stress. In this study, we demonstrated a pivotal role of OsBADH1 in stress tolerance without altering GB biosynthesis capacity, using the RNA interference (RNAi) technique. OsBADH1 was ubiquitously expressed in different organs, including roots, stems, leaves and flowers. Transgenic rice lines downregulating OsBADH1 exhibited remarkably reduced tolerance to NaCl, drought and cold stresses. The decrease of stress tolerance occurring in the OsBADH1-RNAi repression lines was associated with an elevated level of malondialdehyde content and hydrogen peroxidation. No GB accumulation was detected in transgene-positive and transgene-negative lines derived from heterozygous transgenic T0 plants. Moreover, transgenic OsBADH1-RNAi repression lines showed significantly reduced seed set and yield. In conclusion, the downregulation of OsBADH1, even though not causing any change of GB content, was accounted for the reduction of ability to dehydrogenate the accumulating metabolism-derived aldehydes and subsequently resulted in decreased stress tolerance and crop productivity. These results suggest that OsBADH1 possesses an enzyme activity to catalyze other aldehydes in addition to betaine aldehyde (the precursor of GB) and thus alleviate their toxic effects under abiotic stresses.
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SpyAvidin hubs enable precise and ultrastable orthogonal nanoassembly.
J. Am. Chem. Soc.
PUBLISHED: 08-21-2014
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The capture of biotin by streptavidin is an inspiration for supramolecular chemistry and a central tool for biological chemistry and nanotechnology, because of the rapid and exceptionally stable interaction. However, there is no robust orthogonal interaction to this hub, limiting the size and complexity of molecular assemblies that can be created. Here we combined traptavidin (a streptavidin variant maximizing biotin binding strength) with an orthogonal irreversible interaction. SpyTag is a peptide engineered to form a spontaneous isopeptide bond to its protein partner SpyCatcher. SpyTag or SpyCatcher was successfully fused to the C-terminus of Dead streptavidin subunits. We were able to generate chimeric tetramers with n (0 ? n ? 4) biotin binding sites and 4-n SpyTag or SpyCatcher binding sites. Chimeric SpyAvidin tetramers bound precise numbers of ligands fused to biotin or SpyTag/SpyCatcher. Mixing chimeric tetramers enabled assembly of SpyAvidin octamers (8 subunits) or eicosamers (20 subunits). We validated assemblies using electrophoresis and native mass spectrometry. Eicosameric SpyAvidin was used to cluster trimeric major histocompatibility complex (MHC) class I:?2-microglobulin:peptide complexes, generating an assembly with up to 56 components. MHC eicosamers surpassed the conventional MHC tetramers in acting as a powerful stimulus to T cell signaling. Combining ultrastable noncovalent with irreversible covalent interaction, SpyAvidins enable a simple route to create robust nanoarchitectures.
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The combined toxicological effects of titanium dioxide nanoparticles and bisphenol A on zebrafish embryos.
Nanoscale Res Lett
PUBLISHED: 08-20-2014
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Environmental pollutants co-exist and exhibit interaction effects that are different from those associated with a single pollutant. As one of the more commonly manufactured nanomaterials, titanium dioxide nanoparticles (TiO2-NPs) are most likely to bind to other contaminants in water. In this paper, we aimed to study the combined toxicological effects of TiO2-NPs and bisphenol A (BPA) on organism. First, in vitro adsorption experiments were conducted to determine the adsorptive interaction between TiO2-NPs and BPA. Second, zebrafish embryo toxicity tests were performed to monitor for changes in the toxicological effects associated with the two chemicals. The study results demonstrated that adsorptive interactions exist between the two chemicals and increased toxicity effects which included an advanced toxicological effect time, decreased survival, increased morphological abnormalities, and delayed embryo hatching. Also, we suggest that the mode of combined action has a synergistic effect. Based on this, we postulate that concomitant exposure to TiO2-NPs and BPA increased BPA bioavailability and uptake into cells and organisms. Further studies are required to understand the mechanisms of interactions of this mixture.
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Controlling catalytic selectivity on metal nanoparticles by direct photoexcitation of adsorbate-metal bonds.
Nano Lett.
PUBLISHED: 08-14-2014
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Engineering heterogeneous metal catalysts for high selectivity in thermal driven reactions typically involves the synthesis of nanostructures with well-controlled geometries and compositions. However, inherent relationships between the energetics of elementary steps limit the control of catalytic selectivity through these approaches. Photon excitation of metal catalysts can induce chemical reactivity channels that cannot be accessed using thermal energy, although the potential for targeted activation of adsorbate-metal bonds is limited because the processes of photon absorption and adsorbate-metal bond photoexcitation are typically separated spatially. Here, we show that the use of sub-5-nanometer metal particles as photocatalysts enables direct photoexcitation of hybridized adsorbate-metal states as the dominant mechanism driving photochemistry. Activation of targeted adsorbate-metal bonds through direct photoexcitation of hybridized electronic states enabled selectivity control in preferential CO oxidation in H2 rich streams. This mechanism opens new avenues to drive selective catalytic reactions that cannot be achieved using thermal energy.
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In vivo and in vitro evaluation of effects of Mg-6Zn alloy on apoptosis of common bile duct epithelial cell.
Biometals
PUBLISHED: 08-09-2014
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Biodegradable magnesium alloy implants have attracted much attention because of their excellent biocompatibility and good mechanical properties. However, effects of Mg alloy on cell apoptosis remain unclear. The aim of this study was to investigate the effects of the Mg-6Zn alloy on the apoptosis and necrosis of common bile duct (CBD) epithelial cells. In the in vitro experiments, primary mouse extrahepatic bile epithelial cells (MEBECs) were exposed to Mg-6Zn alloy extracts with different concentrations (0, 40, 80, and 100 %). Flow cytometry analysis indicated that low concentration Mg-6Zn extract can induce apoptosis of MEBECs, and high concentration Mg-6Zn extracts may relate to necrosis and/or 'apoptotic necrosis'. Real-time PCR results showed that when MEBECs were treated with 40 % extracts for 3 days, the relative apoptotic genes including Bax, Bax/Bcl-2 ratio, NF-?B and caspase-3 were higher than those in the control group. In the in vivo experiments, Mg-6Zn alloy stents were implanted into rabbits' CBD for 1, 2, 3 weeks, respectively. Based on the hematoxylin and eosin (H&E) staining of peri-implant CBD tissue, no apoptotic bodies and necrotic cells were observed. Results of immunohistochemical staining also showed Mg-6Zn stents did not increase expression levels of apoptosis related gene such as Bax, Bcl-2, Bax/Bcl-2 ratio, TNF-?, NF-?B and caspase-3 in CBD, which indicating Mg-6Zn did not induce significant apoptosis in the in vivo experiments. The different results of in vitro and in vivo experiment may result from the low corrosion rate of Mg-6Zn alloy stents in vivo and local Mg(2+) ion concentration in CBD.
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[The unique reflection spectra and IR characteristics of golden-color seawater cultured pearl].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 08-07-2014
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A comparative study on the natural-color golden seawater cultured pearls and the treated-color golden seawater cultured pearls were carried out by UV-Vis reflectance spectra. Furthermore, the frequency variations of v3, v1 , v2 and v4 bands of the aragonites (a crystal form of calcium carbonate) with the positions of nacreous layer and nucleus in natural or treated-color golden-color seawater cultured pearls were firstly systematically measured. The results showed that: (1) based on the results of UV-Vis reflectance spectra of natural or treated-color golden seawater cultured pearls, interestingly, it was firstly found that the natural-color golden one displays slight varied UV-Vis reflection spectra because of its different surface microstructure located on the outer nacreous layer. Meanwhile, according to the characteristic of UV-Vis reflectance spectra of treated-color golden ones, the treated-color ones were firstly classified to four categories. (2) The frequency of v2 band of aragonite in nacreous layer of natural-color or treated-color golden pearls was greater than the other one from theirs corresponding nucleus, namely A clear blue shift was observed in the former. But the other bands were not altered in the positions of nacreous layer and nucleus, and had the same valves with synthetic aragonites. Additionally, the location of absorption bands of aragonite in nacreous layer of natural or treated-color golden pearls had no frequency shift, which indicates that the behavior of color-treating had no effect on the crystal structure of golden pearls.
