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Find video protocols related to scientific articles indexed in Pubmed.
Kinetically-controlled growth of cubic and octahedral Rh-Pd alloy oxygen reduction electrocatalysts with high activity and durability.
Nanoscale
PUBLISHED: 11-20-2014
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Rh is a promising candidate as an indispensible component in bimetallic catalysts due to its unique capability to resist against the aggressive corrosion from the reaction medium. However, Rh has a very strong oxygen binding ability and is generally not suitable for the oxygen reduction reaction (ORR). Here, we have demonstrated shape-controlled synthesis of Rh-Pd alloy nanocrystals with high activity and durability for ORR by retarding the reaction kinetics at an ultra-slow injection rate of metal salts using a syringe pump. Under precise control of sluggish reaction kinetics, Pd followed a preferential overgrowth along the <100> direction, whereas the growth behavior of Rh was dominant along the <111> direction. These different kinetically-controlled growth behaviors associated with Rh and Pd were essential for achieving the shape transition between the cube and the octahedron of their alloys. The Rh8Pd92 alloy octahedra exhibited the highest mass activity with a value of 0.18 mA ?g(-1) in terms of the equivalent Pt cost, and were two-fold higher than that of commercial Pt/C. Significantly, all Rh-Pd alloy nanocrystals were highly stable with only less than 25% loss in mass activity after 30?000 CV cycles in O2 saturated acid solution compared to ?56% loss of the commercial Pt/C (E-TEK). Indeed, the mass activity of Rh8Pd92 was 3.3 times higher than that of commercial Pt/C after the accelerated stability test (ADT). This improvement in activity and durability may arise possibly from synergistic effects between the facet and the surface composition.
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1,1-Carboboration to tellurium-boron intramolecular frustrated Lewis pairs.
Dalton Trans
PUBLISHED: 11-20-2014
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The tellurium acetylide Ph(CH2)2TeCCPh reacts with boranes via 1,1-carboboration to give a series of borylated vinyl telluroethers. The product Ph(CH2)2TeC(Ph)C(C6F5) B(C6F5)2 reacts with phenylacetylene and iodine to give novel tellurium-boron heterocyclic compounds.
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Single-molecule analysis of the self-assembly process facilitated by host-guest interactions.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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The self-assembly process from a 1?:?1 to a 1?:?2 complex, facilitated by para-sulfonatocalix[6]arenes (SC6) as host and methyl viologen (MV(2+)) as guest, was analyzed at the single-molecule level through an ?-hemolysin nanopore. Especially, the assembled complex structures were discriminated in real time in the mixture of SC6 and MV(2+).
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Visible/Infrared Dissociation of NO3: Roaming in the Dark or Roaming on the Ground?
J Phys Chem A
PUBLISHED: 11-20-2014
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We present a DC slice imaging study of roaming dynamics in the photodissociation of the nitrate radical, NO3, contrasting pure visible excitation with a combination of visible and CO2 laser excitation at 10.6 ?m. Images of specific rotational levels of NO are seen to reflect dissociation on the ground and first excited electronic states, as reported in previous work. The branching is obtained for specific rotational levels by comparison to quasiclassical trajectory calculations of the dynamics on these two surfaces. The results for the visible dissociation are found to be very similar to the combination of visible and infrared, raising questions about the nature of the coupling of these surfaces, the extent to which roaming takes place on both, and how the final product branching is determined.
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The direct electrophilic cyanation of ?-keto esters and amides with cyano benziodoxole.
Org. Biomol. Chem.
PUBLISHED: 11-20-2014
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The direct electrophilic ?-cyanation of ?-keto esters and amides has been developed using a hypervalent iodine benziodoxole-derived cyano reagent. The procedure is accomplished within 10 min and without the use of any catalyst in DMF, at room temperature. Thus, the highly functionalized quaternary carbon-centered nitriles were produced in high to excellent yields.
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Synthesis and Biological Evaluation of Sophoridinol Derivatives as a Novel Family of Potential Anticancer Agents.
ACS Med Chem Lett
PUBLISHED: 11-13-2014
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New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 ?M. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentration-time curve (AUC) of 10.3 ?M·h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
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Scopine as a Novel Brain-Targeting Moiety Enhances the Brain Uptake of Chlorambucil.
Bioconjug. Chem.
PUBLISHED: 11-06-2014
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The blood brain barrier (BBB) represents the biggest challenge for therapeutic drugs to enter the brain. In our study, we selected chlorambucil (CHL), an alkylating agent, as the model therapeutic agent, and used scopine as a novel brain-targeting moiety. Here, we synthesized Chlorambucil-Scopine (CHLS) prodrug and evaluated its brain-targeting efficacy. The tissue distribution study after i.v. injection revealed that the AUC0-t and Cmax of CHLS in the brain were 14.25- and 12.20-fold of CHL, respectively. Specifically, CHLS accumulated in bEnd.3 and C6 cells in an energy-dependent manner. In C6 cells, superior anti-glioma activity with a significantly decreased IC50 of 65.42 nM/mL was observed for CHLS compared to CHL (IC50 > 400 nM/mL). The safety evaluation, including acute toxicity, pathology, and hematology study, showed minimal toxicity toward nontargeting tissues, and also reached a lower systemic toxicity at 5 mg/kg (i.v.). Our results suggested that scopine is a potential brain-targeting moiety for enhancing the brain uptake efficiency of CHL.
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Non-small cell lung cancer with EML4-ALK translocation in Chinese male never-smokers is characterized with early-onset.
BMC Cancer
PUBLISHED: 10-30-2014
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The translocations of the anaplastic lymphoma kinase (ALK) gene with the echinoderm microtubule-associated protein-like 4 (EML4) gene on chromosome 2p have been identified in non-small-cell lung cancers (NSCLCs) as oncogenic driver mutations. It has been suggested that EML4-ALK fusion is associated with the resistance in NSCLCs to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), such as gefitinib and erlotinib. In contrast, ALK tyrosine kinase inhibitor (ALK TKI) crizotinib has shown superior effects in combating NSCLCs with EML4-ALK. Thus, characterization of EML4-ALK fusion genes and clinical features of resulting carcinomas would be a great benefit to disease diagnosis and designing customized treatment plans. Studies have suggested that EML4-ALK translocation occurs more frequently in never-smokers with NSCLC, especially in female patients. However, it is not clear whether this is the case in male patients, too. In this study, we have determined the frequency of EML4-ALK translocation in male never-smokers with NSCLC in a cohort of Chinese patients. The clinical features associated with EML4-ALK translocation were also investigated.
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Prevalence and Risk Factors for Farmer's Lung in Greenhouse Farmers: An Epidemiological Study of 5,880 Farmers from Northeast China.
Cell Biochem. Biophys.
PUBLISHED: 10-27-2014
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The objectives of this epidemiological study were to evaluate the prevalence of farmer's lung disease (FLD) and to explore the potential risk factors for FLD among Chinese greenhouse farmers. A total of 835 plastic film greenhouses, including 5,880 active farmers who engaged in crop cultivation or poultry farming, were randomly selected from the rural regions of Northeastern China. These farmers participated in the study by answering a medical questionnaire. 5,420 greenhouse farmers accepted and answered questionnaires in full (response rate, 92.18 %). Prevalence of FLD among these farmers was 5.7 % (308/5,420). Besides, a number of classic risk factors for FLD were identified, such as years of age, shorter time interval for re-entry greenhouse, ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m(2) but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, and et al. FLD is and will continue to be a real health problem for Chinese farmers. If these preventive measures are implemented, the prevalence of FLD in Chinese greenhouse farmers might be greatly reduced.
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Targeted transplantation of human umbilical cord blood endothelial progenitor cells with immunomagnetic nanoparticles to repair corneal endothelium defect.
Stem Cells Dev.
