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Find video protocols related to scientific articles indexed in Pubmed.
Development of sol-gel icephobic coatings: effect of surface roughness and surface energy.
ACS Appl Mater Interfaces
PUBLISHED: 11-11-2014
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Sol-gel coatings with different roughness and surface energy were prepared on glass substrates. Methyl triethoxysilane (MTEOS), 3-Glycidyloxypropyl trimethoxysilane (GLYMO) and fluoroalkylsilane (FAS) were used to obtain a mechanically robust icephobic coating. Different amount of hydrophobic silica nano particles was added as fillers to introduce different roughness and surface energy to the coatings. The microstructure, roughness, and surface energy, together with elemental information and surface chemical state were investigated at room temperature. The contact angle and sliding angle were measured at different temperatures to correlate the wetting behavior at low temperature with the anti-icing performance. The ice adhesion shear strength was measured inside an ice chamber using a self-designed tester. The factors influencing the ice adhesion were discussed, and the optimum anti-icing performance found in the series of coatings. It was found that lower surface energy leads to lower ice adhesion regardless of the roughness, while the roughness plays a more complicated role. The wetting behavior of the droplet on surface changes as temperature decreases. The anti-icing performance is closely related to the anti-wetting property of the surfaces at sub-zero temperatures.
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Ophiopogonin D Attenuates Doxorubicin-Induced Autophagic Cell Death by Relieving Mitochondrial Damage in vitro and in vivo.
J. Pharmacol. Exp. Ther.
PUBLISHED: 11-08-2014
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It has been reported that Ophiopogonin D (OP-D), a steroidal glycoside and an active component extracted from Ophiopogon japonicas, promotes antioxidative protection of the cardiovascular system. However, it is unknown whether OP-D exerts protective effects against DOX-induced autophagic cardiomyocyte injury. Here, we demonstrate that DOX induced excessive autophagy through the generation of ROS in H9c2 cells and in mouse hearts, which was indicated by a significant increase in the number of autophagic vacuoles, LC3-II/LC3-I ratio and up-regulation of the expression of GFP-LC3. Pretreatment with OP-D partially attenuated the above phenomena, similar to the effects of treatment with 3-methyladenine (3-MA). In addition, OP-D treatment significantly relieved the disruption of the mitochondrial membrane potential by anti-oxidative effects through down-regulating the expression of both phosphorylated JNK and ERK. The ability of OP-D to reduce the generation of ROS due to mitochondrial damage and, consequently, to inhibit autophagic activity partially accounts for its protective effects in the hearts against DOX-induced toxicity.
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Triple-layered nanostructured WO3 photoanodes with enhanced photocurrent generation and superior stability for photoelectrochemical solar energy conversion.
Nanoscale
PUBLISHED: 10-14-2014
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Unique nanorods/nanoparticles/nanoflakes (NRs/NPs/NFs) WO3 triple-layers are grown on a metallic W foil by a simple one-step anodization method. The triple-layered structure is formed through a self-organization process, the film thickness (up to 3 ?m) being controlled by the anodization time. A first layer made of an array of WO3 densely-packed vertically-aligned NRs (1.2-1.4 ?m in height) grow atop the tungsten foil, followed by a second layer of small NPs (50-80 nm) and finally a third layer made of rectangular NFs (200-300 nm). When irradiated by white light in a photoelectrochemical cell these WO3 triple-layers generate a photocurrent as high as 0.9 mA cm(-2) at 1.2 V/RHE. Moreover, we show that the stability of the triple-layered WO3 photoanodes can be considerably enhanced by adding an ultrathin (10 nm) TiO2 protective overlayer.
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CK2 Phosphorylates and Inhibits TAp73 Tumor Suppressor Function to Promote Expression of Cancer Stem Cell Genes and Phenotype in Head and Neck Cancer.
Neoplasia
PUBLISHED: 10-01-2014
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Cancer stem cells (CSC) and genes have been linked to cancer development and therapeutic resistance, but the signaling mechanisms regulating CSC genes and phenotype are incompletely understood. CK2 has emerged as a key signal serine/threonine kinase that modulates diverse signal cascades regulating cell fate and growth. We previously showed that CK2 is often aberrantly expressed and activated in head and neck squamous cell carcinomas (HNSCC), concomitantly with mutant (mt) tumor suppressor TP53, and inactivation of its family member, TAp73. Unexpectedly, we observed that classical stem cell genes Nanog, Sox2, and Oct4, are overexpressed in HNSCC with inactivated TAp73 and mtTP53. However, the potential relationship between CK2, TAp73 inactivation, and CSC phenotype is unknown. We reveal that inhibition of CK2 by pharmacologic inhibitors or siRNA inhibits the expression of CSC genes and side population (SP), while enhancing TAp73 mRNA and protein expression. Conversely, CK2 inhibitor attenuation of CSC protein expression and the SP by was abrogated by TAp73 siRNA. Bioinformatic analysis uncovered a single predicted CK2 threonine phosphorylation site (T27) within the N-terminal transactivation domain of TAp73. Nuclear CK2 and TAp73 interaction, confirmed by co-immunoprecipitation, was attenuated by CK2 inhibitor, or a T27A point-mutation of this predicted CK2 threonine phospho-acceptor site of TAp73. Further, T27A mutation attenuated phosphorylation, while enhancing TAp73 function in repressing CSC gene expression and SP cells. A new CK2 inhibitor, CX-4945, inhibited CSC related SP cells, clonogenic survival, and spheroid formation. Our study unveils a novel regulatory mechanism whereby aberrant CK2 signaling inhibits TAp73 to promote the expression of CSC genes and phenotype.
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Complete mitochondrial genome sequence of a chronic obstructive pulmonary disease Rattus norvegicus C57CE strain.
Mitochondrial DNA
PUBLISHED: 09-27-2014
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Abstract We sequenced a chronic obstructive pulmonary disease Rattus norvegicus C57CE strain mitochondrial genome for the first time (GenBank Accession No. KM114607). Its mitogenome was 16,307?bp and coding 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. This genome will provide definite information for genetic perspective into this disease.
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Transition metal-doped BiFeO3 nanofibers: forecasting the conductivity limit.
Phys Chem Chem Phys
PUBLISHED: 09-25-2014
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We investigate the limiting electrical conductivity of BiFeO3 (BFO) nanofibers via first-principles modelling and experiments. Based on a semi-empirical approach, all transition metals are first screened for their suitability to form an acceptor in BFO. The resultant candidates (e.g., Ni, Cu and Ag) are further studied by more sophisticated electronic structure theory and experiments. Accordingly, a systematic approach in forecasting the electrical conduction in BFO nanofibers is established. The calculated results show that Ag(+) cations prefer substitutions of Bi(3+) while Ni(2+) and Cu(2+) prefer substitution of Fe(3+) sites to form acceptors. All three metals contribute to an increased overall hole concentration which may lead to a conductivity limit in BFO. These predictions were confirmed consistently through the synthesis and electrical testing of Ni-, Cu- and Ag-doped BFO nanofibers. Finally, our results indicate that the conductivity limit is approached by Ni doping in BFO. The methodology presented here may be extended to search for the doping conductivity limits of other semiconductors of interest.
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Accelerated NMR Spectroscopy with Low-Rank Reconstruction.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 09-19-2014
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Accelerated multi-dimensional NMR spectroscopy is a prerequisite for high-throughput applications, studying short-lived molecular systems and monitoring chemical reactions in real time. Non-uniform sampling is a common approach to reduce the measurement time. Here, a new method for high-quality spectra reconstruction from non-uniformly sampled data is introduced, which is based on recent developments in the field of signal processing theory and uses the so far unexploited general property of the NMR signal, its low rank. Using experimental and simulated data, we demonstrate that the low-rank reconstruction is a viable alternative to the current state-of-the-art technique compressed sensing. In particular, the low-rank approach is good in preserving of low-intensity broad peaks, and thus increases the effective sensitivity in the reconstructed spectra.
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Fast 3D gradient shimming by only 2×2 pixels in XY plane for NMR-solution samples.