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Patients' adoption of the e-appointment scheduling service: A case study in primary healthcare.
Stud Health Technol Inform
PUBLISHED: 08-05-2014
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The aim of this study is to investigate patients' initial acceptance and ongoing use of a simple but typical type of consumer e-health service - an e-appointment scheduling (EAS) system - in order to identify facilitators and barriers for patients' adoption of e-health services in primary healthcare. In-depth, semi-structured interviews were conducted to gather patients' background information, their awareness of the system, their feedbacks on the characteristics of the system, and their reasons for use or not use the system. A total of 125 patients aged between 17 and 74 were interviewed. Study results show that 89% of the interviewed patients had shown reluctance to adopt this online service. The identified barriers for acceptance include many patients' lack of access to the internet, lack of awareness of the service, low computer skills and incompatibility of the online appointment service with many patients' habits of face-to-face or phone-call based medical appointment making. Health service providers need to consider the general public's acceptance for online services before implementing consumer e-health systems.
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Two-year prospective case-controlled study of a case management program for community-dwelling individuals with schizophrenia.
Shanghai Arch Psychiatry
PUBLISHED: 07-24-2014
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A community-based rehabilitation program is an essential element of the comprehensive treatment of individuals with schizophrenia.
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Outcomes of coronary transfer for anomalous origin of the left coronary artery from the pulmonary artery†
Eur J Cardiothorac Surg
PUBLISHED: 07-10-2014
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To determine outcomes of patients presenting with an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) who underwent coronary transfer, and to investigate the role of the left ventricular ejection fraction (LVEF) and preoperative myocardial viability as the predictors for incomplete LV functional recovery.
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New multi-target-directed small molecules against Alzheimer's disease: a combination of resveratrol and clioquinol.
Org. Biomol. Chem.
PUBLISHED: 07-03-2014
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Alzheimer's disease (AD) is currently one of the most difficult and challenging diseases to treat. Based on the ‘multi-target-directed ligands’ (MTDLs) strategy, we designed and synthesised a series of new compounds against AD by combining the pharmacophores of resveratrol and clioquinol. The results of biological activity tests showed that the hybrids exhibited excellent MTDL properties: a significant ability to inhibit self-induced ?-amyloid (A?) aggregation and copper(II)-induced A? aggregation, potential antioxidant behaviour (ORAC-FL value of 0.9–3.2 Trolox equivalents) and biometal chelation. Among these compounds, (E)-5-(4-hydroxystyryl)quinoline-8-ol (10c) showed the most potent ability to inhibit self-induced A? aggregation (IC50 = 8.50 ?M) and copper(II)-induced A? aggregation and to disassemble the well-structured A? fibrils generated by self- and copper(II)-induced A? aggregation. Note that 10c could also control Cu(I/II)-triggered hydroxyl radical (OH?) production by halting copper redox cycling via metal complexation, as confirmed by a Cu–ascorbate redox system assay. Importantly, 10c did not show acute toxicity in mice at doses of up to 2000 mg kg?1 and was able to cross the blood–brain barrier (BBB), according to a parallel artificial membrane permeation assay. These results indicate that compound 10c is a promising multifunctional compound for the development of novel drugs for AD.
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Design and fabrication of memory devices based on nanoscale polyoxometalate clusters.
Nature
PUBLISHED: 06-26-2014
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Flash memory devices-that is, non-volatile computer storage media that can be electrically erased and reprogrammed-are vital for portable electronics, but the scaling down of metal-oxide-semiconductor (MOS) flash memory to sizes of below ten nanometres per data cell presents challenges. Molecules have been proposed to replace MOS flash memory, but they suffer from low electrical conductivity, high resistance, low device yield, and finite thermal stability, limiting their integration into current MOS technologies. Although great advances have been made in the pursuit of molecule-based flash memory, there are a number of significant barriers to the realization of devices using conventional MOS technologies. Here we show that core-shell polyoxometalate (POM) molecules can act as candidate storage nodes for MOS flash memory. Realistic, industry-standard device simulations validate our approach at the nanometre scale, where the device performance is determined mainly by the number of molecules in the storage media and not by their position. To exploit the nature of the core-shell POM clusters, we show, at both the molecular and device level, that embedding [(Se(iv)O3)2](4-) as an oxidizable dopant in the cluster core allows the oxidation of the molecule to a [Se(v)2O6](2-) moiety containing a {Se(v)-Se(v)} bond (where curly brackets indicate a moiety, not a molecule) and reveals a new 5+ oxidation state for selenium. This new oxidation state can be observed at the device level, resulting in a new type of memory, which we call 'write-once-erase'. Taken together, these results show that POMs have the potential to be used as a realistic nanoscale flash memory. Also, the configuration of the doped POM core may lead to new types of electrical behaviour. This work suggests a route to the practical integration of configurable molecules in MOS technologies as the lithographic scales approach the molecular limit.
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Abundance and diversity of soybean-nodulating rhizobia in black soil are impacted by land use and crop management.
Appl. Environ. Microbiol.
PUBLISHED: 06-20-2014
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To investigate the effects of land use and crop management on soybean rhizobial communities, 280 nodule isolates were trapped from 7 fields with different land use and culture histories. Besides the known Bradyrhizobium japonicum, three novel genospecies were isolated from these fields. Grassland (GL) maintained a higher diversity of soybean bradyrhizobia than the other cultivation systems. Two genospecies (Bradyrhizobium spp. I and III) were distributed widely in all treatments, while Bradyrhizobium sp. II was found only in GL treatment. Cultivation with soybeans increased the rhizobial abundance and diversity, except for the soybean monoculture (S-S) treatment. In monoculture systems, soybeans favored Bradyrhizobium sp. I, while maize and wheat favored Bradyrhizobium sp. III. Fertilization decreased the rhizobial diversity indexes but did not change the species composition. The organic carbon (OC) and available phosphorus (AP) contents and pH were the main soil parameters positively correlated with the distribution of Bradyrhizobium spp. I and II and Bradyrhizobium japonicum and negatively correlated with Bradyrhizobium sp. III. These results revealed that different land uses and crop management could not only alter the diversity and abundance of soybean rhizobia, but also change interactions between rhizobia and legume or nonlegume plants, which offered novel information about the biogeography of rhizobia.
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Roles of small RNAs in soybean defense against Phytophthora sojae infection.
Plant J.
PUBLISHED: 06-11-2014
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The genus Phytophthora consists of many notorious pathogens of crops and forestry trees. At present, battling Phytophthora diseases is challenging due to a lack of understanding of their pathogenesis. We investigated the role of small RNAs in regulating soybean defense in response to infection by Phytophthora sojae, the second most destructive pathogen of soybean. Small RNAs, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are universal regulators that repress target gene expression in eukaryotes. We identified known and novel small RNAs that differentially accumulated during P. sojae infection in soybean roots. Among them, miR393 and miR166 were induced by heat-inactivated P. sojae hyphae, indicating that they may be involved in soybean basal defense. Indeed, knocking down the level of mature miR393 led to enhanced susceptibility of soybean to P. sojae; furthermore, the expression of isoflavonoid biosynthetic genes was drastically reduced in miR393 knockdown roots. These data suggest that miR393 promotes soybean defense against P. sojae. In addition to miRNAs, P. sojae infection also resulted in increased accumulation of phased siRNAs (phasiRNAs) that are predominantly generated from canonical resistance genes encoding nucleotide binding-leucine rich repeat proteins and genes encoding pentatricopeptide repeat-containing proteins. This work identifies specific miRNAs and phasiRNAs that regulate defense-associated genes in soybean during Phytophthora infection.
