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Find video protocols related to scientific articles indexed in Pubmed.
An Economical Online Solid-Phase Extraction LC-MS/MS Method for Quantifying Methylprednisolone.
J Chromatogr Sci
PUBLISHED: 11-19-2014
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An economical, reproducible and automated online solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry method was developed to quantify methylprednisolone in human plasma. The method was validated in terms of selectivity, precision/accuracy, process efficiency, stability, cartridge reproducibility and carryover studies. Sample pretreatment was performed by protein precipitation and elimination using methanol followed by water dilution. Then, the mixture was passed onto the HySphere C8 EC-SE online solid-phase extraction cartridge followed by the separation of the analytes on an Agilent Eclipse XDB column. Electrospray ionization in positive ion mode and multiple reaction monitoring were used to monitor the ion transitions at m/z 375.4/160.8 for methylprednisolone, and m/z 361.2/147.0 for prednisolone. The calibration curve ranged from 5.25 to 525 ng/mL. Meanwhile both the intra-day and inter-day precision values (relative standard deviation) were within 4.45%. The method which turns out to be less laborious, faster and lower consumable cost per sample has already been successfully applied to a pharmacokinetic study in which the oral administration of 16 mg methylprednisolone was conducted in Chinese volunteers.
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5.2-W high-repetition-rate eye-safe laser at 1525 nm generated by Nd:YVO4-YVO4 stimulated Raman conversion.
Opt Express
PUBLISHED: 11-18-2014
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We report herein an efficient eye-safe Raman laser, which is based upon Nd:YVO4-YVO4 and in-band pumped by a wavelength-locked laser diode array at 878.6 nm. By virtue of mitigated thermal load and improved pump absorption, a maximum average output power of 5.2 W at 1525 nm is obtained under the incident pump power of 30.6 W with the pulse repetition frequency of 140 kHz, corresponding to an optical efficiency of 17.0%.
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Subcellular localization of MTA proteins in normal and cancer cells.
Cancer Metastasis Rev.
PUBLISHED: 11-16-2014
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The subcellular localization of a protein is closely linked to and indicates its function. The metastatic tumor antigen (MTA) family has been under continuous investigation since its identification two decades ago. MTA1, MTA2, and MTA3 are the main members of the MTA family. MTA1, as the representative member of this family, has been shown to be widely expressed in both embryonic and adult tissues, as well as in normal and cancerous conditions, indicating that MTA1 has functions both in physiological and pathological contexts. MTA1 is expressed at a higher level in most cancers than in their normal tissue counterparts. Even in normal cells, MTA1 levels vary a great deal from tissue to tissue. Importantly, MTA1 shows a multiple localization pattern in the cell, as do MTA2 and MTA3. Different MTA components in different subcellular compartments may exert different molecular functions in the cell. Previous studies revealed that MTA1 and MTA2 are predominately localized to the nucleus, while MTA3 is observed in both the nucleus and cytoplasm. Recent studies have reported that MTA1 is located in the nucleus, cytoplasm, and the nuclear envelope. In the nucleus, MTA1 dynamically interacts with chromatin in a MTA1-K532 methylation-dependent manner, whereas cytoplasmic MTA1 binds to the microtubule skeleton. MTA1 also shows a dynamic distribution during the cell cycle. Further investigations are needed to identify the exact subcellular localizations of MTA proteins. We review the sub-cellular localization patterns of the MTA family members and give a comprehensive overview of their respective molecular activities in multiple contexts.
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[Construction of age group vegetation index and preliminary application].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 11-01-2014
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In the present paper, one remote sensing index-age group vegetation index (AGVI) was put forward, and its feasibility was verified. Taking 518 groups of pine forest age group data collected in 13 counties (cities) of Sanming, Jiangle, Shaxian, Nanping, Huaan, Yunxiao, Nanping, Anxi, Putian, Changting, Jianyang, Ningde and Fuqing, Fujian Province and HJ-1 CCD multi-spectral image at the same time-phase as the basis, the spectrum differences of blue, green, red, near infrared and NDVI of each age group were analyzed, showing the characteristics of young forest>middle-aged forest>over-mature forest>mature forest>near mature forest at near infrared band and mature forest>near mature forest>over-mature forest>young forest>middle-aged forest at NDVI, thus the age group vegetation index (AGVI) was constructed; the index could increase the absolute and relative spectrum differences among age groups. For the pine forest AGVI, cluster analysis was conducted with K-mean method, showing that the division accuracy of pine forest age group was 80.45%, and the accurate rate was 90.41%. Therefore, the effectiveness of age group vegetation index constructed was confirmed.
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Comparative study of contrast-enhanced ultrasound qualitative and quantitative analysis for identifying benign and malignant breast tumor lumps.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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To compare the value of contrast-enhanced ultrasound (CEUS) qualitative and quantitative analysis in the identification of breast tumor lumps.
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12.45??W wavelength-locked 878.6??nm laser diode in-band pumped multisegmented Nd:YVO4 laser operating at 1342??nm.
Appl Opt
PUBLISHED: 10-17-2014
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A multisegmented Nd:YVO4 laser operating at 1342 nm that is in-band pumped by a wavelength-locked 878.6 nm laser diode is reported here. We achieve an output power of 12.45 W at 1342 nm for an absorbed pump power of 35.6 W, corresponding to an optical-to-optical efficiency of 34.9% and a slope efficiency of 36.1%. To the best of our knowledge, it is the highest optical-to-optical efficiency of Nd:YVO4 lasers operating at 1342 nm with an output power more than 10 W.
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Femtosecond fiber laser welding of dissimilar metals.
Appl Opt
PUBLISHED: 10-17-2014
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In this paper, welding of dissimilar metals was demonstrated for the first time, to the best of our knowledge, by using a high-energy high-repetition-rate femtosecond fiber laser. Metallurgical and mechanical properties were investigated and analyzed under various processing parameters (pulse energy, repetition rate, and welding speed). Results showed that the formation of intermetallic brittle phases and welding defects could be effectively reduced. Strong welding quality with more than 210 MPa tensile strength for stainless steel-aluminum and 175 MPa tensile strength for stainless steel-magnesium has been demonstrated. A minimal heat affected zone and uniform and homogenous phase transformation in the welding region have been demonstrated. This laser-welding technique can be extended for various applications in semiconductor, automobile, aerospace, and biomedical industries.
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Resolution properties of transmission-mode exponential-doping Ga0.37Al0.63As photocathodes.
Appl Opt
PUBLISHED: 10-17-2014
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Using the modulation transfer function obtained by establishing and solving the two-dimensional continuity equation, we have calculated and comparatively analyzed the resolution characteristics of transmission-mode exponential-doping and uniform-doping Ga0.37Al0.63As photocathodes. The calculations show that compared with a uniform-doping Ga0.37Al0.63As photocathode, the exponential-doping structure can significantly improve not only the resolution, but also the quantum efficiency of the photocathode. This improvement is different from the approach for high resolution by reducing the emission layer thickness Te and electron diffusion length LD, or by increasing the recombination velocity of the back-interface, SV, which results in low quantum efficiency. Furthermore, the improvement in resolution and quantum efficiency for the transmission-mode exponential-doping Ga0.37Al0.63As photocathodes is the result of the effect of the built-in electric field on electron transport and lateral diffusion.
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Ginsenoside-Rb2 inhibits dexamethasone-induced apoptosis through promotion of GPR120 induction in bone marrow-derived mesenchymal stem cells.
Stem Cells Dev.
PUBLISHED: 10-16-2014
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Apoptosis of bone marrow-derived mesenchymal stem cells (BMMSCs) is an essential pathogenic factor of osteoporosis. Ginsenoside-Rb2 (Rb2), a 20(S)-protopanaxadiol glycoside extracted from ginseng, is a potent treatment for bone loss which raises interest regarding the bone metabolism area. In the present study, we found that dose-response Rb2 inhibited high dosage of dexamethasone (Dex)-induced apoptosis in primary murine BMMSCs. Interestingly, Rb2 promoted GPR120 induction, which is the unsaturated long chain fatty acid receptor. We further confirmed that GPR120-specific ShRNA reversed the inhibition of Rb2 on Dex-induced apoptosis by activating caspase-3 and reducing cell viability. In addition, Rb2 notably increased phosphorylated ERK1/2 levels and Ras kinase activity dependently via the GPR120. The ERK1/2 activity-specific inhibitor U0126 remarkably blocked Rb2-induced anti-apoptotic effect in response to Dex-induced apoptosis. Together, dose-response Rb2 protected BMMSCs against Dex-induced apoptosis dependently by inducing GPR120 promoted Ras-ERK1/2 signaling pathway. Therefore, in the prevalence of the abuse of Dex in the clinic, our findings suggest for the first time that Rb2 is not only a key to understand the link between Chinese medicine and the pathology of osteoporosis but also an underlying target for the treatment of bone complications in the foreseeable future.
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Selective growth and integration of silver nanoparticles on silver nanowires at room conditions for transparent nano-network electrode.
