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Find video protocols related to scientific articles indexed in Pubmed.
[Serum hydrogen sulfide levels in children with benign infantile convulsions associated with mild gastroenteritis.]
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 11-20-2014
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To study the changes and significance of serum hydrogen sulfide (H2S) levels in children with benign infantile convulsions associated with mild gastroenteritis (BICE).
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Association between Reversal in the Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel and Age-Related Atrial Fibrillation.
Med. Sci. Monit.
PUBLISHED: 11-19-2014
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Background We compared cardiac electrophysiological indicators and regional expression levels of cardiac hyperpolarization-activated cyclic nucleotide-gated (HCN) channels between adult and aged dogs to identify possible mechanisms of age-related atrial fibrillation. Material and Methods Corrected sinus node recovery time (SNRTc) and effective refractory period (ERP) of the atrium and pulmonary veins were measured in 10 adult (3-6 years old) and 10 aged dogs (>9 years old). Expression levels of HCN2 and HCN4 channel mRNAs and proteins were measured in the sinoatrial node, atrium, and pulmonary veins by real-time PCR and Western blotting. Results Aged dogs exhibited a higher induction rate of atrial fibrillation (AF) in response to electrical stimulation, longer AF duration after induction, longer SNRTc, longer right atrial effective refractory period (AERP), shorter left AERP, and increased AERP dispersion compared to adults. Expression levels of HCN2 and HCN4 channel mRNAs and proteins were lower in the sinoatrial node but higher in the atrium and pulmonary veins of aged dogs. Conclusions Changes in atrial electrophysiological indicators in aged dogs revealed sinoatrial node dysfunction. There was a reversal in the local tissue distribution of HCN2 and HCN4 channel mRNA and protein, a decrease in sinoatrial node expression, and increase in atrial and pulmonary vein expression with age. Changes in atrial electrophysiological characteristics and regional HCN channel expression patterns were associated with the onset and maintenance of age-related atrial fibrillation.
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A Novel EOG/EEG Hybrid Human-Machine Interface Adopting Eye Movements and ERPs: Application to Robot Control.
IEEE Trans Biomed Eng
PUBLISHED: 11-15-2014
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This study presents a novel human-machine interface (HMI) based on both electrooculography (EOG) and electroencephalography (EEG). This hybrid interface works in two modes: an EOG mode recognizes eye movements such as blinks, and an EEG mode detects event related potentials (ERPs) like P300. While both eye movements and ERPs have been separately used for implementing assistive interfaces which help patients with motor disabilities in performing daily tasks, the proposed hybrid interface integrates them together. In this way, both the eye movements and ERPs complement each other. Therefore, it can provide a better efficiency and a wider scope of application. In this study, we design a threshold algorithm which can recognize four kinds of eye movements including blink, wink, gaze, and frown. In addition, an oddball paradigm with stimuli of inverted faces is used to evoke multiple ERP components including P300, N170, and VPP. To verify the effectiveness of the proposed system, two different online experiments are carried out. One is to control a multi-functional humanoid robot, and the other is to control four mobile robots. In both experiments, the subjects can complete tasks effectively by using the proposed interface whereas the best completion time is relatively short and very close to the one operated by hand.
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n-BuLi as a Highly Efficient Precatalyst for Hydrophosphonylation of Aldehydes and Unactivated Ketones.
Org. Lett.
PUBLISHED: 11-15-2014
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It was found for the first time that organic alkali metal compounds serve as highly efficient precatalysts for the hydrophosphonylation reactions of aldehydes and unactivated ketones with dialkyl phosphite under mild conditions. For ketone substrates, a reversible reaction was observed, and the influence of catalyst loading and reaction temperature on the reaction equilibrium was studied in detail. Overall, the hydrophosphonylation reactions catalyzed by 0.1 mol % n-BuLi were completed within 5 min for a broad range of substrates and generated a series of ?-hydroxy phosphonates in high yields.
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A new schistosomicidal and antioxidative phenylpropanoid from Astragalus englerianus.
J Asian Nat Prod Res
PUBLISHED: 11-14-2014
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A new phenylpropanoid, (E)-2,3,4-trimethoxy-5-(1-propenyl)phenol (1), along with five known aromatic compounds (2-6), was isolated from the methanol extract of roots of Astragalus englerianus. Their structures were elucidated based on the analyses of extensive spectroscopic data and comparison of their physicochemical properties. Compounds 1 and 2 were evaluated schistosomicidal activities, and all the isolated compounds were tested for their antioxidant activities in vitro. Compound 1 showed significant schistosomicidal activity with worm mortality rates of 66.7% and 83.3% within 12 and 24 h in a drug-containing (1.16 mM) RPMI 1640 medium, respectively. Also, compound 1 exhibited excellent antioxidant activity (2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl free radical-scavenging capability) with an IC50 value of 81.3 ± 1.3 ?M.
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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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Syntheses, structures and properties of two new organic-inorganic hybrid materials based on ?-Zn Keggin units {?-PMo(V)8Mo(VI)4O40-x(OH)xZn4}
Dalton Trans
PUBLISHED: 11-12-2014
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Two novel organic-inorganic hybrids, Na[PMo(V)8Mo(VI)4O38(OH)2Zn4][pyim]2·1.5H2O [?(pyim)2] (pyim = 2-(2-pyridyl)-imidazole) and [PMo(V)8Mo(VI)4O37(OH)3Zn4]2[pyim]6·4H2O [?2(pyim)6], based on ?-Zn Keggin units {?-PMo(V)8Mo(VI)4O40-x(OH)xZn4}, have been successfully synthesized under hydrothermal conditions by controlling the pH values. Structural analysis indicates that the framework of ?(pyim)2 is a 1D chain constructed by monomeric ?-Zn units modified by pyim ligands, while ?2(pyim)6 is an isolated structural compound with dimeric ?-Zn units modified by pyim ligands. This is the first isolated structure of the ?-Keggin POMs system. The luminescent and electrochemical properties of ?(pyim)2 and ?2(pyim)6 were investigated. ?2(pyim)6 also shows high catalytic activity for the esterification of phosphoric acid with equimolar lauryl alcohol to monoalkyl phosphate ester (MAP).
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Super-resolution reconstruction for 4D computed tomography of the lung via the projections onto convex sets approach.
Med Phys
PUBLISHED: 11-06-2014
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The use of 4D computed tomography (4D-CT) of the lung is important in lung cancer radiotherapy for tumor localization and treatment planning. Sometimes, dense sampling is not acquired along the superior-inferior direction. This disadvantage results in an interslice thickness that is much greater than in-plane voxel resolutions. Isotropic resolution is necessary for multiplanar display, but the commonly used interpolation operation blurs images. This paper presents a super-resolution (SR) reconstruction method to enhance 4D-CT resolution.
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Schistosomicidal and Antioxidant Flavonoids from Astragalus englerianus.
Planta Med.
PUBLISHED: 11-05-2014
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Astragalus englerianus is a close relative of the traditional Chinese medicine plant Radix Astragali (Huang-qi) and is mainly distributed in Yunnan. It has been traditionally used as a substitute of "Huang-qi" for reducing fatigue and enhancing immunity by local folks. A phytochemical study of the methanol extract of the roots led to the isolation of three new flavonoids including one aurone (1) and two chalcones (2 and 3), as well as two known flavonoids (4 and 5). Their structures were elucidated based on the analyses of extensive spectroscopic data and comparison of their physicochemical properties. This is the first report on the occurrence of ?-hydroxydihydrochalcone, 2',5'-dioxygenchalcones, and 2',5'-dioxygenaurone in the genus Astragalus. All the isolated compounds were tested in vitro for their schistosomicidal and antioxidant activities. Compounds 2 and 4 showed schistosomicidal activities with worm mortality rates of 100?% within 12?h in a drug-containing (0.70 and 0.77?mM, respectively) RPMI 1640 medium. Compounds 1 and 2 exhibited antioxidant activities in 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl free radical scavenging assays, with IC50 values of 35.9?±?1.1 and 12.2?±?1.1?µM, respectively.
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Tunable near-Infrared Luminescence of PbSe Quantum Dots for Multigas Analysis.
Anal. Chem.
PUBLISHED: 11-04-2014
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Multigas sensing is highly demanded in the fields of environmental monitoring, industrial production, and coal mine security. Three near-infrared emission wavelengths from PbSe quantum dots (QDs) were used to analyze the concentration of three gases simultaneously through direct absorption spectroscopy, including acetylene (C2H2), methane (CH4), and ammonia (NH3). The corresponding lower detection limits for the three gases were 20, 100, and 20 ppm, respectively, with an accuracy of 2%. This study demonstrates that QDs with tunable emissions have great potential for simultaneous and uninterfered multiplex gas analysis and detection due to the advantages of the easy tunability of multiplex emitting wavelengths from QDs.
