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Find video protocols related to scientific articles indexed in Pubmed.
Flexible Single Crystal Silicon Nanomembrane Photonic Crystal Cavity.
ACS Nano
PUBLISHED: 11-20-2014
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Flexible inorganic electronic devices promise numerous applications, especially in fields that could not be covered satisfactorily by conventional rigid devices. Benefits on a similar scale are also foreseeable for silicon photonic components. However, the difficulty in transferring intricate silicon photonic devices has deterred widespread development. In this paper, we demonstrate a flexible single crystal silicon nanomembrane photonic crystal microcavity through a bonding and substrate removal approach. The transferred cavity shows a quality factor of 2.2×10^4, and could be bended to a curvature of 5 mm radius without deteriorating the performance compared to its counterparts on rigid substrates. A thorough characterization of the device reveals that the resonant wavelength is a linear function of the bending-induced strain. The device also shows a curvature-independent sensitivity to the ambient index variation.
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Effect of biaxial strain induced by piezoelectric PMN-PT on the upconversion photoluminescence of BaTiO3:Yb/Er thin films.
Opt Express
PUBLISHED: 11-18-2014
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Thin films of Yb3+/Er3+ co-doped BaTiO3 (BTO:Yb/Er) have been epitaxially grown on piezoelectric Pb(Mg1/3Nb2/3)0.7Ti0.3O3 (PMN-PT) substrates. Biaxial strain can be effectively controlled by applying electric field on PMN-PT substrate. A reversible, in situ and dynamic modification of upconversion photoluminescence in BTO:Yb/Er film was observed via converse piezoelectric effect. Detailed analysis and in situ X-ray diffraction indicate that such modulations are possibly due to the change in the lattice deformation of the thin films. This result suggests an alternative method to rationally tune the upconversion emissions via strain engineering.
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Proteomic basis of stress responses in the gills of the Pacific oyster Crassostrea gigas.
J. Proteome Res.
PUBLISHED: 11-13-2014
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The Pacific oyster Crassostrea gigas is one of the dominant sessile inhabitants of the estuarine intertidal zone, which is a physically harsh environment due to the presence of a number of stressors. Oysters have adapted to highly dynamic and stressful environments, but the molecular mechanisms underlying such stress adaptation are largely unknown. In the present study, we examined the proteomic responses in the gills of C. gigas exposed to three stressors (high temperature, low salinity and aerial exposure) they often encounter in the field. We quantitatively compared the gill proteome profiles using iTRAQ-coupled two dimensional LC-MS/MS. There were 3,165 identified proteins among which 2,379 proteins could be quantified. Heat shock, hypo-salinity and aerial exposure resulted in 50, 15 and 33 differentially expressed gill proteins, respectively. Venn diagram analysis revealed substantial different responses to the three stressors. Only xanthine dehydrogenase/oxidase (XOR) showed similar expression pattern across the three stress treatments, suggesting that reduction of ROS accumulation may be a conserved response to these stressors. Heat shock caused significant over-expression of molecular chaperones and production of S-adenosyl-L-methionine (SAM), indicating their crucial protective roles against protein denature. In addition, heat shock also activated immune responses, Ca2+ binding protein expression. By contrast, hypo-salinity and aerial exposure resulted in the up-regulation of 3-demethylubiquinone-9 3-methyltransferase (UbiG), indicating that increase in ubiquinone synthesis may contribute to withstanding both the osmotic and desiccation stress. Strikingly, the majority of desiccation responsive proteins, including those involved in metabolism, ion transportation, immune responses, DNA duplication and protein synthesis, were down-regulated, indicating conservation of energy as an important strategy to cope with desiccation stress. There was a high consistency between the expression levels determined by iTRAQ and Western blotting, highlighting the high reproducibility of our proteomic approach and its great value in revealing molecular mechanisms of stress responses.
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Changes in Anti-thyroglobulin IgG Glycosylation Patterns in Hashimoto's Thyroiditis Patients.
J. Clin. Endocrinol. Metab.
PUBLISHED: 11-08-2014
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Objective: Sera of Hashimoto's thyroiditis (HT) patients are known to exhibit elevated levels of anti-thyroglobulin IgG (TgAb IgG). Therefore, TgAb IgG represents a hallmark of this debilitating autoimmune disease. The aim of our study was to investigate the differential expression of specific glycosylation patterns of TgAb IgG from HT patients and healthy blood donors. Methods: HT patients (n=32) were divided into two subgroups - medium level group (mHT, n=15) and high level group (hHT, n=17) - according to the serum levels of TgAb detected by electrochemiluminescence immunoassay. TgAb IgG was purified by affinity chromatography from the sera of HT group and control group (n=15). MALDI-QIT-TOF-MS/MS spectrometry was performed to identify the glycosylation profiles of purified TgAb IgG. Lectin microarray technology was used to compare the abundance of different glycans found on TgAb IgG between HT patients and controls, and between the mHT and hHT groups. Results: The results by MALDI-QIT-TOF-MS/MS showed that the glycosylation profiles of TgAb IgG were similar between the mHT, hHT and control groups. Furthermore, the lectin microarray showed that compared with the control group (all P<0.001), there were higher levels present of: 1) mannose (detected as lectin LCA, VFA and MNA-M); 2) terminal sialic acid (detected as SNA-I and PSA); 3) core fucose (detected as LcH); and 4) Gal(?1-4)GlcNAc(?1-2)Man glycans (detected as PHA-L) on TgAb IgG from the HT group. A similar trend was observed between the hHT and mHT group, with elevated levels of mannose, terminal sialic acid, core fucose and Gal(?1-4)GlcNAc(?1-2)Man glycans on TgAb IgG found in the hHT group compared with the mHT group ( all P<0.05). Conclusions: TgAb IgG of HT patients exhibits higher glycosylation levels than those observed for TgAb IgG of healthy controls. Our results provide new clues for exploring the role of TgAb in the pathogenesis of HT.
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Preclinical pharmacokinetics, tolerability and pharmacodynamics of Metuzumab, a novel CD147 human mouse chimeric and glycoengineered antibody.
Mol. Cancer Ther.
PUBLISHED: 11-08-2014
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Metuzumab is an affinity optimized and non-fucosylated anti CD147 human-mouse chimeric IgG1 monoclonal antibody with enhanced antibody dependent cellular cytotoxicity (ADCC). The purpose of these studies was to characterize the pharmacokinetics (PK), safety and anti-tumor activities of Metuzumab in mouse, rat and monkey. The ADCC activity was assessed by lactate dehydrogenase release assay. The pharmacokinetics of Metuzumab were determined in Sprague-Dawley rats and in Cynomolgus monkeys. Single- and repeat- dose toxicology studies of the intravenous administration of high-dose Metuzumab were conducted in cynomolgus monkeys. Mice bearing human tumor xenografts were used to evaluate the anti-tumor efficacy of Metuzumab. The ADCC potency of Metuzumab was enhanced compared with the non-glycoengineered parental antibody. Metuzumab was also effectively inhibited tumor growth in A549 and NCI-H520 xenograft models. In the monkey model, the total clearance of Metuzumab decreased with increasing dose. The non-specific clearance in monkeys was estimated to be 0.53-0.92 mL/h/kg. In single- and repeat-dose toxicology studies in cynomolgus monkeys, Metuzumab did not induce any distinct or novel adverse findings and was well tolerated at all tested doses. This preclinical safety data facilitated the initiation of an ongoing clinical trial of Metuzumab for the treatment of non-small cell lung cancer (NSCLC) in China.
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Tunable-Color Luminescence via Energy Transfer in NaCa13/18Mg5/18PO4:A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+)) Phosphors for Solid State Lighting.
Inorg Chem
PUBLISHED: 11-06-2014
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A series of NaCa13/18Mg5/18PO4(NCMPO):A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+)) phosphors have been prepared by the high-temperature solid-state reaction method. The X-ray diffraction (XRD) and Rietveld refinement, X-ray photoelectron spectroscopy (XPS), photoluminescence (PL), cathodoluminescence (CL), decay lifetimes, and PL quantum yields (QYs) were utilized to characterize the phosphors. The pure crystalline phase of as-prepared samples has been demonstrated via XRD measurement and Rietveld refinements. XPS reveals that the Eu(2+)/Tb(3+)/Mn(2+) can be efficiently doped into the crystal lattice. NCMPO:Eu(2+)/Tb(3+)/Mn(2+) phosphors can be effectively excited under UV radiation, which show tunable color from purple-blue to red including white emission based on energy transfer from Eu(2+) to Tb(3+)/Mn(2+) ions. Under low-voltage electron beam bombardment, the NCMPO:A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+)) display their, respectively, characteristic emissions with different colors, and the CL spectrum of NCMPO:0.04Tb(3+) has the comparable intensity to the ZnO:Zn commercial product. In addition, the calculated CIE coordinate of NCMPO:0.04Tb(3+) (0.252, 0.432) is more saturated than it (0.195, 0.417). These results reveal that NCMPO:A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+)) may be potential candidate phosphors for WLEDs and FEDs.
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A Novel Total Cervical Prosthesis for Single-level Cervical Subtotal Corpectomy: Radiological and Histomorphometric Analysis in a Caprine Model.
J Spinal Disord Tech
PUBLISHED: 10-30-2014
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A novel total cervical prosthesis for single level cervical subtotal corpectomy was assessed in a caprine animal model.
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[Prediction of new long non-coding RNA of laryngeal carcinoma by high-throughput RNA-Seq data].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 10-30-2014
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To screen and identify the new long non-coding RNAs from transcriptome of laryngeal squamous cell cancer using strand-specific RNA-Seq technology and bioinformatics tools, and to analyze the difference expression of these LncRNAs.