ACS Nano
PUBLISHED: 10-10-2014
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Recently, metal nanowires have received great research interests due to their potential as next-generation flexible transparent electrodes. While great efforts have been devoted to develop enabling nanowire electrodes, reduced contact resistance of the metal nanowires and improved electrical stability under continuous bias operation are key issues for practical applications. Here, we propose and demonstrate an approach through a low-cost, robust, room temperature and room atmosphere process to fabricate a conductive silver nano-network comprising silver nanowires and silver nanoparticles. To be more specific, silver nanoparticles are selectively grown and chemically integrated in situ at the junction where silver nanowires meet. The site-selective growth of silver nanoparticles is achieved by a plasmon-induced chemical reaction using a simple light source at very low optical power density. Compared to silver nanowire electrodes without chemical treatment, we observe tremendous conductivity improvement in our silver nano-networks, while the loss in optical transmission is negligible. Furthermore, the silver nano-networks exhibit superior electrical stability under continuous bias operation compared to silver nanowire electrodes formed by thermal annealing. Interestingly, our silver nano-network is readily peeled off in water, which can be easily transferred to other substrates and devices for versatile applications. We demonstrate the feasibly transferrable silver conductive nano-network as the top electrode in organic solar cells. Consequently, the transparent and conductive silver nano-networks formed by our approach would be an excellent candidate for various applications in optoelectronics and electronics.
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Discovery of a Potent and Selective DGAT1 Inhibitor with a Piperidinyl-oxy-cyclohexanecarboxylic Acid Moiety.
ACS Med Chem Lett
PUBLISHED: 10-09-2014
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We report the discovery of a novel series of DGAT1 inhibitors in the benzimidazole class with a piperdinyl-oxy-cyclohexanecarboxylic acid moiety. This novel series possesses significantly improved selectivity against the A2A receptor, no ACAT1 off-target activity at 10 ?M, and higher aqueous solubility and free fraction in plasma as compared to the previously reported pyridyl-oxy-cyclohexanecarboxylic acid series. In particular, 5B was shown to possess an excellent selectivity profile by screening it against a panel of more than 100 biological targets. Compound 5B significantly reduces lipid excursion in LTT in mouse and rat, demonstrates DGAT1 mediated reduction of food intake and body weight in mice, is negative in a 3-strain Ames test, and appears to distribute preferentially in the liver and the intestine in mice. We believe this lead series possesses significant potential to identify optimized compounds for clinical development.
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Preparation, Characterization and Origin of Highly Active and Thermally Stable Pd-Ce0.8Zr0.2O2 Catalysts via Sol-Evaporation Induced Self-Assembly Method.
Environ. Sci. Technol.
PUBLISHED: 10-06-2014
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The Pd-Ce-Zr solid solution catalysts were in situ synthesized by a sol-evaporation induced self-assembly (SEISA) method. The catalytic performances of the as-prepared catalysts for CO oxidation and their physicochemical properties were investigated with various characterization techniques. The catalysts with low doping amount of Pd exhibited unique thermal stability and high activity toward CO oxidation. The CO oxidation activities of the catalysts showed a volcano type relationship with the content of Pd doping in Ce-Zr oxides. Pd-Ce0.8Zr0.2O2 with 1.0% Pd doping gave the highest catalytic activity. Its CO complete conversion temperature was 110 °C with a turnover frequency of 1.52 s(-1). Density functional theory (DFT) calculations suggested strong effects of Pd doping on the crystal structure, charge distribution and formation of oxygen vacancy of the Ce-based catalysts. The calculations also suggested that CO oxidation on Pd doped Ce-based catalysts follows Eley-Rideal mechanism, and the direct reaction of CO with a surface oxygen atom appears to be the main pathway of the oxidation.
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[The effect of Xinfeng capsule treatment on the number of BTLA(+)T cells and oxidative stress of patients with ankylosing spondylitis].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 10-02-2014
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Objective To investigate the changes of B and T lymphocyte attenuator (BTLA), reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total antioxidative capacity (TAOC) in the patients with ankylosing spondylitis (AS) and the effect of Xinfeng capsule (XFC) on them. Methods AS patients (n=140) were randomly divided into two groups, XFC group (3 tablets each time, tid, n=70) and salicylazosulfapyridine (SASP) group (4 pills each time, bid, n=70). Continuous treatment lasts 3 months. The study also enrolled 60 healthy volunteers as a control group. Flow cytometry was used to test BTLA expression. ELISA was performed to detect the oxidative stress indicators (ROS, RNS, MDA, SOD, CAT, TAOC) and cytokines (IL-4, IL-10, IL-1?, TNF-?). Western blotting was adopted to examine the blood sedimentation (ESR). HITACHI 7060 automatic biochemical analyzer was used to determine the level of high sensitive C-reactive protein (Hs-CRP). Results Clinical efficacy of XFC group was significantly better than that of SASP group (P<0.01). Compared with the healthy control group, AS patients had significantly lower BTLA expression in CD3(+) T cells and CD4(+) T cells from the peripheral blood (P<0.01 or P<0.05), the decreased levels of SOD, CAT and TAOC, and significantly increased ROS, RNS and MDA values (P<0.01 or P<0.05). In addition, the levels of serum IL-1?, TNF-?, ESR and Hs-CRP were significantly higher (P<0.01) and IL-4, IL-10 were significantly lower in AS patients (P<0.01 or P<0.05). Compared with pre-treatment, both XFC and SASP significantly elevated the expressions of BTLA(+)CD3(+) T, BTLA(+)CD4(+) T, BTLA, SOD, TAOC, IL-4, SF-36 (PF, SF, RP, RE, BP, MH, VT, GH) eight dimension scores, and reduced ROS, MDA, TNF-?, ESR, Hs-CRP, VAS, BASDAI, BASFI and BAS-G in the peripheral blood (P<0.01 or P<0.05). The differences between XFC group and SASP group were statistically significant (P<0.01 or P<0.05). Pearson correlation analysis showed that BTLA expression level in the peripheral blood was positively correlated with SOD, RP, BP, SF and RE. BTLA(+)CD3(+) T cells and BTLA*CD4(+) T cells were significantly negatively correlated with ROS, MDA, IL-1?, TNF-?, ESR, VAS and BASDAI, and they were positively correlated with TAOC, IL-4 and IL-10. BTLA(+)CD3(+) T cells were significantly negatively correlated with RNS, Hs-CRP and BASFI; BTLA(+)CD4(+) T cells were positively correlated with CAT. Conclusion XFC can improve BTLA expression in the peripheral blood of AS patients and regulate negatively the activation and proliferation of T cells.
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Facile synthesis of carbon-doped mesoporous anatase TiO2 for the enhanced visible-light driven photocatalysis.
Chem. Commun. (Camb.)
PUBLISHED: 10-01-2014
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Here we report a low-cost and facile synthesis approach for carbon-doped mesoporous anatase TiO2 by using Ti(BuO)4 as a source for both Ti and carbon through xerogel carbonization in a hypoxic atmosphere. The resultant mesoporous C-TiO2 with high crystallinity exhibits excellent photocatalytic activities for degradation of methyl orange (MO) and phenol under visible light irradiation.
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Attenuation of Morphine Analgesic Tolerance by Rosuvastatin in Naïve and Morphine Tolerance Rats.
Inflammation
PUBLISHED: 09-28-2014
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Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. Since inflammation in the central nervous system was highly related to morphine tolerance, we sought to investigate whether statins could affect morphine tolerance by mediating glia-derived proinflammatory cytokines secretion. We have undertaken two separate studies: Firstly, we determined the effect of rosuvastatin on naïve rats during induction of morphine tolerance. Secondly, we investigated whether rosuvastation could attenuate the morphine analgesic tolerance in rats that the morphine tolerance established previously. Results demonstrated that peroral rosuvastatin not only delays, but also partially reverses the tolerance to morphine analgesia in rats. The administration of rosuvastatin during induction of morphine tolerance attenuated the activation of ERK and the release of proinflammatory cytokines in the lumbar spinal cord. Similar outcomes were observed in rats were morphine tolerance was established previously. Moreover, our study also found that repeated administration of morphine could activate the astrocytes in the spinal cord while rosuvastation succeeds in suppressing the activation of astrocytes. Our results support the idea that targeting glia-derived proinflammatory effects during morphine treatment is a novel and clinically promising method for enhancing analgesic effects of morphine. We identify a potential new application of statins in the treatment of morphine analgesic tolerance.
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Extremely Stable Platinum Nanoparticles Encapsulated in a Zirconia Nanocage by Area-Selective Atomic Layer Deposition for the Oxygen Reduction Reaction.
Adv. Mater. Weinheim
PUBLISHED: 09-17-2014
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Encapsulation of Pt nanoparticles (NPs) in a zirconia nanocage by area-selective atomic layer deposition (ALD) can significantly enhance both the Pt stability and activity. Such encapsulated Pt NPs show 10 times more stability than commercial Pt/C catalysts and an oxygen reduction reaction (ORR) activity 6.4 times greater than that of Pt/C.
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Evidence of an unusual N-H···N hydrogen bond in proteins.