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Risk Factors Associated with Prolonged Mechanical Ventilation after Corrective Surgery for Tetralogy of Fallot.
Congenit Heart Dis
PUBLISHED: 06-09-2014
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This study examined early postoperative results to identify perioperative factors that are associated with prolonged mechanical ventilation (PMV) in tetralogy of Fallot (TOF) patients undergoing corrective surgery.
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Systematic review of severe acute liver injury caused by terbinafine.
Int J Clin Pharm
PUBLISHED: 06-04-2014
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Terbinafine is an effective antimicrobial agent against dermatophytes, cryptococcus and other fungi. It is the preferred drug to treat onychomycosis. However, severe acute hepatitis from oral terbinafine administration has been recently reported.
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Expression of the enhancer of zeste homolog 2 in biopsy specimen predicts chemoresistance and survival in advanced non-small cell lung cancer receiving first-line platinum-based chemotherapy.
Lung Cancer
PUBLISHED: 05-30-2014
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Enhancer of zeste homolog 2 (EZH2) plays a key role in tumorigenesis and cancer progression through epigenetic gene silencing and chromatin remodeling. The objective of this study was to investigate the correlation between EZH2 expression and platinum-based chemotherapy response as well as survival of patients with advanced non-small cell lung cancer (NSCLC).
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Non-viral oligonucleotide antimiR-138 delivery to mesenchymal stem cell sheets and the effect on osteogenesis.
Biomaterials
PUBLISHED: 05-25-2014
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Cell-sheet technology has already constituted an important part in the regenerative medicine. Nonetheless, oligonucleotide delivery that has been widely performed on isolated stem cells to foster specific function is rarely conducted on the cell sheets. This study is designed with the two-fold aims of verifying the feasibility of non-viral oligonucleotide delivery for the cell sheets and confirming the osteogenesis enhancing effect of antimiR-138 on the cell sheets composed of bone marrow mesenchymal stem cells (BMSCs). The BMSC sheets are fabricated by a vitamin C inducing method, which can be successfully delivered with the oligonucleotides with a high delivery efficiency of nearly 100% by the properly adapted and optimized Lipofactamine2000 based formulation. The antimiR-138 delivery significantly enhances the in vitro osteogenic differentiation of BMSC sheets, indicated by the higher alkaline phosphatase (ALP) production, denser extracellular matrix mineralization and up-regulated osteogenesis related genes including runt-related transcription factor-2 (RUNX2), osterix, ALP, osteocalcin and bone morphogenetic protein-2 at both mRNA and protein levels, compared to controls. Regarding the underlying mechanism, the antimiR-138 delivery down-regulates the endogenous miR-138 levels in the BMSC sheets, consequently activates the extracellular signal regulated kinases 1/2 pathway and enhances the RUNX2 expression. The in vivo results indicate a robust enhancing effect of the antimiR-138 delivery on the bone regeneration ability of BMSC sheets. Massive bone with good vascularization is regenerated by the antimiR-138 delivered BMSC sheets, showing immense clinical significance for bone defect repair/regeneration applications. More importantly, the feasibility of non-viral oligonucleotide delivery system for the cell sheets as verified by our study shall hold a general significance for the cell sheets of various cell type and therapeutic purposes.
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Comparative functional genomics of adaptation to muscular disuse in hibernating mammals.
Mol. Ecol.
PUBLISHED: 05-23-2014
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Hibernation is an energy-saving adaptation that involves a profound suppression of physical activity that can continue for 6-8 months in highly seasonal environments. While immobility and disuse generate muscle loss in most mammalian species, in contrast, hibernating bears and ground squirrels demonstrate limited muscle atrophy over the prolonged periods of physical inactivity during winter, suggesting that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional programmes that underlie molecular mechanisms preventing muscle loss, we conducted a large-scale gene expression screen in hind limb muscles comparing hibernating and summer-active black bears and arctic ground squirrels using custom 9600 probe cDNA microarrays. A molecular pathway analysis showed an elevated proportion of overexpressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during torpor of hibernation that suggests induction of translation at different hibernation states. The induction of protein biosynthesis probably contributes to attenuation of disuse muscle atrophy through the prolonged periods of immobility of hibernation. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction in multiple genes involved in oxidation-reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation.
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Function of ghrelin and ghrelin receptors in the network regulation of gastric motility.
Mol Med Rep
PUBLISHED: 05-21-2014
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Numerous previous studies have demonstrated that ghrelin promotes gastric motility when administered peripherally. This effect appears to be regulatory but not directly stimulatory, and therefore may involve a number of complex mechanisms. In the periphery, ghrelin may affect gastric motility through intercellular networks among interstitial cells of Cajal, myenteric nerve cells and smooth muscle cells. The aim of the present study was to investigate the effects and possible mechanisms underlying this hypothesis. The effects of ghrelin on the contraction force of gastric antrum smooth muscle strips of rats were studied in the presence or absence of carbachol (CCh), [D?Lys3]?GHRP?6, atropine, tetrodotoxin (TTX) and nimodipine in vitro. The expression of ghrelin receptors (GHS?Rs) on different cell types in gastric muscle layers was observed by means of immunofluorescence. Ghrelin enhanced smooth muscle strip contraction induced by CCh, but when CCh was absent, this effect was eliminated. Atropine and nimodipine eradicated the muscle strip contraction enhanced by ghrelin, while [D?Lys3]?GHRP?6 was only able to partly block this effect and TTX had no effect on muscle strip contraction. It was identified that ghrelin had no effect on the contractive rhythm of the strips. GHS?R1s were located differentially depending on the cell type, including myenteric nerve cells, interstitial cells of Cajal and smooth muscle cells. In conclusion the present study demonstrated that ghrelin may act as an adjuvant to regulate gastric smooth muscle contraction induced by CCh through GHS?R1s, which are expressed on myenteric nerve cells, Cajal cells and smooth muscle cells. Ghrelin may exert its effects by influencing the functional status of different cell types in the gastric muscle layer to subsequently enhance the contractive effect of cholinergic neurotransmitters and enhance gastric motility.
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Protein adsorption behavior and immunoglobulin separation with a mixed-mode resin based on p-aminohippuric acid.
J Sep Sci
PUBLISHED: 05-13-2014
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p-Aminohippuric acid is a newly developed ligand for mixed-mode chromatography with a commercial resin name of Nuvia cPrime. In this study, bovine immunoglobulin G and bovine serum albumin were used as two model proteins, and the adsorption isotherms with Nuvia cPrime were investigated under different pH and salt concentrations. The results showed that pH had a strong but different influence on the adsorption of these two proteins. The adsorption capacity for bovine immunoglobulin G and BSA was 170.4 and 28.1 mg/g at pH 6.0, respectively. Different salts also showed varying effects on the protein adsorption. Moreover, the adsorption and elution behaviors of the two proteins in a column were determined under varying pH and salt concentrations. An optimized process showed that feedstock loaded under pH 6.0 with 0.8 M (NH4)2SO4 and eluted under pH 8.0 with 1.0 M NaCl could effectively purify bovine immunoglobulin G from feedstock containing BSA. The purity of bovine immunoglobulin G could reach 99.8% and the recovery was 92.7%. The results demonstrated that the control of pH and salt addition during the loading and elution processes were two key factors in improving separation efficiency with Nuvia cPrime resin.
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Quantum molecular dynamics study of expanded beryllium: evolution from warm dense matter to atomic fluid.
