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Find video protocols related to scientific articles indexed in Pubmed.
Anion A- • HX Clusters with Reduced Electron Binding Energies: Proton vs Hydrogen Atom Relocation Upon Electron Detachment.
J. Am. Chem. Soc.
PUBLISHED: 11-20-2014
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Clustering an anion with one or more neutral molecules is a stabilizing process that enhances the oxidation potential of the complex relative to the free ion. Several hydrogen bond clusters (i.e., A- • HX, where A- = H2PO4- and CF3CO2- and HX = MeOH, PhOH, and Me2NOH or Et2NOH) are examined by photoelectron spectroscopy and M06-2X and CCSD(T) computations. Remarkably, these species are experimentally found to have adiabatic detachment energies that are smaller than those for the free ion and reductions of 0.47 to 1.87 eV are predicted computationally. Hydrogen atom and proton transfers upon vertical photodetachment are two limiting extremes on the neutral surface in a continuum of mechanistic pathways that account for these results, and the whole gamut of possibilities are predicted to occur.
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Fullerene cyanation does not always increase electron affinity: an experimental and theoretical study.
Phys Chem Chem Phys
PUBLISHED: 11-20-2014
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The electron affinities of C70 derivatives with trifluoromethyl, methyl and cyano groups were studied experimentally and theoretically using low-temperature photoelectron spectroscopy (LT PES) and density functional theory (DFT). The electronic effects of these functional groups were determined and found to be highly dependent on the addition patterns. Substitution of CF3 for CN for the same addition pattern increases the experimental electron affinity by 70 meV per substitution. The synthesis of a new fullerene derivative, C70(CF3)10(CN)2, is reported for the first time.
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Comparison of waveguide properties and Raman spectroscopic visualization of C and O ion implantation on LaAlO3 crystals.
Appl Opt
PUBLISHED: 11-18-2014
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LaAlO3 crystals were implanted by C ions and O ions at an energy of 6.0 MeV with a fluence of 1.5×1015??ions/cm2. The profiles of the guided modes were measured through prism coupling and end-face coupling methods with a 633 nm laser source. A nonleaky waveguide structure in the TM mode was fabricated by O ion implantation after a proper annealing treatment. Characteristics of the implanted C and O ions were compared. Some changes of the full width at half of the maximum and intensity of the Raman spectra were observed between the waveguide and substrate regions in LaAlO3 crystals. Thus, the Raman spectra can be used to visualize any damage or defects in the LaAlO3 crystals during the implantation process.
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Up-Regulation of miR-21 and miR-23a Contributes to As2 O3 -induced hERG Channel Deficiency.
Basic Clin. Pharmacol. Toxicol.
PUBLISHED: 11-15-2014
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Arsenic trioxide (As2 O3 ) is used to treat acute promyelocytic leukaemia. However, the cardiotoxicity of long QT syndrome restricts its clinical application. Previous studies showed that As2 O3 can damage the hERG current via disturbing its trafficking to cellular membrane. Consistent with these findings, in this study we reported that As2 O3 inhibited hERG channel at both protein and mRNA levels, damage hERG current but did not affect channel kinetics. Further, we demonstrated that As2 O3 up-regulated miR-21 and miR-23a expression in hERG-HEK293 cells and neonatal cardiomyocytes. In addition, knockdown of miR-21 by its specific antisense molecules AMO-21 was able to rescue Sp1 and hERG inhibition caused by As2 O3 . Consistently, phosphorylation of NF-?B, the upstream regulatory factor of miR-21, was significantly up-regulated by As2 O3 . This finding revealed that regulation of the NF-?B-miR-21-Sp1 signalling pathway is a novel mechanism for As2 O3 -induced hERG inhibition. Meanwhile, the expression of HSP90 and hERG was rescued by transfection with AMO-23a. And the hERG channel inhibition induced by As2 O3 was rescued after being transfected with AMO-23a, which may be a molecular mechanism for the role of As2 O3 in hERG trafficking deficiency. In brief, our study revealed that miR-21 and miR-23a are involved in As2 O3 -induced hERG deficiency at transcriptional and transportational levels. This discovery may provide a novel mechanism of As2 O3 -induced hERG channel deficiency and these miRNAs may serve as potential therapeutic targets for the handling of As2 O3 cardiotoxicity. This article is protected by copyright. All rights reserved.
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PubAngioGen: a database and knowledge for angiogenesis and related diseases.
Nucleic Acids Res.
PUBLISHED: 11-11-2014
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Angiogenesis is the process of generating new blood vessels based on existing ones, which is involved in many diseases including cancers, cardiovascular diseases and diabetes mellitus. Recently, great efforts have been made to explore the mechanisms of angiogenesis in various diseases and many angiogenic factors have been discovered as therapeutic targets in anti- or pro-angiogenic drug development. However, the resulted information is sparsely distributed and no systematical summarization has been made. In order to integrate these related results and facilitate the researches for the community, we conducted manual text-mining from published literature and built a database named as PubAngioGen (http://www.megabionet.org/aspd/). Our online application displays a comprehensive network for exploring the connection between angiogenesis and diseases at multilevels including protein-protein interaction, drug-target, disease-gene and signaling pathways among various cells and animal models recorded through text-mining. To enlarge the scope of the PubAngioGen application, our database also links to other common resources including STRING, DrugBank and OMIM databases, which will facilitate understanding the underlying molecular mechanisms of angiogenesis and drug development in clinical therapy.
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Behavior of Shiga Toxigenic Escherichia coli Relevant to Lettuce Washing Processes and Consideration of Factors for Evaluating Washing Process Surrogates.
J. Food Prot.
PUBLISHED: 11-04-2014
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Postharvest processes for fresh produce commonly include washing in water containing antimicrobial chemicals, such as chlorine; however, if the antimicrobials are not present in sufficient levels, washing can promote the spread of contamination that might be present. To understand cross-contamination risk during washing, we tested a collection of Shiga toxigenic Escherichia coli (STEC), including O157:H7 and other non-O157 strains, for certain traits during washing of fresh-cut lettuce, i.e., sensitivity to sublethal chlorine levels and ability to cross-contaminate (detach from and attach to) lettuce in the presence of sublethal chlorine levels. Nonpathogenic E. coli Nissle 1917 (EcN) and Pediococcus pentosaceus lactic acid bacterial species (LAB) were included as potential washing process validation surrogates. As measured by extension of the lag phase of growth in media containing 0.15 ppm of chlorine, chlorine sensitivity varied among the STECs. Cross-contamination was assessed by evaluating transfer of bacteria from inoculated to uninoculated leaves during washing. Without chlorine, similar transfer to wash water and uninoculated leaves was shown. In 1 ppm of chlorine, cross-contamination was not detected with most strains, except for the substantial transfer by a STEC O111 strain and EcN in some replicates. Strain O111 and EcN showed less inactivation in 0.25 ppm of chlorine water compared with O157 (P < 0.05). LAB showed similar transfer and similar chlorine inactivation to O157. Considering together the sublethal chlorine sensitivity and detachment/attachment traits, neither EcN nor LAB displayed optimal characteristics as washing process surrogates for the STEC strains, although further evaluation is needed. This work demonstrated a range of behaviors of STEC strains during lettuce washing and may be helpful in hazard characterization, identifying factors to consider for evaluating washing process efficacy, and identifying phenotypic traits to select surrogates to validate washing processes.
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Topical corticosteroids as adjunctive therapy for bacterial keratitis.
Cochrane Database Syst Rev
PUBLISHED: 10-17-2014
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Bacterial keratitis is a serious ocular infectious disease that can lead to severe visual disability. Risk factors for bacterial corneal infection include contact lens wear, ocular surface disease, corneal trauma, and previous ocular or eyelid surgery. Topical antibiotics constitute the mainstay of treatment in cases of bacterial keratitis, whereas the use of topical corticosteroids as an adjunctive therapy to antibiotics remains controversial. Topical corticosteroids are usually used to control inflammation using the smallest amount of the drug. Their use requires optimal timing, concomitant antibiotics, and careful follow-up.
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Tailored synthesis of hierarchical spinous hollow titania hexagonal prisms via a self-template route.
Nanoscale
PUBLISHED: 10-14-2014
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Novel hierarchical spinous hollow titania hexagonal prisms are prepared through a facile fluorine-free self-template route using Ti2O3(H2O)2(C2O4)·H2O (TC) hexagonal prisms as a precursor. The hollowing transformation can be elucidated by the template-free Kirkendall effect, and diverse nanostructures can also be synthesized during the conversion process, such as the spinous core-shell and yolk-shell nanocomposites. The hierarchical hollow microparticles are composed of ultrathin nanobelts of 50-100 nm in length and about 10 nm in thickness, and possess a higher surface area of up to 163 m(2) g(-1) compared with solid microparticles (49 m(2) g(-1)). This type of morphology is of great interest for lithium-ion batteries because of its shorter length for Li(+) transport and better electrode-electrolyte contact.
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DnaJA1/Hsp40 is co-opted by influenza A virus to enhance its viral RNA polymerase activity.
