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Find video protocols related to scientific articles indexed in Pubmed.
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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Extracts of Celastrus orbiculatus exhibit anti-proliferative and anti-invasive effects on human gastric adenocarcinoma cells.
Chin J Integr Med
PUBLISHED: 11-10-2014
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To assess the effect of Celastrus orbiculatus (COE) on growth, invasion and migration of human gastric cancer MGC-803 cells and to explore the possible mechanism.
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Lanreotide-conjugated PEG-DSPE micelles: an efficient nanocarrier targeting to somatostatin receptor positive tumors.
J Drug Target
PUBLISHED: 11-05-2014
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Abstract Lanreotide is an octapeptide analog of endogenous somatostatin, specifically binding with tumors over-express somatostatin receptor 2 (SSTR2). In this study, we conjugated lanreotide to 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (poly-(ethylene glycol))-2000] (PEG-DSPE), constructed active targeted micelles (lanreotide-PM), characterized their in vitro and in vivo targeting effect, and explored the receptor mediated transportion. The uptake of lanreotide-PM was found to be related to the expression level of SSTR2 in different cell lines and the competitive inhibition phenomenon indicated that the cellular uptake of lanreotide-PM was via a receptor meditated mechanism. In vivo, more lanreotide-PM accumulated in SSTR2 high expression tumor xenografts, endocytosed by the tumor cells, induced more apoptosis of tumor cells, and suppressed tumor growth efficiently. In conclusion, lanreotide-modified micelles containing antitumor drugs provide a promising strategy for the treatment of SSTR-expressing tumors.
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Broader implications of SILAC-based proteomics for dissecting signaling dynamics in cancer.
Expert Rev Proteomics
PUBLISHED: 10-27-2014
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Large-scale transcriptome and epigenome analyses have been widely utilized to discover gene alterations implicated in cancer development at the genetic level. However, mapping of signaling dynamics at the protein level is likely to be more insightful and needed to complement massive genomic data. Stable isotope labeling with amino acids in cell culture (SILAC)-based proteomic analysis represents one of the most promising comparative quantitative methods that has been extensively employed in proteomic research. This technology allows for global, robust and confident identification and quantification of signal perturbations important for the progress of human diseases, particularly malignancies. The present review summarizes the latest applications of in vitro and in vivo SILAC-based proteomics in identifying global proteome/phosphoproteome and genome-wide protein-protein interactions that contribute to oncogenesis, highlighting the recent advances in dissecting signaling dynamics in cancer.
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One-Year Outcomes of Emergency Department Patients With Atrial Fibrillation: A Prospective, Multicenter Registry in China.
Angiology
PUBLISHED: 10-26-2014
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There is lack of data about patient characteristics, practice patterns, and long-term adverse outcomes in patients with atrial fibrillation (AF) attending emergency departments (EDs) in China. A total of 2016 patients from 20 representative EDs were included. During 1 year, all-cause mortality was 291 (14.6%) cases, stroke/noncentral nervous system systemic embolism rate was 159 (8.0%) cases, and major bleeding was 26 (1.3%) cases. Heart failure, the major cause of mortality, accounted for 43.0% of deaths. Of 375 (18.6%) patients who used warfarin at baseline, only 217 (57.9%) patients were still on anticoagulation therapy during 1-year follow-up. Compared with the patients who continued on warfarin, the mortality rate was higher in those who did not continue (15.9% vs 5.5%, P < .001). Patients seen in ED with AF appear to have a high incidence rate of long-term all-cause mortality and inadequate anticoagulation rate.
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[Scoring formula research and equivalence evaluation of mandarin quick speech-in-noise test materials in mainland China].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 10-18-2014
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To discuss the scoring formula and evaluate the lists equivalence of Mandarin Quick Speech-in-Noise (M-Quick SIN) test materials in mainland China, and for standardizing our research.
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Intestinal microbial variation may predict early acute rejection after liver transplantation in rats.
Transplantation
PUBLISHED: 10-17-2014
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Acute rejection (AR) remains a life-threatening complication after orthotopic liver transplantation (OLT) and there are few available diagnostic biomarkers clinically for AR. This study aims to identify intestinal microbial profile and explore potential application of microbial profile as a biomarker for AR after OLT.
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Q-switched mode-locked erbium-doped fiber laser based on topological insulator Bi2Se3 deposited fiber taper.
Appl Opt
PUBLISHED: 10-17-2014
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We have demonstrated the passive Q-switching mode-locking operation in an erbium-doped fiber (EDF) laser by using topological insulator Bi2Se3 deposited on fiber taper, whose damage threshold can be further increased by the large evanescent field interacting length. Due to the low saturation intensity, stable Q-switched mode-locked fiber lasers centered at 1562 nm can be generated at a pump power of 10 mW. The temporal and spectral characteristics for different pump strengths have also been investigated. To the best of our knowledge, it is the first time a Q-switched mode-locked EDF laser based on the fiber taper deposited by Bi2Se3 was generated.
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T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.
Lancet
PUBLISHED: 10-17-2014
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Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with acute and chronic lymphocytic leukaemia and B-cell lymphomas, but feasibility, toxicity, and response rates of consecutively enrolled patients treated with a consistent regimen and assessed on an intention-to-treat basis have not been reported. We aimed to define feasibility, toxicity, maximum tolerated dose, response rate, and biological correlates of response in children and young adults with refractory B-cell malignancies treated with CD19-CAR T cells.
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Excessive autophagy induces the failure of trophoblast invasion and vasculature: possible relevance to the pathogenesis of preeclampsia.
J. Hypertens.
PUBLISHED: 10-17-2014
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Preeclampsia affects 5-7% of all healthy pregnancies and is characterized by hypertension and proteinuria. Although the pathogenesis of preeclampsia is still not fully understood, a failure of spiral artery transformation and aberrant placental vasculature are considered to be facets of this disease. Studies have also implicated increased autophagic activity. In this study, we investigated whether oxidative stress could increase autophagic activity and consequently affect trophoblast invasion and the placental vasculature.
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Surgical treatment of traumatic lower limb pseudoaneurysm.
Chin. J. Traumatol.
PUBLISHED: 10-09-2014
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To summarize our experience in surgical treatment of traumatic lower limb pseudoaneurysm.
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Two-dimensional transition metal dichalcogenide nanosheet-based composites.
Chem Soc Rev
PUBLISHED: 10-09-2014
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Ultrathin two-dimensional (2D) nanosheets of layered transition metal dichalcogenides (TMDs), such as MoS2, TiS2, TaS2, WS2, MoSe2, WSe2, etc., are emerging as a class of key materials in chemistry and electronics due to their intriguing chemical and electronic properties. The ability to prepare these TMD nanosheets in high yield and large scale via various methods has led to increasing studies on their hybridization with other materials to create novel functional composites, aiming to engineer their chemical, physical and electronic properties and thus achieve good performance for some specific applications. In this critical review, we will introduce the recent progress in hybrid nanoarchitectures based on 2D TMD nanosheets. Their synthetic strategies, properties and applications are systematically summarized and discussed, with emphasis on those new appealing structures, properties and functions. In addition, we will also give some perspectives on the challenges and opportunities in this promising research area.
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[Correlation analysis of bacterial biofilm formation and bacterial culture in chronic otitis media].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-25-2014
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To study the correlation between the bacterial biofilm formation and bacterial culture in chronic otitis media.
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Novel Free-Paclitaxel-Loaded Redox-Responsive Nanoparticles Based on a Disulfide-Linked Poly(ethylene glycol)-Drug Conjugate for Intracellular Drug Delivery: Synthesis, Characterization, and Antitumor Activity in Vitro and in Vivo.
Mol. Pharm.
PUBLISHED: 09-24-2014
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To address the obstacles facing cancer chemotherapeutics, including toxicity, side effects, water insolubility, and lack of tumor selectivity, a novel stimuli-responsive drug-delivery system was developed based on paclitaxel-loaded poly(ethylene glycol)-disulfide-paclitaxel conjugate nanoparticles (PEG-SS-PTX/PTX NPs). The formulation emphasizes several benefits, including polymer-drug conjugates/prodrugs, self-assembled NPs, high drug content, redox responsiveness, and programmed drug release. The PTX-loaded, self-assembled NPs, with a uniform size of 103 nm, characterized by DLS, TEM, XRD, DSC, and (1)H NMR, exhibited excellent drug-loading capacity (15.7%) and entrapment efficiency (93.3%). PEG-SS-PTX/PTX NPs were relatively stable under normal conditions but disassembled quickly under reductive conditions, as indicated by their triggered-aggregation phenomena and drug-release profile in the presence of dithiothreitol (DTT), a reducing agent. Additionally, by taking advantage of the difference in the drug-release rates between physically loaded and chemically conjugated drugs, a programmed drug-release phenomenon was observed, which was attributed to a higher concentration and longer action time of the drugs. The influence of PEG-SS-PTX/PTX NPs on in vitro cytotoxicity, cell cycle progression, and cellular apoptosis was determined in the MCF-7 cell line, and the NPs demonstrated a superior anti-proliferative activity associated with PTX-induced cell cycle arrest in G2/M phase and apoptosis compared to their nonresponsive counterparts. Moreover, the redox-responsive NPs were more efficacious than both free PTX and the non-redox-responsive formulation at equivalent doses of PTX in a breast cancer xenograft mouse model. This redox-responsive PTX drug delivery system is promising and can be explored for use in effective intracellular drug delivery.
