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Find video protocols related to scientific articles indexed in Pubmed.
A Chemical Tuned Strategy to Develop Novel Irreversible EGFR-TK Inhibitors with Improved Safety and Pharmacokinetic Profiles.
J. Med. Chem.
PUBLISHED: 11-20-2014
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Gatekeeper T790M mutation in EGFR is the most prevalent factor underlying acquired resistance. Acrylamide-bearing quinazoline derivatives are powerful irreversible inhibitors for overcoming resistance. Nevertheless, concerns about the risk of non-specific covalent modification have motivated the development of novel cysteine-targeting inhibitors. In this paper, we demonstrate that fluoro-substituted olefins can be tuned to alter Michael addition reactivity. Incorporation of these olefins into the quinazoline templates produced potent EGFR inhibitors with improved safety and pharmacokinetic properties. A lead compound 5a was validated against EGFRWT, EGFR T790M as well as A431 and H1975 cancer cell lines. Additionally, compound 5a displayed a weaker inhibition against the EGFR-independent cancer cell line SW620 when compared withafatinib. Oral administration of 5a at a dose of 30mg/kg induced tumor regression in a murine-EGFRL858R/T790M driven H1975 xenograft model. Also, 5a exhibited improved oral bioavailability and safety, as well as favorable tissue distribution properties and enhanced brain uptake. These findings provide the basis of a promising strategy toward the treatment of NSCLC patients with drug resistance.
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Refractive index dependent real-time plasmonic nanoprobes on a single silver nanocube for ultrasensitive detection of the lung cancer-associated miRNAs.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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We developed a novel method for the real-time monitoring of the delicate change in refractive index (RI) when DNA or RNA hybridize near a DNA-capped silver nanocube (AgNC) surface. This method offers an alternative platform in the quantitative analysis of the trace lung cancer-associated miRNAs in label-free detection.
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Graded-index optical fiber tweezers with long manipulation length.
Opt Express
PUBLISHED: 11-18-2014
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Long manipulation length is critical for optical fiber tweezers to enhance the flexibility of non-contact trapping. In this paper a long manipulation distance of more than 40 ?m is demonstrated experimentally by the graded-index fiber (GIF) tweezers, which is fabricated by chemically etching a GIF taper with a large cone angle of 58°. The long manipulation distance is obtained by introducing an air cavity between the lead-in single mode fiber and the GIF as well as by adjusting the laser power in the existence of a constant background flow. The influence of the cavity length and the GIF length on the light distribution and the focusing length of the GIF taper is investigated numerically, which is helpful for optimizing the parameters to perform stable optical trapping. This kind of optical fiber tweezers has advantages including low-cost, easy-to-fabricate and easy-to-use.
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Microfluidic assistant beat-frequency interferometer based on a single-hole-infiltrated dual-mode microstructured optical fiber.
Opt Express
PUBLISHED: 11-18-2014
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A microfluidic assistant beat-frequency interferometer based on a single-hole-infiltrated dual-mode microstructured optical fiber (DM-MOF) is proposed and demonstrated. The interferometer is constructed by inserting a piece of fluid-filled DM-MOF into two sections of single-mode fiber with slight core-offset. The mode-mismatch induced interferences with high-frequency dips and low-frequency envelope are observed in the transmission spectrum. Theoretical and experimental investigations reveal that the beat-frequency spectrum works from the interferences between LP01 core mode and the components of LP11 core mode with close but different frequencies. The deliberately infiltrated liquid rod in the air hole located at the second ring near the core of the DM-MOF enhances the sensitivity of the envelope to temperature or axial force. However, it shows little impact on the high-frequency dips. The distinguishing sensitivities of -959.22 pm/°C (-70.59 pm/°C) and 24.26 nm/N (-3.14 nm/N) for the envelope (dips) are simultaneously achieved in experiment, allowing for dual parameter measurement in such a compact structure.
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Clinical application of a novel clinical scale for the pre-operative risk evaluation of cerebral herniation from traumatic epidural hematoma.
J. Neurotrauma
PUBLISHED: 11-14-2014
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Secondary massive cerebral infarction (MCI), the predominant prognostic factor of cerebral herniation from epidural hematoma (EDH), determines a need for decompressive craniectomy. However, few predictive indices have focused on it. In this study, we tested the clinical feasibility and reliability of a novel pre-operative risk scoring system (EDH-MCI scale) in the guidance of surgical decision-making. The scale is comprised of 6 risk factors, including location and volume of hematoma, duration and extent of preoperative cerebral herniation, Glasgow Coma Scale score, and presence of preoperative shock, with a total score ranging from 0 to 18 points. Results suggest that the accuracy of the surgical modality adapted for initial hematoma-evacuation surgery of 65 patients whose surgical modality were guided by the EDH-MCI scale (prospective cohort, 2012.02-2014.01) were significantly improved (95.38% vs. 77.95%, P=0.002) compared with those of an independent set of 126 patients (retrospective cohort, 2007.01-2012.01) whose surgical modalities were decided empirically. The EDH-MCI scale exhibited a satisfactory predictive capacity for the development of secondary MCI and discriminative performance for patients who were at high risk and thus required radical surgical treatments. It is suggested that simple hematoma-evacuation craniotomy was sufficient for patients with low risk scores (<=9 points), whereas decompressive craniectomy in combination with duraplasty were necessary for those with high risk scores (>=13 points). In patients with borderline risk scores (10-12 points), those having one or more of unstable vital signs, coexistence of severe secondary brainstem injury, and irresponsiveness of dilated pupils to emergent burr-hole hematoma-drainage had a significantly increased incidence of posttraumatic MCI, which underlined a high priority for radical surgical treatments. In conclusion, this novel pre-operative risk evaluation scale is easy to use and has a satisfactory predictive capacity forthe development of secondary MCI, thereby providing an objective reference for surgical-decision making and postoperative medical care.
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miR168 influences phase transition, leaf epinasty, and fruit development via SlAGO1s in tomato.
J. Exp. Bot.
PUBLISHED: 11-08-2014
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In Arabidopsis thaliana, ARGONAUTE1 (AGO1) interacts with miR168 to modulate the small RNA regulatory pathway. However, the underlying mechanism of regulation and relationship between AGO1 and miR168 is poorly understood in the cash crop Solanum lycopersicum (tomato). We previously found that SlAGO1A and SlAGO1B were cleaved by miR168 in tomato. In this study, we show that SlAGO1A and SlAGO1B accumulate in miR168-sponge transgenic plants, and that expression of miR168-resistant SlAGO1A (4m-SlAGO1A) and SlAGO1B (4m-SlAGO1B) in tomato results in a series of defects affecting growth rate, floral timing, leaves, and fruit. Accumulation of miR156 was found when 4m-SlAGO1A was at an early developmental stage compared to the wild type and original SlAGO1A transgenic plants, and miR172 was highly expressed in adult 4m-SlAGO1A compared to the controls. In addition, the expression of multiple small RNAs was altered in 4m-SlAGO1A. Taken together, our data provide novel insights into the interaction between SlAGO1s and miR168 in determining growth rate, phase change, leaf epinasty, fruit initiation and expansion, and other developmental processes in tomato.
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Multicolor (Vis-NIR) mesoporous silica nanospheres linked with lanthanide complexes using 2-(5-bromothiophen)imidazo[4,5-f][1,10]phenanthroline for in vitro bioimaging.
Dalton Trans
PUBLISHED: 11-07-2014
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A novel mesoporous nanosphere functionalized with 3-(aminopropyl)triethoxysilane (APTES) and 2-(5-bromothiophen)imidazo[4,5-f][1,10]phenanthroline (5-Br-Tip) was synthesized (denoted as Tip-MSS). With the coordinating function of the 5-Br-Tip to lanthanide (Ln) ions, for the first time, LnL3(5-Br-Tip) complexes were linked to the mesoporous nanospheres. The derived materials, named Ln-Tip-MSS (Ln = Eu, Tb, Sm, Nd, Yb), were characterized by Fourier-transform infrared (FT-IR) spectroscopy, TEM, XRD (wide-angle and small-angle), N2 adsorption/desorption analysis, and fluorescence spectroscopy. Upon excitation in the ligand absorption, the Ln-Tip-MSS nanomaterials show characteristic visible (Eu, Tb, Sm) and NIR (Sm, Nd, Yb) luminescence (multicolor emission covered from 450 nm to 1400 nm spectral region). Of importance is that, with low cytotoxicity and good biocompatibility given by the methyl thiazolyl tetrazolium (MTT) assay, the Eu-Tip-MSS was successfully applied to cell imaging in vitro based on the Eu(3+) luminescence (under 405 nm excitation).
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Efficient synthesis of ?-extended phenazasilines for optical and electronic applications.
Chem. Commun. (Camb.)