Sci Rep
PUBLISHED: 05-06-2014
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By performing quantum molecular dynamics (QMD) simulations, we investigate the equation of states, electrical and optical properties of the expanded beryllium at densities two to one-hundred lower than the normal solid density, and temperatures ranging from 5000 to 30000 K. With decreasing the density of Be, the optical response evolves from the one characteristic of a simple metal to the one of an atomic fluid. By fitting the optical conductivity spectra with the Drude-Smith model, it is found that the conducting electrons become localized at lower densities. In addition, the negative derivative of the electrical resistivity on temperature at density about eight lower than the normal solid density demonstrates that the metal to nonmetal transition takes place in the expanded Be. To interpret this transition, the electronic density of states is analyzed systematically. Furthermore, a direct comparison of the Rosseland opacity obtained by using QMD and the standard opacity code demonstrates that QMD provides a powerful tool to validate plasma models used in atomic physics approaches in the warm dense matter regime.
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In vitro and in vivo corrosion measurements of Mg-6Zn alloys in the bile.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 05-06-2014
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Mg-6Zn alloy was studied as candidate biodegradable metallic implants for the common bile duct (CBD) in terms of its in vitro corrosion and in vivo corrosion. Electrochemical measurements, immersion tests and hydrogen evolution were performed in the bile and Hanks' solution to evaluate the in vitro degradation behavior of Mg-6Zn alloy. The results showed that the degradation rate and hydrogen evolution were higher when Mg-6Zn alloy immersed in the bile than in the Hanks' solution. The polarization resistance of the samples in the Hanks' solution was about 1.5 times to that in the bile. In the in vivo experiment, Mg-6Zn alloy stents were inserted in CBD of 42 rabbits, and CT scans, the value of total bilirubin (TB) and in vivo corrosion rate were determined. From the results of CT images and the fluctuations of TB values, it can be seen that the stent was degraded gradually in CBD. After 1 week post-implantation, the majority of the Mg-6Zn alloy sample remained in the CBD. Usually the required support time for CBD stent was approximately 7-10 days, thus the Mg-6Zn alloy stent was very close to the clinical requirement for CBD support materials. After three weeks, the residual weight of the Mg-6Zn alloy was only 9% of the original weight. The in vivo corrosion rate of Mg-6Zn alloy was ~0.107 mm·year(-1), which was much lower than that calculated in vitro (~0.72 mm·year(-1) by electrochemical test). Based on our research, there is promising for the Mg-6Zn alloy in CBD applications.
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Differential developmental requirement and peripheral regulation for dermal V?4 and V?6T17 cells in health and inflammation.
Nat Commun
PUBLISHED: 04-29-2014
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Dermal IL-17-producing ??T cells have a critical role in skin inflammation. However, their development and peripheral regulation have not been fully elucidated. Here we demonstrate that dermal ??T cells develop from the embryonic thymus and undergo homeostatic proliferation after birth with diversified TCR repertoire. V?6T cells are bona fide resident, but precursors of dermal V?4T cells may require extrathymic environment for imprinting skin-homing properties. Thymic V?6T cells are more competitive than V?4 for dermal ??T cell reconstitution and TCR?(-/-) mice reconstituted with V?6 develop psoriasis-like inflammation after IMQ-application. Although both IL-23 and IL-1? promote V?4 and V?6 proliferation, V?4 are the main source of IL-17 production that requires IL-1 signalling. Mice with deficiency of IL-1RI signalling have significantly decreased skin inflammation. These studies reveal a differential developmental requirement and peripheral regulation for dermal V?6 and V?4 ??T cells, implying a new mechanism that may be involved in skin inflammation.
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RNAIII suppresses the expression of LtaS via acting as an antisense RNA in Staphylococcus aureus.
J. Basic Microbiol.
PUBLISHED: 04-25-2014
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RNAIII is known as the key effector of staphylococcal accessory gene regulator (agr) quorum-sensing system, which plays a central role in the pathogenesis of Staphylococcus aureus. As a regulatory RNA, RNAIII regulates multiple targets, including exoproteins and cell-wall-associated proteins. Lipoteichoic acid synthase (LtaS) is involved in the synthesis of lipoteichoic acid (LTA) that is one of the major components of cell wall. The chemical compound targeting to LtaS decreases S. aureus growth via blocking LTA production. Until now, the regulatory mechanism of LtaS expression is still not clear. The level of ltaS mRNA in S. aureus is analyzed by semi-quantitative RT-PCR analysis and qRT-PCR. The protein level of LtaS is determined by Western blotting. The putative interaction sites between RNAIII and LtaS mRNA are predicted. And LtaS-5'UTR-lacZ and LtaS-5'UTR-mutant-lacZ reporter vectors are constructed according to the putative interaction sites. Our data show that the expression of ltaS is regulated by RNAIII in S. aureus. The level of LtaS is significantly higher in the RNAIII deficient strain compared to its parent strain. In the further investigation, 5'UTR of ltaS was predicted to be the putative interaction site of RNAIII. The results of detection of ?-galactosidase activities suggest that RNAIII can inhibit the expression level of LtaS through acting on the 5'UTR region of LtaS mRNA. Our finding presents that LtaS is another target of RNAIII and RNAIII suppresses the expression of LtaS via acting as an antisense RNA in S. aureus.
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A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival.
Int. J. Biochem. Cell Biol.
PUBLISHED: 04-19-2014
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Sox2 overlapping transcript (Sox2ot) is a long noncoding RNA (lncRNA), localized on human chromosome 3q26.33, which is frequently amplified in lung squamous cell carcinomas (SCCs). However, its roles in lung cancer remain under investigation. In this study, we found that Sox2ot was up-regulated over two folds in 53.01% of human primary lung cancers (44/83). The expression level of Sox2ot is significantly higher in SCCs than that in adenocarcinomas (ADCs) of the lung. Further study found high Sox2ot expression predicted poor survival in lung cancer patients (P=0.0053), implying Sox2ot is a novel prognostic factor. In two human lung cancer cell lines, HCC827 and SK-MES-1, knocking down Sox2ot inhibited cell proliferation by inducing G2/M arrest, with a concomitant decrease of cells in S phase. Reduced protein levels of Cyclin B1 and Cdc2 were also observed. Importantly, knocking down Sox2ot decreased EZH2 expression and reintroduction of EZH2 allowed Sox2ot knockdown cells progressed through G2/M phase, which correlates with the restoration of Cyclin B1 and Cdc2 expressions. Altogether, our data suggested that Sox2ot plays an important role in regulating lung cancer cell proliferation, and may represent a novel prognostic indicator for the disease.
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Overexpression of HP1? is associated with poor prognosis in non-small cell lung cancer cell through promoting cell survival.
Tumour Biol.
PUBLISHED: 04-06-2014
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Heterochromatin protein 1? (HP1?), which binds to di- or trimethylated lysine 9 on histone H3 (H3K9), plays an important role in chromatin packaging and gene transcriptional regulation. Recently, HP1? has been implicated in cancer development. However, its clinical relevance and functional role in non-small cell lung cancer (NSCLC) remain elusive. In this study, we found that HP1? expression was elevated in NSCLC samples at the messenger RNA (mRNA) level compared to adjacent normal lung tissues. In a cohort of 108 NSCLC patients, HP1? overexpression is significantly associated with N stage (P?=?0.003), pathological tumor-node-metastasis (TNM) stage (P?=?0.013), smoking status (P?=?0.009), and gender (P?=?0.042). Patients with a high level of HP1? expression showed a poorer overall survival rate than those with low HP1? expression (P?=?0.017). Multivariate analysis revealed that HP1? expression is an independent prognostic marker. We also found knockdown of HP1? in A549 and NCI-H1975 cells induced apoptosis accompanied with suppressed cell proliferation and colony formation. Consistently, pro-apoptotic proteins, Bax and GADD45?, were upregulated in response to HP1? depletion. Altogether, our data suggested that HP1? plays an important role in promoting NSCLC and may represent a novel prognostic biomarker and therapeutic target for the disease.
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Surgical outcomes of 380 patients with double outlet right ventricle who underwent biventricular repair.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 04-03-2014
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The study objective was to report the outcomes of biventricular repair in patients with double outlet right ventricle.
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Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity.