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Encapsulation of nanoscale metal oxides into an ultra-thin Ni matrix for superior Li-ion batteries: a versatile strategy.
Nanoscale
PUBLISHED: 09-20-2014
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Li-ion batteries' (LIBs) performance proves to be highly correlated with ionic and electrical transport kinetics in electrodes. Although continual progress has been achieved in rational design of ideal electrode systems, their energy density, cyclic endurance and productivity are still far from perfect for practical use. Herein we propose an interesting, facile and versatile strategy to encapsulate various nanoscale metal oxides (covering both nanopowders and nanostructured arrays) into an ultrathin Ni matrix (metal oxide@Ni) for superior LIBs. Evolutions of such metal oxide@Ni hybrids (taking MnO@Ni and CoO@Ni as models) are thoroughly studied by monitoring their whole fabrication process. Putting "armors" on nanoscale metal oxides is thought helpful for the promotion of the LIB performance since the outer Ni matrix provides both mechanical protection against huge volume changes and effective routes for electron transfer. As a proof-of-concept demonstration, all metal oxide@Ni hybrid electrodes exhibit drastic improvements in the capacity retention (e.g. ?452% capacity rise for the MnO@Ni case while ?551% for CoO@Ni NWs), long-term cyclic stability and rate capabilities. This designed strategy can be further extended to make other advanced oxide@metal hybrids, not only for LIBs but also for other potential fields.
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Telbivudine or lamivudine use in late pregnancy safely reduces perinatal transmission of hepatitis B virus in real-life practice.
Hepatology
PUBLISHED: 09-18-2014
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Little observational data exist describing telbivudine (LdT) or lamivudine (LAM) use in late pregnancy for preventing hepatitis B mother-to-child transmission (MTCT) in real-world settings. During the period of January 2009 to March 2011, we enrolled hepatitis B e antigen-positive mothers with HBV DNA >6 log10 copies/mL in China. At gestation week 28, the mothers received LdT or LAM until postpartum week 4 or no treatment (NTx). The study endpoints were the safety of LdT/LAM use and MTCT rates. Of the 700 mothers enrolled, 648 (LdT/LAM/NTx?=?252/51/345) completed the 52-week study with 661 infants (LdT/LAM/NTx?=?257/52/352). On treatment, viral rebound occurred in 1.6% of mothers, all resulting from medication noncompliance. There was no genotypic mutation detected. At delivery, significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx. Alanine aminotransferase flares were observed in 17.1% of treated mothers versus 6.3% of untreated mothers (P?
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[Stabilized thiomer PAA-Cys-6MNA].
Yao Xue Xue Bao
PUBLISHED: 09-13-2014
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The aimed of this study was to prepare stabilized thiomers to overcome the poor stability character of traditional thiomers. Poly(acrylic acid)-cysteine (PAA-Cys) was synthesized by conjugating cysteine with poly(acrylic acid) and poly(acrylic acid)-cysteine-6-mercaptonicotinic acid (PAA-Cys-6MNA, stabilized thiomers) was synthesized by grafting a protecting group 6-mercaptonicotinic acid (6MNA) with PAA-Cys. The free thiol of PAA-Cys was determined by Ellmann's reagent method and the ratio of 6MNA coupled was determined by glutathione reduction method. The study of permeation enhancement and stabilized function was conducted by using Franz diffusion cell method, with fluorescein isothiocyanate dextran (FD4) used as model drug. The influence of polymers on tight junctions of Caco-2 cell monolayer was detected with laser scanning confocal fluorescence microscope. The results indicated that both PAA-Cys and PAA-Cys-6MNA could promote the permeation of FD4 across excised rat intestine, and the permeation function of PAA-Cys-6MNA was not influence by the pH of the storage environment and the oxidation of air after the protecting group 6MNA was grafted. The distribution of tight junction protein of Caco-2 cell monolayer F-actin was influenced after incubation with PAA-Cys and PAA-Cys-6MNA. In conclusion, stabilized thiomers (PAA-Cys-6MNA) maintained the permeation function compared with the traditional thiomers (PAA-Cys) and its stability was improved. The mechanism of the permeation enhancement function of the polymers might be related to their influence on tight junction relating proteins of cells.
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Phosphine-Free, Low-Temperature Synthesis of Tetrapod-Shaped CdS and Its Hybrid with Au Nanoparticles.
Small
PUBLISHED: 09-12-2014
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Tetrapod-shaped CdS colloidal nanocrystals are synthesized using a facile, phosphine-free synthesis approach at low temperature. The arm length and diameter of CdS tetrapods can be easily tuned by using different source of sulphureous precursors, i.e., sulfur powder, thioacetamide, and sodium diethyldithiocarbamate. Moreover, the growth of Au nanoparticles onto CdS to form metal-semiconductor hybrid nanocrystals is also demonstrated. The tetrapod-shaped CdS nanocrystals exhibit strong arm-diameter-dependent absorption and photoluminescence characteristics. Importantly, the as-obtained CdS tetrapods exhibit promising photocatalytic activity for the water-splitting reaction in photoelectrochemical cells.
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Liquid-phase growth of platinum nanoparticles on molybdenum trioxide nanosheets: an enhanced catalyst with intrinsic peroxidase-like catalytic activity.
Nanoscale
PUBLISHED: 09-05-2014
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A facile method for the synthesis of metal nanostructure-decorated two-dimensional (2D) semiconductor nanosheets was developed. The solution-processable molybdenum trioxide (MoO3) nanosheet was used as a template for direct liquid-phase growth of platinum nanoparticles (Pt NPs) under ambient conditions. Results show that the Pt NPs with sizes of 1-3 nm were uniformly grown on the MoO3 surface. Importantly, the Pt-MoO3 hybrid nanomaterial exhibits an enhanced peroxidase-like catalytic activity compared to the MoO3 nanosheet, Pt NPs, and their physical mixture under the same conditions. As a proof-of-concept application, the Pt-MoO3 hybrid nanomaterial was used as a high-efficiency peroxidase-mimic for ultrasensitive colorimetric detection of glucose in serum samples. This work provides a promising strategy for design and development of biomimetic catalysts by smart assembly of different dimensional nanomaterials.
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Telbivudine or lamivudine use in late pregnancy safely reduces perinatal transmission of hepatitis B virus in real-life practice.
Hepatology
PUBLISHED: 09-05-2014
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Little observational data exist describing telbivudine (LdT) or lamivudine (LAM) use in late pregnancy for preventing hepatitis B mother-to-child transmission (MTCT) in real-world settings. During the period of January 2009 to March 2011, we enrolled hepatitis B e antigen-positive mothers with HBV DNA >6 log10 copies/mL in China. At gestation week 28, the mothers received LdT or LAM until postpartum week 4 or no treatment (NTx). The study endpoints were the safety of LdT/LAM use and MTCT rates. Of the 700 mothers enrolled, 648 (LdT/LAM/NTx=252/51/345) completed the 52-week study with 661 infants (LdT/LAM/NTx=257/52/352). On treatment, viral rebound occurred in 1.6% of mothers, all resulting from medication noncompliance. There was no genotypic mutation detected. At delivery, significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx. Alanine aminotransferase flares were observed in 17.1% of treated mothers versus 6.3% of untreated mothers (P < 0.001). At birth, hepatitis B surface antigen (HBsAg) was detected in 20% and 24% of newborns in the treated and NTx groups, respectively. At week 52, an intention-to-treat analysis indicated 2.2% (95% confidence [CI]: 0.6-3.8) of HBsAg+ infants from the treated group versus 7.6% (95% CI: 4.9-10.3) in the NTx group (P50.001) and no difference of HBsAg+ rate between infants in the LdT and LAM groups(1.9% vs. 3.7%; P=0.758). On-treatment analysis indicated 0% of HBsAg+ infants in the treated group versus 2.84% in the NTx group (P=0.002). There were no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates between infants from the treated and untreated groups.
