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Find video protocols related to scientific articles indexed in Pubmed.
Three-dimensionalization of ultrathin nanosheets in a two-dimensional nano-reactor: macroporous CuO microstructures with enhanced cycling performance.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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Three-dimensional (3D) macroporous CuO structures composed of ultrathin nanosheets were successfully synthesized by employing a liquid-liquid interface as a two-dimensional (2D) nano-reactor. The macroporous structure helped CuO to retain the exposed surface during reactions, thus significantly enhancing the long term cycling performance both in photocatalysis and lithium ion batteries.
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The Landscape of MicroRNA, Piwi-Interacting RNA, and Circular RNA in Human Saliva.
Clin. Chem.
PUBLISHED: 11-08-2014
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Extracellular RNAs (exRNAs) in human body fluids are emerging as effective biomarkers for detection of diseases. Saliva, as the most accessible and noninvasive body fluid, has been shown to harbor exRNA biomarkers for several human diseases. However, the entire spectrum of exRNA from saliva has not been fully characterized.
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Phylogenomics resolves the timing and pattern of insect evolution.
Bernhard Misof, Shanlin Liu, Karen Meusemann, Ralph S Peters, Alexander Donath, Christoph Mayer, Paul B Frandsen, Jessica Ware, Tomáš Flouri, Rolf G Beutel, Oliver Niehuis, Malte Petersen, Fernando Izquierdo-Carrasco, Torsten Wappler, Jes Rust, Andre J Aberer, Ulrike Aspöck, Horst Aspöck, Daniela Bartel, Alexander Blanke, Simon Berger, Alexander Böhm, Thomas R Buckley, Brett Calcott, Junqing Chen, Frank Friedrich, Makiko Fukui, Mari Fujita, Carola Greve, Peter Grobe, Shengchang Gu, Ying Huang, Lars S Jermiin, Akito Y Kawahara, Lars Krogmann, Martin Kubiak, Robert Lanfear, Harald Letsch, Yiyuan Li, Zhenyu Li, Jiguang Li, Haorong Lu, Ryuichiro Machida, Yuta Mashimo, Pashalia Kapli, Duane D McKenna, Guanliang Meng, Yasutaka Nakagaki, José Luis Navarrete-Heredia, Michael Ott, Yanxiang Ou, Günther Pass, Lars Podsiadlowski, Hans Pohl, Björn M von Reumont, Kai Schütte, Kaoru Sekiya, Shota Shimizu, Adam Slipinski, Alexandros Stamatakis, Wenhui Song, Xu Su, Nikolaus U Szucsich, Meihua Tan, Xuemei Tan, Min Tang, Jingbo Tang, Gerald Timelthaler, Shigekazu Tomizuka, Michelle Trautwein, Xiaoli Tong, Toshiki Uchifune, Manfred G Walzl, Brian M Wiegmann, Jeanne Wilbrandt, Benjamin Wipfler, Thomas K F Wong, Qiong Wu, Gengxiong Wu, Yinlong Xie, Shenzhou Yang, Qing Yang, David K Yeates, Kazunori Yoshizawa, Qing Zhang, Rui Zhang, Wenwei Zhang, Yunhui Zhang, Jing Zhao, Chengran Zhou, Lili Zhou, Tanja Ziesmann, Shijie Zou, Yingrui Li, Xun Xu, Yong Zhang, Huanming Yang, Jian Wang, Jun Wang, Karl M Kjer, Xin Zhou.
Science
PUBLISHED: 11-06-2014
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Insects are the most speciose group of animals, but the phylogenetic relationships of many major lineages remain unresolved. We inferred the phylogeny of insects from 1478 protein-coding genes. Phylogenomic analyses of nucleotide and amino acid sequences, with site-specific nucleotide or domain-specific amino acid substitution models, produced statistically robust and congruent results resolving previously controversial phylogenetic relations hips. We dated the origin of insects to the Early Ordovician [~479 million years ago (Ma)], of insect flight to the Early Devonian (~406 Ma), of major extant lineages to the Mississippian (~345 Ma), and the major diversification of holometabolous insects to the Early Cretaceous. Our phylogenomic study provides a comprehensive reliable scaffold for future comparative analyses of evolutionary innovations among insects.
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Essential oil from Zanthoxylum bungeanum Maxim. and its main components used as transdermal penetration enhancers: a comparative study.
J Zhejiang Univ Sci B
PUBLISHED: 11-05-2014
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Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. (Z. bungeanum oil) could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine (TCM) active components. Toxicities of Z. bungeanum oil and three selected terpene compounds (terpinen-4-ol, 1,8-cineole, and limonene) in epidermal keratinocytes (HaCaT) and dermal fibroblast (CCC-ESF-1) cell lines were measured using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Five model drugs in TCM external preparations, namely osthole (OT), tetramethylpyrazine (TMP), ferulic acid (FA), puerarin (PR), and geniposide (GP), which were selected based on their lipophilicity denoted by logKo/w, were tested using in vitro permeation studies in which vertical Franz diffusion cells and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum (SC) and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared (FTIR) spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order: terpinen-4-ol?1,8-cineole
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Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study.
