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Find video protocols related to scientific articles indexed in Pubmed.
Graphene cover-promoted metal-catalyzed reactions.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-19-2014
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Graphitic overlayers on metals have commonly been considered as inhibitors for surface reactions due to their chemical inertness and physical blockage of surface active sites. In this work, however, we find that surface reactions, for instance, CO adsorption/desorption and CO oxidation, can take place on Pt(111) surface covered by monolayer graphene sheets. Surface science measurements combined with density functional calculations show that the graphene overlayer weakens the strong interaction between CO and Pt and, consequently, facilitates the CO oxidation with lower apparent activation energy. These results suggest that interfaces between graphitic overlayers and metal surfaces act as 2D confined nanoreactors, in which catalytic reactions are promoted. The finding contrasts with the conventional knowledge that graphitic carbon poisons a catalyst surface but opens up an avenue to enhance catalytic performance through coating of metal catalysts with controlled graphitic covers.
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Cauda equina-derived extracellular matrix for fabrication of nano-structured hybrid scaffolds applied to neural tissue engineering.
Tissue Eng Part A
PUBLISHED: 11-05-2014
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Extracellular matrix (ECM) components have become important candidate materials as neural scaffolds for neural tissue engineering. In this study, we prepared cauda equina-derived ECM material for producing scaffolds. Natural porcine cauda equina was decellularized with use of TritonX-100 and sodium deoxycholate, then physically shattered and made into a suspension by differential centrifugation. The decellularization procedure resulted in the removal of > 94% nuclear material and well preserved the extracellular collagen, sulfated glycosaminoglycan (sGAG). Immunofluorescence staining confirmed the presence of collagen type I, laminin, and fibronectin in ECM. Cauda equina ECM was blended with poly(l-lactide-co-glycolide) (PLGA) to fabricate nano-structured scaffolds by electrospinning. The incorporation of ECM increased the hydrophilicity of scaffolds. Fourier transform infrared spectroscopy and multiphoton-induced autofluorescence images showed the presence of ECM in the scaffolds. ECM/PLGA scaffolds were beneficial to the survival of Schwann cells as compared with PLGA-alone scaffolds, and aligned fibers could regulate cell morphologic features by inducing cell orientation. Axons in dorsal root ganglia explants extended to a greater extent along ECM/PLGA than PLGA-alone fibers. Cauda equina ECM may be promising material of scaffolds for neural tissue engineering.
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True Composition and Structure of Hexagonal "YAlO3", Actually Y3Al3O8CO3.
Inorg Chem
PUBLISHED: 11-01-2014
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The discovery of a brilliant-blue color upon the introduction of Mn(3+) to the trigonal-bipyramidal (TBP) sites in YInO3 has led to a search for other hosts for Mn(3+) in TBP coordination. An obvious choice would be YAlO3. This compound, which has only been prepared through a citrate precursor route, has long been considered isostructural with YInO3. However, Mn(3+) substitutions into YAlO3 have failed to produce a product with the anticipated color. We find that the hexagonal structure for YAlO3 with Al in TBP coordination proposed in 1963 cannot be correct based on its unit cell dimensions and bond-valence sums. Our studies indicate instead that all, or nearly all, of the Al in this compound has a coordination number (CN) of 6. Upon heating in air, this compound transforms to YAlO3, with the perovskite structure liberating CO2. The compound long assumed to be a hexagonal form of YAlO3 is actually an oxycarbonate with the ideal composition Y3Al3O8CO3. The structure of this compound has been characterized by powder neutron and X-ray diffraction data obtained as a function of temperature, magic-angle-spinning (27)Al NMR, Fourier transform infrared, and transmission electron microscopy. Refinement of neutron diffraction data indicates a composition of Y3Al3O8CO3. We find that the hexagonal structures of YGaO3 and YFeO3 from the citrate route are also stabilized by small amounts of carbonate. Surprisingly, Y3Al3O8CO3 forms a complete solid solution with YBO3 having tetrahedral borate groups. Other unlikely solid solutions were prepared in the YAlO3-YMnO3, YAlO3-YFeO3, YAlO3-YBO3, YBO3-YMnO3, YBO3-YFeO3, and YBO3-YGaO3 systems.
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Oil/Water separation performances of superhydrophobic and superoleophilic sponges.
Langmuir
PUBLISHED: 10-31-2014
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Superhydrophobic and superoleophilic sponges were fabricated by immersion in an ethanol solution of octadecyltrichlorosilane. The resulting coating strongly adheres to the sponges after curing at 45 °C for 24 h. Absorption capacities of 42-68 times the polymerized octadecylsiloxane sponge weight were obtained for toluene, light petroleum, and methylsilicone oil. These adsorption capacities were maintained after 50 cycles.
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Optimal SVM parameter selection for non-separable and unbalanced datasets.
Struct Multidiscipl Optim
PUBLISHED: 09-27-2014
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This article presents a study of three validation metrics used for the selection of optimal parameters of a support vector machine (SVM) classifier in the case of non-separable and unbalanced datasets. This situation is often encountered when the data is obtained experimentally or clinically. The three metrics selected in this work are the area under the ROC curve (AUC), accuracy, and balanced accuracy. These validation metrics are tested using computational data only, which enables the creation of fully separable sets of data. This way, non-separable datasets, representative of a real-world problem, can be created by projection onto a lower dimensional sub-space. The knowledge of the separable dataset, unknown in real-world problems, provides a reference to compare the three validation metrics using a quantity referred to as the "weighted likelihood". As an application example, the study investigates a classification model for hip fracture prediction. The data is obtained from a parameterized finite element model of a femur. The performance of the various validation metrics is studied for several levels of separability, ratios of unbalance, and training set sizes.
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Improving Production of Thermostable and Fluorescent Holo-?-allophycocyanin by Metabolically Engineered Escherichia coli Using Response Surface Methodology.
Prep. Biochem. Biotechnol.
PUBLISHED: 09-02-2014
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A stable fluorescent holo-?-allophycocyanin (holo-ApcB) was produced by metabolically engineered Escherichia coli. The E. coli cells harbored two plasmids for expression of five genes, which was involved in the holo-apcB production. Response surface methodology was employed to investigate the individual and interactive effects of four variables, i.e., initial pH of culture medium, IPTG concentration, post-induction temperature, and induction start time, on holo-ApcB production by E. coli. The experimental results showed that the IPTG concentration, post-induction temperature, and induction start time had significant individual effects on holo-ApcB production. A significant interactive effect was also found between the initial pH of culture and induction start time. The maximum holo-ApcB production of 45.3 mg/L was predicted under the following optimized culture conditions: a post-induction temperature of 28.4 °C, initial pH of culture of 7.3, IPTG concentration of 1.1 mM, and post-induction time of 66 min. Holo-ApcB production under the optimized culture conditions increased 5.8-fold, compared with that under the non-optimized conditions. Response surface methodology proved to be a valuable tool for optimization of holo-ApcB production by metabolically engineered E. coli.
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Cholelithiasis and risk of pancreatic cancer: systematic review and meta-analysis of 21 observational studies.
Cancer Causes Control
PUBLISHED: 08-22-2014
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To investigate the association between cholelithiasis and risk of pancreatic cancer (PaC).
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The regulatory effect of UL-16 binding protein-3 expression on the cytotoxicity of NK cells in cancer patients.
Sci Rep
PUBLISHED: 08-20-2014
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The activating immunoreceptor NKG2D (natural killer group 2, member D) and its ligands play important roles in the innate and adaptive immune responses. UL16-binding protein 3 (ULBP3), an NKG2D ligand, is overexpressed on certain epithelial tumor cells. In this study, we investigated the effect of ULBP3 expression on the cytotoxic activity of natural killer (NK) cells. ULBP3 were measured by flow cytometry analysis, immunohistochemistry, and time-resolved fluoroimmunoassay. The cytotoxicity of NK cells was determined with the lactate dehydrogenase release assay. We found that ULBP3 was overexpressed on tumor cell lines and tumor tissues. Serum from cancer patients, but not from healthy donors, contained elevated levels of soluble ULBP3 (sULBP3). Importantly, high expression of ULBP3 on the cell surface of tumor cells augmented NKG2D-mediated NK cell cytotoxicity. However, low levels of sULBP3 (<15 ng/ml) weakened the cytotoxicity of NK cells by decreasing NKG2D expression on NK cells. Further analysis showed that serum samples from most cancer patients (>70%) contained the low level of sULBP3. Our results demonstrate that tumor cells express surface and soluble ULBP3, which regulate NK cell activity. Thus, ULBP3 is a potential therapeutic target for improving the immune response against cancer.
