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Find video protocols related to scientific articles indexed in Pubmed.
Phage Display-Mediated Discovery of Novel Tyrosinase-Targeting Tetrapeptide Inhibitors Reveals the Significance of N-Terminal Preference of Cysteine Residues and Their Functional Sulfur Atom.
Mol. Pharmacol.
PUBLISHED: 11-19-2014
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Tyrosinase, a key copper-containing enzyme involved in melanin biosynthesis, is closely associated with hyperpigmentation disorders, cancer, and neurodegenerative diseases, and as such, it is an essential target in medicine and cosmetics. Known tyrosinase inhibitors possess adverse side effects, and there are no safety regulations, so there is the necessity to develop new inhibitors with fewer side effects and less toxicity. Peptides are exquisitely specific to their in vivo targets, with high potencies and relatively few off-target side effects. Thus, we systematically and comprehensively investigated the tyrosinase-inhibitory abilities of N- and C-terminal cysteine/tyrosine-constrained tetrapeptides by constructing a phage-display random tetrapeptide library and conducting computational molecular docking studies on novel tyrosinase tetrapeptide inhibitors. We found that N-terminal cysteine-constrained tetrapeptides exhibited the most potent tyrosinase-inhibitory abilities. The positional preference of cysteine residues at the N-terminus in the tetrapeptides significantly contributed to their tyrosinase-inhibitory function. The sulfur atom in cysteine moieties of N- and C-terminal cysteine-constrained tetrapeptides coordinated with copper ions which then tightly blocked substrate-binding sites. N- and C-terminal tyrosine-constrained tetrapeptides functioned as competitive inhibitors against mushroom tyrosinase by using the phenol ring of tyrosine to stack with the imidazole ring of His263, thus competing for the substrate-binding site. The N-terminal cysteine-constrained tetrapeptide, CRVI, exhibited the strongest tyrosinase-inhibitory potency (with an IC50 of 2.7 ± 0.5 ?M) which was superior to those of the known tyrosinase inhibitors (arbutin and kojic acid) and outperformed kojic acid-tripeptides, mimosine-FFY, and short-sequence oligopeptides at inhibiting mushroom tyrosinase.
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Efficacy and safety of low dose lenalidomide plus dexamethasone in patients with relapsed or refractory POEMS syndrome.
Eur. J. Haematol.
PUBLISHED: 11-18-2014
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Although autologous stem cell transplantation or melphalan-based chemotherapy has significantly improved the prognosis of POEMS syndrome, a few patients will relapse or be refractory to primary therapy, and there is a lack of studies regarding these patients. In the present study, we used low dose lenalidomide (10 mg daily) and dexamethasone (40 mg, once-weekly) to treat twelve patients with relapsed (n = 8) or refractory (n = 4) POEMS syndrome. After a median follow-up time of 20 months, the overall hematologic response rate was 77% with 44% having a complete response. Eight (67%) patients had neurological response and the median overall neuropathy limitation scale score was reduced from 3 (range, 1-9) to 2 (range, 0-6). Serum vascular endothelial growth factor response rate was 91% and 46% of patients had normal serum VEGF levels. One patient had progression of the disease 3 months after the end of treatment and subsequently died from the disease. Therefore, the estimated 2 year overall survival and progression-free survival were 92%. The low-dose lenalidomide and dexamethasone regimen was well tolerated, with no treatment-related death or any grade 3 or 4 toxicity. In conclusion, low dose lenalidomide plus dexamethasone therapy is an effective and safe regimen for patients with relapsed or refractory POEMS syndrome. This article is protected by copyright. All rights reserved.
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Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2).
Eur. Respir. J.
PUBLISHED: 11-15-2014
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Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three-times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m (n = 172) versus CHEST-1 baseline (n = 237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n = 176) versus CHEST-1 baseline (n = 236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year.
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RAD6 promotes homologous recombination repair by activating the autophagy-mediated degradation of heterochromatin protein HP1.
Mol. Cell. Biol.
PUBLISHED: 11-12-2014
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Efficient DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. Unrepaired or mis-repaired DSBs cause chromosomal rearrangements that can result in severe consequences such as tumorigenesis. RAD6 is an E2 ubiquitin-conjugating enzyme that plays a pivotal role in repairing UV-induced DNA damage. Here, we present evidence that RAD6 is also required for DNA DSB repair via homologous recombination (HR) by specifically regulating the degradation of heterochromatin protein 1? (HP1?). Our study indicates that RAD6 physically interacts with HP1? and ubiquitinates HP1? at residue K154, thereby promoting HP1? degradation through the autophagy pathway and eventually leading to an open chromatin structure that facilitates efficient HR DSB repair. Furthermore, bioinformatics studies have indicated that the expression of RAD6 and HP1? exhibits an inverse relationship and correlates with the survival rate of patients.
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Highly efficient photodimerization of olefins in a nanotemplate on HOPG by scanning tunneling microscopy.
Phys Chem Chem Phys
PUBLISHED: 10-31-2014
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Efficient photochemical reactions on a surface are of great importance for their potential applications in optoelectronic devices. In this work, a highly efficient photodimerization reaction of an olefin cocrystal built from two trans-1,2-bis(4-pyridyl)ethylenes (4,4'-bpe) and two isophthalic acid molecules via NH-O hydrogen bonds in between was achieved in a nanotemplate on a highly oriented pyrolytic graphite (HOPG) surface. 4,4'-Bpe molecules first undergo the trans-cis isomerization followed by [2+2] photodimerization in the nanotemplate on HOPG upon UV irradiation. The efficiency of the isomerization as well as the photodimerization in the presence of the nanotemplate is much higher than that in its absence. These results provide a facile way to achieve highly efficient photodimerization of olefins on a large scale on surfaces.
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A eukaryotic expression plasmid carrying chicken IL-18 enhances the response to Newcastle disease vaccine.
Clin. Vaccine Immunol.
PUBLISHED: 10-31-2014
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Interleukin-18 (IL-18) is an important cytokine involved in innate and acquired immunity. In this study, we cloned full-length chicken IL-18 (ChIL-18) gene from SPF chicken embryo spleen cells and provided evidence that ChIL-18 gene in recombinant plasmid was successfully expressed in chicken DT40 cell. ChIL18 significantly enhanced interferon-? mRNA expression in chicken splenocytes, which increased interferon-?-induced nitric oxide (NO) synthesis by macrophages. The potential genetic adjuvant activity of ChIL-18 plasmid was examined in chickens by co-injection of ChIL-18 plasmid and Newcastle disease (ND) inactivated vaccine. ChIL-18 markedly elevated serum hemagglutination inhibition (HI) titers and anti-hemagglutinin-neuraminidase (anti-HN) specific antibody levels, induced the secretion of both Th1 (interferon-?) and Th2 (interleukin-4) type cytokines, promoted the proliferation of T and B lymphocytes, and increased populations of CD3(+)T cells and their subsets, CD3(+)CD4(+) and CD3(+)CD8(+) T cells. Furthermore, virus challenge revealed that ChIL-18 contributed to protection against Newcastle disease virus challenge. Taken together, our data indicate that the co-administration of ChIL-18 plasmid and ND vaccine induces a strong immune response at both the humoral and cellular levels and that ChIL-18 is a novel immunoadjuvant suitable for ND vaccination.
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Measuring and Modeling the Salting-out Effect in Ammonium Sulfate Solutions.
Environ. Sci. Technol.
PUBLISHED: 10-30-2014
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The presence of inorganic salts significantly influences the partitioning behavior of organic compounds between environmentally relevant aqueous phases, such as seawater or aqueous aerosol, and other, nonaqueous phases (gas phase, organic phase, etc.). In this study, salting-out coefficients (or Setschenow constants) (KS [M(-1)]) for 38 diverse neutral compounds in ammonium sulfate ((NH4)2SO4) solutions were measured using a shared headspace passive dosing method and a negligible depletion solid phase microextraction technique. The measured KS were all positive, varied from 0.216 to 0.729, and had standard errors in the range of 0.006-0.060. Compared to KS for sodium chloride (NaCl) in the literature, KS values for (NH4)2SO4 are always higher for the same compound, suggesting a higher salting-out effect of (NH4)2SO4. A polyparameter linear free energy relationship (pp-LFER) for predicting KS in (NH4)2SO4 solutions was generated using the experimental data for calibration. pp-LFER predicted KS agreed well with measured KS reported in the literature. KS for (NH4)2SO4 was also predicted using the quantum-chemical COSMOtherm software and the thermodynamic model AIOMFAC. While COSMOtherm generally overpredicted the experimental KS, predicted and experimental values were correlated. Therefore, a fitting factor needs to be applied when using the current version of COSMOtherm to predict KS. AIOMFAC tends to underpredict the measured KS((NH4)2SO4) but always overpredicts KS(NaCl). The prediction error is generally larger for KS(NaCl) than for KS((NH4)2SO4). AIOMFAC also predicted a dependence of KS on the salt concentrations, which is not observed in the experimental data. In order to demonstrate that the models developed and calibrated in this study can be applied to estimate Setschenow coefficients for atmospherically relevant compounds involved in secondary organic aerosol formation based on chemical structure alone, we predicted and compared KS for selected ?-pinene oxidation products.