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[New progress of airborne pollen].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-05-2014
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With the growth of disease incidence in allergic diseases of upper respiratory tract year by year, airborne pollen has been considered the most important cause of the diseases. There is an obvious positive correlation between the concentration of airborne pollen and the symptoms of the diseases. The data is collected which includes environment that patient lives in about the kinds of airborne pollen and their seasonal distribution and latest conditions of the airborne pollen at home and abroad. It is benefit for the further developments of the researches of airborne pollen and has a clinical significance for the prevention, diagnosis and treatments of allergic diseases in our country.
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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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Suppression of the asymmetric modes for experimentally achieving gigawatt-level radiation from a Ku-band Cerenkov type oscillator.
Rev Sci Instrum
PUBLISHED: 09-01-2014
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We present the analysis and suppression of asymmetric modes in a Ku-band Cerenkov-type oscillator numerically and experimentally. The asymmetric modes generated in the initial experiments were identified to be HE11, HE21, and HE31 modes, respectively, by analyzing of the dispersion relationships, the simulation results and the experiment phenomenon. The factors, such as the cathode emission uniformity, the diode voltage, guiding magnetic field, and the concentricity play key roles in the excitation and suppression of these asymmetric modes. In the improved experiments, the asymmetric modes were suppressed effectively. In the improved experiments the asymmetric modes are suppressed effectively, and the designed TM01 mode microwave is generated at a frequency of 13.76 GHz with a power of 1.1 GW, which is in good agreement with numerically predications.
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Correlation between KLK6 expression and the clinicopathological features of glioma.
Contemp Oncol (Pozn)
PUBLISHED: 08-30-2014
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We measured the impact of changing KLK6 expression levels on the pathological grade of gliomas and on proliferation rate, cell cycle progression, and apoptosis in the U251 glioblastoma cell line.
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Bioavailability of tramadol hydrochloride after administration via different routes in rats.
Biopharm Drug Dispos
PUBLISHED: 08-29-2014
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Tramadol is a synthetic non-opiate analgesic drug and effective for many kinds of chronic and acute pain. This study compared the bioavailability of tramadol after different administration routes in rats (oral, buccal and nasal). A simple HPLC analytical approach was used to determine the concentration of tramadol in plasma. The pharmacokinetic behavior and bioavailability of tramadol after administration via different routes in rats were investigated. Nasal and buccal administration of tramadol resulted in a fast increase followed by a rapid decrease in the plasma tramadol concentration. The Cmax values following buccal and nasal administration were 6 times and 20 times higher than that of oral administration, respectively, (6827.85?±?7970.87?ng/ml, 22191.84?±?5364.86?ng/ml, vs 1127.03?±?778.34?ng/ml). The relative bioavailabilities of the nasal- and buccal-administered drug when compared with the oral route were 504.8% and 183.4%, respectively, which is much higher than that of oral administration. Nasal and buccal administration increased the bioavailability of tramadol, which may allow for a reduction in the dose of tramadol and a subsequent decrease in both side effects and toxicity. Therefore, this approach provides an effective choice for the delivery of tramadol, an analgesic drug. Copyright © 2014 John Wiley & Sons, Ltd.
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Highly sensitive naphthalene-based two-photon fluorescent probe for in situ real-time bioimaging of ultratrace cyclooxygenase-2 in living biosystems.
Anal. Chem.
PUBLISHED: 08-27-2014
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Detecting and imaging of ultratrace cyclooxygenase-2 in living biosystems could provide much important valuable information for the diagnosis and intervention of cancer. Molecular probes, whose fluorescent signals are generated by cyclooxygenase-2, hold great potential for identification and enumeration of cyclooxygenase-2 in living biosystems. Although quite a few fluorescent probes have been reported for cyclooxygenase-2, the use fluorogenic probe with the excellent two-photon properties for the determination of ultratrace cyclooxygenase-2 has been scarce. Herein, an "off-on" fluorescence probe (BTDAN-COX-2), able to report and image the presence of ultratrace cyclooxygenase-2 in living biosystems, has been designed and evaluated. In order to improve sensitivity and specific selectivity of probe for ultratrace cyclooxygenase-2, BTDAN-COX-2 employed cyclooxygenase-2's inhibitor as recognition group, because it is a classical and efficient recognition group for cyclooxygenase-2. A polarity-sensitive naphthalene derivative (BTDAN) as fluorophore was introduced into the molecule to enhance two-photon properties of BTDAN-COX-2. In the absent of cyclooxygenase-2, BTDAN-COX-2 mainly exists in a folded conformation where probe fluorescence is quenched through photoinduced electron transfer between the fluorophore and the recognition group. Under the condition of existence of cyclooxygenase-2, fluorescence of probe is turned on, because photoinduced electron transfer between the fluorophore and the recognition group is restrained. BTDAN-COX-2 provides high signal-to-background staining for the ultratrace cyclooxygenase-2 and has been successfully used to rapidly detect and image ultratrace cyclooxygenase-2 in living biosystems.
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Triangular Ag-Pd alloy nanoprisms: rational synthesis with high-efficiency for electrocatalytic oxygen reduction.
Nanoscale
PUBLISHED: 08-26-2014
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We report the generation of triangular Ag-Pd alloy nanoprisms through a rationally designed synthetic strategy based on silver nanoprisms as sacrificial templates. The galvanic replacement between Ag nanoprisms and H2PdCl4 along with co-reduction of Ag(+)/Pd(2+) is responsible for the formation of final prismatic Ag-Pd alloy nanostructures. Significantly, these Ag-Pd alloy nanoprisms exhibited superior electrocatalytic activity for the oxygen reduction reaction (ORR) as compared with the commercial Pd/C catalyst. Such a high catalytic activity is attributed to not only the alloyed Ag-Pd composition but also the dominant {111} facets of the triangular Ag-Pd nanoprisms. This work demonstrates the rational design of bimetallic alloy nanostructures with control of selective crystal facets that are critical to achieve high catalytic activity for fuel cell systems.
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A novel marRAB operon contributes to the rifampicin resistance in Mycobacterium smegmatis.
PLoS ONE
PUBLISHED: 08-25-2014
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The multiple-antibiotic resistance regulator (MarR) plays an important role in modulating bacterial antibiotic resistance. However, the regulatory model of the marRAB operon in mycobacteria remains to be characterized. Here we report that a MarR, encoded by Ms6508, and its marRAB operon specifically contribute to rifampicin (RIF) resistance in Mycobacterium smegmatis. We show that the MarR recognizes a conserved 21-bp palindromic motif and negatively regulates the expression of two ABC transporters in the operon, encoded by Ms6509-6510. Unlike other known drug efflux pumps, overexpression of these two ABC transporters unexpectedly increased RIF sensitivity and deletion of these two genes increased mycobacterial resistance to the antibiotic. No change can be detected for the sensitivity of recombinant mycobacterial strains to three other anti-TB drugs. Furthermore, HPLC experiments suggested that Ms6509-Ms6510 could pump RIF into the mycobacterial cells. These findings indicated that the mycobacterial MarR functions as a repressor and constitutively inhibits the expression of the marRAB operon, which specifically contributes to RIF resistance in M. smegmatis. Therefore, our data suggest a new regulatory mechanism of RIF resistance and also provide the new insight into the regulatory model of a marRAB operon in mycobacteria.
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Optimize the Separation of Fluorinated Amphiles Using High-Performance Liquid Chromatography.
J Fluor Chem
PUBLISHED: 08-23-2014
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Using the set of fluorinated amphiles that contain the same fluorocarbon moiety but differ in their fluorine content percentage F% (25-45%), the optimal condition for a F%-based separation of these analytes using reverse-phase chromatography was explored. It is found that optimal separation can be achieved by pairing a regular reverse-phase column (such as C8) with a fluorinated eluent (such as trifluoroethanol). Separation is further improved at higher chromatographic temperature with baseline separation achieved at 45°C. This result indicates that the separation of fluorocarbon-tagged molecules can be based on the fluorine content percentage rather than the number of fluorine atoms.
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Intermittent hypoxia preconditioning-induced epileptic tolerance by upregulation of monocarboxylate transporter 4 expression in rat hippocampal astrocytes.
Neurochem. Res.
