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Find video protocols related to scientific articles indexed in Pubmed.
A Chemical Tuned Strategy to Develop Novel Irreversible EGFR-TK Inhibitors with Improved Safety and Pharmacokinetic Profiles.
J. Med. Chem.
PUBLISHED: 11-20-2014
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Gatekeeper T790M mutation in EGFR is the most prevalent factor underlying acquired resistance. Acrylamide-bearing quinazoline derivatives are powerful irreversible inhibitors for overcoming resistance. Nevertheless, concerns about the risk of non-specific covalent modification have motivated the development of novel cysteine-targeting inhibitors. In this paper, we demonstrate that fluoro-substituted olefins can be tuned to alter Michael addition reactivity. Incorporation of these olefins into the quinazoline templates produced potent EGFR inhibitors with improved safety and pharmacokinetic properties. A lead compound 5a was validated against EGFRWT, EGFR T790M as well as A431 and H1975 cancer cell lines. Additionally, compound 5a displayed a weaker inhibition against the EGFR-independent cancer cell line SW620 when compared withafatinib. Oral administration of 5a at a dose of 30mg/kg induced tumor regression in a murine-EGFRL858R/T790M driven H1975 xenograft model. Also, 5a exhibited improved oral bioavailability and safety, as well as favorable tissue distribution properties and enhanced brain uptake. These findings provide the basis of a promising strategy toward the treatment of NSCLC patients with drug resistance.
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A novel fluorene-based aggregation-induced emission (AIE)-active gold(i) complex with crystallization-induced emission enhancement (CIEE) and reversible mechanochromism characteristics.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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A new fluorene-based AIE-active gold(i) complex was designed and synthesized. The novel luminogen exhibits a crystallization-induced emission enhancement (CIEE) effect and reversible mechanochromic behavior with fluorescence changes between green and yellow emissions.
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Blockade of the Activation of T Cells Around ?-Cell by the Targeted CTLA-4 Ig at the Surface of ?-Cell.
Cell Biochem. Biophys.
PUBLISHED: 11-20-2014
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Diabetes mellitus affects 347 million people worldwide, and over 80 % of diabetes deaths occur in low- and middle-income countries. Type 1 diabetes (T1D) is characterized by the attacks of the body's own immune system on the pancreatic ?-cells. In this work, we present a new CTLA-4 Ig targeting at the surface of ?-cell and prepare it from Escherichia coli aiming at clearing activated T cells around ?-cells and avoiding all-round decline in systematic immunity. This fusion protein is composed of CTLA-4-Ig part and ?-cell-targeting part, with properties of the therapeutic effect of CTLA-4-Ig and selective binding to ?-cells. In preliminary biological activity assay, our results verified the feasibility of ?-cell-targeting strategy and its activity of CTLA-4-Ig part. The fusion protein recognizes and binds specifically to CD80(+) and CD86(+) cells as well as ?-cell, but not to control cells, displaying the potential to be used as a feasible and effective treatment of T1D with lessened side effect.
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WemIQ: An accurate and robust isoform quantification method for RNA-seq data.
Bioinformatics
PUBLISHED: 11-20-2014
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The deconvolution of isoform expression from RNA-seq remains challenging because of non-uniform read sampling and subtle differences among isoforms.
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Nanoparticles with Precise Ratiometric Co-Loading and Co-Delivery of Gemcitabine Monophosphate and Cisplatin for Treatment of Bladder Cancer.
Adv Funct Mater
PUBLISHED: 11-15-2014
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Combination chemotherapy is a common practice in clinical management of malignancy. Synergistic therapeutic outcome is only achieved when tumor cells are exposed to cells in an optimal ratio. However, due to diverse physicochemical properties of drugs, no free drug cocktails or nanomaterials are capable of co-loading and co-delivering drugs at an optimal ratio. Herein, we develop a novel nano-platform with precise ratiometric co-loading and co-delivery of two hydrophilic drugs for synergistic anti-tumor effects. Based on previous work, we utilize a solvent displacement method to ratiometrically load dioleoyl phosphatidic acid (DOPA)-gemcitabine monophosphate and DOPA coated cisplatin-precipitate nanocores into the same PLGA NP. These cores are designed to have similar hydrophobic surface properties. GMP and cisplatin are engineered into PLGA NP at an optimal synergistic ratio (5:1, mol:mol) with over 70% encapsulation efficiency and were ratiometrically taken up by tumor cells in vitro and in vivo. These PLGA NP exhibit synergistic anti-cancer effects in a stroma-rich bladder tumor model. A single injection of dual drugs in PLGA NP can significantly inhibit tumor growth. This nanomaterial-system solves problems related to ratiometric co-loading and co-delivery of different hydrophilic moieties and provides possibilities for co-loading hydrophilic drugs with hydrophobic drugs for combination therapy.
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Protein Tyrosine Phosphatase 1B Impairs Diabetic Wound Healing Through Vascular Endothelial Growth Factor Receptor 2 Dephosphorylation.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 11-15-2014
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Impaired wound healing is a major complication of diabetes mellitus. The mechanisms that govern wound healing, however, are complex and incompletely understood. In the present study, we determined the inhibitory role of protein tyrosine phosphatase 1B (PTP1B) in the process of diabetic wound healing.
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[Evolution of brain temperature in ischemic tissues by (1)H magnetic resonance spectroscopy].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 11-14-2014
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To explore the application of temperature measurement technique by (1)H magnetic resonance spectroscopy (MRS) in an ischemia monkey model.
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Changes of serum cytokines-related Th1/Th2/Th17 concentration in patients with postmenopausal osteoporosis.
Gynecol. Endocrinol.
PUBLISHED: 11-12-2014
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Abstract Background: Postmenopausal osteoporosis is now hypothetically considered to be an autoimmune and inflammatory process in which many pro-inflammatory and T cell-derived cytokines play important roles in the loss of bone mass. For instance, interleukin-2 (IL-2), interferon-? (IFN-?), and tumor necrosis factor-? (TNF-?) secreted by Th1 and IL-6, IL-4, and IL-10 secreted by Th2 have been shown to be involved in the pathogenesis of osteoporosis. Interleukin-17 (IL-17) is a characteristic cytokine secreted by Th17 cells of the CD4?+?subgroup. Although IL-17 has been shown to enhance bone resorption in ovariectomized mouse model, bone cells and genetic research, human-related studies of IL-17 are few. Methods: According to WHO classification of osteoporosis by the T scores of BMD, the subjects were divided into the postmenopausal osteoporosis group (T scores?-2.5), the postmenopausal osteopenia group (-2.5?
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[Enolase of Streptococcus suis serotype 2 is involved in the antiphagocytosis of Streptococcus suis].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 11-07-2014
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Objective To prepare the recombinant enolase of Streptococcus suis (SsEno), analyze the effect of SsEno on the antiphagocytosis by antibody-blocking assay in the human blood bactericidal model, and identify the human fibrinogen (hFg)-binding activity of SsEno protein. Methods SsEno gene was amplified using the primers designed according to 05ZYH33 genome sequences and cloned into the expression vector pET28a to construct recombinant plasmids. The plasmids were transformed into E.coli BL21(DE3) and induced to express by IPTG. The expression level was analyzed by SDS-PAGE. The recombinant proteins were purified by nickel affinity chromatography and identified by Western blotting. High-titer specific antiserum against SsEno was prepared by immunizing rabbits with the purified recombinant proteins. The impact of SsEno on antiphagocytosis was analyzed by antibody-blocking assay in the human blood bactericidal model. In addition, the specific binding activity with hFg was identified by Far-Western blotting and ELISA. Results The prokaryotic expression vector of hisSsEno (SsEno with His tag) was constructed and high-purity recombinant expressed protein was purified. In specific antibody blocking assay, antiserum against the SsEno significantly decreased the percent of survival bacteria as observed in high virulent strain 05ZYH33. Additionally, hisSsEno was proved to have the specific binding activity with hFg. Conclusion SsEno was found to be a potential antiphagocytic factor of S. suis with a specific binding to hFg, suggesting that SsEno play an important role in antiphagocytosis of S. suis.