PUBLISHED: 11-06-2014
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The rhodium-catalyzed synthesis of phenazasilines from readily achievable biarylhydrosilanes is presented. This highly efficient method offers opportunities for preparing ?-extended phenazasilines with enhanced optoelectronic properties for device applications in organic electronics.
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Robotic Versus Laparoscopic Total Mesorectal Excision for Rectal Cancer: a Meta-analysis of Eight Studies.
J. Gastrointest. Surg.
PUBLISHED: 11-02-2014
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Robotic surgery has been used successfully in many branches of surgery, but there is little evidence in the literature on its use in rectal cancer (RC). We conducted this meta-analysis of randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) to evaluate whether the safety and efficacy of robotic total mesorectal excision (RTME) in patients with RC are equivalent to those of laparoscopic TME (LTME).
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Increased Plasma S-Adenosylhomocysteine-Accelerated Atherosclerosis Is Associated With Epigenetic Regulation of Endoplasmic Reticulum Stress in apoE-/- Mice.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 11-01-2014
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S-Adenosylhomocysteine (SAH) is a better predictor of cardiovascular disease than homocysteine is, and it has been implicated in mediating the pathogenicity of hyperhomocysteinemia in atherosclerosis via an epigenetic mechanism. However, the underlying mechanism remains unclear. Here, we tested the hypothesis whether the effect of SAH on atherosclerosis is involved in epigenetic regulation of endoplasmic reticulum stress.
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ERG Oncoprotein Inhibits ANXA2 Expression and Function in Prostate Cancer.
Mol. Cancer Res.
PUBLISHED: 10-26-2014
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Overexpression of ERG in the prostate epithelium, due to chromosomal translocations, contributes to prostate tumorigenesis. Here, genomic analysis of ERG siRNA-treated prostate cells harboring the endogenous TMPRSS2-ERG fusion revealed an inverse relationship between ERG and Annexin A2 (ANXA2) expression at both the RNA and protein level. ANXA2, a Ca2+-dependent and phospholipid-binding protein, is involved in various cellular functions, including maintenance of epithelial cell polarity. Mechanistic studies defined the prostate-specific transcription start site of ANXA2 and showed that the recruitment of ERG to the ANXA2 promoter is required for transcriptional repression by ERG. Knockdown of ERG enhanced the apical localization of ANXA2, the bundling of actin filaments at cell-cell junctions and formation of a polarized epithelial phenotype. ERG overexpression disrupted ANXA2 mediated cell polarity and promoted epithelial mesenchymal transition (EMT) by inhibiting CDC42 and RHOA, and by activating cofilin. Immunohistochemistry (IHC), demonstrated a reciprocal relationship of ANXA2 and ERG expression in a large fraction of primary prostate cancer clinical specimens. ANXA2 was absent or markedly reduced in ERG(+) tumors, which were mostly well-differentiated. ERG(-) tumors, meanwhile, expressed moderate to high levels of ANXA2, and were either poorly-differentiated or displayed subsets of poorly-differentiated cells. Taken together, the transcriptional repression of ANXA2 by ERG in prostate epithelial cells plays a critical role in abrogating differentiation, promoting EMT, and in the reciprocal correlation of ERG and ANXA2 expression observed in human prostate cancer. Implications: ANXA2 is a new component of the ERG network with potential to enhance biological stratification and therapeutic targeting of ERG stratified prostate cancers.
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Time-variant clustering model for understanding cell fate decisions.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-22-2014
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Both spatial characteristics and temporal features are often the subjects of concern in physical, social, and biological studies. This work tackles the clustering problems for time course data in which the cluster number and clustering structure change with respect to time, dubbed time-variant clustering. We developed a hierarchical model that simultaneously clusters the objects at every time point and describes the relationships of the clusters between time points. The hidden layer of this model is a generalized form of branching processes. A reversible-jump Markov Chain Monte Carlo method was implemented for model inference, and a feature selection procedure was developed. We applied this method to explore an open question in preimplantation embryonic development. Our analyses using single-cell gene expression data suggested that the earliest cell fate decision could start at the 4-cell stage in mice, earlier than the commonly thought 8- to 16-cell stage. These results together with independent experimental data from single-cell RNA-seq provided support against a prevailing hypothesis in mammalian development.
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Porous hollow Co3O4 with rhombic dodecahedral structures for high-performance supercapacitors.
Nanoscale
PUBLISHED: 10-21-2014
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Porous hollow Co3O4 with rhombic dodecahedral structures were prepared by the calcination of ZIF-67 ([Co(mim)2; mim = 2-methylimidazolate]) rhombic dodecahedral microcrystals. A supercapacitor was successfully constructed by adopting the resulting porous hollow Co3O4 rhombic dodecahedral structure as the electrode material, which showed a large specific capacitance of 1100 F g(-1) and retained more than 95.1% of the specific capacitance after 6000 continuous charge-discharge cycles. The excellent capacitive properties and stability mark the porous hollow Co3O4 with the rhombic dodecahedral structure as one of the most promising electrode materials for high-performance supercapacitors.
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Vector rectangular-shape laser based on reduced graphene oxide interacting with a long fiber taper.
Appl Opt
PUBLISHED: 10-17-2014
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A vector dual-wavelength rectangular-shape laser (RSL) based on a long fiber taper deposited with reduced graphene oxide is proposed, where nonlinearity is enhanced due to a large evanescent-field-interacting length and strong field confinement of an 8 mm fiber taper with a waist diameter of 4 ?m. Graphene flakes are deposited uniformly on the taper waist with light pressure effect, so this structure guarantees both excellent saturable absorption and high nonlinearity. The RSL with a repetition rate of 7.9 MHz shows fast polarization switching in two orthogonal polarization directions, and temporal and spectral characteristics are investigated.
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Propagation factors of cosine-Gaussian-correlated Schell-model beams in non-Kolmogorov turbulence.
Opt Express
PUBLISHED: 10-17-2014
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Based on the extended Huygens-Fresnel principle and second-order moments of the Wigner distribution function (WDF), we have studied the relative root-mean-square (rms) angular width and the propagation factor of cosine-Gaussian-correlated Schell-model (CGSM) beams propagating in non-Kolmogorov turbulence. It has been found that the CGSM beam has advantage over the Gaussian Schell-model (GSM) beam for reducing the turbulence-induced degradation, and this advantage will be more obvious for the beams with larger parameter n and spatial coherence ? or under the condition of stronger fluctuation of turbulence. The CGSM beam with larger parameter n or smaller spatial coherence ? will be less affected by the turbulence. In addition, the effects of the slope-parameter ?, inner and outer scale and the refractive-index structure constant of the non-Kolmogorov's power spectrum on the propagation factor are also analyzed in detailed.
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Q-switched mode-locked erbium-doped fiber laser based on topological insulator Bi2Se3 deposited fiber taper.
Appl Opt
PUBLISHED: 10-17-2014
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We have demonstrated the passive Q-switching mode-locking operation in an erbium-doped fiber (EDF) laser by using topological insulator Bi2Se3 deposited on fiber taper, whose damage threshold can be further increased by the large evanescent field interacting length. Due to the low saturation intensity, stable Q-switched mode-locked fiber lasers centered at 1562 nm can be generated at a pump power of 10 mW. The temporal and spectral characteristics for different pump strengths have also been investigated. To the best of our knowledge, it is the first time a Q-switched mode-locked EDF laser based on the fiber taper deposited by Bi2Se3 was generated.
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Transferring biomarker into molecular probe: melanin nanoparticle as a naturally active platform for multimodality imaging.
J. Am. Chem. Soc.
PUBLISHED: 10-16-2014
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Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (<10 nm) water-soluble melanin nanoparticle (MNP) was developed and showed unique photoacoustic property and natural binding ability with metal ions (for example, (64)Cu(2+), Fe(3+)). Therefore, MNP can serve not only as a photoacoustic contrast agent, but also as a nanoplatform for positron emission tomography (PET) and magnetic resonance imaging (MRI). Traditional passive nanoplatforms require complicated and time-consuming processes for prebuilding reporting moieties or chemical modifications using active groups to integrate different contrast properties into one entity. In comparison, utilizing functional biomarker melanin can greatly simplify the building process. We further conjugated ?v?3 integrins, cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation due to its targeting property combined with the enhanced permeability and retention (EPR) effect. The multimodal properties of MNPs demonstrate the high potential of endogenous materials with multifunctions as nanoplatforms for molecular theranostics and clinical translation.
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Study on the Influence of Silyl Protections on the Anomeric Reactivity of Galactofuranosyl Thioglycosides and Application of the Silylated Thiogalactofuranosides to One-Pot Synthesis of Diverse beta-D-Oligogalactofuranosides.
