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Find video protocols related to scientific articles indexed in Pubmed.
Multitarget inhibitors derived from crosstalk mechanism involving VEGFR2.
Future Med Chem
PUBLISHED: 11-20-2014
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Seven VEGFR small-molecule inhibitors have been approved by the US FDA as anticancer drugs, which confirms the therapeutic value of angiogenesis inhibitors. However, much more evidence indicates that VEGFR inhibition alone is usually not sufficient to block the tumor progress. The potential of some agents targeting VEGFR owes partially to the simultaneous inhibition of additional targets in other signaling pathways. In this review, the crosstalk between VEGFR2 and the additional targets in other signaling pathways, such as EGFR, MET, FGFR, PDGFR, c-Kit, Raf, PI3K and HDAC, and the synergistic effects derived from multitarget activities against these crosstalks are discussed. We also briefly describe the multitarget inhibitors in clinical trials or reported in the literature and patents under the different multitarget categories involving VEGFR2.
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Docking to multiple pockets or ligand fields for screening, activity prediction and scaffold hopping.
Future Med Chem
PUBLISHED: 11-20-2014
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Background: Two recent technological advances dramatically reducing the rate of false-negatives in activity prediction by docking flexible 3D models of compounds include multi-conformational docking (mPockDock) and the docking of candidates to atomic property fields derived by co-crystallized ligands (mApfDock). Results: The mApfDock and mPockDock provide the AUC of 90.4 and 83.8%, respectively. The mApfDock gave better performance when compounds required large induced-fit pocket changes unseen in crystallography, whereas the mPockDock is superior when the co-crystallized ligands do not represent sufficient chemical and binding location diversity. Conclusion: Both approaches proved to be efficient for scaffold hopping; they are complementary when the coverage of the co-crystallized complexes is poor but become convergent when the complexes are diverse enough.
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Activation of ENaC by AVP Contributes to Urinary Concentrating Mechanism and Dilution of Plasma.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 11-14-2014
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Vasopressin (AVP) activates the epithelial Na+ channel (ENaC). The physiological significance of this activation is unknown. The current studies test if activation of ENaC contributes to AVP-sensitive urinary concentration. Consumption of a 3% NaCl solution induced hypernatremia and plasma hypertonicity in mice. Plasma [AVP] and urine osmolality increased in hypernatremic mice in an attempt to compensate for increases in plasma tonicity. ENaC activity was elevated in mice consuming 3% NaCl solution compared to mice consuming a diet enriched in Na+ with ad libitum tap water. The latter diet does not cause hypernatremia. To determine whether the increase in ENaC activity in mice consuming 3% NaCl solution served to compensate for hypernatremia, mice were treated with the ENaC inhibitor benzamil. Co-administration of benzamil with 3% NaCl solution decreased urinary osmolality and increased urine flow so that urinary Na+ excretion increased with no effect on urinary [Na+]. This decrease in urinary concentration further increased plasma [Na+], osmolality, and [AVP] in these already hypernatremic mice. Benzamil similarly compromised urinary concentration in water deprived mice and in mice treated with desmopressin. These results demonstrate that stimulation of ENaC by AVP plays a critical role in water homeostasis by facilitating urinary concentration, which can compensate for hypernatremia or exacerbate hyponatremia. The current findings are consistent with ENaC in addition to serving as a final effector of the renin-angiotensin-aldosterone system and blood pressure homeostasis, also playing a key role in water homeostasis by regulating urine concentration and dilution of plasma.
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HBx transfection limits proliferative capacity of podocytes through cell cycle regulation.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 11-13-2014
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Our previous studies have shown that podocyte number is significantly decreased in glomeruli of children with hepatitis B virus (HBV)-associated glomerulonephritis. In this study, we aimed to explore whether exogenous expression of HBx protein could directly inhibit podocyte proliferation in vitro, and to investigate its role in cell cycle regulation. HBx gene was delivered into cultured mouse podocytes through an adenovirus-based vector. Cell morphology was evaluated with Wright-Giemsa staining. Cell growth and proliferation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5,6-carboxyfluorescein diacetate, succinimidyl ester (CFSE)-based proliferation assays. Cell cycle phase was analyzed by flow cytometry, and the expression of cell cycle regulatory proteins was examined by western blot analysis. It was found that the aberrant nuclear changes like double and multiple micronuclei, which reflect mitotic catastrophe, accumulated in podocytes after 5 days post-infection. MTT assays showed that Ad.HBx-infected podocytes grew much more slowly than controls at day 4 post-infection and thereafter. Furthermore, CFSE-based proliferation assay also showed that the proliferation of HBx-expressing podocytes was significantly inhibited than that of controls at 3-day post-infection, and that the difference became much more obvious at day 5 post-infection. Cell cycle analysis showed that the transfection of HBx resulted in significant up-regulation of both cyclin B1 and CDK-inhibitor p21 expression and G2/M phase arrest, and slight down-regulation of cyclin A expression. These results demonstrated that exogenous expression of HBx might limit the proliferative capacity of podocytes through cell cycle regulation, thus suggesting that HBx may play a role in podocyte injuries in HBV-associated glomerulonephritis.
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Identifying actionable targets through integrative analyses of GEM model and human prostate cancer genomic profiling.
Mol. Cancer Ther.
PUBLISHED: 11-09-2014
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Copy number alterations (CNAs) are among the most common molecular events in human prostate cancer genomes and are associated with worse prognosis. Identification of the oncogenic drivers within these CNAs is challenging due to the broad nature of these genomic gains or losses which can include large numbers of genes within a given region. Here we profiled the genomes of four genetically engineered mouse prostate cancer models that reflect oncogenic events common in human prostate tumors, with the goal of integrating these data with human prostate cancer datasets to identify shared molecular events. Met was amplified in 67% of prostate tumors from Pten p53 prostate conditional null mice and in approximately 30% of metastatic human prostate cancer specimens, often in association with loss of PTEN and TP53. In murine tumors with Met amplification, Met copy number gain and expression was present in some cells but not others, revealing intratumoral heterogeneity. Forced MET overexpression in non-MET amplified prostate tumor cells activated PI3K and MAPK signaling and promoted cell proliferation and tumor growth, whereas MET kinase inhibition selectively impaired the growth of tumors with Met amplification. However, the impact of MET inhibitor therapy was compromised by the persistent growth of non-Met amplified cells within Met-amplified tumors. These findings establish the importance of MET in prostate cancer progression but reveal potential limitations in the clinical use of MET inhibitors in late state prostate cancer.
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Facile synthesis of hydrophilic multi-colour and upconversion photoluminescent mesoporous carbon nanoparticles for bioapplications.
Chem. Commun. (Camb.)
PUBLISHED: 11-06-2014
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Hydrophilic mesoporous carbon nanoparticles (MCNs) have been synthesized via an extremely facile precursor carbonization-in-hot solvent route. The synthesized MCNs show well-defined particle and pore size distribution at around 100 nm and 2.7 nm, respectively, and multicolor and upconversion photoluminescence, which endow the MCNs with multicolor/upconversion bioimaging and drug delivery properties.
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Phenolic glycosides from Glycosmis pentaphylla.
J Asian Nat Prod Res
PUBLISHED: 11-05-2014
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Three new phenolic glycosides, named as glycopentosides A-C (1-3), along with nine known compounds were isolated from the n-BuOH extract of stems of Glycosmis pentaphylla. Their structures were determined by using spectroscopic and chemical methods. Bioassay showed that compound 10 (tachioside) could inhibit nitric oxide production in lipopolysaccharides-stimulated RAW 264.7 cells with IC50 value of 12.14 ?M.
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Nanomedicine: Break-up of Two-Dimensional MnO2 Nanosheets Promotes Ultrasensitive pH-Triggered Theranostics of Cancer (Adv. Mater. 41/2014).
Adv. Mater. Weinheim
PUBLISHED: 11-04-2014
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Exfoliated 2D MnO2 nanosheets described by J. Shi, L. Wang, and co-workers on page 7019, show a unique break-up nature in mild acidic microenvironment of tumor tissues, which could substantially enhance the in vitro and in vivo performances of T1 -weighted magnetic resonance imaging. Such a pH-triggered break-up nature can also promote the fast release of loaded anticancer drugs for concurrent pH-responsive theranostics of cancer.
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Solution processable colloidal nanoplates as building blocks for high-performance electronic thin films on flexible substrates.
Nano Lett.