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All-fiber self-accelerating Bessel-like beam generator and its application.
Opt Lett
PUBLISHED: 11-01-2014
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We demonstrate an all-fiber transverse self-accelerating Bessel-like beam generator and its optical trapping application. The theoretical and experimental studies have been provided to verify this beam properties. We produce the Bessel-like beam by splicing the single-mode fiber and multimode fiber with a defined offset and then modulating the output light beam phase by fabricating a small hemispherical-lens fiber tip; therefore, the phase-modulated Bessel-like beam generates the properties of transverse self-accelerating. The transverse acceleration of the the Bessel-like beam generated here is ?10-4???m-1, which is almost 100 times larger than that of the beam generated in the free-space optical circuit based on the lens. The experimental and simulated results have good consistencies. The realization of the microparticle transverse acceleration transporting with this Bessel-like beam provides a new method for microparticles to be transported in a bending trajectory. This all-fiber transverse self-accelerating Bessel-like beam generator structure is simple, with high integration and small size, and constitutes a new development for high-precision biological cell experiments and manipulations.
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Enhanced 2.7- and 2.84-?m emissions from diode-pumped Ho3+/Er3+-doped fluoride glass.
Opt Lett
PUBLISHED: 11-01-2014
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This work reports the intense emissions at 2.7 and 2.84 ?m in a Ho3+/Er3+-codoped fluoride glass (ZrF4-BaF2-YF3-AlF3). An extensive transmission spectrum and the absence of strong OH- absorption guarantee the observation of mid-infrared (IR) emissions. For the Ho3+/Er3+-codoped sample, the 2.7- and 2.84-?m emissions are 5.8 and 3.8 times higher with larger emission cross-sections (10.2×10-21 and 9.8×10-21??cm2), respectively. Meanwhile, other near to middle infrared emissions (1200, 2045 nm emissions from Ho3+ and 980, and 1535 nm emissions from Er3+ ions) are all enhanced. The collective enhanced effect originates from the disappearance of nonradiative decay processes after codping Er3+ and Ho3+ ions. Hence, the advantageous spectroscopic characteristics of Ho3+/Er3+-codoped ZBYA glass indicate that this kind of fluoride glass may be an attractive host to develop solid-state lasers for 3 ?m.
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Immunoprophylaxis Failure Against Vertical Transmission of Hepatitis B Virus in the Chinese Population: A Hospital-based Study and a Meta-analysis.
Pediatr. Infect. Dis. J.
PUBLISHED: 11-01-2014
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Despite effective immunoprophylaxis, vertical transmission of hepatitis B virus (HBV) from infected mothers still occurs. This study aimed to provide an estimate of the prevalence of immunoprophylaxis failure and evaluate associated risk factors.
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Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.
Blood
PUBLISHED: 11-01-2014
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Germline, loss-of-function mutations in the transcription factor STAT3 cause immunodeficiency, while somatic, gain-of-function mutations in STAT3 are associated with large granular lymphocytic leukemic, myelodysplastic syndrome, and aplastic anemia. Recently, germline mutations in STAT3 have also been associated with autoimmune disease. Here we report thirteen individuals from ten families with lymphoproliferation and early-onset, solid organ autoimmunity associated with nine different germline, heterozygous mutations in STAT3. Patients exhibited a variety of clinical features, with most having lymphadenopathy, autoimmune cytopenias, multi-organ autoimmunity (lung, gastrointestinal, hepatic, and/or endocrine dysfunction), infections and short stature. Functional analyses demonstrate that these mutations confer a gain-of-function in STAT3 leading to secondary defects in STAT5 and STAT1 phosphorylation and the regulatory T cell compartment. Treatment targeting a cytokine pathway that signals through STAT3 lead to clinical improvement in one patient, suggesting a potential therapeutic option for such patients. These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly-described disorder. Some patients for this study were enrolled in a trial registered at ClinicalTrials.gov #NCT00001350.
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[Influence of urea formaldehyde resin on pyrolysis of biomass: a modeling study by TG-FTIR].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 11-01-2014
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Pyrolysis is an efficient and recycling way to utilize waste wood-based panels, in which urea-formaldehyde resin (UF) is the main difference between wood-based board and other kinds of biomass. The present paper studied the three main components (cellulose, hemicelluloses, lignin) of poplar wood, in order to effectively and environmentally utilize or dispose of waste wood-based panels with pyrolysis technique, to study the influence of urea formaldehyde resin on pyrolytic characteristic of wood during the process of the pyrolysis of waste wood-based panels, and to in-depth explore the mechanism of the effect of UF on each component of wood. Innovatively, the weight-loss character and gas evolution rule of the model (made from cellulose, xylan and lignin, based on the chemical components stud of poplar wood), the main components as well as the ones mixed with UF were analyzed by TG-FTIR (thermogravimetric analyzer coupled to a Fourier transform infrared spectrometer). Results indicated that UF promoted the generation of water and carboxylic acid substances during the cellulose pyrolysis process. UF combined with lignin, formed some kind of unstable nitrogenous structure which produced a large amount of NH3, which took part in the low-temperature (200-300 degrees C) pyrolysis of lignin, and directly affected the production of pyrolysis products. It can be concluded that during the process of the pyrolysis of waste wood-based panels, lignin was the one that UF mainly impacted among the three main components of wood.
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An array sensor consisting of a single indicator with multiple concentrations and its application in ion discrimination.
Chem. Commun. (Camb.)
PUBLISHED: 10-28-2014
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Optical sensor arrays typically require a large set of chemically responsive colorants to enhance discrimination capability. Conversely, we have proven that by using multiple concentrations of one indicator, the discrimination of various analytes could be realized.
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Overexpression of Special AT-Rich Sequence-Binding Protein 1 in Endometrial Cancer: A Clinicopathologic Study.
Int. J. Gynecol. Cancer
PUBLISHED: 10-28-2014
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Special AT-rich sequence-binding protein 1 (SATB1), as a genome organizer, serves important functions in tumor progression and metastasis. The SATB1 is overexpressed in various malignant tumors. However, the expression and prognostic value of SATB1 in endometrial cancer remain unknown. The aim of this study was to explore the prognostic values of SATB1 expression in endometrial cancer.
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[Effect of different functional groups on self-assembled monolayers on the biological characteristics of skeletal muscle cells in vitro].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 10-28-2014
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To explore the effect of different functional groups on self-assembled monolayers on the biological characteristics of rabbit skeletal muscle cells in vitro.
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Prognostic values of VEGF and endostatin with malignant pleural effusions in patients with lung cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent.
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[Expression of biomarkers related with bone marrow cells in patients with acute myelogenous leukemia].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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This study was aimed to investigate the expression of biomarkers (PTEN, mTOR, NF-kB, CD44, PI3K) related with bone marrow cells in patients with acute myelogenous leukemia. The immunohistochemical method was used to detect the expression of PTEN, mTOR, NF-kB, CD44, PI3K in 20 patients. The AML patients were divided into remission group and non-remission group after calculating the percentage of leukemia cells in bone marrow. The results showed that by optical microscopy, the positive expression rates of PTEN, mTOR, NF-kB, CD44 and PI3K in remission group were 33.3%, 33.3%, 77.8%, 22.2%, 0, respectively; meanwhile, in non-remission group, the positive expression rates of above-menthioned biomarkers were 63.6%, 18.2, 90.9, 63.6%, 0, respectively. The percentage and mean OD for PTEN and CD44 were statistically different between the two groups (P < 0.05), but for mTOR, NF-kB and PI3K were not statistically differenly (P > 0.05). It is concluded that the high expression of PTEN and CD44 can be regarded as an important index for diagnosis and prognosis in acute myelogenous leukemia.
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The complete mitochondrial genome of Teratoscincus roborowskii (Squamata: Gekkonidae).
Mitochondrial DNA
PUBLISHED: 10-21-2014
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Abstract The complete nucleotide sequence of the mitochondrial genome of Teratoscincus roborowskii was sequenced here. It was determined to be 16,644 base pairs in length and contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control region. The 22 tRNA genes could be folded into the typical cloverleaf structure described for vertebrate mitochondrial tRNAs. The base composition of the heavy strand was 30.33% A, 30.35% C, 14.65% G and 24.67% T. The control region was located between the tRNA-Pro and tRNA-Phe genes and is 1248?bp in length and some tandem repeat sequences were found in it.