J. Org. Chem.
PUBLISHED: 10-14-2014
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We describe in this paper the tuning effect of silyl protecting groups on the donor reactivity of galactofuranosyl phenyl thioglycosides. Silyl ethers on galactofuranose ring are found to have an arming effect on the glycosylation reactivity, but the cyclic 3,5-acetal protecting group decreases the reactivity. The reactive phenyl 2,6-di-O-Bz-3,5-di-O-TBS-1-thio-?-D-galactofuranoside 3 is proved to be a useful glycosyl building block. By taking advantage of this donor, we achieved the highly efficient one-pot solution-phase assembly of a panel of beta-D-galactofuranosyl tri- and tetrasaccharides possessing diverse glycosidic linkages.
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Graphene nanomesh: new versatile materials.
Nanoscale
PUBLISHED: 10-14-2014
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Graphene, an atomic-scale honeycomb crystal lattice, is increasingly becoming popular because of its excellent mechanical, electrical, chemical, and physical properties. However, its zero bandgap places restrictions on its applications in field-effect transistors (FETs). Graphene nanomesh (GNM), a new graphene nanostructure with a tunable bandgap, shows more excellent performance. It can be widely applied in electronic or photonic devices such as highly sensitive biosensors, new generation of spintronics and energy materials. These illustrate significant opportunities for the industrial use of GNM, and hence they push nanoscience and nanotechnology one step toward practical applications. This review briefly describes the current status of the design, synthesis, and potential applications of GNM. Finally, the perspectives and challenges of GNM development are presented and some suggestions are made for its further development and exploration.
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A distinguishable photovoltaic performance on dye-sensitized solar cells using ruthenium sensitizers with a pair of isomeric ancillary ligands.
Dalton Trans
PUBLISHED: 10-14-2014
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A pair of isomeric ruthenium sensitizers and , having TIP based ancillary ligands with a 9-phenylcarbazole tail at the ? or ? position of the thiophene unit, shows a distinguishable photovoltaic performance on DSCs (PCEs: 7.33% and 5.33% for and as compared with 6.07% for the standard N3-dye).
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Cationic Conjugated Polymer/Fluoresceinamine-Hyaluronan Complex for Sensitive Fluorescence Detection of CD44 and Tumor-Targeted Cell Imaging.
ACS Appl Mater Interfaces
PUBLISHED: 10-14-2014
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Simple, rapid, and sensitive detection of CD44 is of paramount importance since it plays pivotal roles in tumor initiation, growth and metastasis. Herein, we describe a novel method for sensitive, visual and facile fluorescence detection of CD44 and CD44-mediated cancer cell imaging, using a probe based on cationic conjugated polymer (CCP)-PFEP and fluoresceinamine-hyaluronan (FA-HA). HA is an anionic natural glycosaminoglycan that can specifically bind to the overexpressed CD44 on various kinds of cancer cells. PFEP and FA-HA formed a complex through electronic interactions, resulting in a highly efficient fluorescence resonance energy transfer (FRET) from PFEP to FA-HA; moreover, the efficiencies of FRET correlated with the concentrations of CD44 because the specific binding of HA-CD44 would separate FA-HA away from PFEP. This method did not require laborious and expensive dual-labeling or protein-labeling needed in previously reported detection methods of CD44. Just mix the sample and test solution containing the PFEP/FA-HA complex, and the results allowed naked-eye detection by observing fluorescent color of solutions with the assistance of a UV lamp. Most importantly, the use of a conjugated polymer with excellent amplification property as well as the specific binding of HA-CD44 endowed this method with high sensitivity and specificity, making it applicable for reliable quantitative detection of CD44. Furthermore, the PFEP/FA-HA complex formed nanoparticles in aqueous solution, and the nanoparticles can be selectively taken up by MCF-7 cells (cancer cell) through the HA-CD44 interaction, thereby giving rise to a dual-color tumor-targeted imaging probe with good photostability. The development of this fluorescent probe showed promising potential to make a reliable and routine method available for early diagnosis of cancer.
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Decreased N(6)-methyladenosine in peripheral blood RNA from Diabetic Patients Is Associated with FTO Expression Rather than ALKBH5.
J. Clin. Endocrinol. Metab.
PUBLISHED: 10-11-2014
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Context: N(6)-methyladenosine (m(6)A) modification plays a fundamental role in epigenetic regulation of the mammalian transcriptome. m(6)A can be demethylated by fat mass and obesity associated (FTO) protein and ALKBH5 protein. However, the importance of m(6)A alteration in type 2 diabetes mellitus (T2DM) has not been explored. Objective: To investigate whether m(6)A content was reduced in T2DM patients and whether m(6)A content was correlated with the mRNA expression levels of FTO and ALKBH5 genes. Methods: In this case-control study, peripheral blood samples were obtained from 88 T2DM patients and 92 healthy controls. For the diabetic animal model experiment, blood samples were obtained from 7 diabetic and 8 nondiabetic rats. A sensitive liquid chromatography- electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the determination of m(6)A content in RNA, quantitative real-time PCR (qPCR) was used to examine the mRNA expression levels of FTO and ALKBH5 genes, and high-resolution melting (HRM) and DNA sequencing were used to detect FTO single nucleotide polymorphisms (SNPs). Results: Our results showed that m(6)A contents in RNA from T2DM patients and diabetic rats were significantly lower compared to the control groups (p = 2.6×10(-24) for T2DM patients; p = 0.001 for diabetic rats, respectively) and T2DM can be characterized by the content of m(6)A. The mRNA expression level of FTO was significantly higher in T2DM patients than that of the controls (p=0.0007), and associated with the risk of T2DM (odds ratio (OR) 2.797, 95% confidence interval (CI) 1.452 - 5.389, p= 0.002). Moreover, m(6)A contents were correlated with FTO mRNA expression. Conclusions: These data suggest that the increased mRNA expression of FTO could be responsible for the reduction of m(6)A in T2DM, which may further increase the risk of complications of T2DM. Low m(6)A should be investigated further as a novel potential biomarker of T2DM.
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A retrospective 3- to 5-year study of the reconstruction of oral function using implant-supported prostheses in patients with hypohidrotic ectodermal dysplasia.
J Oral Implantol
PUBLISHED: 10-09-2014
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The aim of this study was to evaluate oral function rehabilitation in patients with hypohidrotic ectodermal dysplasia (HED) using implant-supported prostheses based on bone augmentation. From September 2005 and March 2009, 25 HED patients were chosen for clinical data analysis in this study. The criteria for patient selection included the following: the display of clinical features of HED, the number of congenitally missing teeth (>5), the patient age (>16 years), the patient's willingness, and the patient's tolerance for bone graft surgery and implant placement. Follow-up evaluations were initiated from the time of implant prosthetic placement and scheduled annually for 3-5 years. The effects of oral function reconstruction were assessed based on the cumulative survival and success rates of implants, the health of the peri-implant area, and the degree of patient satisfaction. Twenty-five HED patients received 169 conventional implants and 10 zygomatic implants (179 total implants). During 3-5 years of post-loading evaluations, 5 of the 179 implants failed and 3 implants were removed. The 3-year success and cumulative survival rates were 97.2% and 98.3%, respectively. Furthermore, periodontal probing and radiographic assessments showed that the 3-year incidence of peri-implantitis was 4.5%. Finally, HED patients expressed high degrees of satisfaction with their facial contours, masticatory function, pronunciation ability, and comfort with the implant-supported prostheses. The results of this 3- to 5-year retrospective study indicate that the oral function of HED patients can be effectively reconstructed using bone augmentation and implant-supported prostheses; however, longer term results are warranted in the future.
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Minimally invasive percutaneous compression plating versus dynamic hip screw for intertrochanteric fractures: a randomized control trial.
Chin. J. Traumatol.
PUBLISHED: 10-09-2014
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Intertrochanteric femur fracture is a common injury in elderly patients. The dynamic hip screw (DHS) has served as the standard choice for fixation; however it has several drawbacks. Studies of the percutaneous compression plate (PCCP) are still inconclusive in regards to its efficacy and safety. By comparing the two methods, we assessed their clinical therapeutic outcome.
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Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance.
J. Antimicrob. Chemother.
PUBLISHED: 10-05-2014
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Dolutegravir has been recently approved for treatment-naive and -experienced HIV-infected subjects, including integrase inhibitor (INI)-experienced patients. Dolutegravir is a second-generation INI that can overcome many prior raltegravir and elvitegravir failures. Here, we report the evolution of resistance to dolutegravir in a highly treatment-experienced patient harbouring the major N155H mutation consequent to raltegravir treatment failure.
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Heat shock factors in carrot: genome-wide identification, classification, and expression profiles response to abiotic stress.
Mol. Biol. Rep.