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Serendipitous Discovery of Short Peptides from Natural Products as Tyrosinase Inhibitors.
J Chem Inf Model
PUBLISHED: 10-30-2014
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Tyrosinase, which is the crucial copper-containing enzyme involved in melanin synthesis, is strongly associated with hyperpigmentation disorders, cancer, and neurodegenerative disease; thus, it has attracted considerable interest in the fields of medicine and cosmetics. The known tyrosinase inhibitors show numerous adverse side effects, and there is a lack of safety regulations governing their use. As a result, there is a need to develop novel inhibitors with no toxicity and long-term stability. In this study, we use molecular docking and pharmacophore modeling to construct a reasonable and reliable pharmacophore model, called Hypo 1, that could be used for identifying potent natural products with crucial complementary functional groups for mushroom tyrosinase inhibition. It was observed that, out of 47?263 natural compounds, A5 structurally resembles a dipeptide (WY) and natural compound B16 is the equivalent of a tripeptide (KFY), revealing that the C-terminus tyrosine residues play a key role in tyrosinase inhibition. Tripeptides RCY and CRY, which show high tyrosinase inhibitory potency, revealed a positional and functional preference for the cysteine residue at the N-terminus of the tripeptides, essentially determining the capacity of tyrosinase inhibition. CRY and RCY used the thiol group of cysteine residues to coordinate with the Cu ions in the active site of tyrosinase and showed reduced tyrosinase activity. We discovered the novel tripeptide CRY that shows the most striking inhibitory potency against mushroom tyrosinase (IC50 = 6.16 ?M); this tripeptide is more potent than the known oligopeptides and comparable with kojic acid-tripeptides. Our study provides an insight into the structural and functional roles of key amino acids of tripeptides derived from the natural compound B16, and the results are expected to be useful for the development of tyrosinase inhibitors.
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[Risk factors for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae colonization in neonates].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 10-26-2014
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To identify risk factors for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) colonization in neonates hospitalized in the neonatal intensive care unit (NICU).
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Design of Au@ZnO Yolk-Shell Nanospheres with Enhanced Gas Sensing Properties.
ACS Appl Mater Interfaces
PUBLISHED: 10-17-2014
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The Au@ZnO yolk-shell nanospheres with a distinctive core@void@shell configuration have been successfully synthesized by deposition of ZnO on Au@carbon nanospheres. Various techniques were employed for the characterization of the structure and morphology of as-obtained hybrid nanostructures. The results indicated that the Au@ZnO yolk-shell nanospheres have an average diameter of about 280 nm and the average thickness of the ZnO shell is ca. 40 nm. To demonstrate how such a unique structure might bring about more excellent gas sensing property, we carried out a comparison of the sensing performances of ZnO nanospheres with different inner structures. It was found that Au@ZnO yolk-shell nanospheres exhibited an obvious improvement in response to acetone compared with the pure ZnO nanospheres with hollow and solid inner structures. For instance, the response of the Au@ZnO nanospheres to 100 ppm acetone was about 37, which was about 2 (3) times higher than that of ZnO hollow (solid) nanostructures. The enhanced sensing properties were attributed to their unique microstructures (porous shell and internal voids) and the catalytic effect of the encapsulated Au nanoparticles.
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The efficacy of a thrombin-based hemostatic agent in primary total knee arthroplasty: a meta-analysis.
J Orthop Surg Res
PUBLISHED: 10-15-2014
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PurposeTotal knee arthroplasty (TKA) is a popular procedure in severe osteoarthritis. But perioperative bleeding remains a problem. Floseal® is a mixture of thrombin and bovine gelatin which can benefit a lot on reducing intraoperative and postoperative bleeding. However, there is no enough evidence judging its safety and efficiency. So a meta-analysis is conducted by us to evaluate the efficacy and safety of a thrombin-based hemostatic agent compared with conventional methods in TKA.MethodTwo independent reviewers selected literatures published before August 2014 from MEDLINE, Embase, and The Cochrane Central Register of Controlled Trials. Other internet databases were also performed to identify trials according to the Cochrane Collaboration guidelines. High-quality randomized controlled trials (RCTs), prospective control trials (PCTs), and case controlled trials (CCTs) were selected. The meta-analysis was undertaken using RevMan 5.1 for Windows.ResultsThree RCTs, one PCT, and one CCT met the inclusion criteria. There were significant differences in hemoglobin decline and calculated total blood loss between the Floseal® group and control group. There were no significant differences in postoperative drainage volume, rate of transfusion requirement, incidence of wound infection, deep vein thrombosis (DVT), and pulmonary embolism (PE) between treatment and control groups.ConclusionsThe present meta-analysis indicates that a thrombin-based hemostatic agent can reduce hemoglobin decline and calculated total blood loss after TKA and is not related to adverse reactions or complications such as wound infection, DVT, and PE.
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[Clinical characteristic and outcomes of lung cancer patients with venous thromboembolism].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-15-2014
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To explore the clinical characteristics and outcomes of lung cancer patients with venous thromboembolism (VTE).
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Statistical Analysis of Bicyclists' Injury Severity at Unsignalized Intersections.
Traffic Inj Prev
PUBLISHED: 10-14-2014
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ABSTRACT Objectives This study investigated factors correlated with the severity of injuries sustained by bicyclists in bicycle-motor vehicle crashes at unsignalized intersections to develop site-specific countermeasures and interventions to improve bicycle safety. Method Crash data were extracted from accident reports entered into the Kentucky State Police's Kentucky Collision Database in 2002-2012. A partial proportional odds model was developed for data analysis. Results According to our modeling results, stop-controlled intersections, one-lane approaches, helmet usage, and lower speed limits were associated with decreased injury severity, while uncontrolled intersections, older (age>55) drivers and bicyclists, child (age<16) bicyclists, foggy and rainy weather, inadequate use of lights in dark conditions, and wet road surfaces were linked with increased injury severity. Conclusions Based on these results, we suggest the development of educational programs focused on the following groups: child bicyclists, older bicyclists, and older drivers. Investigating and modifying street lighting could improve bicycle safety. Implementing road diets/traffic calming methods could create a safer traffic environment. Certain traffic control strategies (e.g., stop control) could be considered for uncontrolled intersection s with high bicycle exposure, and helmet campaigns should be launched to increase helmet awareness and use. The study also suggests some interesting future research directions, including examining driver/bicyclist behaviors at uncontrolled intersections and studying the riding behaviors of child bicyclists in Kentucky.
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Label-free detection and discrimination of poly-brominated diphenylethers using molecularly imprinted photonic cross-reactive sensor arrays.
Chem. Commun. (Camb.)
PUBLISHED: 10-03-2014
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Molecularly imprinted photonic polymers can serve as ideal sensing elements for efficiently creating cross-reactive sensor arrays. Based on this concept, a new method for sensitive and label-free detection of challenging PBDEs was developed, by which the direct detection and discrimination of trace levels of PBDEs against a high-background of interferents was achieved with 100% accuracy.
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Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer.
J. Natl. Cancer Inst.
PUBLISHED: 10-01-2014
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Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification. Survival differed statistically significantly between de novo subtypes (log rank, P = .006) and was the best for the immunoreactive-like subtype, but statistically significantly worse for the proliferative- or mesenchymal-like subtypes (adjusted hazard ratio = 1.89, 95% confidence interval = 1.18 to 3.02, P = .008, and adjusted hazard ratio = 2.45, 95% confidence interval = 1.43 to 4.18, P = .001, respectively). More prognostic information was provided by the de novo than the TCGA classification (Likelihood Ratio tests, P = .003 and P = .04, respectively). All statistical tests were two-sided. These findings were replicated in an external data set of 185 HGSOCs and confirm the presence of four prognostically relevant molecular subtypes that have the potential to guide therapy decisions.