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Molecularly Imprinted Solid-Phase Extraction for Selective Extraction of Bisphenol Analogues in Beverages and Canned Food.
J. Agric. Food Chem.
PUBLISHED: 11-07-2014
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This study aimed to develop a selective analytical method for the simultaneous determination of seven bisphenol analogues in beverage and canned food samples by using a new molecularly imprinted polymer (MIP) as a sorbent for solid-phase extraction (SPE). Liquid chromatography coupled to triple-quadruple tandem mass spectrometry (LC-MS/MS) was used to identify and quantify the target analytes. The MIP-SPE method exhibited a higher level of selectivity and purification than the traditional SPE method. The developed procedures were further validated in terms of accuracy, precision, and sensitivity. The obtained recoveries varied from 50% to 103% at three fortification levels and yielded a relative standard deviation (RSD, %) of less than 15% for all of the analytes. The limits of quantification (LOQ) for the seven analytes varied from 0.002 to 0.15 ng/mL for beverage samples and from 0.03 to 1.5 ng/g for canned food samples. This method was used to analyze real samples that were collected from a supermarket in Beijing. Overall, the results revealed that bisphenol A and bisphenol F were the most frequently detected bisphenols in the beverage and canned food samples and that their concentrations were closely associated with the type of packaging material. This study provides an alternative method of traditional SPE extraction for screening bisphenol analogues in food matrices.
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Class I KNOX transcription factors promote differentiation of cambial derivatives into xylem fibers in the Arabidopsis hypocotyl.
Development
PUBLISHED: 11-06-2014
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The class I KNOX transcription factors SHOOT MERISTEMLESS (STM) and KNAT1 are important regulators of meristem maintenance in shoot apices, with a dual role of promoting cell proliferation and inhibiting differentiation. We examined whether they control stem cell maintenance in the cambium of Arabidopsis hypocotyls, a wood-forming lateral meristem, in a similar fashion as in the shoot apical meristem. Weak loss-of-function alleles of KNAT1 and STM led to reduced formation of xylem fibers - highly differentiated cambial derivatives - whereas cell proliferation in the cambium was only mildly affected. In a knat1;stm double mutant, xylem fiber differentiation was completely abolished, but residual cambial activity was maintained. Expression of early and late markers of xylary cell differentiation was globally reduced in the knat1;stm double mutant. KNAT1 and STM were found to act through transcriptional repression of the meristem boundary genes BLADE-ON-PETIOLE 1 (BOP1) and BOP2 on xylem fiber differentiation. Together, these data indicate that, in the cambium, KNAT1 and STM, contrary to their function in the shoot apical meristem, promote cell differentiation through repression of BOP genes.
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Enhanced visible light photocatalytic activity of ZnO doped with down-conversion NaSrBO3:Tb(3+) phosphors.
Dalton Trans
PUBLISHED: 11-05-2014
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ZnO-NaSrBO3:Tb(3+) (ZNT) composites were successfully synthesized via microwave-assisted reaction of the ZnO precursor with a NaSrBO3:Tb(3+) suspension using a microwave synthesis system. The morphology, structure and photocatalytic performance in the degradation of methylene blue (MB) were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, UV-vis absorption spectroscopy, fluorescence spectrophotometry and electrochemical impedance spectroscopy, respectively. The results show that the ZNT composites exhibit enhanced photocatalytic activity in the degradation of MB with a maximum degradation rate of 97% under visible light irradiation compared with pure ZnO (12%), which is ascribed to the increased light absorption and the reduction of photoelectron-hole pair recombination in ZnO with the introduction of NaSrBO3:Tb(3+), as well as the light down-converting effect of NaSrBO3:Tb(3+), which facilitates the self-sensitized degradation of MB.
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Asymmetric inheritance of cytoophidia in Schizosaccharomyces pombe.
Biol Open
PUBLISHED: 11-02-2014
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A general view is that Schizosaccharomyces pombe undergoes symmetric cell division with two daughter cells inheriting equal shares of the content from the mother cell. Here we show that CTP synthase, a metabolic enzyme responsible for the de novo synthesis of the nucleotide CTP, can form filamentous cytoophidia in the cytoplasm and nucleus of S. pombe cells. Surprisingly, we observe that both cytoplasmic and nuclear cytoophidia are asymmetrically inherited during cell division. Our time-lapse studies suggest that cytoophidia are dynamic. Once the mother cell divides, the cytoplasmic and nuclear cytoophidia independently partition into one of the two daughter cells. Although the two daughter cells differ from one another morphologically, they possess similar chances of inheriting the cytoplasmic cytoophidium from the mother cell, suggesting that the partition of cytoophidium is a stochastic process. Our findings on asymmetric inheritance of cytoophidia in S. pombe offer an exciting opportunity to study the inheritance of metabolic enzymes in a well-studied model system.
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Atomic connectomics signatures for characterization and differentiation of mild cognitive impairment.
Brain Imaging Behav
PUBLISHED: 10-31-2014
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In recent years, functional connectomics signatures have been shown to be a very valuable tool in characterizing and differentiating brain disorders from normal controls. However, if the functional connectivity alterations in a brain disease are localized within sub-networks of a connectome, then accurate identification of such disease-specific sub-networks is critical and this capability entails both fine-granularity definition of connectome nodes and effective clustering of connectome nodes into disease-specific and non-disease-specific sub-networks. In this work, we adopted the recently developed DICCCOL (dense individualized and common connectivity-based cortical landmarks) system as a fine-granularity high-resolution connectome construction method to deal with the first issue, and employed an effective variant of non-negative matrix factorization (NMF) method to pinpoint disease-specific sub-networks, which we called atomic connectomics signatures in this work. We have implemented and applied this novel framework to two mild cognitive impairment (MCI) datasets from two different research centers, and our experimental results demonstrated that the derived atomic connectomics signatures can effectively characterize and differentiate MCI patients from their normal controls. In general, our work contributed a novel computational framework for deriving descriptive and distinctive atomic connectomics signatures in brain disorders.
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[Simultaneous determination of sugar alcohols and sugars in functional foods by precolumn ultraviolet derivatization--high performance liquid chromatography].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-25-2014
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To establish a method using precolumn ultraviolet derivatization coupled with high performance liquid chromatography (HPLC) for simultaneous determination of erythritol, xylitol, galactitol, sorbitol, mannitol, maltitol, glucose and sucrose in functional foods.
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[Influencing factors for operational performance of a biofilm reactor with microbubble aeration using SPG membrane].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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The microbubble-aerated biofilm reactor provides a feasibility to apply microbubble aeration in aerobic wastewater treatment processes. In this study, Shirasu porous glass (SPG) membranes were used for microbubble aeration in a fixed bed biofilm reactor treating synthetic municipal wastewater. The influencing factors for operational performance of the bioreactor were investigated, including operating parameters, SPG membrane fouling and its structural changes. The results indicated that there was no significant influences of air flux, organic loading rate and packed bed on COD removal and an average COD removal efficiency of 80% -90% could be achieved under different operating conditions. On the other hand, the dissolved oxygen (DO) concentrations decreased significantly along with reducing air flux or increasing organic loading rate. As a result, the ammonia removal deteriorated gradually and the average ammonia removal efficiency decreased from 80% -90% to 20% -30% At the same time, the total nitrogen (TN) removal achieved in the simultaneous nitrification and denitrification process was also reduced from 30% -40% to about 20% , due to nitrification inhibition. Higher available porosity could be obtained when ring packing was used in the fixed bed, resulting in improvement of contaminant removal performance. An oxygen utilization efficiency of close to 100% could be achieved at low air fluxes or high organic loading rates during microbubble aeration. Both biofilm growth and organic foulant accumulation on SPC, membrane surface contributed to membrane fouling after long-term operation. The average pore size and porosity of SPG membrane increased significantly due to the chemical corrosion caused by alkali NaClO solution used for online cleaning. Then the air permeation of SPG membrane was affected by membrane fouling and destroyed pore structure.