PUBLISHED: 09-30-2014
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Heat shock factors (HSFs) play key roles in the response to abiotic stress in eukaryotes. In this study, 35 DcHSFs were identified from carrot (Daucus carota L.) based on the carrot genome database. All 35 DcHSFs were divided into three classes (A, B, and C) according to the structure and phylogenetic relationships of four different plants, namely, Arabidopsis thaliana, Vitis vinifera, Brassica rapa, and Oryza sativa. Comparative analysis of algae, gymnosperms, and angiosperms indicated that the numbers of HSF transcription factors were related to the plant's evolution. The expression profiles of five DcHsf genes (DcHsf 01, DcHsf 02, DcHsf 09, DcHsf 10, and DcHsf 16), which selected from each subfamily (A, B, and C), were detected by quantitative real-time PCR under abiotic stresses (cold, heat, high salinity, and drought) in two carrot cultivars, D. carota L. cvs. Kurodagosun and Junchuanhong. The expression levels of DcHsfs were markedly increased by heat stress, except that of DcHsf 10, which was down regulated. The expression profiles of different DcHsfs in the same class also differed under various stress treatments. The expression profiles of these DcHsfs were also different in tissues of two carrot cultivars. This study is the first to identify and characterize the DcHSF family transcription factors in plants of Apiaceae using whole-genome analysis. The results of this study provide an in-depth understanding of the DcHSF family transcription factors' structure, function, and evolution in carrot.
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[One case report of Vogt-Koyanagi-Halada syndrome misdiagnosed of sudden hearing loss].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-25-2014
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Vogt-Koyanagi-Halada syndrome is an autoimmune disease attacking melanocytes, which involves eye, ear, meninge and skin. Patient offen has uveitis and extraocular symptoms and signs and the misdiagnosis of missed diagnosis of VKHS is very common. Patients have good prognosis after hormone therapy.
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Value of metabolic tumor volume on repeated 18F-FDG PET/CT for early prediction of survival in locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.
J. Nucl. Med.
PUBLISHED: 09-11-2014
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The aim of this study was to investigate the value of standardized uptake values (SUVs) and metabolic tumor volume (MTV) in (18)F-FDG PET/CT to predict the survival of patients with locally advanced non-small cell lung cancer during the early stage of concurrent chemoradiotherapy.
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Fabrication and properties of irradiation-cross-linked poly(vinyl alcohol)/clay aerogel composites.
ACS Appl Mater Interfaces
PUBLISHED: 09-08-2014
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Poly(vinyl alcohol) (PVOH)/clay aerogel composites were fabricated by an environmentally friendly freeze-drying of the aqueous precursor suspensions, followed by cross-linking induced by gamma irradiation without chemical additives. The influences of cross-linking conditions, i.e., absorbed dose and polymer loading as well as density on the aerogel structure and properties, were investigated. The absorbed dose of 30 kGy was found to be the optimum dose for fabricating strong PVOH composites; the compressive modulus of an aerogel prepared from an aqueous suspension containing 2 wt % PVOH/8 wt % clay increased 10-fold, and that containing 1 wt % PVOH/9 wt % clay increased 12 times upon cross-linking with a dose of 30 kGy. Increasing the solids concentration led to an increase in the mechanical strength, in accordance with the changes in microstructure from layered structure to network structure. The increase of absorbed dose also led to decreased porous size of the network structure. Cross-linking and the increase of the PVOH lead to decreased thermal stability. The strengthened PVOH/clay aerogels possess very low flammability, as measured by cone calorimetry, with heat, smoke, and volatile products release value decreasing as increasing clay content. The mechanism of flame retardation in these materials was investigated with weight loss, FTIR, WAXD, and SEM of the burned residues. The proposed mechanism is that with decreasing fuel content (increasing clay content), increased heat and mass transport barriers are developed; simultaneously low levels of thermal conductivity are maintained during the burning.
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Distinguishable Zn(II) and Pb(II) template effects on forming pendant-armed Schiff-base macrocyclic complexes including a remarkable Pb(II)-? macrocyclic complex.
Dalton Trans
PUBLISHED: 09-05-2014
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36-Membered [2 + 2] half-fold Schiff-base macrocyclic dinuclear Zn(II) complexes (1a and 1b) and 18-membered [1 + 1] Schiff-base macrocyclic mononuclear Pb(II) complexes (2 and 3) are produced from the condensation between 1,3-propanediamine and a pair of extended dialdehydes with different functional pendant arms (H2hpdd and H2pdd) because of the distinguishable cationic template effects. It is very interesting to mention that a unique intramolecular Pb(II)-? macrocyclic complex 2 with an uncommon ?(3)-coordination type is achieved under ambient conditions and it can remain stable both in the solid state and in solution. The subtle variations of pendant-arms in the macrocyclic ligands H2hpdd and H2pdd yield different Pb(II) complexes, where the competition between Pb(II)-? and Pb(II)-NO3(-) electrostatic interactions as well as the combination of steric and electronic effects of pendant arms are believed to play important roles.
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Baseline CD4+ T cell counts correlates with HIV-1 synonymous rate in HLA-B*5701 subjects with different risk of disease progression.
PLoS Comput. Biol.
PUBLISHED: 09-04-2014
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HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although risk of progression may vary among patients carrying this allele. The interplay between HIV-1 evolutionary rate variation and risk of progression to AIDS in HLA-B*5701 subjects was studied using longitudinal viral sequences from high-risk progressors (HRPs) and low-risk progressors (LRPs). Posterior distributions of HIV-1 genealogies assuming a Bayesian relaxed molecular clock were used to estimate the absolute rates of nonsynonymous and synonymous substitutions for different set of branches. Rates of viral evolution, as well as in vitro viral replication capacity assessed using a novel phenotypic assay, were correlated with various clinical parameters. HIV-1 synonymous substitution rates were significantly lower in LRPs than HRPs, especially for sets of internal branches. The viral population infecting LRPs was also characterized by a slower increase in synonymous divergence over time. This pattern did not correlate to differences in viral fitness, as measured by in vitro replication capacity, nor could be explained by differences among subjects in T cell activation or selection pressure. Interestingly, a significant inverse correlation was found between baseline CD4+ T cell counts and mean HIV-1 synonymous rate (which is proportional to the viral replication rate) along branches representing viral lineages successfully propagating through time up to the last sampled time point. The observed lower replication rate in HLA-B*5701 subjects with higher baseline CD4+ T cell counts provides a potential model to explain differences in risk of disease progression among individuals carrying this allele.
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Challenge of Representing Entropy at Different Levels of Resolution in Molecular Simulation.
J Phys Chem B
PUBLISHED: 09-04-2014
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The role of entropic contributions in processes involving biomolecules is illustrated using the process of vaporization or condensation of the solvents water and methanol and the process of polypeptide folding in solution using molecular models at different levels of resolution: subatomic, atomic, supra-atomic, and supramolecular. For the folding process, a ?-hexapeptide that adopts, as inferred from NMR experiments, both a right-handed 2.710/12-helical fold and a left-handed 314-helical fold in methanol, is used to illustrate the challenge of modeling thermodynamically driven processes at different levels of resolution.
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Current Practices of Screening for Incident Hepatitis C Virus (HCV) Infection Among HIV-Infected, HCV-Uninfected Individuals in Primary Care.
Clin. Infect. Dis.
PUBLISHED: 09-03-2014
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?Human immunodeficiency virus (HIV)-infected, hepatitis C virus (HCV)-uninfected patients are at risk for incident HCV infection, but little is known about screening practices for incident HCV among HIV-infected individuals in HIV primary care clinics.
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Cash incentives improve participation rate in a face-to-face survey: an intervention study.
J Clin Epidemiol
PUBLISHED: 09-01-2014
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Our study examined the effect of a ChinaYuan (CNY) 10 cash incentive on the participation rate in a face-to-face health survey among the general Chinese population.
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Population-based cohort study on the risk of malignancy in East Asian children with juvenile idiopathic arthritis.
BMC Cancer
PUBLISHED: 08-29-2014
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To investigate the association and magnitude of risk between JIA, its associated treatment and cancer development in Taiwanese children.
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Theoretical study of the hydration of atmospheric nucleation precursors with acetic acid.
J Phys Chem A
PUBLISHED: 08-29-2014
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While atmosphere is known to contain a significant fraction of organic substance and the effect of acetic acid to stabilize hydrated sulfuric acids is found to be close that of ammonia, the details about the hydration of (CH3COOH)(H2SO4)2 are poorly understood, especially for the larger clusters with more water molecules. We have investigated structural characteristics and thermodynamics of the hydrates using density functional theory (DFT) at PW91PW91/6-311++G(3df,3pd) level. The phenomena of the structural evolution may exist during the early stage of the clusters formation, and we tentatively proposed a calculation path for the Gibbs free energies of the clusters formation via the structural evolution. The results in this study supply a picture of the first deprotonation of sulfuric acids for a system consisting of two sulfuric acid molecules, an acetic acid molecule, and up to three waters at 0 and 298.15 K, respectively. We also replace one of the sulfuric acids with a bisulfate anion in (CH3COOH)(H2SO4)2 to explore the difference of acid dissociation between two series of clusters and interaction of performance in clusters growth between ion-mediated nucleation and organics-enhanced nucleation.