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MiR-605 represses PSMD10/Gankyrin and inhibits intrahepatic cholangiocarcinoma cell progression.
FEBS Lett.
PUBLISHED: 08-14-2014
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The aberrant expression of PSMD10 has important functions in various malignancies. This study showed that PSMD10 was highly expressed and inversely correlated with the expression of miR-605 in intrahepatic cholangiocarcinoma (ICC) specimens. MiR-605 directly targeted and repressed PSMD10 expression. In addition, over-expression of miR-605 inhibited ICC cell progression both in vitro and in vivo. This effect of miR-605 on ICC cells was similar to that of PSMD10 knock-down by RNAi. Moreover, restoration of PSMD10 could reverse the phenotypic alteration caused by miR-605 in ICC cells. These results suggest a new therapeutic strategy in ICC by restoring miR-605, which is regulated by p53.
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MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes.
Genome Biol.
PUBLISHED: 08-07-2014
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We propose a statistical algorithm MethylPurify that uses regions with bisulfite reads showing discordant methylation levels to infer tumor purity from tumor samples alone. MethylPurify can identify differentially methylated regions (DMRs) from individual tumor methylome samples, without genomic variation information or prior knowledge from other datasets. In simulations with mixed bisulfite reads from cancer and normal cell lines, MethylPurify correctly inferred tumor purity and identified over 96% of the DMRs. From patient data, MethylPurify gave satisfactory DMR calls from tumor methylome samples alone, and revealed potential missed DMRs by tumor to normal comparison due to tumor heterogeneity.
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Simultaneous determination of seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill by liquid chromatography-electrospray ionization-tandem mass spectrometry: application to a pharmacokinetic study.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 08-04-2014
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A liquid chromatography-electrospray ionization-tandem mass spectrometry method was described for the simultaneous determination of resibufogenin, bufalin, gamabufotalin, telibufagin, arenobufagin, cinobufagin and bufotalin in rat plasma. Plasma samples were pretreated by liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out on an ACQUITY HSS T3 column with gradient elution using mobile phase consisting of acetonitrile-0.1% formic acid in water at a flow rate of 0.3 mL/min. All analytes showed good linearity over a wide concentration range (r>0.99). The lower limit of quantification was in the range of 0.5-10 ng/mL for seven bufadienolides. The mean recovery of the analytes ranged from 94.36 to 104.18%. The intra- and inter-day precisions were in the range of 1.74-13.78% and the accuracies were between 89.37 and 101.38%. The validated method was successfully applied to a pharmacokinetic (PK) study of the seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill (SBP). The selected PK marker compounds with typical efficacy/toxicity may provide a practical solution for marker compound selection and dosage design for the therapeutic drug monitoring and PK study of SBP in its clinical applications.
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Aberrant expression of nuclear KPNA2 is correlated with early recurrence and poor prognosis in patients with small hepatocellular carcinoma after hepatectomy.
Med. Oncol.
PUBLISHED: 06-28-2014
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Karyopherin ?2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. Emerging evidence suggests that KPNA2 plays a crucial role in oncogenesis and early recurrence. In the present study, we evaluated the expression pattern of KPNA2 in 221 hepatocellular carcinoma (HCC) specimens and matching adjacent, non-tumorous tissues (NT) by immunohistochemical assays. We found that nuclear KPNA2 expression was significantly upregulated (30.3 %, 67/221) in HCC tissues; however, no nuclear expression of KPNA2 in NT tissues was observed. A correlation analysis demonstrated that nuclear KPNA2 expression was positively associated with serum AFP level, tumor differentiation, vascular invasion, BCLC stage and early recurrence (all p < 0.05). Nuclear KPNA2 expression was associated with a poor prognosis in HCC patients. Univariate and multivariate analyses demonstrated that KPNA2 was an independent prognostic factor for both overall survival (p < 0.001) and time to recurrence (p < 0.001) in HCC patients. Furthermore, in a validation cohort, nuclear expression of KPNA2 was observed in 16 of 47 (34.0 %) small hepatocellular carcinoma patients. Importantly, the risk of recurrence associated with nuclear KPNA2 expression (9/16, 56.2 %) was significantly higher than the risk associated with an absence of nuclear KPNA2 expression (6/31, 19.3 %; p = 0.01). Our results demonstrate that nuclear KPNA2 expression is a poor prognostic biomarker for HCC, especially for early-stage HCC.
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Role of astroglia in Down's syndrome revealed by patient-derived human-induced pluripotent stem cells.
Nat Commun
PUBLISHED: 06-17-2014
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Down's syndrome (DS), caused by trisomy of human chromosome 21, is the most common genetic cause of intellectual disability. Here we use induced pluripotent stem cells (iPSCs) derived from DS patients to identify a role for astrocytes in DS pathogenesis. DS astroglia exhibit higher levels of reactive oxygen species and lower levels of synaptogenic molecules. Astrocyte-conditioned medium collected from DS astroglia causes toxicity to neurons, and fails to promote neuronal ion channel maturation and synapse formation. Transplantation studies show that DS astroglia do not promote neurogenesis of endogenous neural stem cells in vivo. We also observed abnormal gene expression profiles from DS astroglia. Finally, we show that the FDA-approved antibiotic drug, minocycline, partially corrects the pathological phenotypes of DS astroglia by specifically modulating the expression of S100B, GFAP, inducible nitric oxide synthase, and thrombospondins 1 and 2 in DS astroglia. Our studies shed light on the pathogenesis and possible treatment of DS by targeting astrocytes with a clinically available drug.
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A measure to assess the ablative margin using 3D-CT image fusion after radiofrequency ablation of hepatocellular carcinoma.
HPB (Oxford)
PUBLISHED: 06-11-2014
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To examine the feasibility of three-dimensional computed tomography (3D-CT) image fusion in facilitating assessment of the ablative margin (AM) after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC).
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MPBind: a Meta-motif-based statistical framework and pipeline to Predict Binding potential of SELEX-derived aptamers.
Bioinformatics
PUBLISHED: 05-28-2014
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Aptamers are 'synthetic antibodies' that can bind to target molecules with high affinity and specificity. Aptamers are chemically synthesized and their discovery can be performed completely in vitro, rather than relying on in vivo biological processes, making them well-suited for high-throughput discovery. However, a large fraction of the most enriched aptamers in Systematic Evolution of Ligands by EXponential enrichment (SELEX) rounds display poor binding activity. Here, we present MPBind, a Meta-motif-based statistical framework and pipeline to Predict the BIND: ing potential of SELEX-derived aptamers. Using human embryonic stem cell SELEX-Seq data, MPBind achieved high prediction accuracy for binding potential. Further analysis showed that MPBind is robust to both polymerase chain reaction amplification bias and incomplete sequencing of aptamer pools. These two biases usually confound aptamer analysis.
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New advances in treating thrombotic diseases: GPVI as a platelet drug target.
Drug Discov. Today
PUBLISHED: 04-30-2014
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The recent introduction of highly effective antiplatelet drugs has contributed to the significant improvement in the treatment of acute coronary syndromes. However, limitations remain. Recurrence of ischaemic vascular events results in poor prognosis. Drugs of high antithrombotic efficacy are associated with an increased risk of bleeding, which is important in patients at risk of stroke. An attractive target for the development of new antithrombotics is platelet glycoprotein VI (GPVI) because its blockade seems to combine ideally efficiency and safety. In this review, we summarise current knowledge on the physiological role of GPVI in haemostasis and thrombosis. We also discuss evidence regarding the effectiveness and safety of strategies to inhibit GPVI.
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Eosinophilic cystitis in a patient with hypereosinophila syndrome: A case report.
Exp Ther Med
PUBLISHED: 04-29-2014
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Hypereosinophilic syndrome (HES) is a rare disorder that is characterized by hypereosinophilia and organ damage, caused by the infiltration of eosinophils. In rare cases, the urinary bladder may also be involved. The current case report presented a 56-year-old male with gross hematuria and hypereosinophilia. The diagnosis of eosinophilic cystitis associated HES was established. Oral prednisone with a slow tapering regimen was administered as the primary treatment for the patient, which achieved partial hematological remission and complete relief of cystitis during a six-month follow-up period. Although eosinophilic cystitis is not commonly the primary manifestation of HES, eosinophilic cystitis should be taken into consideration following the onset of urinary symptoms in patients with HES.
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Regulation of the pentose phosphate pathway in cancer.