J. Virol.
PUBLISHED: 09-24-2014
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The RNA-dependent RNA polymerase (RdRp) of influenza A virus is a heterotrimeric complex composed by PB1, PB2 and PA subunits. The interplay between host factors and the three subunits of the RdRp is critical to enable viral RNA synthesis to occur in the nucleus of infected cells. In this report, we newly identified a host factor DnaJA1, a member of the type I DnaJ/Hsp40 family, acting as a positive regulator for influenza virus replication. We found that DnaJA1 associates with PB2 and PA subunits and enhances viral RNA synthesis both in vivo and in vitro. Moreover, DnaJA1 could be translocated from cytoplasm into the nucleus upon influenza virus infection. The translocation of DnaJA1 is specifically accompanied by the PB1-PA nuclear import. Interestingly, we observed that the effect of DnaJA1 on viral RNA synthesis is mainly dependent on its C-terminal substrate-binding domain but not on its typical J-domain, while the J-domain normally mediates the Hsp70-DnaJ interaction required for regulating Hsp70 ATPase activity. Therefore, we propose that DnaJA1 is co-opted by the influenza A virus to entre nucleus and to enhance its RNA polymerase activity in an Hsp70 cochaperone-independent manner.
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Asymmetric Connectivity between the Anterior Temporal Lobe and the Language Network.
J Cogn Neurosci
PUBLISHED: 09-23-2014
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The anterior temporal lobe (ATL) sits at the confluence of auditory, visual, olfactory, transmodal, and limbic processing hierarchies. In keeping with this anatomical heterogeneity, the ATL has been implicated in numerous functional domains, including language, semantic memory, social cognition, and facial identification. One question that has attracted considerable discussion is whether the ATL contains a mosaic of differentially specialized areas or whether it provides a domain-independent amodal hub. In the current study, based on task-free fMRI in right-handed neurologically intact participants, we found that the left lateral ATL is interconnected with hubs of the temporosylvian language network, including the inferior frontal gyrus and middle temporal gyrus of the ipsilateral hemisphere and, to a lesser extent, with homotopic areas of the contralateral hemisphere. In contrast, the right lateral ATL had much weaker functional connectivity with these regions in either hemisphere. Together with evidence that has been gathered in lesion-mapping and event-related neuroimaging studies, this asymmetry of functional connectivity supports the inclusion of the left ATL within the language network, a relationship that had been overlooked by classic aphasiology. The asymmetric domain selectivity for language of the left ATL, together with the absence of such an affiliation in the right ATL, is inconsistent with a strict definition of uniformly domain-independent amodal functionality in this region of the brain.
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[Effect of estradiol on cholesterol metabolism in J774a.1 mouse mononuclear/macrophage cells].
Yao Xue Xue Bao
PUBLISHED: 09-20-2014
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To explore the anti-atherosclerotic mechanism of estrogen and especially observe the effect of estradiol on the content of cholesterol in J774a.1 mouse mononuclear/macrophage-derived foam cells which were incubated with oxidized low-density lipoproteins (ox-LDL). J774a.1 mouse mononuclear/macrophages were incubated with ox-LDL or with both ox-LDL and estradiol (1, 0.1 or 0.01 micromol x L(-1)). Oil red O staining was used to observe the formation of foam cells, and cholesterol oxidase fluorometric was used to determine the content of cellular cholesterol content. Western blotting and RTFQ-PCR were used to observe the expressions of scavenger receptor class B type I (SR-B I ) in J774a.1 foam cells. Compared with the control cells, J774a.1 mouse mononuclear/macrophage-derived foam cells showed significantly increased contents of total cholesterol and cholesterol ester (P < 0.001) and decreased SR-B I mRNA expression (P < 0.01). Estradiol treatment significantly lowered the contents of total cholesterol and cholesterol ester (P < 0.05), and increased SR-B I protein and mRNA expression (P < 0.01) in the foam cells in a dose-dependent manner. Estradiol can inhibit the formation of mononuclear/macrophage-derived foam cells by decreasing the contents of total cholesterol and cholesterol ester and up-regulating the expression of SR-B I in the foam cells.
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Acupuncture for acute hordeolum.
Cochrane Database Syst Rev
PUBLISHED: 09-13-2014
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This is the protocol for a review and there is no abstract. The objectives are as follows: The objective of this review is to determine the effects and, when possible, the safety of acupuncture for the treatment of acute hordeola, in comparison to no specific treatment (e.g., observation), sham acupuncture, or other active treatments. Acupuncture as an adjuvant to another treatment also will be compared to that treatment alone.
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Resting-state functional connectivity in women with Major Depressive Disorder.
J Psychiatr Res
PUBLISHED: 09-03-2014
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Limited research has focused on whole-brain functional connectivity in a well-characterized sample of subjects with current Major Depressive Disorder (MDD). We aimed to investigate resting-state functional connectivity and the extent to which this is correlated with depression severity in unmedicated depressed subjects without comorbidities.
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[Effects of Corbicula fluminea bioturbation on the community composition and abundance of ammonia-oxidizing archaea and bacteria in surface sediments].
Huan Jing Ke Xue
PUBLISHED: 08-28-2014
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To better understand the effects of Corbicula fluminea bioturbation on the ammonia-oxidizing microorganisms in the surface sediment, sediment-water microcosms with different densities of Corbicula fluminea were constructed. Clone libraries and real-time qPCR were applied to analyze the community composition and abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in the surface sediments. The results obtained indicated that the bioturbation of Corbicula fluminea accelerated the release of nitrogen from the surface sediment. In the amoA gene clone libraries, the identified AOA amoA gene sequences affiliated with the two known clusters (marine and soil clusters). The identified AOB amoA gene sequences mostly belonged to the Nitrosomonas of beta-Proteobacteria. The abundance of the bacterial amoA gene was higher than that of the archaeal amoA gene in all treatments. With increasing density of Corbicula fluminea, decreased abundances of the bacterial amoA gene were observed. At the same time, the diversity of AOA and AOB reduced in the Corbicula fluminea containing microcosms. In conclusion, the bioturbation of Corbicula fluminea could affected the community composition and abundance of ammonia-oxidizing microorganisms in surface sediments.
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RVboost: RNA-seq variants prioritization using a boosting method.
Bioinformatics
PUBLISHED: 08-27-2014
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RNA-seq has become the method of choice to quantify genes and exons, discover novel transcripts and detect fusion genes. However, reliable variant identification from RNA-seq data remains challenging because of the complexities of the transcriptome, the challenges of accurately mapping exon boundary spanning reads and the bias introduced during the sequencing library preparation.
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Analysis of COQ2 gene in multiple system atrophy.
Mol Neurodegener
PUBLISHED: 08-26-2014
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Loss of function COQ2 mutations results in primary CoQ10 deficiency. Recently, recessive mutations of the COQ2 gene have been identified in two unrelated Japanese families with multiple system atrophy (MSA). It has also been proposed that specific heterozygous variants in the COQ2 gene may confer susceptibility to sporadic MSA. To assess the frequency of COQ2 variants in patients with MSA, we sequenced the entire coding region and investigated all exonic copy number variants of the COQ2 gene in 97 pathologically-confirmed and 58 clinically-diagnosed MSA patients from the United States.
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Biomass-directed synthesis of 20 g high-quality boron nitride nanosheets for thermoconductive polymeric composites.
ACS Nano
PUBLISHED: 08-25-2014
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Electrically insulating boron nitride (BN) nanosheets possess thermal conductivity similar to and thermal and chemical stabilities superior to those of electrically conductive graphenes. Currently the production and application of BN nanosheets are rather limited due to the complexity of the BN binary compound growth, as opposed to massive graphene production. Here we have developed the original strategy "biomass-directed on-site synthesis" toward mass production of high-crystal-quality BN nanosheets. The strikingly effective, reliable, and high-throughput (dozens of grams) synthesis is directed by diverse biomass sources through the carbothermal reduction of gaseous boron oxide species. The produced BN nanosheets are single crystalline, laterally large, and atomically thin. Additionally, they assemble themselves into the same macroscopic shapes peculiar to original biomasses. The nanosheets are further utilized for making thermoconductive and electrically insulating epoxy/BN composites with a 14-fold increase in thermal conductivity, which are envisaged to be particularly valuable for future high-performance electronic packaging materials.
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The negative ion photoelectron spectrum of cyclopropane-1,2,3-trione radical anion, (CO)3(•-)--a joint experimental and computational study.
J. Am. Chem. Soc.
PUBLISHED: 08-22-2014
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Negative ion photoelectron (NIPE) spectra of the radical anion of cyclopropane-1,2,3-trione, (CO)3(•-), have been obtained at 20 K, using both 355 and 266 nm lasers for electron photodetachment. The spectra show broadened bands, due to the short lifetimes of both the singlet and triplet states of neutral (CO)3 and, to a lesser extent, to the vibrational progressions that accompany the photodetachment process. The smaller intensity of the band with the lower electron binding energy suggests that the singlet is the ground state of (CO)3. From the NIPE spectra, the electron affinity (EA) and the singlet-triplet energy gap of (CO)3 are estimated to be, respectively, EA = 3.1 ± 0.1 eV and ?EST = -14 ± 3 kcal/mol. High-level, (U)CCSD(T)/aug-cc-pVQZ//(U)CCSD(T)/aug-cc-pVTZ, calculations give EA = 3.04 eV for the (1)A1' ground state of (CO)3 and ?EST = -13.8 kcal/mol for the energy gap between the (1)A1' and (3)A2 states, in excellent agreement with values from the NIPE spectra. In addition, simulations of the vibrational structures for formation of these states of (CO)3 from the (2)A2? state of (CO)3(•-) provide a good fit to the shapes of broad bands in the 266 nm NIPE spectrum. The NIPE spectrum of (CO)3(•-) and the analysis of the spectrum by high-quality electronic structure calculations demonstrate that NIPES can not only access and provide information about transition structures but NIPES can also access and provide information about hilltops on potential energy surfaces.