PUBLISHED: 08-22-2014
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Noxious stimuli applied at doses close to but below the threshold of cell injury induce adaptive responses that provide a defense against additional stress. Epileptic preconditioning protects neurons against status epilepticus and ischemia; however, it is not known if the converse is true. During hypoxia/ischemia (H/I), lactate released from astrocytes is taken up by neurons and is stored for energy, a process mediated by monocarboxylate transporter 4 (MCT4) in astroglia. The present study investigated whether H/I preconditioning can provide protection to neurons against epilepsy through upregulation of MCT4 expression in astrocytes in vitro and in vivo. An oxygen/glucose deprivation protocol was used in primary astrocyte cultures, while rats were subjected to an intermittent hypoxia preconditioning (IHP) paradigm followed by lithium-pilocarpine-induced epilepsy as well as lactate transportation inhibitor injection, with a subsequent evaluation of protein expression as well as behavior. H/I induced an upregulation of MCT4 expression, while an IHP time course of 5 days provided the greatest protection against epileptic seizures, which was most apparent by 3 days after IHP. However, lactate transport function disturbances can block the protective effect induced by IHP. These findings provide a potential basis for the clinical treatment of epilepsy.
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Aberrant expression of p-STAT3 in peripheral blood CD4+ and CD8+ T cells related to hepatocellular carcinoma development.
Mol Med Rep
PUBLISHED: 08-21-2014
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Hepatocellular carcinoma (HCC) is one of the most common cancer types worldwide. The signal transducer and activator of transcription 3 (STAT3) protein is a member of the STAT transcription factor family. Oncogenesis, invasion, and metastasis of HCC are associated with activation of STAT3. However, whether aberrant expression of phosphorylated STAT3 (p-STAT3) in peripheral CD4+ and CD8+ T cells relates to HCC pathogenesis remains unclear. In this study, the expression of p-STAT3 in CD4+ and CD8+ T cells, and the levels of interferon-? (IFN-?), interleukin-4 (IL-4), IL-6 and IL-10 in the human hepatoma cell line Huh7 co-cultured with peripheral blood mononucleated cells (PBMCs) of healthy volunteers were measured. The correlations between p-STAT3 and IFN-?/IL-4, IFN-?, IL-4, IL-6 and IL-10 were then analyzed. Results showed that the p-STAT3 level is higher in CD4+ and CD8+ T cells in the peripheral blood of HCC patients, and in PBMCs co-cultured with Huh7 cells compared to controls. The cytokine (IL-4, IL-6 and IL-10) levels were increased and the IFN-? level was decreased in the serum of HCC patients and in supernatants of PBMCs co-cultured with Huh7 cells. Correlation analyses demonstrated that the IFN-?/IL-4 ratio and the IFN-? level negatively correlate to the p-STAT3 level in CD4+ and CD8+ T cells in samples from patients and in cells cultured in vitro. By contrast, the levels of IL-4, IL-6 and IL-10 positively correlated to the p-STAT3 level. This study indicated that the expression of p-STAT3 is upregulated in peripheral CD4+ and CD8+ T cells of HCC patients, and which may result in abnormal immune surveillance and thereby, contribute to HCC pathogenesis.
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Thermochemical reaction mechanism of lead oxide with poly(vinyl chloride) in waste thermal treatment.
Chemosphere
PUBLISHED: 08-21-2014
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Poly(vinyl chloride) (PVC) as a widely used plastic that can promote the volatilization of heavy metals during the thermal treatment of solid waste, thus leading to environmental problems of heavy metal contamination. In this study, thermogravimetric analysis (TGA) coupled with differential scanning calorimeter, TGA coupled with Fourier transform infrared spectroscopy and lab-scale tube furnace experiments were carried out with standard PVC and PbO to explicate the thermochemical reaction mechanism of PVC with semi-volatile lead. The results showed that PVC lost weight from 225 to 230°C under both air and nitrogen with an endothermic peak, and HCl and benzene release were also detected. When PbO was present, HCl that decomposed from PVC instantly reacted with PbO via an exothermal gas-solid reaction. The product was solid-state PbCl2 at <501°C, which was the most volatile lead-containing compound with a low melting point and high vapor pressure. At >501°C, PbCl2 melted, volatilized and transferred into flue gas or condensed into fly ash. Almost all PbCl2 volatilized above 900°C, while PbO just started to volatilize slowly at this temperature. Therefore, the chlorination effect of PVC on lead was apt to lower-temperature and rapid. Without oxygen, Pb2O was generated due to the deoxidizing by carbon, with oxygen, the amount of residual Pb in the bottom ash was significantly decreased.
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Effects of the biosynthesis and signaling pathway of ecdysterone on silkworm (Bombyx mori) following exposure to titanium dioxide nanoparticles.
J. Chem. Ecol.
PUBLISHED: 08-20-2014
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Silkworm (Bombyx mori), a model Lepidoptera insect, is economically important. Its growth and development are regulated by endogenous hormones. During the process of transition from larvae to pupae, 20-hydroxyecdysone (20E) plays an important role. The recent surge in consumer products and applications using metallic nanoparticles has increased the possibility of human or ecosystem exposure due to their unintentional release into the environment. We investigated the effects of exposure to titanium dioxide nanoparticles (TiO2 NPs) on the action of 20E in B. mori. Titanium dioxide nanoparticle treatment shortened the molting duration by 8 hr and prolonged the molting peak period by 10 %. Solexa sequencing profiled the changes in gene expression in the brain of fifth-instar B. mori in response to TiO2NPS exposure for 72 hr, to address the effects on hormone metabolism and regulation. Thirty one genes were differentially expressed. The transcriptional levels of pi3k and P70S6K, which are involved in the target of the rapamycin (TOR) signaling pathway, were up-regulated. Transcriptional levels of four cytochrome P450 genes, which are involved in 20E biosynthesis, at different developmental stages (48, 96, 144, and 192 hr) at 5th instars of all displayed trends of increasing expression. Simultaneously, the ecdysterone receptors, also displayed increasing trends. The 20E titers at four developmental stages during the 5th instar were 1.26, 1.23, 1.72, and 2.16 fold higher, respectively, than the control group. These results indicate that feeding B. mori with TiO2 NPs stimulates 20E biosynthesis, shortens the developmental progression, and reduces the duration of molting. Thus, application of TiO2 NPs is of high significance for saving the labor force in sericulture, and our research provides a reference for the ecological problems in the field of Lepidoptera exposured to titanium dioxide nanoparticles.
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[Investigation of skin prick test on patients with allergic rhinitis in Urumqi area].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 08-19-2014
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To investigate the geographic distribution of air-borne allergens which caused allergic rhinitis in Urumqi, and offer guide for prevention and treatment of the patients with allergic rhinitis.
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Genetic variation in retinal vascular patterning predicts variation in pial collateral extent and stroke severity.
Angiogenesis
PUBLISHED: 08-14-2014
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The presence of a native collateral circulation in tissues lessens injury in occlusive vascular diseases. However, differences in genetic background cause wide variation in collateral number and diameter in mice, resulting in large variation in protection. Indirect estimates of collateral perfusion suggest that wide variation also exists in humans. Unfortunately, methods used to obtain these estimates are invasive and not widely available. We sought to determine whether differences in genetic background in mice result in variation in branch patterning of the retinal arterial circulation, and whether these differences predict strain-dependent differences in pial collateral extent and severity of ischemic stroke. Retinal patterning metrics, collateral extent, and infarct volume were obtained for 10 strains known to differ widely in collateral extent. Multivariate regression was conducted, and model performance was assessed using K-fold cross-validation. Twenty-one metrics varied with strain (p < 0.01). Ten metrics (e.g., bifurcation angle, lacunarity, optimality) predicted collateral number and diameter across seven regression models, with the best model closely predicting (p < 0.0001) number (±1.2-3.4 collaterals, K-fold R (2) = 0.83-0.98), diameter (±1.2-1.9 ?m, R (2) = 0.73-0.88), and infarct volume (±5.1 mm(3), R (2) = 0.85-0.87). An analogous set of the most predictive metrics, obtained for the middle cerebral artery (MCA) tree in a subset of the above strains, also predicted (p < 0.0001) collateral number (±3.3 collaterals, K-fold R (2) = 0.78) and diameter (±1.6 ?m, R(2)  = 0.86). Thus, differences in arterial branch patterning in the retina and the MCA trees are specified by genetic background and predict variation in collateral extent and stroke severity. If also true in human, and since genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar "retinal predictor index" could serve as a non- or minimally invasive biomarker for collateral extent in brain and other tissues. This could aid prediction of severity of tissue injury in the event of an occlusive event or development of obstructive disease and in patient stratification for treatment options and clinical studies.
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Hierarchically porous three-dimensional electrodes of CoMoO? and ZnCo?O? and their high anode performance for lithium ion batteries.