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Intraductal carcinoma of the prostate: interobserver reproducibility survey of 39 urologic pathologists.
Ann Diagn Pathol
PUBLISHED: 08-26-2014
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The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, ?(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.
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Highway proximity and black carbon from cookstoves as a risk factor for higher blood pressure in rural China.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-25-2014
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Air pollution in China and other parts of Asia poses large health risks and is an important contributor to global climate change. Almost half of Chinese homes use biomass and coal fuels for cooking and heating. China's economic growth and infrastructure development has led to increased emissions from coal-fired power plants and an expanding fleet of motor vehicles. Black carbon (BC) from incomplete biomass and fossil fuel combustion is the most strongly light-absorbing component of particulate matter (PM) air pollution and the second most important climate-forcing human emission. PM composition and sources may also be related to its human health impact. We enrolled 280 women living in a rural area of northwestern Yunnan where biomass fuels are commonly used. We measured their blood pressure, distance from major traffic routes, and daily exposure to BC (pyrolytic biomass combustion), water-soluble organic aerosol (organic aerosol from biomass combustion), and, in a subset, hopane markers (motor vehicle emissions) in winter and summer. BC had the strongest association with systolic blood pressure (SBP) (4.3 mmHg; P < 0.001), followed by PM mass and water-soluble organic mass. The effect of BC on SBP was almost three times greater in women living near the highway [6.2 mmHg; 95% confidence interval (CI), 3.6 to 8.9 vs. 2.6 mmHg; 95% CI, 0.1 to 5.2]. Our findings suggest that BC from combustion emissions is more strongly associated with blood pressure than PM mass, and that BC's health effects may be larger among women living near a highway and with greater exposure to motor vehicle emissions.
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Effects of lentiviral infection of mesenchymal stem cells on the expression of octamer transcription factor 4.
Mol Med Rep
PUBLISHED: 08-21-2014
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The present study aimed to investigate the effects of lentiviral infection of human umbilical cord mesenchymal stem cells (hUCMSCs) on the expression of octamer transcription factor 4 (Oct4). hUCMSCs were infected with lentivirus carrying the green fluorescent protein gene (GFP) at different multiplicities of infection (MOI), and the optimal MOI was determined by flow cytometry; the proliferation of non?infected and GFP-carrying lentivirus?infected hUCMSCs was evaluated by the MTT assay; and the expression of the Oct4 gene was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunofluorescence staining in hUCMSCs cultured in vitro for eight weeks. Positive GFP staining of hUCMSCs was estimated at >75% at 48 h following infection with the GFP-carrying lentivirus (MOI=20); no effect on hUCMSC proliferation was detected by the MTT assay following the infection; immunofluorescence analysis detected positive Oct4 expression in the cell nuclei at two and eight weeks of culture, while the relative expression of Oct4 assessed by qRT-PCR was 0.9075±0.0124. The GFP gene carried by the lentivirus was successfully expressed in hUCMSCs and had no significant effect on Oct4 expression, which lays a solid foundation for future studies investigating gene functions via the use of exogenous markers.
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Upregulation of GRIM-19 suppresses the growth of oral squamous cell carcinoma in vitro and in vivo.
Oncol. Rep.
PUBLISHED: 08-20-2014
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Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) and its upregulation contribute to the progression and metastasis of several different tumor types. The gene associated with retinoid?interferon?induced mortality-19 (GRIM-19) is known to functionally interact with STAT3 and inhibit its transcriptional activity. It has been reported that upregulation of genes associated with GRIM-19 can significantly reduce the tumor growth of several types of tumors. However, little is known in regards to its role in oral squamous cell carcinoma (OSCC). In the present study, a recombinant eukaryotic expression plasmid carrying GRIM-19 was constructed to evaluate its effects on OSCC cancer growth. Upregulation of GRIM-19 in OSCC cells significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Moreover, we found that upregulation of GRIM-19 reduced cyclin D1, Bcl-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) expression whose protein is involved in STAT3 activation. Taken together, these findings suggest that GRIM-19 plays an inhibitory role in the progression of OSCC, and contribute to the future development of STAT3-based gene therapeutic approaches for OSCC.
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A functional polymorphism affecting the APOA5 gene expression is causally associated with plasma triglyceride levels conferring coronary atherosclerosis risk in Han Chinese Population.
Biochim. Biophys. Acta
PUBLISHED: 08-20-2014
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Apolipoprotein A5 (APOA5) gene plays a key role in plasma triglyceride (TG) metabolism, and shows the involvement in coronary artery disease (CAD). A set of single nucleotide polymorphisms around the APOA5 gene was identified to be associated with plasma TG levels. It is of biological and clinical importance to discern the genuine genetic determinants. A polymorphism in 3' untranslated region of the APOA5 gene, rs2266788, is deserving of investigation for suggestive clues from the association in multiple independent studies. In this study, rs2266788 was genotyped in 3222 unrelated subjects consisting of 2062 CAD cases and 1160 controls. The statistical analyses indicated that the minor C allele of rs2266788 was significantly associated with elevated plasma TG levels and higher CAD risk. In normal human liver tissues, comparison of global APOA5 mRNA levels among genotypes and allelic expression imbalance analysis showed the decreased gene expression for the C allele. Luciferase assays confirmed a concordant result that transcriptional activity was lowered for the C allele compared with the T allele in four cell lines. Multiple lines of evidence in our study supported that rs2266788 was causally associated with plasma TG levels conferring CAD risk in Han Chinese population owing to a cis-acting effect to the APOA5 gene expression.
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Skeletal defects in Osterix-Cre transgenic mice.
Transgenic Res.
PUBLISHED: 08-20-2014
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Cre/loxP recombination is a powerful strategy widely used for in vivo conditional gene targeting. This technique has made possible many important discoveries of gene function in normal and disease biology. However, due to the transgenic nature of most Cre mouse strains undesired phenotypes occasionally occur in Cre mice. Here we report skeletal defects in Osterix-Cre (Osx-Cre) transgenic mice including delayed calvarial ossification and fracture calluses at multiple skeletal sites. These data suggest that Osx-Cre containing controls should be used for both in vivo and in vitro skeletal analyses of conditional knockout mice generated with this Osx-Cre mouse strain.
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Group search optimizer for the mobile location management problem.
ScientificWorldJournal
PUBLISHED: 08-11-2014
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We propose a diversity-guided group search optimizer-based approach for solving the location management problem in mobile computing. The location management problem, which is to find the optimal network configurations of management under the mobile computing environment, is considered here as an optimization problem. The proposed diversity-guided group search optimizer algorithm is realized with the aid of diversity operator, which helps alleviate the premature convergence problem of group search optimizer algorithm, a successful optimization algorithm inspired by the animal behavior. To address the location management problem, diversity-guided group search optimizer algorithm is exploited to optimize network configurations of management by minimizing the sum of location update cost and location paging cost. Experimental results illustrate the effectiveness of the proposed approach.
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Fabrication of Ultralong Hybrid Microfibers from Nanosheets of Reduced Graphene Oxide and Transition-Metal Dichalcogenides and their Application as Supercapacitors.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-11-2014
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Two-dimensional materials have attracted increasing research interest owing to their unique electronic, physical, optical, and mechanical properties. We thus developed a general strategy for the fabrication of ultralong hybrid microfibers from a mixture of reduced graphene oxide and transition-metal dichalcogenides (TMDs), including MoS2 , TiS2 , TaS2 , and NbSe2 . Furthermore, we prepared fiber-based solid-state supercapacitors as a proof-of-concept application. The performance of thus-prepared supercapacitors was greatly improved by the introduction of the TMDs.
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Extremely low-frequency electromagnetic fields cause G1 phase arrest through the activation of the ATM-Chk2-p21 pathway.