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Spectacle correction versus no spectacles for prevention of strabismus in hyperopic children.
Cochrane Database Syst Rev
PUBLISHED: 08-18-2014
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Hyperopia (far-sightedness) in infancy requires accommodative effort to bring images into focus. Prolonged accommodative effort has been associated with an increased risk of strabismus (eye misalignment). Strabismus makes it difficult for the eyes to work together and may result in symptoms of asthenopia (eye strain) and intermittent diplopia (double vision), and makes near work tasks difficult to complete. Untreated strabismus may result in the development of amblyopia (lazy eye). The prescription of spectacles to correct hyperopic refractive error is believed to prevent the development of strabismus.
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Associations between AT-rich interactive domain 5B gene polymorphisms and risk of childhood acute lymphoblastic leukemia: a meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 08-16-2014
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Previous genome-wide association studies (GWAS) have implicated several single nucleotide polymorphisms (SNPs) in the AT-rich interactive domain 5B (ARID5B) gene with childhood acute lymphoblastic leukemia (ALL). However, replicated studies reported some inconsistent results in different populations. Using meta-analysis, we here aimed to clarify the nature of the genetic risks contributed by the two polymorphisms (rs10994982, rs7089424) for developing childhood ALL. Through searches of PubMed, EMBASE, and manually searching relevant references, a total of 14 articles with 16 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated to assess the associations. Both SNPs rs10994982 and rs7089424 showed significant associations with childhood ALL risk in all genetic models after Bonferroni correction. Furthermore, subtype analyses of B-lineage ALL provided strong evidence that SNP rs10994982 is highly associated with the risk of developing B-hyperdiploid ALL. These results indicate that SNPs rs10994982 and rs7089424 are indeed significantly associated with increased risk of childhood ALL.
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Zwitterionic nanoparticles constructed with well-defined reduction-responsive shell and pH-sensitive core for "spatiotemporally pinpointed" drug delivery.
ACS Appl Mater Interfaces
PUBLISHED: 08-13-2014
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Enabling nanocarriers to complete the sophisticated journey from the initial injection site to the targeted tumor cells and achieve "spatiotemporally pinpointed" drug release intracellularly is a challenging task in anticancer drug delivery. Herein, versatile shell-cross-linked nanoparticles (SCNPs) were prepared by one-step assembly of triblock zwitterionic copolymers, polycarboxybetaine methacrylate-block-poly(N-(2-(2-pyridyl disulde) ethyl methacrylamide-block-poly(2-(diisopropylamino) ethyl methacrylate) (PCB-b-PDS-b-PDPA, termed as PCSSD), which was well-defined via reversible additive fragment transfer (RAFT) polymerization, followed by functionalization with Arg-Gly-Asp (RGD). Thus, the RGD-PCSSD SCNPs cooperatively combine the ultra pH-sensitive PDPA core for efficient drug loading and pH-responsive drug release, the disulfide-cross-linked PDS shell that prevents premature drug release, the zwitterionic PCB corona to stabilize the SCNPs and prolong its systemic circulation, the RGD ligand for active tumor targeting and receptor-mediated endocytosis. Doxorubicin (DOX) was loaded as a model medicine (termed as RGD-PCSSD/DOX SCNPs). The dual-sensitivity studies showed that the pH-sensitivity of PDPA core could be adjusted by the shell-cross-linking density, accompanied by better control over premature drug release. Furthermore, results obtained by flow cytometry and fluorescence microscopy analysis demonstrated that once the RGD-PCSS10D/DOX SCNPs were internalized into tumor cells via receptor-mediated endocytosis, boost drug release was observed with considerable cytotoxicity in vitro. The results of ex vivo imaging studies further confirmed the successful drug delivery from the injection site to the tumor tissue. In summary, the well-constructed RGD-PCSS10D/DOX SCNPs with cooperative multifunctionality showed great potential as novel nanocarriers for tumor targeted anticancer drug delivery.
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Re-description of the gudgeon species Saurogobio gracilicaudatus Yao & Yang in Luo, Yue & Chen, 1977 (Teleostei: Cyprinidae) from the Chang-Jiang basin, South China, with a note on its generic classification.
Zootaxa
PUBLISHED: 08-07-2014
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Saurogobio gracilicaudatus, originally described from the middle Yangtze River (Chang-Jiang in Chinese) basin at Yichang and Guanghua (now Laohekou), Hubei Province, South China, is here re-described, with particular concern for oromandibular structures in the mouth. It is uniquely distinguishable from all other species of Saurogobio in having a rostral cap with a slightly crenulated median portion, lips covered with brush-like, conical papillae, and a lower lip with a small, smooth and protruded central pad anteriorly free and posteriorly confluent with lateral lobes. The generic classification of this species is also discussed on the basis of oromandibular structures, which are of taxonomic importance in generic classification of gudgeons. 
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[Effect of Glomus versiforme and Trichoderma harzianum on growth and quality of Salvia miltiorrhiza].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 08-07-2014
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The present study aimed to investigate the effect of Glomus versiforme and Trichodema harzianum on the growth and quality of Salvia miltiorrhiza continuous cropping under field conditions. The field plot experiment was conducted, these active components in the plant were analyzed by HPLC, the root diseases incidence rate of S. miltiorrhiza determined by observation and counting, and relative parameters were measured. The data was statistically processed. The result showed that inoculation of G. versiforme and combined inoculation of G. versiforme with T. harzianum significantly decreased the root diseases incidence rate of S. miltiorrhiza, and combined inoculation of G. versiforme with T. harzianum was better than other treatments. All treatments improved accumulation of active ingredients in root. Inoculation of G. versiforme and combined inoculation of G. versiforme with T. harzianum significantly increased the content of salvianolic acid B and cryptotanshinone of root (P < 0.05), Inoculation of G. versiforme, T. harzianum and combined inoculation of G. versiforme with T. harzianum significantly enhanced the content of tanshinone I and tanshinone II(A) of the root (P < 0.05). It may conclude that inoculation of G. versiforme and combined inoculation of G. versiforme with T. harzianum can effectively reduce the root diseases incidence of continuous cropping S. miltiorrhiza, and improve the quality of S. miltiorrhiza.
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Visible and near-infrared optical properties of a proton-implanted KTP waveguide.
Appl Opt
PUBLISHED: 08-05-2014
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In this work, the optical properties of potassium titanyl phosphate (KTP) waveguides in the visible and near-infrared region are reported. The KTP waveguides were fabricated using 550 keV proton implantation at room temperature, and the refractive index profiles of the implanted region in the visible and near-infrared region were reconstructed. The profiles of the guided modes were measured through the end-face coupling method with both 632.8 and 1539 nm laser sources and then compared with the simulation results using the beam propagation method. Optical transmission and Raman spectra in the original substrate and waveguide active region were measured to study microstructural changes. The propagation loss of the TM0-mode at 632.8 nm was also measured.
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Integrin-targeted zwitterionic polymeric nanoparticles with acid-induced disassembly property for enhanced drug accumulation and release in tumor.
Biomacromolecules
PUBLISHED: 07-30-2014
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Reasonably structural design of nanoparticles (NPs) to combine functions of prolonged systemic circulation, enhanced tumor targeting and specific intracellular drug release is crucial for antitumor drug delivery. Combining advantages of Arg-Gly-Asp (RGD) for active tumor targeting, zwitterionic polycarboxybetaine methacrylate (PCB) for prolonged systemic circulation, poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) for acid-triggered intracellular release, novel RGD-PCB-b-PDPA (RGD-PCD) block copolymers were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization and followed by functionalization with RGD. Doxorubicine (DOX) was encapsulated within the RGD-PCD NPs as model medicine (RGD-PCD/DOX NPs). With ultra pH-sensitivity of PDPA, the drug release was restrained at pH 7.4 for only 24% within 36 h, which was increased to 60% at pH 6.0 within 24 h, and released more rapidly at pH 5.0 for 100% within 5 h, indicating that the RGD-PCD/DOX NPs were able to turn drug release "off" at neutral pH (e.g., systemic circulation) whereas "on" under acidic conditions (e.g., inside endo/lysosomes). Furthermore, the results of fluorescence microscopy and flow cytometry analysis demonstrated improved internalization of RGD-PCD/DOX NPs in HepG2 cells via integrin-mediated endocytosis with rapid DOX release intracellularly. Consequently, the RGD-PCD/DOX NPs showed considerable cytotoxicity against HepG2 and HeLa cells in comparison with free DOX. Importantly, the RGD-PCD/DOX NPs exhibited little protein adsorption property with excellent serum stability, which led to prolonged systemic circulation and enhanced tumor accumulation in tumor-bearing nude mice. Therefore, this multifunctional RGD-PCD NPs, which represented the flexible design approach, showed great potential for the development of novel nanocarriers in tumor-targeted drug delivery.
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A preorganized hydrogen bond network and its effect on anion stability.