Nanoscale
PUBLISHED: 08-13-2014
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Ternary metal oxides have been receiving wide attention in electrochemical energy storage due to their rich redox reactions and tuneable conductivity. We present a simple solution-based method to prepare a 3D interconnected porous network of ternary metal oxide (CoMoO? and ZnCo?O?) nanostructures on macroporous nickel foam. The open-structured networks with different degrees of porosity endow them with high surface areas of electro-active sites. The Li ion storage properties of both anodes are investigated. High rate capability and long term cycling stability are achieved for both systems.
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Comparison of the clinical features and outcomes in two age-groups of elderly patients with atrial fibrillation.
Clin Interv Aging
PUBLISHED: 08-12-2014
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Atrial fibrillation (AF) disproportionately affects older adults. However, direct comparison of clinical features, medical therapy, and outcomes in AF patients aged 65-74 and ? 75 years is rare. The objective of the present study was to evaluate the differences in clinical characteristics and prognosis in these two age-groups of geriatric patients with AF.
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Fabrication of Ultralong Hybrid Microfibers from Nanosheets of Reduced Graphene Oxide and Transition-Metal Dichalcogenides and their Application as Supercapacitors.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-11-2014
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Two-dimensional materials have attracted increasing research interest owing to their unique electronic, physical, optical, and mechanical properties. We thus developed a general strategy for the fabrication of ultralong hybrid microfibers from a mixture of reduced graphene oxide and transition-metal dichalcogenides (TMDs), including MoS2 , TiS2 , TaS2 , and NbSe2 . Furthermore, we prepared fiber-based solid-state supercapacitors as a proof-of-concept application. The performance of thus-prepared supercapacitors was greatly improved by the introduction of the TMDs.
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Activation of PI3K/Akt pathway limits JNK-mediated apoptosis during EV71 infection.
Virus Res.
PUBLISHED: 08-10-2014
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Apoptosis is frequently induced to inhibit virus replication during infection of Enterovirus 71 (EV71). On the contrary, anti-apoptotic pathway, such as PI3K/Akt pathway, is simultaneously exploited by EV71 to accomplish the viral life cycle. The relationship by which EV71-induced apoptosis and PI3K/Akt signaling pathway remains to be elucidated. In this study, we demonstrated that EV71 infection altered Bax conformation and triggered its redistribution from the cytosol to mitochondria in RD cells. Subsequently, cytochrome c was released from mitochondria to cytosol. We also found that c-Jun NH2-terminal kinase (JNK) was activated during EV71 infection. The JNK specific inhibitor significantly inhibited Bax activation and cytochrome c release, suggesting that EV71-induced apoptosis was involved into a JNK-dependent manner. Meanwhile, EV71-induced Akt phosphorylation involved a PI3K-dependent mechanism. Inhibition of the PI3K/Akt pathway enhanced JNK phosphorylation and the JNK-mediated apoptosis upon EV71 infection. Moreover, PI3K/Akt pathway phosphorylated apoptosis signal-regulating kinase 1 (ASK1) and negatively regulated the ASK1 activity. Knockdown of ASK1 significantly decreased JNK phosphorylation, which implied that ASK1 phosphorylation by Akt inhibited ASK1-mediated JNK activation. Collectively, these data reveal that activation of the PI3K/Akt pathway limits JNK-mediated apoptosis by phosphorylating and inactivating ASK1 during EV71 infection.
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Improved prediction of residue flexibility by embedding optimized amino acid grouping into RSA-based linear models.
Amino Acids
PUBLISHED: 08-09-2014
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Knowledge of protein flexibility is vital for deciphering the corresponding functional mechanisms. This knowledge would help, for instance, in improving computational drug design and refinement in homology-based modeling. We propose a new predictor of the residue flexibility, which is expressed by B-factors, from protein chains that use local (in the chain) predicted (or native) relative solvent accessibility (RSA) and custom-derived amino acid (AA) alphabets. Our predictor is implemented as a two-stage linear regression model that uses RSA-based space in a local sequence window in the first stage and a reduced AA pair-based space in the second stage as the inputs. This method is easy to comprehend explicit linear form in both stages. Particle swarm optimization was used to find an optimal reduced AA alphabet to simplify the input space and improve the prediction performance. The average correlation coefficients between the native and predicted B-factors measured on a large benchmark dataset are improved from 0.65 to 0.67 when using the native RSA values and from 0.55 to 0.57 when using the predicted RSA values. Blind tests that were performed on two independent datasets show consistent improvements in the average correlation coefficients by a modest value of 0.02 for both native and predicted RSA-based predictions.
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Hydrogen Sulfide-Induced Processing of the Amyloid Precursor Protein in SH-SY5Y Human Neuroblastoma Cells Involves the PI3-K/Akt Signaling Pathway.
Cell. Mol. Neurobiol.
PUBLISHED: 08-08-2014
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Hydrogen sulfide (H2S) has been recently categorized as a gasotransmitter, and it may be involved in the pathology of Alzheimer's disease. However, whether H2S induces amyloid precursor protein (APP) processing remains unknown. In the present study, we tested the ability of H2S to mediate APP processing in SH-SY5Y human neuroblastoma cells. We treated SH-SY5Y human neuroblastoma cells with a range of sodium hydrosulfide (H2S donor) concentrations. Western blot analysis showed that H2S increased the generation of C83 and decreased the production of C99. Meanwhile, H2S increased the levels of a disintegrin and metalloprotease 10 (ADAM10) mRNA and protein, but had no effect on TNF-?-converting enzyme (TACE, also known as ADAM17) mRNA and protein levels. H2S also induced a significant decrease of extracellular amyloid-?42 (A?42). Furthermore, SH-SY5Y human neuroblastoma cells were assayed for activation of the phosphoinositide 3-kinase (PI3-K) pathway. H2S activated the PI3-K pathway. Using specific inhibitor of PI3-K, we determined that the effects of H2S on APP processing and A?42 were blocked by LY 294002 (PI3-K inhibitor). These data indicate that H2S can induce APP processing, and this effect is dependent on activation of the PI3-K signaling pathway.
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Nucleus-targeted Dmp1 transgene fails to rescue dental defects in Dmp1 null mice.
Int J Oral Sci
PUBLISHED: 08-08-2014
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Dentin matrix protein 1 (DMP1) is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is considered as an extracellular matrix protein that promotes hydroxyapatite formation and activates intracellular signaling pathway via interacting with ?v?3 integrin. Recent in vitro studies suggested that DMP1 might also act as a transcription factor. In this study, we examined whether full-length DMP1 could function as a transcription factor in the nucleus and regulate odontogenesis in vivo. We first demonstrated that a patient with the DMP1 M1V mutation, which presumably causes a loss of the secretory DMP1 but does not affect the nuclear translocation of DMP1, shows a typical rachitic tooth defect. Furthermore, we generated transgenic mice expressing (NLS)DMP1, in which the endoplasmic reticulum (ER) entry signal sequence of DMP1 was replaced by a nuclear localization signal (NLS) sequence, under the control of a 3.6?kb rat type I collagen promoter plus a 1.6?kb intron 1. We then crossbred the (NLS)DMP1 transgenic mice with Dmp1 null mice to express the (NLS)DMP1 in Dmp1-deficient genetic background. Although immunohistochemistry demonstrated that (NLS)DMP1 was localized in the nuclei of the preodontoblasts and odontoblasts, the histological, morphological and biochemical analyses showed that it failed to rescue the dental and periodontal defects as well as the delayed tooth eruption in Dmp1 null mice. These data suggest that the full-length DMP1 plays no apparent role in the nucleus during odontogenesis.
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Self-powered glucose-responsive micropumps.
ACS Nano
PUBLISHED: 08-07-2014
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A self-powered polymeric micropump based on boronate chemistry is described. The pump is triggered by the presence of glucose in ambient conditions and induces convective fluid flows, with pumping velocity proportional to the glucose concentration. The pumping is due to buoyancy convection that originates from reaction-associated heat flux, as verified from experiments and finite difference modeling. As predicted, the fluid flow increases with increasing height of the chamber. In addition, pumping velocity is enhanced on replacing glucose with mannitol because of the enhanced exothermicity associated with the reaction of the latter.
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Effects of Sodium Fluoride Treatment In Vitro on Cell Proliferation, BMP-2 and BMP-3 Expression in Human Osteosarcoma MG-63 Cells.