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Annexin A8 Is a Prognostic Marker and Potential Therapeutic Target for Pancreatic Cancer.
Pancreas
PUBLISHED: 10-01-2014
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We investigated whether annexin A8 (A-A8), a Ca-binding protein overexpressed in pancreatic cancer, plays a role in cell growth and migration and investigated its association with pancreatic cancer prognosis.
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MACE: model based analysis of ChIP-exo.
Nucleic Acids Res.
PUBLISHED: 09-23-2014
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Understanding the role of a given transcription factor (TF) in regulating gene expression requires precise mapping of its binding sites in the genome. Chromatin immunoprecipitation-exo, an emerging technique using ? exonuclease to digest TF unbound DNA after ChIP, is designed to reveal transcription factor binding site (TFBS) boundaries with near-single nucleotide resolution. Although ChIP-exo promises deeper insights into transcription regulation, no dedicated bioinformatics tool exists to leverage its advantages. Most ChIP-seq and ChIP-chip analytic methods are not tailored for ChIP-exo, and thus cannot take full advantage of high-resolution ChIP-exo data. Here we describe a novel analysis framework, termed MACE (model-based analysis of ChIP-exo) dedicated to ChIP-exo data analysis. The MACE workflow consists of four steps: (i) sequencing data normalization and bias correction; (ii) signal consolidation and noise reduction; (iii) single-nucleotide resolution border peak detection using the Chebyshev Inequality and (iv) border matching using the Gale-Shapley stable matching algorithm. When applied to published human CTCF, yeast Reb1 and our own mouse ONECUT1/HNF6 ChIP-exo data, MACE is able to define TFBSs with high sensitivity, specificity and spatial resolution, as evidenced by multiple criteria including motif enrichment, sequence conservation, direct sequence pileup, nucleosome positioning and open chromatin states. In addition, we show that the fundamental advance of MACE is the identification of two boundaries of a TFBS with high resolution, whereas other methods only report a single location of the same event. The two boundaries help elucidate the in vivo binding structure of a given TF, e.g. whether the TF may bind as dimers or in a complex with other co-factors.
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Bonding of an opaque resin to silane-treated porcelain.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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The repair of a fractured porcelain surface with a resin composite was investigated. The effects of applying an opaque resin to porcelain surfaces, which were silanated by a ceramic primer from a repair kit or by an experimental silane coupling agent, were studied. The porcelain surfaces were silanated for 10 sec and 60 min. Three types of adherents were evaluated: opaque resin with light irradiation (OWL), opaque resin without light irradiation (ONL), and no opaque resin (NAO). The shear bond strengths of the resins to the porcelain surfaces were measured before and after thermocycling. The maximum shear bond strength (6.7 MPa) after thermocycling was observed when the silanating period of the ceramic primer was 60 min. The opaque resin had no effect on the bond strength. Moreover, the bond strength obtained with the experimental silane coupling agent was found to be reduced by only 2 MPa, even after thermocycling.
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Anatomy of the Sural Nerve with an Emphasis on the Incision for Medial Displacement Calcaneal Osteotomy.
J Foot Ankle Surg
PUBLISHED: 09-10-2014
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An inappropriately positioned skin incision for medial displacement calcaneal osteotomy can put the sural nerve at risk; however, unanimous agreement has not been reached about the optimal strategy for making this incision. In the present cadaveric study, 20 cadaveric specimens were dissected to describe the anatomic course of the sural nerve within the operative area and to provide a more practical reference for surgeons to make a safe incision. The following points were used in the analyses: point A, the tip of the lateral malleolus; point B, the inferior margin of the calcaneus on the plumb line through point A; point C, the posteroinferior margin of the calcaneus; and point D, the lateral border of the Achilles tendon on the same level (collinear) with point A. With careful dissection, the distances of the sural nerve to points A and B in the vertical direction (lines D1 and D2, respectively), to points A and C in the diagonal direction (lines D3 and D4, respectively), and to points A and D in the horizontal direction (lines D5 and D6, respectively) were measured. The landmarks were identified and the distances measured by 3 independent researchers. The median ratio of D1 to D1+D2, D3 to D3+D4, and D5 to D5+D6 was 0.36 (range 0.20 to 0.47), 0.26 (range 0.19 to 0.32), and 0.43 (range 0.34 to 0.52), respectively. Accordingly, we believe it is relatively safe to make an oblique incision that runs through the point that is no less than one third of the distance from the tip of the lateral malleolus to the posteroinferior margin of the calcaneus.
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Molecular tethering effect of C-terminus of amyloid peptide a?42.
ACS Nano
PUBLISHED: 09-10-2014
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Amyloid peptides are considered to be the main contributor for the membrane disruption related to the pathogenesis of degenerative diseases. The variation of amino acids at the carboxylic terminus of amyloid peptide has revealed significant effects on the modulation of abnormal assemblies of amyloid peptides. In this work, molecular binding agents were tethered to the C-terminus of ?-amyloid peptide 1-42 (A?42). The molecular interaction between A?42 and molecule tethers was identified at single molecule level by using scanning tunneling microscopy (STM). The mechanistic insight into the feature variation of the self-assembly of A?42 peptide caused by molecular tethering at C-terminus was clearly revealed, which could appreciably affect the nucleation of amyloid peptide, thus reducing the membrane disruptions.
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Electroluminescence and Photocurrent Generation from Atomically Sharp WSe2/MoS2 Heterojunction p-n Diodes.
Nano Lett.
PUBLISHED: 09-08-2014
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The p-n diodes represent the most fundamental device building blocks for diverse optoelectronic functions, but are difficult to achieve in atomically thin transition metal dichalcogenides (TMDs) due to the challenges in selectively doping them into p- or n-type semiconductors. Here, we demonstrate that an atomically thin and sharp heterojunction p-n diode can be created by vertically stacking p-type monolayer tungsten diselenide (WSe2) and n-type few-layer molybdenum disulfide (MoS2). Electrical measurements of the vertically staked WSe2/MoS2 heterojunctions reveal excellent current rectification behavior with an ideality factor of 1.2. Photocurrent mapping shows rapid photoresponse over the entire overlapping region with a highest external quantum efficiency up to 12%. Electroluminescence studies show prominent band edge excitonic emission and strikingly enhanced hot-electron luminescence. A systematic investigation shows distinct layer-number dependent emission characteristics and reveals important insight about the origin of hot-electron luminescence and the nature of electron-orbital interaction in TMDs. We believe that these atomically thin heterojunction p-n diodes represent an interesting system for probing the fundamental electro-optical properties in TMDs and can open up a new pathway to novel optoelectronic devices such as atomically thin photodetectors, photovoltaics, as well as spin- and valley-polarized light emitting diodes, on-chip lasers.
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[Relationship between IL-18 gene polymorphism and unexplained recurrent spontaneous abortion].
Zhejiang Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 09-05-2014
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To investigate the association between IL-18 polymorphisms and the risk of unexplained recurrent spontaneous abortion (URSA).
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Photonic metal-organic framework composite spheres: a new kind of optical material with self-reporting molecular recognition.
Nanoscale
PUBLISHED: 09-02-2014
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Exploiting metal-organic framework (MOF) materials as novel building blocks to construct superstructures with extended and enhanced functions represents a big challenge. In biological systems, the ordering of many components is not achieved by interaction of the components with each other, but by interaction of each component with the host protein which provides a matrix to support the entire assembly. Inspired by biological systems, in this work, a general strategy for efficient spatial arrangement of MOF materials was developed by using spherical colloidal crystals as host matrices, affording a new class of highly tunable MOF composite spheres with a series of distinctive properties. It was found that the synergetic combination of the unique features of both MOF and photonic colloidal crystal imparted these hierarchically structured spheres intrinsic optical properties, specific molecular recognition with self-reporting signalling, derivatization capability, and anisotropy. More importantly, the unique photonic band-gap structure integrated in these composite spheres provides a more convenient means to manipulate the photophysical and photochemical behaviour of the trapped guest molecules in MOF nanocavities.
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Flow characteristics of the proximal pulmonary arteries and vena cava in patients with chronic thromboembolic pulmonary hypertension: correlation between 3.0 T phase-contrast MRI and right heart catheterization.