J Phys Chem A
PUBLISHED: 07-25-2014
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Rigid tricyclic locked in all axial 1,3,5-cyclohexanetriol derivatives with 0-3 trifluoromethyl groups were synthesized and photoelectron spectra of their conjugate bases and chloride anion clusters are reported along with density functional computations. The resulting vertical and adiabatic detachment energies span 4.07-5.50 eV (VDE) and 3.75-5.00 (ADE) for the former ions and 5.60-6.23 eV (VDE) and 5.36-6.00 eV (ADE) for the latter species. These results provide measures of the anion stabilization due to the hydrogen bond network and inductive effects. The latter mechanism is found to be transmitted through space via hydrogen bonds, and the presence of three ring skeleton oxygen atoms and up to three trifluoromethyl groups enhance the ADEs by 1.61-2.88 eV for the conjugate bases and 1.01-1.60 eV for the chloride anion clusters. Computations indicate that the most favorable structures of the latter complexes have two hydrogen bonds to the chloride anion and one bifurcated interaction between the remote OH substituent and the two hydroxyl groups that directly bind to Cl(-).
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New insights into the nonconserved noncoding region of the subtype-determinant hemagglutinin and neuraminidase segments of influenza A viruses.
J. Virol.
PUBLISHED: 07-23-2014
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The noncoding regions (NCRs) of the eight-segmented viral RNAs (vRNAs) of influenza A virus consist of the highly conserved promoter region and the nonconserved segment-specific NCRs at both the 3' and 5' ends. The roles of the segment-specific NCRs of the eight segments have been extensively studied. However, the diversities in the same region of the two subtype-determinant hemagglutinin (HA) and neuraminidase (NA) segments have received little attention. In this study, we bioinformatically analyzed all available NCRs of HA and NA vRNAs of influenza A viruses and found that nucleotides in the segment-specific NCRs of HA and NA vRNAs are subtype specific and vary significantly in sequence and length at both the 3' and 5' ends among different subtypes. We then systematically studied the biological significance of the HA subtype-specific NCRs (HA ssNCRs) of the common HA subtypes (H1 to H7 and H9) in the context of the WSN (H1N1) reverse genetics system. We found that the HA ssNCRs play a critical role in HA vRNA virion incorporation. Upon HA vRNA incorporation, the 3'-end HA ssNCR plays a more critical role than the 5'-end HA ssNCR, and no stringent compatibility between the two ends is required. Furthermore, our data imply that, in addition to a particular nucleotide(s), the length of the HA ssNCR is involved in regulating HA vRNA incorporation efficiency. These results provide new insights into the HA segment virion incorporation that is critical for the emergence of epidemic and pandemic influenza A virus strains.
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Parthenolide-induced apoptosis, autophagy and suppression of proliferation in HepG2 cells.
Asian Pac. J. Cancer Prev.
PUBLISHED: 07-08-2014
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To investigate the anticancer effects and underlying mechanisms of parthenolide on HepG2 human hepatocellular carcinoma cells.
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Examining the amine functionalization in dicarboxylates: photoelectron spectroscopy and theoretical studies of aspartate and glutamate.
J Phys Chem A
PUBLISHED: 07-07-2014
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Aspartate (Asp(2-)) and glutamate (Glu(2-)), two doubly charged conjugate bases of the corresponding amino acids, were investigated using low-temperature negative ion photoelectron spectroscopy (NIPES) and ab initio calculations. The effect of amine functionalization was studied by a direct comparison to the parent dicarboxylate species ((-)CO2-(CH2)n-CO2(-), DCn(2-)), succinate (DC2(2-)) and propionate (DC3(2-)). Experimentally, the addition of the amine group for the n = 2 case (DC2(2-), Asp(2-)) significantly improves the stability of the resultant Asp(2-) dianionic species, albeit that NIPES shows only a small increase in adiabatic electron detachment energy (ADE) (+0.05 eV). In contrast, for n = 3 (DC3(2-), Glu(2-)), a much larger ADE increase is observed (+0.15 eV). Similar results are obtained through ab initio calculations. The latter indicates that increased stability of Asp(2-) can be attributed to the lowering of the energy of the singlet dianion state due to hydrogen bonding effects. The effect of the amino group on the doublet monoanion state is more complicated and results in the weakening of the binding of the adjacent carboxylate group due to electronic structure resonance effects. This conclusion is confirmed by the analysis of NIPES results that show enhanced production of near-zero kinetic energy electrons observed experimentally for amine-functionalized species.
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Copper(I)-catalyzed multicomponent reaction providing a new access to fully substituted thiophene derivatives.
Org. Lett.
PUBLISHED: 07-02-2014
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Readily available triethylammonium 1-(2-oxoindolin-3-ylidene)-2-aroylethanethiolates are efficiently converted into a variety of fully substituted thiophene derivatives by copper(I)-catalyzed denitrogenative reactions with terminal alkynes and N-sulfonyl azides. This new reaction simultaneously installs C-N, C-S, and C-C bonds, allowing direct formation of highly functionalized thiophenes with a wide diversity in substituents in a one-pot manner. A plausible mechanism for the domino process is proposed.
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Measurement of DCF fluorescence as a measure of reactive oxygen species in murine islets of Langerhans.
Anal Methods
PUBLISHED: 06-24-2014
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In islets of Langerhans, oxidative stress induced by reactive oxygen species (ROS) is thought to be critically involved in ?-cell dysfunction during the development of diabetes. However, ROS have also been hypothesized to play a role in cellular signalling. To aid in delineating the effects of ROS in living islets of Langerhans, the endocrine portion of the pancreas that contain ?-cells, we sought to develop a robust and reproducible protocol to measure these species using the fluorescent dye, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA). The protocol that was developed minimized photobleaching and leakage of H2DCF from murineislets and utilized a normalization procedure to further reduce experimental variability. The method allowed for ~25 min of DCF measurement in living islets. We used the developed protocol to compare DCF fluorescence from batches of islets incubated in varying glucose concentrations and observed ~1.5-fold higher fluorescence signals in 3 vs. 20 mM glucose. The effects of diazoxide, which clamps open K(+) ATP channels reducing intracellular [Ca(2+)] ([Ca(2+)]i) without affecting glucose metabolism, were also investigated. The presence of diazoxide increased DCF fluorescence at all glucose concentrations tested while addition of 30 mM K(+) to increase [Ca(2+)]i reduced the fluorescence by ~15%. With the developed protocol, all experimental methods tested to increase [Ca(2+)]i resulted in a decrease in DCF fluorescence, potentially indicating involvement of ROS in intracellular signalling cascades.
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[Method for Japanese encephalitis virus NS3 protease activity analysis and high-throughput screening assay for inhibitors].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 06-20-2014
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Japanese encephalitis virus (JEV) is a single-stranded and positive-sense RNA, which has a single ORF (open reading frame), encoding a polyprotein precursor. Non-structural protein 3 (NS3) plays an important role in processing the polyprotein precursor and has become an important drug target of flavivirus. In this study, NS2BH-NS3 gene was amplified by PCR and subcloned to the prokaryotic expression plasmid, resulting pET30a-NS2BH-NS3. The fusion protein was expressed in Escherichia coli BL21 (DE3) in soluble form after induction by Isopropyl beta-D-1-Thiogalactopyranoside (IPTG). The recombinant protein was purified by Ni-NTA affinity column. Then a fluorescence resonance energy transfer (FRET) method was used to determine enzymatic activity and the assay conditions were optimized. After screening 113 compounds, we found two compounds inhibiting the activity of NS2BH-NS3. This study provides a convenient and cost-effective method for screening of JEV NS3 protease inhibitor.
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Cdc42 inhibitor ML141 enhances G-CSF-induced hematopoietic stem and progenitor cell mobilization.
Int. J. Hematol.
PUBLISHED: 06-18-2014
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G-CSF is the most often used agent in clinical hematopoietic stem and progenitor cell (HSPC) mobilization. However, in about 10 % of patients, G-CSF does not efficiently mobilize HSPC in clinically sufficient amounts. Cdc42 activity is involved in HSPC mobilization. In the present study, we explore the impact of Cdc42 inhibitor ML141 on G-CSF-mediated HSPC mobilization in mice. We found that the use of ML141 alone only triggered modest HSPC mobilization effect in mice. However, combination of G-CSF and ML141 significantly promoted HPSC counts and colony forming units in peripheral blood, as compared to mice treated with G-CSF alone. ML141 did not significantly alter the levels of SDF-1 and MMP-9 in the bone marrow, when used alone or in combination with G-CSF. We also found that G-CSF administration significantly increases the level of GTP-bound Cdc42, but does not alter the expression of Cdc42 in the bone marrow. Our data indicate that the Cdc42 signal is a negative regulator in G-CSF-mediated HSPC mobilization, and that inhibition of the Cdc42 signal efficiently improves mobilization efficiency. These findings may provide a new strategy for efficient HSPC mobilization, especially in patients with poor G-CSF response.
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Balancing the stability and drug release of polymer micelles by the coordination of dual-sensitive cleavable bonds in cross-linked core.