PLoS ONE
PUBLISHED: 08-11-2014
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In daily life, humans are exposed to the extremely low-frequency electromagnetic fields (ELF-EMFs) generated by electric appliances, and public concern is increasing regarding the biological effects of such exposure. Numerous studies have yielded inconsistent results regarding the biological effects of ELF-EMF exposure. Here we show that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, inhibiting cell proliferation. To present well-founded results, we comprehensively evaluated the biological effects of ELF-EMFs at the transcriptional, protein, and cellular levels. Human HaCaT cells from an immortalized epidermal keratinocyte cell line were exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h. The ELF-EMF could cause G1 arrest and decrease colony formation. Protein expression experiments revealed that ELF-EMFs induced the activation of the ATM/Chk2 signaling cascades. In addition, the p21 protein, a regulator of cell cycle progression at G1 and G2/M, exhibited a higher level of expression in exposed HaCaT cells compared with the expression of sham-exposed cells. The ELF-EMF-induced G1 arrest was diminished when the CHK2 gene expression (which encodes checkpoint kinase 2; Chk2) was suppressed by specific small interfering RNA (siRNA). These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase. Based on the precise control of the ELF-EMF exposure and rigorous sham-exposure experiments, all transcriptional, protein, and cellular level experiments consistently supported the conclusion. This is the first study to confirm that a specific pathway is triggered by ELF-EMF exposure.
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"Old" metal oxide affinity chromatography as "novel" strategy for specific capture of cis-diol-containing compounds.
J Chromatogr A
PUBLISHED: 08-07-2014
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The metal oxide affinity chromatography (MOAC) materials have been extensively used for extraction of phosphate compounds in the past decade. Actually, some of these materials also possess adsorption affinity towards cis-diol-containing compounds, which was seldom explored in separation field so far. Here we present the proof-of-concept study to evaluate the feasibility of expanding MOAC for specific capture of cis-diol biomolecules. Benefitting from the high commercialisation of the metal oxide materials, such MOAC strategy possesses several advantages, like synthesis-free, low cost and high expandability. Firstly, the recognition of adenosine against 2'-deoxyadenosine was performed using zirconium oxide and cerium oxide, two typical commercial MOAC materials. The results showed that efficient adsorption and elution could be achieved easily by pH switching from basic to acidic. The isotherm curves demonstrated the adsorption process fitted well with Freundlich isotherm model and was spontaneous at room temperature (?G(0)<0) with an exothermic nature (?H(0)<0). Afterwards, the highly efficient and selective enrichment of various model cis-diol biomolecules, including ribonucleosides, glycopeptides and glycoproteins, was achieved using this MOAC strategy. Finally, the endogenous ribonucleosides and modified ribonucleosides were successfully purified from human urine sample, which demonstrated the potential application of MOAC materials in the enrichment of target compounds from complex biological samples. Besides the excellent performance of extraction for cis-diol-containing compounds, equally important is that these materials are commercially available with low cost, which makes the MOAC a promising strategy for the study of cis-diol biomolecules in metabolomics and proteomics.
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Intermediate long-term clinical performance of dental implants placed in sites with a previous early implant failure: a retrospective analysis.
Clin Oral Implants Res
PUBLISHED: 08-06-2014
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The aim of this retrospective case-control study was to evaluate the intermediate long-term clinical performance and success rate of dental implants inserted into sites of previous early implant failure.
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MiR-451 inhibits cell growth and invasion by targeting CXCL16 and is associated with prognosis of osteosarcoma patients.
Tumour Biol.
PUBLISHED: 08-06-2014
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Recent studies have shown that microRNA-451 (miR-451) was significantly decreased in osteosarcoma tissues and was identified as a tumor suppressor in other types of human cancers. However, its clinical significance and molecular mechanisms in osteosarcoma are still not well understood. MiR-451 levels are evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in osteosarcoma cell lines and in 68 pairs of osteosarcoma and adjacent noncancerous tissues. Then, the associations of miR-451 expression with clinicopathological features of patients were determined. The effects of miR-451 in osteosarcoma cells were examined by MTT and Matrigel invasion assay. The functional target of miR-451 were determined by bioinformatics analysis and validated by luciferase reporter analyses and Western blot assay. Our results showed that the expression of miR-451 was significantly downregulated in osteosarcoma tissues compared with corresponding noncancerous tissues (P?
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Carborane Tuning Phosphorescence of Iridium Tetrazolate Complexes.
Chemistry
PUBLISHED: 08-05-2014
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New iridium tetrazolate complexes containing o-, m-, or p-carboranyl substitution in different positions of a phenylpyridine ligand have been prepared. The carborane isomers and the effect of their substitution position in the tuning of optical properties have been examined. The neutral complexes with the carboranyl substituent on the phenyl ring in meta position relative to the metal exhibit redshifted emission bands in contrast to blueshifts for those with carboranyl in para position. All cationic complexes display evidently blueshifted dual-peak emission compared with the carborane-free complex (c-TZ) with a broad single-peak emission. Introduction of carborane leads to a blueshift over 70?nm relative to c-TZ. Carboranes also significantly improve phosphorescence efficiency (?P ) and lifetime (?), that is, ?P =0.64 versus 0.21 (c-TZ) and ?=880?ns versus 241?ns (c-TZ). The unique hydrophilic nido-carborane-based Ir(III) complex nido-o-1 shows the largest phosphorescence efficiency (abs ?P =0.57) among known water-soluble iridium complexes, long emission lifetime (?=4.38??s), as well as varying emission efficiency and lifetime with O2 content in aqueous solution. Therefore, nido-o-1 has been used as an excellent oxygen-sensitive phosphor for intracellular O2 sensing and hypoxia imaging.
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Gene mutations in Mycobacterium tuberculosis: Multidrug-resistant TB as an emerging global public health crisis.
Tuberculosis (Edinb)
PUBLISHED: 07-26-2014
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Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. TB poses formidable challenges to the global health at the public health and scientific level by acquiring gene mutation into anti TB drugs specially rifampin and isoniazid which leads resistant to drug regime and treatment forms. Our tools to combat MDR (multidrug resistant) TB are dangerously out of date and ineffective. Besides new tools (TB drugs, vaccines, diagnostics), we also need new strategies to identify key Mycobacterium tuberculosis and human host interaction. It is all equally important that we build up high quality clinical trial capacity and bio banks for TB biomarkers identification. But most important is global commitment at all levels to roll back TB before it expose us again. Rapid development of drug resistance caused by M. tuberculosis has lead to measure resistance accurately and easily. This knowledge will certainly help us to understand how to prevent the occurrence of drug resistance as well as identifying genes associated with new drug resistance.
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Discovery and in vivo evaluation of novel RGD-modified lipid-polymer hybrid nanoparticles for targeted drug delivery.
Int J Mol Sci
PUBLISHED: 07-25-2014
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In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg-Gly-Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD-lpNPs) could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid))-mPEG (methoxyl poly(ethylene- glycol)), RGD-polyethylene glycol (PEG)-cholesterol (Chol) copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD-lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD-lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD-lpNPs was increased for human umbilical vein endothelial cells (HUVEC). Furthermore, Cur loaded RGD-lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD-lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD-lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD-lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy.
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Advantage of the N-Alkylation Strategy for Retaining the Molecular Planarity for Oligothiophene/Imidazole/1,10-Phenanthroline-Based Heterocyclic Semiconducting and Fluorescent Compounds.
Chem Asian J
PUBLISHED: 07-19-2014
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A family of planar oligothiophene/imidazole/1,10-phenanthroline (OTIP)-based heterocyclic, aromatic, semiconducting, and fluorescent compounds with N-substituted alkyl chains (allyl, n-butyl, n-octyl, n-dodecyl, and n-cetyl) have been designed and synthesized. They all have specific N-coordination sites, various donor-acceptor spacers, good molecular planarity, suitable solubility, and high thermal stability. In comparison with conventional double ?-alkylation of the thiophene ring, our results reveal that the single imidazole N-alkylation strategy for OTIPs has the advantage of maintaining the planarity of the whole molecule, in addition to improving the solubility, which can be clearly verified by the small dihedral angles between adjacent thiophene/imidazole/1,10-phenanthroline (TIP) rings in eight X-ray single-crystal structures. In particular, n-dodecyl- and n-cetyl-substituted OTIPs (7 and 8) with the same molecular length of 2.37?nm (MW =939 and 1052), show good molecular planarity with the aforementioned dihedral angles of 8.9(5) and 10.4(5)°. Furthermore, special attention has been paid to the physicochemical properties of seven symmetrical OTIPs (6-8, 13-15, and 19), including two to six thiophene rings in the middle of their molecular structures. To the best of our knowledge, this is the first synthetic, structural, and spectral investigation into the N-alkylation of OTIP-based compounds.
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Analysis of the private, collective, and relational self-cognitions among Han and Tibetan Chinese.
Psychol Rep
PUBLISHED: 07-15-2014
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Differences in the concepts of private, collective, and relational selves between two Chinese ethnic groups, the Han and Tibetan-adhering to the philosophies of Confucianism and Tibetan Buddhism, respectively-were examined. 128 students (54 men, 74 women; M age = 20.9 yr., SD = 2.2) completed the revised Twenty Statements Test and self-reference paradigm. Study 1 found that for Han participants relational and private selves were ranked similarly and as more important than the collective self. Studies 2 and 3 found that adjective words describing private and relational selves were recalled in greater proportions than words describing the collective self. Tibetan participants showed no significant differences between the three self-cognitions. The findings correspond to differences in self-identity among these two subcultures.