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Fast Responsive and Highly Efficient Optical Upconverter Based on Phosphorescent OLED.
ACS Appl Mater Interfaces
PUBLISHED: 10-23-2014
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In this work, an organic-inorganic hybrid optical upconverter that can convert irradiated 980 nm IR light to 510 nm green phosphorescence sensitively was fabricated and studied. fac-Tris(2-phenylpyridine) iridium (Ir(ppy)3) doped 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (CBP) was used as emitting layer in the phosphorescent organic light-emitting diode (OLED) unit. The upconverter using a phosphorescent OLED as display unit can achieve a higher upconversion efficiency and a low power consumption when compared with the one using fluorescent. An upconversion efficiency of 4.8% can be achieved for phosphorescent device at 15 V, much higher than that of fluorescent one (2.0%). The upconverter's transient optical and electric response to IR pulse were also investigated for the first time. The response time was found to be influenced by IR intensity and applied voltage. It has a response time as short as 60 ?s. The rapid response property of the upconverter makes it feasible to be applied to high-speed IR imaging systems.
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[Expression, purification and functional identification of human PSMP recombinant protein in Chinese hamster ovary cells].
Beijing Da Xue Xue Bao
PUBLISHED: 10-22-2014
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To construct a new human chemotactic cytokine PSMP eukaryotic expression vector to express PSMP in Chinese hamster ovary (CHO) cells and to obtain the purified recombinant PSMP protein for its functional mechanism study.
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Multiwavelet packet entropy and its application in transmission line fault recognition and classification.
IEEE Trans Neural Netw Learn Syst
PUBLISHED: 10-21-2014
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Multiwavelets possess better properties than traditional wavelets. Multiwavelet packet transformation has more high-frequency information. Spectral entropy can be applied as an analysis index to the complexity or uncertainty of a signal. This paper tries to define four multiwavelet packet entropies to extract the features of different transmission line faults, and uses a radial basis function (RBF) neural network to recognize and classify 10 fault types of power transmission lines. First, the preprocessing and postprocessing problems of multiwavelets are presented. Shannon entropy and Tsallis entropy are introduced, and their difference is discussed. Second, multiwavelet packet energy entropy, time entropy, Shannon singular entropy, and Tsallis singular entropy are defined as the feature extraction methods of transmission line fault signals. Third, the plan of transmission line fault recognition using multiwavelet packet entropies and an RBF neural network is proposed. Finally, the experimental results show that the plan with the four multiwavelet packet energy entropies defined in this paper achieves better performance in fault recognition. The performance with SA4 (symmetric antisymmetric) multiwavelet packet Tsallis singular entropy is the best among the combinations of different multiwavelet packets and the four multiwavelet packet entropies.
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Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector?
Antioxid. Redox Signal.
PUBLISHED: 10-21-2014
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Significance: Inflammasomes are multiprotein complexes localized within the cytoplasm of the cell that are responsible for the maturation of proinflammatory cytokines such as interleukin-1? (IL-1?) and IL-18, and the activation of a highly inflammatory form of cell death, pyroptosis. In response to infection or cellular stress, inflammasomes are assembled, activated, and involved in host defense and pathophysiology of diseases. Clarification of the molecular mechanisms leading to the activation of this intracellular inflammatory machinery may provide new insights into the concept of inflammation as root of and route to human diseases. Recent Advances: The activation of inflammasomes, specifically the most fully characterized inflammasome - the NOD-like receptor containing pyrin domain 3 (NLRP3) inflammasome, is now emerging as a critical molecular mechanism for many degenerative diseases. Several models have been developed to describe how NLRP3 inflammasomes are activated, including K+ efflux, lysosome function, endoplasmic reticulum (ER) stress, intracellular calcium, ubiquitination, microRNAs, and, in particular, reactive oxygen species (ROS). Critical Issues: ROS may serve as a 'kindling' or triggering factor to activate NLRP3 inflammasomes as well as 'bonfire' or 'effector' molecules resulting in pathological processes. Increasing evidence seeks to understand how this temporospatial action of ROS occurs during NLRP3 inflammasome activation, which will be a major focus of this review. Future Directions: It is imperative to know how this dual action of ROS works during NLRP3 inflammation activation upon different stimuli and what relevance such temporospatial redox regulation of NLRP3 inflammasomes has on cell or organ functions and possible human diseases.
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A Meta-Analysis of the Correlation Between the HLA-DRB1*03 Allele and Chronic Hepatitis B in the Han Chinese Population.
Genet Test Mol Biomarkers
PUBLISHED: 10-18-2014
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Objective: This study sought to use a meta-analysis approach to comprehensively evaluate correlations between the human leukocyte antigen-DR beta 1 (HLA-DRB1)*03 allele and chronic hepatitis B (CHB) in the Han Chinese population. Methods: The China Biomedical Literature database (CBMdisc), the Chongqing VIP database (VIP), and the PubMed database were searched. Using the inclusion and exclusion criteria of this study, all relevant case-control studies retrieved in these searches that satisfied the conditions of this investigation were collected. Review Manager (RevMan) 5.2 software was used to conduct a meta-analysis on the results of these studies. Results: There were 9 publications that satisfied the inclusion criteria. These publications included a total of 970 cases in the CHB group and 1185 cases in the normal control group. Egger's test revealed no significant publication bias. A comprehensive analysis indicated that the pooled odds ratio (OR) value was 1.94 with a 95% confidence interval (CI) of 1.23-3.06 (Z=2.84, p=0.004); these findings suggested that in the Han Chinese population, the HLA-DRB1*03 allele is a susceptibility allele related to the occurrence of CHB. Conclusion: There is a statistically significant correlation between the HLA-DRB1*03 allele and the occurrence of CHB in the Han Chinese population, and the HLA-DRB1*03 allele may be a susceptibility allele for this disease.
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High GINS2 transcript level predicts poor prognosis and correlates with high histological grade and endocrine therapy resistance through mammary cancer stem cells in breast cancer patients.
Breast Cancer Res. Treat.
PUBLISHED: 10-10-2014
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GINS2, a subunit of the GINS complex, is overexpressed in lung adenocarcinoma and metastatic breast tumor; however, its prognostic power and possible molecular mechanisms in breast cancer (BC) remain unclear. In this study, we aimed to explore the function of GINS2 in BC. The association between GINS2 transcript level and the clinical outcome of BC patients were estimated using Kaplan-Meier plots, multivariate cox regression analysis, forest plots, and receiver operating characteristics curves. Gene set enrichment analysis (GSEA) was performed to explore the mechanisms underlying the effects of the GINS2 transcript. High GINS2 transcript level was correlated with poor relapse free survival (log-rank P ? 0.001 in six cohorts; forest plot: total n = 1,420, total RR = 1.72, 95 % CI 1.45-2.03; multivariate cox regression analysis: n = 906, HR 2.36, 95 % CI 1.88-2.97), and distant metastasis free survival (log-rank P < 0.01 in 3 cohorts; forest plot: total n = 691, total RR 1.91, 95 % CI 1.36-2.67; multivariate cox regression analysis: n = 442, HR 2.43, 95 % CI 1.70-3.47). BC patients with higher GINS2 transcript levels showed poorer tamoxifen efficacy in a dose-dependent manner. GINS2 expression was significantly downregulated under mutated p53-depleted condition in MDA-468 and MDA-MB-231 cells, upregulated in mammary cancer stem cells (MaCSCs) (P = 0.003), and correlated with upregulated genes in mammary stem cells (GSEA: P < 0.01). Our study, for the first time, demonstrates that GINS2 is an independent prognostic marker and is associated with lung metastasis, histological grade, and endocrine therapy resistance in BC patients, which may attribute to mutant p53 and MaCSCs.
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Computational study on the interaction between CCR5 and HIV-1 entry inhibitor maraviroc: insight from accelerated molecular dynamics simulation and free energy calculation.
Phys Chem Chem Phys
PUBLISHED: 10-10-2014
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C-C chemokine receptor type 5 (CCR5) is the co-receptor of human immunodeficiency virus type 1 (HIV-1) and plays an important role in HIV-1 virus infection. Maraviroc has been proved to be effective for anti-HIV-1 by targeting CCR5. Understanding the detailed interaction mechanism between CCR5 and Maraviroc will be of great help to the rational design of a more potential inverse agonist to block HIV-1 infection. Here, we performed molecular dynamics (MD) simulation and accelerated MD simulation (aMD) to study the interaction mechanism between CCR5 and Maraviroc based on a recently reported crystal structure. The results of MD simulation demonstrate that Maraviroc can form stable hydrogen bonds with residues Tyr37(1.39), Tyr251(6.51) and Glu283(7.39). The results of aMD simulation indicate that the carboxamide moiety is more flexible than the tropane group of Maraviroc in the pocket of CCR5. The electrostatic potential analysis proves that Maraviroc can escape from the pocket of CCR5 along the negative electrostatic potential pathway during the dissociation process. The free energy calculation illustrates that there exist three binding pockets during the dissociation process of Maraviroc. Our results will be useful for understanding the interaction mechanism between CCR5 and Maraviroc as well as for the rational design of a more potent inverse agonist.
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A double-blind, randomized phase II study of dicycloplatin plus paclitaxel versus carboplatin plus paclitaxel as first-line therapy for patients with advanced non-small-cell lung cancers.
Arch Med Sci
PUBLISHED: 10-03-2014
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The aim of this study was to compare the efficacy and toxicity of dicycloplatin plus paclitaxel with those of carboplatin plus paclitaxel as first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC).