Diagn Interv Radiol
PUBLISHED: 08-29-2014
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We aimed to determine the correlation between flow characteristics of the proximal pulmonary arteries and vena cava obtained by 3.0 T phase-contrast magnetic resonance imaging (MRI) and hemodynamic characteristics by right heart catheterization in patients with chronic thromboembolic pulmonary hypertension.
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RVboost: RNA-seq variants prioritization using a boosting method.
Bioinformatics
PUBLISHED: 08-27-2014
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RNA-seq has become the method of choice to quantify genes and exons, discover novel transcripts and detect fusion genes. However, reliable variant identification from RNA-seq data remains challenging because of the complexities of the transcriptome, the challenges of accurately mapping exon boundary spanning reads and the bias introduced during the sequencing library preparation.
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[Effects of gender on severity and pulmonary artery vascular reactivity in chronic hypoxic pulmonary hypertension in mice].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-26-2014
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To explore the effects of gender on pathology and pulmonary vascular reactivity in chronic hypoxic pulmonary hypertension (HPH) in mice.
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Dynamic contrast-enhanced(DCE) MRI Assessment of microvascular characteristics in the murine orthotopic pancreatic cancer model.
Magn Reson Imaging
PUBLISHED: 08-25-2014
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Object To assess the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)-derived pharmacokinetic parameters between two contrast agents in a murine orthotopic pancreatic cancer model and to evaluate the tumor heterogenity and the potential association between kinetic parameters and angiogenic markers such as the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression by immunohistochemistry.
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Highly sensitive assay for acetylcholinesterase activity and inhibition based on a specifically reactive photonic nanostructure.
ACS Appl Mater Interfaces
PUBLISHED: 08-22-2014
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Assays for acetylcholinesterase (AChE) with high sensitivity and high selectivity as well as facile manipulation have been urgently required in various fields. In this work, a reaction-based photonic strategy was developed for the efficient assay of AChE activity and inhibition based on the synergetic combination of the specific thiol-maleimide addition reaction with photonic porous structure. It was found that various applications including detection of AChE activity, measurement of the related enzymatic kinetics, and screening of inhibitors could be efficiently implemented using such strategy. Remarkably, the unique photonic nanostructure endows the constructed sensing platform with high sensitivity with a limit of detection (LOD) of 5 mU/mL for AChE activity, high selectivity, and self-reporting signaling. Moreover, the label-free solid film-based sensing approach described here has advantages of facile manipulation and bare-eye readout, compared with conventional liquid-phase methods, exhibiting promising potential in practical application for the AChE assay.
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miR-203 suppresses the proliferation and migration and promotes the apoptosis of lung cancer cells by targeting SRC.
PLoS ONE
PUBLISHED: 08-20-2014
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SRC, also known as proto-oncogene c-Src, is a non-receptor tyrosine kinase that plays an important role in cancer progression by promoting survival, angiogenesis, proliferation, and invasion pathways. In this study, we found that SRC protein levels were consistently upregulated in lung cancer tissues, but that SRC mRNA levels varied randomly, suggesting that a post-transcriptional mechanism was involved in SRC regulation. Because microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for miRNAs that potentially target SRC. We identified specific targeting sites for miR-203 in the 3'-untranslated region (3'-UTR) of SRC. We then experimentally validated miR-203 as a direct regulator of SRC using cell transfection and luciferase assays and showed that miR-203 inhibited SRC expression and consequently triggered suppression of the SRC/Ras/ERK pathway. Finally, we demonstrated that the repression of SRC by miR-203 suppressed the proliferation and migration and promoted the apoptosis of lung cancer cells. In summary, this study provides the first clues regarding the role of miR-203 as a tumor suppressor in lung cancer cells through the inhibition of SRC translation.
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Effect of a novel motion correction algorithm (SSF) on the image quality of coronary CTA with intermediate heart rates: segment-based and vessel-based analyses.
Eur J Radiol
PUBLISHED: 08-19-2014
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To evaluate the effect of SnapShot Freeze (SSF) reconstruction at an intermediate heart-rate (HR) range (65-75bpm) and compare this method with single-sector reconstruction and bi-sector reconstruction on segmental and vessel bases in retrospective coronary computed tomography angiography (CCTA).
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A randomized controlled clinical trial of levofloxacin 750 mg versus 500 mg intravenous infusion in the treatment of community-acquired pneumonia.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 08-19-2014
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The objective of this study was to compare the efficacy and safety of levofloxacin 750 mg for 5 days versus 500 mg for 7-14 days intravenous (IV) in the treatment of community-acquired pneumonia (CAP). This clinical trial was the first of its kind conducted in Chinese people and also in Asian population. A total of 241 were enrolled and randomized to 750 mg group (n = 121) or 500 mg (n = 120) group from 10 study centers. The median treatment duration was 5.0 days in 750 mg and 9.0 days in 500 mg group. The median total dose was 3750 mg in 750 mg and 4500 mg in 500 mg group. The bacterial eradication rate was 100% in both groups. The overall efficacy rate in 750 mg group was 86.2% (94/109), and 84.7% (94/111), in 500 mg group of full analysis set visit 4, 95% confidence interval of 1.6% (-7.8-10.9%); the statistical results showed that 750 mg group was non-inferior to 500 mg group. The most common clinical adverse drug reactions were injection site adverse reactions in both 750 mg group and 500 mg group; the other common adverse drug reactions were insomnia, nausea, skin rash, etc. The most common drug-related laboratory abnormalities were neutrophil percentage decreased, decreased white blood cell count, alanine aminotransferase, and aspartate aminotransferase elevation in both 750 mg group and 500 mg group. Most of adverse drug reactions were mild in severity and well-tolerated. In summary, the regimen of levofloxacin 750 mg IV for 5 days was at least as effective and well tolerated as 500 mg IV for 7-14 days for the treatment of CAP.
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Multiplexed aberration measurement for deep tissue imaging in vivo.
Nat. Methods
PUBLISHED: 08-17-2014
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We describe an adaptive optics method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine the sample-induced aberration. Applicable to fluorescent protein-labeled structures of arbitrary complexity, it allowed us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improved structural and functional imaging of fine neuronal processes over a large imaging volume.
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Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study.
Crit Care
PUBLISHED: 08-12-2014
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Since 2008, severe cases of emerging human adenovirus type 55 (HAdV-55) in immunocompetent adults have been reported sporadically in China. The clinical features and outcomes of the most critically ill patients with severe acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) are lacking.
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Comparison of the effect of 'metabolically healthy but obese' and 'metabolically abnormal but not obese' phenotypes on development of diabetes and cardiovascular disease in Chinese.
Endocrine
PUBLISHED: 08-11-2014
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The present study was designed to determine the prevalence of 'metabolically healthy but obese' (MHO) and 'metabolically abnormal but not obese' (MANO) phenotypes in Chinese population, and to investigate the association of these two phenotypes with the risk of diabetes and cardiovascular disease (CVD). A total of 2,764 subjects aged 30-90 were followed up over a mean period of 43.80 ± 11.25 months. The metabolic syndrome was defined according to the joint committee for developing Chinese guidelines on prevention and treatment of dyslipidemia in adults. Subjects with body fat percentage (BF %) >25 % for men or BF % >35 % for women were defined as being obese. The proportion of MHO and MANO phenotypes were 22.9, 7.6 % in men, and 26.2, 6.0 % in women, respectively. The MANO phenotype was associated with increased risk for diabetes both in men [hazard ratios (HR): 4.44 (1.21-16.26)] and women [HR: 8.68 (2.87-24.96)] after adjustment of age, serum total cholesterol (TC), triglycerides (TG), and family history of diabetes. This association held for CVD in women [HR: 2.87 (1.44-5.73)], but not in men after adjustment of age, serum TC, TG, and family history of CVD. No association was observed between the MHO phenotype and incident diabetes or CVD. MHO and MANO phenotypes are common in Chinese population. Metabolic risk factors appeared to play a more important role in the development of diabetes and CVD than body fat alone.
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An ALS-mutant TDP-43 neurotoxic peptide adopts an anti-parallel ?-structure and induces TDP-43 redistribution.
Hum. Mol. Genet.