Protein Cell
PUBLISHED: 04-07-2014
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Energy metabolism is significantly reprogrammed in many human cancers, and these alterations confer many advantages to cancer cells, including the promotion of biosynthesis, ATP generation, detoxification and support of rapid proliferation. The pentose phosphate pathway (PPP) is a major pathway for glucose catabolism. The PPP directs glucose flux to its oxidative branch and produces a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), an essential reductant in anabolic processes. It has become clear that the PPP plays a critical role in regulating cancer cell growth by supplying cells with not only ribose-5-phosphate but also NADPH for detoxification of intracellular reactive oxygen species, reductive biosynthesis and ribose biogenesis. Thus, alteration of the PPP contributes directly to cell proliferation, survival and senescence. Furthermore, recent studies have shown that the PPP is regulated oncogenically and/or metabolically by numerous factors, including tumor suppressors, oncoproteins and intracellular metabolites. Dysregulation of PPP flux dramatically impacts cancer growth and survival. Therefore, a better understanding of how the PPP is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway.
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CD44v/CD44s expression patterns are associated with the survival of pancreatic carcinoma patients.
Diagn Pathol
PUBLISHED: 04-01-2014
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CD44 variants have been associated with tumor invasion and metastasis, but CD44 expression patterns have not been systematically investigated in pancreatic carcinoma. This study systematically investigated whether CD44 expression patterns are involved in pancreatic carcinoma metastasis and prognosis.
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Tempofilter II implantation in patients with lower extremity fractures and proximal deep vein thrombosis.
Diagn Interv Radiol
PUBLISHED: 03-29-2014
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We aimed to examine the efficacy and safety of Tempofilter II (B. Braun, Melsungen, Germany) implantation to prevent pulmonary embolism in patients with lower-extremity fractures and proximal deep vein thrombosis (DVT).
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Co-expression of CD133, CD44v6 and human tissue factor is associated with metastasis and poor prognosis in pancreatic carcinoma.
Oncol. Rep.
PUBLISHED: 03-14-2014
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The metastasis-related molecules CD133, CD44v6 and human tissue factor (TF) have been shown to be associated with tumor invasion and metastasis. This study aimed to determine whether co-expression of these three molecules was associated with metastasis and overall prognosis in pancreatic carcinoma. We analyzed the expression profiles of these three molecules by immunohistochemistry and evaluated the relationship of their expression profiles with metastasis and prognosis in 109 pancreatic carcinomas. The results showed that the expression levels of CD133, CD44v6 and TF were increased in pancreatic carcinoma. Co-expression of CD133, CD44v6 and TF (tri-expression) was also detected in pancreatic carcinoma. Clinical analysis showed that individual expression of CD133, CD44v6 or TF was associated with vessel invasion, lymph node metastasis and liver metastasis, while tri-expression was associated with lymph node metastasis. Survival analysis showed that patients with co-expression of CD133 and TF or tri-expression had lower and the lowest overall survival rates, respectively. Univariate analysis showed that T-factor, lymph node metastasis, TNM stage, and individual levels or tri-expression of CD133, CD44v6 and TF were survival risk factors. Multivariate analysis showed that tri-expression of CD133, CD44v6 and TF was an independent predictor of survival. These results suggest that overexpression of CD133, CD44v6 and TF is associated with pancreatic carcinoma metastasis. Tri-expression of these three molecules may be a useful predictor for pancreatic carcinoma prognosis.
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Identification and pharmacokinetics of multiple constituents in rat plasma after oral administration of Yinchenzhufu decoction.
J Ethnopharmacol
PUBLISHED: 03-14-2014
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Yinchenzhufu decoction (YCZFD) is a classical Chinese herbal formula and has been used to treat severe jaundice in chronic liver injuries since the Qing Dynasty (18th century CE). To identify the components absorbed into the blood in YCZFD and explore their pharmacokinetic profile for understanding the effective ingredients of YCZFD.
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Ag nanoparticle-ZnO nanowire hybrid nanostructures as enhanced and robust antimicrobial textiles via a green chemical approach.
Nanotechnology
PUBLISHED: 03-12-2014
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A new approach for fabrication of a long-term and recoverable antimicrobial nanostructure/textile hybrid without increasing the antimicrobial resistance is demonstrated. Using in situ synthesized Ag nanoparticles (NPs) anchored on ZnO nanowires (NWs) grown on textiles by a 'dip-in and light-irradiation' green chemical method, we obtained ZnONW@AgNP nanocomposites with small-size and uniform Ag NPs, which have shown superior performance for antibacterial applications. These new Ag/ZnO/textile antimicrobial composites can be used for wound dressings and medical textiles for topical and prophylactic antibacterial treatments, point-of-use water treatment to improve the cleanliness of water and antimicrobial air filters to prevent bioaerosols accumulating in ventilation, heating, and air-conditioning systems.
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67 laminin receptor promotes the malignant potential of tumour cells up-regulating lysyl oxidase-like 2 expression in cholangiocarcinoma.
Dig Liver Dis
PUBLISHED: 02-26-2014
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67 laminin receptor (67LR) plays an important role in the invasion and metastasis of cholangiocarcinoma, but its mechanism remains unclear.
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Investigating the pathological processes of rhegmatogenous retinal detachment and proliferative vitreoretinopathy with metabolomics analysis.
Mol Biosyst
PUBLISHED: 02-22-2014
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Proliferative vitreoretinopathy (PVR) develops as a complication of rhegmatogenous retinal detachment (RRD). The unclear pathological pathways of PVR and RRD have been the biggest obstacle for successful retinal reattachment. In this study, a metabolomics approach using reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) was developed to obtain a systematic view of the pathological processes of RRD and PVR. Through a partial least squares discriminant analysis (PLS-DA) method, 31 biomarkers were identified in the vitreous samples of RRD and PVR patients. Sixteen pathways participated in the development of RRD and PVR. Through analyzing the biological effects of those identified biomarkers, inflammation, proliferation and energy consumption were the three major disturbed biological processes involved in the RRD and PVR development. Inflammation happened in the pathological processes of RRD, and proliferation mainly happened during PVR formation. The established network of biomarkers indicated that the histidine metabolism and citrate cycle were seriously disturbed during the RRD and PVR development. The metabolomics study supplied a systematic view of the development and progression of RRD and PVR on a metabolite level.
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The efficacy of molecular subtyping in predicting postoperative recurrence in breast-conserving therapy: a 15-study meta-analysis.
World J Surg Oncol
PUBLISHED: 02-21-2014
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Recent research displays that breast cancer (BC) is a heterogeneous disease and distinct molecular subtypes yield different prognostic outcomes.
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Variations of ABCB4 and ABCB11 genes are associated with primary intrahepatic stones.
Mol Med Rep
PUBLISHED: 01-17-2014
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Variations of the ABCB4 and ABCB11 genes affect the composition of bile and are associated with cholestasis and cholelithiasis. However, their roles in the formation of primary intrahepatic stones (PIS) remains to be elucidated. The aim of the present study was to determine whether there is an association between PIS and variations in these genes. Exon sequencing was performed in order to analyze the ABCB4 and ABCB11 genes of 176 patients with PIS and 178 healthy subjects. One mutation in ABCB4 (no. 69233, G>A) and two other mutations in ABCB11, reference single nucleotide polymorphism (rs)118109635 and rs497692, were identified in association with PIS (P<0.001, P=0.04 and P=0.02, respectively). A synonymous mutation at no. 69233 G>A was detected in exon 26 of ABCB4 in 23 heterozygous patients with PIS. This mutation was not detected in healthy individuals or in the Single Nucleotide Polymorphism Database. No. 69233 G>A in ABCB4 was not associated with altered protein expression but with a reduced rate of PIS recurrence (P=0.01). The missense mutation rs118109635 was located on exon 21 of ABCB11 and was associated with the increased expression of ABCB11 protein (P=0.032) as well as altered bile salt export pump function. Another synonymous mutation, rs497692 in exon 24 was reported to decrease ABCB11 protein expression (P=0.001). In addition, the mutations of ABCB11 were associated with preoperative jaundice (P<0.001 and P=0.03, respectively). Consistently decreased levels of ABCB11 protein were associated with recurrent episodes of cholangitis (P=0.006) and preoperative jaundice (P=0.015). By contrast, ABCB4 expression was not found to be associated with clinical manifestations of PIS.
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Imaging investigation of intracranial arterial dissecting aneurysms by using 3 T high-resolution MRI and DSA: from the interventional neuroradiologists' view.
Acta Neurochir (Wien)
PUBLISHED: 01-14-2014
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The purpose of this study was to investigate vessel wall imaging features combined with the luminal shapes of intracranial dissecting aneurysms (IDAs) by using 3 Tesla (3T) high-resolution magnetic resonance imaging (MRI) and digital subtraction angiography (DSA).
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Transcriptome-wide discovery of microRNA binding sites in human brain.