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HNO?-assisted polyol synthesis of ultralarge single-crystalline Ag microplates and their far propagation length of surface plasmon polariton.
ACS Appl Mater Interfaces
PUBLISHED: 07-14-2014
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We developed a HNO3-assisted polyol reduction method to synthesize ultralarge single-crystalline Ag microplates routinely. The edge length of the synthesized Ag microplates reaches 50 ?m, and their top facets are (111). The mechanism for dramatically enlarging single-crystalline Ag structure stems from a series of competitive anisotropic growths, primarily governed by carefully tuning the adsorption of Ag(0) by ethylene glycol and the desorption of Ag(0) by a cyanide ion on Ag(100). Finally, we measured the propagation length of surface plasmon polaritons along the air/Ag interface under 534 nm laser excitation. Our single-crystalline Ag microplate exhibited a propagation length (11.22 ?m) considerably greater than that of the conventional E-gun deposited Ag thin film (5.27 ?m).
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Perylene-Diimide-Based Nanoparticles as Highly Efficient Photoacoustic Agents for Deep Brain Tumor Imaging in Living Mice.
Adv. Mater. Weinheim
PUBLISHED: 07-04-2014
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In order to promote the preclinical and clinical applications of photoacoustic imaging, novel photoacoustic contrast agents are highly desired for molecular imaging of diseases, especially for deep tumor imaging. Here, we first reported the perylene-3,4,9,10-tetracarboxylic diimide -based near-infrared-absorptive organic nanoparticles as an efficient agent for photoacoustic imaging of deep brain tumor in living mice with enhanced permeability and retention effect.
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Phase-controlled synthesis of ?-NiS nanoparticles confined in carbon nanorods for High Performance Supercapacitors.
Sci Rep
PUBLISHED: 07-01-2014
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A facile and phase-controlled synthesis of ?-NiS nanoparticles (NPs) embedded in carbon nanorods (CRs) is reported by in-situ sulfurating the preformed Ni/CRs. The nanopore confinement by the carbon matrix is essential for the formation of ?-NiS and preventing its transition to ?-phase, which is in strong contrast to large aggregated ?-NiS particles grown freely without the confinement of CRs. When used as electrochemical electrode, the hybrid electrochemical charge storage of the ultrasmall ?-NiS nanoparticels dispersed in CRs is benefit for the high capacitor (1092, 946, 835, 740?F g(-1) at current densities of 1, 2, 5, 10?A g(-1), respectively.). While the high electrochemical stability (approximately 100% retention of specific capacitance after 2000 charge/discharge cycles) is attributed to the supercapacitor-battery electrode, which makes synergistic effect of capacitor (CRs) and battery (NiS NPs) components rather than a merely additive composite. This work not only suggests a general approach for phase-controlled synthesis of nickel sulfide but also opens the door to the rational design and fabrication of novel nickel-based/carbon hybrid supercapacitor-battery electrode materials.
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Characterization of a novel antimicrobial peptide with chiting-biding domain from Mytilus coruscus.
Fish Shellfish Immunol.
PUBLISHED: 06-27-2014
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Using reverse phase high performance liquid chromatography (RP-HPLC), a novel antimicrobial peptide with 55 amino acid residues was isolated from the hemolymph of Mytilus coruscus. This new antimicrobial peptide displays predominant antimicrobial activity against fungi and Gram-positive bacteria. The molecular mass and the N-terminal sequence of this peptide were analyzed by Mass Spectrometry and Edman degradation, respectively. This antimicrobial peptide, with molecular mass of 6621.55 Da, is characterized by a chitin-biding domain and by 6 Cysteine residues engaged in three intra-molecular disulfide bridges. The full-length of cDNA sequence of this new peptide was obtained by rapid amplification of cDNA ends (RACE) and the encoded precursor was turn out to be a chitotriosidase-like protein. Therefore, we named the precursor with mytichitin-1 and the new antimicrobial peptide (designated as mytichitin-CB) is the carboxyl-terminal part of mytichitin-1. The mRNA transcripts of mytichitin-1 are mainly detected in gonad and the expression level of mytichitin-1 in gonad was up-regulated and reached the highest level at 12 h after bacterial challenge, which was 9-fold increase compared to that of the control group. These results indicated that mytichitin-1 was involved in the host immune response against bacterial infection and might contribute to the clearance of invading bacteria.
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Thermally Activated Delayed Fluorescence Materials Towards the Breakthrough of Organoelectronics.
Adv. Mater. Weinheim
PUBLISHED: 06-08-2014
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The design and characterization of thermally activated delayed fluorescence (TADF) materials for optoelectronic applications represents an active area of recent research in organoelectronics. Noble metal-free TADF molecules offer unique optical and electronic properties arising from the efficient transition and interconversion between the lowest singlet (S1 ) and triplet (T1 ) excited states. Their ability to harvest triplet excitons for fluorescence through facilitated reverse intersystem crossing (T1 ?S1 ) could directly impact their properties and performances, which is attractive for a wide variety of low-cost optoelectronic devices. TADF-based organic light-emitting diodes, oxygen, and temperature sensors show significantly upgraded device performances that are comparable to the ones of traditional rare-metal complexes. Here we present an overview of the quick development in TADF mechanisms, materials, and applications. Fundamental principles on design strategies of TADF materials and the common relationship between the molecular structures and optoelectronic properties for diverse research topics and a survey of recent progress in the development of TADF materials, with a particular emphasis on their different types of metal-organic complexes, D-A molecules, and fullerenes, are highlighted. The success in the breakthrough of the theoretical and technical challenges that arise in developing high-performance TADF materials may pave the way to shape the future of organoelectronics.
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Protection of Radial Glial-Like Cells in the Hippocampus of APP/PS1 Mice: a Novel Mechanism of Memantine in the Treatment of Alzheimer's Disease.
Mol. Neurobiol.
PUBLISHED: 05-12-2014
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The failure of adult neurogenesis in the hippocampal dentate gyrus (DG) is closely correlated with memory decline in Alzheimer's disease (AD). Radial glial-like cells (RGLs) localized to the adult DG generate intermediate progenitor cells and immature neurons and thus contribute to adult hippocampus neurogenesis. Memantine (MEM) has been indicated to dramatically increase hippocampal neurogenesis by promoting the proliferation of RGLs. In this study, we examined the effect of MEM on the capacity for hippocampal cell proliferation and the amount of RGLs in APPswe/PS1?E9 transgenic (APP/PS1) mice between 9 and 13 months of age. MEM could enhance hippocampal neurogenesis and increase the number of RGLs in the DG subgranular zone (DG-SGZ) of APP/PS1 mice of both ages. Moreover, MEM decreased amyloidogenesis in 13-month-old APP/PS1 mice and protected cultured radial glia cells (RGCs, L2.3 cells) from apoptosis induced by the ? amyloid peptide (A?). Additionally, MEM inhibited microglial activation in a vertical process in DG-SGZ of APP/PS1 mice and decreased interacting with RGL processes. Reelin is involved in the proliferation of RGLs in the hippocampus, which was typically upregulated in the hippocampus of APP/PS1 mice by MEM and thought to be an active signaling pathway associated with the MEM-induced increase in RGLs. Our data suggest a previously uncharacterized role for MEM in treating AD.
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Transcriptome profiling in imipenem-selected Acinetobacter baumannii.
BMC Genomics
PUBLISHED: 05-11-2014
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Carbapenem-resistance in Acinetobacter baumannii has gradually become a global challenge. To identify the genes involved in carbapenem resistance in A. baumannii, the transcriptomic responses of the completely sequenced strain ATCC 17978 selected with 0.5 mg/L (IPM-2 m) and 2 mg/L (IPM-8 m) imipenem were investigated using RNA-sequencing to identify differences in the gene expression patterns.
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Acarbose treatment and the risk of cardiovascular disease in type 2 diabetic patients: a nationwide seven-year follow-up study.
J Diabetes Res
PUBLISHED: 04-30-2014
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To investigate the potential benefits of acarbose treatment on cardiovascular disease (CVD) in patients with type 2 diabetes by using nationwide insurance claim dataset.
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Species-specific defence responses facilitate conspecifics and inhibit heterospecifics in above-belowground herbivore interactions.