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[Atrazine wastewater treatment in a SPG membrane-aerated genetically engineered microorganism biofilm reactor].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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Membrane-aerated biofilm reactor (MABR) represent a novel membrane-biological wastewater treatment technology. In addition, bioaugmented treatment using genetically engineered microorganism (GEM) biofilm in MABR is proposed to improve refractory pollutant removal. In the present study, a SPG membrane aerated-biofilm reactor (SPG-MABR) with GEM biofilm formed on the SPG membrane surface was applied to treat atrazine wastewater. The influences of air pressure, biofilm biomass and liquid velocity on the performance of the SPG-MABR were investigated. The variation of GEM biofilm during the SPG-MABR operation was observed. The results indicated that the increased air pressure could promote atrazine and COD removal as well as re-oxygenation by increasing oxygen permeability coefficient. A higher biofilm biomass could also enhance atrazine and COD removal, but simultaneously reduce the re-oxygenation rate because biofilm thickness and oxygen transfer resistance increased. When liquid velocity in the SPG-MABR was decreased under laminar flow condition, atrazine and COD removal was improved due to the facilitated contaminant diffusion from wastewater to biofilm. The atrazine removal efficiency reached to 98.6% in the SPG-MABR after 5d treatment at air pressure of 300 kPa, biofilm biomass of 25 g x m(-2) and liquid velocity of 0.05 m x s(-1). The microbial polymorphism of GEM biofilm was observed during the SPG-MABR operation. The surface of GEM biofilm was gradually covered by other microbial cells and the distribution of GEM cells reduced, but inside the GEM biofilm, the GEM cells were still dominant.
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Exhaled Hydrogen Sulfide Predicts Airway Inflammation Phenotype in COPD.
Respir Care
PUBLISHED: 10-23-2014
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The role of exhaled H2S as a marker of airway inflammation and its relationship with COPD severity remain to be determined.
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CD8 T Cells Are Involved in Skeletal Muscle Regeneration through Facilitating MCP-1 Secretion and Gr1high Macrophage Infiltration.
J. Immunol.
PUBLISHED: 10-22-2014
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Inflammatory microenvironments play a key role in skeletal muscle regeneration. The infiltration of CD8 T cells into injured muscle has been reported. However, the role of CD8 T cells during skeletal muscle regeneration remains unclear. In this study, we used cardiotoxin-induced mouse skeletal muscle injury/regeneration model to investigate the role of CD8 T cells. Muscle regeneration was impaired and matrix deposit was increased in CD8?-deficient mice compared with wild-type (WT) mice whose CD8 T cells were infiltrated into damaged muscle after cardiotoxin injection. Adoptive transfer of CD8 T cells to CD8?-deficient mice improved muscle regeneration and inhibited matrix remodeling. Compared with WT mice, CD8? deficiency limited the recruitment of Gr1(high) macrophages (MPs) into muscle, resulting in the reduction of satellite cell number. The expression of MCP-1 (MCP-1/CCL2), which regulates the migration of Gr1(high) MPs, was reduced in CD8?-deficient mice compared with WT mice. Coculture CD8 T cells with MPs promoted MCP-1 secretion. The i.m. injection of MCP-1 markedly promoted the recruitment of Gr1(high) MPs and improved muscle regeneration in CD8?-deficient mice. We conclude that CD8 T cells are involved in skeletal muscle regeneration by regulating the secretion of MCP-1 to recruit Gr1(high) MPs, which facilitate myoblast proliferation.
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[ALK protein expression and gene fusion in bronchoscopic specimens of lung adenocarcinoma].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 10-21-2014
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To explore ALK protein expression and gene fusion in formalin-fixed and paraffin-embedded (FFPE) specimens obtained from lung cancer by bronchoscopy, and to investigate the relationship between ALK status and clinicopathological characteristics of the patients.
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[Effects of miR-106b expression on the proliferation of human hepatocellular carcinoma cells].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 10-21-2014
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To investigate the effects of miR-106b expression on the proliferation of human hepatocellular carcinoma cells.
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[Chemical constituents of lateral roots of Aconitum carmichaelii Debx].
Yao Xue Xue Bao
PUBLISHED: 10-18-2014
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In order to find the cardiotonic constituents of lateral roots of Aconitum carmichaelii Debx., the investigation was carried out. Silica gel column chromatography, Sephadex LH-20, medium-pressure MCI and reverse phase ODS column chromatography were used to separate the 90% EtOH extract of the lateral roots of Aconitum carmichaelii Debx. The structures of the isolated compounds have been identified by chemical properties and spectroscopic analyses. Ten compounds were isolated and their structures were elucidated as benzoic acid-5-hydroxy-2-benzoyl-amino methyl ester (1), honokiol (2), pinoresinol (3), salicylic acid (4), p-hydroxy-cinnamic acid (5), songorine (6), karakoline (7), mesaconitine (8), hypaconitine (9) and 14-benzoylhypaconitine (10), separetely. Compound 1 is a new compound and its structure has been established by NMR, HR-ESI-MS, UV, IR and X-Ray. Compound 2-5 are isolated from the lateral roots of Aconitum carmichaelii Debx. for the first time.
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Orthogonally polarized dual-wavelength Nd:YAlO3 laser at 1341 and 1339??nm and sum-frequency mixing for an emission at 670??nm.
Appl Opt
PUBLISHED: 10-17-2014
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We report a diode-pumped continuous wave (cw) orthogonally polarized dual-wavelength laser at 1339 and 1341 nm with a single b-cut Nd:YAlO3 (Nd:YAP) crystal. By adjusting the tilt angle of the uncoated glass plate inserted in the laser cavity, we can control the cavity losses of two polarized directions. The output wavelengths are 1339 nm in a-axis polarization and 1341 nm in c-axis polarization, respectively, which are orthogonal to each other. At an incident pump power of 17.3 W, the cw output power obtained at 1339 and 1341 nm is 1.6 and 2.3 W, respectively. Furthermore, intracavity sum-frequency mixing at 1339 and 1341 nm was then realized in a KTiOPO4 (KTP) crystal to reach the red range. To our knowledge, this is the first work realizing an orthogonally polarized dual-wavelength Nd:YAP laser based on the F43/2-4I13/2 transition. Such a dual-wavelength laser would be especially valuable as a compact laser source to generate terahertz emission because the frequency difference between 1339 and 1341 nm is about 0.9 THz.
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Total Syntheses of Menisporphine and Daurioxoisoporphine C Enabled by Photoredox-Catalyzed Direct C-H Arylation of Isoquinoline with Aryldiazonium Salt.
J. Org. Chem.
PUBLISHED: 10-15-2014
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Isoquinoline alkaloids are attractive natural products due to their diverse chemical structures as well as remarkable bioactivities. Herein, we report the concise total syntheses of two isoquinoline alkaloids, menisporphine and daurioxoisoporphine C, through a mild and efficient photoredox-catalyzed direct C-H arylation of isoquinoline core with aryldiazonium salt. This new strategy is complementary to the conventional isoquinoline synthesis and would provide us a useful means to achieve a more convergent and flexible approach to access diverse isoquinoline structures.
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Ultraselective electrochemiluminescence biosensor based on locked nucleic acid modified toehold-mediated strand displacement reaction and junction-probe.
Analyst
PUBLISHED: 10-10-2014
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Locked nucleic acid (LNA) is applied in toehold-mediated strand displacement reaction (TMSDR) to develop a junction-probe electrochemiluminescence (ECL) biosensor for single-nucleotide polymorphism (SNP) detection in the BRCA1 gene related to breast cancer. More than 65-fold signal difference can be observed with perfectly matched target sequence to single-base mismatched sequence under the same conditions, indicating good selectivity of the ECL biosensor.
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MethBank: a database integrating next-generation sequencing single-base-resolution DNA methylation programming data.
Nucleic Acids Res.