Neuron
PUBLISHED: 01-02-2014
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The orchestration of brain function requires complex gene regulatory networks that are modulated, in part, by microRNAs (miRNAs). These noncoding RNAs associate with argonaute (Ago) proteins in order to direct posttranscriptional gene suppression via base pairing with target transcripts. In order to better understand how miRNAs contribute to human-specialized brain processes and neurological phenotypes, identifying their targets is of paramount importance. Here, we address the latter by profiling Ago2:RNA interactions using HITS-CLIP to generate a transcriptome-wide map of miRNA binding sites in human brain. We uncovered ? 7,000 stringent Ago2 binding sites that are highly enriched for conserved sequences corresponding to abundant brain miRNAs. This interactome points to functional miRNA:target pairs across >3,000 genes and represents a valuable resource for accelerating our understanding of miRNA functions in brain. We demonstrate the utility of this map for exploring clinically relevant miRNA binding sites that may facilitate the translation of genetic studies of complex neuropsychiatric diseases into therapeutics.
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Chloroplast transformation of Platymonas (Tetraselmis) subcordiformis with the bar gene as selectable marker.
PLoS ONE
PUBLISHED: 01-01-2014
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The objective of this research was to establish a chloroplast transformation technique for Platymonas (Tetraselmis) subcordiformis. Employing the gfp gene as a reporter and the bar gene as a selectable marker, transformation vectors of P. subcordiformis chloroplast were constructed with endogenous fragments rrn16S-trnI (left) and trnA-rrn23S (right) as a recombination site of the chloroplast genome. The plasmids were transferred into P. subcordiformis via particle bombardment. Confocal laser scanning microscopy indicated that the green fluorescence protein was localized in the chloroplast of P. subcordiformis, confirming the activity of the Chlamydomonas reinhardtii promoter. Cells transformed with the bar gene were selected using the herbicide Basta. Resistant colonies were analyzed by PCR and Southern blotting, and the results indicated that the bar gene was successfully integrated into the chloroplast genome via homologous recombination. The technique will improve genetic engineering of this alga.
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Xenoimplantation of an extracellular-matrix-derived, biphasic, cell-scaffold construct for repairing a large femoral-head high-load-bearing osteochondral defect in a canine model.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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This study was aimed to develop an ECM-derived biphasic scaffold and to investigate its regeneration potential loaded with BM-MSCs in repair of large, high-load-bearing osteochondral defects of the canine femoral head. The scaffolds were fabricated using cartilage and bone ECM as a cartilage and bone layer, respectively. Osteochondral constructs were fabricated using induced BM-MSCs and the scaffold. Osteochondral defects (11 mm diameter × 10 mm depth) were created on femoral heads of canine and treated with the constructs. The repaired tissue was evaluated for gross morphology, radiography, histological, biomechanics at 3 and 6 months after implantation. Radiography revealed that femoral heads slightly collapsed at 3 months and severely collapsed at 6 months. Histology revealed that some defects in femoral heads were repaired, but with fibrous tissue or fibrocartilage, and femoral heads with different degrees of collapse. The bone volume fraction was lower for subchondral bone than normal femoral bone at 3 and 6 months. Rigidity was lower in repaired subchondral bone than normal femoral bone at 6 months. The ECM-derived, biphasic scaffold combined with induced BM-MSCs did not successfully repair large, high-load-bearing osteochondral defects of the canine femoral head. However, the experience can help improve the technique of scaffold fabrication and vascularization.
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CCAT: Combinatorial Code Analysis Tool for transcriptional regulation.
Nucleic Acids Res.
PUBLISHED: 12-23-2013
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Combinatorial interplay among transcription factors (TFs) is an important mechanism by which transcriptional regulatory specificity is achieved. However, despite the increasing number of TFs for which either binding specificities or genome-wide occupancy data are known, knowledge about cooperativity between TFs remains limited. To address this, we developed a computational framework for predicting genome-wide co-binding between TFs (CCAT, Combinatorial Code Analysis Tool), and applied it to Drosophila melanogaster to uncover cooperativity among TFs during embryo development. Using publicly available TF binding specificity data and DNaseI chromatin accessibility data, we first predicted genome-wide binding sites for 324 TFs across five stages of D. melanogaster embryo development. We then applied CCAT in each of these developmental stages, and identified from 19 to 58 pairs of TFs in each stage whose predicted binding sites are significantly co-localized. We found that nearby binding sites for pairs of TFs predicted to cooperate were enriched in regions bound in relevant ChIP experiments, and were more evolutionarily conserved than other pairs. Further, we found that TFs tend to be co-localized with other TFs in a dynamic manner across developmental stages. All generated data as well as source code for our front-to-end pipeline are available at http://cat.princeton.edu.
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A critical role of glucose-6-phosphate dehydrogenase in TAp73-mediated cell proliferation.
Cell Cycle
PUBLISHED: 11-21-2013
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The pentose phosphate pathway (PPP) provides ribose and NADPH that support biosynthesis and antioxidant defense. Our recent findings suggest that the p53-related protein TAp73 enhances the PPP flux. TAp73 stimulates the expression of glucose-6-phophate dehydrogenase (G6PD), the rate-limiting enzymes of the PPP. Through this regulation, TAp73 promotes the accumulation of macromolecules and increases cellular capability to withstand oxidative stresses. TAp73 also regulates other metabolic enzymes, and the relative importance of these targets in TAp73-mediated cell growth is not well understood. Here we show that, like in other cell lines, TAp73 is required for supporting proliferation and maintaining the expression of G6PD in the human lung cancer H1299 cells. Restoration of G6PD expression almost fully rescues the defects in cell growth caused by TAp73 knockdown, suggesting that G6PD is the major proliferative target of TAp73 in these cells. G6PD expression is elevated in various tumors, correlating with the upregulation of TAp73. These results indicate that TAp73 may function as an oncogene, and that G6PD is likely a focal point of regulation in oncogenic growth.
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Proteomic analysis of surface proteins of Trichinella spiralis muscle larvae by two-dimensional gel electrophoresis and mass spectrometry.
Parasit Vectors
PUBLISHED: 10-28-2013
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Trichinella spiralis is a zoonotic tissue-dwelling parasitic nematode that infects humans and other mammals. Its surface proteins are recognized as antigenic in many infected hosts, being directly exposed to the hosts immune system and are the main target antigens that induce the immune responses. The larval surface proteins may also interact with intestinal epithelial cells and may play an important role in the invasion and development process of T. spiralis. The purpose of this study was to analyze and characterize the surface proteins of T. spiralis muscle larvae by two-dimensional gel electrophoresis (2-DE) and mass spectrometry.
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Pharmacokinetics of liposomal-encapsulated and un-encapsulated vincristine after injection of liposomal vincristine sulfate in beagle dogs.
Cancer Chemother. Pharmacol.
PUBLISHED: 10-16-2013
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Vincristine sulfate (VCR) is a potent and widely used anti-tumor drug. Encapsulating VCR with liposomes improves its therapeutic index. However, there is little known about the pharmacokinetic features of un-encapsulated VCR (UE-VCR) and encapsulated VCR (E-VCR).
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[Insertion of double inferior vena cava filter in patients with deep venous thromboembolism].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-16-2013
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To explore the characteristic, diagnosis and treatment of deep venous thromboembolism (DVT) patients with congenital double inferior vena cava.
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Photosystem II Photochemistry and Phycobiliprotein of the Red Algae Kappaphycus alvarezii and Their Implications for Light Adaptation.
Biomed Res Int
PUBLISHED: 09-01-2013
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Photosystem II photochemistry and phycobiliprotein (PBP) genes of red algae Kappaphycus alvarezii, raw material of ? -carrageenan used in food and pharmaceutical industries, were analyzed in this study. Minimum saturating irradiance (I k ) of this algal species was less than 115? ? mol?m(-2)?s(-1). Its actual PSII efficiency (yield II) increased when light intensity enhanced and decreased when light intensity reached 200? ? mol?m(-2)?s(-1). Under dim light, yield II declined at first and then increased on the fourth day. Under high light, yield II retained a stable value. These results indicate that K. alvarezii is a low-light-adapted species but possesses regulative mechanisms in response to both excessive and deficient light. Based on the PBP gene sequences, K. alvarezii, together with other red algae, assembled faster and showed a closer relationship with LL-Prochlorococcus compared to HL-Prochlorococcus. Many amino acid loci in PBP sequences of K. alvarezii were conserved with those of LL-Prochlorococcus. However, loci conserved with HL-Prochlorococcus but divergent with LL-Prochlorococcus were also found. The diversities of PE and PC are proposed to have played some roles during the algal evolution and divergence of light adaption.