PUBLISHED: 10-16-2014
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Corneal endothelial dysfunction involves progressive corneal edema and loss of visual acuity, which result in the need for corneal transplantation. The global shortage of donor corneas limits the development of the surgery. Reconstruction of a bioengineered corneal endothelium might resolve this problem. Various scaffolds have been used, but poor biocompatibility and degradation limit their applications. In this study, a novel method of targeted cellular transplantation without permanent residence of cell carriers in the host was proposed. Human umbilical cord blood endothelial progenitor cells (UCB EPCs) were labeled with CD34 immunomagnetic nanoparticles. The efficiency of the magnet attraction was evaluated in vitro with a simple device simulating the anterior chamber. The UCB EPCs labeled with nanoparticles were transplanted into the anterior chamber of rabbits with magnet attraction. The results indicated that labeling the nanoparticles did not affect the proliferation of the UCB EPCs. The in vitro study indicated that the magnet could directionally attract UCB EPCs labeled with nanoparticles. The in vivo study indicated that the corneas in rabbits transplanted with UCB EPCs labeled with nanoparticles and magnet attraction became relatively transparent with little edema. These results indicate that UCB EPCs labeled with CD34 immunomagnetic nanoparticles could be attracted directionally by a magnet and could repair corneal endothelial defects, providing a promising cell therapy for corneal endothelial dysfunction.
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Development and evaluation on an intelligent traceability system for frozen tilapia fillet processing.
J. Sci. Food Agric.
PUBLISHED: 09-26-2014
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The main export varieties are brand-name, high-quality bred aquatic products in China.?Among of them, tilapia?has become the most important and fast growing species since extensive consumers market in North America and Europe has evolved due to commodity prices of year round availability and quality of fresh and frozen products. As the biggest tilapia farming country, China has over 1/3 tilapia produce for further processing and meeting foreign market demand.
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MicroRNA-27a promotes proliferation and suppresses apoptosis by targeting PLK2 in laryngeal carcinoma.
BMC Cancer
PUBLISHED: 09-17-2014
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miRNA-27a has been confirmed as an important regulator in carcinogenesis and other pathological processes. Whether and how it plays a role in the laryngeal carcinoma is unknown.
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Expedient Synthesis of Chiral ?-Amino Acids through Nickel-Catalyzed Reductive Cross-Coupling.
Chemistry
PUBLISHED: 09-16-2014
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A novel method for the synthesis of non-natural L- and D-amino acids by a Ni-catalyzed reductive cross-coupling reaction is described. This strategy enables the racemization-free cross-coupling of serine/homoserine- derived iodides with aryl/acyl/alkyl halides. It provides convenient access to varieties of enantiopure and functionalized amino acids, which are important building blocks in bioactive compounds and pharmaceuticals.
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Copper-catalyzed endo-type trifluoromethylarylation of alkynes.
Chem. Commun. (Camb.)
PUBLISHED: 09-13-2014
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A new copper-catalyzed trifluoromethylarylation reaction of alkynes has been developed. The transformation represents the first example of endo-type carbotrifluoromethylation of unsaturated carbon-carbon bonds and provides efficient access to a variety of CF3-substituted dihydronaphthalenes and chromenes.
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Copper-catalyzed reductive cross-coupling of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides.
Chemistry
PUBLISHED: 09-11-2014
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A copper-catalyzed reductive cross-coupling reaction of nonactivated alkyl tosylates and mesylates with alkyl and aryl bromides was developed. It provides a practical method for efficient and cost-effective construction of aryl-alkyl and alkyl-alkyl C?C bonds with stereocontrol from readily available substrates. When used in an intramolecular fashion, the reaction enables convenient access to various substituted carbo- or heterocycles, such as 2,3-dihydrobenzofuran and benzochromene derivatives.
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Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and ? cells.
Elife
PUBLISHED: 09-05-2014
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Epigenetic modifiers are an emerging class of anti-tumor drugs, potent in multiple cancer contexts. Their effect on spontaneously developing autoimmune diseases has been little explored. We report that a short treatment with I-BET151, a small-molecule inhibitor of a family of bromodomain-containing transcriptional regulators, irreversibly suppressed development of type-1 diabetes in NOD mice. The inhibitor could prevent or clear insulitis, but had minimal influence on the transcriptomes of infiltrating and circulating T cells. Rather, it induced pancreatic macrophages to adopt an anti-inflammatory phenotype, impacting the NF-?B pathway in particular. I-BET151 also elicited regeneration of islet ?-cells, inducing proliferation and expression of genes encoding transcription factors key to ?-cell differentiation/function. The effect on ? cells did not require T cell infiltration of the islets. Thus, treatment with I-BET151 achieves a 'combination therapy,' currently advocated by many diabetes investigators, operating by a novel mechanism that coincidentally dampens islet inflammation and enhances ?-cell regeneration.
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Subcutaneously injected ivermectin-loaded mixed micelles: formulation, pharmacokinetics and local irritation study.
Drug Deliv
PUBLISHED: 09-04-2014
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Abstract Clinical application of ivermectin (IVM) is limited by several unfavorable properties, induced by its insolubility in water. Slight differences in formulation may change the plasma pharmacokinetics and efficacy. In this study, an IVM-loaded Soy phosphatidylcholine-sodium deoxycholate mixed micelles (IVM-SPC-SDC-MMs) were developed to improve its aqueous solubility, aiming to make it more applicable for clinical use. First, IVM-SPC-SDC-MMs were prepared using the co-precipitation method. After formulation optimization, the particle size was 9.46?±?0.16?nm according to dynamic light scattering. The water solubility of IVM in SPC-SDC-MMs (4.79?±?0.02?mg/mL) was improved by 1200-fold, comparing with free IVM (0.004?mg/mL). After subcutaneous administration, the pharmacokinetic study showed that IVM-SPC-SDC-MMs and commercially available IVM injection were bioequivalent. Also, the local irritation study confirmed that IVM-SPC-SDC-MMs reduced side reactions of the commercially available IVM injection. These results indicated that IVM-SPC-SDC-MMs represented a promising new drug formulation suitable for subcutaneous delivery of IVM.
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Accurate predictions of C-SO2R bond dissociation enthalpies using density functional theory methods.
Phys Chem Chem Phys
PUBLISHED: 08-29-2014
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The dissociation of the C-SO2R bond is frequently involved in organic and bio-organic reactions, and the C-SO2R bond dissociation enthalpies (BDEs) are potentially important for understanding the related mechanisms. The primary goal of the present study is to provide a reliable calculation method to predict the different C-SO2R bond dissociation enthalpies (BDEs). Comparing the accuracies of 13 different density functional theory (DFT) methods (such as B3LYP, TPSS, and M05 etc.), and different basis sets (such as 6-31G(d) and 6-311++G(2df,2p)), we found that M06-2X/6-31G(d) gives the best performance in reproducing the various C-S BDEs (and especially the C-SO2R BDEs). As an example for understanding the mechanisms with the aid of C-SO2R BDEs, some primary mechanistic studies were carried out on the chemoselective coupling (in the presence of a Cu-catalyst) or desulfinative coupling reactions (in the presence of a Pd-catalyst) between sulfinic acid salts and boryl/sulfinic acid salts.
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Wireless and Simultaneous Detections of Multiple Bio-Molecules in a Single Sensor Using Love Wave Biosensor.
Sensors (Basel)
PUBLISHED: 08-27-2014
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A Love wave-based biosensor with a 440 MHz center frequency was developed for the simultaneous detection of two different analytes of Cartilage Oligomeric Matrix Protein (COMP) and rabbit immunoglobulin G (IgG) in a single sensor. The developed biosensor consists of one-port surface acoustic wave (SAW) reflective delay lines on a 41° YX LiNbO3 piezoelectric substrate, a poly(methyl methacrylate) (PMMA) waveguide layer, and two different sensitive films. The Love wave biosensor was wirelessly characterized using two antennas and a network analyzer. The binding of the analytes to the sensitive layers induced a large change in the time positions of the original reflection peaks mainly due to the mass loading effect. The assessed time shifts in the reflection peaks were matched well with the predicted values from coupling of mode (COM) modeling. The sensitivities evaluated from the sensitive films were ~15 deg/µg/mL for the rabbit IgG and ~1.8 deg/ng/mL for COMP.