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Relationship of Serum Mannose-Binding Lectin Levels with the Development of Sepsis: a Meta-analysis.
Inflammation
PUBLISHED: 10-18-2014
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Many studies have evaluated the association between serum levels of mannose-binding lectin (MBL) and sepsis; however, the findings are inconclusive and conflicting. For a better understanding of MBL in sepsis, we conducted a comprehensive meta-analysis. Potential relevant studies were identified covering Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, and Current Contents Index databases. Two reviewers extracted data and assessed studies independently. Statistical analyses were conducted with the version 12.0 STATA statistical software. Ten papers were collected for meta-analysis. Results identified that sepsis patients had considerably lower MBL level than those in the controls (standardized mean difference (SMD)?=?1.59, 95 % confidence interval (95%CI)?=?0.86?2.31, P?
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Silica-based nanocapsules: synthesis, structure control and biomedical applications.
Chem Soc Rev
PUBLISHED: 10-14-2014
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Synergistically combining the merits of silica (e.g., mechanical robustness, biocompatibility and great versatility in surface functionalization) and capsular configurations (e.g., a large inner cavity, low density and favourable colloidal properties), silica-based nanocapsules (SNCs) with a size cutoff of ?100 nm have gained growing interest in encapsulating bioactive molecules for bioimaging and controlled delivery applications. Within this context, this review provides a comprehensive overview of the synthetic strategies, structural control and biomedical applications of SNCs. Special emphasis is placed on size control at the nanoscale and material composition manipulation of each strategy and the newly emerging synthetic strategies. The applications of SNCs in bioimaging/diagnosis and drug delivery/therapy and the structure engineering that is critically important for the bio-performance of SNCs are also addressed in this review.
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The effect of a solid surface on the segregation and melting of salt hydrates.
J. Am. Chem. Soc.
PUBLISHED: 10-14-2014
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Considering the importance of salt and water on earth, the crystallization of salt hydrates next to solid surfaces has important implications in physical and biological sciences. Heterogeneous nucleation is driven by surface interactions, but our understanding of hydrate formation near surfaces is limited. Here, we have studied the hydrate formation of three commonly prevalent salts, MgCl2, CaCl2, and NaCl, next to a sapphire substrate using surface sensitive infrared-visible sum frequency generation (SFG) spectroscopy. SFG spectroscopy can detect the crystallization and melting of salt hydrates at the interface by observing the changes in the intensity and the location of the cocrystallized water hydroxyl peaks (3200-3600 cm(-1)). The results indicate that the surface crystal structures of these three hydrates are similar to those in the bulk. For the NaCl solution, the brine solution is segregated next to the sapphire substrate after the formation of the ice phase. In contrast, the MgCl2 and CaCl2 surface hydrate crystals are interdispersed with nanometer-size ice crystals. The nanosize ice crystals melt at much lower temperatures than bulk ice crystals. For NaCl and MgCl2 solution, the NaCl hydrates prefer to crystallize next to the sapphire substrate instead of the ice crystals and MgCl2 hydrates.
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Three-dimensional attosecond resonant stimulated X-ray Raman spectroscopy of electronic excitations in core-ionized glycine.
Phys Chem Chem Phys
PUBLISHED: 10-10-2014
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We investigate computationally the valence electronic excitations of the amino acid glycine prepared by a sudden nitrogen core ionization induced by an attosecond X-ray pump pulse. The created superposition of cationic excited states is probed by two-dimensional transient X-ray absorption and by three dimensional attosecond stimulated X-ray Raman signals. The latter, generated by applying a second broadband X-ray pulse combined with a narrowband pulse tuned to the carbon K-edge, reveal the complex coupling between valence and core-excited manifolds of the cation.
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Self?assembled monolayers of alkanethiolates on surface chemistry groups in osteosarcoma cells.
Mol Med Rep
PUBLISHED: 10-08-2014
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Cell biomedical behavior is influenced by a number of factors, and the extracellular matrix (ECM) of the cellular microenvironment affects certain cancer cells. In the current study, U?2OS cells were cultured on gold surfaces modified with different terminal chemical groups [methyl (?CH3), amino (?NH2), hydroxyl (?OH) and carboxyl (?COOH)]. The results revealed that different chemical surfaces convey different behaviors. The density of the different functional surfaces was confirmed by atomic force microscopy. Cell morphology, proliferation rate and cell cycle were investigated using scanning electron microscopy, cell counting and flow cytometry. In conclusion, the type of chemical group on a biomaterial is an important property for the growth of osteosarcoma cells; ?NH2 and ?COOH surfaces sustained visible cell adhesion and promoted cell growth.
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Double oxidation of ?-(alkylideneamino)nitriles to imides by molecular oxygen under mild basic conditions.
Chem. Commun. (Camb.)
PUBLISHED: 10-07-2014
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We reveal here the unique reactivity of ?-(alkylideneamino)nitriles toward molecular oxygen. Thus, ?-(alkylideneamino)nitriles can serve as the imide building block for the efficient synthesis of imides in the absence of transition metals under extremely mild conditions.
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Improving Trichoderma reesei Cel7B Thermostability by Targeting the Weak Spots.
J Chem Inf Model
PUBLISHED: 10-06-2014
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For proteins that denature irreversibly, the denaturation is typically triggered by a partial unfolding, followed by a permanent change (e.g., aggregation). The regions that initiate the partial unfolding are named "weak spots". In this work, a molecular dynamics (MD) simulation and data analysis protocol is developed to identify the weak spots of Trichoderma reesei Cel7B, an important endoglucanase in cellulose hydrolysis, through assigning the local melting temperature (Tmp) to individual residue pairs. To test the predicted weak spots, a total of eight disulfide bonds were designed in these regions and all enhanced the enzyme thermostability. The increased stability, quantified by ?T50 (which is the T50 difference between the mutant and the wild type enzyme), is negatively correlated with the MD-predicted Tmp, demonstrating the effectiveness of the protocol and highlighting the importance of the weak spots. Strengthening interactions in these regions proves to be a useful strategy in improving the thermostability of Tr. Cel7B.
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Characterization of the Promoter of Grapevine vein clearing virus.
J. Gen. Virol.
PUBLISHED: 10-05-2014
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Grapevine Vein Clearing Virus (GVCV) is a newly discovered DNA virus in grapevine that is closely associated with grapevine vein clearing syndrome observed in vineyards in Missouri and surrounding states. The genome sequence of GVCV indicates that it belongs to the genus Badnavirus in the family Caulimoviridae. To identify the GVCV promoter, we cloned portions of the GVCV large intergenic region in front of a GFP gene present in an Agrobacterium tumefaciens binary vector. GFP expression was assessed by ELISA three days after agroinfiltration of Nicotiana benthamiana leaves. We found that the GVCV DNA segment between nucleotides 7,332 and 7,672 directed expression of GFP and it was stronger than the Cauliflower mosaic virus 35S promoter. 5' and 3' RACE revealed that transcription was initiated predominantly at nucleotide 7,571 and terminated at nucleotide 7,676.
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Rituximab-Au nanoprobes for simultaneous dark-field imaging and DAB staining of CD20 over-expressed on Raji cells.
Analyst
PUBLISHED: 10-03-2014
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A novel dual-modal cell immunodetection method based on both dark-field imaging and catalysis functions of gold nanoparticles has been established, where the Rituximab-Au conjugates were used as nanoprobes to label and image specifically the CD20 overexpressed on the surface of malignant lymphoma cells of Raji with high affinity.
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Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke.
J. Neurosci.
PUBLISHED: 10-03-2014
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Stroke is a major public health concern. The lack of effective therapies heightens the need for new therapeutic targets. Mammalian brain has the ability to rewire itself to restore lost functionalities. Promoting regenerative repair, including neurogenesis and dendritic remodeling, may offer a new therapeutic strategy for the treatment of stroke. Here, we report that interaction of neuronal nitric oxide synthase (nNOS) with the protein postsynaptic density-95 (PSD-95) negatively controls regenerative repair after stroke in rats. Dissociating nNOS-PSD-95 coupling in neurons promotes neuronal differentiation of neural stem cells (NSCs), facilitates the migration of newborn cells into the injured area, and enhances neurite growth of newborn neurons and dendritic spine formation of mature neurons in the ischemic brain of rats. More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of regenerative repair in rats. Histone deacetylase 2 in NSCs may mediate the role of nNOS-PSD-95 association. Thus, nNOS-PSD-95 can serve as a target for regenerative repair after stroke.