J. Magn. Reson.
PUBLISHED: 09-06-2014
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Shimming is an essential process for most NMR experiments, and time saving in this process is desired. Here we propose a fast 3D gradient shimming with a low resolution of only 2×2 pixels in the XY plane, and the number of pixels in the Z direction remains unchanged. The proposed pulse sequences employ the selective excitation and the convection compensation. Consequently, the fast 3D gradient shimming adapts to a wide range of samples on regular NMR spectrometers.
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Unravelling the Correlation between the Aspect Ratio of Nanotubular Structures and Their Electrochemical Performance To Achieve High-Rate and Long-Life Lithium-Ion Batteries.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-28-2014
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The fundamental understanding of the relationship between the nanostructure of an electrode and its electrochemical performance is crucial for achieving high-performance lithium-ion batteries (LIBs). In this work, the relationship between the nanotubular aspect ratio and electrochemical performance of LIBs is elucidated for the first time. The stirring hydrothermal method was used to control the aspect ratio of viscous titanate nanotubes, which were used to fabricate additive-free TiO2 -based electrode materials. We found that the battery performance at high charging/discharging rates is dramatically boosted when the aspect ratio is increased, due to the optimization of electronic/ionic transport properties within the electrode materials. The proof-of-concept LIBs comprising nanotubes with an aspect ratio of 265 can retain more than 86?% of their initial capacity over 6000 cycles at a high rate of 30?C. Such devices with supercapacitor-like rate performance and battery-like capacity herald a new paradigm for energy storage systems.
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Dysfunction of thermoregulation contributes to the generation of hyperthermia-induced seizures.
Neurosci. Lett.
PUBLISHED: 08-27-2014
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Febrile seizures (FS) are generally defined as seizures taking place during fever. Long-term prognosis, including development of epilepsy and malformation of cognitive function, has been demonstrated after infantile FS. However, the mechanism that triggers seizures in hyperthermic environment is still unclear. We here found that the body temperature of rat pups that experienced experimental FS was markedly decreased (?28°C) after they were removed from the hyperthermic environment. Both the seizure generation and the temperature drop after seizure attack were abolished by either pre-treatment with chlorpromazine (CPZ), which impairs the thermoregulation, or by an electrolytic lesion of the preoptic area and anterior hypothalamus (PO/AH). However, the non-steroidal anti-inflammatory drug celecoxib did not affect the seizure incidence and the decrease in body temperature after seizure attack. In addition, pentobarbital prevented the generation of seizures, but did not reverse the decrease of body temperature after FS. Therefore, our work indicates that an over-regulation of body temperature occurs during hyperthermic environment, and that the dysfunction of thermoregulation in the PO/AH following hyperthermia contributes to the generation of FS.
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Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.
Cell
PUBLISHED: 08-07-2014
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Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.
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Reverse detection for spectral width improvements in spatially encoded dimensions of ultrafast two-dimensional NMR spectra.
Magn Reson Chem
PUBLISHED: 08-07-2014
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Recently, the spatially encoded technique has been broadly used in the fast analyses of chemical systems and real-time detections of chemical reactions. In spatially encoded ultrafast 2D spectra, spectral widths and resolution in spatially encoded dimensions are contradictive, leading to the risk of insufficient spectral widths when providing satisfactory resolution values for all resonances. Here, a method named as reverse detection is proposed to improve the spectral width in the spatially encoded dimension. Experimental results show that spectral width improvements are at least twofold with reverse detection solely, and more improvements can be expected along with the gradient-controlled folding method. The proposed method can be applied to almost any spatially encoded scheme with echo planar spectroscopic imaging-like detection module and may promote wide applications of ultrafast 2D spectroscopy techniques in chemical analyses. Copyright © 2014 John Wiley & Sons, Ltd.
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Interplay between longitudinal and transverse contrasts in Fe3O4 nanoplates with (111) exposed surfaces.
ACS Nano
PUBLISHED: 08-06-2014
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Iron oxide has been developed as either T1 or T2 magnetic resonance imaging (MRI) contrast agents by controlling the size and composition; however, the underlying mechanism of T1 and T2 contrasts in one iron oxide entity is still not well understood. Herein, we report that freestanding superparamagnetic magnetite nanoplates with (111) exposed facets have significant but interactional T1 and T2 contrast effects. We demonstrate that the main contribution of the T1 contrast of magnetic nanoplates is the chemical exchange on the iron-rich Fe3O4(111) surfaces, whereas the T2 relaxation is dominated by the intrinsic superparamagnetism of the nanoplates with an enhanced perturbation effect. We are able to regulate the balance of T1 and T2 contrasts by controlling structure and surface features, including morphology, exposed facets, and surface coating. This study provides an insightful understanding on the T1 and T2 contrast mechanisms, which is urgently needed to allow more sophisticated design of high-performance MRI contrast agents.
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Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury: Involvement of PARK2-dependent mitophagy.
Autophagy
PUBLISHED: 08-05-2014
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Transient cerebral ischemia leads to endoplasmic reticulum (ER) stress. However, the contributions of ER stress to cerebral ischemia are not clear. To address this issue, the ER stress activators tunicamycin (TM) and thapsigargin (TG) were administered to transient middle cerebral artery occluded (tMCAO) mice and oxygen-glucose deprivation-reperfusion (OGD-Rep.)-treated neurons. Both TM and TG showed significant protection against ischemia-induced brain injury, as revealed by reduced brain infarct volume and increased glucose uptake rate in ischemic tissue. In OGD-Rep.-treated neurons, 4-PBA, the ER stress releasing mechanism, counteracted the neuronal protection of TM and TG, which also supports a protective role of ER stress in transient brain ischemia. Knocking down the ER stress sensor Eif2s1, which is further activated by TM and TG, reduced the OGD-Rep.-induced neuronal cell death. In addition, both TM and TG prevented PARK2 loss, promoted its recruitment to mitochondria, and activated mitophagy during reperfusion after ischemia. The neuroprotection of TM and TG was reversed by autophagy inhibition (3-methyladenine and Atg7 knockdown) as well as Park2 silencing. The neuroprotection was also diminished in Park2(+/-) mice. Moreover, Eif2s1 and downstream Atf4 silencing reduced PARK2 expression, impaired mitophagy induction, and counteracted the neuroprotection. Taken together, the present investigation demonstrates that the ER stress induced by TM and TG protects against the transient ischemic brain injury. The PARK2-mediated mitophagy may be underlying the protection of ER stress. These findings may provide a new strategy to rescue ischemic brains by inducing mitophagy through ER stress activation.
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Tunable T1 and T2 contrast abilities of manganese-engineered iron oxide nanoparticles through size control.
Nanoscale
PUBLISHED: 07-31-2014
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In this paper, we demonstrate the tunable T1 and T2 contrast abilities of engineered iron oxide nanoparticles with high performance for liver contrast-enhanced magnetic resonance imaging (MRI) in mice. To enhance the diagnostic accuracy of MRI, large numbers of contrast agents with T1 or T2 contrast ability have been widely explored. The comprehensive investigation of high-performance MRI contrast agents with controllable T1 and T2 contrast abilities is of high importance in the field of molecular imaging. In this study, we synthesized uniform manganese-doped iron oxide (MnIO) nanoparticles with controllable size from 5 to 12 nm and comprehensively investigated their MRI contrast abilities. We revealed that the MRI contrast effects of MnIO nanoparticles are highly size-dependent. By controlling the size of MnIO nanoparticles, we can achieve T1-dominated, T2-dominated, and T1-T2 dual-mode MRI contrast agents with much higher contrast enhancement than the corresponding conventional iron oxide nanoparticles.
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Correlation between serum uric Acid and renal function in patients with stable coronary artery disease and type 2 diabetes.
J Clin Med Res
PUBLISHED: 07-08-2014
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The aim of this study was to investigate the relationship between serum uric acid and renal function, expressed as estimated glomerular filtration rate (eGFR), in patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) in China.
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The alteration of protein prenylation induces cardiomyocyte hypertrophy through Rheb/mTORC1 signaling and leads to chronic heart failure.