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[Effects of postconditioning on autophagy of lung ischemic reperfusion injury in rats].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-23-2014
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To explore the effects of postconditioning on autophagy of lung injury in situ during lung ischemic reperfusion.
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Aerobic Oxidation of Hydroxymethylfurfural and Furfural by Using Heterogeneous Cox Oy -N@C Catalysts.
ChemSusChem
PUBLISHED: 08-17-2014
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2,5-Furandicarboxylic acid (FDCA) is considered to be a promising replacement for terephthalic acid since they share similar structures and properties. In contrast to FDCA, 2,5-furandicarboxylic acid methyl (FDCAM) has properties that allow it to be easily purified. In this work, we reported an oxidative esterification of 5-hydroxymethylfurfural (HMF) and furfural to prepare corresponding esters over Cox Oy -N@C catalysts using O2 as benign oxidant. High yield and selectivity of FDCAM and methyl 2-furoate were obtained under optimized conditions. Factors which influenced the product distribution were examined thoroughly. The Cox Oy -N@C catalysts were recycled five times and no significant loss of activity was detected. Characterization of the catalysts could explain such phenomena. Using XPS and TGA, we made a thorough investigation of the effects of ligand and pyrolysis temperature on catalyst activity.
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On computing stress in polymer systems involving multi-body potentials from molecular dynamics simulation.
J Chem Phys
PUBLISHED: 08-10-2014
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Hardy stress definition has been restricted to pair potentials and embedded-atom method potentials due to the basic assumptions in the derivation of a symmetric microscopic stress tensor. Force decomposition required in the Hardy stress expression becomes obscure for multi-body potentials. In this work, we demonstrate the invariance of the Hardy stress expression for a polymer system modeled with multi-body interatomic potentials including up to four atoms interaction, by applying central force decomposition of the atomic force. The balance of momentum has been demonstrated to be valid theoretically and tested under various numerical simulation conditions. The validity of momentum conservation justifies the extension of Hardy stress expression to multi-body potential systems. Computed Hardy stress has been observed to converge to the virial stress of the system with increasing spatial averaging volume. This work provides a feasible and reliable linkage between the atomistic and continuum scales for multi-body potential systems.
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Cu-catalyzed Suzuki-Miyaura reactions of primary and secondary benzyl halides with arylboronates.
Chem. Commun. (Camb.)
PUBLISHED: 08-07-2014
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A copper-catalyzed Suzuki-Miyaura coupling of benzyl halides with arylboronates is described. Varieties of primary benzyl halides as well as more challenging secondary benzyl halides with ? hydrogens or steric hindrance could be successfully converted into the corresponding products. Thus it provides access to diarylmethanes, diarylethanes and triarylmethanes.
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Brain-specific delivery of dopamine mediated by n,n-dimethyl amino group for the treatment of Parkinson's disease.
Mol. Pharm.
PUBLISHED: 08-06-2014
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Parkinson's disease (PD) has become one of the most deadly diseases due to a lack of effective treatment. Herein, N-3,4-bis(pivaloyloxy)dopamine-3-(dimethylamino)propanamide (PDDP), a brain-specific derivative of dopamine, was designed and synthesized, which consists of a brain targeted ligand, N,N-dimethyl amino group, and two dipivaloyloxy groups for lipophilic modification. PDDP was investigated both in vitro and in vivo by comparing with L-DOPA and another derivative (BPD) without N,N-dimethyl amino group. PDDP showed a more pronounced accumulation in mouse brain microvascular endothelial cells (bEnd.3) than BPD via an active transport process. The increased cellular uptake of PDDP was proven to be mediated by putative pyrilamine cationic transporters. Following intravenous administration, the concentration of PDDP in the brain was 269.28-fold and 6.41-fold higher than that of L-DOPA and BPD at 5 min, respectively. Additionally, PDDP effectively attenuated the striatum lesion caused by 6-hydroxydopamine (6-OHDA) in rats. More importantly, PDDP presented antioxidant and antiapoptotic effects on 6-OHDA-induced toxicity in human neuroblastoma cells (SH-SY5Y). Thus, N,N-dimethyl amino group-based PDDP represents an effective and safe treatment for PD.
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Effects of Melatonin on the Proliferation and Apoptosis of Sheep Granulosa Cells under Thermal Stress.
Int J Mol Sci
PUBLISHED: 07-30-2014
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The cross-talk between oocyte and somatic cells plays a crucial role in the regulation of follicular development and oocyte maturation. As a result, granulosa cell apoptosis causes follicular atresia. In this study, sheep granulosa cells were cultured under thermal stress to induce apoptosis, and melatonin (MT) was examined to evaluate its potential effects on heat-induced granulosa cell injury. The results demonstrated that the Colony Forming Efficiency (CFE) of granulosa cells was significantly decreased (heat 19.70% ± 1.29% vs. control 26.96% ± 1.81%, p < 0.05) and the apoptosis rate was significantly increased (heat 56.16% ± 13.95% vs. control 22.80% ± 12.16%, p < 0.05) in granulosa cells with thermal stress compared with the control group. Melatonin (10-7 M) remarkably reduced the negative effects caused by thermal stress in the granulosa cells. This reduction was indicated by the improved CFE and decreased apoptotic rate of these cells. The beneficial effects of melatonin on thermal stressed granulosa cells were not inhibited by its membrane receptor antagonist luzindole. A mechanistic exploration indicated that melatonin (10-7 M) down-regulated p53 and up-regulated Bcl-2 and LHR gene expression of granulosa cells under thermal stress. This study provides evidence for the molecular mechanisms of the protective effects of melatonin on granulosa cells during thermal stress.
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Metal-templated enantioselective enamine/H-bonding dual activation catalysis.
Chem. Commun. (Camb.)
PUBLISHED: 07-29-2014
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An octahedral bis-cyclometalated iridium(III) complex catalyzes the enantioselective ?-amination of aldehydes with catalyst loadings down to 0.1 mol%. In this metal-templated design, the metal serves as a structural center and provides the exclusive source of chirality, whereas the catalysis is mediated through the organic ligand sphere.
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Widespread genetic epistasis among cancer genes.
Nat Commun
PUBLISHED: 07-28-2014
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Quantitative genetic epistasis has been hypothesized to be an important factor in the development and progression of complex diseases. Cancers in particular are driven by the accumulation of mutations that may act epistatically during the course of the disease. However, as cancer mutations are uncovered at an unprecedented rate, determining which combinations of genetic alterations interact to produce cancer phenotypes remains a challenge. Here we show that by using combinatorial RNAi screening in cell culture, dense and often previously undetermined interactions among cancer genes were revealed by assessing gene pairs that are frequently co-altered in primary breast cancers. These interacting gene pairs are significantly associated with survival time when co-altered in patients, indicating that genetic interaction mapping may be leveraged to improve risk assessment. As many of these interacting gene pairs involve known drug targets, personalized treatment regimens may be improved by overlaying genetic interactions with mutational profiling.
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Rifampicin Loaded Mannosylated Cationic Nanostructured Lipid Carriers for Alveolar Macrophage-specific Delivery.
Pharm. Res.
PUBLISHED: 07-11-2014
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In this study, cationic mannosylated nanostructured lipid carriers (Man-NLCs) were developed for the targeted delivery of rifampicin to alveolar macrophages.
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Adenosine Triphosphate-Induced Rabbit Corneal Endothelial Cell Proliferation in vitro via the P2Y2-PI3K/Akt Signaling Axis.