J. Am. Chem. Soc.
PUBLISHED: 09-16-2014
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Many residues within proteins adopt conformations that appear to be stabilized by interactions between an amide N-H and the amide N of the previous residue. To explore whether these interactions constitute hydrogen bonds, we characterized the IR stretching frequencies of deuterated variants of proline and the corresponding carbamate, as well as the four proline residues of an Src homology 3 domain protein. The C?D2 stretching frequencies are shifted to lower energies due to hyperconjugation with Ni electron density, and engaging this density via protonation or the formation of the Ni+1-H···Ni interaction ablates this hyperconjugation and thus induces an otherwise difficult to explain blue shift in the C-D absorptions. Along with density functional theory calculations, the data reveal that the Ni+1-H···Ni interactions constitute H-bonds and suggest that they may play an important and previously underappreciated role in protein folding, structure, and function.
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Separation of Catalpol from Rehmannia glutinosa Libosch. by High-Speed Countercurrent Chromatography.
J Chromatogr Sci
PUBLISHED: 09-13-2014
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The bioactive iridoid component catalpol was successfully separated by high-speed countercurrent chromatography with high purity from the partially purified crude extract of Rehmannia glutinosa. A polar two-phase solvent system composed of ethyl acetate-n-butanol-water (2:1:3, v/v/v) was selected by thin-layer chromatography and run on a preparative scale where the lower aqueous phase was used as the mobile phase with a head-to-tail elution mode. A 105 mg quantity of the partially purified sample containing 39.2% catalpol was loaded on a 270-mL capacity high-speed countercurrent separation column, yielding 35 mg of catalpol at 95.6% purity. The chemical structure of catalpol was determined by comparison with the high-performance liquid chromatography retention time of standard substance as well as the (1)H NMR spectrum.
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Mitogen-activated protein kinase 6 regulates NPR1 gene expression and activation during leaf senescence induced by salicylic acid.
J. Exp. Bot.
PUBLISHED: 09-12-2014
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Plant senescence is a highly regulated process that can be induced by a range of factors. The nonexpressor of pathogenesis-related genes 1 (npr1) mutant is defective in the salicylic acid (SA) signalling pathway, displaying delayed yellowing during developmental senescence. However, the regulating mechanism of NPR1 on exogenous SA-induced senescence in detached Arabidopsis leaves has not yet been clarified. It was shown here that mitogen-activated protein kinase 6 (MPK6) is involved in promoting exogenous SA-induced detached leaf senescence. During the process of SA-induced senescence, the expression of NPR1 and senescence-related transcription factor WRKY6 was suppressed in mpk6 mutant plants. Further analyses showed that the NPR1 mRNA level is reduced in wrky6 mutants and enhanced in WRKY6 overexpressing lines. Meanwhile, chromatin immunoprecipitation experiments revealed that WRKY6 binds directly to the NPR1 promoter containing W-box motifs. Moreover, inhibition of MPK6 function diminished SA-induced monomerization and nuclear localization of NPR1. In addition, the expression of Trx h5, which catalyses the SA-induced NPR1 activation, was suppressed in the mpk6 mutant, suggesting that MPK6 promotes NPR1 activation, possibly by regulating the expression of Trx h5. Collectively, MPK6-mediated WRKY6 and Trx h5 transcriptional activation co-regulated the expression of the NPR1 gene and the monomerization of NPR1 protein, allowing it to enter the nucleus, thereby promoting SA-induced leaf senescence. These results provide new insight into the mechanism of exogenous SA-induced detached leaf senescence.
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Chemoenzymatic synthesis of heparan sulfate and heparin.
Nat Prod Rep
PUBLISHED: 09-08-2014
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Covering: up to May 2014Heparan sulfate is a polysaccharide that plays essential physiological functions in the animal kingdom. Heparin, a highly sulfated form of heparan sulfate, is a widely prescribed anticoagulant drug worldwide. The heparan sulfate and heparin isolated from natural sources are highly heterogeneous mixtures differing in their polysaccharide chain lengths and sulfation patterns. The access to structurally defined heparan sulfate and heparin is critical to probe the contribution of specific sulfated saccharide structures to the biological functions as well as for the development of the next generation of heparin-based anticoagulant drugs. The synthesis of heparan sulfate and heparin, using a purely chemical approach, has proven extremely difficult, especially for targets larger than octasaccharides having a high degree of site-specific sulfation. A new chemoenzymatic method has emerged as an effective alternative approach. This method uses recombinant heparan sulfate biosynthetic enzymes combined with unnatural uridine diphosphate-monosaccharide donors. Recent examples demonstrate the successful synthesis of ultra-low molecular weight heparin, low-molecular weight heparin and bioengineered heparin with unprecedented efficiency. The new method provides an opportunity to develop improved heparin-based therapeutics.
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Reaction moment at the l5/s1 joint during simulated forward slipping with a handheld load.
Int J Occup Saf Ergon
PUBLISHED: 09-06-2014
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The purpose of the study was to investigate the effects of load on the net moment response at the L5/S1 joint during simulated slip events. Six young individuals were instructed to take one step with a handheld load. Sudden floor movement was randomly introduced to simulate unexpected slips. Different loads conditions (0%, 10%, 20%, 30% of body weight) were introduced at random. Three-dimensional net moments at the L5/S1 joint were computed via downward inverse dynamic model. Peak joint moment generated at 30% load level was found to be significantly higher compared to no-load condition. No peak moment differences were found among no-load, 10% or 20% load levels. Additionally, the findings from this study indicated a flexiondominant net L5/S1 joint moment pattern during motion phase associated with slip-induced falls.
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Iron(III) complexes of multidentate pyridinyl ligands: synthesis, characterization and catalysis of the direct hydroxylation of benzene.
Dalton Trans
PUBLISHED: 09-05-2014
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Three multidentate ligands, L?-L?, derived from bis(pyridin-2-ylmethyl)amine (L?) were synthesized. Reaction of these ligands with FeCl3·6H2O in methanol led to the formation of the iron complexes Fe?-Fe? (Fe?: [FeL?Cl3]; Fe?: [FeL?Cl3]; Fe?: [FeL?Cl3]) in good yields. These complexes have been fully characterized. The structures of complexes Fe?-Fe? have been determined using X-ray single crystal diffraction analysis. Electrochemical investigation revealed that complex Fe? partially converts to Fe? ([FeL?Cl2]PF6) by the replacement of one of its three chlorides with its pendant triazolyl group in solution. Fe? was also synthesized by dechlorination using AgPF6 as the Cl(-) abstractor and its composition was further confirmed by both elemental analysis and X-ray single crystal diffraction analysis. All four complexes catalyze the direct hydroxylation of benzene to phenol with hydrogen peroxide as an oxidant in a mixed medium of water and acetonitrile. The reactivity of the complexes correlates well with their reduction potentials. The more negative the potential, the more reactive (high conversion rate) the catalysts. These complexes catalyze not only the oxidation of benzene, but also the further oxidation of the product, phenol. In the oxidation, a radical mechanism is certainly involved but an alternative pathway may also exist.
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Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds.
Diabetes
PUBLISHED: 09-03-2014
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Re-epithelialization is an important part in mucosal wound healing. Surprisingly little is known about the impact of diabetes on the molecular events of mucosal healing. We examined the role of the transcription factor forkhead box O1 (Foxo1) in oral wounds of diabetic and normoglycemic mice with keratinocyte specific Foxo1 deletion. Diabetic mucosal wounds had significantly delayed healing with reduced cell migration and proliferation. Foxo1 deletion rescued the negative impact of diabetes on healing but had the opposite effect in normoglycemic mice. Diabetes in vivo and high glucose in vitro enhanced expression of chemokine (C-C motif) ligand 20 (CCL20) and interleukin-36? (IL-36?) in a Foxo1 dependent manner. High glucose stimulated Foxo1 binding to CCL20 and IL36? promoters and CCL20 and IL-36? significantly inhibited migration of these cells in high glucose. In normal healing Foxo1 was needed for transforming growth factor-?1 (TGF-?1) expression and in standard glucose TGF-?1 rescued the negative effect of Foxo1 silencing on migration in vitro. We propose that Foxo1 under diabetic or high glucose conditions impairs healing by promoting high levels of CCL20 and IL-36? expression but under normal conditions enhances it by inducing TGF-?1. This finding provides mechanistic insight into how Foxo1 mediates the impact of diabetes on mucosal wound healing.
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Role of NSD1 in H2O2-induced GSTM3 suppression.
Cell. Signal.
PUBLISHED: 09-02-2014
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Nuclear receptor-binding SET domain-containing protein 1 (NSD1) has been proved to act as a histone methyltransferase and a transcription co-factor to regulate gene expression. However, the role of NSD1 in oxidative stress remains poorly understood. In the present study, we focused on the NSD1 regulation of antioxidant enzyme gene glutathione S-transferase M3 (GSTM3) expression in response to oxidative stress. H2O2 treatment caused the decrease of both NSD1 and GSTM3 expression, and the depletion of NSD1 expression by specific siRNA reversed the H2O2-reduced GSTM3 expression. Furthermore, we investigated NSD1 modulating the transcription of GSTM3 promoter with -63A/C polymorphism closed to TATA box in response to H2O2 by luciferase and in vitro or in vivo DNA-protein binding assays. The promoter activity of GSTM3 with -63A was higher than -63C, and was increased or decreased by the overexpression or depletion of NSD1, but -63C was not influenced. H2O2 repressed the promoter activity of GSTM3 with -63A more than -63C, and the depletion of NSD1 expression weakened H2O2 inhibition on the -63A promoter, but augmented H2O2 inhibition on the -63C promoter. In addition, NSD1 interacted with RNAPII and bound to GSTM3 -63A/C TATA box, with higher binding affinity to -63A than to -63C. These data indicated that NSD1 implicated in H2O2-induced oxidative stress, and H2O2-induced NSD1 suppression resulted in the decrease of GSTM3 expression through the -63A/C TATA box.