PUBLISHED: 10-09-2014
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DNA methylation plays crucial roles during embryonic development. Here we present MethBank (http://dnamethylome.org), a DNA methylome programming database that integrates the genome-wide single-base nucleotide methylomes of gametes and early embryos in different model organisms. Unlike extant relevant databases, MethBank incorporates the whole-genome single-base-resolution methylomes of gametes and early embryos at multiple different developmental stages in zebrafish and mouse. MethBank allows users to retrieve methylation levels, differentially methylated regions, CpG islands, gene expression profiles and genetic polymorphisms for a specific gene or genomic region. Moreover, it offers a methylome browser that is capable of visualizing high-resolution DNA methylation profiles as well as other related data in an interactive manner and thus is of great helpfulness for users to investigate methylation patterns and changes of gametes and early embryos at different developmental stages. Ongoing efforts are focused on incorporation of methylomes and related data from other organisms. Together, MethBank features integration and visualization of high-resolution DNA methylation data as well as other related data, enabling identification of potential DNA methylation signatures in different developmental stages and accordingly providing an important resource for the epigenetic and developmental studies.
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Visible-light-induced chemoselective reductive decarboxylative alkynylation under biomolecule-compatible conditions.
Chem. Commun. (Camb.)
PUBLISHED: 10-04-2014
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We report a visible-light-induced reductive decarboxylative C(sp(3))-C(sp) bond coupling reaction to construct aryl, alkyl and silyl substituted alkynes at room temperature in organic solvents or neutral aqueous solutions. This chemoselective alkynylation was compatible with various functional groups and biomolecules, and did not affect the protein enzyme activity.
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MicroRNA-105 suppresses cell proliferation and inhibits PI3K/AKT signaling in human hepatocellular carcinoma.
Carcinogenesis
PUBLISHED: 10-03-2014
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A growing amount of evidence supports that microRNA (miRNA) dysregulation is involved in cancer progression by directly downregulating multiple targets. Elucidating the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. In the current study, we found that miR-105 expression was markedly downregulated in both hepatocellular carcinoma (HCC) cell lines and clinical HCC tissues, compared with normal human hepatocyte and adjacent non-cancerous tissues, respectively. Ectopic miR-105 expression suppressed, whereas inhibiting miR-105 promoted the proliferation and tumorigenicity of HCC cells both in vitro and in vivo. Furthermore, we demonstrated that miR-105 could deactivated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway by downregulating insulin receptor substrate-1, 3-phosphoinositide-dependent protein kinase-1 and AKT1 directly, resulting in increasing cyclin-dependent kinase inhibitors 1A and 1B (p21(Cip1) and p27(Kip1)) and decreasing cyclin D1 expression in HCC. Therefore, our results suggest that miR-105 functions as a potential tumor suppressor by inhibiting the PI3K/AKT signaling pathway and might represent a potential therapeutic target for HCC patients.
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Glaucoma secondary to systemic lupus erythematosus.
Chin. Med. J.
PUBLISHED: 10-02-2014
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Glaucoma secondary to systemic lupus erythematosus (SLE) is an uncommon but serious complication that threatens vision and therefore cannot be neglected. A few cases of secondary glaucoma resulting from lupus-induced or iatrogenic ocular impairments have been reported in association with SLE. However, a systematic analysis of the diagnosis and treatment of glaucoma secondary to SLE has not been reported in the literature. The aim of this study is to further investigate the relationship between glaucoma and SLE.
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Characterizing and Differentiating Brain State Dynamics via Hidden Markov Models.
Brain Topogr
PUBLISHED: 09-30-2014
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Functional connectivity measured from resting state fMRI (R-fMRI) data has been widely used to examine the brain's functional activities and has been recently used to characterize and differentiate brain conditions. However, the dynamical transition patterns of the brain's functional states have been less explored. In this work, we propose a novel computational framework to quantitatively characterize the brain state dynamics via hidden Markov models (HMMs) learned from the observations of temporally dynamic functional connectomics, denoted as functional connectome states. The framework has been applied to the R-fMRI dataset including 44 post-traumatic stress disorder (PTSD) patients and 51 normal control (NC) subjects. Experimental results show that both PTSD and NC brains were undergoing remarkable changes in resting state and mainly transiting amongst a few brain states. Interestingly, further prediction with the best-matched HMM demonstrates that PTSD would enter into, but could not disengage from, a negative mood state. Importantly, 84 % of PTSD patients and 86 % of NC subjects are successfully classified via multiple HMMs using majority voting.
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Total Syntheses of (-)-Huperzine Q and (+)-Lycopladines B and C.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 09-25-2014
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Utilizing a late-stage enamine bromofunctionalization strategy, the twelve-step total synthesis of (-)-huperzine Q was accomplished. Furthermore, the first total syntheses of (+)-lycopladines B and C are described. An unprecedented X-ray crystal structure of an unusual epoxyamine intermediate is also reported, and the synthetic application of this intermediate in natural product synthesis is demonstrated.
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[HPLC determination of two phenylpropanoid amides in solani melongenae radix from different cultivation regions].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-24-2014
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A quantitative HPLC-DAD method was developed for simultaneous determination of N-trans-p-coumaroyloctopamine and N-trans-p-coumaroyltyramine in Solani Melongenae Radix from different cultivation regions in China The separation was performed on an Agilent Eclipse XDB C18 column (4.6 mm x 250 mm, 5 microm) at 30 degrees C with a gradient elution of methanol and 0.1% formic acid in water as mobile phase. The flow rate was set at 1.0 mL x min(-1) and the detection wavelength was 300 nm. The calibration curves of N-trans-p-coumaroyloctopamine and N-trans-p-coumaroyltyramine were linear over the ranges of 2.84-68.16, 3.10-74.40 mg x L(-1), and the average recoveries (n = 9) were 99.30% and 102.8%, respectively. The developed method was successfully applied for the analysis of sixteen samples from different cultivation regions in China, which indicated that the method is simple, rapid, accurate, and reliable for quality evaluation of Solani Melongenae Radix.
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Neurotrophic Factor Artemin Promotes Invasiveness and Neurotrophic Function of Pancreatic Adenocarcinoma in Vivo and in Vitro.
Pancreas
PUBLISHED: 09-23-2014
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The aim of this study was to investigate the effect of the neurotrophic factor Artemin on neuroplasticity and perineural invasion of pancreatic adenocarcinoma.
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[Diagnosis and clinical characteristics of patients with non-allergic rhinitis].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-23-2014
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To explore a step-by-step exclusive diagnosis and analyze the clinical characters of non-allergic rhinitis (NAR).
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Mammalian cell display for rapid screening scFv antibody therapy.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 09-22-2014
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Human antibodies are beginning to draw attention for use in immune gene therapy. The efficient generation of effective therapeutic monoclonal antibodies suitable for the treatment of cancers and infectious diseases would be enormously valuable. Antibody display methods are increasingly used to screen human monoclonal antibodies. Here we report the construction of a mammalian cell display method derived from a naive antibody repertoire, for which human single-chain variable fragments (scFv) have been transiently displayed on 293T cell surfaces based on a pDisplay vector. The sizes of the current pDisplay-scFv antibody repertoires have been estimated to be 0.74 × 10(7). An immunoblot assay confirmed the expression of the scFv antibody library. The subcellular distribution of ErbB3-scFv expression plasmid facilitated the display of ErbB3 scFv on the cell membrane surface and the efficiency of the display was evaluated by fluorescence-activated cell sorting. This method of mammalian cell display was verified by successfully screening ErbB3 scFv candidates. A published scFv control was used to confirm the feasibility of the ErbB3 scFv screening process. Three ErbB3 scFv candidates were produced and they were found to have affinity similar to the published scFv candidate. Thus, the present screening system provided an optimal alternative for rapid acquisition of a novel candidate scFv sequence to target genes with high affinity in vitro.
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Resting state cortical oscillations of PD patients without and with Subthalamic deep brain stimulation, a MEG study.
J Clin Neurophysiol
PUBLISHED: 09-19-2014
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In this study, we investigate the modification to cortical oscillations of Parkinson's disease (PD) patients by subthalamic deep brain stimulation (STN-DBS).