J Zhejiang Univ Sci B
PUBLISHED: 11-05-2014
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A rapid, reliable, and sensitive method was developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionization (ESI) source for determination of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets (GBTs). The method simultaneously detects bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) for pharmacokinetic study. The analytes and internal standard (IS) were extracted from rat plasma by acetidin. An MS/MS detection was conducted using multiple reaction monitoring (MRM) and operating in the negative ionization mode. The calibration curve ranges were 5-500, 5-500, 2.5-250, 1-100, 1-100, 1-100, and 1-100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery of the analytes ranged from 68.11% to 84.42%. The intra- and inter-day precisions were in the range of 2.33%-9.86% and the accuracies were between 87.67% and 108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The pharmacokinetic parameters of seven compounds were analyzed using a non-compartment model. Plasma concentrations of the seven compounds were determined up to 48 h after administration, and their pharmacokinetic parameters were in agreement with previous studies.
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Melanoma Differentiation Associated Gene-7/Interleukin-24 Induces Caspase-3 Denitrosylation to Facilitate the Activation of Cancer Cell Apoptosis.
J. Interferon Cytokine Res.
PUBLISHED: 10-28-2014
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Melanoma differentiation-associated gene-7 (mda-7)/interleukin-24 (IL-24) induces caspase-3 cleavage and subsequent activation via the intrinsic or extrinsic pathway to result in cancer cell-selective apoptosis, but whether mda-7/IL-24 may directly regulate caspase-3 through the post-translational modification remains unknown. Here, we reported that tumor-selective replicating adenovirus ZD55-IL-24 led to caspase-3 denitrosylation and subsequent activation, indicating that caspase-3 denitrosylation played a crucial role in ZD55-IL-24-induced cancer cell apoptosis. To confirm the relationship between caspase-3 denitrosylation and its activation in response to ZD55-IL-24, we treated carcinoma cells with the different nitric oxide (NO) regulators to modulate caspase-3 denitrosylation level, then observed the corresponding caspase-3 cleavage. We found that NO inhibitor 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (PTIO) promoted caspase-3 denitrosylation and caspase-3 cleavage, thereby exacerbating ZD55-IL-24-induced cancer cell apoptosis, whereas NO donor sodium nitroprusside (SNP) showed the opposite effect. Moreover, caspase-3 denitrosylation facilitated its downstream target poly ADP-ribose polymerase (PARP) degradation that further increased the apoptotic susceptibility. Although caspase-3 activation controlled by denitrosylation modification has emerged as an important regulator of programmed cell death, the detailed molecular mechanism by which caspase-3 exerts its denitrosylation modification in response to ZD55-IL-24 still needs to be elucidated. Thus, our results demonstrated that ZD55-IL-24 increased Fas expression to enhance thioredoxin reductase 2 (TrxR2), which was responsible for caspase-3 denitrosylation. Collectively, these findings elucidate that ZD55-IL-24 induces caspase-3 denitrosylation through Fas-mediated TrxR2 enhancement, thereby facilitating caspase-3 cleavage and the downstream caspase signaling pathway activation, which provides a novel insight into ZD55-IL-24-induced cancer-specific apoptosis by post-translational modification of the apoptotic executor caspase-3.
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A general approach for the development of fluorogenic probes suitable for no-wash imaging of kinases in live cells.
Chem. Commun. (Camb.)
PUBLISHED: 10-27-2014
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A general approach is presented for developing small molecule-based fluorogenic probes suitable for no-wash imaging of endogenous kinases in live cells. Probe 1, including a fluorophore-quencher system, was only "turned on" upon reacting with its target kinase Btk, and disclosed Btk's cellular location in live cells without any washing.
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[Effect of PI3K? inhibitor CAL-101 on myeloma cell lines and preliminary study of ynergistic effects with other new drugs].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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To investigate the proliferation inhibitory role and mechanism of PI3K? inhibitor CAL-101 on multiple myeloma (MM) cells, and to provide new therapeutic options for MM treatment.
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Efficacy and Toxicity of Anti-VEGF Agents in Patients with Castration-Resistant Prostate Cancer: a Meta-analysis of Prospective Clinical Studies.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC.
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miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma.
Oncotarget
PUBLISHED: 10-22-2014
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High-grade serous ovarian carcinoma (HGSOC), the most common and aggressive subtype of epithelial ovarian cancer, is characterized by TP53 mutations and genetic instability. Using miRNA profiling analysis, we found that miR-145, a p53 regulated miRNA, was frequently down-regulated in HGSOC. miR-145 down-regulation was further validated in a large cohort of HGSOCs by qPCR. Overexpression of miR-145 in ovarian cancer cells significantly suppressed proliferation, migration and invasion in vitro and inhibited tumor growth and metastasis in vivo. Metadherin (MTDH) was subsequently identified as a direct target of miR-145, and was found to be significantly up-regulated in HGSOC. Furthermore, overexpression of MTDH rescued the inhibitory effects of miR-145 in ovarian cancer cells. Finally, we found that high level of MTDH expression correlated with poor prognosis of HGSOC. Therefore, lack of suppression of MTDH by miR-145 when p53 is dysfunctional leads to increased tumor growth and metastasis of HGSOC. Our study established a new link between p53, miR-145 and MTDH in the regulation of tumor growth and metastasis in HGSOC.
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[Screening and structure analysis of the aptamer target to Escherichia coli tolC protein].
Beijing Da Xue Xue Bao
PUBLISHED: 10-22-2014
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To screen and characterize the aptamer of Escherichia coli outer member protein tolC.