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A class-information-based penalized matrix decomposition for identifying plants core genes responding to abiotic stresses.
PLoS ONE
PUBLISHED: 09-02-2014
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In terms of making genes expression data more interpretable and comprehensible, there exists a significant superiority on sparse methods. Many sparse methods, such as penalized matrix decomposition (PMD) and sparse principal component analysis (SPCA), have been applied to extract plants core genes. Supervised algorithms, especially the support vector machine-recursive feature elimination (SVM-RFE) method, always have good performance in gene selection. In this paper, we draw into class information via the total scatter matrix and put forward a class-information-based penalized matrix decomposition (CIPMD) method to improve the gene identification performance of PMD-based method. Firstly, the total scatter matrix is obtained based on different samples of the gene expression data. Secondly, a new data matrix is constructed by decomposing the total scatter matrix. Thirdly, the new data matrix is decomposed by PMD to obtain the sparse eigensamples. Finally, the core genes are identified according to the nonzero entries in eigensamples. The results on simulation data show that CIPMD method can reach higher identification accuracies than the conventional gene identification methods. Moreover, the results on real gene expression data demonstrate that CIPMD method can identify more core genes closely related to the abiotic stresses than the other methods.
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Europium(III) complex-functionalized magnetic nanoparticle as a chemosensor for ultrasensitive detection and removal of copper(II) from aqueous solution.
Nanoscale
PUBLISHED: 08-27-2014
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Ultrasensitive, accurate detection and separation of heavy metal ions is very important in environmental monitoring and biological detection. In this paper, a highly sensitive and specific detection method for Cu(2+) based on the fluorescence quenching of a europium(III) hybrid magnetic nanoprobe is presented. This nanoprobe can detect Cu(2+) over a wide pH range (5.0-10.0) with a detection limit as low as 0.1 nM and it can be used for detecting Cu(2+) in living cells. After the magnetic separation, the Cu(2+) concentration decreased to 1.18 ppm, which is less than the US EPA drinking water standard (1.3 ppm), and more than 70% Cu(2+) could be removed when the amount of nanocomposite 1 reached 1 mg.
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Cyclooxygenase-2-dependent oxidative stress mediates palmitate-induced impairment of endothelium-dependent relaxations in mouse arteries.
Biochem. Pharmacol.
PUBLISHED: 08-19-2014
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Palmitic acid, one of the saturated free fatty acids, impairs cardiovascular function as manifested by inducing vascular inflammation, apoptosis and over-production of reactive oxygen species (ROS) although the origin for ROS remains unclear. The present study investigated the cellular mechanisms underlying palmitate-induced impairment of endothelial function. Ex vivo treatment in tissue culture with palmitate concentration-dependently attenuated acetylcholine-induced endothelium-dependent relaxations, up-regulated the expression of cyclooxygenase-2 (COX-2) and elevated superoxide formation in mouse aortic endothelial cells (MAECs) measured by dihydroethidium (DHE) staining and electron paramagnetic resonance (EPR) spectroscopy. Superoxide scavengers, COX-2 inhibitor and thromboxane prostanoid (TP) receptor antagonist, but not COX-1 inhibitor reversed the harmful effects of palmitate. Furthermore, palmitate impaired acetylcholine-induced relaxations and raised superoxide in en face endothelium of aortas only from COX-1(-/-) mice but not from COX-2(-/-) mice. Palmitate increased the production and release of TXB2, a stable thromboxane A2 metabolite in mouse aortas, which was abolished by COX-2 inhibitor. Superoxide scavenger did not affect palmitate-induced up-regulated expression of COX-2 in MAECs. Both real time PCR and luciferase reporter gene assay confirmed COX-2 up-regulation in palmitate-treated MAECs and NF-?B was substantially involved in this up-regulation. The present study provides novel evidence that palmitate up-regulates COX-2 through NF-?B-dependent mechanism and resultant COX-2-associated oxidative stress impairs endothelium-dependent relaxations in mouse aortas.
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The Pleckstrin and Sec7 domain-containing gene as a novel epigenetic modification marker in human gastric cancer and its clinical significance.
Int. J. Oncol.
PUBLISHED: 08-15-2014
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The Pleckstrin and Sec7 domain-containing (PSD) gene has been recently found to participate in the progression of several types of cancer. In the present study, we identified PSD as a candidate tumor suppressor gene silenced through epigenetic modification in gastric cancer (GC). PSD mRNA expression and DNA methylation were evaluated by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and methylation-specific PCR in GC cell lines and tissue samples. Involvement of histone modification in GC cell lines was examined by chromatin immunoprecipitation assay. We also used an siRNA-mediated approach to knock down the PSD gene in SGC7901 cells, which was utilized to detect the role of PSD in GC progression, followed by analysis of cell apoptosis and invasion. PSD gene expression was reduced in all GC cell lines compared with GES1 (an immortalized normal gastric cell line). In addition, PSD expression was markedly downregulated in gastric carcinoma tissues when compared to adjacent non-tumor tissues. Our data also indicated that PSD mRNA and protein levels were associated with tumor differentiation and lymph node metastasis. Aberrant DNA methylation status and histone modification were also found in GC cell lines. Enhanced gene expression was detected when the HGC27, AGS and BGC823 GC cell lines were treated with the DNA-demethylating agent 5-aza-2'-deoxycytidine. However, treatment with trichostatin A, a histone deacetylase inhibitor, had no effect on PSD expression in any of the GC cell lines. Suppression of PSD by siRNA led to enhanced SGC7901 cell invasion. The depletion of PSD expression inhibited cell proliferation and decreased apoptosis in SGC7901 cell lines. Knockdown of the PSD expression decreased caspase-3 and -7 protein levels in SGC7901 cells. PSD gene may func-tion as a tumor suppressor in GC suggesting a vital role for DNA methylation and histone modification in PSD silencing. PSD expression might be a useful biomarker for epigenetic-based GC early diagnosis and may lead to the identification of new targets for pharmacological intervention.
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Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines.
Toxicol. Appl. Pharmacol.
PUBLISHED: 08-15-2014
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Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPAR?2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis.
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Preventive effects of Escherichia coli strain Nissle 1917 with different courses and different doses on intestinal inflammation in murine model of colitis.
Inflamm. Res.
PUBLISHED: 08-14-2014
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To analyze the in vivo effect of Escherichia coli Nissle 1917 (EcN) with different courses and different doses to Sprague-Dawley rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis.
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Synthesis and biological evaluation of hydroxycinnamic acid hydrazide derivatives as inducer of caspase-3.
Eur J Med Chem
PUBLISHED: 08-12-2014
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In order to generate compounds with superior antitumor activity and reduced toxicity, twelve new hydroxycinnamic acid hydrazide derivatives were synthesized and evaluated for their antiproliferative activities against two cancer cell lines (H1299 lung carcinoma cells and MCF-7 breast cancer cells), and compared to two normal counterparts (NL-20 lung epithelial cells and H184B5F5/M10 breast cells) by MTT method. The results demonstrated that some of these compounds possessed good antiproliferative activity against the two cancer cell lines. Among them, compound 2c was active against the growth of H1299 lung carcinoma cells with IC50 values of 1.50 ?M, which was more active than the positive topotecan (IC50 = 4.18 ?M). Simultaneously, it showed lower cytotoxic effects on normal NL-20 lung epithelial cells (IC50 > 10 ?M). Mechanism studies indicated that it induced cell cycle arrest at G2/M phase followed by activation of caspase-3, and consequently caused the cell death. Further studies on the structure optimization are ongoing.
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Implantable collamer lens versus iris-fixed phakic intraocular lens implantation to correct myopia: a meta-analysis.
PLoS ONE
PUBLISHED: 08-12-2014
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This study is a meta-analysis comparing the efficacy, predictability, and safety of correcting myopia via implantation of two types of phakic intraocular lens (PIOLs): the implantable collamer lens (ICL) and iris-fixed PIOL. The Cochrane library, Pubmed, and EMBASE were searched. Study selection, data exclusion, and quality assessment were performed by two independent observers. The pooled relative risk (RR), pooled standardized mean difference (SMD), and their 95% confidence intervals (CIs) were used to compare lenses. Seven studies, involving 511 eyes, were included. The pooled SMD in postoperative uncorrected distance visual acuity (UDVA) comparing ICLs to iris-fixed PIOLs was -0.22 (95% CI, -0.58 to 0.13; P =?.22). The pooled RR values of UDVA of 20/20 or better and of 20/40 or better comparing ICLs to iris-fixed PIOLs were 1.15 (95% CI, 0.89 to 1.47; P =?.29) and 1.01 (95% CI, 0.95 to 1.08; P =?.75), respectively. The pooled RR of loss of best spectacle-corrected visual acuity (BSCVA) and gain in BSCVA comparing ICLs to iris-fixed PIOLs were 1.20 (95% CI, 0.24 to 6.00; P =?.82) and 1.14 (95% CI, 0.89 to 1.48; P =?.31), respectively. The pooled RR comparing ICLs to iris-fixed PIOLs was 0.78 (95% CI, 0.29 to 2.12; P =?.63) for all reported complications and 2.80 (95% CI, 1.04 to 7.52; P =?.04) for severe complications. The pooled RR of achieving a result within ± 0.5 D (diopter) of the intended target comparing ICLs to iris-fixed PIOLs was 1.35 (95% CI, 1.04 to 1.77; P =?.03). Overall, there is no significant difference in efficacy between the two types of PIOLs or in safety, except that the ICL is associated with a greater incidence of severe complications, especially anterior subcapsular cataract, primarily in the Version 2 and Version 3 groups. However, ICL has better predictability.