PUBLISHED: 11-03-2014
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Low-temperature solution-processed electronic materials on plastic substrates are of considerable interest for flexible electronics. Solution dispersible inorganic nanostructures (e.g., zero-dimensional (0D) quantum dots or one-dimensional (1D) nanowires) have emerged as interesting ink materials for low-temperature solution processing of electronic thin films on flexible substrates, but usually with limited performance due to the large number of grain boundaries (0D) or incomplete surface coverage (1D). Here, we report two-dimensional (2D) colloidal nanoplates of layered materials as a new ink material for solution assembly of high-performance electronic thin films. The 2D colloidal nanoplates exhibit few dangling bonds and represent an ideal geometry for the assembly of highly uniform continuous thin films with greatly reduced grain boundaries dictated by large-area conformal plane-plane contact with atomically flat/clean interfaces. It can therefore promise efficient charge transport across neighboring nanoplates and throughout the entire thin film to enable unprecedented electronic performance. We show that Bi2Se3 and Bi2Te3 nanoplates can be synthesized with well-controlled thickness (6-15 nm) and lateral dimension (0.5-3 ?m) and can be used for the assembly of highly uniform continuous thin films with a full surface coverage and an excellent room temperature carrier mobility >100 cm(2)·V(-1)·s(-1), approaching that of chemical vapor deposition grown materials. Our study demonstrates a general strategy to using 2D nanoplates as a unique building block for the construction of high-performance electronic thin films on plastic substrates for future flexible electronics and optoelectronics.
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Clinical Application of High-pitch Excretory Phase Images during Dual-source CT Urography with Stellar Photon Detector.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 11-01-2014
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Objective To retrospectively evaluate the clinical feasibility of high-pitch excretory phase images during dual-source CT urography with Stellar photon detector. Methods Totally 100 patients received dual-source CT high-pitch urinary excretory phase scanning with Stellar photon detector[80 kV,ref.92 mAs,CARE Dose 4D and CARE kV,pitch of 3.0,filter back projection reconstruction algorithm (FBP)](group A). Another 100 patients received dual-source CT high-pitch urinary excretory phase scanning with common detector(100 kV,ref.140 mAs,CARE Dose 4D,pitch of 3.0,FBP)(group B). Quantitative measurement of CT value of urinary segments(Hounsfield units),image noise(Hounsfield units),and effective radiation dose(millisievert)were compared using independent-samples t test between two groups. Urinary system subjective opacification scores were compared using Mann-Whitney U test between two groups. Results There was no significant difference in subjective opacification score of intrarenal collecting system and ureters between two groups(all P>0.05). The group A images yielded significantly higher CT values of all urinary segments(all P<0.01). There was no significant difference in image noise(P>0.05). The effective radiation dose of group A(1.1 mSv)was significantly lower than that of group B(3.79 mSv)(P<0.01). Conclusion High-pitch low-tube-voltage during excretory phase dual-source CT urography with Stellar photon detector is feasible,with acceptable image noise and lower radiation dose.
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Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine.
J. Med. Chem.
PUBLISHED: 10-31-2014
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CXCL12 binds to CXCR4, promoting both chemotaxis of lymphocytes and metastasis of cancer cells. We previously identified small molecule ligands that bind CXCL12 and block CXCR4-mediated chemotaxis. We now report a 1.9 Å resolution X-ray structure of CXCL12 bound by such a molecule at a site normally bound by sY21 of CXCR4. The complex structure reveals binding hot spots for future inhibitor design and suggests a new approach to targeting CXCL12-CXCR4 signaling in drug discovery.
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[Electromagnetic navigation bronchoscopy real-time guidance lung biopsy for the diagnosis of small peripheral pulmonary lesions].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 10-30-2014
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To evaluate the diagnostic value and safety of electromagnetic navigation bronchoscopy real-time guidance lung biopsy (ENB-guided TBLB) of small peripheral lung lesions (diameter < 3 cm).
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Efficacy of intraperitoneal and intravenous chemotherapy for advanced gastric cancer with peritoneal metastasis.
Tumori
PUBLISHED: 10-25-2014
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Aims and background. Peritoneal metastasis (PM) in patients with advanced gastric cancer (AGC) is a poor prognostic indicator. The aim of this study was to compare the response of AGC patients with PM to paclitaxel-based systemic multidrug chemotherapy with and without additional intraperitoneal (IP) chemotherapy through retrospective analysis. Methods and study design. Two hundred and sixty-three AGC patients with PM were enrolled. Eighty-two patients received systemic paclitaxel/oxaliplatin and leucovorin/5-fluorouracil (POF) and 181 patients received 2-drug systemic therapies, PO (paclitaxel + oxaliplatin) or PF (paclitaxel + 5-fluorouracil + leucovorin), and IP infusion of a third drug. Results. Patients who received the POF regimen had longer progression-free survival (PFS) and overall survival (OS) than patients who received PO/PF + IP therapy (P = 0.026 and P = 0.046), respectively. In subgroup analysis, no significant differences in PFS and OS were observed between the POF regimen and PF/PO + IP regimens in patients with isolated peritoneal metastatic disease. Patients with multiorgan metastatic disease receiving POF had better PFS and better OS than patients receiving PO/PF + IP chemotherapy (P = 0.005 and P = 0.036, respectively). In multivariate analysis, ECOG performance status and the interaction between different therapeutic strategies and multiorgan metastasis were independent prognostic factors for survival. Leukopenia, fatigue and peripheral neuropathy were higher on the triplet regimen than the doublet regimens. Conclusions. Paclitaxel-based doublet therapy combined with IP chemotherapy had more manageable toxicity and equal efficiency compared to triplet therapy for AGC patients with isolated PM. The POF regimen may be a good choice for AGC patients with multiorgan metastasis, especially those having a good performance status.
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Hollow Mesoporous Organosilica Nanoparticles: A Generic Intelligent Framework-Hybridization Approach for Biomedicine.
J. Am. Chem. Soc.
PUBLISHED: 10-25-2014
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Chemical construction of molecularly organic-inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) with silsesquioxane framework is expected to substantially improve their therapeutic performance and enhance the biological effects beneficial for biomedicine. In this work, we report on a simple, controllable, and versatile chemical homology principle to synthesize multiple-hybridized HMONs with varied functional organic groups homogeneously incorporated into the framework (up to quintuple hybridizations). As a paradigm, the hybridization of physiologically active thioether groups with triple distinctive disulfide bonds can endow HMONs with unique intrinsic reducing/acidic- and external high intensity focused ultrasound (HIFU)-responsive drug-releasing performances, improved biological effects (e.g., lowered hemolytic effect and improved histocompatibility), and enhanced ultrasonography behavior. The doxorubicin-loaded HMONs with concurrent thioether and phenylene hybridization exhibit drastically enhanced therapeutic efficiency against cancer growth and metastasis, as demonstrated both in vitro and in vivo.
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Association between Cigarette Smoking and RASSF1A Gene Promoter Hypermethylation in Lung Cancer Patients: a Meta- analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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Epidemiological studies have shown that molecular mechanisms underlying the development of lung cancers differ between smokers and unsmokers. Aberrant promoter methylation in some tumor suppressor genes is frequent in lung tumors from smokers but rare in those from non-smokers. Recently, many studies have investigated the association between cigarette smoking and RASSF1A gene promoter hypermethylation in lung cancer patients, but a unanimous conclusion could not be reached. We therefore performed this meta-analysis to derive a more precise estimation of any association.
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Targeting Nucleus DNA with a Cyclometalated Dipyridophenazineruthenium(II) Complex.
J. Med. Chem.
PUBLISHED: 10-23-2014
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Recently, coordinatively saturated and substitutionally inert Ru(II) complexes have been investigated as anticancer agents. Herein a cyclometalated Ru(II) complex, [Ru(bpy)(phpy)(dppz)](+), was found to be rapidly taken up by cancer cells, and nearly 90% of the complex accumulated in the nuclei of cancer cells after a 2 h incubation. The anticancer activity of this complex was screened against a panel of cancer cell lines. Remarkably, it exhibited IC50 values that were an order of magnitude lower than those of cisplatin. This complex also displayed potencies superior to those of cisplatin against 3D tumor spheroids. Further studies revealed that the high DNA binding affinity of [Ru(bpy)(phpy)(dppz)](+) resulted in effective disruption of the binding of transcription factor NF-?B to DNA sequences, thereby inhibiting cellular transcription and leading to irreversible cancer cell apoptosis. Our work provides new insights into understanding the biological interactions and anticancer molecular mechanisms of DNA-specific Ru(II) polypyridyl complexes.
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Draft Genome Sequence of Halotolerant Polycyclic Aromatic Hydrocarbon-Degrading Pseudomonas bauzanensis Strain W13Z2.
Genome Announc
PUBLISHED: 10-18-2014
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Pseudomonas bauzanensis W13Z2 is a halotolerant polycyclic aromatic hydrocarbon (PAH)-degrading bacterium isolated from petroleum-contaminated drill cuttings in the Bohai Sea. Here, we report the 8.6-Mb draft genome sequence of this strain, which will provide insights into the diversity of Pseudomonas and the mechanism of PAHs degradation in drill cuttings.
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Ion collision crosssection measurements in quadrupole ion traps using a time-frequency analysis method.