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Tuning the redox activity of encapsulated metal clusters via the metallic and semiconducting character of carbon nanotubes.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-26-2013
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We demonstrate that reactions confined within single-walled carbon nanotube (SWCNT) channels are modulated by the metallic and semiconducting character of the hosts. In situ Raman and X-ray absorption near-edge structure spectroscopies provide complementary information about the electronic state of carbon nanotubes and the encapsulated rhenium species, which reveal electronic interactions between encapsulated species and nanotubes. More electrons are transferred from metallic tubes (m-SWCNTs) to oxidic rhenium clusters, leading to a lower valence state rhenium oxide than that in semiconducting tubes (s-SWCNTs). Reduction in 3.5% (vol/vol) H2/Ar leads to weakened host-guest electronic interaction. The high valence state Re within s-SWCNTs is more readily reduced when raising the temperature, whereas only a sluggish change is observed for Re within m-SWCNTs. Only at 400 °C does Re reach a similar electronic state (mixture of Re(0) and Re(4+)) in both types of tubes. Subsequent oxidation in 1% O2/Ar does not show changes for Re in s-SWCNTs up to 200 °C. In comparison, m-SWCNTs facilitate the oxidation of reduced rhenium (160 °C). This can be exploited for rational design of active catalysts with stable species as a desired valence state can be obtained by selecting specific-type SWCNTs and a controlled thermal treatment. These results also provide a chemical approach to modulate reversibly the electronic structure of SWCNTs without damaging the sidewalls of SWCNTs.
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hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury.
Nat Commun
PUBLISHED: 06-26-2013
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Human pluripotent stem cells (hPSCs) have been differentiated to astroglia, but the utilization of hPSC-derived astroglia as cell therapy for neurological diseases has not been well studied. Astroglia are heterogeneous, and not all astroglia are equivalent in promoting neural repair. A prerequisite for cell therapy is to derive defined cell populations with superior therapeutic effects. Here we use an Olig2-GFP human embryonic stem cell (hESC) reporter to demonstrate that hESC-derived Olig2(+) progenitors generate a subtype of previously uncharacterized astroglia (Olig2PC-Astros). These Olig2PC-Astros differ substantially from astroglia differentiated from Olig2-negative hESC-derived neural progenitor cells (NPC-Astros), particularly in their neuroprotective properties. When grafted into brains subjected to global ischaemia, Olig2PC-Astros exhibit superior neuroprotective effects and improved behavioural outcome compared to NPC-Astros. Thus, this new paradigm of human astroglial differentiation is useful for studying the heterogeneity of human astroglia, and the unique Olig2PC-Astros may constitute a new cell therapy for treating cerebral ischaemia and other neurological diseases.
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Large-scale fabrication of nanodimple arrays for surface-enhanced Raman scattering.
Phys Chem Chem Phys
PUBLISHED: 06-25-2013
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Here we report a simple bottom-up technology for scalably fabricating gold nanodimple arrays with tunable nanostructures for surface-enhanced Raman scattering (SERS). Double-layer silica colloidal crystal-polymer nanocomposites with an unusual non-close-packed structure created using a spin-coating technique are utilized as structural templates. A variety of nanodimple structures, including simple monolayer voids, nanoring-like nanodimples, and binary-void nanodimples, can be reproducibly templated over wafer-sized areas by simply controlling the conditions during an oxygen plasma etching process. Normal-incidence specular reflection measurements show that the resulting gold nanodimple arrays exhibit tunable surface plasmon properties. The efficient electromagnetic coupling between neighboring nanodimples and inner-outer walls of nanoring-like nanodimples leads to high SERS enhancement factors (>10(8)). Numerical simulations based on a finite-difference time-domain model complement the experimental measurements, showing the spatial distribution of electromagnetic "hot spots" surrounding the periodic gold nanodimple arrays.
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Apigenin potentiates the growth inhibitory effects by IKK-?-mediated NF-?B activation in pancreatic cancer cells.
Toxicol. Lett.
PUBLISHED: 06-18-2013
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Apigenin is a potential chemopreventive agent for cancer prevention. Because of the central role of transcription factor nuclear factor-?B (NF-?B) in pancreatic cancer, we investigated the roles of NF-?B in apigenin-induced growth inhibition in pancreatic cancer cells. It showed that apigenin reduced cell growth and induced apoptosis in the cells. Apigenin treatment down-regulated not only basal but also TNF-?-induced NF-?B DNA binding activity, NF-?B transcription activity, inhibitor of ?B (I?B)-? phosphorylation together with translocation of p65 and p50, and it accompanied with the blockade of I?B kinase (IKK)-? activity. Moreover, IKK blockage potentiated the anticancer efficacy of apigenin and IKK-? overexpression attenuated the apigenin-induced cell growth inhibition. Additionally, apigenin (30mg/kg) administration suppressed pancreatic cancer growth and IKK-? activation in nude mice xenograft. These results indicated that apigenin had a potential to inhibit IKK-?-mediated NF-?B activation, and was a valuable agent for the pancreatic cancer treatment.
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Generalized fabrication of monolayer nonclose-packed colloidal crystals with tunable lattice spacing.
Langmuir
PUBLISHED: 06-14-2013
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Here, we report a simple colloidal transfer technology that enables scalable fabrication of monolayer nonclose-packed silica colloidal crystals on a large variety of substrates. Two-dimensional colloidal crystals with an unusual nonclose-packed structure are first assembled on silicon wafers by a spin-coating technique. A poly(vinyl alcohol) (PVA) film cast upon the spin-coated colloidal crystal is used to transfer the nonclose-packed particle arrays onto various substrates. The lattice spacing of the transferred monolayer colloidal crystal can easily be adjusted by thermally treating the PVA-silica spheres composite film for varied durations. We also have demonstrated the templating fabrication of periodic arrays of gold nanodots using a transferred monolayer nonclose-packed colloidal crystal as a structural template. The resultant plasmonic array exhibits high surface-enhanced Raman scattering enhancement factor (~3.8 × 10(7)) for adsorbed benzenethiol molecules.
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Periodic arrays of metal nanorings and nanocrescents fabricated by a scalable colloidal templating approach.
J Colloid Interface Sci
PUBLISHED: 05-28-2013
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Here, we report a scalable bottom-up approach for fabricating periodic arrays of metal nanorings and nanocrescents. Wafer-scale monolayer silica colloidal crystals with an unusual non-close-packed structure prepared by a simple and rapid spin-coating technology are used as both etching and shadowing masks to create nanoring-shaped trenches in between templated polymer posts and sacrificial nanoholes. Directional deposition of metals in the trenches followed by liftoff of the polymer posts and the sacrificial nanoholes results in forming ordered metal nanorings. The inner and outer radii of the final nanorings are determined by the sizes of the templated polymer posts and the silica microspheres which can be easily adjusted by tuning the spin-coating and templating conditions. Most importantly, by simply controlling the tilt angle of the substrate toward the directional metal beams, continuous geometric transition from concentric nanorings to eccentric nanorings to nanocrescents can be achieved. This new colloidal templating approach is compatible with standard semiconductor microfabrication, promising for mass-production and on-chip integration of periodic nanorings and nanocrescents for a wide spectrum of technological applications ranging from nanooptical devices and ultrasensitive biosensing to magnetic memories and logic circuits.
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Aberrant expression of laminin ?2 correlates with poor prognosis and promotes invasion in extrahepatic cholangiocarcinoma.
J. Surg. Res.
PUBLISHED: 05-16-2013
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To investigate the potential role of laminin ?2 and its correlation with prognosis in patients with extrahepatic cholangiocarcinoma (CCA).
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TAp73 enhances the pentose phosphate pathway and supports cell proliferation.
Nat. Cell Biol.
PUBLISHED: 05-16-2013
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TAp73 is a structural homologue of the pre-eminent tumour suppressor p53. However, unlike p53, TAp73 is rarely mutated, and instead is frequently overexpressed in human tumours. It remains unclear whether TAp73 affords an advantage to tumour cells and if so, what the underlying mechanism is. Here we show that TAp73 supports the proliferation of human and mouse tumour cells. TAp73 activates the expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP). By stimulating G6PD, TAp73 increases PPP flux and directs glucose to the production of NADPH and ribose, for the synthesis of macromolecules and detoxification of reactive oxygen species (ROS). The growth defect of TAp73-deficient cells can be rescued by either enforced G6PD expression or the presence of nucleosides plus an ROS scavenger. These findings establish a critical role for TAp73 in regulating metabolism, and connect TAp73 and the PPP to oncogenic cell growth.