J. Pathol.
PUBLISHED: 07-05-2014
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G protein-regulated cell function is crucial for cardiomyocytes, and any deregulation of its gene expression or protein modification can lead to pathological cardiac hypertrophy. Herein, we report that protein prenylation, a lipidic modification of G proteins that facilitates their association with the cell membrane, might control the process of cardiomyocyte hypertrophy. We found that geranylgeranyl diphosphate synthase (GGPPS), a key enzyme involved in protein prenylation, played a critical role in the postnatal heart growth through regulating the cardiomyocyte size. Cardiac-specific knockout of GGPPS in mice led to spontaneous cardiac hypertrophy beginning from 4(th) week, accompanied with the persistent enlargement of cardiomyocytes. This hypertrophic effect occurred by altered prenylation of G proteins. Evaluation of the prenylation, membrane association and hydrophobicity showed that Rheb was hyperactivated and increased mTORC1 signaling pathway after GGPPS deletion. Protein farnesylation or mTORC1 inhibition blocked GGPPS knockdown-induced mTORC1 activation and suppressed the larger neonatal rat ventricle myocyte size and cardiomyocyte hypertrophy in vivo, demonstrating a central role of FPP/Rheb/mTORC1 axis for GGPPS deficiency-induced cardiomyocyte hypertrophy. The sustained cardiomyocyte hypertrophy progressively provoked cardiac decompensation and dysfunction, ultimately causing heart failure and adult death. Importantly, GGPPS was downregulated in the hypertrophic hearts of mice subjected to transverse aortic constriction (TAC) and in the failing human hearts. Moreover, HPLC-MS/MS detection revealed that myocardial farnesyl diphosphate (FPP) to geranylgeranyl diphosphate (GGPP) ratio was enhanced after pressure overload. Our observations conclude that the alteration of protein prenylation promotes cardiomyocyte hypertrophic growth, which acts as a potential cause for pathogenesis of heart failure and may provide a new molecular target for hypertrophic heart disease clinical therapy.
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Mono- and co-doped NaTaO3 for visible light photocatalysis.
Phys Chem Chem Phys
PUBLISHED: 06-27-2014
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Electronic structures of doped NaTaO3 compounds are of significant interest to visible light photocatalysis. This work involves the study of the band gap, band edge potentials, and thermodynamic stability of certain mono-doped and co-doped NaTaO3 systems, using DFT-PBE as well as hybrid (PBE0) functional calculations. Doping of certain non-magnetic cations (Ti, V, Cu, Zn, W, In, Sn, Sb, Ce, and La), certain anions (N, C, and I), and certain co-dopant pairs (W-Ti, W-Ce, N-I, N-W, La-C, Pb-I, and Cu-Sn) is investigated. Our calculations suggest that substitutional doping of Cu at the Ta site, Cu at the Na site, and C at the O site narrows the band gap of NaTaO3 to 2.3, 2.8, and 2.1 eV, respectively, inducing visible light absorption. Additionally, passivated co-doping of Pb-I and N-W narrows the band gap of NaTaO3 to the visible region, while maintaining the band potentials at favorable positions. Hybrid density of states (DOS) accurately describe the effective band potentials and the location of mid-gap states, which shed light on the possible mechanism of photoexcitation in relation to the photocatalysis reactions. Furthermore, the thermodynamic stability of the doped systems and defect pair binding energies of co-doped systems are discussed in detail. The present results provide useful insights into designing new photocatalysts based on NaTaO3.
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Palladium-catalyzed formylation of aryl halides with tert-butyl isocyanide.
Org. Lett.
PUBLISHED: 06-23-2014
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A novel palladium-catalyzed formylation of aryl halides with isocyanide in the presence of Et3SiH has been demonstrated, which provides a strategy toward important aldehydes with moderate to excellent yield. The advantage of this reaction includes milder conditions, convenient operation, lower toxicity, and wide functional group tolerance.
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Study of seed hair growth in Populus tomentosa, an important character of female floral bud development.
BMC Genomics
PUBLISHED: 06-11-2014
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Poplar seed hair is an environmental annoyance in northern China due to its abundance and widespread airborne distribution after maturation. The morphogenesis and molecular mechanisms of its development are not well understood, and little attention has been focused on the dynamics of its development. To better understand the mechanism of poplar seed hair development, paraffin sections were used to examine the initiation and elongation of poplar seed hairs. RNA-seq technology was also employed to provide a comprehensive overview of transcriptional changes that occur during seed hair development.
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KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission.
Antimicrob. Agents Chemother.
PUBLISHED: 06-09-2014
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Renewed global efforts toward malaria eradication have highlighted the need for novel antimalarial agents with activity against multiple stages of the parasite life cycle. We have previously reported the discovery of a novel class of antimalarial compounds in the imidazolopiperazine series that have activity in the prevention and treatment of blood stage infection in a mouse model of malaria. Consistent with the previously reported activity profile of this series, the clinical candidate KAF156 shows blood schizonticidal activity with 50% inhibitory concentrations of 6 to 17.4 nM against P. falciparum drug-sensitive and drug-resistant strains, as well as potent therapeutic activity in a mouse models of malaria with 50, 90, and 99% effective doses of 0.6, 0.9, and 1.4 mg/kg, respectively. When administered prophylactically in a sporozoite challenge mouse model, KAF156 is completely protective as a single oral dose of 10 mg/kg. Finally, KAF156 displays potent Plasmodium transmission blocking activities both in vitro and in vivo. Collectively, our data suggest that KAF156, currently under evaluation in clinical trials, has the potential to treat, prevent, and block the transmission of malaria.
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F-01A, an antibiotic, inhibits lung cancer cells proliferation.
Chin J Nat Med
PUBLISHED: 05-28-2014
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In an effort to identify novel, small molecules which can affect the proliferation of lung cancer cells, F-01A, a polyether antibiotic isolated from the fermentation broth of Streptomyces was tested.
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Histamine upregulates Nav1.8 expression in primary afferent neurons via H2 receptors: involvement in neuropathic pain.
CNS Neurosci Ther
PUBLISHED: 05-27-2014
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The upregulation of Nav1.8 in primary afferents plays a critical role in the development and persistence of neuropathic pain. The mechanisms underlying the upregulation are not fully understood.
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The structural network of Interleukin-10 and its implications in inflammation and cancer.
BMC Genomics
PUBLISHED: 05-20-2014
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Inflammation has significant roles in all phases of tumor development, including initiation, progression and metastasis. Interleukin-10 (IL-10) is a well-known immuno-modulatory cytokine with an anti-inflammatory activity. Lack of IL-10 allows induction of pro-inflammatory cytokines and hinders anti-tumor immunity, thereby favoring tumor growth. The IL-10 network is among the most important paths linking cancer and inflammation. The simple node-and-edge network representation is useful, but limited, hampering the understanding of the mechanistic details of signaling pathways. Structural networks complete the missing parts, and provide details. The IL-10 structural network may shed light on the mechanisms through which disease-related mutations work and the pathogenesis of malignancies.
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Cytotoxic triterpenoid glycosides from the roots of Camellia oleifera.
Planta Med.
PUBLISHED: 05-19-2014
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Eight new triterpenoid saponins, oleiferosides A-H (1-8), were isolated from the EtOH extract of the roots of Camellia oleifera. Their structures were elucidated by a combination of 1D and 2D?NMR techniques, mass spectrometry, and chemical methods. All were characterized to be oleanane-type saponins with sugar moieties linked to C-3 of the aglycone. Cytotoxic activities of these saponins were evaluated against four human tumor cell lines (A549, B16, BEL-7402, and MCF-7) by using the MTT in vitro assay. Compound 3 exhibited potent cytotoxic activitiy against all the tested cell lines with IC50 values
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Palladium-catalyzed one-pot synthesis of quinazolinones via tert-butyl isocyanide insertion.
J. Org. Chem.
PUBLISHED: 05-19-2014
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A novel palladium-catalyzed three-component reaction for the synthesis of quinazolin-4(3H)-ones from readily available 2-aminobenzamides and aryl halides via a palladium-catalyzed isocyanide insertion/cyclization sequence has been developed. This methodology efficiently constructs quinazolin-4(3H)-ones in moderate to excellent yields with the advantages of operational simplicity.
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Positive Response to Cardiac Resynchronization Therapy Reduces Arrhythmic Events After Elective Generator Change in Patients with Primary Prevention CRT-D.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 05-18-2014
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Cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillators (ICD) are effective therapies for heart failure (HF) patients with cardiac dyssynchrony. Patients receiving primary prevention CRT-defibrillator that positively remodel might no longer qualify for ICD indication due to CRT-induced left ventricular ejection fraction (LVEF) improvement. We aimed to evaluate the outcome of CRT-D patients at the time of device replacement (DR).