Analyst
PUBLISHED: 10-17-2014
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In this study, a method for measuring ion collision crosssections (CCSs) was proposed through time-frequency analysis of ion trajectories in quadrupole ion traps. A linear ion trap with added high-order electric fields was designed and simulated. With the presence of high-order electric fields and ion-neutral collisions, ion secular motion frequency within the quadrupole ion trap will be a function of ion motion amplitude, thus a function of time and ion CCS. A direct relationship was then established between ion CCS and ion motion frequency with respect to time, which could be obtained through time-frequency analysis of ion trajectories (or ion motion induced image currents). To confirm the proposed theory, realistic ion trajectory simulations were performed, where the CCSs of bradykinin, angiotensin I and II, and ubiquitin ions were calculated from simulated ion trajectories. As an example, differentiation of isomeric ubiquitin ions was also demonstrated in the simulations.
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Growth and Raman spectra of single-crystal trilayer graphene with different stacking orientations.
ACS Nano
PUBLISHED: 10-08-2014
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Understanding the growth mechanism of graphene layers in chemical vapor deposition (CVD) and their corresponding Raman properties is technologically relevant and of importance for the application of graphene in electronic and optoelectronic devices. Here, we report CVD growth of single-crystal trilayer graphene (TLG) grains on Cu and show that lattice defects at the center of each grain persist throughout the growth, indicating that the adlayers share the same nucleation site with the upper layers and these central defects could also act as a carbon pathway for the growth of a new layer. Statistics shows that ABA, 30-30, 30-AB, and AB-30 make up the major stacking orientations in the CVD-grown TLG, with distinctive Raman 2D characteristics. Surprisingly, a high level of lattice defects results whenever a layer with a twist angle of ? = 30° is found in the multiple stacks of graphene layers.
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A real-time fluorescence polarization activity assay to screen for inhibitors of bacterial ribonuclease P.
Nucleic Acids Res.
PUBLISHED: 09-23-2014
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Ribonuclease P (RNase P) is an essential endonuclease that catalyzes the 5' end maturation of precursor tRNA (pre-tRNA). Bacterial RNase P is an attractive potential antibacterial target because it is essential for cell survival and has a distinct subunit composition compared to the eukaryal counterparts. To accelerate both structure-function studies and discovery of inhibitors of RNase P, we developed the first real-time RNase P activity assay using fluorescence polarization/anisotropy (FP/FA) with a 5' end fluorescein-labeled pre-tRNA(Asp) substrate. This FP/FA assay also detects binding of small molecules to pre-tRNA. Neomycin B and kanamycin B bind to pre-tRNA(Asp) with a Kd value that is comparable to their IC50 value for inhibition of RNase P, suggesting that binding of these antibiotics to the pre-tRNA substrate contributes to the inhibitory activity. This assay was optimized for high-throughput screening (HTS) to identify specific inhibitors of RNase P from a 2880 compound library. A natural product derivative, iriginol hexaacetate, was identified as a new inhibitor of Bacillus subtilis RNase P. The FP/FA methodology and inhibitors reported here will further our understanding of RNase P molecular recognition and facilitate discovery of antibacterial compounds that target RNase P.
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The dynamic process of atmospheric water sorption in [EMIM][Ac] and mixtures of [EMIM][Ac] with biopolymers and CO2 capture in these systems.
J Phys Chem B
PUBLISHED: 09-23-2014
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There are mainly three findings related to the dynamic process of atmospheric water sorption in the ionic liquid (IL) 1-ethyl-3-methlyl-imidazolium acetate ([EMIM][Ac]) and its mixtures with biopolymers (i.e., cellulose, chitin, and chitosan), and CO2 capture in these systems above. The analytical methods mainly include gravimetric hygroscopicity measurement and in situ infrared spectroscopy with the techniques of difference, derivative, deconvoluted attenuated total reflectance and two-dimensional correlation. These three findings are listed as below. (1) Pure [EMIM][Ac] only shows a two-regime pattern, while all the mixtures of [EMIM][Ac] with biopolymers (i.e., cellulose, chitin, and chitosan) present a three-regime tendency for the dynamic process of atmospheric water sorption. Specifically, the IL/chitosan mixture has a clear three-regime mode; the [EMIM][Ac]/chitin mixture has an unclear indiscernible regime 3; and the [EMIM][Ac]/cellulose mixture shows an indiscernible regime 2. (2) [EMIM][Ac] and its mixtures with biopolymers could physically absorb a trace amount of and chemically react with a much larger amount of CO2 from the air. The chemisorption capacity of CO2 in these pure and mixed systems is ordered as chitosan/[EMIM][Ac] mixture > chitin/[EMIM][Ac] mixture > cellulose/[EMIM][Ac] mixture > pure [EMIM][Ac] (ca. 0.09 mass ratio % g/g CO2/IL). (3) The CO2 solubility in [EMIM][Ac] decreases about 50% after being exposed to the atmospheric moist air for some specific time period.
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Draft Genome Sequence of Brachybacterium phenoliresistens Strain W13A50, a Halotolerant Hydrocarbon-Degrading Bacterium.
Genome Announc
PUBLISHED: 09-20-2014
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Brachybacterium phenoliresistens strain W13A50 was isolated from a petroleum-contaminated saline site, which could degrade hydrocarbon under high salinity conditions. Here, we present 4.2-Mb draft genome sequence of this strain, which will provide insights into the diversity of Brachybacterium and the mechanism of hydrocarbon degradation in saline environments.
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Molecular characterization and different expression patterns of the FABP gene family during goat skeletal muscle development.
Mol. Biol. Rep.
PUBLISHED: 09-18-2014
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The FABP (adipocyte fatty acid-binding protein) genes play an important role in intracellular fatty acid transport and considered to be candidate genes for fatness traits in domestic animal. In this study, we cloned the cDNA sequences of goat FABP family genes and their expression patterns were detected by semi-quantitative RT-PCR and quantitative real time RT-PCR. Expression analysis showed that goat FABP1 gene was predominantly expressed in liver, kidney and large intestine. While FABP4 was widely expressed in many tissues with a high expression level was observed in the fat, skeletal muscle, stomach and lung. Notably, FABP2 gene was expressed specifically in small intestine. Moreover, goat FABP3 was expressed at 60 day with the highest level, then significantly (p < 0.01) decreased at the 90 day. No significant expression differences were observed in longissimus dorsi muscles among 3 day, 30 day and 60 day. Goat FABP4 was expressed at 3 day with the lowest level, then significantly (p < 0.01) increased to a peak at the 60 day. In addition, a significant relationship between FABP3 mRNA expression levels and intramuscular fat (IMF) content was observed. These results suggest that the FABP3 and FABP4 may be important genes for meat quality and provides useful information for further studies on their roles in skeletal muscle IMF deposit.
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Fiducial markers configuration optimization in image-guided surgery.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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The rigid registration is a key step of Image Guided Surgery (IGS), and the point-pair method is the main way used for registration. However the configuration of fiducial points has a great influence on the registration accuracy at the target point. Now almost all the optimization method of fiducial points configuration relies on the empirical simulation-based Fitzpatrick's target registration error (TRE). In this paper, a phantom and some markers were designed and some experiments were conducted to measure and compare the affecting factors on the registration. By the markers repeated selections, the fiducial location error (FLE) has a small deviation of maximum 0.4 mm, and the average of the Fitzpatrick's TRE (F-TRE) has almost 86% proportion to the average of the actual TRE (A-TRE), but the standard deviation (STD) just has 7% proportion. Also, the experiment result showed that six fiducial markers already had the 86% accuracy, and spreading the fiducial markers led to 30% reduction in mean of A-TRE and 40% reduction in STD of A-TRE comparing with the centralized. Overall, to find a strategy of optimization, reducing the TRE has the great meaning to support safer and more accurate minimally IGS procedures.
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Combinatorial screening of an in situ generated library of tungsten oxyhalide and imido complexes for olefin metathesis.
ACS Comb Sci
PUBLISHED: 09-17-2014
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A series of substituted tungsten(VI) halides with general formula WECl4 (E = O or -NR (imido)) were screened via a high throughput study to identify potential new olefin metathesis catalysts. The tungsten species were treated with a series of aluminum alkyl activators and modifier ligands to generate active catalyst species in situ. Ring-opening metathesis polymerization (ROMP) of cyclooctene was used as a primary screen to identify potential metathesis catalysts and active catalysts were subjected to a secondary screen to evaluate tolerance toward polar functional groups. Several combinations from the high throughput campaign yielded active metathesis catalysts for the ROMP of cyclooctene. However, none of the catalysts examined in this study exhibited any evidence of significant polar functional group tolerance as determined by the results of the secondary cyclooctene/butyl acetate screen.