Cells Tissues Organs (Print)
PUBLISHED: 07-01-2014
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Purpose: To investigate the effect of the ATP-P2Y2-PI3K/Akt signaling axis on promoting rabbit corneal endothelial cell (RCEC) proliferation in vitro. Methods: Five concentrations of adenosine triphosphate (ATP; 1, 10, 25, 50 and 100 ?M) were added to RCECs, and the cell proliferation was detected using Cell Counting Kit-8 (CCK8) and Ki67 immunohistochemical staining. Other P2Y2 receptor agonists and antagonists were added to the cells, and the proliferation effect was evaluated using CCK8 to determine the involvement of the P2Y2 receptor. Changes in the expression of phosphorylated Akt in RCECs treated with different concentrations of extracellular ATP and the duration of extracellular ATP on Akt phosphorylation were investigated using Western blotting. The pharmacological profiles with or without the PI3K/Akt pathway inhibitors were also determined using Western blotting. Results: We found that 10 ?M ATP strongly promoted RCEC proliferation in vitro. Additionally, 25 ?M ATP had a proliferation effect, whereas other concentrations (1, 50 and 100 ?M) had no effect compared with the control group. Selective P2Y2 receptor agonists (UTP, ATP?S and Ap4A) showed the same promotion effect, while P2Y2 antagonists and PI3K/Akt inhibitors inhibited the effect of ATP. Moreover, phosphorylated Akt could be induced by the addition of extracellular ATP at all five concentrations and lasted for 1 h. This phosphorylation was prevented by PI3K/Akt inhibitors and a P2Y2 antagonist. Conclusions: These findings showed that 10 ?M ATP markedly promoted RCEC proliferation via the P2Y2-PI3K/Akt signaling axis. © 2014 S. Karger AG, Basel.
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Type 1 Diabetes in NOD Mice Unaffected by Mast Cell Deficiency.
Diabetes
PUBLISHED: 06-10-2014
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Mast cells have been invoked as important players in immune responses associated with autoimmune diseases. Based on in vitro studies, or in vivo through the use of Kit mutant mice, mast cells have been suggested to play immunological roles in direct antigen presentation to both CD4(+) and CD8(+) T cells, in the regulation of T-cell and dendritic cell migration to lymph nodes, and in Th1 versus Th2 polarization, all of which could significantly impact the immune response against self-antigens in autoimmune disease, including type 1 diabetes (T1D). Until now, the role of mast cells in the onset and incidence of T1D has only been indirectly tested through the use of low-specificity mast cell inhibitors and activators, and published studies reported contrasting results. Our three laboratories have generated independently two strains of mast cell-deficient nonobese diabetic (NOD) mice, NOD.Cpa3(Cre/+) (Heidelberg) and NOD.Kit(W-sh/W-sh) (Leuven and Boston), to address the effects of mast cell deficiency on the development of T1D in the NOD strain. Our collective data demonstrate that both incidence and progression of T1D in NOD mice are independent of mast cells. Moreover, analysis of pancreatic lymph node cells indicated that lack of mast cells has no discernible effect on the autoimmune response, which involves both innate and adaptive immune components. Our results demonstrate that mast cells are not involved in T1D in the NOD strain, making their role in this process nonessential and excluding them as potential therapeutic targets.
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Mechanistic study of chemoselectivity in Ni-catalyzed coupling reactions between azoles and aryl carboxylates.
J. Am. Chem. Soc.
PUBLISHED: 05-27-2014
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Itami et al. recently reported the C-O electrophile-controlled chemoselectivity of Ni-catalyzed coupling reactions between azoles and esters: the decarbonylative C-H coupling product was generated with the aryl ester substrates, while C-H/C-O coupling product was generated with the phenol derivative substrates (such as phenyl pivalate). With the aid of DFT calculations (M06L/6-311+G(2d,p)-SDD//B3LYP/6-31G(d)-LANL2DZ), the present study systematically investigated the mechanism of the aforementioned chemoselective reactions. The decarbonylative C-H coupling mechanism involves oxidative addition of C(acyl)-O bond, base-promoted C-H activation of azole, CO migration, and reductive elimination steps (C-H/Decar mechanism). This mechanism is partially different from Itami's previous proposal (Decar/C-H mechanism) because the C-H activation step is unlikely to occur after the CO migration step. Meanwhile, C-H/C-O coupling reaction proceeds through oxidative addition of C(phenyl)-O bond, base-promoted C-H activation, and reductive elimination steps. It was found that the C-O electrophile significantly influences the overall energy demand of the decarbonylative C-H coupling mechanism, because the rate-determining step (i.e., CO migration) is sensitive to the steric effect of the acyl substituent. In contrast, in the C-H/C-O coupling mechanism, the release of the carboxylates occurs before the rate-determining step (i.e., base-promoted C-H activation), and thus the overall energy demand is almost independent of the acyl substituent. Accordingly, the decarbonylative C-H coupling product is favored for less-bulky group substituted C-O electrophiles (such as aryl ester), while C-H/C-O coupling product is predominant for bulky group substituted C-O electrophiles (such as phenyl pivalate).
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PEGylated fluorescent carbon nanoparticles for noninvasive heart imaging.
Bioconjug. Chem.
PUBLISHED: 05-22-2014
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Fluorescent carbon nanoparticles (CNP) have gained much attention due to their unique fluorescent properties and safety. In this study, we evaluated the potential application of CNP and PEGylated CNP (PEG-CNP) in noninvasive heart imaging. CNP was prepared by hydrothermal treatment of silk. The particle size and zeta potential of CNP were 121.8 nm and -3.7 mV, respectively, which did not change significantly after PEGylation with a PEG density of 4.43 ± 0.02 ?g/mg CNP. FTIR and XPS showed that CNP possessed several functional groups, such as -COOH, -OH, and NH2, which could be utilized for PEGylation and other modifications. CNP displayed strong blue fluorescence after excitation at the wavelength of 375 nm. PEG-CNP displayed better serum stability compared to CNP. The hemolysis rate of PEG-CNP was lower than that of CNP, suggesting PEGylation could enhance the hemocompatibility of CNP. Both CNP and PEG-CNP showed higher uptake capacity by H9c2 cells (a heart cell line) than that by human umbilical vein endothelial cells (HUVEC), suggesting the particles tend to be selectively taken up by heart cells. Both CNP and PEG-CNP were proven to be taken up through endosome-mediated pathway, and the colocalization of nanoparticles with mitochondria was also observed. In vivo results demonstrated that CNP could target heart with much higher fluorescent intensity than liver and spleen. Although PEGylation could decrease the distribution in heart, it remained high for PEG-CNP. In conclusion, CNP could be used for heart imaging, and moreover, PEGylation could improve the stability and biocompatibility of CNP.
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Facile synthesis of Rh-Pd alloy nanodendrites as highly active and durable electrocatalysts for oxygen reduction reaction.
Nanoscale
PUBLISHED: 05-21-2014
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In addition to activity, durability of Pd-based catalysts in a highly corrosive medium has become one of the most important barriers to limit their industrial applications such as low-temperature fuel cell technologies. Here, Rh with a unique capability to resist against oxidation etching was incorporated into Pd-based catalysts to enhance both their activity and durability for oxygen reduction reaction (ORR). This idea was achieved through the synthesis of the Rh-Pd alloy nanodendrites by co-reducing Rh and Pd salt precursors in oleylamine (OAm) containing cetyltrimethylammonium bromide (CTAB). In this synthesis, Rh-Pd alloy nanostructures with Rh-Pd atomic ratios from 19 : 1 to 1 : 4 were generated by varying the molar ratios of Rh and Pd salt precursors. Interestingly, this variation of the molar ratios of the precursors from Rh rich to Pd rich would lead to the shape evolution of Rh-Pd alloy from dendritic nanostructures to spherical aggregations. We found that Br(-) ions derived from CTAB were also indispensible to the production of Rh-Pd alloy nanodendrites. Owing to the addition of highly stable Rh as well as the radical structure with a large number of low-coordinated sites on the arms, Rh-Pd alloy nanodendrites with a Rh-Pd atomic ratio of 4 : 1 (Rh80Pd20) exhibited a substantially enhanced electrocatalytic performance towards ORR with a 5% loss of mass activity during the accelerated stability test for 10?000 cycles compared to ? 50% loss of the commercial Pt/C (E-TEK).
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Evaluation of clinical application of ESICM acute gastrointestinal injury grading system: a single-center observational study.
Chin. Med. J.
PUBLISHED: 05-15-2014
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In 2012, the working group on abdominal problems of the European Society of Intensive Care Medicine (ESICM) proposed a definition and also guidelines for the grading system and treatment of acute gastrointestinal injury (AGI). Until now, clinical reports on this topic have not been available, and the practicality of using the AGI grading system requires further validation in the clinic. Therefore, we conducted this study to evaluate the feasibility of utilizing the current AGI grading system in a clinical environment, and to provide evidence for its usefulness in assessing the severity and prognosis of critically ill patients with gastrointestinal dysfunction.