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[Isolation, identification and genetic analysis of a murine norovirus strain].
Bing Du Xue Bao
PUBLISHED: 10-03-2014
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Murine norovirus (MNV) was first discovered in mice in 2003. MNV is a member of the genus Norovirus in the family Caliciviridae. It is one of the most important and prevalent pathogens of laboratory mice, and almost all mouse strains are susceptible to MNV infection. In this study, a MNV strain was isolated from the cecal contents of infected mice and identified by the cytopathic effect (CPE) assay, virus plaque assay, 50% tissue culture infectious dose (TCID50) assay, electron microscopy, indirect immunofluorescence assay (IFA) and nucleotide sequencing. On infection, the RAW264.7 cell line showed obvious cytopathic effects within 24 to 48 hours post-inoculation, as infected cells became rounded, bright and shrunken, with ultimate disintegration of the cell sheet. After the isolation of the MNV virus, the virus was plaque-purified in RAW264.7 cells. The TCID50 of the virus was 10(5.25/0.1 mL. Electron microscopic observations of the purified virus showed the presence of spherical and non-enveloped viral particles that were 30 to 35 nm in diameter. According to the identification results, the isolate was named as MNV Guangzhou/K162/09/CHN. Thereafter, five overlapping gene fragments that covered the entire open reading frame (ORF) were amplified by RT-PCR, and the 3'-untranslated region (UTR) and 5'-UTR were amplified using the 3'-rapid amplification of cDNA ends (RACE) and the 5'-RACE method, respectively. Each of the gene fragments were cloned and sequenced, and whole genome sequences of the strain were obtained by assembling the cDNA fragment sequences. The results showed that the length of the complete genome was 7 380 nucleotides (GenBank accession number: HQ317203). The comparison of nucleotide and deduced amino acid sequences of the isolate was performed against other MNV strains in the GenBank database. A phylogenetic tree based on VP1 nucleotide sequences was constructed using MEGA5.0 software. The homology of nucleotides between the MNV Guangzhou/K162/09/CHN strain and other MNV isolates ranged from 87.4% to 89.7%. Phylogenetic analysis showed that there was a close genetic relationship between the Guangzhou/K162/09/CHN strain and MNV strains isolated from Japan (S7-P2 and S7-PP3 isolates), Korea (K4 isolate), and Germany (Berlin/04/06/DE and Berlin/05/06/DE isolates). This is the first report of the isolation and identification of MNV in China, and the first report of the genetic analysis of its complete genome.
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Increased incidence of bowel and psychological symptoms in Chinese female D-IBS patients with premenstrual syndrome.
Gastroenterol Nurs
PUBLISHED: 10-02-2014
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The purpose of this study was to investigate levels of stress, gynecological events, bowel, and psychological symptoms in Chinese women of reproductive age who experienced both diarrhea-predominant irritable bowel syndrome (D-IBS) and premenstrual syndrome. A cross-sectional study used the self-reported questionnaire based on previous studies done abroad with the Rome III criteria and Symptom Checklist-90 Scale. The research was performed on 233 reproductive age women in China. A descriptive, comparative approach was used to (a) describe general characteristics and the history of disease both of the overlapping group and the D-IBS group, (b) compare stress and gynecological experience of the 2 groups, (c) compare the characteristics of defecation and bowel habits by group, and (d) compare psychological symptoms between groups. Percentage distribution and chi-square tests were used to analyze data. The results revealed that compared to simple D-IBS patients, the patients in the overlapping syndromes group had increased stress and gynecological events and more severe bowel and psychological symptoms. Overlapping syndromes were associated with repeated episodes of longer duration and delayed recovery. Future studies with expanded sample size and blood collection may verify and explain the results of this study.
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A Gain-of-Function Mutation in Tnni2 Impeded Bone Development through Increasing Hif3a Expression in DA2B Mice.
PLoS Genet.
PUBLISHED: 10-01-2014
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Distal arthrogryposis type 2B (DA2B) is an important genetic disorder in humans. However, the mechanisms governing this disease are not clearly understood. In this study, we generated knock-in mice carrying a DA2B mutation (K175del) in troponin I type 2 (skeletal, fast) (TNNI2), which encodes a fast-twitch skeletal muscle protein. Tnni2K175del mice (referred to as DA2B mice) showed typical DA2B phenotypes, including limb abnormality and small body size. However, the current knowledge concerning TNNI2 could not explain the small body phenotype of DA2B mice. We found that Tnni2 was expressed in the osteoblasts and chondrocytes of long bone growth plates. Expression profile analysis using radii and ulnae demonstrated that Hif3a expression was significantly increased in the Tnni2K175del mice. Chromatin immunoprecipitation assays indicated that both wild-type and mutant tnni2 protein can bind to the Hif3a promoter using mouse primary osteoblasts. Moreover, we showed that the mutant tnni2 protein had a higher capacity to transactivate Hif3a than the wild-type protein. The increased amount of hif3a resulted in impairment of angiogenesis, delay in endochondral ossification, and decrease in chondrocyte differentiation and osteoblast proliferation, suggesting that hif3a counteracted hif1a-induced Vegf expression in DA2B mice. Together, our data indicated that Tnni2K175del mutation led to abnormally increased hif3a and decreased vegf in bone, which explain, at least in part, the small body size of Tnni2K175del mice. Furthermore, our findings revealed a new function of tnni2 in the regulation of bone development, and the study of gain-of-function mutation in Tnni2 in transgenic mice opens a new avenue to understand the pathological mechanism of human DA2B disorder.
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Chemical vapour deposition of group-VIB metal dichalcogenide monolayers: engineered substrates from amorphous to single crystalline.
Chem Soc Rev
PUBLISHED: 09-27-2014
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As structural analogues of graphene but with a sizeable band gap, monolayers of group-VIB transition metal dichalcogenides (MX2, M = Mo, W; X = S, Se, Te, etc.) have emerged as the ideal two dimensional prototype for exploring fundamental issues in physics such as valley polarization, and for engineering a wide range of nanoelectronic, optoelectronic and photocatalytic applications. Recently, chemical vapour deposition (CVD) was introduced as a more efficient preparation method than traditional chemical or physical exfoliation options, and has allowed for the successful synthesis of large-area MX2 monolayers possessing a large domain size, high thickness uniformity and continuity, and satisfactory crystal quality. This tutorial review therefore focuses on introducing the more recent advances in the CVD growth of MX2 (MoS2, WS2, MoS2(1-x)Se2xetc.) monolayers via the sulphurisation/decomposition of pre-deposited metal-based precursors, or the one-step reaction and deposition of gaseous metal and chalcogen feedstocks. Differences in growth behaviour caused by commonly used amorphous SiO2/Si, and newly adopted insulating single crystal substrates such as sapphire, mica and SrTiO3, are also comparatively presented. Also discussed are the essential parameters that influence the growth of MX2, such as the temperature, the source-substrate distance and the composition of the carrier gas (Ar/H2). Finally, an assessment is provided for viable future pathways for fine-tuning of the domain size and orientation, thickness uniformity, and the bandgap of MX2 and its alloys.
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[Comparison of clinical efficacy between HLA-mismatched related and HLA-matched unrelated donor hematopoietic stem cell transplantation for hematopoietic malignancies].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 09-24-2014
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To compare the clinical efficacy of HLA- mismatched related donor (MRD) and HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies.
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[Mechanisms of myeloid cell RelA/p65 in cigarette smoking-induced lung cancer growth in mice].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 09-23-2014
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The aim of this study was to investigate the mechanism of cigarette smoking (CS)-induced lung cancer growth in mice.
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Proteomic profiling during the pre-competent to competent transition of the biofouling polychaete Hydroides elegans.
Biofouling
PUBLISHED: 09-20-2014
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The polychaete, Hydroides elegans, is a tube-building worm that is widely distributed in tropical and subtropical seas. It is a dominant fouling species and thus a major target organism in antifouling research. Here, the first high-throughput proteomic profiling of pre-competent and competent larvae of H. elegans is reported with the identification of 1,519 and 1,322 proteins, respectively. These proteins were associated with a variety of biological processes. However, a large proportion was involved in energy metabolism, redox homeostasis, and microtubule-based processes. A comparative analysis revealed 21 proteins that were differentially regulated in larvae approaching competency.
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Quantitative determination of euphol in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.
Biomed. Chromatogr.