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Identification of glutathione S-transferase genes responding to pathogen infestation in Populus tomentosa.
Funct. Integr. Genomics
PUBLISHED: 05-12-2014
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Stem blister canker, caused by Botryosphaeria dothidea, is becoming the most serious disease of poplar in China. The molecular basis of the poplar in response to stem blister canker is not well understood. To reveal the global transcriptional changes of poplar to infection by B.?dothidea, Solexa paired-end sequencing of complementary DNAs (cDNAs) from control (NB) and pathogen-treated samples (WB) was performed, resulting in a total of 339,283 transcripts and 183,881 unigenes. A total of 206,586 transcripts were differentially expressed in response to pathogen stress (false discovery rate ?0.05 and an absolute value of log2Ratio (NB/WB) ?1). In enrichment analysis, energy metabolism and redox reaction-related macromolecules were accumulated significantly in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses, indicating components of dynamic defense against the fungus. A total of 852 transcripts (575 upregulated and 277 downregulated transcripts) potentially involved in plant-pathogen interaction were also differentially regulated, including genes encoding proteins linked to signal transduction (putative leucine-rich repeat (LRR) protein kinases and calcium-binding proteins), defense (pathogenesis-related protein 1), and cofactors (jasmonate-ZIM-domain-containing proteins and heat shock proteins). Moreover, transcripts encoding glutathione S-transferase (GST) were accumulated to high levels, revealing key genes and proteins potentially related to pathogen resistance. Poplar RNA sequence data were validated by quantitative real-time PCR (RT-qPCR), which revealed a highly reliability of the transcriptomic profiling data.
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Highly sensitive electrochemical aptasensor based on a ligase-assisted exonuclease III-catalyzed degradation reaction.
ACS Appl Mater Interfaces
PUBLISHED: 05-09-2014
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In this paper, we have proposed a new electrochemical aptasensor based on a novel ligase-assisted Exo III-catalyzed degradation reaction (LAECDR), which consists of DNA ligase-catalyzed ligation of thrombin-binding aptamer (TBA) with an extension strand (E-strand) and Exo III-catalyzed selective degradation of probe DNA, by using an improved target-induced strand displacement strategy. As a result of LAECDR, methylene blue (MB)-labeled mononucleotides can be released from the 3'-terminal of probe DNA and captured by cucurbit[7]uril-functionalized electrode to induce noticeable electrochemical response. Nevertheless, in the presence of the target protein, thrombin, the TBA that is partially complementary to probe DNA is preferentially binding with the target protein, thereby inhibiting LAECDR from taking place. The remaining intact probe DNA will prevent the terminal-attached MB from approaching to the electrode surface due to strong electrostatic repulsion, so the electrochemical response will be changed by thrombin. By tracing the electrochemical response of adsorbed MB, our aptasensor can exhibit high sensitivity for thrombin detection with a wide linear range from 100 fM to 1 nM and an extremely low detection limit of 33 fM, which can also easily distinguish thrombin in the complex serum samples with high specificity. Therefore, our aptasensor might have great potential in clinical applications in the future.
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Morphology and functions of astrocytes cultured on water-repellent fractal tripalmitin surfaces.
Biomaterials
PUBLISHED: 05-08-2014
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In the brain, astrocytes play an essential role with their multiple functions and sophisticated structure, as surrounded by a fractal environment which has not been available in our traditional cell culture. Water-repellent fractal tripalmitin (PPP) surfaces can imitate the fractal environment in vivo, so the morphology and biochemical characterization of astrocytes on these surfaces are examined. Water-repellent fractal PPP surface can induce astrocytes to display sophisticated morphology with smaller size of cell area, longer and finer filopodium-like processes, and higher morphological complexity. The super water-repellent fractal PPP surface with water contact angle of 150°?160° produces the maximal effects compared with other surfaces at lower water contact angles. The trends of characteristic protein expression, including that of nestin, vimentin, GFAP and glutamine synthetase, for astrocytes cultured on super water-repellent fractal PPP surfaces approximate more to in vivo pattern. The super water-repellent PPP surface also render astrocytes to perform more pronounced promotion of neurogenesis by increasing the release of nerve growth factor in a co-culture system. Altogether, our results suggest that the super water-repellent fractal PPP surface facilitates the astrocytes to mimic their in vivo performance, thus provides a closer-to-natural culture environment for experimental assessment of glial structure and functions.
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Mechanical force-driven growth of elongated bending TiO2 -based nanotubular materials for ultrafast rechargeable lithium ion batteries.
Adv. Mater. Weinheim
PUBLISHED: 05-04-2014
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A stirring hydrothermal process that enables the formation of elongated bending TiO2 -based nanotubes is presented. By making use of its bending nature, the elongated TiO2 (B) nanotubular crosslinked-network anode electrode can cycle over 10 000 times in half cells while retaining a relatively high capacity (114 mA h g(-1)) at an ultra-high rate of 25 C (8.4 A g(-1)).
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Recurrent linezolid-resistant Enterococcus faecalis infection in a patient with pneumonia.
Int. J. Infect. Dis.
PUBLISHED: 04-15-2014
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It has been reported that LZD-resistant Enterococcus in the gastrointestinal tract of mice colonizes persistently and shows variable minimum inhibitor concentration (MIC) values. However, the colonization characteristics of Enterococcus with LZD resistance in patients remain elusive. Here, we report the case of a patient with recurrent pneumonia due to infection with LZD-resistant Enterococcus faecalis strains. The colonization characteristics of the strains isolated from this patient were analyzed.
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Complete genome sequencing and comparative analysis of the linezolid-resistant Enterococcus faecalis strain DENG1.
Arch. Microbiol.
PUBLISHED: 04-12-2014
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Genome level analysis of bacterial strains provides information on genetic composition and resistance mechanisms to clinically relevant antibiotics. To date, whole genome characterization of linezolid-resistant Enterococcus faecalis isolated in the clinic is lacking. In this study, we report the entire genome sequence, genomic characteristics and virulence factors of a pathogenic E. faecalis strain, DENG1. Our results showed considerable differences in genomic characteristics and virulence factors compared with other E. faecalis strains (V583 and OG1RF). The genome of this LZD-resistant E. faecalis strain can be used as a reference to study the mechanism of LZD resistance and the phylogenetic relationship of E. faecalis strains worldwide.
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Literature review and clinical presentation of cervical spondylitis due to salmonella enteritidis in immunocompetent.
Asian Spine J
PUBLISHED: 04-08-2014
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A 48-year-old woman was presented to our clinic with some fever and neck pains for about one month. Based on the symptoms and results of image, an empirical diagnosis of tuberculous cervical spondylitis was made. The pain was not significantly decreased after anti-tuberculosis therapy. And, 3 weeks later, she was re-admitted to our hospital for the unbearable pain. An exploration of the C4/5 by the anterior medial approach was recommended to evaluate the germ and debridement. Bacteriological tests showed that the pathogen was Salmonella Enteritidis. The pain was relieved significantly after operation and sensitive antibiotic treatments. Infections with Salmonella Typhi or Salmonella Paratyphi have been well-documented, while there are few reports of cervical spondylitis caused by Salmonella Enteritidis. We reported a case of a healthy woman with whom pyogenic cervical spondylitis of Salmonella Enteritidis was corroborated and treated and reviewed according to previous reports about spondylitis caused by Salmonella Enteritidis in the literature.
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Parallel computing of patch-based nonlocal operator and its application in compressed sensing MRI.
Comput Math Methods Med
PUBLISHED: 04-01-2014
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Magnetic resonance imaging has been benefited from compressed sensing in improving imaging speed. But the computation time of compressed sensing magnetic resonance imaging (CS-MRI) is relatively long due to its iterative reconstruction process. Recently, a patch-based nonlocal operator (PANO) has been applied in CS-MRI to significantly reduce the reconstruction error by making use of self-similarity in images. But the two major steps in PANO, learning similarities and performing 3D wavelet transform, require extensive computations. In this paper, a parallel architecture based on multicore processors is proposed to accelerate computations of PANO. Simulation results demonstrate that the acceleration factor approaches the number of CPU cores and overall PANO-based CS-MRI reconstruction can be accomplished in several seconds.