PUBLISHED: 08-11-2014
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TDP-43 proteinopathies are clinically and genetically heterogeneous diseases that had been considered distinct from classical amyloid diseases. Here, we provide evidence for the structural similarity between TDP-43 peptides and other amyloid proteins. Atomic force microscopy and electron microscopy examination of peptides spanning a previously defined amyloidogenic fragment revealed a minimal core region that forms amyloid fibrils similar to the TDP-43 fibrils detected in FTLD-TDP brain tissues. An ALS-mutant A315E amyloidogenic TDP-43 peptide is capable of cross-seeding other TDP-43 peptides and an amyloid-? peptide. Sequential Nuclear Overhauser Effects and double-quantum-filtered correlation spectroscopy in nuclear magnetic resonance (NMR) analyses of the A315E-mutant TDP-43 peptide indicate that it adopts an anti-parallel ? conformation. When added to cell cultures, the amyloidogenic TDP-43 peptides induce TDP-43 redistribution from the nucleus to the cytoplasm. Neuronal cultures in compartmentalized microfluidic-chambers demonstrate that the TDP-43 peptides can be taken up by axons and induce axonotoxicity and neuronal death, thus recapitulating key neuropathological features of TDP-43 proteinopathies. Importantly, a single amino acid change in the amyloidogenic TDP-43 peptide that disrupts fibril formation also eliminates neurotoxicity, supporting that amyloidogenesis is critical for TDP-43 neurotoxicity.
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Mollanol A, a diterpenoid with a new C-nor-D-homograyanane skeleton from the fruits of Rhododendron molle.
Org. Lett.
PUBLISHED: 08-04-2014
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Two new grayanoids, mollanol A (1) and rhodomollein XXV (2), were isolated from the fruits of Rhododendron molle. Their structures were elucidated by spectroscopic methods and X-ray diffraction analyses. Mollanol A (1) possesses a new C-nor-D-homograyanane carbon skeleton, while rhodomollein XXV (2) is the first example of an 11,16-epoxygrayanane and features a caged oxa-tricyclo[3.3.1.0(3.7)]nonane ring system. Plausible biogenetic pathways for 1 were proposed. Compound 1 exhibited transcriptional activation effects on the xbp1 upstream promoter in IEC-6, 293T, and RAW264.7 cells.
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Molecularly Imprinted Photonic Polymers as Sensing Elements for the Creation of Cross-Reactive Sensor Arrays.
Chemistry
PUBLISHED: 06-24-2014
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By combining molecular imprinting and colloidal crystal templating, molecularly imprinted inverse-opal photonic polymers (MIPPs) acting as sensing elements have been exploited to create sensor arrays for the first time. With this new strategy, abundant sensing elements with differential sensing abilities were easily accessible. Because of the unique hierarchical porous structure integrated in each sensing element, high sensitivity and selectivity, fast response and self-reporting (label-free) detection could be simultaneously achieved. All these fascinating features indicate that MIPPs are ideal sensing elements for creating sensor arrays. By integrating the individual sensing elements on a substrate, the formed array chip delivers better portability and high-throughput capability. As a demonstration, six kinds of contaminants were selected as analytes. The detection and discrimination of these analytes and even their mixtures in a wide range of concentrations, particularly trace amounts of analyte against a high background of other components, could be achieved, indicating the powerful capability of MIPPs-based sensor array for sensing. These results suggest that the described strategy opens a new route for sensor array creation and should find important applications in a wide range of areas.
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G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids.
Int J Mol Sci
PUBLISHED: 06-24-2014
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Steroids hormones possess two distinct actions, a delayed genomic effect and a rapid non-genomic effect. Rapid steroid-triggered signaling is mediated by specific receptors localized most often to the plasma membrane. The nature of these receptors is of great interest and accumulated data suggest that G protein-coupled receptors (GPCRs) are appealing candidates. Increasing evidence regarding the interaction between steroids and specific membrane proteins, as well as the involvement of G protein and corresponding downstream signaling, have led to identification of physiologically relevant GPCRs as steroid extranuclear receptors. Examples include G protein-coupled receptor 30 (GPR30) for estrogen, membrane progestin receptor for progesterone, G protein-coupled receptor family C group 6 member A (GPRC6A) and zinc transporter member 9 (ZIP9) for androgen, and trace amine associated receptor 1 (TAAR1) for thyroid hormone. These receptor-mediated biological effects have been extended to reproductive development, cardiovascular function, neuroendocrinology and cancer pathophysiology. However, although great progress have been achieved, there are still important questions that need to be answered, including the identities of GPCRs responsible for the remaining steroids (e.g., glucocorticoid), the structural basis of steroids and GPCRs' interaction and the integration of extranuclear and nuclear signaling to the final physiological function. Here, we reviewed the several significant developments in this field and highlighted a hypothesis that attempts to explain the general interaction between steroids and GPCRs.
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Triarylboranes with a 2-Dimesitylboryl-2'-(N,N-dimethylamino)biphenyl Core Unit: Structure-Property Correlations and Sensing Abilities to Discriminate Between F(-) and CN(-) Ions.
Chemistry
PUBLISHED: 06-15-2014
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A series of triarylboranes, in which different substituents are introduced at the para position of the dimethylamino group of a 2-dimesitylboryl-2'-(N,N-dimethylamino)biphenyl core unit, have been comprehensively investigated to explore the effect of structural modification on photophysical properties. The introduction of electron-accepting substituents would facilitate the HOMO?LUMO charge transfer (CT) transition. In contrast, the intramolecular CT transition is significantly prohibited when electron-donating substituents are incorporated. Notably, the HOMO?LUMO CT transition mainly consists of the transition from the electron-donating amino group to an electron acceptor other than boryl when a strong electron acceptor such as the dicyanovinyl group is present. This dicyanovinyl-substituted compound displays sensing abilities to discriminate fluoride and cyanide ions. In solution in THF, the fluoride ions first bind to the boron center, then attack the ?-carbon atom of the dicyanovinyl group, whereas the cyanide anion acts on the electron-accepting centers in the reverse sequence. As a result, the absorption and emission change in different manners upon addition of fluoride and cyanide ions.
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Lateral epitaxial growth of two-dimensional layered semiconductor heterojunctions.
Nat Nanotechnol
PUBLISHED: 06-12-2014
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Two-dimensional layered semiconductors such as MoS2 and WSe2 have attracted considerable interest in recent times. Exploring the full potential of these layered materials requires precise spatial modulation of their chemical composition and electronic properties to create well-defined heterostructures. Here, we report the growth of compositionally modulated MoS2-MoSe2 and WS2-WSe2 lateral heterostructures by in situ modulation of the vapour-phase reactants during growth of these two-dimensional crystals. Raman and photoluminescence mapping studies demonstrate that the resulting heterostructure nanosheets exhibit clear structural and optical modulation. Transmission electron microscopy and elemental mapping studies reveal a single crystalline structure with opposite modulation of sulphur and selenium distributions across the heterostructure interface. Electrical transport studies demonstrate that the WSe2-WS2 heterojunctions form lateral p-n diodes and photodiodes, and can be used to create complementary inverters with high voltage gain. Our study is an important advance in the development of layered semiconductor heterostructures, an essential step towards achieving functional electronics and optoelectronics.
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Functional Nanomaterials Can Optimize the Efficacy of Vaccines.
Small
PUBLISHED: 06-12-2014
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Nanoscale materials can improve the efficacy of vaccines. Herein we review latest developments that use nanomaterials for vaccines. By highlighting the relationships between the nanoscale physicochemical characteristics and working mechanisms of nanomaterials, this paper shows the current status of the developments where researchers employ functional nanomaterials as vector and/or immunoregulators for vaccines. It also provides us some clues for improving the design and application of nanomaterials to optimize the efficacy of vaccines.
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A designed peptide targeting CXCR4 displays anti-acute myelocytic leukemia activity in vitro and in vivo.
Sci Rep
PUBLISHED: 06-05-2014
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Leukemia cells highly expressing chemokine receptor CXCR4 can actively response to stroma derived factor 1? (CXCL12), trafficking and homing to the marrow microenvironment, which causes poor prognosis and relapse. Here we demonstrate that a novel designed peptide (E5) targeting CXCR4 inhibits CXCL12- and stroma-induced activation in multiple acute myelocytic leukemia (AML) cell lines and displays anti-AML activity. We show that E5 has high affinity to multiple AML cells with high CXCR4 level in a concentration dependent manner. E5 significantly inhibits CXCL12- or murine stromal cell (MS-5)-induced migration of leukemia cells and prevents the cells from adhering to stromal cells. Mechanistic studies demonstrate that E5 down-regulates CXCL12-induced phosphorylation of Akt, Erk, and p38, which affects the cytoskeleton F-actin organization and ultimately results in the inhibition of CXCL12- and stroma-mediated leukemia cell responses. E5 can induce concentration-dependent apoptosis in the four AML cell lines tested while did not affect the viability of MS-5 or human umbilical vein cell (ea.hy926) even at 80?µM, both of which have a low level of CXCR4. In vivo experimental results show that immunocompromised mice transplanted with HL-60 cells survived longer when treated with E5 twice a week in comparison to those treated with cyclophosphamide.