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FunSeq2: A framework for prioritizing noncoding regulatory variants in cancer.
Genome Biol.
PUBLISHED: 04-17-2014
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Identification of noncoding drivers from thousands of somatic alterations in a typical tumor is a difficult and unsolved problem. We report a computational framework, FunSeq2, to annotate and prioritize these mutations. The framework combines an adjustable data context integrating large-scale genomics and cancer resources with a streamlined variant-prioritization pipeline. The pipeline has a weighted scoring system combining: inter- and intra-species conservation; loss- and gain-of function events for transcription-factor binding; enhancer-gene linkages and network centrality; and per-element recurrence across samples. We further highlight putative drivers with information specific to a particular sample, such as differential expression. FunSeq2 is available from funseq2.gersteinlab.org.
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Six-dimensional quantum dynamics study for the dissociative adsorption of DCl on Au(111) surface.
J Chem Phys
PUBLISHED: 04-17-2014
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We carried out six-dimensional quantum dynamics calculations for the dissociative adsorption of deuterium chloride (DCl) on Au(111) surface using the initial state-selected time-dependent wave packet approach. The four-dimensional dissociation probabilities are also obtained with the center of mass of DCl fixed at various sites. These calculations were all performed based on an accurate potential energy surface recently constructed by neural network fitting to density function theory energy points. The origin of the extremely small dissociation probability for DCl/HCl (v = 0, j = 0) fixed at the top site compared to other fixed sites is elucidated in this study. The influence of vibrational excitation and rotational orientation of DCl on the reactivity was investigated by calculating six-dimensional dissociation probabilities. The vibrational excitation of DCl enhances the reactivity substantially and the helicopter orientation yields higher dissociation probability than the cartwheel orientation. The site-averaged dissociation probability over 25 fixed sites obtained from four-dimensional quantum dynamics calculations can accurately reproduce the six-dimensional dissociation probability.
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Dynamic changes of tear fluid after cosmetic transcutaneous lower blepharoplasty measured by optical coherence tomography.
Am. J. Ophthalmol.
PUBLISHED: 03-27-2014
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To investigate the dynamic changes of tear fluid after cosmetic transcutaneous lower blepharoplasty.
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Combined application of eGFR and albuminuria for the precise diagnosis of stage 2 and 3a CKD in the elderly.
J. Nephrol.
PUBLISHED: 03-08-2014
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Estimated glomerular filtration rate (eGFR) is the sole diagnostic criterion for stage 3a chronic kidney disease (CKD). Because eGFR decreases with age, its prognostic utility in the elderly is controversial. Albuminuria is an important prognostic factor. To confirm that eGFR use may lead to the overdiagnosis of CKD and to examine the utility of eGFR combined with albuminuria for diagnosing stage 3a CKD in the elderly.
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Synthesis, preliminary bioevaluation and computational analysis of caffeic acid analogues.
Int J Mol Sci
PUBLISHED: 03-01-2014
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A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO) generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for further structural optimization. Moreover, predication of the potential targets was also carried out by the PharmMapper server. These amide analogues represent a promising class of anti-inflammatory scaffold for further exploration and target identification.
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DNA methylation ratio variability may impede clinical application of cancer diagnostic markers.
Anal Bioanal Chem
PUBLISHED: 02-28-2014
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Hypermethylation at promoter regions of tumour suppressor genes is diagnostic for many cancers. Many genomic regions that may be the targets for clinical diagnostic assays have been identified through use of measuring systems reliant on bisulphite conversion, but few of these promising markers are in clinical use. The comparability of a widely used DNA methylation measuring system involving bisulphite conversion was evaluated by supplying three experienced centres with methylated DNA reference material mixtures that were independently prepared and characterised by mass spectrometry and high-pressure liquid chromatography. A replication scheme was designed to evaluate reproducibility of key analytical steps within and between laboratories by regression analysis. In general, methylation was underestimated and methylation ratio values were highly variable. The difference in methylation ratio between CpG sites was the key contributor to variable results. The CpG site effect followed a similar pattern at all centres and at all methylation levels examined indicating that sequence context had a major effect on methylation ratio measurement using the bisulphite conversion process. The magnitude of underestimation combined with the variability of measurements between CpG sites compromises the concept of measuring genomic regional methylation by averaging the methylation ratios of many CpG sites. There were no significant differences in replicate bisulphite conversions or sample work-up and instrument analysis at each centre thus making this technique suitable for comparative intralaboratory investigations. However, it may not be suitable for a routine diagnostic assay without extensive standardisation efforts.
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Ranolazine attenuates the enhanced reverse Na?-Ca²? exchange current via inhibiting hypoxia-increased late sodium current in ventricular myocytes.
J. Pharmacol. Sci.
PUBLISHED: 02-27-2014
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Ranolazine (RAN), a novel antianginal agent, inhibits the increased late sodium current (INa.L) under many pathological conditions. In this study, the whole-cell patch-clamp technique was used to explore the effects of RAN on INa.L and reverse Na(+)/Ca(2+) exchange current (INCX) in rabbit ventricular myocytes during hypoxia.Tetrodotoxin (TTX) at 2 ?M or RAN at 9 ?M decreased significantly INa.L and reverse INCX under normoxia and RAN had no further effects on both currents in the presence of TTX. RAN (3, 6, and 9 ?M) attenuated hypoxia-increased INa.L and reverse INCX in a concentration-dependent manner. Hypoxia-increased INa.L and reverse INCX were inhibited by 2 ?M TTX, whereas 9 ?M RAN applied sequentially did not further decrease both currents. In another group, after both currents were decreased by 9 ?M RAN, 2 ?M TTX had no further effects in the presence of Ran. In monophasic action potential (MAP) recording, early after-depolarizations (EADs) were suppressed by RAN (9 ?M) during hypoxia. In conclusion, RAN decreased reverse INCX by inhibiting INa.L in normoxia, concentration-dependently attenuated the increase of INa.L, which thereby decreased the reverse INCX, and obviously relieved EADs during hypoxia.
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Nickel-tungsten carbide catalysts for the production of 2,5-dimethylfuran from biomass-derived molecules.
ChemSusChem
PUBLISHED: 02-26-2014
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The development of new catalytic systems for the conversion of biomass-derived molecules into liquid fuels has attracted much attention. We propose a non-noble bimetallic catalyst based on nickel-tungsten carbide for the conversion of the platform molecules 5-(hydroxymethyl)furfural into the liquid-fuel molecule 2,5-dimethylfuran (DMF). Different catalysts, metal ratios and reaction conditions have been tested and give rise to a 96% yield of DMF. The catalysts have been characterized and are discussed. The reaction mechanism is also explored through capture of reaction intermediates. The analysis of the reaction mixture over different catalysts is presented and helps to understand the role of nickel and tungsten carbide during the reaction.
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Asymmetric catalysis with substitutionally labile yet stereochemically stable chiral-at-metal iridium(III) complex.
J. Am. Chem. Soc.
PUBLISHED: 02-15-2014
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A metal-coordination-based high performance asymmetric catalyst utilizing metal centrochirality as the sole element of chirality is reported. The introduced substitutionally labile chiral-at-metal octahedral iridium(III) complex exclusively bears achiral ligands and effectively catalyzes the enantioselective Friedel-Crafts addition of indoles to ?,?-unsaturated 2-acyl imidazoles (19 examples) with high yields (75%-99%) and high enantioselectivities (90-98% ee) at low catalyst loadings (0.25-2 mol %). Counterintuitively, despite its substitutional lability, which is mechanistically required for coordination to the 2-acyl imidazole substrate, the metal-centered chirality is maintained throughout the catalysis. This novel class of reactive chiral-at-metal complexes will likely be of high value for a large variety of asymmetric transformations.
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Hollow LiMn(2)O(4) nanocones as superior cathode materials for lithium-ion batteries with enhanced power and cycle performances.