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[Th17/Treg unbalance is involved in the pathogenesis of experimental autoimmune encephalomyelitis].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 10-02-2014
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Objective To investigate the role of Th17/Treg unbalance in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Methods EAE was modeled in mice and the number of regulatory T cells (Tregs) in spleen of EAE mice was detected by flow cytometry. The expressions of Foxp3 and RoR-?t mRNA in the spleen of EAE mice and IL-17 mRNA in the brain of EAE mice were evaluated by real-time quantitative PCR and the levels of IL-6, TGF-? and IL-17 in the serum of EAE mice were examined by ELISA. Results Compared with control group, the number of CD4(+)CD25(+) Foxp3(+) Tregs and the expression of Foxp3 mRNA in the spleen of EAE mice dramatically decreased in the early and peak stage of EAE (P<0.05), but increased in chronic stage of EAE (P<0.05); the RoR-?t mRNA expression from mouse spleen at the early stage of EAE was significant raised (P<0.05), but was not significantly different at the peak and chronic stage of EAE from that in control group (P>0.05). The levels of IL-6 and TGF-? in the serum of EAE group dramatically increased compared with control group (P<0.05). With the development of EAE, the level of IL-6 gradually decreased, and there was no statistical difference in the chronic stage of EAE compared with control group (P>0.05). However, the level of TGF-? was higher than that in control group in the chronic stage of EAE (P<0.05). Compared with those in control group, the concentration of IL-17A and the expression of IL-17 mRNA dramatically increased in different stages of EAE group, especially in peak stage (P<0.05). Conclusion Th17/Treg unbalance may be involved in the pathogenesis of EAE.
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Newcastle disease virus vaccine encapsulated in biodegradable nanoparticles for mucosal delivery of a human vaccine.
Hum Vaccin Immunother
PUBLISHED: 09-30-2014
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An overwhelming number of medicines on the market are oral medicine with the disadvantage of lower bioavailability universally. Newcastle disease (ND) has become a serious disease that threatens the poultry industries in many countries, and there are no treatments available for ND. The biodegradable materials could be surface modified and protect antigen or DNA from damage. Furthermore, nanoparticles are also a potential drug delivery with proper size. However, Newcastle disease virus (NDV) vaccines encapsulated in nanoparticles were widely used due to their proved a high safety and induced quicker and better mucosal and humoral immune responses. Here we review the results of mucosal immune delivery system for ND. Due to the safety, low toxicity, and better immunogenicity of the mucosal immune delivery system, our studies provide a clearly view that used the biodegradable materials to research and develop the human vaccines to save more patients' lives. These promising results provide a foundation for testing the approach in humans.
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The CD8? gene in duck (Anatidae): cloning, characterization, and expression during viral infection.
Mol. Biol. Rep.
PUBLISHED: 09-28-2014
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Cluster of differentiation 8 alpha (CD8?) is critical for cell-mediated immune defense and T-cell development. Although CD8? sequences have been reported for several species, very little is known about CD8? in ducks. To elucidate the mechanisms involved in the innate and adaptive immune responses of ducks, we cloned CD8? coding sequences from domestic, Muscovy, Mallard, and Spotbill ducks using reverse transcription polymerase chain reaction (RT-PCR). Each sequence consisted of 714 nucleotides and encoded a signal peptide, an IgV-like domain, a stalk region, a transmembrane region, and a cytoplasmic tail. We identified 58 nucleotide differences and 37 amino acid differences among the four types of duck; of these, 53 nucleotide and 33 amino acid differences were between Muscovy ducks and the other duck species. The CD8? cDNA sequence from domestic duck consisted of a 61-nucleotide 5' untranslated region (UTR), a 714-nucleotide open reading frame, and an 849-nucleotide 3' UTR. Multiple sequence alignments showed that the amino acid sequence of CD8? is conserved in vertebrates. RT-PCR revealed that expression of CD8? mRNA of domestic ducks was highest in the thymus and very low in the kidney, cerebrum, cerebellum, and muscle. Immunohistochemical analyses detected CD8? on the splenic corpuscle and periarterial lymphatic sheath of the spleen. CD8? mRNA in domestic ducklings was initially up-regulated, and then down-regulated, in the thymus, spleen, and liver after treatment with duck hepatitis virus type I (DHV-1) or the immunostimulant polyriboinosinic polyribocytidylic acid (poly I:C).
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[Three-dimensional positions and forms of temporomandibular joints in Class II devision 1 malocclusion patients associated with different vertical skeletal patterns].
Zhonghua Kou Qiang Yi Xue Za Zhi
PUBLISHED: 09-27-2014
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To evaluate the positions and forms of temporomandibular joints (TMJ) with different vertical skeletal patterns in Class II division 1 patients.
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Optimized Protein Kinase C? (PKC?) Inhibitors Reveal Only Modest Anti-inflammatory Efficacy in a Rodent Model of Arthritis.
J. Med. Chem.
PUBLISHED: 09-26-2014
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We previously demonstrated that selective inhibition of protein kinase C? (PKC?) with triazinone 1 resulted in dose-dependent reduction of paw swelling in a mouse model of arthritis.1,2 However, a high concentration was required for efficacy, thus providing only a minimal safety window. Herein we describe a strategy to deliver safer compounds based on the hypothesis that optimization of potency in concert with good oral pharmacokinetic (PK) properties would enable in vivo efficacy at reduced exposures, resulting in an improved safety window. Ultimately, transformation of 1 yielded analogues that demonstrated excellent potency and PK properties and fully inhibited IL-2 production in an acute model. In spite of good exposure, twice-a-day treatment with 17l in the glucose-6-phosphate isomerase chronic in vivo mouse model of arthritis yielded only moderate efficacy. On the basis of the exposure achieved, we conclude that PKC? inhibition alone is insufficient for complete efficacy in this rodent arthritis model.
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Efficient synthesis of kinsenoside and goodyeroside a by a chemo-enzymatic approach.
Molecules
PUBLISHED: 09-24-2014
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Kinsenoside (1) and goodyeroside A (2), two naturally occurring stereoisomers with diverse biological activities, have been synthesized efficiently by a chemo-enzymatic approach with a total yield of 12.7%. The aglycones, (R)- and (S)-3-hydroxy-?-butyrolactone, were prepared from D- and L-malic acid by a four-step chemical approach with a yield of 75%, respectively. These butyrolactones were then successfully glycosidated using ?-D-glucosidase as a catalyst in a homogeneous organic-water system. Under the optimized enzymatic conditions, the yields of kinsenoside and goodyeroside A in the enzymatic steps both reached 16.8%.
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Radiotherapeutic treatment of a fighter pilot with nasopharyngeal carcinoma.
Aviat Space Environ Med
PUBLISHED: 09-24-2014
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Radiotherapy is the standard and most effective treatment for nasopharyngeal carcinoma (NPC) in its early stages. However, its application in fighter pilots returning to flying duties with NPC has not been previously reported, presumably due to post-radiotherapeutic complications.
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Application of a novel particle tracking algorithm in the flow visualization of an artificial abdominal aortic aneurysm.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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A novel Particle Tracking Velocimetry (PTV) algorithm based on Voronoi Diagram (VD) is proposed and briefed as VD-PTV. The robustness of VD-PTV for pulsatile flow is verified through a test that includes a widely used artificial flow and a classic reference algorithm. The proposed algorithm is then applied to visualize the flow in an artificial abdominal aortic aneurysm included in a pulsatile circulation system that simulates the aortic blood flow in human body. Results show that, large particles tend to gather at the upstream boundary because of the backflow eddies that follow the pulsation. This qualitative description, together with VD-PTV, has laid a foundation for future works that demand high-level quantification.
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Histologic investigation of gingival epithelium implantation and the nonincision placement of miniscrews.
Int J Oral Maxillofac Implants
PUBLISHED: 09-13-2014
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This study investigated whether the nonincision placement of miniscrews could lead to ectopic implantation of epithelium at the bone-implant interface and, if so, whether the epithelial cells could survive. The fate of grafted epithelial cells was also investigated.
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Contrast enhanced computed tomography is indicative for angiogenesis pattern and display prognostic significance in breast cancer.
BMC Cancer
PUBLISHED: 09-12-2014
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The Prognostic value of microvessel density in cancer remains unclear. Recent studies have suggested that the uneven distribution of microvessels in tumours caused the variation in sample selection which led to different prognostic outcome. The enhancement pattern of Contrast-enhanced computed tomography (CECT) is determined in part by the microvessel distribution in solid tumors. Therefore, survival analysis of tumors grouping by the enhancement pattern and the pattern of microvessel distribution is important.
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[Ectopic expression of duck albumin down-regulates the expressions of IFN-? and myxovirus resistance 1 mRNA in DF-1 cells].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 09-10-2014
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Objective To investigate the impact of duck albumin (ALB) gene on the mRNA expression levels of interferon ? (IFN-?) and myxovirus resistance-1 (Mx1). Methods The duck ALB gene was subcloned into pEGFP-C1 eukaryotic expression vector, and then the pEGFP-C1-ALB was transiently transfected into chick fibroblast DF-1 by Lipofectamine(TM) 2000. Twenty-four hours later, real-time quantitative PCR was applied to detect the dynamic change of IFN-? and Mx1 mRNA expressions under the stimulation of polyinosinic polycytidylic acid (PolyI:C). Results The pEGFP-C1-ALB was constructed successfully, and transfected into DF-1 effectively. The expression levels of IFN-? and Mx1 gene in cells transfected with pEGFP-C1-ALB were significantly lower than those transfected with pEGFP-C1 after 12-hour stimulation of PolyI:C (P<0.05 or P<0.01). Conclusion The expression levels of IFN-? and Mx1 mRNA were down-regulated by over-expression of duck ALB gene.
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New insight into modulated up-conversion luminescent silica nanotubes as efficient adsorbents for colored effluents.