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Targeting endothelin receptors A and B attenuates the inflammatory response and improves locomotor function following spinal cord injury in mice.
Int. J. Mol. Med.
PUBLISHED: 04-01-2014
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After spinal cord injury (SCI), the disruption of blood-spinal cord barrier by activation of the endothelin (ET) system is a critical event leading to leukocyte infiltration, inflammatory response and oxidative stress, contributing to neurological disability. In the present study, we showed that blockade of ET receptor A (ETAR) and/or ET receptor B (ETBR) prevented early inflammatory responses directly via the inhibition of neutrophil and monocyte diapedesis and inflammatory mediator production following traumatic SCI in mice. Long-term neurological improvement, based on a series of tests of locomotor performance, occurred only in the spinal cord?injured mice following blockade of ETAR and ETBR. We also examined the post?traumatic changes of the micro-environment within the injured spinal cord of mice following blockade of ET receptors. Oxidative stress reflects an imbalance between malondialdehyde and superoxide dismutase in spinal cord?injured mice treated with vehicle, whereas blockade of ETAR and ETBR reversed the oxidation state imbalance. In addition, hemeoxygenase-1, a protective protease involved in early SCI, was increased in spinal cord?injured mice following the blockade of ETAR and ETBR, or only ETBR. Matrix metalloproteinase-9, a tissue-destructive protease involved in early damage, was decreased in the injured spinal cord of mice following blockade of ETAR, ETBR or a combination thereof. The findings of the present study therefore suggested an association between ETAR and ETBR in regulating early pathogenesis of SCI and determining the outcomes of long?term neurological recovery.
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Angiopep-conjugated electro-responsive hydrogel nanoparticles: therapeutic potential for epilepsy.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-31-2014
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A safe and effective therapy for epilepsy requires a drug delivery system that can penetrate the blood-brain barrier and subsequently release antiepileptic drugs rapidly to suppress neuronal discharges in a timely manner. We have developed electro-responsive hydrogel nanoparticles (ERHNPs) modified with angiopep-2 (ANG) to facilitate the delivery of the antiepileptic drug phenytoin sodium. The resulting ANG-ERHNPs had an average diameter of (102.3±16.8)?nm and were electro-sensitive with regard to particle size and drug release in?vitro. ANG-ERHNPs have the characteristics of penetrate the BBB easily, resulting in a higher distribution in the central system. The improved antiepileptic effects were investigated with the amygdala kindling model. The results demonstrate that the ANG-ERHNPs were able to transport antiepileptic drugs into the brain and release them under electroencephalograph epileptiform abnormalities to greatly improve the therapeutic index of existing drugs in clinical use.
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A U-shaped type II contraction pattern in patients with strict left bundle branch block predicts super-response to cardiac resynchronization therapy.
Heart Rhythm
PUBLISHED: 03-31-2014
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New criteria to define strict left bundle branch block (LBBB) on the basis of pathophysiological principles predict response to cardiac resynchronization therapy (CRT). Heterogeneous activation and contraction patterns have been identified in patients with classical LBBB. Cardiac magnetic resonance (CMR) imaging has demonstrated that a U-shaped (type II) contraction predicts reverse remodeling post-CRT. A homogeneous spread of (type I) contraction is less predictive.
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Water-fat separation from a single spatiotemporally encoded echo based on nominal k-space peaking and joint regularized estimation.
Magn Reson Med
PUBLISHED: 03-26-2014
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To present a new high-resolution single-point water-fat separation algorithm based on the spatiotemporally encoded chemical shift imaging technique.
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Epirubicin-Loaded Superparamagnetic Iron-Oxide Nanoparticles for Transdermal Delivery: Cancer Therapy by Circumventing the Skin Barrier.
Small
PUBLISHED: 03-22-2014
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The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron-oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI-SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI-SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g(-1) . They feature specific pH-sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose-dependent. In vitro transdermal studies demonstrate that the EPI-SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic-field-assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION-based vector for feasible transdermal therapy of skin cancer.
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High-resolution two-dimensional J-resolved NMR spectroscopy for biological systems.
Biophys. J.
PUBLISHED: 03-13-2014
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NMR spectroscopy is a principal tool in metabolomic studies and can, in theory, yield atom-level information critical for understanding biological systems. Nevertheless, NMR investigations on biological tissues generally have to contend with field inhomogeneities originating from variations in macroscopic magnetic susceptibility; these field inhomogeneities broaden spectral lines and thereby obscure metabolite signals. The congestion in one-dimensional NMR spectra of biological tissues often leads to ambiguities in metabolite identification and quantification. We propose an NMR approach based on intermolecular double-quantum coherences to recover high-resolution two-dimensional (2D) J-resolved spectra from inhomogeneous magnetic fields, such as those created by susceptibility variations in intact biological tissues. The proposed method makes it possible to acquire high-resolution 2D J-resolved spectra on intact biological samples without recourse to time-consuming shimming procedures or the use of specialized hardware, such as magic-angle-spinning probes. Separation of chemical shifts and J couplings along two distinct dimensions is achieved, which reduces spectral crowding and increases metabolite specificity. Moreover, the apparent J coupling constants observed are magnified by a factor of 3, facilitating the accurate measurement of small J couplings, which is useful in metabolic analyses. Dramatically improved spectral resolution is demonstrated in our applications of the technique on pig brain tissues. The resulting spectra contain a wealth of chemical shift and J-coupling information that is invaluable for metabolite analyses. A spatially localized experiment applied on an intact fish (Crossocheilus siamensis) reveals the promise of the proposed method in in vivo metabolite studies. Moreover, the proposed method makes few demands on spectrometer hardware and therefore constitutes a convenient and effective manner for metabonomics study of biological systems.
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Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures.
Neurosci Bull
PUBLISHED: 03-11-2014
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Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological state such as complex febrile seizures (FSs) in infancy. Here we used a well-established complex FS model in rats and showed that: (1) the susceptibility to seizures induced by hyperthermia, pentylenetetrazol (PTZ), and maximal electroshock (MES) was similar in male and female rat pups, while males were more susceptible to PTZ- and MES-induced seizures than age-matched females in normal adult rats; (2) adult rats with complex FSs in infancy acquired higher seizure susceptibility than normal rats; importantly, female FS rats were more susceptible to PTZ and MES than male FS rats; and (3) the protein expression of interleukin-1?, an inflammatory factor associated with seizure susceptibility, was higher in adult FS females than in males, which may reflect a gender-difference phenomenon of seizure susceptibility. Our results provide direct evidence that the acquired seizure susceptibility after complex FSs is gender-dependent.
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Observation of true and pseudo NOE signals using CEST-MRI and CEST-MRS sequences with and without lipid suppression.
Magn Reson Med
PUBLISHED: 03-11-2014
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To investigate the characteristics of nuclear Overhauser enhancement (NOE) imaging signals in the brain at 7T.
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In vitro antibacterial analysis of phenoloxidase reaction products from the sea cucumber Apostichopus japonicus.
Fish Shellfish Immunol.
PUBLISHED: 03-05-2014
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Three phenoloxidases (POs) of Apostichopus japonicus, AjPOs (AjPO1, AjPO2 and AjPO3), were partially purified from the coelomocytes with an electrophoretic method, and then employed for the in vitro antibacterial analysis. Using L-3,4-dihydroxyphenylalanine (L-DOPA) as a substrate, AjPO1 and AjPO2-derived compounds inhibited the growth of Vibrio splendidus and Staphylococcus aureus, while AjPO3-derived compounds only inhibited the growth of V. splendidus. When dopamine was used as a substrate, AjPO1 and AjPO3-derived compounds inhibited the growth of V. splendidus and Vibrio harveyi, while AjPO2-derived compounds only inhibited the growth of V. splendidus. Moreover, AjPO1-derived compounds showed stronger inhibition in V. harveyi than AjPO3-derived compounds did. However, all of the three AjPO reaction products showed no inhibitions on the growth of Pseudoalteromonas nigrifaciens, Shewanella baltica, Micrococcus lysodeikticus, Streptococcus dysgalactiae and Nocardiopsis sp. with L-DOPA or dopamine as a substrate. Scanning electron microscope (SEM) observation of V. harveyi treated by AjPOs and dopamine showed that AjPO1-derived compounds resulted in massive bacteriolysis, AjPO2-derived compounds caused no obvious alteration on bacterial morphology, and AjPO3-derived compounds increased the ratio of spheroidal bacteria. All these results suggested that AjPO reaction products derived by L-DOPA and dopamine had different but limited antibacterial spectrum, and the different antibacterial effects observed among three AjPOs resulted from the different reaction products generated by AjPOs with the same substrate.