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Bursin-like peptide (BLP) enhances H9N2 influenza vaccine induced humoral and cell mediated immune responses.
Cell. Immunol.
PUBLISHED: 05-26-2014
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Vaccination with H9N2 avian influenza whole-inactivated virus (WIV) has been shown to be ineffective at eliciting sufficient humoral and cellular immunity against H9N2 avian influenza virus. This study assessed the effects of a synthetic Bursin-like epitope peptide (BLP) as adjuvant for H9N2 WIV in mice. Titers HI and avian influenza virus neutralizing antibodies, subtypes of HA antibodies, T helper (Th) cytokine levels, cytotoxic T-lymphocyte activities and changes in spleen T-cell subsets and natural killer cells were determined. We found that BLP induced a balance between IgG1 and IgG2a secretion levels. WIV antigen alone induced mainly Th1 cytokines secretion, whereas BLP showed increased secretion of Th1 and Th2 cytokines, including interleukin (IL)-2, interferon-? (IFN-?) and IL-4, but not IL-10, and may be resembles a Th0 like response. BLP significantly promoted growth and expansion of natural killer cells and of CD4(+) and CD8(+) T-cell subsets in the spleen. Meanwhile, BLP induced a better cytotoxic T-lymphocyte response to H9N2 virus. Furthermore, virus challenge experiments confirmed that BLP contributed to inhibition replication of the virus from mouse lungs. Taken together, these findings suggest that BLP may be an effective adjuvant for H9N2 avian influenza vaccine.
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Role and mechanisms of microRNA?503 in drug resistance reversal in HepG2/ADM human hepatocellular carcinoma cells.
Mol Med Rep
PUBLISHED: 05-15-2014
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Hepatocellular carcinoma is one of the most common malignancies worldwide and drug resistance is a major cause of treatment failure. In order to investigate the effects and mechanisms of microRNA?503 (miR?503) in the reversal of Adriamycin® (ADM) resistance in the drug?resistant HepG2/ADM hepatocellular cancer cell line, an ADM?resistant HepG2/ADM cell line was established using continuous drug exposure. HepG2/ADM cells overexpressing miR?503 were further established. HepG2/ADM cells overexpressing miR?503 demonstrated an enhanced sensitivity to ADM. Furthermore, miR?503 overexpression was found to increase intracellular rhodamine?123 levels and the rate of apoptosis, block the cell cycle at G0/G1?phase and significantly decrease intracellular superoxide dismutase and glutathione levels. The expression of a number drug resistance?related proteins, including multidrug resistance 1, multi drug resistance?associated protein 1, DNA excision repair protein ERCC?1, survivin and B?cell lymphoma 2, was significantly downregulated by miR?503 overexpression, as indicated by western blotting and a quantitative polymerase chain reaction. By contrast, levels of RhoE were increased. In addition, the phosphorylation of Akt was decreased and expression of cyclin?dependent kinase 1 was decreased by miR?503 overexpression. Furthermore, the secretion of transforming growth factor??, interleukin (IL)?6 and IL?8 was downregulated, and the transcriptional activities of nuclear factor ??light?chain?enhancer of activated B cells and activating protein?1 were significantly reduced. In conclusion, miR?503 was observed to reverse ADM resistance in HepG2/ADM cells by inhibiting drug efflux, downregulating the expression of drug resistance?related proteins, blocking the cell cycle and promoting cell apoptosis.
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Suppression of human and mouse Th17 differentiation and autoimmunity by an endogenous Interleukin 23 receptor cytokine-binding homology region.
Int. J. Biochem. Cell Biol.
PUBLISHED: 05-12-2014
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T-helper 17 (Th17) cells, a recently identified CD4+ T subset with a unique characteristic to produce Interleukin-17 (IL-17), are critical for the development of autoimmune diseases such as multiple sclerosis, in which IL-23 plays an important role in the differentiation of Th17 cells through IL-23/IL-23-receptor/STAT3 pathway. Previously, soluble recombinant human IL-23 receptor cytokine-binding homology region (hIL23R-CHR) was constructed in our laboratory to neutralize IL-23 and inhibit murine Th17 development in vitro. Herein we present that hIL23R-CHR could inhibit both differentiation and function of human/murine Th17 cells. The present in vivo study further demonstrated that hIL23R-CHR inhibited murine Th17 cell development by down regulating IL-17 gene expression and protected mice against the development of experimental autoimmune encephalomyelitis (EAE) through suppression of CNS inflammation and pro-inflammatory cytokine production. In addition to the in vitro inhibition of human Th17 cells in a dose-dependent manner, the antagonizing effect of hIL23R-CHR was confirmed by reduced levels of IL-23 in both blood and brain of EAE mice and STAT3 phosphorylation in vivo. Taken together, our data demonstrated that hIL23R-CHR could be an effective and specific immunosuppressive molecule for the treatment of Th17-related autoimmune diseases.
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Influence of pH, inorganic anions, and dissolved organic matter on the photolysis of antimicrobial triclocarban in aqueous systems under simulated sunlight irradiation.
Environ Sci Pollut Res Int
PUBLISHED: 05-08-2014
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The photolysis of the antimicrobial triclocarban (TCC) in aqueous systems under simulated sunlight irradiation was studied. The effects of several abiotic parameters, including solution pH, initial TCC concentration, presence of natural organic matter, and most common inorganic anions in surface waters, were investigated. The results show that the photolysis of TCC followed pseudo-first-order kinetics. The TCC photolysis rate constant increased with increasing solution pH and decreasing the initial TCC concentration. Compared with the TCC photolysis in pure water, the presence of aqueous bicarbonate, nitrate, humic acids, and its sodium salt decreased the TCC photolysis rate, but fulvic acid increased the TCC photolysis rate. The electron spin resonance and reactive oxygen species scavenging experiments indicated that TCC may undergo two different types of phototransformation reactions: direct photolysis and energy transfer to generate (1)O2. The main degradation products were tentatively identified by gas chromatography interfaced with mass spectrometry (GC-MS), and a possible degradation pathway was also proposed.
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Diagnostic and therapeutic advancements for aerobic vaginitis.
Arch. Gynecol. Obstet.
PUBLISHED: 05-01-2014
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Aerobic vaginitis (AV) is a newly defined clinical entity that is distinct from candidiasis, trichomoniasis and bacterial vaginosis (BV). Because of the poor recognition of AV, this condition can lead to treatment failures and is associated with severe complications, such as pelvic inflammatory disease, infertility, preterm birth and foetal infections.
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Reduced aggregation and cytotoxicity of amyloid peptides by graphene oxide/gold nanocomposites prepared by pulsed laser ablation in water.
Small
PUBLISHED: 04-22-2014
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A novel and convenient method to synthesize the nanocomposites combining graphene oxides (GO) with gold nanoparticles (AuNPs) is reported and their applications to modulate amyloid peptide aggregation are demonstrated. The nanocomposites produced by pulsed laser ablation (PLA) in water show good biocompatibility and solubility. The reduced aggregation of amyloid peptides by the nanocomposites is confirmed by Thioflavin T fluorescence and atomic force microscopy. The cell viability experiments reveals that the presence of the nanocomposites can significantly reduce the cytotoxicity of the amyloid peptides. Furthermore, the depolymerization of peptide fibrils and inhibition of their cellular cytotoxicity by GO/AuNPs is also observed. These observations suggest that the nanocomposites combining GO and AuNPs have a great potential for designing new therapeutic agents and are promising for future treatment of amyloid-related diseases.
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Enhanced cell growth on nanotextured GaN surface treated by UV illumination and fibronectin adsorption.
Colloids Surf B Biointerfaces
PUBLISHED: 04-21-2014
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Semiconductors are important materials used for the development of high-performance biomedical devices. Gallium nitride (GaN) is a well-known III-nitride semiconductor with excellent optoelectronic properties as well as high chemical stability and biocompatibility. The formation of tight interfaces between GaN substrates and cells would be crucial for GaN-based devices used for probing and manipulating biological processes of cells. Here we report a strategy to greatly enhance cell adhesion and survival on nanotextured GaN surface which was treated by UV illumination and fibronectin (FN) adsorption. Cell studies showed that the UV/FN treatment greatly enhanced cell adhesion and growth on nanotextured GaN surfaces. These observations suggest new opportunities for novel nanotextured GaN-based biomedical devices.