Biol Trace Elem Res
PUBLISHED: 08-05-2014
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Chronic excessive fluoride intake may cause fluorosis, which chiefly manifests as bone damage (or skeletal fluorosis). However, the molecular mechanism of skeletal fluorosis has not been clarified up to the present. The objective of this study was to analyze the effects of fluoride treatment on two of bone morphogenetic protein family member (BMP-2 and BMP-3) expression and cell viability using human osteosarcoma MG-63 cells as a model. Sodium fluoride (NaF) had pro-proliferation effects at relatively moderate concentration, with 5?×?10(3) ?mol/L having the best effects. At 2?×?10(4) ?mol/L, NaF inhibits cell proliferation. BMP-2 and BMP-3 expression was significantly induced by 5?×?10(3) ?mol/L NaF and, to lesser extent, by 2?×?10(4) ?mol/L NaF. Correspondingly, mothers against decapentaplegic homolog 1 (Smad-1) increased at both doses of NaF, which indicated the BMP signaling pathway was activated. Notable increases in secreted alkaline phosphatase (ALP) were observed when cells were treated with 5?×?10(3) ?mol/L NaF. A BMP specific inhibitor LDN193189 suppressed cell proliferation induced by 5?×?10(3) ?mol/L NaF. Also, 2?×?10(4) ?mol/L NaF induced apoptosis but likely through a mechanism unrelated to the BMP pathway. Collectively, data show that NaF had dose-dependent effects on cell proliferation as well as BMP-2 and BMP-3 expression in MG-63 cells and suggested that cell proliferation enhanced by NaF-induced BMP members may be a molecular mechanism underlying skeletal fluorosis.
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Effect of compressed sensing reconstruction on target and organ delineation in cone-beam CT of head-and-neck and breast cancer patients.
Radiother Oncol
PUBLISHED: 08-04-2014
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Compressed sensing (CS) based cone-beam computed tomography (CBCT) reconstruction techniques have been shown to improve image quality. This study was to investigate possible improvements of CBCTCS on manual delineation uncertainties of targets and organs-at-risk.
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Effect of hepatitis B virus genotypes on the efficacy of adefovir dipivoxil antiviral therapy.
Hepat Mon
PUBLISHED: 08-01-2014
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Hepatitis B is a common infectious disease in China. Many studies have shown that the genotype of hepatitis B virus (HBV) is probably associated with the efficacy of some antiviral drugs such as interferon ? (IFN-?) and Lamivudine (LAM). However, the association between HBV genotype and adefovir dipivoxil (ADV) is controversial. ADV is the most popular antiviral drug in China due to its low price, good antiviral efficacy, few side effects, and convenient of administration.
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[Effect of Chinese herbs for stasis removing and collaterals dredging upon angiotensin-converting enzyme 2-angiotensin-(1-7)-mas axis in the renal cortex of diabetic nephropathy rats].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 07-23-2014
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To observe the effect of Chinese herbs for stasis removing and collaterals dredging (CHSRCD) upon angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis in the renal cortex of diabetic nephropathy rats.
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Secure privacy-preserving biometric authentication scheme for telecare medicine information systems.
J Med Syst
PUBLISHED: 07-21-2014
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Healthcare delivery services via telecare medicine information systems (TMIS) can help patients to obtain their desired telemedicine services conveniently. However, information security and privacy protection are important issues and crucial challenges in healthcare information systems, where only authorized patients and doctors can employ telecare medicine facilities and access electronic medical records. Therefore, a secure authentication scheme is urgently required to achieve the goals of entity authentication, data confidentiality and privacy protection. This paper investigates a new biometric authentication with key agreement scheme, which focuses on patient privacy and medical data confidentiality in TMIS. The new scheme employs hash function, fuzzy extractor, nonce and authenticated Diffie-Hellman key agreement as primitives. It provides patient privacy protection, e.g., hiding identity from being theft and tracked by unauthorized participant, and preserving password and biometric template from being compromised by trustless servers. Moreover, key agreement supports secure transmission by symmetric encryption to protect patient's medical data from being leaked. Finally, the analysis shows that our proposal provides more security and privacy protection for TMIS.
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MIR125B1 represses the degradation of the PML-RARA oncoprotein by an autophagy-lysosomal pathway in acute promyelocytic leukemia.
Autophagy
PUBLISHED: 07-18-2014
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Acute promyelocytic leukemia (APL) is characterized by the t(15;17)-associated PML-RARA fusion gene. We have previously found that MIR125B1 is highly expressed in patients with APL and may be associated with disease pathogenesis; however, the mechanism by which MIR125B1 exerts its oncogenic potential has not been fully elucidated. Here, we demonstrated that MIR125B1 abundance correlates with the PML-RARA status. MIR125B1 overexpression enhanced PML-RARA expression and inhibited the ATRA-induced degradation of the PML-RARA oncoprotein. RNA-seq analysis revealed a direct link between the PML-RARA degradation pathway and MIR125B1-arrested differentiation. We further demonstrated that the MIR125B1-mediated blockade of PML-RARA proteolysis was regulated via an autophagy-lysosomal pathway, contributing to the inhibition of APL differentiation. Furthermore, we identified DRAM2 (DNA-damage regulated autophagy modulator 2), a critical regulator of autophagy, as a novel target that was at least partly responsible for the function of MIR125B1 involved in autophagy. Importantly, the knockdown phenotypes for DRAM2 are similar to the effects of overexpressing MIR125B1 as impairment of PML-RARA degradation, inhibition of autophagy, and myeloid cell differentiation arrest. These effects of MIR125B1 and its target DRAM2 were further confirmed in an APL mouse model. Thus, MIR125B1 dysregulation may interfere with the effectiveness of ATRA-mediated differentiation through an autophagy-dependent pathway, representing a novel potential APL therapeutic target.
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A novel method for the sensitive detection of mutant proteins using a covalent-bonding tube-based proximity ligation assay.
Anal. Chim. Acta
PUBLISHED: 06-27-2014
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Tumorigenesis is the cumulative result of multiple gene mutations. The mutant proteins that are expressed by mutant genes in cancer cells are secreted into the blood and are useful biomarkers for the early diagnosis of cancer. However, some difficulties exist; for example, the same gene will express different protein mutants in different patients, and early tumors secrete only small amounts of mutant protein. Thus, the presence of mutant proteins in plasma has not previously been exploited for the early diagnosis of cancer. Proximity ligation assay is a protein-detection method that has been developed in recent years and has been widely used because of its high sensitivity. However, this approach still suffers from some shortcomings that should be addressed. In this paper, we develop a covalent-bonding tube-based proximity ligation assay (TB-PLA). The limit of detection of TB-PLA for 0.001pM, and the method exhibited a broad dynamic range of up to seven orders of magnitude. Furthermore, we coupled the conformation-specific antibody PAb240 of p53 mutants to PCR tubes for TB-PLA. The assay was capable of detecting an approximately 500-fold lower concentration of mutant p53 in serum compared with sandwich ELISA. Thus, we demonstrate TB-PLA to be a highly sensitive and effective approach that is suitable for the early clinical diagnosis of cancer using the conformation-specific antibodies of protein mutants.
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Exposure to high levels of glucose increases the expression levels of genes involved in cholesterol biosynthesis in rat islets.
Exp Ther Med
PUBLISHED: 06-26-2014
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Cells continually adjust their gene expression profiles in order to adapt to the availability of nutrients. Glucose is a major regulator of pxancreatic ?-cell function and cell growth. However, the mechanism of ?-cell adaptation to high levels of glucose remains uncertain. To identify the specific targets responsible for adaptation to high levels of glucose, the differentially expressed genes from primary rat islets treated with 3.3 and 16.7 mmol/l glucose for 24 h were detected by DNA microarray. The results revealed that the expression levels of genes that encode enzymes required for de novo cholesterol biosynthesis [3-hydroxy-3-methylglutaryl-CoA synthase 1 (Hmgcs1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), mevalonate (diphospho) decarboxylase (Mvd), isopentenyl-diphosphate ?-isomerase 1 (Idi1), squalene epoxidase (Sqle) and 7-dehydrocholesterol reductase (Dhcr7)] were significantly increased in islets treated with high levels of glucose compared with those in the islets treated with lower glucose levels. Quantitative polymerase chain reaction further confirmed that glucose stimulated the expression levels of these genes in a dose- and time-dependent manner. A similar result was obtained in islets isolated from rats subjected to 12, 24, 48 and 72 h of continuous glucose infusion. It has previously been recognized that cholesterol homeostasis is important for ?-cell function. The present study provides, to the best of our knowledge, the first evidence for the involvement of the de novo cholesterol biosynthesis pathway in the adaptation of rat islets to high levels of glucose in vitro and in vivo.
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Prevention of metabolic disorders with telmisartan and indapamide in a Chinese population with high-normal blood pressure.
Hypertens. Res.