Acta Biomater
PUBLISHED: 06-10-2014
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The optimal structure design of nanocarriers to inhibit premature release of anticancer drugs from nanocarriers during blood circulation and improve drug release inside tumor cells is still a significant issue for polymer micelles applied to antitumor drug delivery. Herein, in order to balance the contradiction between polymer micellar stability and drug release, dual-sensitive cleavable cross-linkages of benzoic imine conjugated disulfide bonds were introduced into the core of the amphiphilic copolymer micelles to form core-cross-linked micelles. First, biodegradable poly(ethylene glycol)-b-(polycaprolactone-g-poly(methacrylic acid-p-hydroxy benzaldehyde-cystamine)), i.e. mPEG-b-(PCL-g-P(MAA-Hy-Cys)) (PECMHC) copolymers were synthesized and assembled into PECMHC micelles (PECMHC Ms). Then, simply by introducing H2O2 to the PECMHC Ms dispersions to oxidate the thiol groups of cystamine moieties in the core, core-cross-linked PECMHC micelles (cc-PECMHC Ms) ?100nm in size were readily obtained in water. In vitro studies of doxorubicin (DOX)-loaded cc-PECMHC Ms show that the cross-linked core impeded the drug release in the physical conditions, owing to the high stability of the micelles against both extensive dilution and salt concentration, while it greatly accelerated DOX release in mildly acidic (pH ?5.0-6.0) medium with glutathione, owing to the coordination of the pH-sensitive cleaving of benzoic imine bonds and the reduction-sensitive cleaving of disulfide bonds. The in vivo tissue distribution and tumor accumulation of the DOX-loaded cc-PECMHC Ms were monitored via fluorescence images of DOX. DOX-loaded cc-PECMHC Ms exhibited enhanced tumor accumulation because of their high stability in blood circulation and less DOX premature release. Therefore, the cc-PECMHC Ms with dual-sensitive cleavable bonds in the cross-linked core were of excellent biocompatibility, high extracellular stability and had intelligent intracellular drug release properties, indicating promise as candidates for anticancer drug delivery.
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Chemical constituents from Euphorbia stracheyi and their biological activities.
Fitoterapia
PUBLISHED: 06-03-2014
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Three new diterpenoids, stracheyioids A-C (1-3), as well as 36 known compounds (4-39) were isolated from the whole plants of Euphorbia stracheyi. Compound 1 was a rare 13-deoxy tigliane diterpenoid and compound 2 was an ingenol diterpenoid characterized by an unique 2Z,4Z-decadienoyl acidic moieties. All the known compounds were isolated from E. stracheyi for the first time. Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 1-39 were tested for their cytotoxicity against five cancer cell lines (A-549, MCF-7, Hep G2, Hela and P388) and showed IC50 values in the range 6.64-42.86 ?M. The antiangiogenic activities of the isolated compounds were also evaluated using a zebrafish model.
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Antitumor activity of electrospun polylactide nanofibers loaded with 5-fluorouracil and oxaliplatin against colorectal cancer.
Drug Deliv
PUBLISHED: 05-30-2014
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Abstract The purpose of this study was to evaluate both in vitro and in vivo anticancer activities against colorectal cancer (CRC) of electrospun polylactide (PLA) nanofibers loaded with 5-fluorouracil (5-Flu) and oxaliplatin. For in vitro evaluation, human CRC HCT8 cells were directly exposed to the drug-loaded fiber mats, followed with MTT and flow cytometry (FCM) assay. For in vivo evaluation, the drug-loaded fiber mats were locally implanted into mouse colorectal CT26 tumor-bearing mice, followed with histological analysis and detection of survival rate. The results showed that the drug-loaded fiber mats was similar to that of the combination of free 5-Flu and oxaliplatin in vitro cytotoxicity but was much superior to intravenous injection of free drug in vivo anticancer activities, presenting with suppressed tumor growth rate and prolonged survival time of mice. In conclusion, anticancer activities of 5-Flu and oxaliplatin against CRC can be significantly improved by using PLA electrospun nanofibers as local drug delivery system.
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Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.
Chin J Nat Med
PUBLISHED: 05-28-2014
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To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects.
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Poly(trifluoromethyl)azulenes: structures and acceptor properties.
Chem. Commun. (Camb.)
PUBLISHED: 05-02-2014
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Six new poly(trifluoromethyl)azulenes prepared in a single high-temperature reaction exhibit strong electron accepting properties in the gas phase and in solution and demonstrate the propensity to form regular ?-stacked columns in donor-acceptor crystals when mixed with pyrene as a donor.
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Clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma.
Chin. J. Cancer Res.
PUBLISHED: 04-24-2014
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To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma (DLBCL).
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Efficacy and safety of voriconazole and CYP2C19 polymorphism for optimised dosage regimens in patients with invasive fungal infections.
Int. J. Antimicrob. Agents
PUBLISHED: 04-23-2014
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The aim of this study was to determine an optimum voriconazole target concentration, to study the influence of CYP2C19 gene status on metabolism of voriconazole and to identify a dose-adjustment strategy for voriconazole according to CYP2C19 polymorphism in patients with invasive fungal infections. A total of 328 voriconazole trough plasma concentrations (Cmin) were collected and monitored from 144 patients. Information on efficacy and safety was obtained. Voriconazole therapy was effective in 81.9% of patients (118/144), and 12.5% (18/144) exhibited signs of hepatotoxicity. The relationships between voriconazole Cmin and clinical response and hepatotoxicity were explored using logistic regression, and a target clinical Cmin range of 1.5-4mg/L was identified. Values of voriconazole Cmin and the ratio of Cmin to concentration of voriconazole-N-oxide (Cmin/CN) of poor metabolisers (PMs) were significantly higher than extensive metabolisers and intermediate metabolisers. Model-based simulations showed that PM patients could be safely and effectively treated with 200mg twice daily orally or intravenously, and non-PM patients with 300mg twice daily orally or 200mg twice daily intravenously. This study highlighted that voriconazole Cmin and Cmin/CN are strongly influenced by CYP2C19 polymorphism, and gene-adjusted dosing is important to achieve therapeutic levels that maximise therapeutic response and minimise hepatotoxicity.
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Electrochemical biosensing platform based on amino acid ionic liquid functionalized graphene for ultrasensitive biosensing applications.
Biosens Bioelectron
PUBLISHED: 04-08-2014
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In this study, a facile non-covalent method was developed for preparing water-soluble graphene with excellent electronic conductivity. Room temperature ionic liquids (ILs) with high ionic conductivity were used for the non-covalent surface functionalization of graphene through ?-? stacking interactions. Compared to other ILs used, amino acid ionic liquids (AAILs) were found to be the most effective for improving the dispersion of graphene in water phase. Electrochemical and spectroscopic results confirmed that the obtained AAIL functionalized GR can retain the excellent electronic conductivity of pristine graphene without damaging the graphene lattice. The obtained water-soluble graphene (GR-AAIL) was exemplified to fabricate an electrochemical biosensor using tyrosinase as a model enzyme, and the sensitivity (12,600 mA cm(-2) M(-1)) of GR-AAIL based biosensor was about 17 times higher than that of graphene oxide and other nanomaterial based biosensor, displaying its unprecedented high sensitivity for biosensing. The detection limit for catechol (one important environmental pollutant) reached as low as 8 nM with a response time of 3s and a linear range from 25 nM to 11,100 nM. The AAIL-GR based biosensor also demonstrated good reproducibility, repeatability, selectivity, long-term stability and high recovery for catechol detection. Amino acid ionic liquid functionalized graphene proves to be a robust and versatile electrochemical biosensing platform for fabricating biosensors with excellent performance.
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Angiotensin-converting enzyme gene polymorphisms and risk for sporadic Alzheimer's disease: a meta-analysis.
J Neural Transm
PUBLISHED: 03-08-2014
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Numerous studies have tested for associations between common polymorphisms of the angiotensin-converting enzyme gene and sporadic Alzheimer disease (SAD), but results have been inconclusive. Using meta-analysis, our study aimed to clarify the nature of the genetic risks contributed by the three polymorphisms (rs4291, rs4343, rs1800764) for developing SAD. Through searching of Pubmed, Embase, Alzgene and manually searching relevant references, a total of 14 articles with 26 independent studies were included. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the association studies. The heterogeneity across the studies was tested, as was publication bias. We observed significant association between SNP rs4291 and SAD using allelic comparison (OR = 1.08, 95 % CI 1.03-1.14), homozygote comparison (OR = 1.16, 95 % CI 1.04-1.30) and the recessive model (OR = 1.10, 95 % CI 1.02-1.18). Association with SNP rs1800764 was revealed but it was not sufficiently robust to withstand the Benjamini-Hochberg method and stepdown Bonferroni correction. Significant association was not identified in the analysis for SNP rs4343. In subgroup analyses, the risk of SAD associated with SNP rs4291 appeared to be significant among Caucasians and in older cases (mean age ?75 years). Our results confirmed a significant but modest association between SNP rs4291 and SAD susceptibility. Further study of the pathogenetic characteristics of this polymorphism and independent confirmation of the association in larger studies are warranted.
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Adenovirus-mediated CCL20/IL-15 gene transfer enhances antitumor immunity in mice.