Cell Res.
PUBLISHED: 03-18-2014
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Mediator complex is a molecular hub integrating signaling, transcription factors, and RNA polymerase II (RNAPII) machinery. Mediator MED23 is involved in adipogenesis and smooth muscle cell differentiation, suggesting its role in energy homeostasis. Here, through the generation and analysis of a liver-specific Med23-knockout mouse, we found that liver Med23 deletion improved glucose and lipid metabolism, as well as insulin responsiveness, and prevented diet-induced obesity. Remarkably, acute hepatic Med23 knockdown in db/db mice significantly improved the lipid profile and glucose tolerance. Mechanistically, MED23 participates in gluconeogenesis and cholesterol synthesis through modulating the transcriptional activity of FOXO1, a key metabolic transcription factor. Indeed, hepatic Med23 deletion impaired the Mediator and RNAPII recruitment and attenuated the expression of FOXO1 target genes. Moreover, this functional interaction between FOXO1 and MED23 is evolutionarily conserved, as the in vivo activities of dFOXO in larval fat body and in adult wing can be partially blocked by Med23 knockdown in Drosophila. Collectively, our data revealed Mediator MED23 as a novel regulator for energy homeostasis, suggesting potential therapeutic strategies against metabolic diseases.
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Agmatine protects against zymosan-induced acute lung injury in mice by inhibiting NF-?B-mediated inflammatory response.
Biomed Res Int
PUBLISHED: 02-16-2014
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Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS) disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson's disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM) challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-?, IL-1?, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of I?B and subsequently blocked the activation of nuclear factor (NF)-?B induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-?B signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI.
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Epinephrine enhances the response of macrophages under LPS stimulation.
Biomed Res Int
PUBLISHED: 02-16-2014
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Trauma associated with infection may directly trigger a neuroendocrine reaction in vivo while the hormone epinephrine is known to mediate immune responses to inflammation after injury. However, the role of epinephrine during the earliest stage of trauma still remains unclear. We therefore explored the role of epinephrine on activated macrophages under LPS stimulation in vitro as well as the mechanisms underlying its effect. Dose- and time-dependent effects of epinephrine on macrophage immune function were assessed after LPS activation. We also employed CD14 siRNA interference to investigate whether CD14 played a role in the mechanism underlying the effect of epinephrine on LPS-induced macrophage responses. Our results showed that epinephrine pretreatment (10?ng/mL) significantly promoted immune responses from LPS stimulated macrophages, including phagocytic rate, phagocytic index, TNF?/IL-1?/IL-10 secretion, and CD14 expression (P < 0.05). Moreover, TNF?/IL-1?/IL-10 levels attained their peak value 1 hour after incubation with 10?ng/mL epinephrine (P < 0.05), and CD14 siRNA transfection dramatically decreased phagocytosis and cytokine secretion by LPS-activated macrophages (P < 0.05). We therefore conclude that 10?ng/mL epinephrine enhances immune responses from macrophages under LPS stimulation and that the underlying mechanism may relate to CD14 upregulation on the surface of macrophages.
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Sensitive room-temperature terahertz detection via the photothermoelectric effect in graphene.
Nat Nanotechnol
PUBLISHED: 02-09-2014
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Terahertz radiation has uses in applications ranging from security to medicine. However, sensitive room-temperature detection of terahertz radiation is notoriously difficult. The hot-electron photothermoelectric effect in graphene is a promising detection mechanism; photoexcited carriers rapidly thermalize due to strong electron-electron interactions, but lose energy to the lattice more slowly. The electron temperature gradient drives electron diffusion, and asymmetry due to local gating or dissimilar contact metals produces a net current via the thermoelectric effect. Here, we demonstrate a graphene thermoelectric terahertz photodetector with sensitivity exceeding 10?V?W(-1) (700?V?W(-1)) at room temperature and noise-equivalent power less than 1,100?pW?Hz(-1/2) (20?pW?Hz(-1/2)), referenced to the incident (absorbed) power. This implies a performance that is competitive with the best room-temperature terahertz detectors for an optimally coupled device, and time-resolved measurements indicate that our graphene detector is eight to nine orders of magnitude faster than those. A simple model of the response, including contact asymmetries (resistance, work function and Fermi-energy pinning) reproduces the qualitative features of the data, and indicates that orders-of-magnitude sensitivity improvements are possible.
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IL-30 (IL27p28) attenuates liver fibrosis through inducing NKG2D-rae1 interaction between NKT and activated hepatic stellate cells in mice.
Hepatology
PUBLISHED: 02-07-2014
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Chronic hepatic diseases, such as cirrhosis, hepatocellular carcinoma, and virus-mediated immunopathogenic infections, affect billions of people worldwide. These diseases commonly initiate with fibrosis. Owing to the various side effects of antifibrotic therapy and the difficulty of diagnosing asymptomatic patients, suitable medication remains a major concern. To overcome this drawback, the use of cytokine-based sustained therapy might be a suitable alternative with minimal side effects. Here, we studied the therapeutic efficacy and potential mechanisms of interleukin (IL)-30 as antifibrosis therapy in murine liver fibrosis models. CCl4 or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) 0.1% (wt/wt) Purina 5015 Chow (LabDiet, St. Louis, MO) was fed for 3 weeks to induce liver fibrosis. Either control vector (pCtr) or pIL30 was injected hydrodynamically once per week. A significant decrease in collagen deposition and reduced expression of alpha-smooth muscle actin (?-SMA) protein indicated that IL-30-based gene therapy dramatically reduced bridging fibrosis that was induced by CCl4 or DDC. Immunophenotyping and knockout studies showed that IL-30 recruits natural-killer-like T (NKT) cells to the liver to remove activated hepatic stellate cells (HSCs) significantly and ameliorate liver fibrosis. Both flow cytometric and antibody-mediated neutralization studies showed that liver NKT cells up-regulate the natural killer group 2, member D (NKG2D) ligand and bind with the NKG2D ligand, retinoic acid early inducible 1 (Rae1), and positively activated HSCs to ameliorate liver fibrosis. Furthermore, adoptive transfer of liver NKT cells in T-cell-deficient mice showed reduction of fibrosis upon IL-30 administration. Conclusions: Highly target-specific liver NKT cells selectively remove activated HSCs through an NKG2D-Rae1 interaction to ameliorate liver fibrosis after IL-30 treatment. (Hepatology 2014).
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A multi-center study of using carbon nanoparticles to track lymph node metastasis in T1-2 colorectal cancer.
Surg Endosc
PUBLISHED: 02-07-2014
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How to identify whether T1-2 colorectal cancers have lymph nodes metastases pre-op or intra-op is a crucial problem in clinic. The purpose of this study was to evaluate the feasibility of using carbon nanoparticles to track lymph nodes metastases in T1-2 colorectal cancers.
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Circulating Muscle-specific miRNAs in Duchenne Muscular Dystrophy Patients.
Mol Ther Nucleic Acids
PUBLISHED: 01-15-2014
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Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for Duchenne muscular dystrophy (DMD) patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the serum levels of six muscle-specific miRNAs (miR-1/206/133/499/208a/208b, also known as myomiRs) were all elevated in DMD patients (P < 0.01). The receiver operating characteristic curves of circulating miR-206, miR-499, miR-208b, and miR-133 levels reflected strong separation between Becker's muscular dystrophy (BMD) and DMD patients (P < 0.05). miR-206, miR-499, and miR-208b levels were positively correlated with both age and type IIc muscle fiber content in DMD patients (2-6 years), indicating that they might represent the stage of disease as well as the process of regeneration. miR-499 and miR-208b levels were correlated with slow and fast fiber content and might reflect the ratio of slow to fast fibers in DMD patient (>6 years). Fibroblast growth factor, transforming growth factor-?, and tumor necrosis factor-? could affect the secretion of myomiRs, suggesting that circulating myomiRs might reflect the effects of cytokines and growth factors on degenerating and regenerating muscles. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for DMD diagnosis and disease progression.