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Anti-epidermal-growth-factor-receptor agents and complete responses in the treatment of advanced non-small-cell lung cancer: a meta-analysis of 17 phase III randomized controlled trials.
Curr Med Res Opin
PUBLISHED: 10-21-2014
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Abstract Purpose: Currently, the anti-epidermal-growth-factor-receptor (EGFR) agents have shown encouraging treatment benefits in patients with various types of solid tumors including non-small-cell lung cancer (NSCLC). Despite these advances, radiological complete response to these therapies is rare. We meta-analyze the incidence of complete response (CR) in advanced NSCLC patients treated with anti-EGFR agents and controls in randomized controlled trials (RCTs). Methods: PubMed, Web of Science, Embase and Cochrane library databases were reviewed for phase III RCTs with EGFR-targeted agents vs. non-EGFR-targeted agents in patients with advanced NSCLC. We calculated the odds ratio of CR in patients assigned to anti-EGFR agents compared to controls. Results: A total of 11,568 patients from 17 RCTs were included for analysis. The incidence of CR in patients treated with anti-EGFR agents was 1.1% (95% CI, 0.7-1.7%) compared to 0.6% (95% CI, 0.4-0.9%) in control arms. Comparing the different types of anti-EGFR agents, the incidence of CR was 1.9% for gefitinib (95% CI: 1.4-2.6%), 1.4% for cetuximab (95% CI: 0.8-2.7%) and 0.9% for erlotinib (95% CI: 0.6-1.5%), respectively. The use of anti-EGFR agents significantly increased the odds ratio of obtaining a CR (OR 2.12, 95% CI: 1.28-3.49, p?=?0.003) compared to controls. This was found to be higher in treatment arms involving more than 50% of: female patients, patients who had never smoked tobacco, patients of Asian descent or patients with adenocarcinoma or EGFR mutation. No significant differences in ORs were observed in any prespecified sub-groups. Conclusion: Although a CR is rare in advanced NSCLC patients receiving anti-EGFR agents, these drugs significantly increase the OR of a CR compared to controls, especially for patients with EGFR mutations. Further studies are needed to investigate whether the increase of CR with anti-EGFR therapy would be translated into survival benefits.
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[Variations of renal vascular score and resistive indices in septic shock patients].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-21-2014
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To assess the variations of renal vascularization scale and resistive index in septic shock patients during the first 6 h in intensive care unit (ICU).
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Light-responsive smart surface with controllable wettability and excellent stability.
Langmuir
PUBLISHED: 10-09-2014
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Novel fluorinated gradient copolymer was designed for smart surface with light-responsive controllable wettability and excellent stability. The switchable mechanism and physicochemical characteristics of the as-prepared surface decorated by designed polymeric material were investigated by ultraviolet-visible (UV-vis) spectrum, scanning electron microscope (SEM), atomic force microscope (AFM), and X-ray photoelectron spectroscopy (XPS). Thanks to the functional film and surface roughening, etched silicon surface fabricated by copolymer involving spiropyran (Sp) moieties possesses a fairly large variation range of WCA (28.1°) and achieves the transformation between hydrophilicity (95.2° < 109.2°) and hydrophobicity (123.3° > 109.2°) relative to blank sample (109.2°). The synthetic strategy and developed smart surface offer a promising application in coating with controllable wettability, which bridge the gap between chemical structure and material properties.
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Learning needs of Chinese patients before undergoing elective percutaneous coronary intervention.
Contemp Nurse
PUBLISHED: 10-01-2014
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Abstract This study aimed to determine the learning needs of Chinese patients going for elective percutaneous coronary intervention (PCI), in order to design nurse-led education programs. A self-administered survey was completed by a total of 395 patients prior to the procedure. Face-to-face communication was chosen by 343 (86.8%) patients as the most preferred way of education. Doctor-in-charge was ranked as the most wanted educator by 372 (94.2%) patients, including 191 (45.4%) patients who chose both doctor-in-charge and nurse-in-charge. Interventional cardiologist was preferred by patients with higher education more than those with lower education (63.6 vs. 48.1%, P < 0.05). Learning items such as self-rescue on heart attack, efficiency of PCI and post-procedural medication were regarded as the most important, which could be affected by age, gender and educational level. These findings would help to develop patient preferred programs that involve brief communications with doctors and more structured education activities led by nurses.
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Internal carbon source from sludge pretreated by microwave-H2O2 for nutrient removal in A(2)/O-membrane bioreactors.
Environ Technol
PUBLISHED: 09-30-2014
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To improve the nutrient removal, the feasibility was studied for the organics released from sludge pretreated by microwave-H2O2 process (MHP) to be used as internal carbon source in two A(2)/O-membrane bioreactors (MBRs). The experiments were conducted for the nutrient removal and the membrane fouling. The results showed that the removal efficiencies of TN and TP were improved by 11% and 28.34%, respectively, as C/N ratio was adjusted to 8 by adding the internal carbon source, and the ratio of soluble chemical oxygen demand (sCOD) consumed easily for denitrification was about 46% of the total sCOD in the internal carbon source. The addition of the internal carbon sources did not lead to severe membrane fouling in the experimental A(2)/O-MBR. It is implied that the organics released from sludge pretreated by MHP could be used as the internal carbon source to enhance the nutrient removal in A(2)/O-MBRs.
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Monocrystalline mesoporous metal oxide with perovskite structure: a facile solid-state transformation of a coordination polymer.
Chem. Commun. (Camb.)