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Peculiar surface-interface properties of nanocrystalline ceria-cobalt oxides with enhanced oxygen storage capacity.
Phys Chem Chem Phys
PUBLISHED: 09-19-2014
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Peculiar surface-interface properties of nanocrystalline ceria-cobalt oxides were evidenced by X-ray diffraction, transmission electron microscopy and X-ray absorption spectroscopy. It was found that cobalt foreign cations modify the surface oxygen vacancies of ceria at the atomic level, inducing the exposure of well-defined reactive faces between the ceria-host and the cobalt oxide interface. These modifications of the surface-interface structure promoted a remarkable increase in the oxygen storage capacity of ceria nanocrystals.
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Effect of ulinastatin on the expression and distribution of high mobility group box 1 in human colon carcinoma cells in vitro.
Mol Med Rep
PUBLISHED: 09-18-2014
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The aim of the present study was to investigate the in vitro effects of ulinastatin (UTI) on the proliferation, invasion, apoptosis, expression and distribution of high mobility group box 1 (HMGB1) and the expression of nuclear factor ?B (NF??B) in human colon carcinoma LoVo cells. The cells were divided into control (untreated), UTI1 (400 U/ml UTI), UTI2 (800 U/ml UTI) and UTI3 (1,600 U/ml UTI) groups. The cell proliferation, invasion, apoptosis and the gene and protein expression of HMGB1 and NF??B were detected using a tetrazolium assay, Transwell cell invasion assays, a caspase?3 activity assay, western blot analysis and reverse transcription quantitative polymerase chain reaction, respectively. The distribution of HMGB1 was detected using immunofluorescence. LoVo cell proilferation decreased the most in the UTI3 group followed, in order, by the UTI2, UTI1 and control groups. UTI inhibited invasion in LoVo cells and the inhibitory effect was enhanced as the UTI concentration increased. The activity of caspase?3 increased the least in the control group followed, in order, by the UTI1, UTI2 and UTI3 groups. UTI inhibited the expression of HMGB1 and NF??B, and decreased the cytoplasmic distribution of HMGB1. Thus, UTI inhibited LoVo cell proliferation and induced LoVo cell apoptosis, the mechanism of which may be associated with a decreased in the expression of HMGB1 and NF??B, and the cytoplasmic distribution of HMGB1.
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Plasma miRNA levels correlate with sensitivity to bone mineral density in postmenopausal osteoporosis patients.
Biomarkers
PUBLISHED: 09-18-2014
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Abstract In our study, we detect the levels of three micro-RNAs (miRNAs; miR-21, miR-133a and miR-146a) in the plasma of 120 Chinese postmenopausal women who were divided into three groups (normal, osteopenia and osteoporosis) according to the T-scores. Downregulation of miR-21, as well as upregulation of miR-133a, was validated in the plasma of osteoporosis and osteopenia patients versus the normal group. The difference in expression regarding the miR-146a level in plasma among the three groups was not significant (p?>?0.01). The circulating miRNA expression levels and bone mineral density (BMD) were examined during a multiple correlation analysis as a dependent variable after adjusting for age, weight and height. We have demonstrated that specific miRNAs species are significantly changed in the plasma of osteoporosis and osteopenia patients and correlated with the BMD. Our study suggested a potential use of miR-21 and miR-133a as sensitive and plasma biomarkers for postmenopausal osteoporosis.
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Divergent Influence of MicroRNA-21 Deletion on Murine Colitis Phenotypes.
Inflamm. Bowel Dis.
PUBLISHED: 09-16-2014
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MicroRNAs (miRNAs) acting as negative regulators of gene expression are differentially expressed in intestinal tissues of patients with inflammatory bowel disease (IBD). Assessing the functions of miRNAs in murine colitis facilitates elucidating the role of specific miRNAs in human IBD. We aimed to determine the miRNA signature of several models of colitis and to assess the influence of miR-21 on intestinal inflammation.
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[Application of temperature sensitive yeast models with definite target in the screening of potential human Pin1 inhibitors].
Yao Xue Xue Bao
PUBLISHED: 09-13-2014
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This study is to explore new lead compounds by inhibition of Pin1 for anticancer therapy using temperature sensitive mutants. As Pin1 is conserved from yeast to human, we established a high-throughput screening method for Pin1 inhibitors, which employed yeast assay. This method led to the identification of one potent hits, 8-11. In vitro, 8-11 inhibited purified Pin1 enzyme activity with IC50 of (10.40 +/- 1.68) micromol x L(-1), induced G1 phase arrest and apoptosis, showed inhibitory effects on a series of cancer cell proliferation, reduced Cyclin D1 expression, was defined as reciprocally matched for protein-ligand complex in virtual docking analysis and reduced cell migration ability. In vivo, we could observe reduction of tumor volume after treatment with 8-11 in xenograft mice compared with vehicle DMSO treatment. Altogether, these results provide for the first time the involvement of 8-11 in the anticancer activity against Pin1.
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[Design of UV annular imaging system for atmospheric limb detection].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 09-12-2014
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In order to meet the requirements of imaging the surrounding 360 degree scene at one time without rotating the optical system and satisfy the UV limb detecting, a panoramic imaging system was presented for atmospheric UV limb detection. First, considering the special working band and innovative application and proceeding from the basic principle of traditional panoramic annular lens, the curvature radius of four spherical surfaces was adjusted, combined with the detector size so that can get the best MTF. Then, based on the aberration theory, the relay lens system was designed to make up the aberration produced by panoramic annular lens. The separation of positive and negative lens combination with different refraction and Abbe number was used. The negative lens used fused silica, while the positive lens used calcium fluoride, so to correct the apochromatism. Finally, the optical system was optimized with CODE-V and the important tolerance parameters were listed, so that the subsequent processing can be requested. The design results show that the diameter of 80% encircled energy of UV panoramic limb imaging system is below 11 microm,which is smaller than the pixel size of CCD, and the MTF value of the system is higher than 0.7 @ 384 mm(-1) over all fields. These data satisfy the requirements of the system and prove the feasibility of panoramic imaging system in atmospheric UV limb detection.
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[Protective role of PTEN inhibition against liver ischemia-reperfusion injury in mice and its underlying mechanisms].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-10-2014
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To investigate whether inhibition of phosphatase and tensin homologue deleted on chromosome ten (PTEN) is protective against liver ischemia-reperfusion injury (IRI) in mice and to explore its possible mechanism.
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The effect of magnetic field on electrochemically deposited calcium phosphate/collagen coatings.
Biomed Mater Eng
PUBLISHED: 09-10-2014
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Nanostructured calcium phosphate/collagen (CaP/COL) coatings were deposited on the carbon/carbon (C/C) composites through electrochemical deposition (ECD) under magnetic field. The effect of magnetic fields with different orientations on the morphology and composition was investigated. Both the morphology and composition of the coatings could be altered by superimposed magnetic field. Under zero magnetic field and magnetic field, three-dimensional network structure consisting of collagen fibers and CaP were formed on the C/C substrate. The applied magnetic field in the electric field helped to form nanostructured and plate-like CaP on collagen fibers. For the ECD under magnetic field, the Ca/P molar ratio of the coatings was lower than the one under B=0. This may be contributed to the decreased electrical resistance or the increased electrical conductivity of electrolyte solutions under magnetic field. The nanosized CaP/COL coatings exhibited the similar morphology to the human bone and could present excellent cell bioactivity and osteoblast functions.
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[Effects of different intensity exercise on blood glucose, adolescent obesity rats insulin sensitivity and RBP4].
Wei Sheng Yan Jiu
PUBLISHED: 09-10-2014
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To discuss the effects of different intensity exercise on blood glucose, adolescent obesity rats insulin sensitivity and RBP4.
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Refolding of a fully functional flavivirus methyltransferase revealed that S-adenosyl methionine but not S-adenosyl homocysteine is co-purified with flavivirus methyltransferase.
Protein Sci.