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Effect of xinfeng capsule on pulmonary function in a adjuvant arthritis rat model.
J Tradit Chin Med
PUBLISHED: 08-09-2014
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To observe the relationship between reduced pulmonary function and regulatory T cells (Tregs) and helper T cells (Th)1/Th2 drift in a rat model of adjuvant arthritis (AA), and to study the impact of Xinfeng capsule (XFC) on pulmonary function and investigate the mechanism of action.
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Inception cohort study of workers exposed to toluene diisocyanate at a polyurethane foam factory: Initial one-year follow-up.
Am. J. Ind. Med.
PUBLISHED: 07-29-2014
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Isocyanates are one of the most commonly reported causes of occupational asthma; however, the risks of developing isocyanate asthma in modern production facilities remain poorly defined. We evaluated TDI exposure and respiratory health among an inception cohort of workers during their first year of employment at a new polyurethane foam production factory.
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[Prokaryotic expression and function analysis of Schistosoma japonicum calpain].
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi
PUBLISHED: 07-29-2014
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To clone and express recombinant calpain of Schistosoma japonicum (Sjcalpain), observe the distribution of Sjcalpain in S. japonicum cercariae and analyze its role in skin invasion.
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Synthesis of Nitrogen-Doped Mesoporous Carbon Spheres with Extra-Large Pores through Assembly of Diblock Copolymer Micelles.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-25-2014
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The synthesis of highly nitrogen-doped mesoporous carbon spheres (NMCS) is reported. The large pores of the NMCS were obtained through self-polymerization of dopamine (DA) and spontaneous co-assembly of diblock copolymer micelles. The resultant narrowly dispersed NMCS possess large mesopores (ca. 16 nm) and small particle sizes (ca. 200 nm). The large pores and small dimensions of the N-heteroatom-doped carbon spheres contribute to the mass transportation by reducing and smoothing the diffusion pathways, leading to high electrocatalytic activity.
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An improved method for guinea pig airway smooth muscle cell culture and the effect of SPFF on intracellular calcium.
Mol Med Rep
PUBLISHED: 07-15-2014
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The aim of the present study was to establish an improved method for in vitro guinea pig airway smooth muscle (ASM) cell culture and to evaluate the effect of 2-(4-amino-3-chloro-5-tri?uomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride (SPFF), a novel ?2-adrenoceptor agonist, on the release of intracellular calcium in cells. A procedure for the efficient isolation, culture, passage and characterization of the cells was described. Primary ASM cells of guinea pigs were cultured by modified tissue cultivation. The cells were identified by their morphological characteristics and immunocytochemistry. The relative inhibition of the release of intracellular calcium by drugs in the cells was measured by fluorometric quantification with fluorochrome Fura-2/AM. The results were as follows: a) The ASM cells of the guinea pigs were successfully cultured and subcultured by using our improved method and typical peak-valley characteristics were observed under the phase contrast microscope; b) data from immunocytochemical staining with specific ?-smooth muscle actin (?-SMA) demonstrated that the cells were ASM cells; c) the growth characteristics and cell viability demonstrated that the cells were in good condition and were able to be applied in the follow-up studies; d) the inhibitory effect of SPFF on the release of intracellular calcium was concentration?dependent when compared with the control and e) the potential mechanisms of SPFF on the inhibition of intracellular calcium may be independent of the ryanodine receptor, but may be closely associated with the inositol 1,4,5-trisphosphate receptor.
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Identification of dust storm source areas in West Asia using multiple environmental datasets.
Sci. Total Environ.
PUBLISHED: 07-11-2014
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Sand and Dust storms are common phenomena in arid and semi-arid areas. West Asia Region, especially Tigris-Euphrates alluvial plain, has been recognized as one of the most important dust source areas in the world. In this paper, a method is applied to extract SDS (Sand and Dust Storms) sources in West Asia region using thematic maps, climate and geography, HYSPLIT model and satellite images. Out of 50 dust storms happened during 2000-2013 and collected in form of MODIS images, 27 events were incorporated as demonstrations of the simulated trajectories by HYSPLIT model. Besides, a dataset of the newly released Landsat images was used as base-map for the interpretation of SDS source regions. As a result, six main clusters were recognized as dust source areas. Of which, 3 clusters situated in Tigris-Euphrates plain were identified as severe SDS sources (including 70% dust storms in this research). Another cluster in Sistan plain is also a potential source area. This approach also confirmed six main paths causing dust storms. These paths are driven by the climate system including Siberian and Polar anticyclones, monsoon from Indian Subcontinent and depression from north of Africa. The identification of SDS source areas and paths will improve our understandings on the mechanisms and impacts of dust storms on socio-economy and environment of the region.
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Investigation of Cardiovascular Effects of Tetrahydro-?-carboline sstr3 antagonists.
ACS Med Chem Lett
PUBLISHED: 07-10-2014
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Antagonism of somatostatin subtype receptor 3 (sstr3) has emerged as a potential treatment of Type 2 diabetes. Unfortunately, the development of our first preclinical candidate, MK-4256, was discontinued due to a dose-dependent QTc (QT interval corrected for heart rate) prolongation observed in a conscious cardiovascular (CV) dog model. As the fate of the entire program rested on resolving this issue, it was imperative to determine whether the observed QTc prolongation was associated with hERG channel (the protein encoded by the human Ether-à-go-go-Related Gene) binding or was mechanism-based as a result of antagonizing sstr3. We investigated a structural series containing carboxylic acids to reduce the putative hERG off-target activity. A key tool compound, 3A, was identified from this SAR effort. As a potent sstr3 antagonist, 3A was shown to reduce glucose excursion in a mouse oGTT assay. Consistent with its minimal hERG activity from in vitro assays, 3A elicited little to no effect in an anesthetized, vagus-intact CV dog model at high plasma drug levels. These results afforded the critical conclusion that sstr3 antagonism is not responsible for the QTc effects and therefore cleared a path for the program to progress.
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Controlling Porosity in Lignin-Derived Nanoporous Carbon for Supercapacitor Applications.
ChemSusChem
PUBLISHED: 07-02-2014
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Low-cost renewable lignin has been used as a precursor to produce porous carbons. However, to date, it has not been easy to obtain high surface area porous carbon without activation processes or templating agents. Here, we demonstrate that low molecular weight lignin yields highly porous carbon with more graphitization through direct carbonization without additional activation processes or templating agents. We found that molecular weight and oxygen consumption during carbonization are critical factors to obtain high surface area, graphitized porous carbons. This highly porous carbon from low-cost renewable lignin sources is a good candidate for supercapacitor electrode materials.
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De novo assembly of soybean wild relatives for pan-genome analysis of diversity and agronomic traits.
Nat. Biotechnol.
PUBLISHED: 07-02-2014
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Wild relatives of crops are an important source of genetic diversity for agriculture, but their gene repertoire remains largely unexplored. We report the establishment and analysis of a pan-genome of Glycine soja, the wild relative of cultivated soybean Glycine max, by sequencing and de novo assembly of seven phylogenetically and geographically representative accessions. Intergenomic comparisons identified lineage-specific genes and genes with copy number variation or large-effect mutations, some of which show evidence of positive selection and may contribute to variation of agronomic traits such as biotic resistance, seed composition, flowering and maturity time, organ size and final biomass. Approximately 80% of the pan-genome was present in all seven accessions (core), whereas the rest was dispensable and exhibited greater variation than the core genome, perhaps reflecting a role in adaptation to diverse environments. This work will facilitate the harnessing of untapped genetic diversity from wild soybean for enhancement of elite cultivars.