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CRL4A(CRBN) E3 ubiquitin ligase restricts BK channel activity and prevents epileptogenesis.
Nat Commun
PUBLISHED: 01-26-2014
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Ion channels regulate membrane excitation, and mutations of ion channels often cause serious neurological disorders including epilepsy. Compared with extensive analyses of channel protein structure and function, much less is known about the fine tuning of channel activity by post-translational modification. Here we report that the large conductance, Ca(2+)- and voltage-activated K(+) (BK) channels are targeted by the E3 ubiquitin ligase CRL4A(CRBN) for polyubiquitination and retained in the endoplasmic reticulum (ER). Inactivation of CRL4A(CRBN) releases deubiquitinated BK channels from the ER to the plasma membrane, leading to markedly enhanced channel activity. Mice with CRL4A(CRBN) mutation in the brain or treated with a CRL4A(CRBN) inhibitor are very sensitive to seizure induction, which can be attenuated by blocking BK channels. Finally, the mutant mice develop spontaneous epilepsy when aged. Therefore, ubiquitination of BK channels before their cell surface expression is an important step to prevent systemic neuronal excitability and epileptogenesis.
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Combined identification of septal flash and absence of myocardial scar by cardiac magnetic resonance imaging improves prediction of response to cardiac resynchronization therapy.
J Interv Card Electrophysiol
PUBLISHED: 01-09-2014
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Septal flash (SF) describes early inward motion of the ventricular septum in patients with left bundle branch block (LBBB), and correction corresponds to increased response to cardiac resynchronization therapy (CRT). SF has traditionally been assessed by echocardiography. We sought to determine if cardiac magnetic resonance (CMR) imaging could identify SF and if the additional assessment of scar would improve the ability of CMR to predict CRT response.
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Oscillatory behavior of ventricular action potential duration in heart failure patients at respiratory rate and low frequency.
Front Physiol
PUBLISHED: 01-01-2014
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Oscillations of arterial pressure occur spontaneously at a frequency of approximately 0.1 Hz coupled with synchronous oscillations of sympathetic nerve activity ("Mayer waves"). This study investigated the extent to which corresponding oscillations may occur in ventricular action potential duration (APD). Fourteen ambulatory (outpatient) heart failure patients with biventricular pacing devices were studied while seated upright watching movie clips to maintain arousal. Activation recovery intervals (ARI) as a measure of ventricular APD were obtained from unipolar electrograms recorded from the LV epicardial pacing lead during steady state RV pacing from the device. Arterial blood pressure was measured non-invasively (Finapress) and respiration monitored. Oscillations were quantified using time frequency and coherence analysis. Oscillatory behavior of ARI at the respiratory frequency was observed in all subjects. The magnitude of the ARI variation ranged from 2.2 to 6.9 ms (mean 5.0 ms). Coherence analysis showed a correlation with respiratory oscillation for an average of 43% of the recording time at a significance level of p < 0.05. Oscillations in systolic blood pressure in the Mayer wave frequency range were observed in all subjects for whom blood pressure was recorded (n = 13). ARI oscillation in the Mayer wave frequency range was observed in 6/13 subjects (46%) over a range of 2.9 to 9.2 ms. Coherence with Mayer waves at the p < 0.05 significance level was present for an average of 29% of the recording time. In ambulatory patients with heart failure during enhanced mental arousal, left ventricular epicardial APD (ARI) oscillated at the respiratory frequency (approximately 0.25 Hz). In 6 patients (46%) APD oscillated at the slower Mayer wave frequency (approximately 0.1 Hz). These findings may be important in understanding sympathetic activity-related arrhythmogenesis.
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Computational analysis reveals a correlation of exon-skipping events with splicing, transcription and epigenetic factors.
Nucleic Acids Res.
PUBLISHED: 12-24-2013
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Alternative splicing (AS), in higher eukaryotes, is one of the mechanisms of post-transcriptional regulation that generate multiple transcripts from the same gene. One particular mode of AS is the skipping event where an exon may be alternatively excluded or constitutively included in the resulting mature mRNA. Both transcript isoforms from this skipping event site, i.e. in which the exon is either included (inclusion isoform) or excluded (skipping isoform), are typically present in one cell, and maintain a subtle balance that is vital to cellular function and dynamics. However, how the prevailing conditions dictate which isoform is expressed and what biological factors might influence the regulation of this process remain areas requiring further exploration. In this study, we have developed a novel computational method, graph-based exon-skipping scanner (GESS), for de novo detection of skipping event sites from raw RNA-seq reads without prior knowledge of gene annotations, as well as for determining the dominant isoform generated from such sites. We have applied our method to publicly available RNA-seq data in GM12878 and K562 cells from the ENCODE consortium and experimentally validated several skipping site predictions by RT-PCR. Furthermore, we integrated other sequencing-based genomic data to investigate the impact of splicing activities, transcription factors (TFs) and epigenetic histone modifications on splicing outcomes. Our computational analysis found that splice sites within the skipping-isoform-dominated group (SIDG) tended to exhibit weaker MaxEntScan-calculated splice site strength around middle, skipping, exons compared to those in the inclusion-isoform-dominated group (IIDG). We further showed the positional preference pattern of splicing factors, characterized by enrichment in the intronic splice sites immediately bordering middle exons. Finally, our analysis suggested that different epigenetic factors may introduce a variable obstacle in the process of exon-intron boundary establishment leading to skipping events.
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KAI407, a potent non 8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.
Antimicrob. Agents Chemother.
PUBLISHED: 12-23-2013
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Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low throughput assay of in vitro cultured hypnozoite-forms of Plasmodium cynomolgi (an excellent and accessible model for P. vivax). In this assay primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days, stained with anti-Hsp70 antibodies and the relative proportion of small (hypnozoite) and large (schizont) forms relative to the untreated controls are counted. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point tenfold dilutions (0.1, 1 and 10 ?M final concentration). A novel compound, designated KAI407 showed an activity profile similar to primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (IC50 for hypnozoites KAI407: 0.69 ?M and PQ: 0.84 ?M, for developing liver stages KAI407: 0.64 ?M and PQ 0.37 ?M). When given as causal prophylaxis, a single oral dose of 100 mg/kg prevented blood stage parasitemia in mice. From these results we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially radical cure.
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Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis.
Sci Transl Med
PUBLISHED: 12-06-2013
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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). We have identified and characterized the indolcarboxamides as a new class of antitubercular bactericidal agent. Genetic and lipid profiling studies identified the likely molecular target of indolcarboxamides as MmpL3, a transporter of trehalose monomycolate that is essential for mycobacterial cell wall biosynthesis. Two lead candidates, NITD-304 and NITD-349, showed potent activity against both drug-sensitive and multidrug-resistant clinical isolates of Mtb. Promising pharmacokinetic profiles of both compounds after oral dosing in several species enabled further evaluation for efficacy and safety. NITD-304 and NITD-349 were efficacious in treating both acute and chronic Mtb infections in mouse efficacy models. Furthermore, dosing of NITD-304 and NITD-349 for 2 weeks in exploratory rat toxicology studies revealed a promising safety margin. Finally, neither compound inhibited the activity of major cytochrome P-450 enzymes or the hERG (human ether-a-go-go related gene) channel. These results suggest that NITD-304 and NITD-349 should undergo further development as a potential treatment for multidrug-resistant TB.
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[Clinical research on surgical treatment for non-small cell lung cancer of diameter less than 2 cm].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 12-05-2013
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To discuss the model of reasonable dissection extent of mediastinal lymph nodes in non-small cell lung cancer of diameter less than 2 cm.