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Frequency-specific corticofugal modulation of the dorsal cochlear nucleus in mice.
Front Syst Neurosci
PUBLISHED: 01-01-2014
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The primary auditory cortex (AI) modulates the sound information processing in the lemniscal subcortical nuclei, including the anteroventral cochlear nucleus (AVCN), in a frequency-specific manner. The dorsal cochlear nucleus (DCN) is a non-lemniscal subcortical nucleus but it is tonotopically organized like the AVCN. However, it remains unclear how the AI modulates the sound information processing in the DCN. This study examined the impact of focal electrical stimulation of AI on the auditory responses of the DCN neurons in mice. We found that the electrical stimulation induced significant changes in the best frequency (BF) of DCN neurons. The changes in the BFs were highly specific to the BF differences between the stimulated AI neurons and the recorded DCN neurons. The DCN BFs shifted higher when the AI BFs were higher than the DCN BFs and the DCN BFs shifted lower when the AI BFs were lower than the DCN BFs. The DCN BFs showed no change when the AI and DCN BFs were similar. Moreover, the BF shifts were linearly correlated to the BF differences. Thus, our data suggest that corticofugal modulation of the DCN is also highly specific to frequency information, similar to the corticofugal modulation of the AVCN. The frequency-specificity of corticofugal modulation does not appear limited to the lemniscal ascending pathway.
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A computational approach to estimate interorgan metabolic transport in a mammal.
PLoS ONE
PUBLISHED: 01-01-2014
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In multicellular organisms metabolism is distributed across different organs, each of which has specific requirements to perform its own specialized task. But different organs also have to support the metabolic homeostasis of the organism as a whole by interorgan metabolite transport. Recent studies have successfully reconstructed global metabolic networks in tissues and cell types and attempts have been made to connect organs with interorgan metabolite transport. Instead of these complicated approaches to reconstruct global metabolic networks, we proposed in this study a novel approach to study interorgan metabolite transport focusing on transport processes mediated by solute carrier (Slc) transporters and their couplings to cognate enzymatic reactions. We developed a computational approach to identify and score potential interorgan metabolite transports based on the integration of metabolism and transports in different organs in the adult mouse from quantitative gene expression data. This allowed us to computationally estimate the connectivity between 17 mouse organs via metabolite transport. Finally, by applying our method to circadian metabolism, we showed that our approach can shed new light on the current understanding of interorgan metabolite transport at a whole-body level in mammals.
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A meta-analysis of robotic-assisted pancreatectomy versus laparoscopic and open pancreatectomy.
Saudi Med J
PUBLISHED: 12-18-2013
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To perform a meta-analysis of eligible studies from multiple medical centers to assess the safety, feasibility, and efficacy of robotic-assisted pancreatectomy (RP).
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Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NF?B Signaling.
Integr Cancer Ther
PUBLISHED: 11-27-2013
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Pao extract, derived from bark of Amazonian tree Pao Pereira, is commonly used in South American medicine. A recent study showed that Pao extract repressed androgen-dependent LNCaP prostate cancer cell growth. We hypothesize that Pao extract asserts its anticancer effects on metastatic castration-resistant prostate cancer (CRPC) cells. Pao extract suppressed CRPC PC3 cell growth in a dose- and time-dependent manner, through induction of apoptosis and cell cycle arrest. Pao extract treatment induced cell cycle inhibitors, p21 and p27, and repressed PCNA, Cyclin A and Cyclin D1. Furthermore, Pao extract also induced the upregulation of pro-apoptotic Bax, reduction of anti-apoptotic Bcl-2, Bcl-xL, and XIAP expression, which were associated with the cleavage of PARP protein. Moreover, Pao extract treatment blocked PC3 cell migration and invasion. Mechanistically, Pao extract suppressed phosphorylation levels of AKT and NF?B/p65, NF?B DNA binding activity, and luciferase reporter activity. Pao inhibited TNF?-induced relocation of NF?B/p65 to the nucleus, NF?B/p65 transcription activity, and MMP9 activity as shown by zymography. Consistently, NF?B/p65 downstream targets involved in proliferation (Cyclin D1), survival (Bcl-2, Bcl-xL, and XIAP), and metastasis (VEGFa, MMP9, and GRO?/CXCL1) were also downregulated by Pao extract. Finally, forced expression of NF?B/p65 reversed the growth inhibitory effect of Pao extract. Overall, Pao extract induced cell growth arrest, apoptosis, partially through inhibiting NF?B activation in prostate cancer cells. These data suggest that Pao extract may be beneficial for protection against CRPC.
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Hampering immune suppressors: therapeutic targeting of myeloid-derived suppressor cells in cancer.
Cancer J
PUBLISHED: 11-26-2013
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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with suppressive properties that preferentially expand in cancer. Myeloid-derived suppressor cells mainly suppress T-cell proliferation and cytotoxicity, inhibit natural killer cell activation, and induce the differentiation and expansion of regulatory T cells. The wide spectrum of MDSC suppressive activity in cancer and its role in tumor progression have rendered these cells a promising target for effective cancer immunotherapy. In this review we briefly discuss the origin of MDSCs and their main mechanisms of suppression and focus more on the approaches developed up to date targeting of MDSCs in tumor-bearing animals and cancer patients.
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Supercapacitors based on graphene-supported iron nanosheets as negative electrode materials.
ACS Nano
PUBLISHED: 11-19-2013
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We report a facile strategy to prepare iron nanosheets directly grown on graphene sheets nanocomposite (C-PGF) through the carbonization of iron ions adsorbed onto polyaniline nanosheet/graphene oxide hybrid material. Because of the synergistic effect of iron nanosheets and graphene sheets, the as-obtained C-PGF exhibits an ultrahigh capacitance of ca. 720 F g(-1) in 6 M KOH aqueous solution. Additionally, the assembled asymmetric supercapacitor (C-PGF//Ni(OH)2/CNTs) delivers a remarkable high power density and a noticeable ultrahigh energy density of ca. 140 Wh kg(-1) (based on the total mass of active materials) and an acceptable cycling performance of 78% retention after 2000 cycles. Therefore, the designed supercapacitors with high energy density, comparable to rechargeable lithium-ion batteries (LIBs), offer an important guideline for future design of advanced next-generation supercapacitors for both industrial and consumer applications.
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Postoperative diaphragmatic paralysis after cardiac surgery in children: incidence, diagnosis and surgical management.
Chin. Med. J.
PUBLISHED: 11-16-2013
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Cardiac surgery for congenital heart disease covers a wide spectrum from simple to complex cardiac and extracardiac malformations. Innovations in pediatric cardiac surgery and perioperative care over the past decades have allowed surgical correction or at least palliation in almost all complex congenital heart defects in the first years of life. Diaphragmatic paralysis (DP) due to phrenic nerve injury after congenital cardiac surgery is an important respiratory complication resulting with respiratory insufficiency, lung infections, prolonged hospital stay time and even death.
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Identification and environmental distribution of dcpA encoding the 1,2-dichloropropane-to-propene reductive dehalogenase in organohalide-respiring Chloroflexi.
Appl. Environ. Microbiol.
PUBLISHED: 11-15-2013
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Dehalococcoides mccartyi (Dhc) strains KS and RC grow with 1,2-dichloropropane (1,2-D) as an electron acceptor in enrichment cultures derived from hydrocarbon-contaminated and pristine river sediments, respectively. Transcription, expression, enzymatic and PCR analyses implicated the reductive dehalogenase gene dcpA in 1,2-D dichloroelimination to propene and inorganic chloride. Quantitative real-time PCR (qPCR) analyses demonstrated Dhc cell increase during growth with 1,2-D and suggested that both Dhc strains carried a single dcpA gene copy per genome. Dhc strain RC and strain KS produced 1.8 ± 0.1 x 10(7) and 1.4 ± 0.5 x 10(7) cells per ?mole of propene formed, respectively. The dcpA gene was identified in 1,2-D-to-propene-dechlorinating microcosms established with sediment samples collected from different geographical locations in Europe and North and South America. Clone library analysis revealed two distinct dcpA phylogenetic clusters, both of which the dcpA gene-targeted qPCR assay captured, suggesting the qPCR assay is useful for site assessment and bioremediation monitoring at 1,2-D-contaminated sites.