Small
PUBLISHED: 02-13-2014
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Single-crystalline LiMn(2)O(4) hollow nanocones are synthesized via a template-engaged low-temperature lithiation reaction. When applied as cathode materials for lithium-ion batteries, they can deliver a high specific capacity of 127.1 mAh g(-1) at 0.1 C and the capacity still maintains 100 mAh g(-1) even at 50°C. After over 1000 cycles at 5°C, 94.8% of the initial capacity is retained.
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Electrospun fibers for dental and craniofacial applications.
Curr Stem Cell Res Ther
PUBLISHED: 02-07-2014
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Electrospinning has been employed extensively in tissue engineering to generate nanofibrous scaffolds from either natural or synthetic biodegradable polymers. Three-dimensional electrospun scaffolds can create a multi-scale environment capable of facilitating cell adhesion, proliferation, and differentiation. One such multi-scale scaffold incorporates nanofibrous features to mimic the extracellular matrix along with a porous network for the regeneration of a variety of tissues. This review will discuss nanofibrous scaffolds and their tissue-engineering applications in bone, cartilage, periodontium, tooth, and incorporated drug delivery systems. Combination with other technologies, electrospun scaffolds can contribute to the field of craniofacial regeneration and advance technology for tissue-engineered replacements in many physiological systems in near future.
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Biomaterial and mesenchymal stem cell for articular cartilage reconstruction.
Curr Stem Cell Res Ther
PUBLISHED: 02-07-2014
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Cartilage has poor ability of spontaneous repair. Traditional treatments such as microfracture, bone drilling and autologous osteochondral graft were not fully satisfactory to fulfill the clinical needs. The idea of mesenchymal stem cell (MSCs-based cartilage regeneration has been put forward for decades. Large number of studies have been conducted on the biological properties of MSCs, the factors which might facilitate chondrogenic differentiation of MSCs, as well as the scaffold materials for tissue engineering. Promising results have been reported for cartilage repair in animal models. But before massive clinical application of MSCs, more efforts are needed on: differentiation improvement toward mature cartilage chondrocytes instead of hypertrophic chondrocyes and in vitro/in vivo phenotype maintenance; engineering an ideal biomaterial, which can meet the needs of the cartilage regeneration; and performing more studies on critical defects of large animals.
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Potential replication of induced pluripotent stem cells for craniofacial reconstruction.
Curr Stem Cell Res Ther
PUBLISHED: 01-30-2014
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The craniofacial region contains many specified tissues, including bone, cartilage, muscle, blood vessels, fat, skin and neurons. A defect or dysfunction of the craniofacial tissue after post-cancer ablative surgery, trauma, congenital malformations and progressive deforming skeletal diseases has a huge influence on the patient's life. Therefore, functional reconstruction of damaged tissues is highly sought. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound-healing. The recently acquired ability to reprogram human adult somatic cells to induced pluripotent stem cells (iPSCs) in culture may provide a powerful tool for in vitro disease modeling and an unlimited source for cell replacement therapy. This review focuses on the generation, biological characterization and discussion of the potential application of iPSCs for craniofacial tissue-engineering applications.
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RNA interference targeting inhibition of S100A4 suppresses cell growth and promotes apoptosis in human laryngeal carcinoma Hep?2 cells.
Mol Med Rep
PUBLISHED: 01-07-2014
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S100A4 is a small Ca2+ binding protein that belongs to the S100 family and is involved in a number of cellular functions, including cell cycle control, proliferation, apoptosis, and has a significant role in angiogenesis and neurite extension. However, the exact function and mechanism of S100A4 in laryngeal carcinogenesis remains to be elucidated. The present study was designed to investigate the potential use of RNA interference to inhibit S100A4 expression and activation, as well as the subsequent effect on human laryngeal cancer cell growth and apoptosis. The present study demonstrated that knockdown of S100A4 decreased the proliferation and growth of the human laryngeal cancer Hep?2 cell line. The percentages of the apoptotic cells were 4.23±1.22, 4.92±1.85 and 11.70±4.02% in the control, negative control and S100A4 short hairpin RNA (shRNA) groups, respectively, indicating significant differences among the different groups. The S100A4?mediated induction of apoptosis was demonstrated to be associated with the activation of caspase?3, caspase?8 and caspase?9. Intratumoral injection of S100A4?shRNA inhibited tumor growth in nude mice. Thus, knockdown of S100A4 inhibited the progression of laryngeal squamous carcinoma, decreased proliferation and promoted apoptosis. S100A4 is a potential candidate for therapeutic targeting of laryngeal carcinoma cells.
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Beneficial effects of melatonin on in vitro bovine embryonic development are mediated by melatonin receptor 1.
J. Pineal Res.
PUBLISHED: 01-06-2014
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In the current study, a fundamental question, that is, the mechanisms related to the beneficial effects of melatonin on mammalian embryonic development, was addressed. To examine the potential beneficial effects of melatonin on bovine embryonic development, different concentrations of melatonin (10(-11), 10(-9), 10(-7), 10(-5), 10(-3) M) were incubated with fertilized embryos. Melatonin in the range of 10(-11) to 10(-5) M significantly promoted embryonic development both in early culture medium (CR1aa +3 mg/mL BSA) and in later culture medium (CR1aa + 6%FBS). The most effective concentrations applied in the current studies were 10(-9) and 10(-7) M. Using quantitative real-time PCR with immunofluorescence and Western blot assays, the expression of melatonin receptor MT1 and MT2 genes was identified in bovine embryos. Further studies indicate that the beneficial effects of melatonin on bovine embryo development were mediated by the MT1 receptor. This is based on the facts that luzindole, a nonselective MT1 and MT2 antagonist, blocked the effect on melatonin-induced embryo development, while 4-P-PDOT, a selective MT2 antagonist, had little effect. Mechanistic explorations uncovered that melatonin application during bovine embryonic development significantly up-regulated the expression of antioxidative (Gpx4, SOD1, bcl-2) and developmentally important genes (SLC2A1, DNMT1A, and DSC2) while down-regulating expression of pro-apoptotic genes (P53, BAX, and Caspase-3). The results obtained from the current studies provide new information regarding the mechanisms by which melatonin promotes bovine embryonic development under both in vitro and in vivo conditions.
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Rh(III)-catalyzed C-H activation with allenes to synthesize conjugated olefins.
Org. Lett.
PUBLISHED: 01-03-2014
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Rh(III)-catalyzed C-H activation with allenes produces highly unsaturated conjugated olefins. The reaction is applicable to both olefin and arene C(sp(2))-H and is compatible with a variety of functional groups. The products can be further transformed into other important skeletons through Diels-Alder reaction and intramolecular transesterification.
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De novo Assembly of the Grass Carp Ctenopharyngodon idella Transcriptome to Identify miRNA Targets Associated with Motile Aeromonad Septicemia.
PLoS ONE
PUBLISHED: 01-01-2014
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De novo transcriptome sequencing is a robust method of predicting miRNA target genes, especially for organisms without reference genomes. Differentially expressed miRNAs had been identified previously in kidney samples collected from susceptible and resistant grass carp (Ctenopharyngodon idella) affected by Aeromonas hydrophila. Target identification for these differentially expressed miRNAs poses a major challenge in this non-model organism.
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Nonlinear mixed-effects (NLME) diameter growth models for individual China-Fir (Cunninghamia lanceolata) trees in Southeast China.
PLoS ONE
PUBLISHED: 01-01-2014
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An individual-tree diameter growth model was developed for Cunninghamia lanceolata in Fujian province, southeast China. Data were obtained from 72 plantation-grown China-fir trees in 24 single-species plots. Ordinary non-linear least squares regression was used to choose the best base model from among 5 theoretical growth equations; selection criteria were the smallest absolute mean residual and root mean square error and the largest adjusted coefficient of determination. To account for autocorrelation in the repeated-measures data, we developed one-level and nested two-level nonlinear mixed-effects (NLME) models, constructed on the selected base model; the NLME models incorporated random effects of the tree and plot. The best random-effects combinations for the NLME models were identified by Akaike's information criterion, Bayesian information criterion and -2 logarithm likelihood. Heteroscedasticity was reduced with two residual variance functions, a power function and an exponential function. The autocorrelation was addressed with three residual autocorrelation structures: a first-order autoregressive structure [AR(1)], a combination of first-order autoregressive and moving average structures [ARMA(1,1)] and a compound symmetry structure (CS). The one-level (tree) NLME model performed best. Independent validation data were used to test the performance of the models and to demonstrate the advantage of calibrating the NLME models.