Nat Commun
PUBLISHED: 04-20-2014
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Conspecific and heterospecific aboveground and belowground herbivores often occur together in nature and their interactions may determine community structure. Here we show how aboveground adults and belowground larvae of the tallow tree specialist beetle Bikasha collaris and multiple heterospecific aboveground species interact to determine herbivore performance. Conspecific aboveground adults facilitate belowground larvae, but other aboveground damage inhibits larvae or has no effect. Belowground larvae increase conspecific adult feeding, but decrease heterospecific aboveground insect feeding and abundance. Chemical analyses and experiments with plant populations varying in phenolics show that all these positive and negative effects on insects are closely related to root and shoot tannin concentrations. Our results show that specific plant herbivore responses allow herbivore facilitation and inhibition to co-occur, likely shaping diverse aboveground and belowground communities. Considering species-specific responses of plants is critical for teasing apart inter- and intraspecific interactions in aboveground and belowground compartments.
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Enhanced Accumulation of Carbohydrate and Starch in Chlorella zofingiensis Induced by Nitrogen Starvation.
Appl. Biochem. Biotechnol.
PUBLISHED: 04-13-2014
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Though less attention has been paid to microalgae as a feedstock for bioethanol production, many microalgae seem to have this potential since they contain no lignin, minor hemicellulose, and abundant carbohydrate. The objective of this study was to investigate the effect of nitrogen starvation on carbohydrate and starch accumulation in green microalga Chlorella zofingiensis and assess the feasibility of using this microalga as a bioethanol feedstock. The results showed that the specific growth rate under nitrogen starvation (0.48 day(-1)) was much lower than that under nitrogen repletion (1.02 day(-1)). However, nitrogen starvation quickly induced the accumulation of carbohydrate, especially starch. After merely 1 day of nitrogen starvation, carbohydrate and starch increased 37 % and 4.7-fold, respectively. The highest carbohydrate content reached 66.9 % of dry weight (DW), and 66.7 % of this was starch. In order to obtain enough carbohydrate productivities for bioethanol production, two-stage cultivation strategy was implemented and found to be effective for enhancing biomass, carbohydrate, and starch simultaneously. The optimal biomass, carbohydrate, and starch productivities of C. zofingiensis were obtained after 5 days of cultivation, and their values were 699, 407, and 268 mg L(-1) day(-1), respectively.
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Bladder extragastrointestinal stromal tumor in an adolescent patient: A case-based review.
Mol Clin Oncol
PUBLISHED: 04-11-2014
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Extragastrointestinal stromal tumors (EGISTs) are mesenchymal tumors occurring outside the gastrointestinal tract, with histological, immunohistochemical and molecular genetic characteristics similar to those of gastrointestinal stromal tumors (GISTs). The immunohistochemical examination usually demonstrates a positive expression for CD117. GISTs are rare neoplasms and EGISTs are even less common. This is the report of a case of EGIST in the urinary bladder of a 15-year-old adolescent female patient who presented with painless gross hematuria. Pelvic computed tomography revealed an irregular soft tissue density mass, sized 5.7×4.8 cm, in the bladder. Partial cystectomy was performed in April, 2011. There was no recurrence during follow-up over the next 35 months, as determined by transabdoninal ultrasonography and cystoscopic examination. The patient in this study did not receive any molecular-targeted drugs. To the best of our knowledge, this is the first reported case of an EGIST of the urinary bladder in an adolescent patient.
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Analysis of 121 fatal passenger car-adult pedestrian accidents in China.
J Forensic Leg Med
PUBLISHED: 03-23-2014
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To study the characteristics of fatal vehicle-pedestrian accidents in China?a team was established and passenger car-pedestrian crash cases occurring between 2006 and 2011 in Beijing and Chongqing, China were collected. A total of 121 fatal passenger car-adult pedestrian collisions were sampled and analyzed. The pedestrian injuries were scored according to Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS). The demographical distributions of fatal pedestrian accidents differed from other pedestrian accidents. Among the victims, no significant discrepancy in the distribution of ISS and AIS in head, thorax, abdomen, and extremities by pedestrian age was found, while pedestrian behaviors prior to the crashes may affect the ISS. The distributions of AIS in head, thorax, and abdomen among the fatalities did not show any association with impact speeds or vehicle types, whereas there was a strong relationship between the ISS and impact speeds. Whether pedestrians died in the accident field or not was not associated with the ISS or AIS. The present results may be useful for not only forensic experts but also vehicle safety researchers. More investigations regarding fatal pedestrian accidents need be conducted in great detail.
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Design of hybrid radial basis function neural networks (HRBFNNs) realized with the aid of hybridization of fuzzy clustering method (FCM) and polynomial neural networks (PNNs).
Neural Netw
PUBLISHED: 02-03-2014
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In this study, we propose Hybrid Radial Basis Function Neural Networks (HRBFNNs) realized with the aid of fuzzy clustering method (Fuzzy C-Means, FCM) and polynomial neural networks. Fuzzy clustering used to form information granulation is employed to overcome a possible curse of dimensionality, while the polynomial neural network is utilized to build local models. Furthermore, genetic algorithm (GA) is exploited here to optimize the essential design parameters of the model (including fuzzification coefficient, the number of input polynomial fuzzy neurons (PFNs), and a collection of the specific subset of input PFNs) of the network. To reduce dimensionality of the input space, principal component analysis (PCA) is considered as a sound preprocessing vehicle. The performance of the HRBFNNs is quantified through a series of experiments, in which we use several modeling benchmarks of different levels of complexity (different number of input variables and the number of available data). A comparative analysis reveals that the proposed HRBFNNs exhibit higher accuracy in comparison to the accuracy produced by some models reported previously in the literature.
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Identification and characterization of lysine-methylated sites on histones and non-histone proteins.
Comput Biol Chem
PUBLISHED: 01-24-2014
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Protein methylation is a kind of post-translational modification (PTM), and typically takes place on lysine and arginine amino acid residues. Protein methylation is involved in many important biological processes, and most recent studies focused on lysine methylation of histones due to its critical roles in regulating transcriptional repression and activation. Histones possess highly conserved sequences and are homologous in most species. However, there is much less sequence conservation among non-histone proteins. Therefore, mechanisms for identifying lysine-methylated sites may greatly differ between histones and non-histone proteins. Nevertheless, this point of view was not considered in previous studies. Here we constructed two support vector machine (SVM) models by using lysine-methylated data from histones and non-histone proteins for predictions of lysine-methylated sites. Numerous features, such as the amino acid composition (AAC) and accessible surface area (ASA), were used in the SVM models, and the predictive performance was evaluated using five-fold cross-validations. For histones, the predictive sensitivity was 85.62% and specificity was 80.32%. For non-histone proteins, the predictive sensitivity was 69.1% and specificity was 88.72%. Results showed that our model significantly improved the predictive accuracy of histones compared to previous approaches. In addition, features of the flanking region of lysine-methylated sites on histones and non-histone proteins were also characterized and are discussed. A gene ontology functional analysis of lysine-methylated proteins and correlations of lysine-methylated sites with other PTMs in histones were also analyzed in detail. Finally, a web server, MethyK, was constructed to identify lysine-methylated sites. MethK now is available at http://csb.cse.yzu.edu.tw/MethK/.
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A novel approach for discovering condition-specific correlations of gene expressions within biological pathways by using cloud computing technology.
Biomed Res Int
PUBLISHED: 01-22-2014
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Microarrays are widely used to assess gene expressions. Most microarray studies focus primarily on identifying differential gene expressions between conditions (e.g., cancer versus normal cells), for discovering the major factors that cause diseases. Because previous studies have not identified the correlations of differential gene expression between conditions, crucial but abnormal regulations that cause diseases might have been disregarded. This paper proposes an approach for discovering the condition-specific correlations of gene expressions within biological pathways. Because analyzing gene expression correlations is time consuming, an Apache Hadoop cloud computing platform was implemented. Three microarray data sets of breast cancer were collected from the Gene Expression Omnibus, and pathway information from the Kyoto Encyclopedia of Genes and Genomes was applied for discovering meaningful biological correlations. The results showed that adopting the Hadoop platform considerably decreased the computation time. Several correlations of differential gene expressions were discovered between the relapse and nonrelapse breast cancer samples, and most of them were involved in cancer regulation and cancer-related pathways. The results showed that breast cancer recurrence might be highly associated with the abnormal regulations of these gene pairs, rather than with their individual expression levels. The proposed method was computationally efficient and reliable, and stable results were obtained when different data sets were used. The proposed method is effective in identifying meaningful biological regulation patterns between conditions.
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Synthesis and evaluation of 4-(2-pyrimidinylamino) benzamides inhibitors of hedgehog signaling pathway.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-11-2014
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A novel series of hedgehog signaling pathway inhibitors has been designed based on the 4-(2-pyrimidinylamino) benzamides scaffold. The synthesis and SAR of these compounds are described. Optimization leads to the identification of compound 3c, a potent and orally available agent with improved physicochemical and pharmacokinetic properties.
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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.