PUBLISHED: 09-08-2014
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Methylation of flavivirus RNA is vital for its stability and translation in the infected host cell. This methylation is mediated by the flavivirus methyltransferase (MTase), which methylates the N7 and 2'-O positions of the viral RNA cap by utilizing S-adenosyl-L-methionine (SAM) as a methyl donor. In this report, we demonstrate that SAM, in contrast to the reaction by-product S-adenosyl-L-homocysteine (SAH) which was assumed previously, is co-purified with the Dengue (DNV) and West Nile virus (WNV) MTases produced in Escherichia coli (E. coli). This endogenous SAM can be removed by denaturation and refolding of the MTase protein. The refolded MTase of DNV serotype 3 (DNV3) displays methylation activity comparable to native enzyme, and its crystal structure at 2.1 Å is almost identical to that of native MTase. We characterized the binding of Sinefungin (SIN), a previously described SAM-analog inhibitor of MTase function, to the native and refolded DNV3 MTase by isothermal titration calorimetry, and found that SIN binds to refolded MTase with more than sixteen times the affinity of SIN binding to the MTase purified natively. Moreover, we show that SAM is also co-purified with other flavivirus MTases, indicating that purification by refolding may be a generally applicable tool for studying flavivirus MTase inhibition.
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Estimating the shape and size of supramolecular assemblies by variable temperature diffusion ordered spectroscopy.
Org. Biomol. Chem.
PUBLISHED: 09-05-2014
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Reported is characterization of the self-assembly of ?-conjugated oligomers, molecules studied recently in photovoltaic devices, using variable temperature diffusion ordered spectroscopy (VT-DOSY). Iterative fitting of diffusion coefficient versus temperature data to a modified Stokes-Einstein equation, molecular modelling, and comparison to non-assembling model compounds, has allowed estimation of assembly size, shape, and molecularity.
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An ultrasensitive label-free electrochemical biosensor for microRNA-21 detection based on a 2'-O-methyl modified DNAzyme and duplex-specific nuclease assisted target recycling.
Chem. Commun. (Camb.)
PUBLISHED: 09-05-2014
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Based on a highly efficient 2'-O-methyl modified G-quadruplex-hemin DNAzyme and duplex-specific nuclease (DSN) assisted target recycling, a novel label-free electrochemical biosensor for microRNA-21 (miR-21) detection is developed here. By employing the strategy, this DNA biosensor can detect as low as 8 aM miR-21 and exhibits high discrimination ability even against a single-base mismatch.
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Using computer-extracted image features for modeling of error-making patterns in detection of mammographic masses among radiology residents.
Med Phys
PUBLISHED: 09-05-2014
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Mammography is the most widely accepted and utilized screening modality for early breast cancer detection. Providing high quality mammography education to radiology trainees is essential, since excellent interpretation skills are needed to ensure the highest benefit of screening mammography for patients. The authors have previously proposed a computer-aided education system based on trainee models. Those models relate human-assessed image characteristics to trainee error. In this study, the authors propose to build trainee models that utilize features automatically extracted from images using computer vision algorithms to predict likelihood of missing each mass by the trainee. This computer vision-based approach to trainee modeling will allow for automatically searching large databases of mammograms in order to identify challenging cases for each trainee.
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Effect of yizhitongxuan decoction on learning and memory ability, Gaq/11 expression and Na(+)-K(+)-ATP enzyme activity in rat models of Alzheimer's disease.
J Tradit Chin Med
PUBLISHED: 09-05-2014
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To study the effects of Yizhitongxuan decoction on learning and memory abilities, Gaq/11 expression and Na(+)-K(+)-ATP enzyme activity in rat models of Alzheimer's disease (AD) caused by injecting Abeta25-35 into the hippocampus.
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Elevated circulating lipocalin-2 levels independently predict incident cardiovascular events in men in a population-based cohort.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 09-04-2014
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Adipose tissue inflammation and perturbation of adipokine secretion may contribute to the pathogenesis of cardiovascular diseases (CVD). Lipocalin-2 (LCN2), mainly released from adipocytes, has been shown to be positively associated with CVD in cross-sectional studies. We aimed to evaluate the association of LCN2 with CVD involving a population-based cohort recruited from the Shanghai Diabetes Study.
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The clinical implications of Crk-like adaptor protein expression in papillary thyroid microcarcinoma.
Tumour Biol.
PUBLISHED: 09-04-2014
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Papillary thyroid microcarcinoma (PMC) is the most common subtype of thyroid carcinomas with satisfactory prognosis. Crk-like (CrkL) adaptor protein was identified in the development of many carcinomas. However, the clinical implications of CrkL protein in PMC were still unknown. Here, we conducted immunohistochemistry to test and analyze CrkL expression in papillary thyroid carcinoma (PTC) (50 cases), PMC (50 cases), and nodular goiter (50 cases), and then western blot further identified the expression of CrkL proteins. In our present study, the positive rate and the mean optical density (MOD) value of CrkL expression in PTC and PMC tissues were statistically significantly different, compared with nodular goiter (p?=?0.021, 0.037) and normal thyroid tissues (p?=?0.003, 0.009), respectively. In addition, CrkL expression was not associated with age, gender, and tumor number. Conversely, significant differences between CrkL expression and metastasis (p?
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Synthesis and biological evaluation of liguzinediol mono- and dual ester prodrugs as promising inotropic agents.
Molecules
PUBLISHED: 09-02-2014
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The potent positive inotropic effect, together with the relatively low safety risk of liguzinediol (LZDO), relative to currently available inotropic drugs, has prompted us to intensively research and develop LZDO as a potent positive inotropic agent. In this study, to obtain LZDO alternatives for oral chronic administration, a series of long-chain fatty carboxylic mono- and dual-esters of LZDO were synthesized, and preliminarily evaluated for physicochemical properties and bioconversion. Enhanced lipophilic properties and decreased solubility of the prodrugs were observed as the side chain length increased. All esters showed conspicuous chemical stability in phosphate buffer (pH 7.4). Moreover, the enzymatic hydrolysis of esters in human plasma and human liver microsomes confirmed that the majority of esters were converted to LZDO, with release profiles that varied due to the size and structure of the side chain. In vivo pharmacokinetic studies following oral administration of monopivaloyl (M5), monodecyl (M10) and monododecyl (M12) esters demonstrated the evidently extended half-lives relative to LZDO dosed alone. In particular the monopivaloyl ester M5 exhibited an optimal pharmacokinetic profile with appropriate physiochemical characteristics.
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Absolute Lymphocyte Count Recovery at 1 month After Transplantation Predicts Favorable Outcomes of Patients With Hepatocellular Carcinoma.
J. Gastroenterol. Hepatol.
PUBLISHED: 09-02-2014
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Absolute Lymphocyte Count(ALC) and the recovery of ALC after treatment have been identified as a prognostic biomarker for several malignancies. In this study, we aimed to investigate the prognostic role of peritransplant ALC and ALC recovery after liver transplantation(LT) in HCC patients.
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Trace metals in estuaries in the Russian Far East and China: case studies from the Amur River and the Changjiang.
Sci. Total Environ.
PUBLISHED: 09-02-2014
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This paper compares the distributions of dissolved and particulate forms of Mn, Fe, Ni, Cu, Zn, Cd, and Pb in the estuaries of the largest rivers in East Asia: the Amur River and the Changjiang (Yangtze River). High suspended solid concentrations, elevated pH, and relatively low dissolved trace metal concentrations are characteristics of the Changjiang. Elevated dissolved Fe and Mn concentrations, neutral pH, and relatively low suspended solid concentrations are characteristics of the Amur River. The transfer of dissolved Fe to suspended forms is typical in the Amur River estuary, though Cd and Mn tend to mobilize to solution, and Cu and Ni are diluted in the estuarine system. Metal concentrations in suspended matter in the Amur River estuary are controlled by the ratio of terrigenous riverine material, enriched in Al and Fe, and marine biogenic particles, enriched in Cu, Mn, Cd, and in some cases Ni. The increase in dissolved forms of Mn, Fe, Ni, Cu, Cd, and Pb compared with river end-member is unique to the Changjiang estuary. Particle-solution interactions are not reflected in bulk suspended-solid metal concentrations in the Changjiang estuary due to the dominance of particulate forms of these metals. Cd is an exception in the Changjiang estuary, where the increase in dissolved Cd is of comparable magnitude to the decrease in particulate Cd. Despite runoff in the Amur River being lower than that in the Changjiang, the fluxes of dissolved Mn, Zn and Fe in the Amur River exceed those in the Changjiang. Dissolved Ni, and Cd fluxes are near equal in both estuaries, but dissolved Cu is lower in the Amur River estuary. The hydrological and physico-chemical river characteristics are dominated at the assessment of river influence on the adjoining coastal sea areas despite differences in estuarine processes.