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Synthesis and Evaluation of Multi-Target-Directed Ligands against Alzheimers Disease Based on the Fusion of Donepezil and Ebselen.
J. Med. Chem.
PUBLISHED: 11-12-2013
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A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimers disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 ?M for Electrophorus electricus acetylcholinesterase and 0.097 ?M for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 ?M), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (?0 = 123.5 ?M min(-1)), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system.
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Adiponectin decreases lipids deposition by p38 MAPK/ATF2 signaling pathway in muscle of broilers.
Mol. Biol. Rep.
PUBLISHED: 10-25-2013
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Adiponectin is an adipokine hormone that influences glucose utilization, insulin sensitivity and energy homeostasis. To investigate the effect of adiponectin on lipids deposition in broilers, rosiglitazone and dexamethasone were used to treat broilers. A total of 120 twenty-three-day-old male Cobb broilers were randomly divided into 3 groups for 3 weeks of drug treatment. Serum adiponectin level and fatty acid composition in muscles were measured. Adiponectin, adiponectin receptors (adipoR1, adipoR2) and lipid metabolism-related genes expression levels in muscles were measured using real-time PCR. Western blot was used to measure the expression levels of lipid metabolism-related proteins and the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK)/activating transcription factor 2 (ATF2) pathway marker proteins. Rosiglitazone increased serum adiponectin concentration and the expression levels of adiponectin and adipoR1 (P < 0.05), while dexamethasone had the opposite effect. Intramuscular fat content, total fatty acid, saturated fatty acid and monounsaturated fatty acid reduced in the rosiglitazone treatment group (P < 0.05). In the rosiglitazone treatment group, the expression levels of lipogenic genes and proteins decreased in the muscles, whereas the expression levels of lipolysis genes increased. Meanwhile, the phosphorylation levels of p38MAPK and ATF2 increased with supplementation of rosiglitazone and decreased in the dexamethasone treatment group (P < 0.01). These results indicated that rosiglitazone and dexamethasone could regulate adiponectin expression in muscle of broilers and adiponectin had an anti-lipogenic effect by p38 MAPK/ATF2 signaling pathway.
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PyDPI: Freely Available Python Package for Chemoinformatics, Bioinformatics, and Chemogenomics Studies.
J Chem Inf Model
PUBLISHED: 10-24-2013
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The rapidly increasing amount of publicly available data in biology and chemistry enables researchers to revisit interaction problems by systematic integration and analysis of heterogeneous data. Herein, we developed a comprehensive python package to emphasize the integration of chemoinformatics and bioinformatics into a molecular informatics platform for drug discovery. PyDPI (drug-protein interaction with Python) is a powerful python toolkit for computing commonly used structural and physicochemical features of proteins and peptides from amino acid sequences, molecular descriptors of drug molecules from their topology, and protein-protein interaction and protein-ligand interaction descriptors. It computes 6 protein feature groups composed of 14 features that include 52 descriptor types and 9890 descriptors, 9 drug feature groups composed of 13 descriptor types that include 615 descriptors. In addition, it provides seven types of molecular fingerprint systems for drug molecules, including topological fingerprints, electro-topological state (E-state) fingerprints, MACCS keys, FP4 keys, atom pair fingerprints, topological torsion fingerprints, and Morgan/circular fingerprints. By combining different types of descriptors from drugs and proteins in different ways, interaction descriptors representing protein-protein or drug-protein interactions could be conveniently generated. These computed descriptors can be widely used in various fields relevant to chemoinformatics, bioinformatics, and chemogenomics. PyDPI is freely available via https://sourceforge.net/projects/pydpicao/ .
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Quantum molecular dynamics simulations of the thermophysical properties of shocked liquid ammonia for pressures up to 1.3 TPa.
J Chem Phys
PUBLISHED: 10-15-2013
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We investigate via quantum molecular-dynamics simulations the thermophysical properties of shocked liquid ammonia up to the pressure 1.3 TPa and temperature 120,000 K. The principal Hugoniot is predicted from the wide-range equation of state, which agrees well with the available experimental measurements up to 64 GPa. Our systematic study of the structural properties demonstrates that the liquid ammonia undergoes a gradual phase transition along the Hugoniot. At about 4800 K, the system transforms into a metallic, complex mixture state consisting of NH3, N2, H2, N, and H. Furthermore, we discuss the implications for the interiors of Uranus and Neptune.
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Physiological Correspondence Dictates Cortical Long-Term Potentiation and Depression by Thalamic Induction.
Cereb. Cortex
PUBLISHED: 09-19-2013
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The auditory cortex exhibits frequency-specific plasticity over a life cycle. Although thalamocortical long-term potentiation (LTP) and depression (LTD) are components of a widely held model underlying the receptive field (RF) plasticity of cortical neurons, the model lacks direct supporting evidence. We show here that conventional high-frequency tetanic stimulation (TS) of the auditory thalamus induced long-term changes in cortical field excitatory postsynaptic potentials, including both LTP and LTD, in mice. Thalamic TS induced LTP when the stimulated thalamic and recorded cortical neurons were tuned to the same frequency and induced LTD when they were tuned to different frequencies. The thalamocortical LTP was N-methyl-d-aspartate-dependent, but the LTD also involved cortical ?-amino-butyric acidergic inhibition. Notably, the frequency-specificity of cortical LTP/LTD was in accordance with the frequency-specific plasticity of spike-based RFs of cortical neurons. Our results suggest that cortical LTP and LTD induced by thalamic induction can be a consequence of identical stimuli, occur in an input-specific manner, and account for frequency-specific remodeling of RFs of auditory cortical neurons.
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A redox-triggered structural rearrangement in an iodate-templated polyoxotungstate cluster cage.
Chem. Commun. (Camb.)
PUBLISHED: 09-12-2013
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The new tungstatoiodate, ?-[H5W18O59(IO3)](6-), containing I(V)O3(-) within a {W18O54} metal oxide framework has been prepared and shown by X-ray crystallography and mass spectrometry to be derived from the fully oxidised [H3W18O56(IO6)](6-) by two-electron reduction accompanied by a redox-triggered structural rearrangement where three I-O covalent bonds are broken.
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Using random forest to classify T-cell epitopes based on amino acid properties and molecular features.
Anal. Chim. Acta
PUBLISHED: 08-27-2013
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T-lymphocyte (T-cell) is a very important component in human immune system. T-cell epitopes can be used for the accurately monitoring the immune responses which activation by major histocompatibility complex (MHC), and rationally designing vaccines. Therefore, accurate prediction of T-cell epitopes is crucial for vaccine development and clinical immunology. In current study, two types peptide features, i.e., amino acid properties and chemical molecular features were used for the T-cell epitopes peptide representation. Based on these features, random forest (RF) algorithm, a powerful machine learning algorithm, was used to classify T-cell epitopes and non-T-cell epitopes. The classification accuracy, sensitivity, specificity, Matthews correlation coefficient (MCC), and area under the curve (AUC) values for proposed method are 97.54%, 97.22%, 97.60%, 0.9193, and 0.9868, respectively. These results indicate that current method based on the combined features and RF is effective for T-cell epitopes prediction.
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Comparison of gene expression profiles and related pathways in chronic thromboembolic pulmonary hypertension.
Int. J. Mol. Med.