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Treatment of chronic deltoid ligament injury using suture anchors.
Orthop Surg
PUBLISHED: 04-11-2014
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To explore the efficacy of overlapping suture-anchor fixation for treatment of chronic deltoid ligament injury.
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Field dissipation of trifloxystrobin and its metabolite trifloxystrobin acid in soil and apples.
Environ Monit Assess
PUBLISHED: 04-03-2014
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The dissipation of trifloxystrobin and its metabolite trifloxystrobin acid in apples and soil was studied, and the half-life (DT50) was estimated in a field study carried out at three different locations for apples and four different locations for soil. Trifloxystrobin was sprayed on apples at 127 g a.i./ha for the dissipation study. Samples of apple and soil for the dissipation experiment were collected at time intervals of 0, 1, 3, 7, 14, 21, 30, and 45 days after treatment. The quantification of residues was done by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The DT50 of trifloxystrobin ranged from 0.54 to 8.8 and 4.8 to 9.5 days in soil and apples at different latitude sites. Photolysis may be the main dissipation pathway for trifloxystrobin, and the number of sunshine hours may be the main factor affecting the trifloxystrobin dissipation rate in the field. For trifloxystrobin acid residues in soil and apples, it first increased and then began decreasing. It was indicated that the risk of trifloxystrobin application in shorter sunshine hour area should be considered.
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Cyclic RGD-modified chitosan/graphene oxide polymers for drug delivery and cellular imaging.
Colloids Surf B Biointerfaces
PUBLISHED: 03-31-2014
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Polymers based on cyclic RGD-modified chitosan/graphene oxide are investigated in this paper as an innovative type of drug delivery system for hepatocellular carcinoma-targeted therapy and imaging. The system was prepared using a simple noncovalent method by coating drug-loaded graphene oxide (GO) with cyclic RGD-modified chitosan (RC). The results show that an efficient loading of doxorubicin (DOX) on GO (1.00mg/mg) was obtained. The system exhibits a pH-responsive behavior because of the hydrogen bonding interaction between GO and RC, and may be very stable under physiological conditions but with release at a lower pH (tumor environment). In addition, cellular uptake and proliferation studies using hepatoma cells (Bel-7402, SMMC-7721, HepG2) indicated that the cRGD-modified chitosan/graphene oxide polymer could recognize hepatoma cells and promote drug uptake by the cells, especially for cells overexpressing integrins. Together, these results demonstrate that the RC/GO polymers provide a multifunctional drug delivery system with the ability to target hepatocarcinoma cells, and are pH-responsive and can be efficiently loaded with a number of therapeutic agents for biomedical applications.
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Leukemic marker detection using a spectro-polarimetric surface plasmon resonance platform.
Biosens Bioelectron
PUBLISHED: 03-26-2014
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In this paper, we present a proof of concept screening for monoclonal immunoglobulin as a leukemia tumor marker using a surface plasmon resonance (SPR) bio-sensing platform. This screening method is based on measurements of immunoglobulin levels in human serum and the determination of the relative concentrations of kappa and lambda light chains. The kappa/lambda ratio is used to determine the presence of monoclonal immunoglobulin. Tests have been performed using standard solutions of immunoglobulins and serum samples from patients with known leukemic diagnoses. This platform has a resolution of 5×10(-7) refractive index unit (RIU) per channel, which is up to 10 times better than other SPR imaging systems for multi-sensing applications. The results obtained with this technique are in agreement with those acquired using conventional methods for immunoglobulin detection, indicating that our polarimetric SPR platform should be suitable for a cheap and efficient tool for early leukemia biomarker screening and monitoring applications.
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Sevoflurane post-conditioning protects isolated rat hearts against ischemia-reperfusion injury via activation of the ERK1/2 pathway.
Acta Pharmacol. Sin.
PUBLISHED: 03-09-2014
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Aim:To investigate the role of extracellular signal-regulated kinases (ERKs) in sevoflurane post-conditioning induced cardioprotection in vitro.Methods:Isolated rat hearts were subjected to 30 min ischemia followed by 120 min reperfusion (I/R). Sevoflurane post-conditioning was carried out by administration of O2-enriched gas mixture with 3% sevoflurane (SEVO) for 15 min from the onset of reperfusion. Cardiac functions, myocardial infarct size, myocardial ATP and NAD(+) contents, mitochondrial ultrastructure, and anti-apototic and anti-oncosis protein levels were measured.Results:Sevoflurane post-conditioning significantly improved the heart function, decreased infarct size and mitochondria damage, and increased myocardial ATP and NAD(+) content in the I/R hearts. Furthermore, sevoflurane post-conditioning significantly increased the levels of p-ERK and p-p70S6K, decreased the levels of porimin, caspase-8, cleaved caspase-3, and cytosolic cytochrome c in the I/R hearts. Co-administration of the ERK1/2 inhibitor PD98059 (20 ?mol/L) abolished the sevoflurane-induced protective effects against myocardial I/R.Conclusion:Sevoflurane post-conditioning protects isolated rat hearts against myocardial I/R injury and inhibits cell oncosis and apoptosis via activation of the ERK1/2 pathway.
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Adjacent-level symptomatic fracture after percutaneous vertebral augmentation of osteoporotic vertebral compression fracture: a retrospective analysis.
J Orthop Sci
PUBLISHED: 03-09-2014
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Vertebral augmentation is an effective and minimally invasive procedure that is used extensively worldwide for the treatment of osteoporosis vertebral compression fractures (OVCFs). New pain from adjacent vertebra fracture (AVF) after initial cement augmentation has gradually been given attention, but the exact causes of AVF are still controversial. The purpose of this study was to analyze the associated incidence, risk factors, and possible causative mechanism of symptomatic AVF, and to evaluate the intrinsic relationship between cement leakage into the disk and AVF.
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Bone regeneration in a rabbit ulna defect model: use of allogeneic adipose-derivedstem cells with low immunogenicity.
Cell Tissue Res.
PUBLISHED: 02-16-2014
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Tissue engineering provides new potential treatments for the repair of bone defects. Bone-marrow-derived mesenchymal stem cells (BMSCs) represent an attractive cell source for therapeutic applications involving tissue engineering, although disadvantages, such as pain of harvest and low proliferation efficiency, are major limitations to the application of BMSCs in the clinic. Adipose-derived stem cells (ASCs) with their multilineage potential and satisfactory proliferation potential can be induced into the osteogenic lineage in vitro and can be anchored onto suitable scaffolds as seed cells to repair bone defects successfully in an autologous setting. Previous studies have indicated that both undifferentiated BMSCs and ASCs exhibit immunosuppression and immunoprivilege properties. We compare the immuno-function of undifferentiated and osteo-differentiated ASCs in vitro and explore the feasibility of applying allogeneic ASCs to the repair of ulnar bone defects in the rabbit model. Our study demonstrates that allogeneic osteogenic differentiated ASCs maintain low immunogenicity and negative immunomodulation. The allogeneic osteogenic differentiated ASCs combined with demineralized bone matrix successfully regenerate ulnar bone defects in rabbits without immunosuppressive therapies.
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Increasing available NADH supply during succinic acid production by Corynebacterium glutamicum.
Biotechnol. Prog.
PUBLISHED: 02-11-2014
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A critical factor in the biotechnological production of succinic acid with Corynebacterium glutamicum is the sufficient supply of NADH. It is conceivable that cofactor availability and the proportion of cofactor in the active form may play an important role in dictating the succinic acid yield. PntAB genes from Escherichia coli can directly catalyze the reversible hydride transfer and adjust the dynamic balance between NADP(H) and NAD(H). Hence, we studied the physiological effect of coenzyme systems by expressing the membrane-bound transhydrogenase pntAB genes. We have shown experimentally that the pntAB genes could function as an alternative source of NADH. In an anaerobic fermentation with C. glutamicum NC-3-pntAB, a 16% higher succinic acid yield and a 57% higher production from glucose were obtained by pntAB expression. Moreover, the formation of by-products was significantly decreased. The concomitant increase in the consumption of intracellular NADPH from 0.6 to 1.2 mmol/g CDW and the increased NADH/NAD(+) ratio resulted from introduction of pntAB, suggesting that the membrane-bound transhydrogenase converted excess NADPH to NADH for succinic acid production. Finally, we explored whether the transhydrogenase had different effects on the succinic acid formation on different carbon sources. The succinic acid yield was increased in the presence of pntAB by 16% on glucose, 7% on sucrose, and without large influence on fructose and xylose. The results of this study demonstrated that the effectiveness of cofactor manipulation could be a promising strategy applied in metabolic engineering. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 2014.