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Transcriptomic analysis of carboxylic acid challenge in Escherichia coli: beyond membrane damage.
PLoS ONE
PUBLISHED: 01-01-2014
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Carboxylic acids are an attractive biorenewable chemical. Enormous progress has been made in engineering microbes for production of these compounds though titers remain lower than desired. Here we used transcriptome analysis of Escherichia coli during exogenous challenge with octanoic acid (C8) at pH 7.0 to probe mechanisms of toxicity. This analysis highlights the intracellular acidification and membrane damage caused by C8 challenge. Network component analysis identified transcription factors with altered activity including GadE, the activator of the glutamate-dependent acid resistance system (AR2) and Lrp, the amino acid biosynthesis regulator. The intracellular acidification was quantified during exogenous challenge, but was not observed in a carboxylic acid producing strain, though this may be due to lower titers than those used in our exogenous challenge studies. We developed a framework for predicting the proton motive force during adaptation to strong inorganic acids and carboxylic acids. This model predicts that inorganic acid challenge is mitigated by cation accumulation, but that carboxylic acid challenge inverts the proton motive force and requires anion accumulation. Utilization of native acid resistance systems was not useful in terms of supporting growth or alleviating intracellular acidification. AR2 was found to be non-functional, possibly due to membrane damage. We proposed that interaction of Lrp and C8 resulted in repression of amino acid biosynthesis. However, this hypothesis was not supported by perturbation of lrp expression or amino acid supplementation. E. coli strains were also engineered for altered cyclopropane fatty acid content in the membrane, which had a dramatic effect on membrane properties, though C8 tolerance was not increased. We conclude that achieving higher production titers requires circumventing the membrane damage. As higher titers are achieved, acidification may become problematic.
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Six-dimensional quantum dynamics study for the dissociative adsorption of HCl on Au(111) surface.
J Chem Phys
PUBLISHED: 12-11-2013
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The six-dimensional quantum dynamics calculations for the dissociative chemisorption of HCl on Au(111) are carried out using the time-dependent wave-packet approach, based on an accurate PES which was recently developed by neural network fitting to density functional theory energy points. The influence of vibrational excitation and rotational orientation of HCl on the reactivity is investigated by calculating the exact six-dimensional dissociation probabilities, as well as the four-dimensional fixed-site dissociation probabilities. The vibrational excitation of HCl enhances the reactivity and the helicopter orientation yields higher dissociation probability than the cartwheel orientation. A new interesting site-averaged effect is found for the title molecule-surface system that one can essentially reproduce the six-dimensional dissociation probability by averaging the four-dimensional dissociation probabilities over 25 fixed sites.
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Larger late sodium current density as well as greater sensitivities to ATX II and ranolazine in rabbit left atrial than left ventricular myocytes.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 12-06-2013
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An increase of cardiac late sodium current (INa.L) is arrhythmogenic in atrial and ventricular tissues, But the densities of INa.L and thus the potential relative contributions of this current to Na(+) influx and arrhythmogenesis in atria and ventricles are unclear. In this study, whole-cell and cell-attached patch clamp techniques were used to measure INa.L in rabbit left atrial and ventricular myocytes under identical conditions. The density of INa.L was 67% greater in atrial (0.50 ± 0.09 pA/pF, n = 20) than in left ventricular cells (0.30 ± 0.07 pA/pF, n = 27, P < 0.01) when elicited by step pulses from -120 to -20 mV at a rate of 0.2 Hz. Similar results were obtained using step pulses from -90 to -20 mV. Anemone toxin II (ATX II) increased INa.L with an EC50 value of 14 ± 2 nM and a Hill slope of 1.4 ± 0.1 (n = 9) in atrial myocytes and with an EC50 of 21 ± 5 nM and a Hill slope of 1.2 ± 0.1 (n = 12) in ventricular myocytes. Na(+) channel open probability (but not mean open time) was greater in atrial than in ventricular cells in the absence and presence of ATX II. The INa.L inhibitor ranolazine (3, 6, 9 ?M) reduced INa.L more in atrial than ventricular myocytes in the presence of 40 nM ATX II. In summary, rabbit left atrial myocytes have a greater density of INa.L and higher sensitivities to ATX II and ranolazine than rabbit left ventricular myocytes.
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Kinetically controlled synthesis of Pt-Cu alloy concave nanocubes with high-index facets for methanol electro-oxidation.
Chem. Commun. (Camb.)
PUBLISHED: 11-22-2013
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Pt-Cu alloy concave nanocubes enclosed by high-index {511} facets were synthesized in high yields and exhibited substantially enhanced electrocatalytic properties for methanol oxidation relative to commercial Pt/C.
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Restoration of the unfolded protein response in pancreatic ? cells protects mice against type 1 diabetes.
Sci Transl Med
PUBLISHED: 11-15-2013
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Perturbations in endoplasmic reticulum (ER) homeostasis can evoke stress responses leading to aberrant glucose and lipid metabolism. ER dysfunction is linked to inflammatory disorders, but its role in the pathogenesis of autoimmune type 1 diabetes (T1D) remains unknown. We identified defects in the expression of unfolded protein response (UPR) mediators ATF6 (activating transcription factor 6) and XBP1 (X-box binding protein 1) in ? cells from two different T1D mouse models and then demonstrated similar defects in pancreatic ? cells from T1D patients. Administration of a chemical ER stress mitigator, tauroursodeoxycholic acid (TUDCA), at the prediabetic stage resulted in a marked reduction of diabetes incidence in the T1D mouse models. This reduction was accompanied by (i) a significant decrease in aggressive lymphocytic infiltration in the pancreas, (ii) improved survival and morphology of ? cells, (iii) reduced ? cell apoptosis, (iv) preserved insulin secretion, and (v) restored expression of UPR mediators. TUDCAs actions were dependent on ATF6 and were lost in mice with ? cell-specific deletion of ATF6. These data indicate that proper maintenance of the UPR is essential for the preservation of ? cells and that defects in this process can be chemically restored for preventive or therapeutic interventions in T1D.
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A Modified Staged Surgical Intervention for Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome: 125 Cases With Encouraging Results.
Ann Plast Surg
PUBLISHED: 10-30-2013
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Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant condition characterized by typical eyelid malformations that include blepharophimosis, ptosis, epicanthus inversus, and telecanthus.
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Linear correlation between the C-H activation barrier and the C-Cu/C-H bond dissociation energy gap in Cu-promoted C-H activation of heteroarenes.
Chem. Commun. (Camb.)
PUBLISHED: 10-16-2013
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DFT calculations indicate a linear correlation between the C-H activation barrier and the C-Cu/C-H bond dissociation energy gap in Cu-promoted C-H activation of heteroarenes.
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Integrative annotation of variants from 1092 humans: application to cancer genomics.
Science
PUBLISHED: 10-05-2013
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Interpreting variants, especially noncoding ones, in the increasing number of personal genomes is challenging. We used patterns of polymorphisms in functionally annotated regions in 1092 humans to identify deleterious variants; then we experimentally validated candidates. We analyzed both coding and noncoding regions, with the former corroborating the latter. We found regions particularly sensitive to mutations ("ultrasensitive") and variants that are disruptive because of mechanistic effects on transcription-factor binding (that is, "motif-breakers"). We also found variants in regions with higher network centrality tend to be deleterious. Insertions and deletions followed a similar pattern to single-nucleotide variants, with some notable exceptions (e.g., certain deletions and enhancers). On the basis of these patterns, we developed a computational tool (FunSeq), whose application to ~90 cancer genomes reveals nearly a hundred candidate noncoding drivers.