Immunobiology
PUBLISHED: 02-20-2014
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The CCL20 chemokine has potent antitumor activities through chemoattracting immature dentritic cells. But the maturation status of tumoral dentritic cells is important limiting factors in DC-based immunity. The endogenous availability of IL-15 was effective in inducing the dentritic cells maturation and IL-15 also shows tumor-specific antitumor activities. We constructed a CCL20/IL-15 bicistronic adenovirus (Ad-CCL20-IL-15) and confirmed its combined antitumor effect in vitro and in vivo. Intratumoral injection of Ad-CCL20-IL-15 into both CT-26 and B16F10 cells resulted in marked reduction of tumor growth in our model. Splenocytes treated by Ad-CCL20-IL-15 developed tumor-specific cytotoxic T cells and IFN-? secretion could protect mice from rechallenging. This study suggests that CCL20/IL-15 can induce a strong antitumor immune response in tumor tissues and it is a suitable candidate for cancer immunotherapy.
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SMN1 duplications contribute to sporadic amyotrophic lateral sclerosis susceptibility: evidence from a meta-analysis.
J. Neurol. Sci.
PUBLISHED: 02-19-2014
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To investigate the association between SMN1 and SMN2 copy number variations (CNVs) and sporadic amyotrophic lateral sclerosis (SALS) by a meta-analysis.
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The negative ion photoelectron spectrum of meta-benzoquinone radical anion (MBQ??): a joint experimental and computational study.
J. Am. Chem. Soc.
PUBLISHED: 02-19-2014
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Negative ion photoelectron (NIPE) spectra of the radical anion of meta-benzoquinone (MBQ, m-OC6H4O) have been obtained at 20 K, using both 355 and 266 nm lasers for electron photodetachment. The spectra show well-resolved peaks and complex spectral patterns. The electron affinity of MBQ is determined from the first resolved peak to be 2.875 ± 0.010 eV. Single-point, CASPT2/aug-cc-pVTZ//CASPT2/aug-cc-pVDZ calculations predict accurately the positions of the 0-0 bands in the NIPE spectrum for formation of the four lowest electronic states of neutral MBQ from the (2)A2 state of MBQ(•-). In addition, the Franck-Condon factors that are computed from the CASPT2/aug-cc-pVDZ optimized geometries, vibrational frequencies, and normal mode vectors, successfully simulate the intensities and frequencies of the vibrational peaks in the NIPE spectrum that are associated with each of these electronic states. The successful simulation of the NIPE spectrum of MBQ(•-) allows the assignment of (3)B2 as the ground state of MBQ, followed by the (1)B2 and (1)A1 electronic states, respectively 9.0 ± 0.2 and 16.6 ± 0.2 kcal/mol higher in energy than the triplet. These experimental energy differences are in good agreement with the calculated values of 9.7 and 15.7 kcal/mol. The relative energies of these two singlet states in MBQ confirm the previous prediction that their relative energies would be reversed from those in meta-benzoquinodimethane (MBQDM, m-CH2C6H4CH2).
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Transcription Factor CREB is Involved in CaSR-mediated Cytoskeleton Gene Expression.
Anat Rec (Hoboken)
PUBLISHED: 02-15-2014
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Our previous studies illustrated that a steady increase of intracellular calcium concentration ([Ca(2+) ]i) was important for maintaining microtubules (MTs) rearrangement in apoptotic cells. However, little is known about the effect of calcium sensing receptor (CaSR)-mediated increase in [Ca(2+) ]i on cytoskeleton gene expression. We examined the impact of taxol or CaSR agonist/antagonist on the regulation of [Ca(2+) ]i concentration, cytoskeleton arrangement, phosphorylated CREB and cytoskeleton gene expressions in HeLa cells with dominant negative plasmid of CREB (PM). The present study demonstrated that Gdcl3 (a specific CaSR agonist) evoked a rapid increase of [Ca(2+) ]i, formed a rigid bundle of MTs which surrounded the nucleus and decreased the cytoskeleton gene expressions in HeLa cells. These effects were rescued by addition of NPS2390 (a specific CaSR antagonist). Moreover, CaSR activity affected cytoskeleton gene expression through transcription factor CREB. Histoscores of pCREB immunoreactivity in tissues of cervical adenocarcinoma, renal clear cell carcinoma, and diffuse large B-cell lymphoma were markedly increased compared with non malignant tissue. These data demonstrate, for the first time, that CaSR-mediated increase in [Ca(2+) ]i probably modulate cytoskeleton organization and gene expression via transcription factor CREB. Anat Rec, 2014. © 2014 Wiley Periodicals, Inc.
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Investigation of a chalcohalide glass optical waveguide structure fabricated by dual-energy carbon-ion implantation.
Appl Opt
PUBLISHED: 02-12-2014
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A planar waveguide structure in a chalcohalide glass was fabricated by dual-energy C ion implantation with energies of 5.5 and 6.0 MeV at fluences of 7.0×10¹? and 8.0×10¹?ions cm?², respectively. A waveguide with a thickness of 5.9 ?m was formed. SRIM 2013 was used to simulate the defect distribution fabricated by C ion implantation. Images of the polished end face of the C-implanted chalcohalide glass were measured with a metallographic microscope using reflected polarized light. The micro-Raman spectra were measured in air. The near-field intensity distributions were investigated at visible (633 nm) and near-infrared (1300, 1400, and 1539 nm) bands.
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Radiosensitization effect of nedaplatin on nasopharyngeal carcinoma cells in different status of Epstein-Barr virus infection.
Biomed Res Int
PUBLISHED: 02-04-2014
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This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0-100 ?g/mL nedaplatin, and inhibitory effects on cell viability and IC50 were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50 values of 34.32 and 63.69 ?g/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase.
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Production and purification of a novel xanthan lyase from a xanthan-degrading Microbacterium sp. strain XT11.
ScientificWorldJournal
PUBLISHED: 01-27-2014
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A xanthan lyase was produced and purified from the culture supernatant of an excellent xanthan-modifying strain Microbacterium sp. XT11. Xanthan lyase was induced by xanthan but was inhibited by its structural monomer glucose. Its production by strain XT11 is much higher than that by all other reported strains. The purified xanthan lyase has a molecular mass of 110 kDa and a specific activity of 28.2?U/mg that was much higher than that of both Paenibacillus and Bacillus lyases. It was specific on the pyruvated mannosyl residue in the intact xanthan molecule, but about 50% lyase activity remained when xanthan was partially depyruvated. Xanthan lyase was optimally active at pH 6.0-6.5 and 40°C and alkali-tolerant at a high pH value of 11.0. The metal ions including K(+), Ca(2+), Na(+), Mg(2+), Mn(2+), and Li(+) strongly stimulated xanthan lyase activity but ions Zn(2+) and Cu(2+) were its inhibitor. Xanthan lyase should be a novel enzyme different from the other xanthan lyases ever reported.
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Heme oxygenase-1 acts as an antiviral factor for porcine reproductive and respiratory syndrome virus infection and over-expression inhibits virus replication in vitro.
Antiviral Res.
PUBLISHED: 01-25-2014
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Virus replication depends upon host-cell processes in infected cells, and this is true for porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of PRRS that is a worldwide threat to the swine industry. Heme oxygenase-1 (HO-1) is a ubiquitously expressed inducible isoform of the first and rate-limiting enzyme for heme degradation. Our previous research suggested that HO-1 may play an important role in PRRSV infection. However, the function of HO-1 in PRRSV infection is unclear. In the present study, Marc-145, PK-15(CD163) cell lines and porcine alveolar macrophages (PAMs) were used to evaluate the effects of HO-1 induction and over-expression on the replication of two different PRRSV strains. Induction of HO-1 markedly decreased the replication of PRRSV strains in the different cells. Similarly, adenoviral-mediated over-expression of HO-1 also greatly decreased the replication of PRRSV. In contrast, ablation of HO-1 using small interfering RNA concomitantly increased PRRSV replication. Therefore, the data were consistent with HO-1 acting as an antiviral factor and these findings suggested that over-expression or induction of HO-1 may provide a potential therapeutic strategy against PRRSV infection.
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Motivational cues: the role of perceived senders' self-control ability in raters' deception judgements.
Int J Psychol
PUBLISHED: 01-20-2014
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Previous studies have found that senders' personal traits may be used by others to make judgements about the senders' truthfulness. Two studies were conducted to examine whether perceived self-control ability has an effect on deception judgement. Perceived self-control was hypothesized to act as a motivational cue that participants would use to assess the sender's motivation to lie, which in turn would influence their deception judgement. Results revealed that when participants assessed the sender as having higher self-control ability, they would consider the sender to be less motivated to lie in daily life (Study 1), and judge the sender more truthful in a text-based deception judgement task (Study 2). However, the effect of perceived self-control ability disappeared in a video-based task (Study 2), likely due to the multitude of various cues available in audio-visual stimuli. The theoretical and applied implications of the results are discussed.
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The relationship between patient safety culture and adverse events: a questionnaire survey.
Int J Nurs Stud
PUBLISHED: 01-15-2014
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Patient safety culture is an important factor in the effort to reduce adverse events in the hospital and improve patient safety. A few studies have shown the relationship between patient safety culture and adverse events, yet no such research has been reported in China.
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Negative feedback synchronizes islets of Langerhans.
Biophys. J.