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Post-transcriptional regulation of cystic fibrosis transmembrane conductance regulator expression and function by microRNAs.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 05-08-2013
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MicroRNAs (miRNAs) are increasingly recognized as important posttranscriptional regulators of gene expression, and changes in their actions can contribute to disease states. Little is understood regarding miRNA functions in the airway epithelium under normal or diseased conditions. We profiled miRNA expression in well-differentiated primary cultures of human cystic fibrosis (CF) and non-CF airway epithelia, and discovered that miR-509-3p and miR-494 concentrations were increased in CF epithelia. Human non-CF airway epithelia, transfected with the mimics of miR-509-3p or miR-494, showed decreased cystic fibrosis transmembrane conductance regulator (CFTR) expression, whereas their respective anti-miRs exerted the opposite effect. Interestingly, the two miRNAs acted cooperatively in regulating CFTR expression. Upon infecting non-CF airway epithelial cells with Staphylococcus aureus, or upon stimulating them with the proinflammatory cytokines TNF-? or IL-1?, we observed an increased expression of both miRNAs and a concurrent decrease in CFTR expression and function, suggesting that inflammatory mediators may regulate these miRNAs. Transfecting epithelia with anti-miRs for miR-509-3p and miR-494, or inhibiting NF-?B signaling before stimulating cells with TNF? or IL-1?, suppressed these responses, suggesting that the expression of both miRNAs was responsive to NF-?B signaling. Thus, miR-509-3p and miR-494 are dynamic regulators of CFTR abundance and function in normal, non-CF airway epithelia.
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ZnO nanowires grown on carbon cloth for flexible cold cathode.
J Nanosci Nanotechnol
PUBLISHED: 05-08-2013
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Nanostructures grown on carbon cloth are recently attracted great interests for flexible field emitter and cold cathode. In this paper, we report high-aspect ratio ZnO nanowires grown on carbon cloth by a low-temperature solution chemical approach that can be used as a flexible and high performance cold cathode. The carbon cloth is covered by outward-grown ZnO nanowires uniformly and densely with spiny structures. The hybrid structures exhibits a turn-on electrical field of 4.36 V/microm and a field enhancement factor of 1157, which benefit from the high-aspect ratios of both ZnO nanowires and carbon cloth. These results demonstrate a low cost and scalable approach for flexible cold cathode lighting and field emission display.
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Synthesis of rhombic dodecahedral gold nanocrystals by dimethylformamide reduction.
J Nanosci Nanotechnol
PUBLISHED: 05-08-2013
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We report a facile and low-cost wet chemical method for preparation of gold (Au) nanocrystals with morphology of well-defined rhombic dodecahedron (RD). The Au nanocrystals with the RD shape have been synthesized by reducing HAuCl4 in N,N-dimethylformamide (DMF) solvent in an autoclave for 15-24 h at 90 degrees C. Thus-synthesized Au nanocrystals have been characterized by a scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected-area electron diffraction (SAED). The results show that the RD nanocrystals are exclusively enclosed by twelve {110}-type facets. Furthermore, concave RD Au nanocrystals can also be produced only by changing reaction time or adding ascorbic acid (AA). A possible evolution mechanism of the RD Au nanocrystals has been suggested.
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Generation and characterization of spiking and non-spiking oligodendroglial progenitor cells from embryonic stem cells.
Stem Cells
PUBLISHED: 05-07-2013
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Pluripotent stem cells (PSCs) have been differentiated into oligodendroglial progenitor cells (OPCs), providing promising cell replacement therapies for many CNS disorders. Studies from rodents have shown that brain OPCs express a variety of ion channels, and that a subset of brain OPCs express voltage-gated sodium channel (NaV ), mediating the spiking properties of OPCs. However, it is unclear whether PSC-derived OPCs exhibit electrophysiological properties similar to brain OPCs and the role of NaV in the functional maturation of OPCs is unknown. Here, using a mouse embryonic stem cell (mESC) GFP-Olig2 knockin reporter line, we demonstrated that unlike brain OPCs, all of the GFP(+) /Olig2(+) mESC-derived OPCs (mESC-OPCs) did not express functional NaV and failed to generate spikes (hence termed "non-spiking mESC-OPCs"), while expressing the delayed rectifier and inactivating potassium currents. By ectopically expressing NaV 1.2 ? subunit via viral transduction, we successfully generated mESC-OPCs with spiking properties (termed "spiking mESC-OPCs"). After transplantation into the spinal cord and brain of myelin-deficient shiverer mice, the spiking mESC-OPCs demonstrated better capability in differentiating into MBP expressing oligodendrocytes and in myelinating axons in vivo than the non-spiking mESC-OPCs. Thus, by generating spiking and non-spiking mESC-OPCs, this study reveals a novel function of NaV in OPCs in their functional maturation and myelination, and sheds new light on ways to effectively develop PSC-derived OPCs for future clinical applications. Stem Cells 2013.
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Computational assessment of the cooperativity between RNA binding proteins and MicroRNAs in Transcript Decay.
PLoS Comput. Biol.
PUBLISHED: 05-01-2013
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Transcript degradation is a widespread and important mechanism for regulating protein abundance. Two major regulators of transcript degradation are RNA Binding Proteins (RBPs) and microRNAs (miRNAs). We computationally explored whether RBPs and miRNAs cooperate to promote transcript decay. We defined five RBP motifs based on the evolutionary conservation of their recognition sites in 3UTRs as the binding motifs for Pumilio (PUM), U1A, Fox-1, Nova, and UAUUUAU. Recognition sites for some of these RBPs tended to localize at the end of long 3UTRs. A specific group of miRNA recognition sites were enriched within 50 nts from the RBP recognition sites for PUM and UAUUUAU. The presence of both a PUM recognition site and a recognition site for preferentially co-occurring miRNAs was associated with faster decay of the associated transcripts. For PUM and its co-occurring miRNAs, binding of the RBP to its recognition sites was predicted to release nearby miRNA recognition sites from RNA secondary structures. The mammalian miRNAs that preferentially co-occur with PUM binding sites have recognition seeds that are reverse complements to the PUM recognition motif. Their binding sites have the potential to form hairpin secondary structures with proximal PUM binding sites that would normally limit RISC accessibility, but would be more accessible to miRNAs in response to the binding of PUM. In sum, our computational analyses suggest that a specific set of RBPs and miRNAs work together to affect transcript decay, with the rescue of miRNA recognition sites via RBP binding as one possible mechanism of cooperativity.
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SIRT1 inhibition by melatonin exerts antitumor activity in human osteosarcoma cells.
Eur. J. Pharmacol.
PUBLISHED: 04-25-2013
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Melatonin, the main secretory product of the pineal gland, has potent antitumor activity against various types of cancer. However, the molecular mechanisms underlying the effects of melatonin remain largely unknown. SIRT1, a conserved nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, has been implicated in modulating transcriptional silencing and cell survival and plays a key role in carcinogenesis through the deacetylation of important regulatory proteins. In this study, we assessed the antitumor activity of melatonin against human osteosarcoma cells (9607 cell line) and explored the role of SIRT1 in the activity of melatonin. Melatonin treatment resulted in strong antitumor activity, as evidenced not only by reductions in tumor cell vitality, adhesion ability, migration ability and glutathione (GSH) levels but also by increase in the apoptotic index and reactive oxygen species. Additionally, melatonin treatment down-regulated SIRT1 and up-regulated acetylated-p53. Sirtinol (a known SIRT1 inhibitor) and SIRT1 siRNA further enhanced the antitumor activity of melatonin, while SRT1720 (a known SIRT1 activator) attenuated the antitumor activity of melatonin. In summary, melatonin is a potent inhibitor of osteosarcoma cell growth that targets SIRT1 signaling, and the inhibition of SIRT1 signaling is a novel mechanism of action for melatonin during therapeutic intervention in osteosarcoma.
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LPS increases MUC5AC by TACE/TGF-?/EGFR pathway in human intrahepatic biliary epithelial cell.
Biomed Res Int
PUBLISHED: 04-04-2013
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Mucin 5AC (MUC5AC) overproduction plays important roles in stone formation and recurrence of hepatolithiasis. We aim to investigate the involved mechanism and the potential target to block this process.
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The effect of energy substrates on PHB accumulation of Acidiphilium cryptum DX1-1.
Curr. Microbiol.