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2-Bromopalmitate modulates neuronal differentiation through the regulation of histone acetylation.
Stem Cell Res
PUBLISHED: 01-18-2014
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In order to evaluate the functional significance of palmitoylation during multi-potent neural stem/progenitor cell proliferation and differentiation, retinoic acid-induced P19 cells were used in this study as a model system. Cell behaviour was monitored in the presence of the protein palmitoylation inhibitor 2-bromopalmitate (2BP). Here, we observed a significant reduction in neuronal differentiation in the 2BP-treated cell model. We further explored the underlying mechanisms and found that 2BP resulted in the decreased acetylation of histones H3 and H4 and interfered with cell cycle withdrawal and neural stem/progenitor cells' renewal. Our results established a direct link between palmitoylation and the regulation of neural cell fate specification and revealed the epigenetic regulatory mechanisms that are involved in the effects of palmitoylation during neural development.
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Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: a systematic review and meta-analysis.
Thromb. Res.
PUBLISHED: 01-14-2014
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According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE.
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Lin28a Protects against Hypoxia/Reoxygenation Induced Cardiomyocytes Apoptosis by Alleviating Mitochondrial Dysfunction under High Glucose/High Fat Conditions.
PLoS ONE
PUBLISHED: 01-01-2014
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The aim of the present study was to investigate the role of Lin28a in protecting against hypoxia/reoxygenation (H/R)-induced cardiomyocytes apoptosis under high glucose/high fat (HG/HF) conditions.
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Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer.
Cancer Metab
PUBLISHED: 01-01-2014
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Loss of the endosulfatase HSulf-1 is common in ovarian cancer, upregulates heparin binding growth factor signaling and potentiates tumorigenesis and angiogenesis. However, metabolic differences between isogenic cells with and without HSulf-1 have not been characterized upon HSulf-1 suppression in vitro. Since growth factor signaling is closely tied to metabolic alterations, we determined the extent to which HSulf-1 loss affects cancer cell metabolism.
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Targeting reactive oxygen species by edaravone inhalation in a rat hyperoxic lung injury model: role of inflammasome.
Undersea Hyperb Med
PUBLISHED: 12-31-2013
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This study was undertaken to investigate the effect of edaravone inhalation on inflammasome activation in a rat hyperoxia-induced lung injury (HILI) model. Sprague Dawley rats (n = 61) were randomly assigned into three groups: Control group, HILI group and Edaravone (Eda) group. Rats in the Control group breathed room air, but those in the HILI group and Eda group were exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) for six hours. Immediately after HILI, rats in the Eda group received inhalation of aerosol edaravone at 0.5 mg/ml for 30 minutes. Twenty-four hours later, rats were sacrificed. The bronchoalveolar lavage fluid (BALF) and lungs were obtained for detection of oxidative stress, IL-1beta, IL-18 and caspase-1; the lungs were collected for HE staining and TUNEL staining. The pathological features of the lungs of rats in the Eda group were significantly improved when compared with the HILI group, accompanied by reduction in apoptotic cells. In addition, in the Eda group, the malonyldialdehyde (MDA) was reduced and total antioxidant capacity (T-AOC) was increased significantly in the lung and BALF when compared with the HILI group (P < 0.05 for both). Moreover, the contents of IL-1beta, IL-18 and caspase-1 in the lung and BALF, downstream factors of inflammasome, were also dramatically lower in the Eda group than in the HILI group (P < 0.05 for all). These findings suggest that edaravone may inhibit inflammasome activation due to its anti-oxidative capacity exerting a protective effect on HILI.
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The perinucleolar compartment associates with malignancy.
Front Biol (Beijing)
PUBLISHED: 12-19-2013
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The perinucleolar compartment (PNC) is a unique nuclear substructure, forming predominantly in cancer cells both in vitro and in vivo. PNC prevalence (percentage of cells containing at least one PNC) has been found to positively correlate with disease progression in several cancers (breast, ovarian, and colon). While there is a clear association between PNCs and cancer, the molecular function of the PNC remains unclear. Here we summarize the current understanding of the association of PNCs with cancer and its possible functions in cancer cells.
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[Gene analysis and literature review of autosomal recessive polycystic kidney disease].
Zhonghua Er Ke Za Zhi
PUBLISHED: 12-17-2013
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The purpose of this study was to investigate the clinical and genetic characteristics of autosomal recessive polycystic kidney disease.
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Effects of Aging, Cytomegalovirus Infection, and EBV Infection on Human B Cell Repertoires.
J. Immunol.
PUBLISHED: 12-11-2013
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Elderly humans show decreased humoral immunity to pathogens and vaccines, yet the effects of aging on B cells are not fully known. Chronic viral infection by CMV is implicated as a driver of clonal T cell proliferations in some aging humans, but whether CMV or EBV infection contributes to alterations in the B cell repertoire with age is unclear. We have used high-throughput DNA sequencing of IGH gene rearrangements to study the BCR repertoires over two successive years in 27 individuals ranging in age from 20 to 89 y. Some features of the B cell repertoire remain stable with age, but elderly subjects show increased numbers of B cells with long CDR3 regions, a trend toward accumulation of more highly mutated IgM and IgG Ig genes, and persistent clonal B cell populations in the blood. Seropositivity for CMV or EBV infection alters B cell repertoires, regardless of the individuals age: EBV infection correlates with the presence of persistent clonal B cell expansions, whereas CMV infection correlates with the proportion of highly mutated Ab genes. These findings isolate effects of aging from those of chronic viral infection on B cell repertoires and provide a baseline for understanding human B cell responses to vaccination or infectious stimuli.
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Electron energy loss spectroscopy of polytetrafluoroethylene: experiment and first principles calculations.
Microscopy (Oxf)
PUBLISHED: 12-01-2013
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We have performed electron energy-loss spectroscopy (EELS) on a 200 kV transmission electron microscope (TEM) equipped with a monochromator to investigate molecular conformation of polytetrafluoroethylene (PTFE). The experimental spectra show several unique features in the low-loss region and the onset of carbon K-edge for PTFE. Density function theory (DFT) methods are employed to calculate the low-loss and core-loss spectra of PTFE with consideration of the effects of phase transitions, chain orientation and polarization. The shape and width of the characteristic peaks of the experimental spectra are well reproduced in DFT calculations. By comparing the spectra from experiments and theory, the detailed information about the conformational dependence of EEL spectra for PTFE can be obtained. In the present work, we have demonstrated an application of combining high-resolution EELS and DFT calculations in both low-loss and core-loss regions to discriminate changes of chain conformation and orientation for the polymer with complex phase transition behavior.
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Biphenyl derivatives incorporating urea unit as novel VEGFR-2 inhibitors: Design, synthesis and biological evaluation.
Bioorg. Med. Chem.
PUBLISHED: 11-05-2013
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A series of novel biphenyl urea derivates were synthesized and investigated for their potential to inhibit vascular endothelial growth factor receptor-2 (VEGFR-2). In particular, A7, B3 and B4 displayed significant enzymatic inhibitory activities, with IC50 values of 4.06, 4.55 and 5.26nM. Compound A7 exhibited potent antiproliferative activity on several cell lines. SAR study suggested that the introduction of methyl at ortho-position of the biphenyl urea and tertiary amine moiety could improve VEGFR-2 inhibitory activity and antitumor effects. Molecular docking indicated that the urea moiety formed four hydrogen bonds with DFG residue. These biphenyl ureas could serve as promising lead compounds for further optimization.
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Noninvasive positive pressure ventilation is required following extubation at the pulmonary infection control window: a prospective observational study.
Clin Respir J
PUBLISHED: 11-05-2013
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Timely extubation and sequential invasive to noninvasive positive pressure ventilation (NPPV) at the pulmonary infection control (PIC) window is beneficial for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, it remains unclear whether patients can breathe independently at the PIC window and if NPPV is indeed necessary after extubation.
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What is Visualize?

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

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

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

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