PUBLISHED: 01-10-2014
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Insulin is released from the pancreas in pulses with a period of ~ 5 min. These oscillatory insulin levels are essential for proper liver utilization and perturbed pulsatility is observed in type 2 diabetes. What coordinates the many islets of Langerhans throughout the pancreas to produce unified oscillations of insulin secretion? One hypothesis is that coordination is achieved through an insulin-dependent negative feedback action of the liver onto the glucose level. This hypothesis was tested in an in vitro setting using a microfluidic system where the population response from a group of islets was input to a model of hepatic glucose uptake, which provided a negative feedback to the glucose level. This modified glucose level was then delivered back to the islet chamber where the population response was again monitored and used to update the glucose concentration delivered to the islets. We found that, with appropriate parameters for the model, oscillations in islet activity were synchronized. This approach demonstrates that rhythmic activity of a population of physically uncoupled islets can be coordinated by a downstream system that senses islet activity and supplies negative feedback. In the intact animal, the liver can play this role of the coordinator of islet activity.
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Berberine Improves Kidney Function in Diabetic Mice via AMPK Activation.
PLoS ONE
PUBLISHED: 01-01-2014
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Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease are required. Berberine (BBR) has several preventive effects on diabetes and its complications. However, the molecular mechanism of BBR on kidney function in diabetes is not well defined. Here, we reported that activation of AMP-activated protein kinase (AMPK) is required for BBR-induced improvement of kidney function in vivo. AMPK phosphorylation and activity, productions of reactive oxygen species (ROS), kidney function including serum blood urea nitrogen (BUN), creatinine clearance (Ccr), and urinary protein excretion, morphology of glomerulus were determined in vitro or in vivo. Exposure of cultured human glomerulus mesangial cells (HGMCs) to BBR time- or dose-dependently activates AMPK by increasing the thr172 phosphorylation and its activities. Inhibition of LKB1 by siRNA or mutant abolished BBR-induced AMPK activation. Incubation of cells with high glucose (HG, 30 mM) markedly induced the oxidative stress of HGMCs, which were abolished by 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK gene overexpression or BBR. Importantly, the effects induced by BBR were bypassed by AMPK siRNA transfection in HG-treated HGMCs. In animal studies, streptozotocin-induced hyperglycemia dramatically promoted glomerulosclerosis and impaired kidney function by increasing serum BUN, urinary protein excretion, and decreasing Ccr, as well as increased oxidative stress. Administration of BBR remarkably improved kidney function in wildtype mice but not in AMPK?2-deficient mice. We conclude that AMPK activation is required for BBR to improve kidney function in diabetic mice.
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Expression and function of SIRT6 in muscle invasive urothelial carcinoma of the bladder.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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SIRT6, a member of the class III histone deacetylase, has been shown to inhibit glycolysis and promote DNA double strand break repairs. Despite of its proposed tumor suppressor role, no significant differences in SIRT6 mRNA levels among normal bladder urothelium, non-muscle invasive, and muscle invasive urothelial carcinoma were noted in the two largest bladder cancer gene expression datasets available in Oncomine(TM). We therefore studied the expression and function of SIRT6 in muscle invasive urothelial carcinoma of the bladder. Immunohistochemistry studies of SIRT6 on radical cystectomy samples showed a dramatic decline of SIRT6 expression when bladder cancer progressed from T2 to T4. Functional study with bladder cancer cell lines confirmed its role in inhibiting glycolysis and cell proliferation. Reducing SIRT6 with siRNA, however, did not sensitize bladder cancer cells to drug induced DNA damage. The differential expression patterns of SIRT6 amongst different T stages of muscle invasive bladder cancers indicate less reliance on glycolysis when urothelial carcinoma invades deeper through the bladder and into the adjacent tissues.
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Angiotensin-converting enzyme insertion/deletion polymorphism is not a major determining factor in the development of sporadic Alzheimer disease: evidence from an updated meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism have long been linked to sporadic Alzheimer disease (SAD), but the established data remained controversial. To clarify this inconsistency, a comprehensive meta-analysis was conducted. Through searching of Pubmed, Embase, Alzgene, China National Knowledge Infrastructure (CNKI) and manually searching relevant references, 53 independent studies from 48 articles were included, involving a total of 8153 cases and 14932 controls. The strength of association was assessed by using odds ratios (ORs) with 95% confidence intervals (CIs). Further stratified analyses and heterogeneity analyses were tested, as was publication bias. Overall, significant associations were revealed between I/D polymorphism and SAD risk using allelic comparison (OR?=?1.09, 95%CI?=?1.01-1.17, p?=?0.030), homozygote comparison (OR?=?1.17, 95%CI?=?1.01-1.34, p?=?0.030) and the dominant model (OR?=?1.16, 95%CI?=?1.04-1.29, p?=?0.008), but they were not sufficiently robust to withstand the false-positive report probability (FPRP) analyses. Otherwise, in subgroup analyses restricted to the high quality studies, the large sample size studies and studies with population-based controls, no significant association was observed in any genetic models. In summary, the current meta-analysis suggested that the ACE I/D polymorphism is unlikely to be a major determining factor in the development of SAD.
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Outcomes in cochrane systematic reviews addressing four common eye conditions: an evaluation of completeness and comparability.
PLoS ONE
PUBLISHED: 01-01-2014
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Choice of outcomes is critical for clinical trialists and systematic reviewers. It is currently unclear how systematic reviewers choose and pre-specify outcomes for systematic reviews. Our objective was to assess the completeness of pre-specification and comparability of outcomes in all Cochrane reviews addressing four common eye conditions.
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Potentiation of mutant CFTR Cl- channel currents by the naturally occurring stilbene compound resveratrol.
Pharmazie
PUBLISHED: 12-31-2013
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Previously, we found that the naturally occurring stilbene compound resveratrol (RES) could potentiate cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity. Because some wild-type CFTR activators also potentiate its mutant forms, we investigated effect of RES on the two most common forms of CF-related mutation (deltaF508 and G551D-CFTR). Cell-based fluorescence studies indicated that RES dose-dependently potentiated both deltaF508 and G551D mutant CFTR Cl- channel activities. Transepithelial Cl- currents were stimulated by RES in deltaF508 and G551D mutant CFTR-expressing FRT cells. Further excised inside-out patch-clamp measurements revealed that RES significantly induced the chloride current of deltaF508 and G551D mutant CFTRs by increasing the open time of the channels. In ex vivo studies, RES stimulated fluid secretion in mouse trachea by optical measurement of single gland secretion. These data suggested that RES is a potent deltaF508 and G551D mutant CFTR potentiator, and RES may present a novel class of therapeutic lead compounds in treating cystic fibrosis.
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Vitamin A and fish oils for retinitis pigmentosa.
Cochrane Database Syst Rev
PUBLISHED: 12-21-2013
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Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to legal blindness. Symptoms may become manifest during childhood or adulthood, and include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). This field loss is progressive and usually does not reduce central vision until late in the disease course.The worldwide prevalence of RP is one in 4000, with 100,000 patients affected in the USA. At this time, there is no proven therapy for RP.
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High-Energy-Surface Engineered Metal Oxide Micro- and Nanocrystallites and Their Applications.
Acc. Chem. Res.
PUBLISHED: 12-17-2013
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Because many physical and chemical processes occur at surfaces, surface atomic structure is a critical factor affecting the properties of materials. Due to the presence of high-density atomic steps and edges and abundant unsaturated coordination sites, micro- and nanocrystallites with high-energy surfaces usually exhibit greater reactivity than those with low-energy surfaces. However, high-energy crystal surfaces are usually lost during crystal growth as the total surface energy is minimized. Therefore, the selective exposure of high-energy facets at the surface of micro- and nanocrystallites is an important and challenging research topic. Metal oxides play important roles in surface-associated applications, including catalysis, gas sensing, luminescence, and antibiosis. The synthesis of metal oxide micro- and nanocrystallites with specific surfaces, particularly those with high surface energies, is more challenging than the synthesis of metal crystals due to the presence of strong metal-oxygen bonds and diverse crystal structures. In this Account, we briefly summarize recent progress in the surface-structure-controlled synthesis of several typical metal oxide micro- and nanocrystallites, including wurtzite ZnO, anatase TiO2, rutile SnO2, and rocksalt-type metal oxides. We also discuss the improvement of surface properties, focusing on high-energy surfaces. Because of the huge quantity and diverse structure of metal oxides, this Account is not intended to be comprehensive. Instead, we discuss salient features of metal oxide micro- and nanocrystallites using examples primarily from our group. We first discuss general strategies for tuning the surface structure of metal oxide micro- and nanocrystallites, presenting several typical examples. For each example, we describe the basic crystallographic characteristics as well as the thermodynamic (i.e., tuning surface energy) or kinetic (i.e., tuning reaction rates) strategies we have used to synthesize micro- and nanocrystallites with high surface energies. We discuss the structural features of the specific facets and analyze the basis for the enhanced performance of the metal oxide micro- and nanocrystallites in water splitting, the degradation of organic pollutants, gas sensing, catalysis, luminescence, and antibiosis. Finally, we note the future trends in high-energy-facet metal oxide micro- and nanocrystallite research. A comprehensive understanding of the properties of metal oxide micro- and nanocrystallites with high-energy crystal surfaces and related synthetic strategies will facilitate the rational design of functional nanomaterials with desired characteristics.
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Covalently Bound Tetracoordinated Organoborons as Superhalogens: A Combined Negative Ion Photoelectron Spectroscopy and Theoretical Study.