Dalton Trans
PUBLISHED: 09-06-2014
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We report a simple and easy method to fabricate silica nanotubes (SNTs) with multicolor up-conversion luminescence by single-nozzle electrospinning based on phase separation effect without any templates. Multicolor up-conversion nanoparticles (UCNPs) were first synthesized by a similar hydrothermal route. Then, the water solution containing NPs were added slowly into the electrospinning precursor solution in a dropwise manner. After electrospinning process and calcination at 600 °C, pure SNTs with uniformly dispersed NPs were obtained. The as-produced up-conversion (UC) luminescent SNTs were used as an adsorbent for the removal of colorful dye from aqueous solutions. Adsorption experiments indicated that the SNTs have good adsorption capacity and that the adsorption amount can be traced by two indicators: the decrease in UV adsorption of the solutions and changes in the UC intensity of the SNTs. More importantly, the UC-SNT adsorbents are piece-like and could be effectively and quickly separated via filtration or centrifugation. Furthermore, the SNTs can regenerate by calcination and retain almost the same absorption capability for recycling use. Considering cost, function and cyclic utilization, UCNPs decorated SNTs may create a new platform for the preconcentration and separation of colored pollutants from waste water.
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Aggregation-Induced Emission Rotors: Rational Design and Tunable Stimuli Response.
Chemistry
PUBLISHED: 09-03-2014
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A novel molecular design strategy is provided to rationally tune the stimuli response of luminescent materials with aggregation-induced emission (AIE) characteristics. A series of new AIE-active molecules (AIE rotors) are prepared by covalently linking different numbers of tetraphenylethene moieties together. Upon gradually increasing the number of rotatable phenyl rings, the sensitivity of the response of the AIE rotors to viscosity and temperature is significantly enhanced. Although the molecular size is further enlarged, the performance is only slightly improved due to slightly increased effective rotors, but with largely increased rotational barriers. Such molecular engineering and experimental results offer more in-depth insight into the AIE mechanism, namely, restriction of intramolecular rotations. Notably, through this rational design, the AIE rotor with the largest molecular size turns out to be the most viscosensitive luminogen with a viscosity factor of up to 0.98.
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Aggregation-Induced Emission Rotors: Rational Design and Tunable Stimuli Response.
Chemistry
PUBLISHED: 09-03-2014
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A novel molecular design strategy is provided to rationally tune the stimuli response of luminescent materials with aggregation-induced emission (AIE) characteristics. A series of new AIE-active molecules (AIE rotors) are prepared by covalently linking different numbers of tetraphenylethene moieties together. Upon gradually increasing the number of rotatable phenyl rings, the sensitivity of the response of the AIE rotors to viscosity and temperature is significantly enhanced. Although the molecular size is further enlarged, the performance is only slightly improved due to slightly increased effective rotors, but with largely increased rotational barriers. Such molecular engineering and experimental results offer more in-depth insight into the AIE mechanism, namely, restriction of intramolecular rotations. Notably, through this rational design, the AIE rotor with the largest molecular size turns out to be the most viscosensitive luminogen with a viscosity factor of up to 0.98.
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Current situation and challenge of registry in China.
Front Med
PUBLISHED: 09-03-2014
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Increasing emphasis has been placed on registries for an organized system used in developing clinical research to improve health care. China has sufficient data that can be applied broadly, but the heterogeneity and irregularity of registries limit their applicability. This article aims to describe the status of registries in China and the related challenges. Patient registries for observational studies were retrieved from the International Clinical Trials Registry to quantitatively evaluate the number of comparatively high-quality registries in China. A literature search was also performed to provide support and updates. A total of 64 patient registries were retrieved from ClinicalTrials.gov using disease, product, and health service as criteria. The sample sizes ranged from 15 to 30,400, with only 12 registries marked as completed. This article describes and compares the detailed information in many aspects. The efficient use of registries has already made considerable progress in China; however, registries still require standardization, high-quality transition, and coordinated development.
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CAV1 promotes HCC cell progression and metastasis through Wnt/?-catenin pathway.
PLoS ONE
PUBLISHED: 09-02-2014
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Caveolin-1 (CAV1) has significant roles in many primary tumors and metastasis, despite the fact that malignant cells from different cancer types have different profiles of CAV1 expression. There is little information concerning CAV1 expression and role in hepatocellular carcinoma (HCC) progresion and metastasis. The role of CAV1 in HCC progression was explored in this study. We reported that CAV1 was overexpressed in highly invasive HCC cell lines compared with poorly invasive ones. The immunohistochemical staining was obviously stronger in metastatic HCC samples than in the non-metastatic specimens via tissue microarrays. Furthermore, CAV1 overexpression enhanced HCC cell invasiveness in vitro, and promoted tumorigenicity and lung metastasis in vivo. By contrast, CAV1 stable knockdown markedly reduced these malignant behaviors. Importantly, we found that CAV1 could induce EMT process through Wnt/?-catenin pathway to promote HCC metastasis. We also identify MMP-7 as a novel downstream target of CAV1. We have determined that CAV1 acts as a mediator between hyperactive ERK1/2 signaling and regulation of MMP-7 transcription. Together, these studies mechanistically show a previously unrecognized interplay between CAV1, EMT, ERK1/2 and MMP-7 that is likely significant in the progression of HCC toward metastasis.
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Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation.
J. Natl. Cancer Inst.
PUBLISHED: 09-01-2014
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To assess the efficacy of combining radioimmunoconjugate [(131)I] metuximab with radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) treatment compared with RFA alone, a single-center randomized controlled trial was conducted on 127 patients with Barcelona Clinic Liver Cancer staging system (BCLC) classifications of 0-B stage. Patients received either RFA followed by [(131)I] metuximab (n = 62) or RFA alone (n = 65). The primary outcome was overall tumor recurrence. Statistical tests were two-sided. The one- and two-year recurrence rates in the combination group were 31.8% and 58.5%, whereas those in the RFA group were 56.3% and 70.9%, respectively. The median time to overall tumor recurrence was 17 months in the combination group and 10 months in the RFA group (P = .03). The RFA-[(131)I] metuximab treatment showed a greater antirecurrence benefit than RFA in the metuximab target (ie, CD147)-positive subpopulation (P = .007). [(131)I] metuximab may yield prevention of tumor recurrence after RFA.
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Naringin prevents ovariectomy-induced osteoporosis and promotes osteoclasts apoptosis through the mitochondria-mediated apoptosis pathway.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-30-2014
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Naringin, the primary active compound of the traditional Chinese medicine Rhizoma drynariae, possesses many pharmacological activities. The present study is an effort to explore the anti-osteoporosis potential of naringin in vivo and in vitro. In vivo, we used ovariectomized rats to clarify the mechanisms by which naringin anti-osteoporosis. In vitro, we used osteoclasts to investigate naringin promotes osteoclasts apoptosis. Naringin was effective at enhancing BMD, trabecular thickness, bone mineralization, and mechanical strength in a dose-dependent manner. The result of RT-PCR analysis revealed that naringin down-regulated the mRNA expression levels of BCL-2 and up-regulated BAX, caspase-3 and cytochrome C. In addition, naringin significantly reduced the bone resorption area in vitro. These findings suggest that naringin promotes the apoptosis of osteoclasts by regulating the activity of the mitochondrial apoptosis pathway and prevents OVX-induced osteoporosis in rats.
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What limits the utilization of health services among the rural population in the Dabie Mountains- evidence from Hubei province, China?
BMC Health Serv Res
PUBLISHED: 08-29-2014
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Individuals living in rural mountain areas tend to use health services less to manage discomfort or illness. This study aims to identify the variables that best explain the health service utilization of a sample of the rural population in the Dabie Mountains in China.
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The Metallofullerene Field-Induced Single-Ion Magnet HoSc2 N@C80.
Chemistry
PUBLISHED: 08-27-2014
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The low-temperature magnetic properties of the endohedral metallofullerene HoSc2 N@C80 have been studied by superconducting quantum interference device (SQUID) magnetometry. Alternating current (ac) susceptibility measurements reveal that this molecule exhibits slow relaxation of magnetization in a small applied field with timescales in the order of milliseconds. The equilibrium magnetic properties of HoSc2 N@C80 indicate strong magnetic anisotropy. The large differences in magnetization relaxation times between the present compound and the previously investigated DySc2 N@C80 are discussed.
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A biomimetic synthesis of (±)-basiliolide?b.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-27-2014
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A highly diastereoselective and practical biomimetic total synthesis of (±)-basiliolide?B has been achieved through the study of the two proposed biosynthetic pathways (O-methylation and O-acylation) for the unprecedented 7-methoxy-4,5-dihydro-3H-oxepin-2-one (C?ring). The synthesis featured a cyclopropanation/ring opening strategy for establishing the stereogenic centers at C8 and C9, a biomimetic 2-pyrone Diels-Alder cycloaddition for the synthesis of the ABD ring system, and finally a highly efficient biomimetic intramolecular O-acylation for the C ring formation. This result provides an important perspective on the biosynthetic origin of the unprecedented 7-membered acyl ketene acetal moiety of the C?ring.
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Tracing the evolution of lineage-specific transcription factor binding sites in a birth-death framework.
PLoS Comput. Biol.
PUBLISHED: 08-21-2014
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Changes in cis-regulatory element composition that result in novel patterns of gene expression are thought to be a major contributor to the evolution of lineage-specific traits. Although transcription factor binding events show substantial variation across species, most computational approaches to study regulatory elements focus primarily upon highly conserved sites, and rely heavily upon multiple sequence alignments. However, sequence conservation based approaches have limited ability to detect lineage-specific elements that could contribute to species-specific traits. In this paper, we describe a novel framework that utilizes a birth-death model to trace the evolution of lineage-specific binding sites without relying on detailed base-by-base cross-species alignments. Our model was applied to analyze the evolution of binding sites based on the ChIP-seq data for six transcription factors (GATA1, SOX2, CTCF, MYC, MAX, ETS1) along the lineage toward human after human-mouse common ancestor. We estimate that a substantial fraction of binding sites (?58-79% for each factor) in humans have origins since the divergence with mouse. Over 15% of all binding sites are unique to hominids. Such elements are often enriched near genes associated with specific pathways, and harbor more common SNPs than older binding sites in the human genome. These results support the ability of our method to identify lineage-specific regulatory elements and help understand their roles in shaping variation in gene regulation across species.