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Vitamin D deficiency promotes nonalcoholic steatohepatitis through impaired enterohepatic circulation in animal model.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 09-11-2014
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Vitamin D deficiency (VDD) or insufficiency is recognized for its association with nonalcoholic steatohepatitis (NASH), whereas the underlying mechanism remains unknown. Using animal models, we found that vitamin D deficiency promoted the high-fat diet (HFD)-initiated simple steatosis into typical NASH, characterized by elevated hepatic inflammation and fat degeneration. The NASH derived from VDD + HFD was related to poor retention of bile acids in the liver and biliary tree, in line with downregulation of the ileal apical sodium-dependent bile acid cotransporter (iASBT). The impediment of hepatic bile acids by the VDD + HFD mice was related to increased expression of hepatic SREBP-1c and fatty acid synthase, suggesting that VDD may upregulate endogenous fatty acid synthesis into NASH through impaired enterohepatic circulation. Administration of 1,25(OH)2VD3 (calcitriol) corrected the NASH phenotypes in line with restoration of iASBT, promotion of bile filling in the biliary tree, suppression of hepatic lipogenesis, and inflammation. Moreover, administration of a bile acid-sequestering agent suppressed ileal fibroblast growth factor 15 expression, leading to increased iASBT expression to restore bile filling in the liver and biliary tree, which ameliorates steatosis and inflammation in the liver. These results suggest a novel mechanism for NASH development, by which VDD downregulates iASBT expression, resulting in a poor bile acid pool and elevation of hepatic lipogenesis and inflammation. In conclusion, vitamin D and bile acid sequestration may be explored as new strategies to treat or prevent NASH.
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[Relationship between CD4+CD25+Treg cells, Th17 cells and IL-6 and the prognosis of hepatitis B virus-related acute-on-chronic liver failure: a meta-analysis].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-10-2014
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To investigate the role ofCD4+CD25+ T regulatory (Treg) cells, T helper (Th)17cells and interleukin (IL)-6 in the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) and determine their value as prognostic markers.
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[Protective role of PTEN inhibition against liver ischemia-reperfusion injury in mice and its underlying mechanisms].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-10-2014
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To investigate whether inhibition of phosphatase and tensin homologue deleted on chromosome ten (PTEN) is protective against liver ischemia-reperfusion injury (IRI) in mice and to explore its possible mechanism.
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Electroluminescence and Photocurrent Generation from Atomically Sharp WSe2/MoS2 Heterojunction p-n Diodes.
Nano Lett.
PUBLISHED: 09-08-2014
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The p-n diodes represent the most fundamental device building blocks for diverse optoelectronic functions, but are difficult to achieve in atomically thin transition metal dichalcogenides (TMDs) due to the challenges in selectively doping them into p- or n-type semiconductors. Here, we demonstrate that an atomically thin and sharp heterojunction p-n diode can be created by vertically stacking p-type monolayer tungsten diselenide (WSe2) and n-type few-layer molybdenum disulfide (MoS2). Electrical measurements of the vertically staked WSe2/MoS2 heterojunctions reveal excellent current rectification behavior with an ideality factor of 1.2. Photocurrent mapping shows rapid photoresponse over the entire overlapping region with a highest external quantum efficiency up to 12%. Electroluminescence studies show prominent band edge excitonic emission and strikingly enhanced hot-electron luminescence. A systematic investigation shows distinct layer-number dependent emission characteristics and reveals important insight about the origin of hot-electron luminescence and the nature of electron-orbital interaction in TMDs. We believe that these atomically thin heterojunction p-n diodes represent an interesting system for probing the fundamental electro-optical properties in TMDs and can open up a new pathway to novel optoelectronic devices such as atomically thin photodetectors, photovoltaics, as well as spin- and valley-polarized light emitting diodes, on-chip lasers.
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Inducing apoptosis effect of caffeic acid 3,4-dihydroxy-phenethyl ester on the breast cancer cells.
Tumour Biol.
PUBLISHED: 09-05-2014
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To explore the antitumor effect of caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) on the breast cancer cell lines and illuminate the related mechanism. After treatment with different concentrations of CADPE for 24, 48, and 72 h, cell proliferation ability of the breast cancer cell lines MDA-MB-231 and MDA-MB-435 was analyzed by the MTT. Changes of the cell cycles were evaluated by PI staining. Cell apoptosis was examined by flow cytometry after Annexin V/7AAD double staining. Nuclear morphologic changes were observed under the inverted fluorescence microscope after staining with Hoechst 33342. Mitochondrial membrane potential and reactive oxygen species (ROS) level were estimated by JC-1 and DCFH-DA staining. In addition, the expression level of mitochondrial signaling pathway proteins Bcl-2, Bax, and caspase-3 were evaluated by Western blot. CADPE has the distinct cytotoxic effect to the breast cancer cells, and the effect is dose dependent. It did not change the cell cycles but induced the cell apoptosis of the breast cancer cells. At the same time, after CADPE treatment, the expression levels of caspase-3 and Bax in the breast cancer cells were upregulated and Bcl-2 expression was declined. The ROS level in the breast cancer cells was enhanced, and mitochondrial membrane potential of the cells was downregulated. CADPE has the antitumor functions. It can induce the cell apoptosis through downregulating Bcl-2 expression, enhancing Bax and caspase-3 expression levels, upregulating ROS level and reducing the mitochondrial membrane potential of the breast cancer cells to trigger the mitochondrial signal pathway.
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The significance of serum xanthine oxidoreductase in patients with nonalcoholic fatty liver disease.
Clin. Lab.
PUBLISHED: 09-05-2014
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Serum uric acid levels are significantly associated with nonalcoholic fatty liver disease (NAFLD). Xanthine oxidoreductase (XOR) is the key enzyme that catalyzes the formation of uric acid. The aim of this study was to investigate the association between serum XOR activity and NAFLD.
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Layer-dependent optical conductivity in atomic thin WS? by reflection contrast spectroscopy.
ACS Appl Mater Interfaces
PUBLISHED: 09-05-2014
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Optical conductivity, which originates from the interband transition due to electron-phonon interaction, is one of the powerful tools used for studying the electronic states in layered transition metal dichalcogenides (TMDCs). Here, we report for the first time the optical conductivity of WS2, one of the emerging classes of TMDCs, prepared directly on SiO2/Si substrate using reflection contrast spectroscopy. The measured optical conductivity at direct excitonic transition point K of the Brillouin zone for monolayer WS2 shows a value of 0.37 e(2)/?? in the visible range of the energy spectrum. Our results reveal that the optical conductivity of WS2 layers is frequency-dependent and show additional features in the conductivity spectra for bilayer to bulk counterparts, signifying a transition from direct band gap to indirect band gap with the evolution of layer numbers as predicted by our calculations.
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[Role of endoplasmic reticulum stress in D-GalN/LPS-induced acute liver failure].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-03-2014
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To study the role of endoplasmic reticulum stress (ERS) in acute liver failure (ALF) using a mouse model of D-Galactosamine/lipopolysaccharide (D-GalN/LPS)-induced ALF.
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Comparison of contrast-enhanced sonography with MRI in the diagnosis of complex cystic renal masses.
J Clin Ultrasound
PUBLISHED: 09-01-2014
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To compare the diagnostic performance of contrast-enhanced ultrasound (CEUS) with MRI for complex cystic renal masses.
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[Changes of regulatory T cells related to CCl?-induced liver fibrosis in mice].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-01-2014
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To investigate liver fibrosis-related changes of CD4?CD25?Foxp3+ regulatory T cells (Tregs) in peripheral blood and in liver-infiltrating lymphocytes (LILs) using a mouse model.
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Hydrothermal synthesis of Pt-Ag alloy nano-octahedra and their enhanced electrocatalytic activity for the methanol oxidation reaction.
Nanoscale
PUBLISHED: 08-30-2014
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The high-quality Pt48Ag52 alloy nano-octahedra are synthesized via one-pot hydrothermal method. The catalytic growth of Ag(0) atoms on Pt nuclei and selective oxidative etching on the Ag(0) atoms contribute to the formation of alloy nano-octahedra. Pt48Ag52 alloy nano-octahedra show excellent electrocatalytic activity and durability for the methanol oxidation reaction (MOR).
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Saturation of the Right-Leg Drive Amplifier in Low-Voltage ECG Monitors.
IEEE Trans Biomed Eng
PUBLISHED: 08-28-2014
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Electrocardiogram (ECG) monitoring is a critical tool in patient care, but its utility is often balanced with frustration from clinicians who are constantly distracted by false alarms. This has motivated the need to readdress the major factors that contribute to ECG noise with the goal of reducing false alarms. In this study, we describe a previously unreported phenomenon in which ECG noise can result from an unintended interaction between two systems: (1) the DC lead-off circuitry that is used to detect whether electrodes fall off the patient, and (2) the right-leg drive (RLD) system that is responsible for reducing AC common-mode noise that couples into the body. Using a circuit model to study this interaction, we found that in the presence of a DC lead-off system, even moderate increases in the right-leg skin-electrode resistance can cause the RLD amplifier to saturate. Such saturation can produce ECG noise because the RLD amplifier will no longer be capable of attenuating AC common-mode noise on the body. RLD saturation is particularly a problem for modern ECG monitors that use low-voltage supply levels. For example, for a 12-lead ECG and a 2 V power supply, saturation will occur when the right-leg electrode resistance reaches only 2 M?. We discuss several design solutions that can be used in low-voltage monitors to avoid RLD saturation.