PUBLISHED: 09-27-2014
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Monocrystalline mesoporous BiFeO3 crystals were obtained via a multi-step single-crystal to single-crystal transformation of a coordination polymer, Bi[Fe(CN)6]·4H2O. This unique transformation process significantly decreased the crystallization temperature of perovskite oxide without losing high crystallinity.
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[Ocular vestibular evoked myogenic potential elicited by different types of stimulus among normal young Chinese people].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-25-2014
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To observe waveform differences among ocular vestibular evoked myogenic potentials (ACS-oVEMP) elicited by different types of air conducted sound in normal young Chinese subjects.
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Elucidating the localized plasmonic enhancement effects from a single ag nanowire in organic solar cells.
ACS Nano
PUBLISHED: 09-15-2014
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The origins of performance enhancement in hybrid plasmonic organic photovoltaic devices are often embroiled in a complex interaction of light scattering, localized surface plasmon resonances, exciton-plasmon energy transfer and even nonplasmonic effects. To clearly deconvolve the plasmonic contributions from a single nanostructure, we herein investigate the influence of a single silver nanowire (NW) on the charge carriers in bulk heterojunction polymer solar cells using spatially resolved optical spectroscopy, and correlate to electrical device characterization. Polarization-dependent photocurrent enhancements with a maximum of ?36% over the reference are observed when the transverse mode of the plasmonic excitations in the Ag NW is activated. The ensuing higher absorbance and light scattering induced by the electronic motion perpendicular to the NW long axis lead to increased exciton and polaron densities instead of direct surface plasmon-exciton energy transfer. Finite-difference time-domain simulations also validate these findings. Importantly, our study at the single nanostructure level explores the fundamental limits of plasmonic enhancement achievable in organic solar cells with a single plasmonic nanostructure.
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Separation of Catalpol from Rehmannia glutinosa Libosch. by High-Speed Countercurrent Chromatography.
J Chromatogr Sci
PUBLISHED: 09-13-2014
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The bioactive iridoid component catalpol was successfully separated by high-speed countercurrent chromatography with high purity from the partially purified crude extract of Rehmannia glutinosa. A polar two-phase solvent system composed of ethyl acetate-n-butanol-water (2:1:3, v/v/v) was selected by thin-layer chromatography and run on a preparative scale where the lower aqueous phase was used as the mobile phase with a head-to-tail elution mode. A 105 mg quantity of the partially purified sample containing 39.2% catalpol was loaded on a 270-mL capacity high-speed countercurrent separation column, yielding 35 mg of catalpol at 95.6% purity. The chemical structure of catalpol was determined by comparison with the high-performance liquid chromatography retention time of standard substance as well as the (1)H NMR spectrum.
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Room-temperature near-infrared high-q perovskite whispering-gallery planar nanolasers.
Nano Lett.
PUBLISHED: 09-10-2014
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Near-infrared (NIR) solid-state micro/nanolasers are important building blocks for true integration of optoelectronic circuitry.1 Although significant progress has been made in III-V nanowire lasers with achieving NIR lasing at room temperature,2-4 challenges remain including low quantum efficiencies and high Auger losses. Importantly, the obstacles toward integrating one-dimensional nanowires on the planar ubiquitous Si platform need to be effectively tackled. Here we demonstrate a new family of planar room-temperature NIR nanolasers based on organic-inorganic perovskite CH3NH3PbI3-aXa (X = I, Br, Cl) nanoplatelets. Their large exciton binding energies, long diffusion lengths, and naturally formed high-quality planar whispering-gallery mode cavities ensure adequate gain and efficient optical feedback for low-threshold optically pumped in-plane lasing. We show that these remarkable wavelength tunable whispering-gallery nanolasers can be easily integrated onto conductive platforms (Si, Au, indium tin oxide, and so forth). Our findings open up a new class of wavelength tunable planar nanomaterials potentially suitable for on-chip integration.
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Green electrochemical sensing platforms: utilizing hydroxyapatite derived from natural fish scales as a novel electrochemical material for the sensitive detection of kidney injury molecule 1 (KIM-1).
Analyst
PUBLISHED: 09-06-2014
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Urinary KIM-1 is an ideal biomarker for acute kidney injury diagnosis. The proof-of-concept is demonstrated by utilizing the hydroxyapatite derived from natural fish scales as an electrode material, where the sensing of KIM-1 is shown to be possible for the first time with a linear range from 0.01 to 0.20 ?g mL(-1) and a detection limit of 0.017 ?g mL(-1) under model conditions; proof-of-concept is demonstrated in spiked urine.
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A comparative study of calcium sulfate artificial bone graft versus allograft in the reconstruction of bone defect after tumor curettage.
Chin. Med. J.
PUBLISHED: 09-06-2014
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Cavity reconstruction after benign bone tumor removal is varied and controversial. Allograft is widely used but is associated with complications. New bone substitutes, such as calcium sulfate artificial bone, have been introduced for bone tumor operation. However, the bone healing response of artificial bone has not been compared with allograft bone. We therefore compared calcium sulfate grafts (study group) with bone allografts (control group) for the treatment of benign bone tumors.
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Long-term follow-up results of the pacing to avoid cardiac enlargement (PACE) trial.
Eur. J. Heart Fail.