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A new oleanane-type triterpenoidal saponin from Pulsatilla chinensis.
Nat. Prod. Res.
PUBLISHED: 11-18-2013
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A new oleanane-type triterpenoidal saponin, 3-O-?-d-glucopyranosyl-hederagenin 23-O-?-d-ribofuranoside (1), was isolated from the roots of Pulsatilla chinensis, and its structure was established on the basis of the spectral data. Compounds 2, 7 and 8 showed moderate cytotoxic activity by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide assay.
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[Influence of photoselective vaporization of prostate on erectile function in patients with benign prostatic hyperplasia].
Zhonghua Nan Ke Xue
PUBLISHED: 11-14-2013
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To assess the influence of photoselective vaporization of the prostate (PVP) on the erectile function of the patient with benign prostatic hyperplasia (BPH).
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The PI3K/Akt/mTOR axis in head and neck cancer: functions, aberrations, crosstalk, and therapies.
Oral Dis
PUBLISHED: 10-23-2013
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Head and neck squamous cell carcinoma (HNSCC) is one of the most morbid, mortal, and genetically diverse malignancies. Although HNSCC is heterogeneous in nature, alterations in major components of the PI3K/Akt/mTOR pathway are consistently observed throughout the majority of HNSCC cases. These alterations include genetic aberrations such as mutations or DNA copy number variations, and dysregulation of mRNA or protein expression. In normal physiology, the PI3K/Akt/mTOR axis regulates cell survival, growth, and metabolism. However, alterations in this pathway lead to the malignant phenotype which characterizes HNSCC, among many other cancers. For this reason, both pharmaceutical companies and academic institutions are actively developing and investigating inhibitors of PI3K, Akt, and mTOR in preclinical and clinical studies of HNSCC. Many of these inhibitors have shown promise, while the effects of others are tempered by the mechanisms through which HNSCC can evade therapy. As such, current research aimed at elucidating the interactions among PI3K/Akt/mTOR and other important signaling pathways which may drive resistance in HNSCC, such as p53, NF-?B, and MAPK, has become a prominent focus toward better understanding how to most effectively treat HNSCC. This article is protected by copyright. All rights reserved.
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Understanding the metabolic fate and assessing the biosafety of MnO nanoparticles by metabonomic analysis.
Nanotechnology
PUBLISHED: 10-21-2013
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Recently, some types of MnO nanoparticle (Mn-NP) with favorable imaging capacity have been developed to improve the biocompatible profile of the existing Mn-based MRI contrast agent Mn-DPDP; however, the overall bio-effects and potential toxicity remain largely unknown. In this study, (1)H NMR-based metabolic profiling, integrated with traditional biochemical analysis and histopathological examinations, was used to investigate the absorption, distribution, metabolism, excretion and toxicity of Mn-NPs as candidates for MRI contrast agent. The metabolic responses in biofluids (plasma and urine) and tissues (liver, spleen, kidney, lung and brain) from rats could be divided into four classes following Mn-NP administration: Mn biodistribution-dependent, time-dependent, dose-dependent and complicated metabolic variations. The variations of these metabolites involved in lipid, energy, amino acid and other nutrient metabolism, which disclosed the metabolic fate and biological effects of Mn-NPs in rats. The changes of metabolic profile implied that the disturbance and impairment of biological functions induced by Mn-NP exposure were correlated with the particle size and the surface chemistry of nanoparticles. Integration of metabonomic technology with traditional methods provides a promising tool to understand the toxicological behavior of biomedical nanomaterials and will result in informed decision-making during drug development.
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DNA-directed gold nanodimers with tailored ensemble surface-enhanced Raman scattering properties.
ACS Appl Mater Interfaces
PUBLISHED: 10-16-2013
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Gold nanodimers (GNDs) are assembled with high uniformity as ideal surface-enhanced Raman scattering (SERS) substrates through DNA-directed self-assembly of gold nanoparticles. The interparticle distance within GNDs is precisely tailored on the order of a few nanometers with changing the molecule length of DNA bridge. The ensemble SERS activity of monodispersed GNDs is then rationally engineered by modifying the structural parameters of GNDs including the particle size and interparticle distance. Theoretical studies on the level of single GND evidence the particle size- and interparticle-distance-dependent SERS effects, consistent with the ensemble averaged measurements.
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Rivaroxaban for the treatment of symptomatic deep-vein thrombosis and pulmonary embolism in Chinese patients: a subgroup analysis of the EINSTEIN DVT and PE studies.
Thromb J
PUBLISHED: 09-20-2013
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The worldwide EINSTEIN DVT and EINSTEIN PE studies randomized 8282 patients with acute symptomatic deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) and, for the first time in trials in this setting, included patients in China. This analysis evaluates the results of these studies in this subgroup of patients.
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An aliasing artifacts reducing approach with random undersampling for spatiotemporally encoded single-shot MRI.
J. Magn. Reson.
PUBLISHED: 09-03-2013
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Compared to the echo planar imaging (EPI), spatiotemporally encoded (SPEN) single-shot MRI holds better immunity to the field inhomogeneity, while retaining comparable spatial and temporal resolutions after the super-resolved reconstruction. Though various reconstruction methods have been proposed, the reconstructed SPEN images usually contain aliasing artifacts because of vast undersampling. A hybrid scheme based on random sampling, singular value decomposition (SVD) and compressed sensing (CS) was introduced to reduce these aliasing artifacts and improve the image quality. The efficiency of this hybrid scheme was demonstrated by numerical simulations and experiments on water phantom and in vivo rat brain. The hybrid scheme provided herein would benefit the SPEN approach in vast undersampling situation.
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[Treatment of osteomyelitis and soft tissue defects at distal region of leg and foot by pedicled peroneus brevis muscle flaps and reverse island flaps with sural nerve and blood supplying vessels].
Zhonghua Shao Shang Za Zhi
PUBLISHED: 08-30-2013
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To observe the clinical effect of distally pedicled peroneus brevis muscle flaps and reverse island flaps with sural nerve and blood supplying vessels on repairing osteomyelitis and soft tissue defects at distal region of leg and foot.
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Receptor-mediated delivery of engineered nucleases for genome modification.
Nucleic Acids Res.
PUBLISHED: 08-16-2013
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Engineered nucleases, which incise the genome at predetermined sites, have a number of laboratory and clinical applications. There is, however, a need for better methods for controlled intracellular delivery of nucleases. Here, we demonstrate a method for ligand-mediated delivery of zinc finger nucleases (ZFN) proteins using transferrin receptor-mediated endocytosis. Uptake is rapid and efficient in established mammalian cell lines and in primary cells, including mouse and human hematopoietic stem-progenitor cell populations. In contrast to cDNA expression, ZFN protein levels decline rapidly following internalization, affording better temporal control of nuclease activity. We show that transferrin-mediated ZFN uptake leads to site-specific in situ cleavage of the target locus. Additionally, despite the much shorter duration of ZFN activity, the efficiency of gene correction approaches that seen with cDNA-mediated expression. The approach is flexible and general, with the potential for extension to other targeting ligands and nuclease architectures.
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Evaluation of current algorithms for segmentation of scar tissue from late Gadolinium enhancement cardiovascular magnetic resonance of the left atrium: an open-access grand challenge.
J Cardiovasc Magn Reson
PUBLISHED: 08-12-2013
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Late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging can be used to visualise regions of fibrosis and scarring in the left atrium (LA) myocardium. This can be important for treatment stratification of patients with atrial fibrillation (AF) and for assessment of treatment after radio frequency catheter ablation (RFCA). In this paper we present a standardised evaluation benchmarking framework for algorithms segmenting fibrosis and scar from LGE CMR images. The algorithms reported are the response to an open challenge that was put to the medical imaging community through an ISBI (IEEE International Symposium on Biomedical Imaging) workshop.
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Effect of a combination of local flap and sequential compression-distraction osteogenesis in the reconstruction of post-traumatic tibial bone and soft tissue defects.
Chin. Med. J.
PUBLISHED: 08-09-2013
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Treatment of extensive post-traumatic composite bone and soft tissue defects remains a complicated therapeutic problem and a challenge for surgeons. We investigated the application of local flaps and Ilizarov osteogenesis in the reestablishment of severe combined defects of tibial bone and soft tissue.