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Hawaiinolides E-G, cytotoxic cassane and cleistanthane diterpenoids from the entomogenous fungus Paraconiothyrium hawaiiense.
Fitoterapia
PUBLISHED: 08-13-2014
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Hawaiinolides E-G (1-3), three additional new secondary metabolites including two cassane (1 and 2) types of diterpene lactones and one cleistanthane (3) diterpenoid, were isolated from the scale-up fermentation extract of Paraconiothyrium hawaiiense, an entomogenous fungus isolated from the Septobasidium-infected insect Diaspidiotus sp. The structures of 1-3 were elucidated by nuclear magnetic resonance experiments, and 1 and 3 were further confirmed by X-ray crystallography. The absolute configurations of 1 and 3 were assigned by single-crystal X-ray diffraction analysis using Cu K? radiation, whereas that of 2 was deduced via the circular dichroism data. Compound 1 showed significant cytotoxic effects against the human tumor cell line T24, with an IC50 value (9.32?M) comparable to that of the positive control cisplatin.
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Oncogenic mutations are associated with histological subtypes but do not have an independent prognostic value in lung adenocarcinoma.
Onco Targets Ther
PUBLISHED: 08-13-2014
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Lung adenocarcinomas have diverse genetic and morphological backgrounds and are usually classified according to their distinct oncogenic mutations (or so-called driver mutations) and histological subtypes (the de novo classification proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society [IASLC/ATS/ERS]). Although both these classifications are essential for personalized treatment, their integrated clinical effect remains unclear. Therefore, we analyzed 981 lung adenocarcinomas to detect the potential correlation and combined effect of oncogenic mutations and histological subtype on prognosis. Analysis for oncogenic mutations included the direct sequencing of EGFR, KRAS, HER2, BRAF, PIK3CA, ALK, and RET for oncogenic mutations/rearrangements, and a rereview of the IASLC/ATS/ERS classification was undertaken. Eligible tumors included 13 atypical adenomatous hyperplasia/adenocarcinoma in situ, 20 minimally invasive adenocarcinomas, 901 invasive adenocarcinomas, 44 invasive mucinous adenocarcinomas, and three other variants. The invasive mucinous adenocarcinomas had a lower prevalence of EGFR mutations but a higher prevalence of KRAS, ALK, and HER2 mutations than invasive adenocarcinomas. Smoking, a solid predominant pattern, and a mucinous component were independently associated with fewer EGFR mutations. The ALK rearrangements were more frequently observed in tumors with a minor mucinous component, while the KRAS mutations were more prevalent in smokers. In addition, 503 patients with stage I-IIIA tumors were analyzed for overall survival (OS) and relapse-free survival. The stage and histological pattern were independent predictors of relapse-free survival, and the pathological stage was the only independent predictor for the OS. Although patients with the EGFR mutations had better OS than those without the mutations, no oncogenic mutation was an independent predictor of survival. Oncogenic mutations were associated with the novel IASLC/ATS/ERS classification, which facilitates a morphology-based mutational analysis strategy. The combination of these two classifications might not increase the prognostic ability, but it provides essential information for personalized treatment.
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The rapid discovery and identification of physalins in the calyx of Physalis alkekengi L.var.franchetii (Mast.) Makino using ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry together with a novel three-step data mining stra
J Chromatogr A
PUBLISHED: 08-12-2014
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Physalins, uniquely discovered from genus physalis, showed significant bioactivities in many aspects. It is therefore very important for the exploration of natural resources rich of physalins. However, there is no efficient approach for rapid discovery and identification of this class of compounds due to their structural complexity. To address the issue, the fragmentation pathways and correspondingly fragmentation rules of physalins in negative MS/MS mode were thoroughly investigated in this study using seven physalin standards. As a result, diagnostic ions for the rapid screening of physalins and classification of different types of physalins were determined based on their MS/MS fragmentation patterns. On top of that, an integrated approach using UHPLC-QTOF-MS/MS together with a novel three-step data mining strategy was developed for the systematic analysis of physalins in complex samples. Consequently, 46 physalins including 20 novel ones were efficiently discovered and identified from the crude extracts of Ph. alkekengi calyx. The present study laid a foundation for future study of different parts of Ph. alkekengi and other physalis species with regard to rapid discovery of novel physalins. In addition, this study provided a base for establishing a quality control method of the raw materials of Ph. alkekengi according to the profile of physalins.
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Nanostructure embedded microchips for detection, isolation, and characterization of circulating tumor cells.
Acc. Chem. Res.
PUBLISHED: 08-11-2014
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Conspectus Circulating tumor cells (CTCs) are cancer cells that break away from either a primary tumor or a metastatic site and circulate in the peripheral blood as the cellular origin of metastasis. With their role as a "tumor liquid biopsy", CTCs provide convenient access to all disease sites, including that of the primary tumor and the site of fatal metastases. It is conceivable that detecting and analyzing CTCs will provide insightful information in assessing the disease status without the flaws and limitations encountered in performing conventional tumor biopsies. However, identifying CTCs in patient blood samples is technically challenging due to the extremely low abundance of CTCs among a large number of hematologic cells. To address this unmet need, there have been significant research endeavors, especially in the fields of chemistry, materials science, and bioengineering, devoted to developing CTC detection, isolation, and characterization technologies. Inspired by the nanoscale interactions observed in the tissue microenvironment, our research team at UCLA pioneered a unique concept of "NanoVelcro" cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with high efficiency. The working mechanism of NanoVelcro cell-affinity substrates mimics that of Velcro: when the two fabric strips of a Velcro fastener are pressed together, tangling between the hairy surfaces on two strips leads to strong binding. Through continuous evolution, three generations (gens) of NanoVelcro CTC chips have been established to achieve different clinical utilities. The first-gen NanoVelcro chip, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, was created for CTC enumeration. Side-by-side analytical validation studies using clinical blood samples suggested that the sensitivity of first-gen NanoVelcro chip outperforms that of FDA-approved CellSearch. In conjunction with the use of the laser microdissection (LMD) technique, second-gen NanoVelcro chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation. The individually isolated CTCs can be subjected to single-CTC genotyping (e.g., Sanger sequencing and next-generation sequencing, NGS) to verify the CTC's role as tumor liquid biopsy. Created by grafting of thermoresponsive polymer brushes onto SiNS, third-gen NanoVelcro chips (i.e., Thermoresponsive NanoVelcro) have demonstrated the capture and release of CTCs at 37 and 4 °C, respectively. The temperature-dependent conformational changes of polymer brushes can effectively alter the accessibility of the capture agent on SiNS, allowing for rapid CTC purification with desired viability and molecular integrity. This Account summarizes the continuous evolution of NanoVelcro CTC assays from the emergence of the original idea all the way to their applications in cancer research. We envision that NanoVelcro CTC assays will lead the way for powerful and cost-efficient diagnostic platforms for researchers to better understand underlying disease mechanisms and for physicians to monitor real-time disease progression.
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Comparative analyses between retained introns and constitutively spliced introns in Arabidopsis thaliana using random forest and support vector machine.
PLoS ONE
PUBLISHED: 08-11-2014
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One of the important modes of pre-mRNA post-transcriptional modification is alternative splicing. Alternative splicing allows creation of many distinct mature mRNA transcripts from a single gene by utilizing different splice sites. In plants like Arabidopsis thaliana, the most common type of alternative splicing is intron retention. Many studies in the past focus on positional distribution of retained introns (RIs) among different genic regions and their expression regulations, while little systematic classification of RIs from constitutively spliced introns (CSIs) has been conducted using machine learning approaches. We used random forest and support vector machine (SVM) with radial basis kernel function (RBF) to differentiate these two types of introns in Arabidopsis. By comparing coordinates of introns of all annotated mRNAs from TAIR10, we obtained our high-quality experimental data. To distinguish RIs from CSIs, We investigated the unique characteristics of RIs in comparison with CSIs and finally extracted 37 quantitative features: local and global nucleotide sequence features of introns, frequent motifs, the signal strength of splice sites, and the similarity between sequences of introns and their flanking regions. We demonstrated that our proposed feature extraction approach was more accurate in effectively classifying RIs from CSIs in comparison with other four approaches. The optimal penalty parameter C and the RBF kernel parameter [Formula: see text] in SVM were set based on particle swarm optimization algorithm (PSOSVM). Our classification performance showed F-Measure of 80.8% (random forest) and 77.4% (PSOSVM). Not only the basic sequence features and positional distribution characteristics of RIs were obtained, but also putative regulatory motifs in intron splicing were predicted based on our feature extraction approach. Clearly, our study will facilitate a better understanding of underlying mechanisms involved in intron retention.
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Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation.
J Proteomics
PUBLISHED: 08-10-2014
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Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts.
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Caffeine and diuresis during rest and exercise: A meta-analysis.
J Sci Med Sport
PUBLISHED: 08-09-2014
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Although ergogenic, acute caffeine ingestion may increase urine volume, prompting concerns about fluid balance during exercise and sport events. This meta-analysis evaluated caffeine induced diuresis in adults during rest and exercise.
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The first invertebrate RIG-I-like receptor (RLR) homolog gene in the pacific oyster Crassostrea gigas.
Fish Shellfish Immunol.