PUBLISHED: 09-20-2014
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Euphol is a potential pharmacologically active ingredient isolated from Euphorbia kansui. A simple, rapid, and sensitive method to determine euphol in rat plasma was developed based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the first time. The analyte and internal standard (IS), oleanic acid, were extracted from plasma with methanol and chromatographied on a C18 short column eluted with a mobile phase of methanol–water–formic acid (95:5:0.1, v/v/v). Detection was performed by positive ion atmospheric pressure chemical ionization in selective reaction monitoring mode. This method monitored the transitions m/z 409.0??109.2 and m/z 439.4???203.2 for euphol and IS, respectively. The assay was linear over the concentration range 27–9000?ng/mL, with a limit of quantitation of 27?ng/mL. The accuracy was between –7.04 and 4.11%, and the precision was <10.83%. This LC-MS/MS method was successfully applied to investigate the pharmacokinetic study of euphol in rats after intravenous (6?mg/kg) and oral (48?mg/kg) administration. Results showed that the absolute bioavailability of euphol was approximately 46.01%.
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Four 2D "fully reduced" polyoxovanadates: vanadium oxide clusters encapsulating different guest molecules.
Inorg Chem
PUBLISHED: 09-19-2014
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Four two-dimensional fully reduced polyoxovanadates, namely, [Cd(DAP)2]4[HV(III)3V(IV)18P6O60(DAP)3(HOCH2CH2OH)]·10H2O (1), [Cd(DAP)2]4[HV(III)3V(IV)18P6O60(DAP)3(CH3OH)]·11H2O (2), [Cd(DAP)2]4[HV(III)3V(IV)18P6O60(DAP)3(CH3CH2OH)]·4H2O (3) and Co(III)(DAP)3[Co(II)(DAP)2]3[V(III)3V(IV)18P6O60(DAP)3(HOCH2CH2OH)]·14H2O (4) were synthesized by virtue of the reducing power of alkylamine in hydrothermal conditions. Single-crystal X-ray structural analysis, magnetic measurement, IR spectroscopy, elemental analysis, and thermogravimetric measurements were performed to analyze the structures and properties of these four compounds. Structural analysis indicates that the four compounds contain the same huge low-valent vanadium oxide anion cages [V(III)3V(IV)18P6O60(DAP)3](9-), and the cages can catch different guest molecules. Four cages are linked by Co or Cd atoms to form a four-membered ring, while adjacent four-membered rings are connected to each other by sharing edges to make an inorganic-organic hybrid layer. The magnetic susceptibility measurements of four compounds indicate ferrimagnetic interactions between vanadium ions.
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Calreticulin Promotes Migration and Invasion of Esophageal Cancer Cells by Upregulating Neuropilin-1 Expression via STAT5A.
Clin. Cancer Res.
PUBLISHED: 09-17-2014
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We previously revealed that the calreticulin (CRT) gene is a candidate oncogene promoting cell migration and invasion and that neuropilin-1 (NRP1) is a possible effector downstream of CRT in esophageal squamous carcinoma cells. This study aims to explore the mechanisms underlying the migration and invasion of esophageal cancer cells regulated by CRT through NRP1.
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Fisetin Inhibits Listeria monocytogenes Virulence by Interfering With the Oligomerization of Listeriolysin O.
J. Infect. Dis.
PUBLISHED: 09-17-2014
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Listeriolysin O (LLO), an essential virulence determinant of Listeria monocytogenes, is a pore-forming toxin whose primary function is to facilitate cytosolic bacterial replication by breaching the phagosomal membranes, which is critical for the pathogen to evade host immune recognition. The critical role of LLO in the virulence of L. monocytogenes renders it an ideal target for designing novel antivirulence therapeutics. We found that fisetin, a natural flavonoid without antimicrobial activity, is a potent antagonist of LLO-mediated hemolysis. Fisetin effectively inhibits L. monocytogenes infection in both tissue culture and animal infection models. Molecular modeling and mutational analysis revealed that fisetin directly engages loop 2 and loop 3 of LLO, leading to the blockage of cholesterol binding and the reduction of its oligomerization, thus inhibiting its hemolytic activity. Our results establish fisetin as an effective antitoxin agent for LLO, which can be further developed into novel therapeutics against infections caused by L. monocytogenes.
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Monitoring Long-Range Electron Transfer Pathways in Proteins by Stimulated Attosecond Broadband X-ray Raman Spectroscopy.
J Phys Chem Lett
PUBLISHED: 09-16-2014
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Long-range electron transfer (ET) is a crucial step in many energy conversion processes and biological redox reactions in living organisms. We show that newly developed X-ray pulses can directly probe the evolving oxidation states and the electronic structure around selected atoms with detail not available through conventional time-resolved infrared or optical techniques. This is demonstrated in a simulation study of the stimulated X-ray Raman (SXRS) signals in Re-modified azurin, which serves as a benchmark system for photoinduced ET in proteins. Nonlinear SXRS signals offer a direct novel window into the long-range ET mechanism.
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Geodesic propagation for semantic labeling.
IEEE Trans Image Process
PUBLISHED: 09-15-2014
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This paper presents a semantic labeling framework with geodesic propagation (GP). Under the same framework, three algorithms are proposed, including GP, supervised GP (SGP) for image, and hybrid GP (HGP) for video. In these algorithms, we resort to the recognition proposal map and select confident pixels with maximum probability as the initial propagation seeds. From these seeds, the GP algorithm iteratively updates the weights of geodesic distances until the semantic labels are propagated to all pixels. On the contrary, the SGP algorithm further exploits the contextual information to guide the direction of propagation, leading to better performance but higher computational complexity than the GP. For video labeling, we further propose the HGP algorithm, in which the geodesic metric is used in both spatial and temporal spaces. Experiments on four public data sets show that our algorithms outperform several state-of-the-art methods. With the GP framework, convincing results for both image and video semantic labeling can be obtained.
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Controllable Growth and Transfer of Monolayer MoS2 on Au Foils and Its Potential Application in Hydrogen Evolution Reaction.
ACS Nano
PUBLISHED: 09-15-2014
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Controllable synthesis of monolayer MoS2 is essential for fulfilling the application potentials of MoS2 in optoelectronics and valleytronics, etc. Herein, we report the scalable growth of high quality, domain size tunable (edge length from ?200 nm to 50 ?m), strictly monolayer MoS2 flakes or even complete films on commercially available Au foils, via low pressure chemical vapor deposition method. The as-grown MoS2 samples can be transferred onto arbitrary substrates like SiO2/Si and quartz with a perfect preservation of the crystal quality, thus probably facilitating its versatile applications. Of particular interest, the nanosized triangular MoS2 flakes on Au foils are proven to be excellent electrocatalysts for hydrogen evolution reaction, featured by a rather low Tafel slope (61 mV/decade) and a relative high exchange current density (38.1 ?A/cm(2)). The excellent electron coupling between MoS2 and Au foils is considered to account for the extraordinary hydrogen evolution reaction activity. Our work reports the synthesis of monolayer MoS2 when introducing metal foils as substrates, and presents sound proof that monolayer MoS2 assembled on a well selected electrode can manifest a hydrogen evolution reaction property comparable with that of nanoparticles or few-layer MoS2 electrocatalysts.
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Chemoenzymatic synthesis of 1,3-dioleoyl-2-palmitoylglycerol.
Biotechnol. Lett.
PUBLISHED: 09-13-2014
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We report the synthesis of 1,3-dioleoyl-2-palmitoylglycerol (OPO) by a three-step method. Vinyl oleate was first synthesized by transvinylation between vinyl acetate and oleic acid. This was further reacted with glycerol at 35 °C for 8 h using 10 % (w/v) Novozym 435 to synthesize 1,3-diolein. The 1,3-diolein content in the crude reaction mixture was 90.8 % and was obtained at 82.3 % (w/w) yield with 98.6 % purity after purification. Finally, OPO was chemically synthesized by reacting purified 1,3-diolein with palmitic acid. 94.8 % OPO was produced in the crude reaction mixture and the regiopurity of OPO after purification was 98.7 % at 90.5 % yield based on positional distribution analysis. This is an innovative approach for the synthesis of 1,3-diolein in a solvent-free system as an alternative to previously presented studies that applied solvent system.
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AGE modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival.