PUBLISHED: 06-19-2014
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High-normal blood pressure is considered a precursor of stage 1 hypertension that is associated with metabolic disorders. This study aims to investigate whether the pharmacologic treatment of high-normal blood pressure affects metabolism, especially in abdominally obese individuals, and the pharmacoeconomics of two antihypertensive agents, telmisartan and indapamide. Subjects with high-normal blood pressure were randomly assigned to receive telmisartan, indapamide or placebo for 3 years. All the subjects were instructed to modify their lifestyle to reduce blood pressure throughout the study. A total of 221 subjects were randomly assigned to telmisartan, 213 to indapamide and 230 to placebo. After the 3-year intervention, blood pressure was lower in the telmisartan and indapamide groups (P<0.05), FPG in the telmisartan group was lower during the first 2 years (P<0.05) and no characteristic differences were found in those with abdominal obesity among the three groups (P>0.05). The percentage of subjects with metabolic syndrome was significantly decreased in the telmisartan and indapamide groups (P<0.05), but was only significantly decreased in the telmisartan group for subjects with abdominal obesity (P<0.05). The acquisition cost for telmisartan was ~1.86 times higher than for indapamide for a similar antihypertensive effect. The intervention for high-normal blood pressure with telmisartan and indapamide appeared to be feasible and reduced the risk of metabolic syndrome. Telmisartan was more effective, whereas indapamide had better pharmacoeconomic benefits.Hypertension Research advance online publication, 2 October 2014; doi:10.1038/hr.2014.148.
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Lead methylammonium triiodide perovskite-based solar cells: an interfacial charge-transfer investigation.
ChemSusChem
PUBLISHED: 06-18-2014
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This work reports on an investigation into interfacial charge transfer in CH3 NH3 PbI3 perovskite solar cells by using anatase TiO2 nanocuboids enclosed by active {100} and {001} facets. The devices show 6.0 and 8.0?% power conversion efficiency with and without hole-transport material. Transient photovoltage/photocurrent decay and charge extraction, as well as impedance spectroscopy measurements, reveal that carbon materials are effective counter electrodes in perovskite solar cells. The photogenerated charges are observed to be stored in mesoporous TiO2 film under illumination and in the CH3 NH3 PbI3 layer in the dark. The use of 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9-spirobifluorene (spiro-MeOTAD) as a hole-transport material accelerates interfacial charge recombination between the photogenerated electrons and holes.
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Effect of ABO blood type on ovarian reserve in Chinese women.
Fertil. Steril.
PUBLISHED: 05-30-2014
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To explore the effect of ABO blood type on ovarian reserve in Chinese women.
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Essential role of Osterix for tooth root but not crown dentin formation.
J. Bone Miner. Res.
PUBLISHED: 05-16-2014
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Tooth is made of crown and root. It is widely believed that dentin formation in crown and root uses the same regulatory mechanism. However, identification of NFIC's unique function in determining root but not crown dentin formation challenges the old thought. In searching for the target molecules downstream of NFIC, we unexpectedly found a sharp reduction of OSX (osterix), the key transcription factor in skeleton formation, in the Nfic knockout (KO) tooth root. We then demonstrated a dose-dependent increase of Osx in the odontoblast cell line due to a transient transfection of Nfic expression plasmid. Studies of global and conditional Osx KO mice revealed no apparent changes in the crown dentin tubules and dentin matrix. However, the OSX conditional KO mice (crossed to the 2.3 kb Col 1-Cre) displayed an increase in cell proliferation but great decreases in expressions of root dentin matrix proteins (DMP1 and DSPP), leading to an inhibition in odontoblast differentiation, and short thin root dentin with few dentin tubules. Compared to the Nfic KO tooth, which contains essentially no dentin tubules and remains in a "root-less" status at adult stages, the Osx cKO root phenotype had partially improved at the late stage, indicating that other factors can compensate for OSX function. Thus, we conclude that OSX, one of the key downstream molecules of NFIC, plays a critical role in root, but not crown, formation.
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The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer.
Mol Clin Oncol
PUBLISHED: 03-21-2014
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It has been demonstrated that erlotinib is effective in treating patients with brain metastasis from non-small-cell lung cancer. However, the number of studies determining the erlotinib concentration in these patients is limited. The purpose of this study was to measure the concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung carcinoma. Six patients were treated with the standard recommended daily dose of erlotinib (150 mg) for 4 weeks. All the patients had previously received chemotherapy, but no brain radiotherapy. At the end of the treatment period, blood plasma and cerebrospinal fluid samples were collected and the erlotinib concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The average erlotinib concentration in the blood plasma and the cerebrospinal fluid was 717.7±459.7 and 23.7±13.4 ng/ml, respectively. The blood-brain barrier permeation rate of erlotinib was found to be 4.4±3.2%. In patients with partial response (PR), stable disease (SD) and progressive disease (PD), the average concentrations of erlotinib in the cerebrospinal fluid were 35.5±19.0, 19.1±8.7 and 16.4±5.9 ng/ml, respectively. In addition, the efficacy rate of erlotinib for metastatic brain lesions was 33.3%, increasing to 50% in patients with EGFR mutations. However, erlotinib appeared to be ineffective in cases with wild-type EGFR. In conclusion, a relatively high concentration of erlotinib was detected in the cerebrospinal fluid of patients with brain metastases from non-small-cell lung cancer. Thus, erlotinib may be considered as a treatment option for this patient population.
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Characterisation of water-soluble proanthocyanidins of Pyracantha fortuneana fruit and their improvement in cell bioavailable antioxidant activity of quercetin.
Food Chem
PUBLISHED: 03-16-2014
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Proanthocyanidins (PCs) with poor bioavailability were argued for their health benefits. In this study, water-soluble polymeric polyphenolic PCs fractions from Pyracanthafortuneana fruit were used to investigate whether the presence of PCs is correlated with the increased cell antioxidant activities (CAA) of quercetin (Q). The results indicated that the most decrement in the values of EC50, which Q inhibited peroxyl radical-induced DCFH oxidation effective in the HepG2 cells, was observed to be 2.91 (vs. control 5.97) in the present of the fraction with 15.8 of the average degree of polymerisation of PCs (ADP). Also, the order of efficacy was the same with the ADP of PCs. Further, this effect is associated with the improvement of the solubility and stability of Q after the addition of the PCs. Our current study suggests that the additive effects of PCs on small molecular polyphenols may be responsible for their antioxidant benefits in vivo.
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Down-regulation of Sp1 suppresses cell proliferation, clonogenicity and the expressions of stem cell markers in nasopharyngeal carcinoma.
J Transl Med
PUBLISHED: 03-16-2014
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Transcription factor Sp1 is multifaceted, with the ability to function as an oncogene or a tumor suppressor, depending on the cellular context. We previously reported that Sp1 is required for the transcriptional activation of the key oncogenes in nasopharyngeal carcinoma (NPC), including B-lymphoma mouse Moloney leukemia virus insertion region 1 (Bmi1) and centromere protein H (CENPH), but the role of Sp1 and its underlying mechanisms in NPC remained largely unexplored. The objective of this study was to investigate the cellular function of Sp1 and to verify the clinical significance of Sp1 as a potential therapeutic target in NPC.
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Fat-mass and obesity-associated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia.
Behav Brain Funct
PUBLISHED: 03-13-2014
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Obesity induced by antipsychotics severely increases the risk of many diseases and significantly reduces quality of life. Genome Wide Association Studies has identified fat-mass and obesity-associated (FTO) gene associated with obesity. The relationship between the FTO gene and drug-induced obesity is unclear.
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Bone marrow-derived mesenchymal stem cells protect against lung injury in a mouse model of bronchopulmonary dysplasia.
Mol Med Rep
PUBLISHED: 02-14-2014
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The aim of the present study was to investigate the effect of bone marrow?derived mesenchymal stem cells (BMSCs) in the treatment of lung injury in a mouse model of bronchopulmonary dysplasia (BPD) and examine the underlying mechanisms. A mouse model of BPD was created using continuous exposure to high oxygen levels for 14 days. BMSCs were isolated, cultured and then labeled with green fluorescent protein. Cells (1x106) were subsequently injected intravenously 1 h prior to high oxygen treatment. Animals were randomly divided into three groups (n=5 in each): Control group, BPD model group and BMSC injection group. At two weeks post?treatment, the expression of transforming growth factor??1 (TGF??1), vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF) was detected using immunohistochemical staining and immunofluorescence. Compared with the BPD model group, the body weight, airway structure and levels of TGF??1 and VEGF were significantly improved in the BMSC?treated group. Immunofluorescence observations indicated that BMSCs were able to differentiate into cells expressing vWF and VEGF, which are markers of vascular tissues. The present study demonstrated that intravenous injection of BMSCs significantly improved lung damage in a neonatal mouse model of BPD at 14 days following hyperoxia?induced injury. This provides novel information which may be used to guide further investigation into the use of stem cells in BPD.