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Fast and robust 2D-shape extraction using discrete-point sampling and centerline grouping in complex images.
IEEE Trans Image Process
PUBLISHED: 08-08-2013
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This paper initially develops the discrete-point sampling operators concept, model, and parameters that we have previously proposed, and makes its belt-shaped regions in a discrete-point sampling map more salient and appropriate for centerline extraction. The cross-sectional features of these belt-shaped regions are then analyzed and seven types of feature points are defined to facilitate descriptions of such features. Based on these feature points, a three-level detection system is proposed, including feature points, line segments, and centerlines, to extract centerlines from the belt-shaped regions. Eight basic types of centerlines and five types of relationships among the centerlines are defined by computational geometry algorithms, and Gestalt laws are used to cluster them into groupings. If some prior information about a desired shape is available, retrieval grouping may be carried out by a discrete-point sampling map, the purpose of which is to find centerlines by best matching with prior information. Discrete-point sampling effectually overcomes the influences of interference from noise, textures, and uneven illumination, and greatly reduces the difficulty of centerline extraction. Centerline clustered groupings and retrieval grouping can offer a strong anti-interference ability with nonlinear deformations such as articulation and occlusion. This method can extract large-scale complex shapes combined of lines and planes from complex images. The wheel location results of noise test and other shape extraction experiments show that our method has a strong capability to persist with nonlinear deformations.
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HSP90 Inhibitor SNX5422/2112 Targets the Dysregulated Signal and Transcription Factor Network and Malignant Phenotype of Head and Neck Squamous Cell Carcinoma.
Transl Oncol
PUBLISHED: 08-01-2013
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Heat shock protein 90 (HSP90) is a chaperone protein that stabilizes proteins involved in oncogenic and therapeutic resistance pathways of epithelial cancers, including head and neck squamous cell carcinomas (HNSCCs). Here, we characterized the molecular, cellular, and preclinical activity of HSP90 inhibitor SNX5422/2112 in HNSCC overexpressing HSP90. SNX2112 inhibited proliferation, induced G2/M block, and enhanced cytotoxicity, chemosensitivity, and radiosensitivity between 25 and 250 nM in vitro. SNX2112 showed combinatorial activity with paclitaxel in wild-type (wt) TP53-deficient and cisplatin in mutant (mt) TP53 HNSCC lines. SNX2112 decreased expression or phosphorylation of epidermal growth factor receptor (EGFR), c-MET, v-akt murine thymoma viral oncogene homolog 1 (AKT), extracellular signal-regulated kinases (ERK) 1 and 2, inhibitor ?B kinase, and signal transducer and transcription factor 3 (STAT3), corresponding downstream nuclear factor ?B, activator protein-1, and STAT3 reporter genes, and target oncogenes and angiogenic cytokines. Furthermore, SNX2112 enhanced re-expression of TP53 and targets p21WAF1 and PUMA, while TP53 inhibitor Pifithrin or siRNA attenuated the antiproliferative activity of SNX2112 in wtTP53 HNSCC in vitro. Prodrug SNX5422 similarly down-modulated key signal targets, enhanced TP53 expression and apoptosis, and inhibited proliferation, angiogenesis, and tumorigenesis in a wtTP53-deficient HNSCC xenograft model. Thus, HSP90 inhibitor SNX5422/2112 broadly modulates multiple key nodes within the dysregulated signaling network, with corresponding effects upon the malignant phenotype. Our data support investigation of SNX5422/2112 in combination with paclitaxel, cisplatin, and radiotherapy in HNSCC with different TP53 status.
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Surfactant-thermal method to synthesize a novel two-dimensional oxochalcogenide.
Chem Asian J
PUBLISHED: 07-31-2013
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A new two-dimensional (2D) oxosulfide, (N2 H4 )2 Mn3 Sb4 S8 (?3 -OH)2 (1), has been successfully synthesized under surfactant-thermal conditions with hexadecyltributylphosphonium bromide as the surfactant. Compound?1 has a layered structure and contains a novel [Mn3 (?3 -OH)2 ]n chain along the b-axis. The photocatalytic activity for compound?1 has been demonstrated under visible-light irradiation and continuous H2 evolution was observed. Our results indicate that surfactant-thermal synthesis could be a promising method for growing novel crystalline oxochalcogenides with interesting structures and properties.
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Phenoloxidase from the sea cucumber Apostichopus japonicus: cDNA cloning, expression and substrate specificity analysis.
Fish Shellfish Immunol.
PUBLISHED: 07-27-2013
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Phenoloxidase (PO) is a crucial component of the immune system of echinoderms. In the present study, the full-length cDNA of PO (AjPO) was cloned from coelomocytes of the sea cucumber Apostichopus japonicus using 3- and 5-rapid amplification of cDNA ends (RACE) PCR method, which is 2508 bp, with an open reading frame (ORF) of 2040 bp encoding 679 amino acids. AjPO contains a transmembrane domain, and three Cu-oxidase domains with copper binding centers formed by 10 histidines, one cysteine and one methionine respectively. Phylogenetic analysis revealed that AjPO was clustered with laccase-type POs of invertebrates. Using the isolated membrane proteins as crude AjPO, the enzyme could catalyze the substrates catechol, L-3,4-dihydroxyphenylalanine (l-DOPA), dopamine and hydroquinone, but failed to oxidize tyrosine. The results described above collectively proved that AjPO was a membrane-binding laccase-type PO. The quantitative real-time PCR (qRT-PCR) analysis revealed that AjPO mRNA was expressed in muscle, body wall, coelomocytes, tube feet, respiratory tree and intestine with the highest expression level in coelomocytes. AjPO could be significantly induced by lipopolysaccharide (LPS), peptidoglycan (PGN), Zymosan A and polyinosinic-polycytidylic acid (PolyI:C), suggesting AjPO is closely involved in the defense against the infection of bacteria, fungi and double-stranded RNA viruses.
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[Impact and related mechanisms of stromal cell-derived factor-1? on serum deprivation-induced cardiac stem cells apoptosis].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 07-15-2013
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To explore the impact and related mechanisms of stromal cell-derived factor-1? (SDF-1?) on serum deprivation-induced apoptosis of cadiac stem cells (CSCs).
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Mercury profiles in surface sediments from ten bays along the coast of Southern China.
Mar. Pollut. Bull.
PUBLISHED: 05-23-2013
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Spatial and temporal variations of mercury (Hg) were investigated from ten representative bays along the coast of Southern China. The total Hg (THg) in surface sediments varied widely with concentrations from 25 to 264 ng/g. As a whole, Hg pollution in several bays occupied by busy sea traffic and industrial activities, such as Shantou (ST) Bay and Dapeng (DP) Bay were remarkably more serious than others, which reflected the direct effects of anthropogenic activities around the coastal areas. Hg variations in sediment cores clearly display upcore rising trend which obviously correlates with the trend of economic development and urbanization in the last five decades. No significant correlations were found between Hg and organic matter and particle size, suggesting that the distribution of Hg is not fully controlled by these variables.
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Bioinspired TiO? nanostructure films with special wettability and adhesion for droplets manipulation and patterning.
Sci Rep
PUBLISHED: 05-15-2013
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Patterned surfaces with special wettability and adhesion (sliding, sticky or patterned superoleophobic surface) can be found on many living creatures. They offer a versatile platform for microfluidic management and other biological functions. Inspired by their precise arrangement of structure and chemical component, we described a facile one-step approach to construct large scale pinecone-like anatase TiO? particles (ATP) film. The as-prepared ATP film exhibits excellent superamphiphilic property in air, changes to underwater superoleophobicity with good dynamical stability. In addition, erasable and rewritable patterned superamphiphobic ATP films or three-dimensional (3D) Janus surfaces were constructed for a versatile platform for microfluidic management and biomedical applications. In a proof-of-concept study, robust super-antiwetting feet for artificial anti-oil strider at the oil/water interface, novel superamphiphobic surface for repeatable oil/water separation, and multifunctional patterned superamphiphobic ATP template for cell, fluorecent probe and inorganic nanoparticles site-selective immobilization were demonstrated.
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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.

How does it work?

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.