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Injectable Smart Phase-Transformation Implants for Highly Efficient In Vivo Magnetic-Hyperthermia Regression of Tumors.
Adv. Mater. Weinheim
PUBLISHED: 08-28-2014
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A minimally invasive, highly efficient and versatile strategy is proposed for localized tumor regression by developing a smart injectable liquid-solid phase-transformation organic-inorganic hybrid composite material, i.e., magnetic Fe powder-dispersed PLGA (Fe/PLGA) implants formagnetic-hyperthermiatherapy of cancer.
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The diagnostic value of the FIB-4 index for staging hepatitis B-related fibrosis: a meta-analysis.
PLoS ONE
PUBLISHED: 08-28-2014
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Liver fibrosis stage is an important factor in determining prognosis and need for treatment in patients infected with hepatitis B virus (HBV). Liver biopsies are typically used to assess liver fibrosis; however, noninvasive alternatives such as the FIB-4 index have also been developed.
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Fibrosis progression in interferon treatment-naive Chinese plasma donors with chronic hepatitis C for 20 years: a cohort study.
Int. J. Infect. Dis.
PUBLISHED: 08-26-2014
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To evaluate the progression of fibrosis and factors influencing this in interferon (IFN) treatment-naive Chinese plasma donors infected with hepatitis C virus (HCV) for approximately 20 years.
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Association between the STK15 polymorphisms and risk of cancer: a meta-analysis.
Mol. Genet. Genomics
PUBLISHED: 08-26-2014
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The previous published data on the association between STK15 F31I and V57I polymorphisms and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and STK15 F31I (42,315 cases and 50,542 controls from 62 studies) and V57I polymorphisms (12,891 cases and 17,391 controls from 18 studies) in different inheritance models. Overall, significant association was observed between F31I and cancer risk when all the eligible studies were pooled into the meta-analysis (recessive model: OR = 1.14, 95 % CI = 1.06-1.24; AA vs. TT: OR = 1.12, 95 % CI = 1.02-1.24; A vs. T: OR = 1.05, 95 % CI = 1.01-1.09). In the further stratified and sensitivity analyses, for STK15 F31I, significantly increased breast cancer (recessive model: OR = 1.16, 95 % CI = 1.02-1.33; AA vs. TT: OR = 1.16, 95 % CI = 1.01-1.33) and ovarian cancer (dominant model: OR = 1.20, 95 % CI = 1.07-1.34; TA vs. TT: OR = 1.19, 95 % CI = 1.06-1.34; A vs. T: OR = 1.15, 95 % CI = 1.05-1.26) risk was found among Caucasians, and significantly decreased lung cancer risk was found among Caucasians (recessive model: OR = 0.65, 95 % CI = 0.49-0.87; AA vs. TT: OR = 0.65, 95 % CI = 0.49-0.88). For V57I polymorphism, significant decreased breast cancer risk was found among Caucasians (recessive model: OR = 0.76, 95 % CI = 0.61-0.95; AA vs. GG: OR = 0.75, 95 % CI = 0.60-0.94; A vs. G: OR = 0.92, 95 % CI = 0.86-0.98). In summary, this meta-analysis suggests that STK15 F31I polymorphism is associated with increased breast cancer and ovarian cancer risk among Caucasians, F31I polymorphism is associated with decreased lung cancer risk among Caucasians, and V57I polymorphism is associated with decreased breast cancer risk among Caucasians.
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Break-up of Two-Dimensional MnO2 Nanosheets Promotes Ultrasensitive pH-Triggered Theranostics of Cancer.
Adv. Mater. Weinheim
PUBLISHED: 08-22-2014
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Chemically exfoliated two-dimensional MnO2 nanosheets are successfully modified with amino-polyethylene glycol as a theranostic platform for ultrasensitive stimuli-responsive theranostics of cancer. The highly dispersed MnO2 nanosheets exhibit a unique break-up in the mildly acidic microenvironment of tumor tissues, which could substantially enhance their in vitro and in vivo performances in T1 -weighted magnetic resonance imaging. Such a pH-triggered breaking-up behavior could further promote the fast release of loaded anticancer drugs for concurrent pH-responsive drug release and circumvent the multidrug resistance of cancer cells.
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GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment.
J. Cell. Sci.
PUBLISHED: 08-08-2014
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Focal adhesions (FAs) undergo maturation culminating in size and composition changes that modulate adhesion, cytoskeleton remodeling and differentiation. While it is well-recognized that stimuli for osteogenesis of mesenchymal stem cells (MSCs) drive FA maturation, actin organization, and stress-fiber polarization, the extent to which FA-mediated signals regulated by the FA protein composition specifies MSC commitment remains largely unknown. Here we demonstrate that, upon dexamethasone (osteogenic induction) treatment, guanine nucleotide exchange factor-H1 (GEF-H1) is significantly enriched in FAs. Perturbation of GEF-H1 inhibits FA formation, anisotropic stress-fiber orientation and MSC osteogenesis in an actomyosin contractility-independent manner. To determine the role of GEF-H1 in MSC osteogenesis, we explore the GEF-H1-modulated FA proteome that reveals non-muscle myosin-II heavy chain-B (NMIIB) as a target of GEF-H1 in FAs. Inhibition of targeting NMIIB into FAs suppresses FA formation, stress-fiber polarization, cell stiffness and osteogenic commitments in MSCs. Our data demonstrate FA signaling in specifying MSC commitment.
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Structures and functions of crotoxin-like heterodimers and acidic phospholipases A2 from Gloydius intermedius venom: Insights into the origin of neurotoxic-type rattlesnakes.
J Proteomics
PUBLISHED: 08-07-2014
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The cDNAs encoding four major phospholipases A2 (PLA2s) were sequenced while the expressed sequence tags of Gloydius intermedius venom glands were constructed. These PLA2s were designated as Gintexin-A precursor, Gintexin-B, Gin-E6a and Gin-E6b, respectively. The deduced amino acid sequences of the former two PLA2s are 80% and 90% identical to those of crotoxin-A-precursor and crotoxin-B1, respectively. We also purified Gintexin-A, Gintexin-B, Gin-E6a and Gin-E6b like PLA2 from the venom. The latter three PLA2s are enzymatically active but not strongly anticoagulant for human plasma. Gin-E6a and E6b-like PLA2s induced mouse platelet aggregation but inhibited rabbit platelet aggregation. The isolated Gintexin, a 1:1 complex of Gintexin-A and Gintexin-B, blocked the twitch of chick biventer cervicis tissue presynaptically. Results of N-terminal sequencing and peptide mass fingerprinting reveal that Gintexin-A undergoes proteolytic processing similar to crotoxin-A. This is the first time heterodimeric ?-neurotoxins are found in Asian pitviper venom, and incompatible neurotoxic- and hemorrhagic-type venoms are found to evolve in parallel within the genus Gloydius, like in Crotalus. Thus, G. intermedius probably is the ancestor of rattlesnakes with type-II venom, and characterization of its venomics helps us to understand the evolution of heterodimeric neurotoxic PLA2s and the paedomorphic trend observed in Neotropical rattlesnake venoms.
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Scalable holey graphene synthesis and dense electrode fabrication toward high-performance ultracapacitors.
ACS Nano
PUBLISHED: 08-05-2014
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Graphene has attracted a lot of attention for ultracapacitor electrodes because of its high electrical conductivity, high surface area, and superb chemical stability. However, poor volumetric capacitive performance of typical graphene-based electrodes has hindered their practical applications because of the extremely low density. Herein we report a scalable synthesis method of holey graphene (h-Graphene) in a single step without using any catalysts or special chemicals. The film made of the as-synthesized h-Graphene exhibited relatively strong mechanical strength, 2D hole morphology, high density, and facile processability. This scalable one-step synthesis method for h-Graphene is time-efficient, cost-efficient, environmentally friendly, and generally applicable to other two-dimensional materials. The ultracapacitor electrodes based on the h-Graphene show a remarkably improved volumetric capacitance with about 700% increase compared to that of regular graphene electrodes. Modeling on individual h-Graphene was carried out to understand the excellent processability and improved ultracapacitor performance.
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Selection and validation of reference genes for target gene analysis with quantitative RT-PCR in leaves and roots of bermudagrass under four different abiotic stresses.