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Maternal periodontal disease and risk of preeclampsia: A meta-analysis.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 06-26-2014
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Research on the association between maternal periodontal disease and the risk of preeclampsia has generated inconsistent results. This meta-analysis was conducted to evaluate the association between maternal periodontal disease and the risk of preeclampsia. A literature search of PubMed and Embase was performed to identify relevant papers published before March 2013. Only observational studies that assessed maternal periodontal disease and the risk of preeclampsia were selected. Patients' periodontal status was examined at different time points during pregnancy or after delivery (at 14-32 weeks of gestation, within 48 h prior to or within 5 days after delivery). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for cases and controls. Cases were defined as women with concurrent hypertension and proteinuria after 20 weeks of gestation. Eleven studies involving 1118 women with preeclampsia and 2798 women without preeclampsia were identified and analyzed. Women with periodontal disease before 32 weeks of gestation had a 3.69-fold higher risk of developing preeclampsia than their counterparts without periodontal disease (OR=3.69; 95% CI=2.58-5.27). Periodontal disease within 48 h prior to delivery was associated with a 2.68-fold higher risk of preeclampsia (OR=2.68; 95% CI=1.39-5.18). Pregnant women with periodontal disease within 5 days after delivery had a 2.22-fold higher risk of preeclampsia than women without periodontal disease (OR=2.22; 95% CI=1.16-4.27). In conclusion, this meta-analysis suggests that maternal periodontal disease is an independent predictor of preeclampsia.
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Effects of Perturbation-Based Slip Training Using a Virtual Reality Environment on Slip-induced Falls.
Ann Biomed Eng
PUBLISHED: 06-15-2014
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The purpose of the current study was to design and evaluate the effectiveness of virtual reality training in improving recovery reactions and reducing fall frequency in older adults. Twenty-four older adults were recruited and randomly assigned to two groups (virtual reality training and control). Both groups underwent three sessions including baseline slip, training and transfer of training on slippery surface. Both groups experienced two slips, one during baseline and the other during the transfer of training trial. The training group underwent 12 simulated slips using a visual perturbation induced by tilting a virtual reality scene while walking on the treadmill and the control group performed normal walking during the training session. Kinematic and kinetic data were collected during all the sessions. Results demonstrated a reduced incidence of falls in the training group during the transfer of training trial as compared to the control group. The training group was able to transfer reactive control strategies learned during training to the second slip trial. The reactive adjustments included reduced slip distance. Additionally, gait parameters reflective of gait instability (stride length, step width, variability in stride velocity) reduced after walking in the VR environment for 15-20 min. The results indicated a beneficial effect of the virtual reality training in reducing slip severity and recovery kinematics in healthy older adults.
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Molecular-scale Hydrophilicity Induced by Solute: Molecular-thick Charged Pancakes of Aqueous Salt Solution on Hydrophobic Carbon-based Surfaces.
Sci Rep
PUBLISHED: 06-10-2014
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We directly observed molecular-thick aqueous salt-solution pancakes on a hydrophobic graphite surface under ambient conditions employing atomic force microscopy. This observation indicates the unexpected molecular-scale hydrophilicity of the salt solution on graphite surfaces, which is different from the macroscopic wetting property of a droplet standing on the graphite surface. Interestingly, the pancakes spontaneously displayed strong positively charged behavior. Theoretical studies showed that the formation of such positively charged pancakes is attributed to cation-? interactions between Na(+) ions in the aqueous solution and aromatic rings on the graphite surface, promoting the adsorption of water molecules together with cations onto the graphite surface; i.e., Na(+) ions as a medium adsorbed to the graphite surface through cation-? interactions on one side while at the same time bonding to water molecules through hydration interaction on the other side at a molecular scale. These findings suggest that actual interactions regarding carbon-based graphitic surfaces including those of graphene, carbon nanotubes, and biochar may be significantly different from existing theory and they provide new insight into the control of surface wettability, interactions and related physical, chemical and biological processes.
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Ambient analysis of leachable compounds from single-use bioreactors with desorption electrospray ionization time-of-flight mass spectrometry.
Rapid Commun. Mass Spectrom.
PUBLISHED: 06-10-2014
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Trace levels of bis(2,4-di-tert-butylphenyl)phosphate (BdtbPP) leaching from single-use bioreactors (SUBs) were recently found to be highly detrimental to mammalian cell growth. The traditional approach to detect the leachable requires time-consuming solvent extraction of SUBs. To assist the qualification of SUBs and/or their manufacturing raw materials in biopharmaceutical development and manufacturing, it is essential to develop a rapid and sensitive analytical approach for detecting this leachable and related compounds, which is described in this study.
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A designed peptide targeting CXCR4 displays anti-acute myelocytic leukemia activity in vitro and in vivo.
Sci Rep
PUBLISHED: 06-05-2014
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Leukemia cells highly expressing chemokine receptor CXCR4 can actively response to stroma derived factor 1? (CXCL12), trafficking and homing to the marrow microenvironment, which causes poor prognosis and relapse. Here we demonstrate that a novel designed peptide (E5) targeting CXCR4 inhibits CXCL12- and stroma-induced activation in multiple acute myelocytic leukemia (AML) cell lines and displays anti-AML activity. We show that E5 has high affinity to multiple AML cells with high CXCR4 level in a concentration dependent manner. E5 significantly inhibits CXCL12- or murine stromal cell (MS-5)-induced migration of leukemia cells and prevents the cells from adhering to stromal cells. Mechanistic studies demonstrate that E5 down-regulates CXCL12-induced phosphorylation of Akt, Erk, and p38, which affects the cytoskeleton F-actin organization and ultimately results in the inhibition of CXCL12- and stroma-mediated leukemia cell responses. E5 can induce concentration-dependent apoptosis in the four AML cell lines tested while did not affect the viability of MS-5 or human umbilical vein cell (ea.hy926) even at 80?µM, both of which have a low level of CXCR4. In vivo experimental results show that immunocompromised mice transplanted with HL-60 cells survived longer when treated with E5 twice a week in comparison to those treated with cyclophosphamide.
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Efficient solution-processed double-layer red OLEDs based on a new europium complex with a carbazole group.
Luminescence
PUBLISHED: 06-01-2014
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A new europium complex EuL3 (Phen) was used as guest dopant, and a blend of Polyvinylcarbazole and 2-(biphenyl-4-yl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole (PVK and PBD) as host matrix. Efficient red organic light-emitting devices (OLEDs) with double-layer structures were manufactured via a solution-processed technique. The guest-doped levels were 1, 3 and 5?wt% relative to the blend mass, respectively. For the 1?wt% doping-level device, the luminous efficiency and luminance were up to 2.96?cd/A and 635.78?cd/m(2) with emissions from both EuL3 (Phen) and from the host; for the 3?wt% doping-level device, the maximum luminous efficiency and luminance were 1.01?cd/A and 370.91?cd/m(2) for the single emission from EuL3 (Phen) only. Copyright © 2014 John Wiley & Sons, Ltd.
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MTA1 regulates higher-order chromatin structure and histone H1-chromatin interaction in-vivo.
Mol Oncol
PUBLISHED: 04-30-2014
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In the current study, for the first time, we found that metastasis-associated gene 1 (MTA1) was a higher-order chromatin structure organizer that decondenses the interphase chromatin and mitotic chromosomes. MTA1 interacts dynamically with nucleosomes during the cell cycle progression, prominently contributing to the mitotic chromatin/chromosome structure transitions at both prophase and telophase. We showed that the decondensation of interphase chromatin by MTA1 was independent of Mi-2 chromatin remodeling activity. H1 was reported to stabilize the compact higher-order chromatin structure through its interaction with DNA. Our data showed that MTA1 caused a reduced H1-chromatin interaction in-vivo. Moreover, the dynamic MTA1-chromatin interaction in the cell cycle contributed to the periodical H1-chromatin interaction, which in turn modulated chromatin/chromosome transitions. Although MTA1 drove a global decondensation of chromatin structure, it changed the expression of only a small proportion of genes. After MTA1 overexpression, the up-regulated genes were distributed in clusters along with down-regulated genes on chromosomes at parallel frequencies.
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Epidemiological situation and genetic analysis of H7N9 influenza viruses in Shanghai in 2013.
Arch. Virol.
PUBLISHED: 04-24-2014
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The first reported human case of H7N9 influenza virus infection in Shanghai prompted a survey of local avian strains of influenza virus, involving the analysis of a large number of samples taken from poultry, wild birds, horses, pigs, dogs and mice. Seven instances of H7N9 virus infection were identified by real-time RT-PCR (1.47 % of samples), all in chickens sold in live-poultry markets. H7N9 antibody was not detected in serum samples collected from local poultry farms since 2006. The two H7N9 virus strains in the live-poultry markets and one H9N2 virus strain in the same market were genetically characterized. Resequencing of two of the seven isolates confirmed that they closely resembled H7N9 virus strains characterized elsewhere. Various strains co-exist in the same market, presenting a continuing risk of strain re-assortment. The closure of live-poultry markets has been an effective short-term means of minimizing human exposure to H7N9 virus.
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FOXO1, TGF-? regulation and wound healing.
Int J Mol Sci
PUBLISHED: 04-07-2014
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Re-epithelialization is a complex process that involves migration and proliferation of keratinocytes, in addition to the production of cytokines and growth factors that affect other cells. The induction of transcription factors during these processes is crucial for successful wound healing. The transcription factor forkhead boxO-1 (FOXO1) has recently been found to be an important regulator of wound healing. In particular, FOXO1 has significant effects through regulation of transforming growth factor-beta (TGF-?) expression and protecting keratinocytes from oxidative stress. In the absence of FOXO1, there is increased oxidative damage, reduced TGF-?1 expression, reduced migration and proliferation of keratinocytes and increased keratinocytes apoptosis leading to impaired re-epithelialization of wounds.