J. Pathol.
PUBLISHED: 09-12-2014
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Biomechanical strain imposed by age related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesised that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation endproduct (AGE)-dependent non-enzymatic crosslinking of its major components collagen IV and laminin. We used this model to demonstrate that antibody targeted blockade of CTLD2, the second of eight C-type lectin-like domains in Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) that can recognise glycosylated collagens, reversed actinomyosin-based contractility (myosin-light chain-2 [MLC2] phosphorylation), loss of cell polarity, loss of cell-cell junctions, luminal infiltration and basal invasion induced by AGE modified basal lamina matrix in PEC acini. Our in vitro results were concordant with luminal occlusion of acini in the prostate glands of adult Endo180(?Ex2) (-6/) (?Ex2) (-6) mice with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour in non-transformed PECs via a molecular mechanism linked to cancer progression. This study provides a rationale for targeting CTLD2 in Endo180 in prostate cancer, and other pathologies, where increased basal lamina thickness and tissue stiffness are driving factors.
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Fluorine-18-deoxyglucose positron emission tomography/computed tomography with Ki67 and GLUT-1 immunohistochemistry for evaluation of the radiosensitization effect of oleanolic acid on C6 rat gliomas.
Nucl Med Commun
PUBLISHED: 09-12-2014
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The aim of this study was to investigate the radiosensitization effect of oleanolic acid (OA) in an in-vivo C6 rat glioma model using fluorine-18-deoxyglucose PET/computed tomography (F-FDG PET/CT) and Ki67 and glucose transporter-1 (GLUT-1) immunohistochemistry (IHC) and evaluate the utility of F-FDG PET/CT in assessing early changes after radiotherapy.
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Pyk2 promotes tumor progression in multiple myeloma.
Blood
PUBLISHED: 09-12-2014
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Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase family that has been recently linked to tumor development. However, its role in modulating multiple myeloma (MM) biology and disease progression remains unexplored. We first demonstrated that patients with MM present with higher expression of Pyk2 compared with healthy individuals. By using loss-of-function approaches, we found that Pyk2 inhibition led to reduction of MM tumor growth in vivo as well as decreased cell proliferation, cell-cycle progression, and adhesion ability in vitro. In turn, overexpression of Pyk2 promoted the malignant phenotype, substantiated by enhanced tumor growth and reduced survival. Mechanistically, inhibition of Pyk2 reduced activation of Wnt/?-catenin signaling by destabilizing ?-catenin, leading to downregulation of c-Myc and Cyclin D1. Furthermore, treatment of MM cells with the FAK/Pyk2 inhibitor VS-4718 effectively inhibited MM cell growth both in vitro and in vivo. Collectively, our findings describe the tumor-promoting role of Pyk2 in MM, thus providing molecular evidence for a novel tyrosine kinase inhibitor as a new therapeutic option in MM.
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The bi-lobe-associated LRRP1 regulates Ran activity in Trypanosoma brucei.
J. Cell. Sci.
PUBLISHED: 09-12-2014
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Cilia and flagella are conserved eukaryotic organelles important for motility and sensory. The RanGTPase, best known for nucleocytoplasmic transport functions, may also play a role in protein trafficking into the specialized flagellar/ciliary compartments, although the regulatory mechanisms controlling Ran activity at the flagellum remain unclear. The unicellular parasite Trypanosoma brucei contains a single flagellum necessary for cell movement, division and morphogenesis. Correct flagellum functions require flagellar attachment to the cell body, which is mediated by a specialized flagellum attachment zone (FAZ) complex that is assembled together with the flagellum during the cell cycle. We have previously identified the leucine-rich-repeat protein 1 LRRP1 on a bi-lobe structure at the proximal base of flagellum and FAZ. LRRP1 is essential for bi-lobe and FAZ biogenesis, consequently affecting flagellum-driven cell motility and division. Here, we show that LRRP1 forms a complex with Ran and a Ran-binding protein, and regulates Ran-GTP hydrolysis in T. brucei. In addition to mitotic inhibition, depletion of Ran inhibits FAZ assembly in T. brucei, supporting the presence of a conserved mechanism that involves Ran in the regulation of flagellum functions in an early divergent eukaryote.
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FOXA1 antagonizes EZH2-mediated CDKN2A repression in carcinogenesis.
Biochem. Biophys. Res. Commun.
PUBLISHED: 09-11-2014
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CDKN2A (p16(INK4a)) is a crucial tumor suppressor involved in many cancers. Our recent investigations revealed that FOXA1 as a forkhead transcription factor mediates CDKN2A activation in cellular senescence. However, the contribution of this axis in carcinogenesis remains unclear. Here, using a comprehensive collection of cancer microarray data, we found FOXA1 is down-regulated in many cancers compared to their normal counterparts and the positive correlation between FOXA1 and CDKN2A could be observed in prostate and breast cancers with lower EZH2 (epigenetic repressor for CDKN2A) expression. Experimentally, epistasis analysis in prostate and breast cancer cells indicated that higher expression of FOXA1 opposes EZH2-mediated CDKN2A repression, as further depletion of FOXA1 reverts the de-silencing of CDKN2A caused by EZH2 inhibition. Concomitantly, EZH2-depletion suppresses cancer cell cycle progression and this regulation is optimized in the presence of FOXA1 and CDKN2A. A further oncogenic transformation assay suggested that overexpression of EZH2 is insufficient to block RAS-induced CDKN2A activation and loss of FOXA1 is mandatory to potentiate EZH2-mediated CDKN2A silencing and to bypass the senescence barrier. Importantly, using an in vitro histone methyltransferase (HMTase) system, we found FOXA1 directly inhibits EZH2's histone methyltransferase activity through its C-terminal histone binding motif. These data support that positive regulation of CDKN2A by FOXA1 counteracts its tumorigenic repression of by EZH2 in cancers.
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Dynamic bayesian testing of sets of variants in complex diseases.
Genetics
PUBLISHED: 09-11-2014
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Rare genetic variants have recently been studied for genome-wide associations with human complex diseases. Existing rare variant methods are based on the hypothesis-testing framework that predefined variant sets need to be tested separately. The power of those methods is contingent upon accurate selection of variants for testing, and frequently, common variants are left out for separate testing. In this article, we present a novel Bayesian method for simultaneous testing of all genome-wide variants across the whole frequency range. The method allows for much more flexible grouping of variants and dynamically combines them for joint testing. The method accounts for correlation among variant sets, such that only direct associations with the disease are reported, whereas indirect associations due to linkage disequilibrium are not. Consequently, the method can obtain much improved power and flexibility and simultaneously pinpoint multiple disease variants with high resolution. Additional covariates of categorical, discrete, and continuous values can also be added. We compared our method with seven existing categories of approaches for rare variant mapping. We demonstrate that our method achieves similar power to the best methods available to date when testing very rare variants in small SNP sets. When moderately rare or common variants are included, or when testing a large collection of variants, however, our method significantly outperforms all existing methods evaluated in this study. We further demonstrate the power and the usage of our method in a whole-genome resequencing study of type 1 diabetes.
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Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4.
Science
PUBLISHED: 09-11-2014
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Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor found on immune cells. The consequences of mutations in CTLA4 in humans are unknown. We identified germline heterozygous mutations in CTLA4 in subjects with severe immune dysregulation from four unrelated families. Whereas Ctla4 heterozygous mice have no obvious phenotype, human CTLA4 haploinsufficiency caused dysregulation of FoxP3(+) regulatory T (Treg) cells, hyperactivation of effector T cells, and lymphocytic infiltration of target organs. Patients also exhibited progressive loss of circulating B cells, associated with an increase of predominantly autoreactive CD21(lo) B cells and accumulation of B cells in nonlymphoid organs. Inherited human CTLA4 haploinsufficiency demonstrates a critical quantitative role for CTLA-4 in governing T and B lymphocyte homeostasis.
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Self-assembly of a thin highly reduced graphene oxide film and its high electrocatalytic activity.
Nanotechnology
PUBLISHED: 09-11-2014
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A thin highly reduced graphene oxide (rGO) film was self-assembled at the dimethyl formamide (DMF)-air interface through evaporation-induced water-assisted thin film formation at the pentane-DMF interface, followed by complete evaporation of pentane. The thin film was transferred onto various solid substrates for film characterization and electrochemical sensing. UV-visible spectrometry, scanning electron microscopy (SEM), atomic force microscopy (AFM) and electrochemistry techniques were used to characterize the film. An rGO film showing 82.8% of the transmittance at 550 nm corresponds to a few layers of rGO nanosheets. The rGO nanosheets cross-stack with each other, lying approximately in the plane of the film. An rGO film collected on a glassy carbon (GC) electrode exhibited improved electrical conductivity compared to GC, with the electrode charge-transfer resistance (Rct) reduced from 31 ? to 22 ?. The as-formed rGO/GC electrode was mechanically very stable, exhibiting significantly enhanced electrocatalytic activity to H(2)O(2) and dopamine. Multiple layers of the rGO films on the GC electrode showed even stronger electrocatalytic activity to dopamine than that of the single rGO film layer. The controllable formation of a stable rGO film on various solid substrates has potential applications for nanoelectronics and sensors/biosensors.