PUBLISHED: 09-01-2014
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We report the results of long-term follow-up of the Pacing to Avoid Cardiac Enlargement (PACE) trial, a prospective, double-blinded, randomized, multicentre study that confirmed the superiority of biventricular (BiV) pacing compared with right ventricular apical (RVA) pacing in prevention of LV adverse remodelling and deterioration of systolic function at 1 and 2 years.
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[Staging treatment for complex tibial metaphyseal fractures with external fixator].
Zhongguo Gu Shang
PUBLISHED: 08-30-2014
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To observe the clinical effects of combined type external fixator in treating complex tibial metaphyseal fractures.
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Mucinous tubular and spindle cell carcinoma of the kidney: the contrast-enhanced ultrasonography and CT features of six cases and review of the literature.
Int Urol Nephrol
PUBLISHED: 08-27-2014
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To report the features of contrast-enhanced ultrasonography (CEUS) and computer tomography (CECT) of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney.
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Inhibitory activities of Lignum Sappan extractives on growth and growth-related signaling of tumor cells.
Chin J Nat Med
PUBLISHED: 08-27-2014
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To investigate the active constituents of Lignum Sappan (Caesalpinia sappan L.) on growth-related signaling and cell mitosis.
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Soluble production and function of vascular endothelial growth factor/basic fibroblast growth factor complex peptide.
Biotechnol. Prog.
PUBLISHED: 08-26-2014
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Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are important proangiogenic factors in tumor procession. The autocrine and paracrine bFGF and the VEGF in tumor tissue can promote tumor angiogenesis, tumor growth, and metastasis. A VEGF/bFGF Complex Peptide (VBP3) was designed on the basis of epitope peptides from both VEGF and bFGF to elicit in vivo production of anti-bFGF and anti-VEGF antibodies. In this study, we reported on the production of recombinant VBP3 using high cell density fermentation. Fed-batch fermentation for recombinant VBP3 production was conducted, and the production procedure was optimized in a 10-L fermentor. The fraction of soluble VBP3 protein obtained reached 78% of total recombinant protein output under fed-batch fermentation. Purified recombinant VBP3 could inhibit tumor cell proliferation in vitro and stimulate C57BL/6 mice to produce high titer anti-VEGF and anti-bFGF antibodies in vivo. A melanoma-grafted mouse model and an immunohistochemistry assay showed that tumor growth and tumor angiogenesis were significantly inhibited in VBP3-vaccinated mice. These results demonstrated that soluble recombinant VBP3 could be produced by large-scale fermentation, and the product, with good immunogenicity, elicited production of high-titer anti-bFGF and anti-VEGF antibodies, which could be used as a therapeutic tumor vaccine to inhibit tumor angiogenesis and tumor growth. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 2014.
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[The effects of prone position ventilation combined with recruitment maneuvers on outcomes in patients with severe acute respiratory distress syndrome].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 08-23-2014
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To evaluate the effects of prone position ventilation combined with recruitment maneuvers (RM) on clinical outcomes in patients with severe acute respiratory distress syndrome (ARDS).
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FOXA2 suppresses the metastasis of hepatocellular carcinoma partially through matrix metalloproteinase-9 inhibition.
Carcinogenesis
PUBLISHED: 08-20-2014
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The forkhead box transcription factor A2 (FOXA2) is a member of the hepatocyte nuclear factor family and plays an important role in liver development and metabolic homeostasis, but its role in the metastasis of hepatocellular carcinoma (HCC) has not been evaluated. In this study, we found that the expression of FOXA2 was decreased in 68.1% (49/72) of human HCC tissues compared with their paired non-cancerous adjacent tissues. Clinicopathological analysis revealed that reduced FOXA2 expression was correlated with aggressive characteristics (venous invasion, poor differentiation, high tumor node metastasis grade). FOXA2 level was even lower in portal vein tumor thrombus compared with primary tumor tissues and correlated with epithelial-mesenchymal transition in HCC cells. Overexpression of FOXA2 inhibited migration and invasion of Focus cells, whereas knockdown of FOXA2 in HepG2 showed the opposite effect. Moreover, upregulation of FOXA2 suppressed HCC metastasis to bone, brain and lung in two distinct mouse models. Finally, we proved that FOXA2 repressed the transcription of matrix metalloproteinase (MMP)-9 and exerted its antimetastasis effect partially through downregulation of MMP-9. In conclusion, our findings indicate that FOXA2 plays a critical role in HCC metastasis and may serve as a novel therapeutic target for HCC.
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The Transcription Factor FOXA2 Suppresses Gastric Tumorigenesis In Vitro and In Vivo.
Dig. Dis. Sci.
PUBLISHED: 08-17-2014
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The transcription factor forkhead box A2 (FOXA2) plays a central role in the development of endoderm-derived organs. It has been reported that FOXA2 acts as a suppressor in many kinds of tumor. However, little is known about the role of FOXA2 in gastric cancer.
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Molecular regulation of ovarian cancer cell invasion.
Tumour Biol.