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Adenovirus-mediated transfer of VEGF into marrow stromal cells combined with PLGA/TCP scaffold increases vascularization and promotes bone repair in vivo.
Arch Med Sci
PUBLISHED: 04-05-2014
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Large osseous defect remains a serious clinical problem due to the lack of sufficient blood supply and it has been proposed that this situation can be relieved by accelerating the formation of new vessels in the process of bone defect repair. The aim of this study was to develop a new type of artificial bone by transferring the VEGF gene into marrow stromal cells (MSCs) and seeding them into a porous scaffold.
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Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint.
Nat Commun
PUBLISHED: 03-30-2014
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The spindle assembly checkpoint arrests mitotic progression until each kinetochore secures a stable attachment to the spindle. Despite fluctuating noise, this checkpoint remains robust and remarkably sensitive to even a single unattached kinetochore among many attached kinetochores; moreover, the checkpoint is silenced only after the final kinetochore-spindle attachment. Experimental observations have shown that checkpoint components stream from attached kinetochores along microtubules towards spindle poles. Here we incorporate this streaming behaviour into a theoretical model that accounts for the robustness of checkpoint silencing. Poleward streams are integrated at spindle poles, but are diverted by any unattached kinetochore; consequently, accumulation of checkpoint components at spindle poles increases markedly only when every kinetochore is properly attached. This step change robustly triggers checkpoint silencing after, and only after, the final kinetochore-spindle attachment. Our model offers a conceptual framework that highlights the role of spatiotemporal regulation in mitotic spindle checkpoint signalling and fidelity of chromosome segregation.
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Biological characteristics of Taxol?resistant ovarian cancer cells and reversal of Taxol resistance by adenovirus expressing p53.
Mol Med Rep
PUBLISHED: 03-25-2014
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The development of acquired drug resistance is the primary cause of chemotherapy failure in the treatment of ovarian cancer. To examine the mechanism underlying Taxol (TAX) resistance in ovarian cancer and attempt to reverse it, the present study induced a TAX?resistant ovarian cancer cell line SKOV3/TAX using a gradient concentration increment method. The properties of the resistant cell line were initially investigated by proliferation, colony formation, adhesion and cell cycle analysis compared with control SKOV3 cells. To examine the mechanism, the expression of p53 upregulated modulator of apoptosis (PUMA) was compared between SKOV3/TAX and SKOV3 cells by western blot analysis. An adenovirus expressing p53 (Ad?p53), alone or in combination with TAX, was used to treat the drug?resistant ovarian cancer cells SKOV3/TAX. The effects of Ad?p53 on pro?apoptosis and the reversal of drug resistance were evaluated using flow cytometric analysis, cleaved?poly ADP?ribose polymerase detection, microscopic observation and MTT measurement. Compared with the control cells, the TAX?resistant ovarian cancer cell line SKOV3/TAX was characterized by reduced sensitivity to TAX treatment, a significantly slower proliferation rate, higher colony?forming efficiency and higher adhesion ability. However, no significant difference in cell cycle distribution was identified. PUMA, a potent pro?apoptotic protein, was markedly suppressed in the SKOV3/TAX cells. Ad?p53 infection stimulated the upregulation of PUMA and re?sensitized the resistant ovarian cancer cells to TAX by an apoptotic mechanism. Therefore, Ad?p53 infection is an effective gene therapy method to re?sensitize the resistant ovarian cancer cells to TAX by restoring the expression of PUMA.
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Reaction analysis and visualization of ReaxFF molecular dynamics simulations.
J. Mol. Graph. Model.
PUBLISHED: 03-02-2014
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ReaxFF MD (Reactive Force Field Molecular Dynamics) is a promising method for investigating complex chemical reactions in relatively larger scale molecular systems. The existing analysis tools for ReaxFF MD lack the capability of capturing chemical reactions directly by analyzing the simulation trajectory, which is critical in exploring reaction mechanisms. This paper presents the algorithms, implementation strategies, features, and applications of VARxMD, a tool for Visualization and Analysis of Reactive Molecular Dynamics. VARxMD is dedicated to detailed chemical reaction analysis and visualization from the trajectories obtained in ReaxFF MD simulations. The interrelationships among the atoms, bonds, fragments, species and reactions are analyzed directly from the three-dimensional (3D) coordinates and bond orders of the atoms in a trajectory, which are accomplished by determination of atomic connectivity for recognizing connected molecular fragments, perception of bond types in the connected fragments for molecules or radicals, indexing of all these molecules or radicals (chemical species) based on their 3D coordinates and recognition of bond breaking or forming in the chemical species for reactions. Consequently, detailed chemical reactions taking place between two sampled frames can be generated automatically. VARxMD is the first tool specialized for reaction analysis and visualization in ReaxFF MD simulations. Applications of VARxMD in ReaxFF MD simulations of coal and HDPE (high-density polyethylene) pyrolysis show that VARxMD provides the capabilities in exploring the reaction mechanism in large systems with complex chemical reactions involved that are difficult to access manually.
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The capsid protein p38 of turnip crinkle virus is associated with the suppression of cucumber mosaic virus in Arabidopsis thaliana co-infected with cucumber mosaic virus and turnip crinkle virus.
Virology
PUBLISHED: 02-28-2014
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Infection of plants by multiple viruses is common in nature. Cucumber mosaic virus (CMV) and Turnip crinkle virus (TCV) belong to different families, but Arabidopsis thaliana and Nicotiana benthamiana are commonly shared hosts for both viruses. In this study, we found that TCV provides effective resistance to infection by CMV in Arabidopsis plants co-infected by both viruses, and this antagonistic effect is much weaker when the two viruses are inoculated into different leaves of the same plant. However, similar antagonism is not observed in N. benthamiana plants. We further demonstrate that disrupting the RNA silencing-mediated defense of the Arabidopsis host does not affect this antagonism, but capsid protein (CP or p38)-defective mutant TCV loses the ability to repress CMV, suggesting that TCV CP plays an important role in the antagonistic effect of TCV toward CMV in Arabidopsis plants co-infected with both viruses.
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Clickable periodic mesoporous organosilicas: synthesis, click reactions, and adsorption of antibiotics.
Chemistry
PUBLISHED: 02-04-2014
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Pharmaceutical antibiotics are not easily removed from water by conventional water-treatment technologies and have been recognized as new emerging pollutants. Herein, we report the synthesis of clickable azido periodic mesoporous organosilicas (PMOs) and their use as adsorbents for the adsorption of antibiotics. Ethane-bridged PMOs, functionalized with azido groups at different densities, were synthesized by the co-condensation of 1,2-bis(trimethoxysilyl)ethane (BTME) and 3-azidopropyltrimethoxysilane (AzPTMS), in the presence of nonionic-surfactant triblock-copolymer P123, in an acidic medium. Four different alkynes were conjugated to azide-terminated PMOs by means of an efficient click reaction. The clicked PMOs showed improved adsorption capacity (241??g?g(-1)) for antibiotics (ciprofloxacin hydrochloride) compared with azido-functionalized PMOs because of the enhanced ?-? stacking interactions. These results indicate that click reactions can introduce multifunctional groups onto PMOs, thus demonstrating the great potential of PMOs for environmental applications.
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Cloning and characterization of a mannose binding C-type lectin gene from salivary gland of Aedes albopictus.
Parasit Vectors
PUBLISHED: 01-28-2014
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The studies on sialomes have shown that hematophagous mosquito saliva consists of a lot of pharmacologically active proteins, in which C-type lectins have been identified and regarded as an important component of saliva. The previous studies showed that C-type lectins play crucial roles not only in innate immunity but also in promoting disease transmission in mammals. However, the function and mechanism of C-type lectins from the mosquito sialome is still elusive.
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Effect of Ce doping of TiO2 support on NH3-SCR activity over V2O5-WO3/CeO2-TiO2 catalyst.
J Environ Sci (China)
PUBLISHED: 01-21-2014
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CeO2-TiO2 composite supports with different Ce/Ti molar ratios were prepared by a homogeneous precipitation method, and V2O5-WO3/CeO2-TiO2 catalysts for the selective catalytic reduction (SCR) of NOx with NH3 were prepared by an incipient-wetness impregnation method. These catalysts were characterized by means of BET, XRD, UV-Vis, Raman and XPS techniques. The results showed that the catalytic activity of V2O5-WO3/TiO2 was greatly enhanced by Ce doping (molar ratio of Ce/Ti=1/10) in the TiO2 support. The catalysts that were predominantly anatase TiO2 showed better catalytic performance than the catalysts that were predominantly fluorite CeO2. The Ce additive could enhance the surface adsorbed oxygen and accelerate the SCR reaction. The effects of O2 concentration, ratio of NH3/NO, space velocity and SO2 on the catalytic activity were also investigated. The presence of oxygen played an important role in NO reduction. The optimal ratio of NH3/NO was 1/1 and the catalyst had good resistance to SO2 poisoning.
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Proteoglycans and glycosaminoglycans improve toughness of biocompatible double network hydrogels.