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A Bim-targeting strategy overcomes adaptive bortezomib resistance in myeloma through a novel link between autophagy and apoptosis.
Blood
PUBLISHED: 09-10-2014
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Bim contributes to resistance to various standard and novel agents. Here we demonstrate that Bim plays a functional role in bortezomib resistance in multiple myeloma (MM) cells and that targeting Bim by combining histone deacetylase inhibitors (HDACIs) with BH3 mimetics (eg, ABT-737) overcomes bortezomib resistance. BH3-only protein profiling revealed high Bim levels (Bim(hi)) in most MM cell lines and primary CD138(+) MM samples. Whereas short hairpin RNA Bim knockdown conferred bortezomib resistance in Bim(hi) cells, adaptive bortezomib-resistant cells displayed marked Bim downregulation. HDACI upregulated Bim and, when combined with ABT-737, which released Bim from Bcl-2/Bcl-xL, potently killed bortezomib-resistant cells. These events were correlated with Bim-associated autophagy attenuation, whereas Bim knockdown sharply increased autophagy in Bim(hi) cells. In Bim(low) cells, autophagy disruption by chloroquine (CQ) was required for HDACI/ABT-737 to induce Bim expression and lethality. CQ also further enhanced HDACI/ABT-737 lethality in bortezomib-resistant cells. Finally, HDACI failed to diminish autophagy or potentiate ABT-737-induced apoptosis in bim(-/-) mouse embryonic fibroblasts. Thus, Bim deficiency represents a novel mechanism of adaptive bortezomib resistance in MM cells, and Bim-targeting strategies combining HDACIs (which upregulate Bim) and BH3 mimetics (which unleash Bim from antiapoptotic proteins) overcomes such resistance, in part by disabling cytoprotective autophagy.
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Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model.
Blood
PUBLISHED: 09-09-2014
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Clonal proliferation of plasma cells within the bone marrow (BM) affects local cells, such as mesenchymal stromal cells (MSCs), leading to osteolysis and fatality in multiple myeloma (MM). Consequently, there is an urgent need to find better mechanisms of inhibiting myeloma growth and osteolytic lesion development. To meet this need and accelerate clinical translation, better models of myeloma within the BM are required. Herein we have developed a clinically-relevant, three-dimensional (3D) myeloma BM co-culture model that mimics bone cell/cancer cell interactions within the bone microenvironment. The co-culture model and clinical samples were utilized to investigate myeloma growth, osteogenesis inhibition, and myeloma-induced abnormalities in MM-MSCs. This platform demonstrated myeloma support of capillary-like assembly of endothelial cells and cell adhesion mediated-drug resistance (CAM-DR). Also, distinct normal donor (ND)- and MM-MSC miRNA signatures were identified and used to uncover osteogenic miRs of interest for osteoblast differentiation. More broadly, our 3D platform provides a simple, clinically-relevant tool to model cancer growth within the bone, useful for investigating skeletal cancer biology, screening compounds, and exploring osteogenesis. Our identification and efficacy validation of novel, bone anabolic miRs in MM opens the floodgate for novel approaches to cancer therapy via stromal miR modulation.
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PIWIL2 induces c-Myc expression by interacting with NME2 and regulates c-Myc-mediated tumor cell proliferation.
Oncotarget
PUBLISHED: 09-07-2014
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c-Myc serves as a crucial regulator in multiple cellular events. Cumulative evidences demonstrate that anomalous c-Myc overexpression correlates with proliferation, invasion and metastasis in various human tumors. However, the transcriptionally activating mechanisms responsible for c-Myc overexpression are complex and continue to be intangible. Here we showed that Piwi-Like RNA-Mediated Gene Silencing 2 (PIWIL2) can upregulate c-Myc via binding with NME/NM23 nucleoside diphosphate kinase 2 (NME2). PIWIL2 promotes c-Myc transcription by interacting with and facilitating NME2 to bind to G4-motif region within c-Myc promoter. Interestingly, in a c-Myc-mediated manner, PIWIL2 upregulates RhoA, which in turn induces filamentary F-actin. Deficiency of PIWIL2 results in obstacle for c-Myc expression, cell cycle progress and cell proliferation. Taken together, our present work demonstrates that PIWIL2 modulates tumor cell proliferation and F-actin filaments via promoting c-Myc expression.
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Genetic Variations rs11892031 and rs401681 Are Associated with Bladder Cancer Risk in a Chinese Population.
Int J Mol Sci
PUBLISHED: 09-05-2014
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Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Here, we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer (adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09-0.81; p = 0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10-2.91; p = 0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (p > 0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Future analyses will be conducted with more participants recruited in a case-control study.
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Strain engineering to prevent norleucine incorporation during recombinant protein production in Escherichia coli.
Biotechnol. Prog.
PUBLISHED: 09-05-2014
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Incorporation of norleucine in place of methionine residues during recombinant protein production in Escherichia coli is well known. Continuous feeding of methionine is commonly used in E. coli recombinant protein production processes to prevent norleucine incorporation. Although this strategy is effective in preventing norleucine incorporation, there are several disadvantages associated with continuous feeding. Continuous feeding increases the operational complexity and the overall cost of the fermentation process. In addition, the continuous feed leads to undesirable dilution of the fermentation medium possibly resulting in lower cell densities and recombinant protein yields. In this work, the genomes of three E. coli hosts were engineered by introducing chromosomal mutations that result in methionine overproduction in the cell. The recombinant protein purified from the fermentations using the methionine overproducing hosts had no norleucine incorporation. Furthermore, these studies demonstrated that the fermentations using one of the methionine overproducing hosts exhibited comparable fermentation performance as the control host in three different recombinant protein production processes. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 2014.
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Procalcitonin guidance for reduction of antibiotic use in patients hospitalized with severe acute exacerbations of asthma: a randomized controlled study with 12-month follow-up.
Crit Care
PUBLISHED: 09-05-2014
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IntroductionPatients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment. We aimed to determine whether serum procalcitonin (PCT) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma.MethodsIn this randomized controlled trial, a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate in this study and 169 completed 12-month follow-up visit. Patients were randomized to either PCT-guided (PCT group) or standard antimicrobial therapy (control group). In the control group, patients received antibiotics according to the attending physician; in the PCT group, patients received antibiotics according to an algorithm based on serum PCT levels. The primary endpoint was antibiotic exposure; secondary endpoints were clinical recovery, length of hospital stay, clinical and laboratory parameters, spirometry, numbers of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma.ResultsPCT guidance reduced antibiotic prescription (48.9% versus 87.8%, respectively; P <0.001) and antibiotic exposure (relative risk, 0.56; 95% confidence interval, 0.44 to 0.70; P <0.001) compared to standard therapy. There were no significant differences in clinical recovery, length of hospital stay, clinical, laboratory, spirometry outcomes in both groups. Numbers of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma were similar during 12-month follow-up period.ConclusionA PCT-guided strategy allows antibiotic exposure to be reduced in patients with severe acute exacerbation of asthma without apparent harm.Trial registrationChinese Clinical Trial Register ChiCTR-TRC-12002534. Registered 26 September 2012.
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[Experimental study on H2-Ab1 gene expression in the nasal mucosa of mice with allergic rhinitis].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-05-2014
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To investigate the level of H2-Ab1 in the nasal mucosa of mice with allergic rhinitis.
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The complete mitochondrial genome of Papilio polytes (Lepidoptera Papilionidae).
Mitochondrial DNA
PUBLISHED: 09-04-2014
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Abstract The complete sequence mitochondrial genome of Papilio polytes was determined using long PCR and conserved primers walking approaches. The genome was 15,260?bp in length and contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region (CR). The gene composition and order of P. polytes were similar to other lepidopteran species. All protein-coding genes begin with ATG and ATT as initiation codon except COI using CGA. 8 genes (ATP8, ATP6, ND3, ND5, ND4L, ND6, Cytb and ND1) ended with TAA and TAG stop codon, the remaining five genes had incomplete stop codon T. The overall base composition of the genome in descending order was 39.51% A, 11.86% C, 40.75% T and 7.88% G, with a A?+?T bias of 80.26%. CR is located between the 12S rRNA and tRNA-Met genes and is 439?bp in length, with an AT content of 83.37%.