PUBLISHED: 08-15-2014
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The molecular mechanism underlying ovarian cancer invasiveness and metastasis remains unclear. Since significant downregulation in microRNA 200 (miRNA200) family (miR200a, miR200b, and miR200c) has been reported in the invasive ovarian cancer cells, here, we used two human ovarian cancer cell lines, OVCAR3 and SKOV3, to study the molecular basis of miR200, matrix metalloproteinase 3 (MMP3) activation, and cancer invasiveness. We found that overexpression of either miR200 family member in OVCAR3 or SKOV3 cells significantly inhibited production and secretion of MMP3 and cancer invasiveness. Moreover, forced MMP3 expression abolished miR200-induced inhibition of ovarian cancer cell invasiveness, suggesting that miR200 family inhibited ovarian cell invasiveness via downregulating MMP3. Furthermore, ZEB1, a major target of miR200, was inhibited by miR200 overexpression. Forced ZEB1 expression abolished miR200-induced inhibition of ovarian cancer cell invasiveness, suggesting that ZEB1 is a direct target of miR200 for inhibiting ovarian cell invasiveness. Finally, phosphorylated SMAD3 (pSMAD3), a major partner of ZEB1, was efficiently inhibited by miR200, which could be restored by forced expression of ZEB1, but not by forced expression of MMP3, suggesting that ZEB1/pSMAD3 is signaling cascade upstream of MMP3 in this model. Taken together, our data suggest that miR200 family inhibited ovarian cancer cell invasiveness and metastasis by downregulating MMP3, possibly through ZEB1/pSMAD3.
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Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease.
Cell Rep
PUBLISHED: 08-14-2014
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Macrophages can fuse to form osteoclasts in bone or multinucleate giant cells (MGCs) as part of the immune response. We use a systems genetics approach in rat macrophages to unravel their genetic determinants of multinucleation and investigate their role in both bone homeostasis and inflammatory disease. We identify a trans-regulated gene network associated with macrophage multinucleation and Kcnn4 as being the most significantly trans-regulated gene in the network and induced at the onset of fusion. Kcnn4 is required for osteoclast and MGC formation in rodents and humans. Genetic deletion of Kcnn4 reduces macrophage multinucleation through modulation of Ca(2+) signaling, increases bone mass, and improves clinical outcome in arthritis. Pharmacological blockade of Kcnn4 reduces experimental glomerulonephritis. Our data implicate Kcnn4 in macrophage multinucleation, identifying it as a potential therapeutic target for inhibition of bone resorption and chronic inflammation.
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Investigation of the role of organic cation transporter 2 (OCT2) in the renal transport of guanfacine, a selective ?2A-adrenoreceptor agonist.
Xenobiotica
PUBLISHED: 08-13-2014
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Abstract 1.? Guanfacine is a selective ?2A-adrenoreceptor agonist primarily excreted as its unchanged form through urine in human. This study was to investigate the involvement of organic cation transporter 2 (OCT2) in the renal tubular secretion of guanfacine. 2.? Transport of guanfacine was characterized using human embryonic kidney (HEK293) cells expressing human OCT2 (hOCT2). The inhibitory effect of cimetidine on guanfacine uptake was also examined. In addition, in vivo pharmacokinetic study was conducted in rats to assess the effects of cimetidine on the pharmacokinetics of guanfacine. 3.? The accumulation of guanfacine in hOCT2-transfected HEK293 cells was both time- and concentration-dependent, and markedly higher than that in mock cells. The apparent Km and Vmax values of guanfacine uptake by hOCT2 were 96.19?±?7.49??M and 13.03?±?0.49?nmol/mg protein/min, respectively. Guanfacine transport mediated by hOCT2 was significantly inhibited by a typical OCT2 inhibitor cimetidine with an IC50 value of 93.82?±?1.13??M. Co-administration of cimetidine significantly decreased the plasma clearance (CLp) as well as the renal clearance (CLr) of guanfacine in rats in a dose-dependent manner, resulting in a noticeable increase in the systemic exposure of guanfacine. 4.? These results indicated that OCT2 may be involved in the renal disposition of guanfacine.
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A room temperature low-threshold ultraviolet plasmonic nanolaser.
Nat Commun
PUBLISHED: 08-11-2014
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Constrained by large ohmic and radiation losses, plasmonic nanolasers operated at visible regime are usually achieved either with a high threshold (10(2)-10(4)?MW?cm(-2)) or at cryogenic temperatures (4-120?K). Particularly, the bending-back effect of surface plasmon (SP) dispersion at high energy makes the SP lasing below 450?nm more challenging. Here we demonstrate the first strong room temperature ultraviolet (~370?nm) SP polariton laser with an extremely low threshold (~3.5?MW?cm(-2)). We find that a closed-contact planar semiconductor-insulator-metal interface greatly lessens the scattering loss, and more importantly, efficiently promotes the exciton-SP energy transfer thus furnishes adequate optical gain to compensate the loss. An excitation polarization-dependent lasing action is observed and interpreted with a microscopic energy-transfer process from excitons to SPs. Our work advances the fundamental understanding of hybrid plasmonic waveguide laser and provides a solution of realizing room temperature UV nanolasers for biological applications and information technologies.
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Redifferentiation of dedifferentiated chondrocytes in a novel three-dimensional microcavitary hydrogel.
J Biomed Mater Res A
PUBLISHED: 08-11-2014
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Although chondrocytes exist in native cartilage all over the body, it is still a challenge to use them as therapeutic cells for cartilage tissue engineering (TE) because of their easy dedifferentiation in in vitro culture. An improved culture system to maintain the characteristics of chondrocytes or recover their chondrocytic phenotype should be developed. In this study, we have set up an innovative microcavitary alginate hydrogel in an easy way. We compared this culture system with the conventional hydrogel and found that the microcavitary hydrogel exhibited outstanding superiorities in helping the dedifferentiated chondrocytes recover the capability for synthesizing cartilaginous extracellular matrix. In addition, we explored the correlation between chondrocyte redifferentiation in microcavitary hydrogels and changes in p38 and Erk1/2 activity. Our findings indicated that this microcavitary hydrogel would be a promising culture system to provide sufficient competent cells for cartilage regeneration and TE. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.