Physiol Plant
PUBLISHED: 08-02-2014
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Quantitative real-time reverse-transcriptase PCR (qRT-PCR) is an effective method for quantifying expression levels of target genes. The accuracy of qRT-PCR results is largely dependent on the selection of stable reference genes. The stability of reference gene expression may vary with plant species and environmental conditions. The objective of this study was to select stable reference genes for qRT-PCR analysis of target genes in different organs under different abiotic stresses for a perennial grass species, bermudagrass (Cynodon dactylon). The stability of eight potential reference genes (TUB, ACT, GAPDH, EF1?, TIP41, PP2A, CACS, UPL7) was evaluated under four different abiotic stresses (salt, drought, cold, and heat) and in leaves and roots of bermudagrass. Four programs (geNorm, NormFinder, BestKeeper, and RefFinder) were employed to evaluate the stability of reference gene expression and to identify the most stable reference genes for bermudagrass. Eight potential reference genes exhibited differential expression stability in leaves and roots under salt, drought, cold, and heat stress. The expression levels of PP2A and CACS were stable in roots and leaves under salt stress, in leaves under drought stress, and in roots exposed to cold and heat stress. EF1? and TIP41 expression were stable in roots of drought-stressed plants. UPL7, TUB and GAPDH were stably expressed in leaves under cold stress. Expression levels of PP2A and TIP41 were stable in leaves under heat stress. The use of the reference genes identified as internal controls for examination of gene expression patterns and quantification of expression levels of target genes will enable accurate qRT-PCR analysis in bermudagrass.
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Detailed characterization of microRNA changes in a canine heart failure model: Relationship to arrhythmogenic structural remodeling.
J. Mol. Cell. Cardiol.
PUBLISHED: 07-30-2014
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Heart failure (HF) causes left-atrial (LA) and left-ventricular (LV) remodeling, with particularly-prominent changes in LA that create a substrate for atrial fibrillation (AF). MicroRNAs (miRs) are potential regulators in cardiac remodeling. This study evaluated time-dependent miR expression-changes in LA and LV tissue, fibroblasts and cardiomyocytes in experimental HF.
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DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells.
J Hematol Oncol
PUBLISHED: 07-24-2014
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BackgroundRenal cell carcinoma (RCC) is a complex with diverse biological characteristics and distinct molecular signature. New target therapies to molecules that drive RCC initiation and progression have achieved promising responses in some patients, but the total effective rate is still far from satisfaction. Dachshund (DACH1) network is a key signaling pathway for kidney development and has recently been identified as a tumor suppressor in several cancer types. However, its role in renal cell carcinoma has not been fully investigated.MethodsImmunohistochemical staining for DACH1, PCNA and cyclin D1 was performed on human renal tissue microaraays and correlation with clinic-pathological characteristics was analyzed. In vitro proliferation, apoptosis and in vivo tumor growth were evaluated on human renal cancer cell lines with decitabine treatment or ectopic expression of DACH1. Downstream targets and potential molecular mechanism were investigated through western blot, immunoprecipitation and reporter gene assays.ResultsExpression of DACH1 was significantly decreased in human renal carcinoma tissue. DACH1 protein abundance was inversely correlated with the expression of PCNA and cyclin D1, tumor grade, and TNM stage. Restoration of DACH1 function in renal clear cell cancer cells inhibited in vitro cellular proliferation, S phase progression, clone formation, and in vivo tumor growth. In mechanism,DACH1 repressed cyclin D1 transcription through association with AP-1 protein.ConclusionOur results indicated that DACH1 was a novel molecular marker of RCC and it attributed to the malignant behavior of renal cancer cells. Re-activation of DACH1 may represent a potential therapeutic strategy.
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Adipose tissue-derived mesenchymal stem cells differentiated into hepatocyte-like cells in vivo and in vitro.
Mol Med Rep
PUBLISHED: 07-22-2014
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Cell?based therapy is a potential alternative to liver transplantation. The goal of the present study was to examine the in vivo and in vitro hepatic differentiation potential of adipose tissue?derived mesenchymal stem cells (AT?MSCs) and to explore its therapeutic use. AT?MSCs were isolated and cultured with hepatic differentiation medium. Bioactivity assays were used to study the properties of AT?MSCs. The morphology of differentiated AT?MSCs in serum?free hepatic differentiation medium changed into polygonal epithelial cells, while the morphology of AT?MSCs in a similar medium containing 2% fetal bovine serum remained unchanged. The differentiated cells cultured without serum showed hepatocyte?like cell morphology and hepatocyte?specific markers, including albumin (ALB) and ??fetoprotein. The bioactivity assays revealed that hepatocyte?like cells could take up low?density lipoprotein (LDL) and store glycogen. Furthermore, trichostatin A (TSA) enhanced ALB production and LDL uptake by the hepatocyte?like cells, analogous to the functions of human liver cells. ALB was detected in the livers of the CCl4?injured mice one month post?transplantation. This suggested that transplantation of the human AT?MSCs could relieve the impairment of acute CCl4?injured livers in nude mice. This therefore implied that adipose tissue was a source of multipotent stem cells which had the potential to differentiate into mature, transplantable hepatocyte?like cells in vivo and in vitro. In addition, the present study determined that TSA was essential to promoting differentiation of human MSC towards functional hepatocyte?like cells. The relief of liver injury following treatment with AT?MSCs suggested their potential as a novel therapeutic method for liver disorders or injury.
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A prospective, randomised, controlled multicentre study comparing cervical disc replacement with anterior cervical decompression and fusion.
Int Orthop
PUBLISHED: 07-22-2014
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Total cervical artificial disc replacement (TDR) simulates normal disc structure, thus avoiding the drawbacks of anterior cervical decompression and fusion (ACDF). This prospective, randomized, controlled and multicentre study aimed to evaluate clinical and radiographic outcomes by comparing cervical disc replacement using Mobi-C disc prostheses with ACDF.
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Transcriptome response of Lactobacillus sakei to meat protein environment.
J. Basic Microbiol.
PUBLISHED: 07-21-2014
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Lactobacillus sakei is a heterofermentative species of lactic acid bacteria that is used in industrial meat fermentation. To investigate adaptation in a meat environment, whole-genome DNA microarrays were used to analyze the gene expression related to growth and survival of L. sakei strain La22 when grown in sarcoplasmic (S-) or myofibrillar (M-) protein-supplemented chemically defined medium (CDM). Differential expression was detected in 551 genes. Genes encoding enzymes involved in peptide hydrolysis were differentially upregulated in M-CDM or/and S-CDM, and only oppB and oppC, involved in the amino acid and peptide transport system, were upregulated. Most genes related to metabolism of peptides, amino acids and related molecules were over-expressed in M-CDM and S-CDM, except for glnA and metK. Expression of certain genes was according to the differential substrate environment. The expression of genes involved in the stress response was not induced by growth in M-CDM.
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Adsorption of anionic MO or cationic MB from MO/MB mixture using polyacrylonitrile fiber hydrothermally treated with hyperbranched polyethylenimine.
J. Hazard. Mater.
PUBLISHED: 07-21-2014
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One-step hydrothermal treatment of polyacrylonitrile fiber (PANF) with hyperbranched polyethylenimine (HPEI) resulted in zwitterionic PANF-g-HPEI that contained not only the grafted HPEI moieties but also many COOH groups generated in situ. Increasing the weight gain of PANF-g-HPEI from 10% to 90% resulted in the increase of its COOH, amino and amide groups from 0.12 to 1.86mmol/g, 1.44 to 8.90mmol/g, and 0.67 to 2.12mmol/g, respectively. Dye adsorption experiments demonstrated that (1) such PANF-g-HPEIs could effectively adsorb anionic Methyl Orange (MO) or cationic Methylene Blue (MB), through the pretreatment with acidic or basic solution, respectively; (2) PANF-g-HPEIs could selectively adsorb the anionic MO or the cationic MB from MO/MB mixture through the pretreatment with solution of pH=5 or 10, respectively; (3) the cationic or anionic dyes adsorbed by PANF-g-HPEIs could be reversibly desorbed by the aqueous solution of pH=1 or 10, respectively; (4) PANF-g-HPEI could be recycled efficiently, and its dye adsorption performances did not show pronounced loss even after 10 adsorption/desorption cycles, superior to PANF treated with the low molar-mass polyamines.
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Gating electron-hole asymmetry in twisted bilayer graphene.
ACS Nano
PUBLISHED: 07-10-2014
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Electron-hole symmetry is one of the unique properties of graphene that is generally absent in most semiconductors because of the different conduction and valence band structures. Here we report on the manipulation of electron-hole symmetry in the low-energy band structure of twisted bilayer graphene, where symmetric saddle points form in the conduction and valence bands as a result of interlayer coupling. By applying a gate voltage to a twisted bilayer with a critical rotation angle, enhanced electron resonance between the two saddle points can be turned on or off, depending on the electron-hole symmetry near the saddle points. The appearance of a 2D(+) peak, a gate-tunable Raman feature found near the critical angle, indicates a reduction of Fermi velocity in the vicinity of the saddle point to/from which electrons are inelastically scattered by phonons in the round trip of the double-resonance process.
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Determination of Anticyclic Citrullinated Peptide Based on Biotin-Streptavidin-Amplified Time-Resolved Fluoroimmunoassay.