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Network analysis of ChIP-Seq data reveals key genes in prostate cancer.
Eur. J. Med. Res.
PUBLISHED: 09-03-2014
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Prostate cancer (PC) is the second most common cancer among men in the United States, and it imposes a considerable threat to human health. A deep understanding of its underlying molecular mechanisms is the premise for developing effective targeted therapies. Recently, deep transcriptional sequencing has been used as an effective genomic assay to obtain insights into diseases and may be helpful in the study of PC.
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Making yttria-stabilized tetragonal zirconia translucent.
Dent Mater
PUBLISHED: 09-02-2014
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The aim of this study was to provide a design guideline for developing tetragonal yttria-stabilized zirconia with improved translucency.
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AN ERP-BASED BCI USING AN ODDBALL PARADIGM WITH DIFFERENT FACES AND REDUCED ERRORS IN CRITICAL FUNCTIONS.
Int J Neural Syst
PUBLISHED: 09-02-2014
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Recent research has shown that a new face paradigm is superior to the conventional "flash only" approach that has dominated P300 brain-computer interfaces (BCIs) for over 20 years. However, these face paradigms did not study the repetition effects and the stability of evoked event related potentials (ERPs), which would decrease the performance of P300 BCI. In this paper, we explored whether a new "multi-faces (MF)" approach would yield more distinct ERPs than the conventional "single face (SF)" approach. To decrease the repetition effects and evoke large ERPs, we introduced a new stimulus approach called the "MF" approach, which shows different familiar faces randomly. Fifteen subjects participated in runs using this new approach and an established "SF" approach. The result showed that the MF pattern enlarged the N200 and N400 components, evoked stable P300 and N400, and yielded better BCI performance than the SF pattern. The MF pattern can evoke larger N200 and N400 components and more stable P300 and N400, which increase the classification accuracy compared to the face pattern.
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Chemical functionalization of bone implants with nanoparticle-stabilized chitosan and methotrexate for inhibiting both osteoclastoma formation and bacterial infection.
J Mater Chem B Mater Biol Med
PUBLISHED: 09-02-2014
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A great challenge in orthopedic tumor operation faced by orthopedic implants is the high recurrence and metastasis of bone tumor as well as the bacterial infection associated with the implants. Thus ideal titanium (Ti)-based bone implants should be able to not only inhibit cancer cell adhesion and proliferation, promote cancer cell apoptosis, but also resist bacterial infections. Towards this end, we developed a new approach to modify the surface of Ti-based bone implants so that they can restrain functions of osteoclastoma (Giant cell tumor of bone) cancer cells (GCTs) and inhibit the adhesion of bacteria. First, the surface of pristine Ti substrates was functionalized with dopamine (DA) to form DA-Ti substrates. Then nanoparticles electrostatically assembled from poly-lysine (PLL) and heparin (Hep) were chemically immobilized onto the DA-Ti substrates to form PLL/Hep-Ti substrates. Chitosan (CH) and methotrexate (MTX) were then electrostatically immobilized onto the PLL/Hep-Ti substrates to generate CH-MTX-Ti substrates. The successful functionalization of the Ti substrates was confirmed by X-ray photoelectron spectroscopy. GCTs cultured on differently functionalized Ti substrates were investigated in terms of cell adhesion, cytoskeleton, proliferation, cytotoxicity and apoptosis. The growth of Staphylococcus aureus bacteria in the presence of different substrates was also assayed. Our results showed that CH-MTX-Ti substrates not only significantly inhibited the adhesion, proliferation and viability of GCTs, promoted the apoptosis of GCTs, but also prevented the adhesion of the bacteria and the subsequent formation of bacterial biofilms, when compared to other Ti substrates. Thus CH-MTX-Ti substrates are expected to be used as orthopedic prostheses in bone tumor surgery that can inhibit both osteoclastoma formation and bacterial infections.
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l-3-n-Butylphthalide attenuates ?-amyloid-induced toxicity in neuroblastoma SH-SY5Y cells through regulating mitochondrion-mediated apoptosis and MAPK signaling.
J Asian Nat Prod Res
PUBLISHED: 09-02-2014
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Alzheimer's disease (AD) is a progressive neurodegenerative disease. Amyloid-? protein (A?), the hallmark of AD, invokes a cascade of mitochondrial dysfunction and eventually leads to neuronal death. l-3-n-Butylphthalide (l-NBP) has shown the potent neuroprotective effects in stroke and AD animal models. The present study is to evaluate the neuroprotective effect of l-NBP on A?25-35-induced neuronal injury and the possible mechanism in the human neuroblastoma SH-SY5Y cells. Our results showed that l-NBP significantly attenuated A?25-35-induced cell death and reduced neuronal apoptosis. l-NBP significantly inhibited A?25-35-induced mitochondrial dysfunction, including mitochondrial membrane potential reduction, and reactive oxygen species production. Furthermore, l-NBP could partially reverse the elevations of A?25-35-induced active caspase-3, caspase-9, and cytochrome c expressions, and the downregulation of anti-apoptosis protein Bcl-2. Moreover, l-NBP markedly inhibited the activations of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase/stress-activated protein kinase signaling pathway. These results demonstrated that l-NBP was capable of protecting neuronal cells from A?25-35-induced toxicity through a mitochondrial-dependent apoptotic pathway. Thus, l-NBP shows promising candidate of multi-target neuronal protective agent for the treatment of AD.
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Up-Regulation of Glis2 Involves in Neuronal Apoptosis After Intracerebral Hemorrhage in Adult Rats.
Cell. Mol. Neurobiol.
PUBLISHED: 09-01-2014
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The novel Krüppel-like zinc finger protein Gli-similar 2 (Glis2), one member of the transcription factors, is involved in controlling the flow of genetic information and the modulation of diverse cellular activities. Accumulating evidence has demonstrated its important roles in adult development and several diseases. However, information regarding the regulation and possible function of Glis2 in the central nervous system is still limited. In this study, we explored the roles of Glis2 during the pathophysiological process of intracerebral hemorrhage (ICH). An ICH rat model was established and assessed by behavioral tests. Expression of Glis2 was significantly up-regulated in brain areas surrounding the hematoma following ICH. Immunofluorescence showed that Glis2 was strikingly increased in neurons, but not astrocytes or microglia. Up-regulation of Glis2 was found to be accompanied by the increased expression of active caspase-3 and Bax and decreased expression of Bcl-2 in vivo and vitro studies. Moreover, knocking down Glis2 by RNA-interference in PC12 cells reduced active caspase-3 and Bax expression while increased Bcl-2. Collectively, we speculated that Glis2 might exert pro-apoptotic function in neurons following ICH.
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Tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects: an open-label, randomized, single-center study.
Eur J Drug Metab Pharmacokinet
PUBLISHED: 08-31-2014
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The tolerability and pharmacokinetics of disodium folinate may vary with different races, and these variations might result in different outcomes. This study assessed the tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects, with gender factor also taken into account. Subjects were randomized to receive a single dose of disodium folinate at 20, 200, or 300 mg/m(2) administered intravenously over a time period of 10 min. Sequential blood samples were collected at regular intervals over 24 h after dosing and were analyzed using a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters, including C max, AUC0-t, t 1/2, V d, and CL, were calculated using non-compartmental models. Tolerability was assessed by collecting adverse events (AEs) and monitoring vital signs, physical examinations, laboratory tests, and electrocardiograms. Following a single intravenous administration of disodium folinate 20, 200, and 300 mg/m(2), the mean (standard deviation) pharmacokinetic parameters were as follows: C max = 5.18 (0.58), 47.80 (10.10), and 69.93 (9.72) µg/mL; AUC0-t = 25.85 (3.36), 194.53 (30.18), and 355.26 (35.31) µg h/mL; AUC0-? = 30.24 (6.19), 215.43 (27.34), and 417.88 (54.81) µg h/mL; t 1/2 = 8.77 (2.57), 7.64 (1.81), and 9.08 (1.64) h; CL = 1.12 (0.18), 1.55(0.25), and 0.78 (0.09) L/h; V d = 13.75 (2.61), 17.38 (6.44), and 10.05 (1.49) L, respectively. The mean C max, AUC0-t, and AUC0-? increased in a dose-proportional manner. No significant differences in pharmacokinetic parameters were noted by gender. The most common AEs reported were mild redness at the injection site and neurological symptoms (headache, dizziness, and fatigue).
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