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[The design and biomechanical evaluation of implantation on the mandibular defect reconstructed with rib graft].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 08-09-2014
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Applying geometric simulation and finite element analysis to an unilateral mandibular defect reconstructed with rib graft to evaluate the biomechanical properties and guide the implant restoration for this kind of mandibular defect.
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Exposure to bisphenol A at physiological concentrations observed in Chinese children promotes primordial follicle growth through the PI3K/Akt pathway in an ovarian culture system.
Toxicol In Vitro
PUBLISHED: 08-07-2014
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The worldwide increase in the use of bisphenol A (BPA) has resulted in increased human exposure, which could affect human reproductive function. Few studies have investigated the effect of BPA exposure on the primordial follicle pool. In this study, we employed a neonatal ovarian culture system comprising organ obtained from female C57BL/6 pups on postnatal day 4 to assess the effect of BPA on the primordial follicle pool. Ovaries were cultured with BPA (0.1 ?M, physiological concentration found in children's blood, and 1 ?M, 10 ?M) or vehicle for 10 days. Our study revealed that the primary follicle number increased during the early time points (?5 days), and we observed a reduction in the primordial follicle pool at a later time point (day 10). This reduction at day 10 was due to increased follicle activation and reduced follicle atresia, as determined by immunohistochemistry for Ki-67 and active caspase-3. Then we examined the phosphatidylinositol-3-kinase (PI3K)/Akt pathway, which is known to be important for early follicle growth. BPA exposure induced the upregulation of the PI3K/Akt pathway, which was reversed by concomitant treatment with PI3K inhibitor. Our results reveal a novel mechanism for BPA-induced primordial follicle activation that involves the PI3K/Akt pathway.
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Bevacizumab increases the risk of severe congestive heart failure in cancer patients: an up-to-date meta-analysis with a focus on different subgroups.
Clin Drug Investig
PUBLISHED: 08-07-2014
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Congestive heart failure (CHF) risk with bevacizumab in breast cancer has been previously investigated in a meta-analysis, but its incidence and the risk of CHF in other tumor types remain unclear. Thus, we performed this meta-analysis to gather current data and evaluate the risk of CHF with bevacizumab in cancer patients, with a focus on different subgroups.
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[Comparative study on remote sensing invertion methods for estimating winter wheat leaf area index].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 08-07-2014
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The present study aims to explore capability of different methods for winter wheat leaf area index inversion by integrating remote sensing image and synchronization field experiment. There were four kinds of LAI inversion methods discussed, specifically, support vector machines (SVM), discrete wavelet transform (DWT), continuous wavelet transform (CWT) and principal component analysis (PCA). Winter wheat LAI inversion models were established with the above four methods respectively, then estimation precision for each model was analyzed. Both discrete wavelet transform method and principal component analysis method are based on feature extraction and data dimension reduction, and multivariate regression models of the two methods showed comparable accuracy (R2 of DWT and PCA model was 0. 697 1 and 0. 692 4 respectively; RMSE was 0. 605 8 and 0. 554 1 respectively). While the model based on continuous wavelet transform suffered the lowest accuracy and didn't seem to be qualified to inverse LAL It was indicated that the nonlinear regression model with support vector machines method is the most eligible model for estimating winter wheat LAI in the study area.
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The possibility of traditional chinese medicine as maintenance therapy for advanced nonsmall cell lung cancer.
Evid Based Complement Alternat Med
PUBLISHED: 08-04-2014
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Lung cancer has become the leading cause of cancer deaths, with nonsmall cell lung cancer (NSCLC) accounting for around 80% of lung cancer cases. Chemotherapy is the main conventional therapy for advanced NSCLC. However, the disease control achieved with classical chemotherapy in advanced NSCLC is usually restricted to only a few months. Thus, sustaining the therapeutic effect of first-line chemotherapy is an important problem that requires study. Maintenance therapy is given for patients with advanced NSCLC if three is no tumor progression after four to six cycles of first-line platinum-based chemotherapy. However, selection of appropriate maintenance therapy depends on several factors, while traditional Chinese medicine (TCM) as maintenance therapy is recommended for all kinds of patients. It has been demonstrated that TCM can prolong the survival time, improve the quality of life (QOL), and reduce the side effects for advanced NSCLC. Although the trials we searched about TCM serving as maintenance therapy is only 9 studies, the results indicate TCM can prolong the progression free survival (PFS) and improve the QOL. So it is possible for TCM to be as maintenance therapy for advanced NSCLC. More rigorous trials are required to further verify its efficacy.
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EXPLORING A TYPE OF CENTRAL PATTERN GENERATOR BASED ON HINDMARSH-ROSE MODEL: FROM THEORY TO APPLICATION.
Int J Neural Syst
PUBLISHED: 08-03-2014
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This paper proposes the idea that Hindmarsh-Rose (HR) neuronal model can be used to develop a new type of central pattern generator (CPG). Some key properties of HR model are studied and proved to meet the requirements of CPG. Pros and cons of HR model are provided. A CPG network based on HR model is developed and the related properties are investigated. We explore the bipedal primary gaits generated by the CPG network. The preliminary applications of HR model are tested on humanoid locomotion model and functional electrical stimulation (FES) walking system. The positive results of stimulation and experiment show the feasibility of HR model as a valid CPG.