PUBLISHED: 08-08-2014
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Retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) is a pivotal receptor that detects numerous RNA and DNA viruses and mediates the innate induction of interferons and pro-inflammatory cytokines upon viral infection. In the present study, we cloned and characterized the first RIG-I gene in a marine mollusk, Crassostrea gigas, and designated it as CgRIG-I. The full-length CgRIG-I cDNA is 3436 bp, including 5'- and 3'-untranslated regions (UTRs) of 93 bp and 286 bp, respectively, and an open reading frame (ORF) of 3057 bp. The gene encodes a 1018 amino acid polypeptide with an estimated molecular mass of 116.5 kDa. SMART analysis showed that the CgRIG-I protein had the typical conserved domains, including the caspase activation and recruitment domains (CARDs), the RNA helicase domain and the C-terminal regulatory domain (RD). Phylogenetic analysis revealed that CgRIG-I was grouped into the clade of its vertebrate homologs. Moreover, CgRIG-I expression could be specifically increased after stimulation by poly(I:C) rather than by other PAMPs such as lipopolysaccharide (LPS), peptidoglycan (PGN), heat-killed Listeria monocytogenes (HKLM) and heat-killed Vibrio alginolyticus (HKVA). Meanwhile, six IRF, three STAT and one NF-?B predicted sites were identified in the CgRIG-I promoter, which was consistent with its high responsiveness to poly(I:C). In summary, this report provides the first CgRIG-I sequence of a mollusk, but its function in the antiviral immune response requires further investigation.
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Aromatase (Cyp19a1b) in the Pituitary Is Dynamically Involved in the Upregulation of lhb But Not fshb in the Vitellogenic Female Ricefield Eel Monopterus albus.
Endocrinology
PUBLISHED: 08-08-2014
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Aromatase, encoded by Cyp19a1, is expressed in the pituitary of vertebrates; however, its physiological relevance remains poorly defined. In teleosts, the duplicated cyp19a1b is preferentially expressed in the pituitary where LH and FSH are synthesized in distinct gonadotropes. Our present study demonstrated that Cyp19a1b is colocalized with Lhb, but not Fshb, during vitellogenesis in female ricefield eels. The immunoreactive levels of Cyp19a1b and Lhb, as well as their colocalization frequency, increased during vitellogenesis toward maturation. The expression of lhb but not fshb in the pituitary fragments of female ricefield eels was induced by both estradiol (E2) and testosterone (T). In agreement, the promoter of lhb but not fshb was activated by both E2 and T. T is more potent than E2 in inducing lhb expression, whereas E2 is much more effective in activating the lhb promoter. T-induced lhb expression in the pituitary fragments was abolished by the estrogen receptor (Esr) antagonist fulvestrant and suppressed by the aromatase inhibitor letrozole, suggesting that the effect of T on lhb expression at the pituitary is largely mediated by E2. Furthermore, Lhb was shown to colocalize with Esr1 but not Esr2a. Taken together, results of the present study suggest that Cyp19a1b in LH cells may greatly upregulate lhb expression during vitellogenesis, possibly via E2 and Esr1 in an intracrine manner. The absence of Cyp19a1b in FSH cells and the insensitivity of fshb to sex steroids may contribute to the differential expression of lhb and fshb in ricefield eels and possibly other vertebrates as well.
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Theoretical study of temperature dependence and Rayleigh scattering properties of chloride hydration clusters.
Phys Chem Chem Phys
PUBLISHED: 08-07-2014
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Cl(-)(H2O)n (n = 5-6) clusters were investigated using a basin hopping (BH) method coupled with density functional theory (DFT). Structures, energetics, thermodynamics, and vibrational frequencies were obtained using high level ab initio calculations. DF-LMP2 (second-order Møller-Plesset perturbation theory using local and density fitting approximations) with an appropriate basis set were employed for final optimization and frequency calculation, which has been benchmarked in a recent study. The global minimum of Cl(-)(H2O)5 was verified and the new competitive local minimum of Cl(-)(H2O)6 was offered. Considering the increasing complexity of the large system and the high flexibility of the hydrogen bonding environment, Boltzmann averaged Gibbs free energy was provided taking into account the contributions of local minima on the potential energy surface. Finally, the temperature dependence of the conformational population for isomers of Cl(-)(H2O)n (n = 5-6) and Rayleigh scattering properties of Cl(-)(H2O)n (n = 1-6) have been investigated systematically for the first time.
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Estimation of the age and amount of brown rice plant hoppers based on bionic electronic nose use.
Sensors (Basel)
PUBLISHED: 08-06-2014
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The brown rice plant hopper (BRPH), Nilaparvata lugens (Stal), is one of the most important insect pests affecting rice and causes serious damage to the yield and quality of rice plants in Asia. This study used bionic electronic nose technology to sample BRPH volatiles, which vary in age and amount. Principal component analysis (PCA), linear discrimination analysis (LDA), probabilistic neural network (PNN), BP neural network (BPNN) and loading analysis (Loadings) techniques were used to analyze the sampling data. The results indicate that the PCA and LDA classification ability is poor, but the LDA classification displays superior performance relative to PCA. When a PNN was used to evaluate the BRPH age and amount, the classification rates of the training set were 100% and 96.67%, respectively, and the classification rates of the test set were 90.67% and 64.67%, respectively. When BPNN was used for the evaluation of the BRPH age and amount, the classification accuracies of the training set were 100% and 48.93%, respectively, and the classification accuracies of the test set were 96.67% and 47.33%, respectively. Loadings for BRPH volatiles indicate that the main elements of BRPHs' volatiles are sulfur-containing organics, aromatics, sulfur-and chlorine-containing organics and nitrogen oxides, which provide a reference for sensors chosen when exploited in specialized BRPH identification devices. This research proves the feasibility and broad application prospects of bionic electronic noses for BRPH recognition.
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Characterization of corncob-derived biochar and pyrolysis kinetics in comparison with corn stalk and sawdust.
Bioresour. Technol.
PUBLISHED: 08-01-2014
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In this study, thermal and physicochemical characterization results of corncob (CC) and its derived biochars were analyzed and differentiated from sawdust (SD) and cornstalk (CS). The pyrolysis temperature shows the largest effect on the yield of biochar produced compare with residing time, heating rate, and feedstock particle size. The CC-derived biochars produced at temperatures ranging from 300 to 600°C were analyzed. The CC was thermochemically altered to a stable biochar when the pyrolysis temperature was set to over 500°C. To deduce the reaction mechanism of the CC during the major thermal decomposition stage, 16 mechanisms in solid-state reactions were applied. The reaction order and nucleation mechanisms described the thermal decomposition of the CC. By using the best-fitted mechanisms, the kinetic parameters were calculated. The weight active energy of the CC was 122.42kJ/mol, which was the lowest value compared to those of CS and SD.
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Inhibitor of the tyrosine phosphatase STEP reverses cognitive deficits in a mouse model of alzheimer's disease.
PLoS Biol.
PUBLISHED: 08-01-2014
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STEP (STriatal-Enriched protein tyrosine Phosphatase) is a neuron-specific phosphatase that regulates N-methyl-D-aspartate receptor (NMDAR) and ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking, as well as ERK1/2, p38, Fyn, and Pyk2 activity. STEP is overactive in several neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease (AD). The increase in STEP activity likely disrupts synaptic function and contributes to the cognitive deficits in AD. AD mice lacking STEP have restored levels of glutamate receptors on synaptosomal membranes and improved cognitive function, results that suggest STEP as a novel therapeutic target for AD. Here we describe the first large-scale effort to identify and characterize small-molecule STEP inhibitors. We identified the benzopentathiepin 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (known as TC-2153) as an inhibitor of STEP with an IC50 of 24.6 nM. TC-2153 represents a novel class of PTP inhibitors based upon a cyclic polysulfide pharmacophore that forms a reversible covalent bond with the catalytic cysteine in STEP. In cell-based secondary assays, TC-2153 increased tyrosine phosphorylation of STEP substrates ERK1/2, Pyk2, and GluN2B, and exhibited no toxicity in cortical cultures. Validation and specificity experiments performed in wild-type (WT) and STEP knockout (KO) cortical cells and in vivo in WT and STEP KO mice suggest specificity of inhibitors towards STEP compared to highly homologous tyrosine phosphatases. Furthermore, TC-2153 improved cognitive function in several cognitive tasks in 6- and 12-mo-old triple transgenic AD (3xTg-AD) mice, with no change in beta amyloid and phospho-tau levels.
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Detection of cyclic di-AMP using a competitive ELISA with a unique pneumococcal cyclic di-AMP binding protein.
J. Microbiol. Methods
PUBLISHED: 07-25-2014
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Cyclic di-AMP (c-di-AMP) is a recently recognized bacterial signaling molecule. In this study, a competitive enzyme-linked immunosorbent assay (ELISA) for the quantification of c-di-AMP was developed using a novel pneumococcal c-di-AMP binding protein (CabP). With this method, c-di-AMP concentrations in biological samples can be quickly and accurately quantified.
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Effects of VBMDMP on the reversal of cisplatin resistance in human lung cancer A549/DDP cells.
Oncol. Rep.