J. Clin. Lab. Anal.
PUBLISHED: 06-25-2014
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A rapid and sensitive time-resolved fluoroimmunoassay (TRFIA) based on the biotin-streptavidin amplification system was developed for the determination of anticyclic citrullinated peptide (anti-CCP).
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Observation of topological transitions in interacting quantum circuits.
Nature
PUBLISHED: 06-24-2014
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Topology, with its abstract mathematical constructs, often manifests itself in physics and has a pivotal role in our understanding of natural phenomena. Notably, the discovery of topological phases in condensed-matter systems has changed the modern conception of phases of matter. The global nature of topological ordering, however, makes direct experimental probing an outstanding challenge. Present experimental tools are mainly indirect and, as a result, are inadequate for studying the topology of physical systems at a fundamental level. Here we employ the exquisite control afforded by state-of-the-art superconducting quantum circuits to investigate topological properties of various quantum systems. The essence of our approach is to infer geometric curvature by measuring the deflection of quantum trajectories in the curved space of the Hamiltonian. Topological properties are then revealed by integrating the curvature over closed surfaces, a quantum analogue of the Gauss-Bonnet theorem. We benchmark our technique by investigating basic topological concepts of the historically important Haldane model after mapping the momentum space of this condensed-matter model to the parameter space of a single-qubit Hamiltonian. In addition to constructing the topological phase diagram, we are able to visualize the microscopic spin texture of the associated states and their evolution across a topological phase transition. Going beyond non-interacting systems, we demonstrate the power of our method by studying topology in an interacting quantum system. This required a new qubit architecture that allows for simultaneous control over every term in a two-qubit Hamiltonian. By exploring the parameter space of this Hamiltonian, we discover the emergence of an interaction-induced topological phase. Our work establishes a powerful, generalizable experimental platform to study topological phenomena in quantum systems.
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Real-time monitoring of hemodynamic changes in tumor vessels during photoimmunotherapy using optical coherence tomography.
J Biomed Opt
PUBLISHED: 06-23-2014
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Photoimmunotherapy (PIT) is a cell-specific cancer therapy based on an armed antibody conjugate that induces rapid and highly selective cancer cell necrosis after exposure to near-infrared (NIR) light. The PIT treatment also induces the superenhanced permeability and retention effect, which allows high concentrations of nanoparticles to accumulate in the tumor bed. In our pilot studies, optical coherence tomography (OCT) reveals dramatic hemodynamic changes during PIT. We developed and applied speckle variance analysis, Doppler flow measurement, bulk motion removal, and automatic region of interest selection to quantify vessel diameter and blood velocity within tumors in vivo. OCT imaging reveals that blood velocity in peripheral tumor vessels quickly drops below the detection limit while the vessel lumen remains open (4 vessels from 3 animals). On the other hand, control tumor vessels (receive NIR illumination but no PIT drug) do not show the sustained blood velocity drop (5 vessels from 3 animals). Ultraslow blood velocity could result in a long drug circulation time in tumor. Increase of the blood pool volume within the central tumor (shown in histology) may be the leading cause of the periphery blood velocity drop and could also increase the drug pool volume in tumor vessels.
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Detection of Hepatitis B Virus Large Surface Protein Using a Time-Resolved Immunofluorometric Assay.
J. Clin. Lab. Anal.
PUBLISHED: 06-17-2014
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To establish a novel method based on time-resolved immunofluorometric assay (TR-IFMA) with higher sensitivity and a broader detection range for detecting serum hepatitis B virus large surface protein (L protein).
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Lateral epitaxial growth of two-dimensional layered semiconductor heterojunctions.
Nat Nanotechnol
PUBLISHED: 06-12-2014
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Two-dimensional layered semiconductors such as MoS2 and WSe2 have attracted considerable interest in recent times. Exploring the full potential of these layered materials requires precise spatial modulation of their chemical composition and electronic properties to create well-defined heterostructures. Here, we report the growth of compositionally modulated MoS2-MoSe2 and WS2-WSe2 lateral heterostructures by in situ modulation of the vapour-phase reactants during growth of these two-dimensional crystals. Raman and photoluminescence mapping studies demonstrate that the resulting heterostructure nanosheets exhibit clear structural and optical modulation. Transmission electron microscopy and elemental mapping studies reveal a single crystalline structure with opposite modulation of sulphur and selenium distributions across the heterostructure interface. Electrical transport studies demonstrate that the WSe2-WS2 heterojunctions form lateral p-n diodes and photodiodes, and can be used to create complementary inverters with high voltage gain. Our study is an important advance in the development of layered semiconductor heterostructures, an essential step towards achieving functional electronics and optoelectronics.
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Paper based platform for colorimetric sensing of dissolved NH3 and CO2.
Biosens Bioelectron
PUBLISHED: 06-06-2014
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Paper, a cheap and ubiquitous material, has great potential to be used as low-cost, portable and biodegradable platform for chemical and biological sensing application. In this paper, we are exploring a low-cost, flexible and reliable method to effectively pattern paper for capturing optical dyes and for flow-based delivery of target samples for colorimetric chemical sensing. In this paper, we target the detection of ammonia (NH3) and carbon dioxide (CO2), two of the important environmental and health biomarkers. By functionalizing the paper platform with diverse cross-reactive dyes sensitive to NH3 and CO2, their selective sensing within a certain pH range, as well as their detection at different concentrations can be achieved. The images of paper based device were captured by a flatbed scanner and processed in MATLAB(®) using a RGB model and PCA for quantitative analysis. Paper based devices with readout using ubiquitous consumer electronic devices (e.g. smartphones, flatbed scanner) are considered promising approaches for disease screening in developing countries with limited resources.
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Few-layer molybdenum disulfide transistors and circuits for high-speed flexible electronics.
Nat Commun
PUBLISHED: 06-04-2014
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Two-dimensional layered materials, such as molybdenum disulfide, are emerging as an exciting material system for future electronics due to their unique electronic properties and atomically thin geometry. Here we report a systematic investigation of MoS2 transistors with optimized contact and device geometry, to achieve self-aligned devices with performance including an intrinsic gain over 30, an intrinsic cut-off frequency fT up to 42?GHz and a maximum oscillation frequency fMAX up to 50?GHz, exceeding the reported values for MoS2 transistors to date (fT~0.9?GHz, fMAX~1?GHz). Our results show that logic inverters or radio frequency amplifiers can be formed by integrating multiple MoS2 transistors on quartz or flexible substrates with voltage gain in the gigahertz regime. This study demonstrates the potential of two-dimensional layered semiconductors for high-speed flexible electronics.
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AMPK-?1 functions downstream of oxidative stress to mediate neuronal atrophy in Huntington's disease.
Biochim. Biophys. Acta
PUBLISHED: 05-27-2014
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Huntington's disease (HD) is an autosomal dominant neurological disorder that is induced by a CAG trinucleotide expansion in exon 1 of the Huntingtin (HTT) gene. We previously reported that the abnormal activation of an important energy sensor, AMP-activated protein kinase ?1 (AMPK-?1), occurs in the brains of mice and patients with HD, which suggests that this abnormal activation may contribute to neuronal degeneration in HD. In the present study, we demonstrated that the elevated oxidative stress that was evoked by a polyQ-expanded mutant HTT (mHTT) caused the abnormal activation of AMPK-?1 and, subsequently, resulted in neurotoxicity in a striatal progenitor cell line (STHdh(Q109)) and in the striatum of a transgenic mouse model of HD (R6/2). The systematic administration of an antioxidant (N-acetyl-cysteine, NAC) to R6/2 mice suppressed the activation of AMPK-?1, reduced neuronal toxicity, which was assessed by the activation of caspases, increased neuronal density, ameliorated ventricle enlargement, and improved motor dysfunction. This beneficial effect of NAC in vivo appears to be direct because NAC also reduced the activation of AMPK-?1 and the death of STHdh(Q109) cells upon elevated oxidative stress. Moreover, the activation of AMPK enhanced the level of oxidative stress in STHdh(Q109) cells, in primary neurons of R6/2 mice, and in the striatum of two different HD mouse models (R6/2 and Hdh(150Q/+)), whereas the inhibition of AMPK reduced the level of oxidative stress. Collectively, our findings suggest that positive feedback regulation between the elevated oxidative stress and the activation of AMPK-?1 contributes to the progression of HD.
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An EPAS1 Haplotype Is Associated With High Altitude Polycythemia in Male Han Chinese at the Qinghai-Tibetan Plateau.
Wilderness Environ Med
PUBLISHED: 05-24-2014
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Hemoglobin concentration at high altitude is considered an important marker of high altitude adaptation, and native Tibetans in the Qinghai-Tibetan plateau show lower hemoglobin concentrations than Han people who have emigrated from plains areas. Genetic studies revealed that EPAS1 plays a key role in high altitude adaptation and is associated with the low hemoglobin concentration in Tibetans. Three single nucleotide polymorphisms (rs13419896, rs4953354, rs1868092) of noncoding regions in EPAS1 exhibited significantly different allele frequencies in the Tibetan and Han populations and were associated with low hemoglobin concentrations in Tibetans.