J Phys Chem A
PUBLISHED: 11-21-2013
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Molecular species with electron affinities (EAs) larger than that of the chlorine atom (3.6131 eV) are superhalogens. The corresponding negative ions, namely, superhalogen anions, are intrinsically very stable with high electron binding energies (EBEs) and widely exist as building blocks of bulk materials and ionic liquids. The most common superhalogen anions proposed and experimentally confirmed to date are either ionic salts or compact inorganic species. Herein, we report a new class of superhalogen species, a series of tetracoordinated organoboron anions [BL4](-) (L = phenyl (1), 4-fluorophenyl (2), 1-imidazolyl (3), L4 = H(pyrazolyl)3 (4)) with bulky organic ligands covalently bound to the central B atom. Negative ion photoelectron spectroscopy (NIPES) reveals that all of these anions possess EBEs higher than that of Cl(-) with the adiabatic/vertical detachment energy (ADE/VDE) of 4.44/4.8 (1), 4.78/5.2 (2), 5.08/5.4 (3), and 4.59/4.9 eV (4), respectively. First-principles calculations confirmed high EBEs of [BL4](-) and predicted that these anions are thermodynamically stable against fragmentation. The unraveled superhalogen nature of these species provides a molecular basis to explain the wide-ranging applications of tetraphenylborate (TPB) (1) and trispyrazolylborate (Tp) (4) in many areas spanning from industrial waste treatment to soft material synthesis and organometallic chemistry.
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Hydrogen-bond networks: strengths of different types of hydrogen bonds and an alternative to the low barrier hydrogen-bond proposal.
J. Am. Chem. Soc.
PUBLISHED: 11-19-2013
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We report quantifying the strengths of different types of hydrogen bonds in hydrogen-bond networks (HBNs) via measurement of the adiabatic electron detachment energy of the conjugate base of a small covalent polyol model compound (i.e., (HOCH2CH2CH(OH)CH2)2CHOH) in the gas phase and the pKa of the corresponding acid in DMSO. The latter result reveals that the hydrogen bonds to the charged center and those that are one solvation shell further away (i.e., primary and secondary) provide 5.3 and 2.5 pKa units of stabilization per hydrogen bond in DMSO. Computations indicate that these energies increase to 8.4 and 3.9 pKa units in benzene and that the total stabilizations are 16 (DMSO) and 25 (benzene) pKa units. Calculations on a larger linear heptaol (i.e., (HOCH2CH2CH(OH)CH2CH(OH)CH2)2CHOH) reveal that the terminal hydroxyl groups each contribute 0.6 pKa units of stabilization in DMSO and 1.1 pKa units in benzene. All of these results taken together indicate that the presence of a charged center can provide a powerful energetic driving force for enzyme catalysis and conformational changes such as in protein folding due to multiple hydrogen bonds in a HBN.
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[Study on accuracy of virtual surgical planning in free fibula mandibular reconstruction by using SurgiCase software].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 11-01-2013
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To evaluate the directional significance of SurgiCase software in free fibula mandibular reconstruction.
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Enhanced near-infrared photocatalysis of NaYF4:Yb, Tm/CdS/TiO2 composites.
Dalton Trans
PUBLISHED: 10-28-2013
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The previous works by our group (Chem. Commun., 2010, 46, 2304-2306; ACS Catal., 2013, 3, 405-412; Phys. Chem. Chem. Phys., 2013, 15, 14681-14688) have reported the near-infrared-driven photocatalysis of broadband semiconductor TiO2 or ZnO that was combined with upconverting luminescence particles to form a core-shell structure. However, the photocatalytic efficiency is low for this new type of photocatalysts. In this work, NaYF4:Yb,Tm/CdS/TiO2 composites for NIR photocatalysis were prepared by linking CdS and TiO2 nanocrystals on the NaYF4:Yb,Tm microcrystal surfaces. CdS and TiO2 were well interacted to form a heterojunction structure. The energy transfer between NaYF4:Yb,Tm and the semiconductors CdS and TiO2 was investigated by steady-state and dynamic fluorescence spectroscopy. The photocatalytic activities of the as-prepared composites were evaluated by the degradation of methylene blue in aqueous solution upon NIR irradiation. Significantly, it was found that the united adhesions of CdS and TiO2 on the NaYF4:Yb,Tm particle surfaces showed much higher catalytic activities than the individual adhesion of CdS or TiO2 on the NaYF4:Yb,Tm surfaces. This was attributed mainly to the effective separation of the photogenerated electron-hole pairs due to the charge transfer across the CdS-TiO2 interface driven by the band potential difference between them. The presented composite structure of upconverting luminescence materials coupled with narrow/wide semiconductor heterojunctions provides a new model for improved NIR photocatalysis.
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CFTR chloride channel is a molecular target of the natural cancer preventive agent resveratrol.
Pharmazie
PUBLISHED: 10-24-2013
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The naturally occurring polyphenol compound resveratrol (RES) has been receiving wide attention because of its variety of health benefits and favourable biological activities. Previous studies have shown that RES could induce intestinal chloride secretion in mouse jejunum and stimulate cAMP-dependent Cl- secretion in T84, primary cultured murine nasal septal and human sinonasal epithelial cells, but the precise molecular target is not clear. We therefore tested the hypothesis that RES may stimulate the activity of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Using cell-based fluorescent assays, transepithelial short-circuit current measurements and excised inside-out patch-clamp analysis; we found that RES dose-dependently potentiate CFTR Cl- channel activities, which was reversed by CFTR inhibitors CFTR(inh)-172 and GlyH101. Transepithelial Cl- secretion by CFTR-expressing FRT cells was stimulated by RES with half maximal concentration -80 microM. Intracellular cAMP content was not elevated by RES in FRT cells. Excised inside-out patch-clamp analysis indicated that RES significantly increased the chloride currents of CFTR. In ex vivo studies, RES stimulated the transmucosal chloride current of rat colon by short-circuit current assay. These data suggested that CFTR is a molecular target of RES. Our findings add a new molecular target to RES, and RES may represent a novel class of therapeutic lead compounds in treating CFTR-related diseases including CF and habitual constipation.
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White matter microstructure changes induced by motor skill learning utilizing a body machine interface.
Neuroimage
PUBLISHED: 10-15-2013
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The purpose of this study is to identify white matter microstructure changes following bilateral upper extremity motor skill training to increase our understanding of learning-induced structural plasticity and enhance clinical strategies in physical rehabilitation. Eleven healthy subjects performed two visuo-spatial motor training tasks over 9 sessions (2-3 sessions per week). Subjects controlled a cursor with bilateral simultaneous movements of the shoulders and upper arms using a body machine interface. Before the start and within 2days of the completion of training, whole brain diffusion tensor MR imaging data were acquired. Motor training increased fractional anisotropy (FA) values in the posterior and anterior limbs of the internal capsule, the corona radiata, and the body of the corpus callosum by 4.19% on average indicating white matter microstructure changes induced by activity-dependent modulation of axon number, axon diameter, or myelin thickness. These changes may underlie the functional reorganization associated with motor skill learning.
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Cetuximab in combination with chemoradiation after induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma: preliminary results.
Future Oncol
PUBLISHED: 10-11-2013
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This article aimed to determine treatment compliance, acute toxicities and the short-term curative effects of combining cetuximab with chemoradiation following induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma (NPC).
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Identification of factors influencing the pharmacokinetics of voriconazole and the optimization of dosage regimens based on Monte Carlo simulation in patients with invasive fungal infections.
J. Antimicrob. Chemother.
PUBLISHED: 10-01-2013
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The objective of this study was to estimate the population pharmacokinetics of voriconazole, to identify the factors influencing voriconazole pharmacokinetics and to identify optimal dosage regimens for attaining target pharmacokinetic/pharmacodynamic indices against Aspergillus and Candida infections in patients with invasive fungal infections (IFIs).
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Salidroside Improves Doxorubicin-induced Cardiac Dysfunction by Suppression of Excessive Oxidative Stress and Cardiomyocyte Apoptosis.
J. Cardiovasc. Pharmacol.
PUBLISHED: 09-28-2013
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: Doxorubicin (DOX) is a potent available antitumor drug; however, its clinical use is limited by the cardiotoxicity. Salidroside (SLD), with strong antioxidative and cytoprotective actions, is of particular interest in the development of antioxidative therapies for oxidative injury in cardiac diseases. Now, the protection and underlying mechanisms of SLD against DOX-induced cardiotoxicity are still unknown. In the present study, we revealed both antioxidative mechanism and Bcl2-dependent survival signaling involved in SLDs protection. We observed that DOX exposure induced mortality elevation, body weight loss, and cardiac dysfunction in mice, increased lactate dehydrogenase leakage and cardiomyocyte apoptosis, but decreased cell viability and size in cardiac tissues and cultured H9c2 cells, respectively, which were effectively antagonized by SLD supplement. We further observed that SLD significantly reduced the intercellular oxidative stress level, partly by inhibiting NOX1 expression and augmenting the expression and activities of the endogenous antioxidative enzymes, catalase, and manganese superoxide dismutase. In addition, SLD treatment upregulated the antiapoptotic Bcl2 and downregulated the proapoptotic Bax and inhibited a downstream pathway of Bcl2/Bax and caspase-3 activity. Our results indicated that SLD effectively protected the cardiomyocytes against DOX-induced cardiotoxicity by suppressing the excessive oxidative stress and activating a Bcl2-mediated survival signaling pathway.
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