PUBLISHED: 07-24-2014
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Tumor drug resistance is a major obstacle to cancer chemotherapy. We previously constructed a fusion protein based on two tumstatin-derived sequences named recombinant VBMDM (rVBMDMP). We preliminarily confirmed its inhibition of HUVEC and colon cancer cell growth. The present study further systematically observed the inhibitory effect of rVBMDMP on lung cancer cell growth and analyzed a possible mechanism to provide a theoretical basis for the development of new antitumor protein drugs. The effect of rVBMDMP on human lung adenocarcinoma (A549) and cisplatin-resistant human lung adenocarcinoma (A549/DDP) cell proliferation was evaluated by MTS assay. Hoechst 33342 staining performed together with fluorescence microscopy and immunoblot analysis were used to examine the effects of rVBMDMP on the apoptosis of A549/DDP cells. A protein phosphorylation chip was used to identify changes in rVBMDMP-induced signaling protein phosphorylation. Changes in the phosphatidylinositol 3 kinase (PI3K)/Akt signal transduction pathway and expression of multidrug resistance protein (MRP-2)-related molecules following rVBMDMP treatment in A549/DDP cells were evaluated by western blot analysis. A lung cancer xenograft model was used to evaluate the reversal effect of rVBMDMP on drug-resistance of A549/DDP cell tumors to cisplatin in vivo. The results demonstrated that rVBMDMP increased the phosphorylation of 79 signaling proteins, including focal adhesion kinase (FAK), caspase-6, Fas, FasL and FAF1 and downregulated 30 signaling proteins, including integrin ?V, integrin ?3, PI3K/Akt, NF-?B and MRP-2 compared with the controls. rVBMDMP also increased the sensitivity of A549 and A549/DDP cells to cisplatin and directly induced apoptosis, which may be related to MRP-2 and Bcl-2 downregulation. The effects of growth inhibition and apoptosis induction of rVBMDMP on A549/DDP cells may be related to the inhibition of integrin ?V?3 and PI3K/Akt protein phosphorylation. Finally, we observed an increase in cancer cell sensitivity to cisplatin by rVBMDMP using the A549/DDP cell xenograft model in nude mice. Our study suggests that rVBMDMP may be an effective potential chemotherapy sensitizer and may be a viable drug candidate in anticancer therapies.
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Meta-analysis of lobectomy, segmentectomy, and wedge resection for stage I non-small cell lung cancer.
J Surg Oncol
PUBLISHED: 07-21-2014
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Survival difference following lobectomy, segmentectomy, and wedge resection in stage I non-small cell lung cancer (NSCLC) and its subgroups remains undetermined.
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The identification of the first molluscan Akirin2 with immune defense function in the Hong Kong oyster Crassostrea hongkongensis.
Fish Shellfish Immunol.
PUBLISHED: 07-08-2014
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The Akirin protein is a nuclear factor in the innate immune system that is highly conserved from insects to mammals and plays key roles in diverse biological processes, including immunity, myogenesis, development and the cellular stress response. However, the function of Akirins in mollusk, the second most diverse group of animals, is still poorly understood. In this study, we report the discovery of an Akirin2 gene homolog (ChAkirin2) and its biological functions in the Hong Kong oyster Crassostrea hongkongensis. ChAkirin2 is 189 amino acids in length and shares significant homology with invertebrate homologs. Phylogenetic analysis results revealed that ChAkirin2 is clustered with invertebrate Akirin2s. A sequence analysis of the 5' flanking regions of ChAkirin2 indicated that it harbors several potential PAMP-activated transcription factor binding sites (TFB), including sites for NF-?B, C/EBP?, AP-1, SRF, Oct-1 and GATA-1. An RT-PCR analysis showed that ChAkirin2 mRNA was ubiquitously expressed in various tissues and at different embryonic and larval stages. Additionally, upon infection by pathogens (Vibrio alginolyticus, Staphylococcus haemolyticus and Saccharomyces cerevisiae) and pathogen-associated molecular patterns (PAMPs: LPS, PGN and polyI:C), the expression of ChAkirin2 was significantly up-regulated. Moreover, fluorescence microscopy observations show that ChAkirin2 is located in the nuclei of HeLa cells, and the overexpression of ChAkirin2 activated the transcriptional activities of the NF-?B reporter gene in HEK293T cells. Altogether, this report provided the first experimental demonstration that mollusks possess a functional Akirin2 that is involved in the innate defense and embryogenesis processes of the oyster.
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Disentangling the multifactorial contributions of fibronectin, collagen and cyclic strain on MMP expression and extracellular matrix remodeling by fibroblasts.
Matrix Biol.
PUBLISHED: 07-05-2014
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Early wound healing is associated with fibroblasts assembling a provisional fibronectin-rich extracellular matrix (ECM), which is subsequently remodeled and interlaced by type I collagen. This exposes fibroblasts to time-variant sets of matrices during different stages of wound healing. Our goal was thus to gain insight into the ECM-driven functional regulation of human foreskin fibroblasts (HFFs) being either anchored to a fibronectin (Fn) or to a collagen-decorated matrix, in the absence or presence of cyclic mechanical strain. While the cells reoriented in response to the onset of uniaxial cyclic strain, cells assembled exogenously added Fn with a preferential Fn-fiber alignment along their new orientation. Exposure of HFFs to exogenous Fn resulted in an increase in matrix metalloproteinase (MMP) expression levels, i.e. MMP-15 (RT-qPCR), and MMP-9 activity (zymography), while subsequent exposure to collagen slightly reduced MMP-15 expression and MMP-9 activity compared to Fn-exposure alone. Cyclic strain upregulated Fn fibrillogenesis and actin stress fiber formation, but had comparatively little effect on MMP activity. We thus propose that the appearance of collagen might start to steer HFFs towards homeostasis, as it decreased both MMP secretion and the tension of Fn matrix fibrils as assessed by Fluorescence Resonance Energy Transfer. These results suggest that HFFs might have a high ECM remodeling or repair capacity in contact with Fn alone (early event), which is reduced in the presence of Col1 (later event), thereby down-tuning HFF activity, a processes which would be required in a tissue repair process to finally reach tissue homeostasis.
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Complementary sequence-mediated exon circularization.
Cell
PUBLISHED: 07-01-2014
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Exon circularization has been identified from many loci in mammals, but the detailed mechanism of its biogenesis has remained elusive. By using genome-wide approaches and circular RNA recapitulation, we demonstrate that exon circularization is dependent on flanking intronic complementary sequences. Such sequences and their distribution exhibit rapid evolutionary changes, showing that exon circularization is evolutionarily dynamic. Strikingly, exon circularization efficiency can be regulated by competition between RNA pairing across flanking introns or within individual introns. Importantly, alternative formation of inverted repeated Alu pairs and the competition between them can lead to alternative circularization, resulting in multiple circular RNA transcripts produced from a single gene. Collectively, exon circularization mediated by complementary sequences in human introns and the potential to generate alternative circularization products extend the complexity of mammalian posttranscriptional regulation.
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New insight into the mechanism underlying fibroin secretion in silkworm, Bombyx mori.
FEBS J.
PUBLISHED: 06-04-2014
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In order to investigate the role of different parts of the fibroin heavy chain (H-chain) in the secretion of fibroin in the silk gland of the silkworm (Bombyx mori) in vivo, two enhanced green fluorescent protein (EGFP)/H-chain fusion genes with deduced protein sequences containing an identical N-terminal region and different C-terminal regions of the H-chain were introduced into the B. mori genome using a piggyBac-mediated germline transformation. EGFP fluorescence and molecular analysis showed the products of two different EGFP/H-chain fusion proteins were secreted into the posterior silk gland lumen and aggregated in the middle silk gland and spun into cocoons. The results revealed that only the non-repetitive N terminus of the H-chain is essential for secretion of the H-chain into the posterior silk gland lumen. In addition, our results also indicated that the most likely post-translational modification of the H-chain is at the C-terminal domain. Here, our results not only provide a theoretical basis for the genetic modification of silk fiber as a functional biomaterial but also are of great significance to establishing a new silk gland bioreactor to mass-produce exogenous proteins in an active form.
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Protein structure prediction provides comparable performance to crystallographic structures in docking-based virtual screening.
Methods
PUBLISHED: 06-02-2014
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Structure based virtual screening has largely been limited to protein targets for which either an experimental structure is available or a strongly homologous template exists so that a high-resolution model can be constructed. The performance of state of the art protein structure predictions in virtual screening in systems where only weakly homologous templates are available is largely untested. Using the challenging DUD database of structural decoys, we show here that even using templates with only weak sequence homology (<30% sequence identity) structural models can be constructed by I-TASSER which achieve comparable enrichment rates to using the experimental bound crystal structure in the majority of the cases studied. For 65% of the targets, the I-TASSER models, which are constructed essentially in the apo conformations, reached 70% of the virtual screening performance of using the holo-crystal structures. A correlation was observed between the success of I-TASSER in modeling the global fold and local structures in the binding pockets of the proteins versus the relative success in virtual screening. The virtual screening performance can be further improved by the recognition of chemical features of the ligand compounds. These results suggest that the combination of structure-based docking and advanced protein structure modeling methods should be a valuable approach to the large-scale drug screening and discovery studies, especially for the proteins lacking crystallographic structures.
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Alisertib (MLN8237), a selective Aurora-A kinase inhibitor, induces apoptosis in human tongue squamous cell carcinoma cell both in vitro and in vivo.
Tumour Biol.
PUBLISHED: 05-29-2014
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Aurora-A kinases are overexpressed in many cancer tissues and cells. Alisertib is an investigational, orally administered, selective, small-molecule Aurora-A kinase inhibitor with preclinical activity against a broad range of tumors. Our study was aimed to detect the effects of alisertib on human tongue squamous cell carcinoma (HTSCC). Treatment of a human tongue squamous cell carcinoma cell line, HSC-3, with alisertib to inhibition of Aurora-A kinases reduced proliferation and induced apoptosis, which was accompanied by activation of the ATM/Chk2/p53 pathway. In vivo, inhibition of Aurora-A kinases in established xenografted tumors decreased tumor size and weight. Kaplan-Meyer survival analysis demonstrated that the cumulative survival time of mice without Aurora-A kinases was significantly longer than those with Aurora-A kinases. Our data provide the basis for developing alisertib to treat human tongue squamous cell carcinoma.