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RNF26 temporally regulates virus-triggered type I interferon induction by two distinct mechanisms.
PLoS Pathog.
PUBLISHED: 09-01-2014
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Viral infection triggers induction of type I interferons (IFNs), which are critical mediators of innate antiviral immune response. Mediator of IRF3 activation (MITA, also called STING) is an adapter essential for virus-triggered IFN induction pathways. How post-translational modifications regulate the activity of MITA is not fully elucidated. In expression screens, we identified RING finger protein 26 (RNF26), an E3 ubiquitin ligase, could mediate polyubiquitination of MITA. Interestingly, RNF26 promoted K11-linked polyubiquitination of MITA at lysine 150, a residue also targeted by RNF5 for K48-linked polyubiquitination. Further experiments indicated that RNF26 protected MITA from RNF5-mediated K48-linked polyubiquitination and degradation that was required for quick and efficient type I IFN and proinflammatory cytokine induction after viral infection. On the other hand, RNF26 was required to limit excessive type I IFN response but not proinflammatory cytokine induction by promoting autophagic degradation of IRF3. Consistently, knockdown of RNF26 inhibited the expression of IFNB1 gene in various cells at the early phase and promoted it at the late phase of viral infection, respectively. Furthermore, knockdown of RNF26 inhibited viral replication, indicating that RNF26 antagonizes cellular antiviral response. Our findings thus suggest that RNF26 temporally regulates innate antiviral response by two distinct mechanisms.
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BMP2-Smad-Mediated SH-SY5Y Neuroblastoma Cell Proliferation and Neurite Outgrowth Are Regulated Through Dynamin-Dependent Endocytosis.
Mol. Neurobiol.
PUBLISHED: 08-28-2014
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Smad signalling plays an important role in the neurobiology, which can be induced by bone morphogenetic protein 2 (BMP2) and be regulated by endocytosis. However, it is still unclear whether endocytosis regulates BMP2-Smad-mediated proliferation and neurite growth in SH-SY5Y. Here we investigated the effects of endocytosis on BMP2-mediated Smad signallings using the neuroblastoma SH-SY5Y cell. In this study, using dynasore, dynamin-dependent endocytosis was assayed; using Western blot and neurite outgrowth assay, BMP2-Smad signalling and SH-SY5Y neurite outgrowth were measured. In the present study, our data showed that dynasore indeed inhibited dynamin-dependent endocytosis in SH-SY5Y. The Smad 1/5/8 phosphorylation level was upregulated in response to exogenous BMP2, while BMP2-induced p-Smad 1/5/8 expression was significantly suppressed due to BMP2 and dynasore co-treatment (p?
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Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: involvement of the tumor suppressor miR30a and its target gene SOX4.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-25-2014
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Tumor metastasis is the leading cause of mortality and morbidity of prostate cancer (PCa) patients. Epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. Recent evidence suggested that diabetic patients treated with metformin have lower PCa risk and better prognosis. This study was aimed to investigate the effects of metformin on EMT in PCa cells and the possible microRNA (miRNA)-based mechanisms. MiRNAs have been shown to regulate various processes of cancer metastasis. We herein showed that metformin significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell cycle arrest and inhibits invasiveness and motility capacity of Vcap cells. Metformin could inhibit TGF-?-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p=0.013), Vimentin (p=0.002) and the decrease of E-cadherin (p=0.0023) and ?-catenin (p=0.034) at mRNA and protein levels. Notably, we demonstrated significant upregulation of miR30a levels by metformin (P<0.05) and further experiments indicated that miR30a significantly inhibits proliferation and EMT process of Vcap cells. Interestingly, we identified that SOX4, a previously reported oncogenic transcriptional factor and modulator of EMT, is a direct target gene of miR30a. Finally, we screened the expression of miR30a and SOX4 in 84 PCa cases with radical prostatectomy. Of note, SOX4 overexpression is significantly associated with decreased levels of miR30a in PCa cases. In all, our study suggested that inhibition of EMT by metformin in PCa cells may involve upregulation of miR30a and downregulation of SOX4.
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Ethanol Activation of PKA Mediates Single-Minded 2 Expression in Neuronal Cells.
Mol. Neurobiol.
PUBLISHED: 08-21-2014
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Prenatal ethanol exposure can cause extensive apoptotic neurodegeneration throughout the developing central nervous system (CNS), which results in cognitive deficits and memory decline. However, the underlying mechanisms need further study. Single-minded 2 (Sim2), a transcriptional repressor, is reportedly involved in diseases that impair learning and memory, such as Down syndrome (DS) and Alzheimer's disease. It is still unknown whether Sim2 is involved in regulating ethanol-mediated neuronal injury that might ultimately lead to neuronal dysfunction and subsequent learning and memory deficits. To study the effects of ethanol on Sim2 expression and neuronal injury, we used animal models and cell culture experiments. Our results indicated that in SH-SY5Y cells, ethanol exposure increased Sim2 expression and levels of cleaved caspase 3, which is a marker for cells undergoing apoptosis. Silencing Sim2 expression attenuated caspase 3 activation and cellular apoptosis. We also found that protein kinase A (PKA) activation induced Sim2 expression, as did ethanol. Inhibiting the PKA signaling pathway with H-89 decreased Sim2 expression and cleavage of caspase 3 that was induced by ethanol in vivo and in vitro. We further found that PKA regulated Sim2 expression at the transcriptional level. These results demonstrate that ethanol leads to increased Sim2 expression via the PKA pathway, ultimately resulting in apoptotic cell death.
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Preparation of poly(vinylphenylboronic acid)-chain-grafted poly(glycidylmethacrylate-co-ethylenedimethacrylate) beads for the selective enrichment of glycoprotein.
J Sep Sci
PUBLISHED: 08-19-2014
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Surface-initiated atom transfer radical polymerization was successfully used to prepare 4-vinylphenylboronic acid-functionalized poly(glycidylmethacrylate-co-ethylenedimethacrylate) beads for the selective enrichment of glycoprotein from complex biological samples in this study. The modified bead surfaces were characterized using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The sorption behaviors, including adsorption isotherms, incubation time and pH effect, were investigated. The results demonstrated that the boronated beads have a high affinity for glycoprotein, which is due to the well-defined boronic acid brushes on the beads surfaces. Furthermore, the polyvinylphenylboronic acid-grafted poly(glycidylmethacrylate-co-ethylenedimethacrylate) beads were used to efficiently enrich and purify glycoprotein from real egg white samples and ?-fetoprotein from human serum samples. The mass spectrometry results demonstrated that the polyvinylphenylboronic acid-grafted poly(glycidylmethacrylate-co-ethylenedimethacrylate) beads are a suitable material for the enrichment of glycosylated protein from complex biological samples. This article is protected by copyright. All rights reserved.
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Alpha synuclein is transported into and out of the brain by the blood-brain barrier.
Peptides
PUBLISHED: 08-19-2014
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Alpha-synuclein (?-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, ?-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of ?-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of ?-Syn to cross the blood-brain barrier (BBB). Here, we found that radioactively labeled ?-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in ?-Syn efflux process, and lipopolysaccharide (LPS)-induced inflammation could increase ?-Syn uptake by the brain by disrupting the BBB.