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Acute Acidosis Attenuates Leucine Stimulated Signal Transduction and Protein Synthesis in Rat Skeletal Muscle.
Am. J. Nephrol.
PUBLISHED: 05-20-2014
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Background: Critical illnesses are often complicated by acute metabolic acidosis, which if persistent, adversely affects outcome. Among the harmful effects that it might cause are impaired utilization of nutrients, increased proteolysis and depressed protein synthesis, leading to muscle wasting. As the amino acid leucine stimulates protein synthesis by activating mTOR signaling, we explored whether in acidosis, impaired leucine-stimulated signaling might be a contributor to the depressed protein synthesis. Methods: Male pair-fed rats were gavaged with NH4Cl (acidosis) or NaCl (control) for 2 days and then gavaged once with leucine and sacrificed 45 min later. Extensor digitorum longus muscles were isolated, incubated with or without leucine and protein synthesis measured. The anterior tibial muscle signaling was analysed by Western immunobloting. Results: Despite pair-feeding, acidotic rats lost body and muscle weight vs. controls. Moreover, leucine-induced protein synthesis in isolated muscle from acidotic rats was impaired. In-vivo, 45 min after an oral leucine load, anterior tibial muscle mTOR and 4E-BP1 phosphorylation increased significantly and comparably in control and acidotic rats. In contrast, leucine-stimulated phosphorylation of S6K1, a regulator of translation initiation and protein synthesis, was attenuated to approximately 56% of the control value (p < 0.05). Conclusion: This study reveals that an acute metabolic acidosis impairs leucine-stimulated protein synthesis and activation of signaling downstream of mTOR at the level of S6K1. We propose that this S6K1abnormality may account in part, for the resistance to leucine-stimulated muscle protein synthesis, and may thereby contribute to the impaired nutrient utilization and ultimately the muscle wasting that develops in acidosis. © 2014 S. Karger AG, Basel.
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In vitro effect of iASPP on cell growth of oral tongue squamous cell carcinoma.
Chin. J. Cancer Res.
PUBLISHED: 05-18-2014
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iASPP is an inhibitory member of the apoptosis-stimulating proteins of P53 (ASPP) family. iASPP is over expressed in several malignant tumors and potentially affects cancer progression. However, the expression and potential role of iASPP in oral tongue squamous cell carcinoma (OTSCC) have not been addressed. In our study, we detected iASPP expression in OTSCC by immunohistochemistry. iASPP expression is up-regulated in OTSCC tissues. Moreover, in clinical pathology specimens, we found that increased iASPP expression correlates with poor differentiation and lymph node metastasis. Using multicellular tumor spheroids (MTS) and flow cytometry, we demonstrated that iASPP down-regulation arrests OTSCC cells at the G0/G1 phase, induces OTSCC cell apoptosis and inhibits OTSCC cell proliferation. These results indicate that iASPP plays a significant role in the progression of OTSCC and may serve as a biomarker or therapeutic target for OTSCC patients.
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Iterative reconstruction using a Monte Carlo based system transfer matrix for dedicated breast positron emission tomography.
J Appl Phys
PUBLISHED: 05-16-2014
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To maximize sensitivity, it is desirable that ring Positron Emission Tomography (PET) systems dedicated for imaging the breast have a small bore. Unfortunately, due to parallax error this causes substantial degradation in spatial resolution for objects near the periphery of the breast. In this work, a framework for computing and incorporating an accurate system matrix into iterative reconstruction is presented in an effort to reduce spatial resolution degradation towards the periphery of the breast. The GATE Monte Carlo Simulation software was utilized to accurately model the system matrix for a breast PET system. A strategy for increasing the count statistics in the system matrix computation and for reducing the system element storage space was used by calculating only a subset of matrix elements and then estimating the rest of the elements by using the geometric symmetry of the cylindrical scanner. To implement this strategy, polar voxel basis functions were used to represent the object, resulting in a block-circulant system matrix. Simulation studies using a breast PET scanner model with ring geometry demonstrated improved contrast at 45% reduced noise level and 1.5 to 3 times resolution performance improvement when compared to MLEM reconstruction using a simple line-integral model. The GATE based system matrix reconstruction technique promises to improve resolution and noise performance and reduce image distortion at FOV periphery compared to line-integral based system matrix reconstruction.
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Inhibition of SATB1 expression in regulatory T cells contributes to hepatitis B virus-related chronic liver inflammation.
Mol Med Rep
PUBLISHED: 05-13-2014
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Regulatory T cells (Tregs) contribute to the pathogenesis of chronic hepatitis B (CHB). Special AT-rich sequence-binding protein 1 (SATB1) may be a key component of this process. In the present study, Tregs and conventional T cells (Tconvs) were isolated by magnetic cell sorting of peripheral blood from CHB patients (n=57), individuals with resolved hepatitis B virus (HBV) infections (n=15), and healthy controls (n=29). SATB1 expression was studied by reverse transcription?quantitative PCR, flow cytometry and immunofluorescence microscopy, and the correlation of SATB1 expression to the expression of liver inflammation serum markers and the HBV DNA load was assessed. CHB patients showed significantly reduced SATB1 expression in Tregs than healthy controls and individuals with resolved HBV infections. Moreover, SATB1 expression in Tregs was significantly lower than in Tconvs of patients with chronic HBV infection. Serum HBV DNA and liver inflammation markers were inversely correlated to the SATB1 mRNA level in Tregs. Antiviral treatment was accompanied by increased expression of the SATB1 gene in Tregs. Thus, Tregs from CHB patients have reduced levels of SATB1, which is resolved with antiviral therapy. Inhibition of SATB1 expression may impair the hepatic inflammatory response and contribute to HBV persistence.
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Ytterbium-doped fiber laser passively mode locked by few-layer Molybdenum Disulfide (MoS2) saturable absorber functioned with evanescent field interaction.
Sci Rep
PUBLISHED: 05-12-2014
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By coupling few-layer Molybdenum Disulfide (MoS2) with fiber-taper evanescent light field, a new type of MoS2 based nonlinear optical modulating element had been successfully fabricated as a two-dimensional layered saturable absorber with strong light-matter interaction. This MoS2-taper-fiber device is not only capable of passively mode-locking an all-normal-dispersion ytterbium-doped fiber laser and enduring high power laser excitation (up to 1 W), but also functions as a polarization sensitive optical modulating component (that is, different polarized light can induce different nonlinear optical response). Thanks to the combined advantages from the strong nonlinear optical response in MoS2 together with the sufficiently-long-range interaction between light and MoS2, this device allows for the generation of high power stable dissipative solitons at 1042.6 nm with pulse duration of 656 ps and a repetition rate of 6.74 MHz at a pump power of 210 mW. Our work may also constitute the first example of MoS2-enabled wave-guiding photonic device, and potential y give some new insights into two-dimensional layered materials related photonics.
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Emulating weak localization using a solid-state quantum circuit.
Nat Commun
PUBLISHED: 04-29-2014
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Quantum interference is one of the most fundamental physical effects found in nature. Recent advances in quantum computing now employ interference as a fundamental resource for computation and control. Quantum interference also lies at the heart of sophisticated condensed matter phenomena such as Anderson localization, phenomena that are difficult to reproduce in numerical simulations. Here, employing a multiple-element superconducting quantum circuit, with which we manipulate a single microwave photon, we demonstrate that we can emulate the basic effects of weak localization. By engineering the control sequence, we are able to reproduce the well-known negative magnetoresistance of weak localization as well as its temperature dependence. Furthermore, we can use our circuit to continuously tune the level of disorder, a parameter that is not readily accessible in mesoscopic systems. Demonstrating a high level of control, our experiment shows the potential for employing superconducting quantum circuits as emulators for complex quantum phenomena.
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PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors.
Nat. Genet.
PUBLISHED: 04-21-2014
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Malignant peripheral nerve sheath tumors (MPNSTs) represent a group of highly aggressive soft-tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1 associated) or after radiotherapy. Using comprehensive genomic approaches, we identified loss-of-function somatic alterations of the Polycomb repressive complex 2 (PRC2) components (EED or SUZ12) in 92% of sporadic, 70% of NF1-associated and 90% of radiotherapy-associated MPNSTs. MPNSTs with PRC2 loss showed complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3) and aberrant transcriptional activation of multiple PRC2-repressed homeobox master regulators and their regulated developmental pathways. Introduction of the lost PRC2 component in a PRC2-deficient MPNST cell line restored H3K27me3 levels and decreased cell growth. Additionally, we identified frequent somatic alterations of CDKN2A (81% of all MPNSTs) and NF1 (72% of non-NF1-associated MPNSTs), both of which significantly co-occur with PRC2 alterations. The highly recurrent and specific inactivation of PRC2 components, NF1 and CDKN2A highlights their critical and potentially cooperative roles in MPNST pathogenesis.
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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.