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Influence of L-carnitine supplementation on serum lipid profile in hemodialysis patients: a systematic review and meta-analysis.
Kidney Blood Press. Res.
PUBLISHED: 02-06-2014
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An increasing body of evidence demonstrates that L-carnitine plays a pivotal role in lipid metabolism of hemodialysis (HD) patients. However, there are still some reservations about its benefits. Therefore, we performed a meta-analysis to assess the effects of L-carnitine supplementation on lipid profile in HD patients.
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Metal oxide-coated three-dimensional graphene prepared by the use of metal-organic frameworks as precursors.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-25-2014
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A simple method for the preparation of metal-oxide-coated three-dimensional (3D) graphene composites was developed. The metal-organic frameworks (MOFs) that served as the precursors of the metal oxides were first synthesized on the 3D graphene networks (3DGNs). The desired metal oxide/3DGN composites were then obtained by a two-step annealing process. As a proof-of-concept application, the obtained ZnO/3DGN and Fe2 O3 /3DGN materials were used in a photocatalytic reaction and a lithium-ion battery, respectively. We believe this method could be extended to the synthesis of other metal oxide/3DGN composites with 3D structures simply through the appropriate choice of specific MOFs as precursors.
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Analysis of synonymous codon usage in Newcastle disease virus hemagglutinin-neuraminidase (HN) gene and fusion protein (F) gene.
Virusdisease
PUBLISHED: 01-16-2014
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Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) is a multifunctional protein, which possesses both the receptor recognition and neuraminidase activities. The fusion (F) protein is a type I membrane glycoprotein that mediates the merger of the viral envelope to the host cell membrane. Although the functions of the HN and F proteins have been well studied, however, the factors shaping synonymous codon usage bias and nucleotide composition in HN and F genes have been few reported. In our study, we analyzed synonymous codon usage using the 69 NDV HN and F genes, respectively. The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in HN and F genes. In addition, other factors, such as the aromaticity and hydrophobicity, also influence the codon usage variation among HN and F genes. This study represents the most comprehensive analysis to date of NDV HN and F genes codon usage patterns and provides a basic understanding of the mechanisms for codon usage bias.
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Morphological evidence for a neurotensinergic periaqueductal gray-rostral ventromedial medulla-spinal dorsal horn descending pathway in rat.
Front Neuroanat
PUBLISHED: 01-01-2014
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Neurotensin (NT) is an endogenous neuropeptide that exerts potent opioid-independent analgesic effects, most likely via the type 2 NT receptor (NTR2). Previous morphological and electrophysiological studies suggested that the NT-NTR2 system is primarily localized in structures that constitute the descending pain control pathway, such as the periaqueductal gray (PAG), the rostral ventromedial medulla (RVM), and the spinal dorsal horn (SDH). However, relevant morphological evidence for this neurotensinergic (NTergic) circuit is lacking. Thus, the aim of the present study was to morphologically elucidate the potential sites and connections in the NT-NTR2 system that are involved in the descending pain control pathway. Based on light and electron microscopy combined with anterograde and retrograde tracing, we found evidence that NTR2-immunoreactive (IR) neurons in the RVM receive NT-IR projections originating from the PAG; express NT, serotonin (5-HT), or both; and send projections that terminate in laminae I and II of the SDH. These results suggest that NTR2 may contribute to pain control by binding to NT in the PAG-RVM-SDH pathway. In conclusion, our data provide morphological evidence for an NTergic PAG-RVM-SDH pathway, implicating novel mechanisms of NT-induced analgesia.
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Physical activity level of urban pregnant women in tianjin, china: a cross-sectional study.
PLoS ONE
PUBLISHED: 01-01-2014
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To determine the physical activity level and factors influencing physical activity among pregnant urban Chinese women.
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An antifungal role of hydrogen sulfide on the postharvest pathogens Aspergillus niger and Penicillium italicum.
PLoS ONE
PUBLISHED: 01-01-2014
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In this research, the antifungal role of hydrogen sulfide (H2S) on the postharvest pathogens Aspergillus niger and Penicillium italicum growing on fruits and under culture conditions on defined media was investigated. Our results show that H2S, released by sodium hydrosulfide (NaHS) effectively reduced the postharvest decay of fruits induced by A. niger and P. italicum. Furthermore, H2S inhibited spore germination, germ tube elongation, mycelial growth, and produced abnormal mycelial contractions when the fungi were grown on defined media in Petri plates. Further studies showed that H2S could cause an increase in intracellular reactive oxygen species (ROS) in A. niger. In accordance with this observation we show that enzyme activities and the expression of superoxide dismutase (SOD) and catalase (CAT) genes in A. niger treated with H2S were lower than those in control. Moreover, H2S also significantly inhibited the growth of Saccharomyces cerevisiae, Rhizopus oryzae, the human pathogen Candida albicans, and several food-borne bacteria. We also found that short time exposure of H2S showed a microbicidal role rather than just inhibiting the growth of microbes. Taken together, this study suggests the potential value of H2S in reducing postharvest loss and food spoilage caused by microbe propagation.
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The global pattern of urbanization and economic growth: evidence from the last three decades.
PLoS ONE
PUBLISHED: 01-01-2014
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The relationship between urbanization and economic growth has been perplexing. In this paper, we identify the pattern of global change and the correlation of urbanization and economic growth, using cross-sectional, panel estimation and geographic information systems (GIS) methods. The analysis has been carried out on a global geographical scale, while the timescale of the study spans the last 30 years. The data shows that urbanization levels have changed substantially during these three decades. Empirical findings from cross-sectional data and panel data support the general notion of close links between urbanization levels and GDP per capita. However, we also present significant evidence that there is no correlation between urbanization speed and economic growth rate at the global level. Hence, we conclude that a given country cannot obtain the expected economic benefits from accelerated urbanization, especially if it takes the form of government-led urbanization. In addition, only when all facets are taken into consideration can we fully assess the urbanization process.
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[Analysis of docosahexenoic acid in human blood using heterocyclic derivatization-gas chromatography-triple quadrupole mass spectrometry].
Se Pu
PUBLISHED: 12-28-2013
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A method was developed and validated for the analysis of docosahexenoic acid (DHA) in human blood by heterocyclic derivatization-gas chromatography coupled with triple quadrupole mass spectrometry (GC-MS/MS). 2-Amino-2-methyl-1-propanol (AMP) was used as the reaction reagent of DHA heterocyclic derivatization and the most optimal reaction conditions of this reaction were optimized. Multiple reaction monitoring and internal standard calibration curve were applied to detect DHA by GC-MS/MS. The linear range for the determination of DHA was 0.07 - 10 microg/mL (r(2) = 0.9991). The limit of detection (S/N = 2.8) was 0.02 microg/mL and the limit of quantification (S/N = 10) was 0.07 microg/mL. The average recoveries of DHA at three spiked levels of 0.5, 1.5 and 2.5 microg ranged from 94.40% to 103.13% and the relative standard deviations (RSD) were in the range of 1.51% - 3.16%. The method was simple, accurate, reliable and small amount of sample was required. It was suitable for detecting the contents of DHA in human blood.
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[Transcellular process of coumarin 6 loaded PEG-PCL micelles on MDCK epithelial cells].
Yao Xue Xue Bao
PUBLISHED: 12-24-2013
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The transcellular process of coumarin 6 (C6) loaded poly(ethyl ethylene phosphate)-co-poly (epsilon-caprolactone) (PEG-PCL) micelles on Madin-Darby Canine Kidney (MDCK) epithelial cells was investigated. C6 loaded PEG-PCL micelles were prepared using the thin-film hydration method. The size of the micelles was characterized by dynamic light scattering analysis using a Malvern Zetasizer Nano ZS. The critical micelle concentration (CMC) was determined by pyrene fluorescence probe method. And the transcellular process of the micelles on MDCK epithelial cells was investigated by using transmission electron microscope, laser confocal scanning microscope and Förster resonance energy transfer technology. It turned out that the size of PEG-PCL micelles was about 30 nm and CMC was 1.01 microg x mL(-1). PEG-PCL micelles were endocytosed in intact form and they could deliver hydrophobic drugs across the basolateral membrane of the epithelial cells. However, PEG-PCL is hardly being transported in micelle formation itself. The transportation of C6 by PEG-PCL micelles was through the transcellular pathway, yet not the paracellular pathway.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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

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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.