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Combination therapy with low molecular weight heparin and Adriamycin results in decreased breast cancer cell metastasis in C3H mice.
Exp Ther Med
PUBLISHED: 08-18-2014
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The aim of this study was to investigate the effect of low molecular weight heparin (LMWH) against breast cancer cell invasion and metastasis in C3H mice and the underlying mechanism. The C3H mouse breast cancer model was established, and the mice were then randomly divided into four groups: normal saline group, LMWH group, Adriamycin positive control group and the combination group (LMWH combined with Adriamycin). Twelve days after inoculation, drug treatment was initiated. During the one-month period of drug administration, tumor growth curves were recorded. At the end of the treatment period, the mice were sacrificed and the solid tumor tissue and lung were removed. Hematoxylin and eosin (H&E) staining was used to observe the overall changes in tumor cell morphology and lung metastasis following the treatment. A terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay was used for detection of apoptosis in tumor cells, and immunohistochemical (IHC) analysis was used to determine the expression of vascular endothelial growth factor (VEGF). The tumor growth curves demonstrated that the overall growth of the combination group was less compared with that of the other three groups, indicating that LMWH inhibited the growth of the tumors. H&E staining showed that the area of tumor cell necrosis in the combination group was significantly greater compared with that in the other groups, and less metastasis was observed in the lung. The results from the TUNEL staining demonstrated that there was an increase in the number of blue-black apoptotic cells, and the expression of VEGF was significantly reduced in the combination group compared with the other three groups. Therefore, this indicates that LMWH, combined with Adriamycin significantly reduced the growth of breast cancer cells in C3H mice. The results suggest that the mechanism may be associated with breast cancer cell apoptosis and inhibition of VEGF expression.
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Small molecule 1'-acetoxychavicol acetate suppresses breast tumor metastasis by regulating the SHP-1/STAT3/MMPs signaling pathway.
Breast Cancer Res. Treat.
PUBLISHED: 08-16-2014
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Signal transducer and activator of transcription 3 (STAT3) is implicated breast cancer metastasis and represents a potential target for developing new anti-tumor metastasis drugs. The purpose of this study is to investigate whether the natural agent 1'-acetoxychavicol acetate (ACA), derived from the rhizomes and seeds of Languas galanga, could suppress breast cancer metastasis by targeting STAT3 signaling pathway. ACA was examined for its effects on breast cancer migration/invasion and metastasis using Transwell assays in vitro and breast cancer skeletal metastasis mouse model in vivo (n = 10 mice per group). The inhibitory effect of ACA on cellular STAT3 signaling pathway was investigated by series of biochemistry analysis. The chavicol preferentially suppressed cancer cell migration and invasion, and this activity was superior to its cytotoxic effects. ACA suppressed both constitutive and interleukin-6-inducible STAT3 activation and diminished the accumulation of STAT3 in the nucleus and its DNA-binding activity. More importantly, ACA treatment led to significant up-regulation of Src homology region 2 domain-containing phosphatase 1 (SHP-1), and the ACA-induced depression of cancer cell migration and STAT3 signaling could be apparently reversed by blockade of SHP-1. Matrix metalloproteinase (MMP)-2 and -9, gene products of STAT3 that regulate cell invasion, were specifically suppressed by ACA. In tumor metastasis model, ACA potently inhibited the human breast cancer cell-induced osteolysis, and had little apparent in vivo toxicity at the test concentrations. ACA is a novel drug candidate for the inhibition of tumor metastasis through interference with the SHP-1/STAT3/MMPs signaling pathway.
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Enhanced deacidification activity in Schizosaccharomyces pombe by genome shuffling.
Yeast
PUBLISHED: 08-07-2014
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A problem frequently occurring in making some kinds of wines, particularly Vitis quinquangularis Rehd wine, is the presence of malic acid at high concentrations, which is detrimental to the quality of wines. Thus, there is a need of the ways for effectively reducing the malic acid levels in wine. This study aimed to generate shuffled fusants of Schizosaccharomyces pombe with enhanced deacidification activity for reducing the excessive malic acid content in wine. Sz. pombe CGMCC 2.1628 was used as the original strain. The starting mutant population was generated by UV treatment. The mutants with higher deacidification activity were selected and subjected to recursive protoplast fusion. The resulting fusants were screened by using the indicator of malic acid concentration of fermentation supernatants on 96-well microtitre plates, measured with bromocresol green. After three rounds of genome shuffling, the best-performing fusant, named GS3-1, was obtained. Its deacidification activity (consumed 4.78?g/l malic acid within 10?days) was increased by 225.2% as compared to that of original strain. In the Vitis quinquangularis Rehd wine fermentation test, GS3-1 consumed 4.0?g/l malic acid during the whole cycle of fermentation, providing up to 185.7% improvement in malic acid consumption compared with that of the original strain. This study shows that GS3-1 has great potential for improving the quality of Vitis quinquangularis Rehd wine. Copyright © 2014 John Wiley & Sons, Ltd.
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Electron-Acceptor-Dependent Light Absorption, Excited-State Relaxation, and Charge Generation in Triphenylamine Dye-Sensitized Solar Cells.
ChemSusChem
PUBLISHED: 08-07-2014
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By choosing a simple triphenylamine electron donor, we herein compare the influence of electron acceptors benzothiadiazole benzoic acid (BTBA) and cyanoacrylic acid (CA), on energy levels, light absorption, and dynamics of excited-state evolution and electron injection. DFT and time-dependent DFT calculations disclosed remarkable intramolecular conformational changes for the excited states of these two donor-acceptor dyes. Photoinduced dihedral angle variation occurs to the triphenylamine unit in the CA dye and backbone planarization happens to conjugated aromatic blocks in the BTBA dye. Femtosecond spectroscopic measurements suggested the crucial role of having a long excited-state lifetime in maintaining a high electron-injection yield because a reduced driving force for a low energy-gap dye can result in slower electron-injection dynamics.
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Diagnostic performance of the three-dimensional fast spin echo-Cube sequence in comparison with a conventional imaging protocol in evaluation of the lachrymal drainage system.
Eur Radiol
PUBLISHED: 08-05-2014
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To compare the three-dimensional (3D)-fast spin-echo (FSE)-Cube with a conventional imaging protocol in evaluation of dacryostenosis.
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Intestinal Uptake and Transport of Vitamin B12-loaded Soy Protein Nanoparticles.
Pharm. Res.
PUBLISHED: 07-22-2014
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Intestinal absorption of vitamin B12 (VB12) is a major challenge in combating pernicious anemia due to intrinsic factor (IF) deficiency.
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In vitro simulation of in vivo pharmacokinetic model with intravenous administration via flow rate modulation.
J Pharmacokinet Pharmacodyn
PUBLISHED: 07-20-2014
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The aim of this paper was to propose a method of flow rate modulation for simulation of in vivo pharmacokinetic (PK) model with intravenous injection based on a basic in vitro PK model. According to the rule of same relative change rate of concentration per unit time in vivo and in vitro, the equations for flow rate modulation were derived using equation method. Four examples from literature were given to show the application of flow rate modulation in the simulation of PK model of antimicrobial agents in vitro. Then an experiment was performed to confirm the feasibility of flow rate modulation method using levo-ornidazole as an example. The accuracy and precision of PK simulations were evaluated using average relative deviation (ARD), mean error and root mean squared error. In vitro model with constant flow rate could mimic one-compartment model, while the in vitro model with decreasing flow rate could simulate the linear mammillary model with multiple compartments. Zero-order model could be simulated using the in vitro model with elevating flow rate. In vitro PK model with gradually decreasing flow rate reproduced the two-compartment kinetics of levo-ornidazole quite well. The ARD was 0.925 % between in vitro PK parameters and in vivo values. Results suggest that various types of PK model could be simulated using flow rate modulation method without modifying the structure. The method provides uniform settings for the simulation of linear mammillary model and zero-order model based on in vitro one-compartment model, and brings convenience to the pharmacodynamic study.
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What is Visualize?

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

How does it work?

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

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.