PUBLISHED: 04-02-2013
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The effect of glucose and elemental sulfur on the growth and PHB accumulation of Acidiphilium cryptum DX1-1 was investigated. Meanwhile, the differential expressions of 19 genes related with PHB accumulation, sulfur metabolism and carbon fixed in heterotrophy, phytotrophy and mixotrophy were studied by RT-qPCR. The results showed that strain DX1-1 could accumulate PHB with sulfur as the energy substance and atmospheric CO2 as carbon resource. Glucose could improve the growth of strain DX1-1 cultured in medium with sulfur as the energy substance, and almost all the key enzyme-encoding genes related with PHB, sulfur metabolism and carbon fixed were basically up-regulated. PHB polymerase (Arcy_3030), ribulose-bisphosphate carboxylase (Acry_0825), ribulose-phosphate-epimerase (Acry_0022), and cysteine synthase A (Acry_2560) played important role in PHB accumulation, the modified expression of which could influence the PHB yield. With CO2 as carbon resource, the main initial substance of PHB accumulation for strain DX1-1 was acetyl-CoA, instead of acetate with the glucose as the carbon resource. Because of accumulating PHB by fixed atmospheric CO2 while independent of light, A. cryptum DX1-1 may have specifically potential in production of PHB.
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Self-assembled biomimetic superhydrophobic hierarchical arrays.
J Colloid Interface Sci
PUBLISHED: 02-22-2013
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Here, we report a simple and inexpensive bottom-up technology for fabricating superhydrophobic coatings with hierarchical micro-/nano-structures, which are inspired by the binary periodic structure found on the superhydrophobic compound eyes of some insects (e.g., mosquitoes and moths). Binary colloidal arrays consisting of exemplary large (4 and 30 ?m) and small (300 nm) silica spheres are first assembled by a scalable Langmuir-Blodgett (LB) technology in a layer-by-layer manner. After surface modification with fluorosilanes, the self-assembled hierarchical particle arrays become superhydrophobic with an apparent water contact angle (CA) larger than 150°. The throughput of the resulting superhydrophobic coatings with hierarchical structures can be significantly improved by templating the binary periodic structures of the LB-assembled colloidal arrays into UV-curable fluoropolymers by a soft lithography approach. Superhydrophobic perfluoroether acrylate hierarchical arrays with large CAs and small CA hysteresis can be faithfully replicated onto various substrates. Both experiments and theoretical calculations based on the Cassies dewetting model demonstrate the importance of the hierarchical structure in achieving the final superhydrophobic surface states.
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Ag?Se quantum dots with tunable emission in the second near-infrared window.
ACS Appl Mater Interfaces
PUBLISHED: 02-11-2013
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Quantum dots (QDs) with fluorescence in the second near-infrared window (NIR-II, 1000-1400 nm) are ideal fluorophores for in vivo imaging of deep tissue with high signal-to-noise ratios. Ag?Se (bulk band gap 0.15 eV) is a promising candidate for preparing NIR-II QDs. By using 1-octanethiol as ligand to effectively balance the nucleation and growth, tuning the fluorescence of Ag?Se QDs was successfully realized in the NIR-II window ranged from 1080 to 1330 nm. The prepared Ag?Se QDs can be conveniently transferred to the aqueous phase by ligand exchange, showing great potential for multicolor NIR-II fluorescence imaging in vivo.
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Mixed epithelial and stromal tumor of the kidney: report of eight cases and literature review.
World J Surg Oncol
PUBLISHED: 02-10-2013
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Mixed epithelial and stromal tumor of the kidney (MESTK) is the term given to a class of uncommon biphasic tumors of the kidney, with few reported cases. We describe eight cases of MESTK with detailed clinicopathological data and follow-up information. With this report, we hope to increase clinical awareness that MESTK should be considered as one of the possible diagnoses for cystic renal mass, especially in peri-menopausal women or those who receive hormone therapy. In addition, regular follow-up is necessary for the any cases with malignant potential.
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Survey of Trichinella infections in domestic pigs from northern and eastern Henan, China.
Vet. Parasitol.
PUBLISHED: 02-05-2013
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The aim of this work was to investigate the current situation of Trichinella infections in swine in the cities of Anyang and Shanqiu in the Henan province historically designated as trichinellosis-free. A total of 475 diaphragm muscle samples were collected from 2010 to 2011 and examined by trichinelloscopy and artificial digestion. No Trichinella larvae were detected by trichinelloscopy; however, using the digestion method, 3.79% (18/475) of domestic pigs were deemed positive for Trichinella. Among the 475 pigs examined, 112 from an industrialized pig farm were negative. However. Trichinella larvae were detected in 10% (9/90) of pigs from small pig farms, which was significantly higher than the 3.3% (9/273) of pigs found positive from backyard farms (P<0.05). The larval burdens in infected animals ranged from 0.1 to 1.58 larvae per gram. The larvae were identified by multiplex PCR as Trichinella spiralis. Our study confirms the existence of porcine trichinellosis in northern and eastern parts of Henan. The results will be useful for evaluating the risk of infection for humans. Given this new found data, public health officials should consider implementing strategies to eliminate human transmission.
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Size-dependent dissociation of carbon monoxide on cobalt nanoparticles.
J. Am. Chem. Soc.
PUBLISHED: 02-04-2013
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In situ soft X-ray absorption spectroscopy (XAS) was employed to study the adsorption and dissociation of carbon monoxide molecules on cobalt nanoparticles with sizes ranging from 4 to 15 nm. The majority of CO molecules adsorb molecularly on the surface of the nanoparticles, but some undergo dissociative adsorption, leading to oxide species on the surface of the nanoparticles. We found that the tendency of CO to undergo dissociation depends critically on the size of the Co nanoparticles. Indeed, CO molecules dissociate much more efficiently on the larger nanoparticles (15 nm) than on the smaller particles (4 nm). We further observed a strong increase in the dissociation rate of adsorbed CO upon exposure to hydrogen, clearly demonstrating that the CO dissociation on cobalt nanoparticles is assisted by hydrogen. Our results suggest that the ability of cobalt nanoparticles to dissociate hydrogen is the main parameter determining the reactivity of cobalt nanoparticles in Fischer-Tropsch synthesis.
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Metabolomic study of collagen-induced arthritis in rats and the interventional effects of huang-lian-jie-du-tang, a traditional chinese medicine.
Evid Based Complement Alternat Med
PUBLISHED: 01-28-2013
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Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional Chinese medicine (TCM) with anti-inflammatory activity. The present study used a metabolomic approach based on LC-Q-TOF-MS to profile rheumatoid-arthritis- (RA-) related metabolic changes and to investigate the interventional mechanisms of HLJDT in collagen-induced arthritis rats. Forty male Wistar rats were randomly divided into five groups: (1) a model group, (2) a normal control group, (3) a dexamethasone group, (4) a HLJDT group, and (5) a group that received 13 components of HLJDT. Plasma samples were collected 8, 15, and 22 days after the rats were injected with bovine type II collagen. By combining variable importance in the projection values with partial least squares discriminant analysis, 18 potential biomarkers were identified in the plasma samples. The biomarkers were primarily involved in glycerophospholipid metabolism, fatty acid metabolism, tryptophan metabolism, linoleic acid metabolism, phenylalanine metabolism, purine metabolism, arachidonic acid metabolism, and bile acid biosynthesis. Using the potential biomarkers as a screening index, the results suggest that HLJDT can potentially reverse the process of RA by partially regulating fatty acid oxidation and arachidonic acid metabolism. This study demonstrates that a metabolomic strategy is useful for identifying potential RA biomarkers and investigating the underlying mechanisms of a TCM in RA treatment.
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Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders.
Nature
PUBLISHED: 01-27-2013
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Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes. Although skeletal muscle accounts for 70-90% of insulin-stimulated glucose disposal, the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1), and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications.
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Is Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography Useful for Detecting Bladder Lesions? A Meta-Analysis of the Literature.
Urol. Int.
PUBLISHED: 01-25-2013
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Objective: To evaluate the diagnostic accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the detection of bladder lesions. Methods: We conducted a systematic PubMed/MEDLINE and Embase database search of articles published before November 2012. Sensitivity, specificity, likelihood ratio and diagnostic odds ratio were pooled. A summary receiver operating characteristic curve was also used to summarize overall test performance. All meta-analyses were performed using the Meta-DiSc software (version 1.4). Results: Six studies met the inclusion criteria. The pooled sensitivity and specificity of PET or PET/CT for the detection of bladder cancer was 80.0% (95% CI: 71.0-87.0%) and 84.0% (95% CI: 69.0-93.0%), respectively. The overall positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 3.47 (95% CI: 1.03-11.65), 0.31 (95% CI: 0.13-0.70) and 13.86 (95% CI: 2.84-67.74), respectively. Besides, the area (± standard error) under the symmetrical summary receiver operating characteristic curve was 0.8574 ± 0.0704. Conclusion: When compared with results of MRI and CT published by other studies, (18)F-FDG PET or PET/CT showed no superiority in detecting local bladder lesions. As a whole body imaging, it is suggested that PET is more appropriate for the detection of metastasis.