PUBLISHED: 08-22-2013
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Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the main causes of severe pulmonary hypertension. However, despite treatment (pulmonary endarterectomy), in approximately 15-20% of patients, pulmonary vascular resistance and pulmonary arterial pressure continue to increase. To date, little is known about the changes that occur in gene expression in CTEPH. The identification of genes associated with CTEPH may provide insight into the pathogenesis of CTEPH and may aid in diagnosis and treatment. In this study, we analyzed the gene expresion profiles of pulmonary artery endothelial cells from 5 patients with CTEPH and 5 healthy controls using oligonucleotide microarrays. Bioinformatics analyses using the Gene Ontology (GO) and KEGG databases were carried out to identify the genes and pathways specifically associated with CTEPH. Signal transduction networks were established to identify the core genes regulating the progression of CTEPH. A number of genes were found to be differentially expressed in the pulmonary artery endothelial cells from patients with CTEPH. In total, 412 GO terms and 113 pathways were found to be associated with our list of genes. All differential gene interactions in the Signal-Net network were analyzed. JAK3, GNA15, MAPK13, ARRB2 and F2R were the most significantly altered. Bioinformatics analysis may help gather and analyze large amounts of data in microarrays by means of rigorous experimental planning, scientific statistical analysis and the collection of complete data. In this study, a novel differential gene expression pattern was constructed. However, further studies are required to identify novel targets for the diagnosis and treatment of CTEPH.
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EZH2 regulates cancer cell migration through repressing TIMP-3 in non-small cell lung cancer.
Med. Oncol.
PUBLISHED: 08-10-2013
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Histone methylations play important roles in human cancer metastasis. Enhancer of zeste homolog 2 (EZH2) is a key component of the polycomb repressor complex 2, which is responsible for histone H3K27 methylation. EZH2 is overexpressed in lung cancer and epigenetically silences tumor suppressor genes. Here, we showed that EZH2 was up-regulated in lung cancer and had a positive correlation with pathologic stage, nodal involvement in lung cancer patients. Moreover, overexpression of EZH2 was correlated with reduced tissue inhibitor of metalloproteinase-3 (TIMP-3) expression, which was shown to be negatively associated with tumor metastasis. Of note, overall survival time of patients with high EZH2/low TIMP-3 expression was significantly shorter than that of patients with low EZH2/high TIMP-3 (P = 0.031). RNA interfering and pharmacologic inhibition of EZH2 reduced histone H3 lysine 27 tri-methylation level and increased TIMP-3 expression level. Knockdown of EZH2 by siRNA significantly reduced A549 cancer cell migration. In contrast, reduction of TIMP-3 in A549 cells partially rescued EZH2 deficiency-induced loss of cell migration capacity. Taken together, our findings indicate that EZH2 accelerates cancer cell migration, in part, via the repression of TIMP-3 expression, suggesting a potential mechanism by which EZH2 promotes lung cancer progression and metastasis.
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The evolutionary analysis reveals domain fusion of proteins with Frizzled-like CRD domain.
Gene
PUBLISHED: 07-16-2013
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Frizzleds (FZDs) are transmembrane receptors in the Wnt signaling pathway and they play pivotal roles in developments. The Frizzled-like extracellular Cysteine-rich domain (Fz-CRD) has been identified in FZDs and other proteins. The origin and evolution of these proteins with Fz-CRD is the main interest of this study. We found that the Fz-CRD exists in FZD, SFRP, RTK, MFRP, CPZ, CORIN, COL18A1 and other proteins. Our systematic analysis revealed that the Fz-CRD domain might have originated in protists and then fused with the Frizzled-like seven-transmembrane domain (7TM) to form the FZD receptors, which duplicated and diversified into about 11 members in Vertebrates. The SFRPs and RTKs with the Fz-CRD were found in sponge and expanded in Vertebrates. Other proteins with Fz-CRD may have emerged during Vertebrate evolution through domain fusion. Moreover, we found a glycosylation site and several conserved motifs in FZDs, which may be related to Wnt interaction. Based on these results, we proposed a model showing that the domain fusion and expansion of Fz-CRD genes occurred in Metazoa and Vertebrates. Our study may help to pave the way for further research on the conservation and diversification of Wnt signaling functions during evolution.
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A randomised, controlled trial comparing the long-term effects of peripherally inserted central catheter placement in chemotherapy patients using B-mode ultrasound with modified Seldinger technique versus blind puncture.
Eur J Oncol Nurs
PUBLISHED: 07-14-2013
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To compare the effects of peripherally inserted central venous catheter (PICC) placement using B-mode ultrasound with the modified Seldinger technique (BUMST) versus the blind puncture.
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Evolution, functional divergence and conserved exon-intron structure of bHLH/PAS gene family.
Mol. Genet. Genomics
PUBLISHED: 07-11-2013
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bHLH/PAS genes encode a family of basic helix-loop-helix (bHLH) transcription factors with bHLH, PAS and PAS_3 domain. bHLH/PAS genes are involved in many essential physiological and developmental processes, such as hypoxic response neural development, the circadian clock, and learning ability. Despite their important functions, the origin and evolution of this bHLH/PAS gene family has yet to be elucidated. In this study, we aim to explore the origin, evolution, gene structure conservation of this gene family and provide a model to analyze the evolution of other gene families. Our results show that genes of the bHLH/PAS family only exist in metazoans. They may have originated from the common ancestor of metazoans and expanded into vertebrates. We identified bHLH/PAS genes in more than ten species representing the main lineages and constructed the phylogenetic trees (Beyasian, ML and NJ) to classify them into three groups. The exon-intron structure analysis revealed that a relatively conserved "1001-0210" eight-exon structure exists in most groups and lineages. In addition, we found the exon fusion pattern in several groups in this conserved eight-exon structure. Further analysis indicated that bHLH/PAS protein paralogs evolved from several gene duplication events followed by functional divergence and purifying selection. We presented a phylogenetic model to describe the evolutionary history of the exon structures of bHLH/PAS genes. Taken together, our study revealed the evolutionary model, functional divergence and gene structure conservation of bHLH/PAS genes. These findings provide clues for the functional and evolutionary mechanism of bHLH/PAS genes.
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Increased expression of the adult stem cell marker Musashi-1 in the ectopic endometrium of adenomyosis does not correlate with serum estradiol and progesterone levels.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 07-09-2013
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To investigate whether abnormal expression of Musashi-1 occurs in eutopic and ectopic endometria from patients with adenomyosis and whether it is correlated with serum estradiol or progesterone levels.
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The Ginger-shaped Asteroid 4179 Toutatis: New Observations from a Successful Flyby of Change-2.
Sci Rep
PUBLISHED: 07-03-2013
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On 13 December 2012, Change-2 conducted a successful flyby of the near-Earth asteroid 4179 Toutatis at a closest distance of 770 ± 120 meters from the asteroids surface. The highest-resolution image, with a resolution of better than 3 meters, reveals new discoveries on the asteroid, e.g., a giant basin at the big end, a sharply perpendicular silhouette near the neck region, and direct evidence of boulders and regolith, which suggests that Toutatis may bear a rubble-pile structure. Toutatis maximum physical length and width are (4.75 × 1.95?km) ±10%, respectively, and the direction of the +z axis is estimated to be (250 ± 5°, 63 ± 5°) with respect to the J2000 ecliptic coordinate system. The bifurcated configuration is indicative of a contact binary origin for Toutatis, which is composed of two lobes (head and body). Change-2 observations have significantly improved our understanding of the characteristics, formation, and evolution of asteroids in general.
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An X-chromosomal association study identifies a susceptibility locus at Xq22.1 for hepatitis B virus-related hepatocellular carcinoma.
Clin Res Hepatol Gastroenterol
PUBLISHED: 06-24-2013
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Genetic epidemiological data in hepatocellular carcinoma (HCC) pedigrees indicate a pattern of X-linked recessive inheritance of HCC susceptibility genes. This study is designed to test the hypothesis that there are genes conferring susceptibility to HCC located on the X-chromosome.
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What is Visualize?

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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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.