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Analysis of the molecular and clinicopathologic features of surgically resected lung adenocarcinoma in patients under 40 years old.
J Thorac Dis
PUBLISHED: 05-25-2014
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The youthful lung cancer may constitute an entity with distinct clinicopathologic characteristics and a controversial prognosis compared with the older counterpart. Whether the youthful lung cancer has the exclusively distinct molecular features has not been well investigated.
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Insulin improves osteogenesis of titanium implants under diabetic conditions by inhibiting reactive oxygen species overproduction via the PI3K-Akt pathway.
Biochimie
PUBLISHED: 05-13-2014
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Clinical evidence indicates that insulin therapy improves implant survival rates in diabetic patients; however, the mechanisms responsible for this effect are unknown. Here, we test if insulin exerts anti-oxidative effects, thereby improving diabetes-associated impaired osteoblast behavior on titanium implants. To test this hypothesis, we cultured primary rabbit osteoblasts in the presence of titanium implants and studied the impact of treatment with normal serum (NS), diabetic serum (DS), DS + insulin, DS + tempol (a superoxide dismutase mimetic), DS + insulin + tempol, and DS + insulin + wortmannin. We analyzed cell function, apoptosis, and reactive oxygen species (ROS) production in osteoblasts following the various treatments. Treatment with DS induced osteoblast dysfunction, evidenced by impaired cell attachment and morphology, decreased cell proliferation and ALP activity, and decreased expression of osteogenesis-related genes. We also observed a significant increase in apoptosis. Importantly, treatment with DS resulted in increased production of ROS in osteoblasts. In contrast, treatment with insulin inhibited ROS production, alleviated cell dysfunction, and decreased apoptosis of osteoblasts on the implants. Scavenging ROS with tempol also attenuated cell dysfunction. Compared to insulin treatment alone, the combination of insulin and tempol failed to further improve osteoblast functional recovery. Moreover, the anti-oxidative and pro-osteogenic effects afforded by insulin were almost completely abolished by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. These results demonstrate, for the first time, that insulin treatment alleviates the impaired osteogenesis of titanium implants under diabetic conditions by inhibiting ROS overproduction via a PI3K/Akt-dependent mechanism. Both the anti-oxidative and metabolic properties of insulin should make it a viable therapeutic option to combat diabetic implant failure.
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Constitutive ERK1/2 activation contributes to production of double minute chromosomes in tumour cells.
J. Pathol.
PUBLISHED: 04-24-2014
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Double minute chromosomes (DMs) are extrachromosomal cytogenetic structures found in tumour cells. As hallmarks of gene amplification, DMs often carry oncogenes and drug-resistance genes and play important roles in malignant tumour progression and drug resistance. The mitogen-activated protein kinase (MAPK) signalling pathway is frequently dysregulated in human malignant tumours, which induces genomic instability, but it remains unclear whether a close relationship exists between MAPK signalling and DMs. In the present study, we focused on three major components of MAPK signalling, ERK1/2, JNK1/2/3 and p38, to investigate the relationship between MAPK and DM production in tumour cells. We found that the constitutive phosphorylation of ERK1/2, but not JNK1/2/3 and p38, was closely associated with DMs in tumour cells. Inhibition of ERK1/2 activation in DM-containing and ERK1/2 constitutively phosphorylated tumour cells was able to markedly decrease the number of DMs, as well as the degree of amplification and expression of DM-carried genes. The mechanism was found to be an increasing tendency of DM DNA to break, become enveloped into micronuclei (MNs) and excluded from the tumour cells during the S/G2 phases of the cell cycle, events that accompanied the reversion of malignant behaviour. Our study reveals a linkage between ERK1/2 activation and DM stability in tumour cells. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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T-cell-associated cellular immunotherapy for lung cancer.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 04-22-2014
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The aim of the present study was to discuss recent findings on the role of T cells in lung cancer to provide information on their potential application, especially in cellular immunotherapy.
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Template-based structure modeling of protein-protein interactions.
Curr. Opin. Struct. Biol.
PUBLISHED: 04-12-2014
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The structure of protein-protein complexes can be constructed by using the known structure of other protein complexes as a template. The complex structure templates are generally detected either by homology-based sequence alignments or, given the structure of monomer components, by structure-based comparisons. Critical improvements have been made in recent years by utilizing interface recognition and by recombining monomer and complex template libraries. Encouraging progress has also been witnessed in genome-wide applications of template-based modeling, with modeling accuracy comparable to high-throughput experimental data. Nevertheless, bottlenecks exist due to the incompleteness of the protein-protein complex structure library and the lack of methods for distant homologous template identification and full-length complex structure refinement.
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Tracking plasma cell differentiation and survival.
Cytometry A
PUBLISHED: 04-05-2014
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Plasma cells play a crucial role for the humoral immune response as they represent the body's factories for antibody production. The differentiation from a B cell into a plasma cell is controlled by a complex transcriptional network and happens within secondary lymphoid organs. Based on their lifetime, two types of antibody secreting cells can be distinguished: Short-lived plasma cells are located in extrafollicular sites of secondary lymphoid organs such as lymph node medullary cords and the splenic red pulp. A fraction of plasmablasts migrate from secondary lymphoid organs to the bone marrow where they can become long-lived plasma cells. Bone marrow plasma cells reside in special microanatomical environments termed survival niches, which provide factors promoting their longevity. Reticular stromal cells producing the chemokine CXCL12, which is known to attract plasmablasts to the bone marrow but also to promote plasma cell survival, play a crucial role in the maintenance of these niches. In addition, hematopoietic cells are contributing to the niches by providing other soluble survival factors. Here, we review the current knowledge on the factors involved in plasma cell differentiation, their localization and migration. We also give an overview on what is known regarding the maintenance of long lived plasma cells in survival niches of the bone marrow.
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Genomic characterization and expression analysis of five novel IL-17 genes in the Pacific oyster, Crassostrea gigas.
Fish Shellfish Immunol.
PUBLISHED: 04-03-2014
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Interleukin-17 (IL-17) is a proinflammatory cytokine that plays an important role in clearing extracellular bacteria and contributes to the pathology of many autoimmune and allergic conditions. In the present study, five novel IL-17 homologs were identified by searching and analyzing the Pacific oyster genome. All six CgIL-17 members (including a previously reported homolog) contained four conserved cysteines that were used in the formation of disulfide bonds. Phylogenetic analysis showed that all invertebrate IL-17s were clustered into one group, implying that invertebrate IL-17s evolved from one common ancestral gene and subsequently diversified. All CgIL-17s shared the same genomic structure, containing two exons and one intron, except for the CgIL-17-3 and CgIL-17-5 genes, which each had only one exon. The expression pattern of the CgIL-17 genes was analyzed by qRT-PCR in a variety of tissues and at different developmental stages, and these genes were highly expressed in the gill and digestive gland tissues. Moreover, the expression of the CgIL-17 family genes was significantly up-regulated in hemocytes challenged with Pathogen-Associated Molecular Patterns (PAMPs). CgIL-17-3 had a strong response to lipopolysaccharide (LPS) and heat-killed Vibrio alginolyticus (HKVA) challenge, while CgIL-17-5 and CgIL-17-6 can be activated by peptidoglycan (PGN), but not by heat-killed Listeria monocytogenes (HKLM). The distinct, up-regulated transcript levels of the CgIL-17s in response to PAMPs challenge further indicate that CgIL-17s are likely to be significant components of immune responses by playing diversified roles in host defense in the Pacific oyster. These findings suggest that CgIL-17s are involved in innate immune responses and further supports their conserved function in mollusks immunity.
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Cassava genome from a wild ancestor to cultivated varieties.
Nat Commun
PUBLISHED: 03-20-2014
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Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology.
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Bone morphogenic protein-4-induced oxidant signaling via protein carbonylation for endothelial dysfunction.
Free Radic. Biol. Med.
PUBLISHED: 03-10-2014
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The increased expression of bone morphogenic protein-4 (BMP-4) under hyperglycemic and diabetic conditions mediates the overgeneration of reactive oxygen species to cause endothelial cell dysfunction and apoptosis. Protein carbonylation plays an important role in oxidant signaling through ligand-receptor interactions in vascular smooth muscle cells, cardiac cells, and bronchial smooth muscle cells to trigger different diseases. However, the role of oxidant signaling via protein carbonylation in endothelial dysfunction is unclear. The level of protein carbonylation was higher in renal arteries from diabetic patients than those from nondiabetic subjects. BMP-4 promoted protein carbonylation, which was followed by decarbonylation or degradation in primary rat aortic endothelial cells. Organ culture of normal C57BL/6J mouse aortas treated with either hydralazine or deferoxamine inhibited the effect of BMP-4 on impairment of acetylcholine-induced endothelium-dependent relaxation (EDR). In isolated diabetic db/db mouse aortas, treatment with hydralazine improved the impaired EDR while deferoxamine had no effect. BMP-4-induced carbonylated proteins in aortic endothelial cells were successfully identified by a proteomic approach. These proteins have important cellular functions and include glyceraldehyde-3-phosphate dehydrogenase, triosephosphate isomerase, alpha-enolase, protein disulfide-isomerase A3, annexin II, 26S protease regulatory subunit, integrin-linked protein kinase, and vimentin. Protein carbonylation induced by BMP-4 was inhibited by BMP-4 antagonist while protein decarbonylation induced by BMP-4 was thiol dependent. The carbonyl signals did not involve 4-hydrononenal and malondialdehyde. The present results suggest that BMP-4- or diabetes-mediated endothelial dysfunction is partly triggered through protein carbonylation and blockade of this metal-catalyzed protein oxidation can be considered as an alternative therapeutic strategy to alleviate diabetic vasculopathy.
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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.