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A reaction cell with sample laser heating for in situ soft X-ray absorption spectroscopy studies under environmental conditions.
J Synchrotron Radiat
PUBLISHED: 01-23-2013
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A miniature (1 ml volume) reaction cell with transparent X-ray windows and laser heating of the sample has been designed to conduct X-ray absorption spectroscopy studies of materials in the presence of gases at atmospheric pressures. Heating by laser solves the problems associated with the presence of reactive gases interacting with hot filaments used in resistive heating methods. It also facilitates collection of a small total electron yield signal by eliminating interference with heating current leakage and ground loops. The excellent operation of the cell is demonstrated with examples of CO and H2 Fischer-Tropsch reactions on Co nanoparticles.
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Siva1 inhibits p53 function by acting as an ARF E3 ubiquitin ligase.
Nat Commun
PUBLISHED: 01-23-2013
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The tumour suppressor alternative reading frame (ARF) is one of the most frequently mutated proteins in human cancer. It has been well established that ARF is able to stabilize and activate p53 by directly inhibiting Mdm2. ARF-mediated p53 activation in response to oncogenic stress is thought to be an important determinant of protection against cancer. However, little is known regarding the control of ARF in cells. Here, we show that Siva1 is a specific E3 ubiquitin ligase of ARF. Siva1 physically interacts with ARF both in vitro and in vivo. Through direct interaction, Siva1 promotes the ubiquitination and degradation of ARF, which in turn affects the stability of p53. Functionally, Siva1 regulates cell cycle progression and cell proliferation in an ARF/p53-dependent manner. Our results uncover a novel regulatory mechanism for the control of ARF stability, thereby revealing an important function of Siva1 in the regulation of the ARF-Mdm2-p53 pathway.
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Intense turquoise and green colors in brownmillerite-type oxides based on Mn5+ in Ba2In(2-x)Mn(x)O(5+x).
Inorg Chem
PUBLISHED: 01-18-2013
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Brownmillerite-type oxides Ba(2)In(2-x)Mn(x)O(5+x) (x = 0.1-0.7) have been prepared and characterized. Magnetic measurements indicate that manganese in as-prepared samples is substituting predominantly as Mn(5+) for all values of x with observed paramagnetic spin-only moments close to values expected for two unpaired electrons. Electron paramagnetic resonance measurements indicate that this Mn(5+) is present in a highly distorted tetrahedral environment. Neutron diffraction structure refinements show that Mn(5+) occupies tetrahedral sites for orthorhombic (x = 0.1) and tetragonal (x = 0.2) phases. For Mn ? 0.3 samples, neutron refinements show that the phases are cubic with disordered cations and oxygen vacancies. The colors of the phases change from light yellow (x = 0) to intense turquoise (x = 0.1) to green (x = 0.2, 0.3) or to dark green (x ? 0.4). Under reducing conditions, Mn(5+) is reduced to Mn(3+), and Ba(2)In(2-x)Mn(x)O(5+x) phases become black Ba(2)In(2-x)Mn(x)O(5) phases still with the brownmillerite structure.
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Experimental and theoretical investigation of the electronic structure of Cu2O and CuO thin films on Cu(110) using x-ray photoelectron and absorption spectroscopy.
J Chem Phys
PUBLISHED: 01-17-2013
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The electronic structure of Cu(2)O and CuO thin films grown on Cu(110) was characterized by X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS). The various oxidation states, Cu(0), Cu(+), and Cu(2+), were unambiguously identified and characterized from their XPS and XAS spectra. We show that a clean and stoichiometric surface of CuO requires special environmental conditions to prevent loss of oxygen and contamination by background water. First-principles density functional theory XAS simulations of the oxygen K edge provide understanding of the core to valence transitions in Cu(+) and Cu(2+). A novel method to reference x-ray absorption energies based on the energies of isolated atoms is presented.
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The effectiveness of borneol on pharmacokinetics changes of four ginsenosides in Shexiang Baoxin Pill in vivo.
Biomed. Chromatogr.
PUBLISHED: 01-15-2013
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Shexiang Baoxin Pill (SBP) is a traditional Chinese medicine, widely used for cardiovascular diseases in the clinic. Ginsenosides are important effective components in SBP, but their pharmacokinetic characteristics are still not known. In this paper, we studied the pharmacokinetics of ginsenoside Rb1, Rc, Re and Rg1 in SBP and investigated the effect of borneol on the pharmacokinetic characteristic of ginsenosides based on an Agilent G6410A triple quadrupole LC/MS system. Results showed that the pharmacokinetic parameters of ginsenoside Rb1, Rc, Re and Rg1 in rat plasma after oral administration of SBP are significantly different with oral administration of SBP without Borneolum Syntheticum. Plasma pharmacokinetic profiles after oral administration of ginsenoside Rb1, Rc, Re, Rg1 and co-administration with borneol at three different ratios (10:1, 1:1 and 1:10 ginsenoside vs borneol, w/w) were also determined. It was demonstrated that borneol can elevate the plasma concentration of ginsenosides after co-admininstration. Copyright © 2013 John Wiley & Sons, Ltd.
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Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence.
Nature
PUBLISHED: 01-13-2013
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Cellular senescence both protects multicellular organisms from cancer and contributes to their ageing. The pre-eminent tumour suppressor p53 has an important role in the induction and maintenance of senescence, but how it carries out this function remains poorly understood. In addition, although increasing evidence supports the idea that metabolic changes underlie many cell-fate decisions and p53-mediated tumour suppression, few connections between metabolic enzymes and senescence have been established. Here we describe a new mechanism by which p53 links these functions. We show that p53 represses the expression of the tricarboxylic-acid-cycle-associated malic enzymes ME1 and ME2 in human and mouse cells. Both malic enzymes are important for NADPH production, lipogenesis and glutamine metabolism, but ME2 has a more profound effect. Through the inhibition of malic enzymes, p53 regulates cell metabolism and proliferation. Downregulation of ME1 and ME2 reciprocally activates p53 through distinct MDM2- and AMP-activated protein kinase-mediated mechanisms in a feed-forward manner, bolstering this pathway and enhancing p53 activation. Downregulation of ME1 and ME2 also modulates the outcome of p53 activation, leading to strong induction of senescence, but not apoptosis, whereas enforced expression of either malic enzyme suppresses senescence. Our findings define physiological functions of malic enzymes, demonstrate a positive-feedback mechanism that sustains p53 activation, and reveal a connection between metabolism and senescence mediated by p53.
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Content determination of the major constituents of Yinchenzhufu decoction via ultra high-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry.
J Pharm Biomed Anal
PUBLISHED: 01-10-2013
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In this study, we developed a method using ultra high-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry for determining the contents of chlorogenic acid, atractylenolide I, atractylenolide III, benzoylaconine, benzoylmesaconine, benzoylhypaconine, glycyrrhizic acid, glycyrrhetic acid, liquiritigenin, and cinnamic acid in Yinchenzhufu decoction, a classic traditional Chinese medicine prescription. Separation was performed on a C18 column (4.6mm i.d.×250mm, 5?m) and achieved with good linearity (r(2)>0.9984) within 35min. Gradient elution was applied using a mobile phase of 0.05% acetic acid/acetonitrile. The analytes were quantified on an LCQ ion trap mass spectrometer in electrospray ionisation full-scan mode. Variations in the intra- and inter-day precision of all analytes were below 4.57%, and the accuracy was evaluated by a recovery test within the range of 97.88-102.25%. The method successfully quantified the 10 compounds in five sample batches of Yinchenzhufu decoction, and the results show that the method is accurate, sensitive, and reliable.
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Simultaneous determination of eleven major components in Fugan Fang using high-performance liquid chromatography coupled with mass spectrometry.
Biomed. Chromatogr.
PUBLISHED: 01-06-2013
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Fugan fang (FGF) is a traditional Chinese medicine (TCM) prescription that has been used in treating hepatic illnesses for many years. In this study, an analytical method is developed for the quantitative analysis of the major components of FGF. This method is based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) on a reverse-phase C18 column. Results show that 0.01% acetic acid and acetonitrile is the optimum mobile phase in gradient elution. All compounds showed good linearity (r(2) ? 0.9948). Recoveries measured at three concentration levels varied from 83.5 to 104.8%. The method was validated with respect to precision, repeatability and accuracy and was successfully applied in the quantification of the 11 components of FGF products. The validated HPLC-MS method provides a basis for assessing the quality of TCM prescriptions containing many bioactive components.
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