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A novel Gaussian Binning (1GB) analysis of vibrational state distributions in highly excited H2O from reactive quenching of OH? by H2.
J Chem Phys
PUBLISHED: 08-02-2013
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As shown in experiments by Lester and co-workers [J. Chem. Phys. 110, 11117 (1999)], the reactive quenching of OH? by H2 produces highly excited H2O. Previous limited analysis of quasiclassical trajectory calculations using standard Histogram Binning (HB) was reported [B. Fu, E. Kamarchik, and J. M. Bowman, J. Chem. Phys. 133, 164306 (2010)]. Here, we examine the quantized internal state distributions of H2O in more detail, using two versions of Gaussian Binning (denoted 1GB). In addition to the standard version of 1GB, which relies on the harmonic energies of the states (1GB-H), we propose a new and more accurate technique based on exact quantum vibrational energies (1GB-EQ). Data from about 42,000 trajectories from previous calculations that give excited water molecules are used in the two versions of 1GB as well as HB. For the vibrationally hot molecules considered in this study, the classical internal energy distribution serves as a benchmark to estimate the accuracy of the different binning methods analyzed. The 1GB discretization methods, especially the one using exact quantum energies, reconstruct the classical distribution much more accurately than HB and also the original, more elaborate Gaussian Binning method. Detailed quantum state distributions are presented for pure overtone excitations as well as several antisymmetric stretch distributions. The latter are focused on because the antisymmetric stretch has the largest emission oscillator strength of the three water modes.
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Mechanistic Study on Ligand-Controlled Cobalt-Catalyzed Regioselectivity-Switchable Hydroarylation of Styrenes.
Chemistry
PUBLISHED: 07-30-2013
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Density functional theory (DFT) calculations have been performed to study the mechanism of the recently reported Co-catalyzed ligand-controlled hydroarylation of styrenes as a means of preparing 1,1- or 1,2-diarylalkanes. The present study corroborates the previously proposed three-step mechanism, comprising C?H activation (C?H oxidative addition), styrene insertion, and reductive elimination. In the C?H activation and reductive elimination steps, our calculations suggest that styrene does not coordinate to the Co center. In the insertion step, styrene is inserted into the Co?H bond rather than the Co?C bond. Furthermore, the rate- and regiodetermining step is found to be C?C reductive elimination. It is significant that the regioselectivity observed experimentally has been successfully reproduced by our calculations. More importantly, in analyzing the origin of the ligand-controlled regioselectivity, we have found that the steric effects of different ligands mainly determine the observed regioselectivity. Both the shape (i.e., "umbrella-up" or "umbrella-down") and bulkiness of the ligand contribute to the steric effect.
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Quasiclassical trajectory studies of 18O(3P) + NO2 isotope exchange and reaction to O2 + NO on D0 and D1 potentials.
J Chem Phys
PUBLISHED: 07-19-2013
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We report quasiclassical trajectory calculations for the bimolecular reaction (18)O((3)P) + NO2 on the recent potential energy surfaces of the ground (D0) and first excited (D1) states of NO3 [B. Fu, J. M. Bowman, H. Xiao, S. Maeda, and K. Morokuma, J. Chem. Theory. Comput. 9, 893 (2013)]. The branching ratio of isotope exchange versus O2 + NO formation, as well as the product angular distributions and energy and rovibrational state distributions are presented. The calculations are done at the collision energy of relevance to recent crossed beam experiments [K. A. Mar, A. L. Van Wyngarden, C.-W. Liang, Y. T. Lee, J. J. Lin, and K. A. Boering, J. Chem. Phys. 137, 044302 (2012)]. Very good agreement is achieved between the current calculations and these experiments for the branching ratio and final translational energy and angular distributions of isotope exchange products (16)O((3)P) + NO2 and O2 + NO formation products. The reactant (18)O atom results in (18)O(16)O but not N(18)O for the O2 + NO formation product channel, consistent with the experiment. In addition, the detailed vibrational and rotational state information of diatomic molecules calculated currently for the (34)O2 + NO formation channel on D0 and D1 states are in qualitative agreement with the previous experimental and theoretical results of the photodissociation of NO3 and are consistent with older thermal bimolecular kinetics measurements.
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A half-sandwich 1,2-azaborolyl ruthenium complex: synthesis, characterization, and evaluation of its catalytic activities.
Dalton Trans
PUBLISHED: 07-12-2013
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A half-sandwich 1,2-azaborolyl (Ab) ruthenium complex, (Ab-C?CPh)RuCl(PPh3)2 (1), has been synthesized by treating RuCl2(PPh3)3 with lithium 1,2-azaborolide L-1, or by treating either RuCl2(PPh3)3 or RuHCl(PPh3)3 directly with 1,2-azaborole LH-1. It is evaluated as a suitable precatalyst in [2 + 2] cycloadditions of norbornene derivatives with DMAD and in atom transfer radical additions of halogenated compounds with olefins.
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Rhodium-catalyzed directed C-H cyanation of arenes with N-cyano-N-phenyl-p-toluenesulfonamide.
J. Am. Chem. Soc.
PUBLISHED: 07-12-2013
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A Rh-catalyzed directed C-H cyanation reaction was developed for the first time as a practical method for the synthesis of aromatic nitriles. N-Cyano-N-phenyl-p-toluenesulfonamide, a user-friendly cyanation reagent, was used in the transformation. Many different directing groups can be used in this C-H cyanation process, and the reaction tolerates a variety of synthetically important functional groups.
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Epigallocatechin-3-gallate induces apoptosis, inhibits proliferation and decreases invasion of glioma cell.
Neurosci Bull
PUBLISHED: 06-03-2013
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Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, has been considered a potential therapeutic and chemopreventive agent for cancer. Glioma is a malignant tumor with high mortality but effective therapy has not yet been developed. In this study, we found that EGCG induced apoptosis in U251 glioma cells via the laminin receptor (molecular weight 67kDa) in a time- and dose-dependent manner, decreased their invasiveness and inhibited their proliferation. The mitogen-activated protein kinase pathway was shown to be involved in glioma cell apoptosis and proliferation. Furthermore, the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9 were reduced after EGCG treatment. These results suggest that EGCG has important therapeutic effects with low toxicity and side-effects, and could be used in cancer chemoprevention.
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Copper-promoted Sandmeyer trifluoromethylation reaction.
J. Am. Chem. Soc.
PUBLISHED: 06-03-2013
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A copper-promoted trifluoromethylation reaction of aromatic amines is described. This transformation proceeds smoothly under mild conditions and exhibits good tolerance of many synthetically relevant functional groups. It provides an alternative approach for the synthesis of trifluoromethylated arenes and heteroarenes. It also constitutes a new example of the Sandmeyer reaction.
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Effects of melatonin on superovulation and transgenic embryo transplantation in small-tailed han sheep (Ovis aries).
Neuro Endocrinol. Lett.
PUBLISHED: 06-01-2013
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In this study, the effects of melatonin on superovulation and the transfer of transgenic embryos were investigated in Small-Tailed Han sheep.
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Production of aromatic hydrocarbons through catalytic pyrolysis of 5-Hydroxymethylfurfural from biomass.
Bioresour. Technol.
PUBLISHED: 05-18-2013
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Catalytic pyrolysis of 5-Hydroxymethylfurfural (HMF) was conducted on a fixed bed reactor at atmospheric pressure. HMF could be converted into aromatic hydrocarbons through catalytic pyrolysis. The catalysts and reaction conditions were both critical in maximizing the aromatic hydrocarbons selectivity. Four catalysts, ?-zeolite, HZSM-5, Ga/HZSM and In/HZSM were tested in this study. HZSM-5 (Si/Al=50) was found to be the most effective catalyst in both reactivity and selectivity among these catalysts. Under the reaction temperature of 600 °C, the highest carbon yield of 48.99% of aromatic hydrocarbons was achieved from catalytic pyrolysis HMF with HZSM-5 (Si/Al=50) as catalyst. Moreover, the HZSM-5 (Si/Al=50) catalyst was recycled for five times without shown deactivation of the catalyst.
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What is Visualize?

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

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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.