Adv. Mater. Weinheim
PUBLISHED: 01-17-2014
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Based on the molecular stent concept, a series of tough double-network hydrogels (St-DN gels) made from the components of proteoglycan aggregates - chondroitin sulfate proteoglycans (1), chondroitin sulfate (2), and sodium hyaluronate (3) - are successfully developed in combination with a neutral biocompatible polymer. This work demonstrates a promising method to create biopolymer-based tough hydrogels for biomedical applications.
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Metastasis-associated gene 1 promotes invasion and migration potential of laryngeal squamous cell carcinoma cells.
Oncol Lett
PUBLISHED: 01-08-2014
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Overexpression of the metastasis-associated gene 1 (MTA1) has previously been found to be associated with progression of various cancer types to the metastasis stage. The function of MTA1 in laryngeal squamous cell carcinoma (LSCC) remains unclear. To explore the significance of MTA1 in the invasion and migration processes in LSCC, gene transfection and RNA interference (RNAi) were performed to study the biological function of MTA1 in the LSCC cell line, HEP-2. Results showed that MTA1 promoted the invasion, adhesion and migration behavior of LSCC cells. RNAi against MTA1 significantly decreased the malignant phenotypes of cancer cells. MTA1 may be important in the process of LSCC invasion and metastasis.
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Epithelial-to-mesenchymal transition in human esophageal cancer associates with tumor progression and patient's survival.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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The epithelial-mesenchymal transition (EMT) is an essential step in invasion and metastasis of human cancers. Identification of EMT status would help us to properly understand the mechanism of cancer metastasis and progression. In the present study, tissue microarray and immunohistochemical staining of two important markers, E-cadherin and Vimentin, were used to characterize the EMT status in human esophageal cancer. We selected the appropriate cut-off values of expression levels of E-cadherin and Vimentin, and found 63 out of 105 cases of esophageal cancers underwent EMT. And we also found that in the subgroup with (T3 + T4), the ratio of patients undergoing EMT was significantly higher than that in the subgroup with (T1 + T2) (P = 0.0097), and in the subgroup with metastasis, the ratio of patients undergoing EMT was significantly higher than that in the subgroup with no metastasis (P = 0.0253). The log-rank survival analysis showed that the overall survival rate of the patients undergoing EMT was significantly poorer than that of the patients with wide type status (P = 0.0278, HR = 2.470, 95% CI: 1.971~2.970). In the COX model analysis, we also found that the EMT status of the esophageal cancer patients could be used as an independent risk factor for the prediction of prognosis of this malignancy (P = 0.026, HR = 2.306, 95% CI: 1.103~4.824). Thus, our present study successfully established a method by using tissue microarray and the markers, E-cadherin and Vimentin, to conveniently and properly identify the EMT status in human esophageal cancer, and revealed that the EMT status significantly associated with invasion, metastasis and prognosis in this malignancy.
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Hypoxia-induced deregulation of miR-126 and its regulative effect on VEGF and MMP-9 expression.
Int J Med Sci
PUBLISHED: 01-01-2014
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miR-126, the miRNA considered to be specially expressed in endothelial cells and hematopoietic progenitor cells, is strongly associated with angiogenesis. The purpose is to evaluate the role of miR-126 in hypoxia-induced angiogenesis and the possible mechanisms.
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Linear relationship between water wetting behavior and microscopic interactions of super-hydrophilic surfaces.
J Chem Phys
PUBLISHED: 12-24-2013
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Using molecular dynamics simulations, we show a fine linear relationship between surface energies and microscopic Lennard-Jones parameters of super-hydrophilic surfaces. The linear slope of the super-hydrophilic surfaces is consistent with the linear slope of the super-hydrophobic, hydrophobic, and hydrophilic surfaces where stable water droplets can stand, indicating that there is a universal linear behavior of the surface energies with the water-surface van der Waals interaction that extends from the super-hydrophobic to super-hydrophilic surfaces. Moreover, we find that the linear relationship exists for various substrate types, and the linear slopes of these different types of substrates are dependent on the surface atom density, i.e., higher surface atom densities correspond to larger linear slopes. These results enrich our understanding of water behavior on solid surfaces, especially the water wetting behaviors on uncharged super-hydrophilic metal surfaces.
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Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis: study protocol of a multicenter randomized controlled trial.
J Integr Med
PUBLISHED: 12-05-2013
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Rheumatoid arthritis (RA), as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA.
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DNA promoter and histone H3 methylation downregulate NGX6 in gastric cancer cells.
Med. Oncol.
PUBLISHED: 11-25-2013
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Nasopharyngeal carcinoma-associated gene 6 (NGX6) is a novel candidate tumor metastasis suppressor gene. Our study was to determine whether DNA hypermethylation and histone modification at the NGX6 gene promoter play important roles in silencing NGX6 expression in gastric cancer. NGX6 expression was downregulated in all gastric cancer cells and 76.19 % tissues. In three GC cell lines, hypermethylated NGX6 loci were characterized by histone H3-K9 hypoacetylation and hypermethylation. Trichostatin A treatment could moderately increase H3-K9 acetylation at the silenced loci; however, it had no effect on DNA and H3-K9 methylation and minimal effects on NGX6 expression. In contrast, 5aza-2-deoxycytidine treatment could rapidly decrease DNA and H3-K9 methylation at the silenced loci, leading to the reexpression of NGX6. Combined treatment with 5aza-2-deoxycytidine and trichostatin A had synergistic effects on the reexpression of NGX6 at the hypermethylation loci. Our current study shows that NGX6 expression is downregulated in GC cancer cells and tissues due to NGX6 promoter methylation and H3-K9 methylation, but not H3-K9 acetylation. Our findings indicate that the downregulation of NGX6 expression contributes to the development and progression of gastric cancer. More studies are needed to determine the precise mechanism of NGX6 in the progression of gastric cancer.
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[Enhanced anticancer effects of 5-DFUR on colorectal cancer cell lines SW480 and LOVO by transfection with thymidine phosphorylase cDNA].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 11-22-2013
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To study the change of ability to transform from 5-deoxy-fluorouracil monophosphate (5-DFUR) to fluorouracil (5-FU) in human colon cancer cell lines SW480 and LOVO which transfected with thymidine phosphorylase (TP) gene. And to discuss the anti-cancer activity of 5-DFUR to SW480 and LOVO cells.
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Ion Enrichment on the Hydrophobic Carbon-based Surface in Aqueous Salt Solutions due to Cation-? Interactions.
Sci Rep
PUBLISHED: 10-23-2013
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By incorporating cation-? interactions to classic all-atoms force fields, we show that there is a clear enrichment of Na(+) on a carbon-based ? electron-rich surface in NaCl solutions using molecular dynamics simulations. Interestingly, Cl(-) is also enriched to some extend on the surface due to the electrostatic interaction between Na(+) and Cl(-), although the hydrated Cl(-)-? interaction is weak. The difference of the numbers of Na(+) and Cl(-) accumulated at the interface leads to a significant negatively charged behavior in the solution, especially in nanoscale systems. Moreover, we find that the accumulation of the cations at the interfaces is universal since other cations (Li(+), K(+), Mg(2+), Ca(2+), Fe(2+), Co(2+), Cu(2+), Cd(2+), Cr(2+), and Pb(2+)) have similar adsorption behaviors. For comparison, as in usual force field without the proper consideration of cation-? interactions, the ions near the surfaces have a similar density of ions in the solution.
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Clickable SBA-15 to Screen Functional Groups for Adsorption of Antibiotics.
Chem Asian J
PUBLISHED: 10-08-2013
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Pharmaceutical antibiotics, as emerging contaminants, are usually composed of several functional groups that endow them with the ability to interact with adsorbents through different interactions. This makes the preparation of adsorbents tedious and time-consuming to screen appropriate functionalized materials. Herein, we describe the synthesis of clickable SBA-15 and demonstrate its feasibility as a screening material for the adsorption of antibiotics based on similar adsorption trends on materials with similar functional groups obtained by a click reaction and cocondensation/grafting methods.
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Berberine Induces Apoptosis in p53-Null Leukemia Cells by Down-Regulating XIAP at the Post-Transcriptional Level.
Cell. Physiol. Biochem.
PUBLISHED: 09-23-2013
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Background: Berberine exerts anticancer activities both in vitro and in vivo through different mechanisms. However, the underlying molecular mechanisms of berberine induced p53-independent apoptosis remain unclear. Methods: The p53-null leukemia cell line EU-4 cells were exposed to berberine. Then the cell viability and apoptosis were determined. Western blot and PCR were employed to detect the expression of apoptosis related protein, XIAP and MDM2. Small interfering RNA (siRNA) was applied to knock down endogenous expression of MDM2 and XIAP. Results: Berberine induced p53-independent, XIAP-mediated apoptotic cell death in p53-null leukemia cells. Treatment with berberine resulted in suppression of XIAP protein in a dose- and time- dependent manner. Berberine induced down-regulation of XIAP protein involving inhibition of MDM2 expression and a proteasome-dependent pathway. Moreover, inhibition of XIAP by berberine or siRNA increased the sensitivity of leukemia cells to doxorubicin-induced apoptosis. Conclusion: Our findings characterize the molecular mechanisms of berberine-induced caspase activation and subsequent apoptosis, and berberine may be a novel candidate inducer of apoptosis in leukemia cells, which normally lack p53 expression. © 2013 S. Karger AG, Basel.
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