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A new group of anti-lipopolysaccharide factors from Marsupenaeus japonicus functions in antibacterial response.
Dev. Comp. Immunol.
PUBLISHED: 07-28-2014
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Anti-lipopolysaccharide factors (ALFs) are a group of critical effector molecules with a broad spectrum of antimicrobial activities in crustaceans. Four groups of ALFs (A, B, C, and D) have been identified in peneaid shrimp. In the study, we identified a new group of ALFs (designated as MjALF-E) from Marsupenaeus japonicus. This new group (group E) included MjALF-E1 and E2. MjALF-E1 was highly expressed in hemocytes, heart, and intestine, whereas E2 was highly expressed in gills, stomach, and intestine. Expressions of both MjALF-E1 and E2 were upregulated by bacterial challenge. Synthesized LPS-binding domain peptides of MjALF-E1 and E2 strongly bind to bacterial cell wall components lipopolysaccharide (LPS) and peptidoglycan (PGN). The recombinant rMjALF-E2 showed relatively weak binding activity to LPS and PGN. Both synthesized peptides and rMjALF-E2 exhibited antimicrobial activity against Gram-negative bacteria, whereas rMjALF-E2 could promote the clearance of bacteria in vivo. After knockdown of MjALF-E2 and infection with Vibrio anguillarum, shrimp showed high and rapid mortality compared with GFPi shrimp. These results suggest that MjALF-Es serves a protective function against bacterial infection in shrimp.
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Composite peptide?based vaccines for cancer immunotherapy (Review).
Int. J. Mol. Med.
PUBLISHED: 07-17-2014
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The use of peptide?based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide?based vaccines are easily synthesized and chemically stable entities, and of note, they are absent of oncogenic potential. However, their application is more complicated as the success of an effective peptide?based vaccine is determined by numerous parameters. The success thus far has been limited by the choice of tumor antigenic peptides, poor immunogenicity and incorporation of strategies to reverse cancer?mediated immune suppression. In the present review, an overview of the mechanisms of peptide?based vaccines is provided and antigenic peptides are categorized with respect to their tissue distribution in order to determine their usefulness as targets. Furthermore, certain approaches are proposed that induce and maintain T cells for immunotherapy. The recent progress indicates that peptide?based vaccines are preferential for targeted therapy in cancer patients.
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Synthesis, photophysical and electrochemical properties of two novel carbazole-based dye molecules.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 07-17-2014
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Two carbazole-based dye molecules: 3-(6-benzothiazol-2-yl-9H-hexylcarbazole-3-yl)-2-cyano-acylic acid (D3) and 3-[5-(6-benzothiazol-2-yl-9H-hexylcarbazole-3-yl)-thiophen-2-yl]-2-cyan-acylic acid (D4) were synthesized by an approach from carbazole derivate using Vilsmeier-Haack, Suzuki cross-coupling and Knoevenagel reactions. Their physical and electrochemical properties were investigated. D3 and D4 exhibit different optical properties, such as UV absorption, photoluminescence, fluorescence quantum yield and fluorescence lifetime in different solvents. Compared with D3 without a thiophene unit, the maximum absorption wavelength of D4 red-shift obviously and its fluorescence intensity is also enhanced. A shift of the EHOMO and ELUMO is observed for D3 (EHOMO=2.06 V, ELUMO=-1.39 V vs. NHE) and D4 (EHOMO=1.73 V, ELUMO=-1.33 V vs. NHE). D3 and D4 can be used as dyes for dye-sensitized solar cells (DSSCs) with TiO2 nanomaterial because their EHOMO are lower than the conduction band edge of TiO2 [-0.5 V (vs. NHE)] and their ELUMO are higher than the I(3-)/I(-) redox potential [0.42 V (vs. NHE)].
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Expression and purification of soluble human cystatin C in Escherichia coli with maltose-binding protein as a soluble partner.
Protein Expr. Purif.
PUBLISHED: 07-16-2014
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Human cystatin C (CYSC) is a 13-kDa endogenous cysteine proteinase inhibitor and was investigated as a replacement for creatinine as a marker of renal function. However, expressing recombinant CYSC is difficult in Escherichia coli because of resulting low yield and insufficient purity and insolubility. Here, we cloned and fused CYSC to the C-terminus of three soluble partners - maltose-binding protein (MBP), glutathione S-transferase (GST) and translation initiation factor 2 domain I (IF2) - to screen for their ability to improve the solubility of recombinant CYSC when expressed in E. coli. MBP was best at enhancing the soluble expression of CYSC, with soluble fractions accounting for 92.8±3.11% of all proteins. For scaled production, we purified the de-tagged CYSC by using a 3C protease-cleaved MBP-T3-CYSC fused protein with immobilized metal affinity chromatography and cation-affinity purification. The molecular weights of the de-tagged CYSC and human natural CYSC were similar, and the former could react specifically with CYSC polyclonal antibody. Moreover, the de-tagged CYSC displayed full biological activity against papain and cathepsin B, which was very similar to that of the human natural CYSC protein standard. We provide a method to produce large amounts of soluble recombinant human CYSC in E. coli.
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The Therapeutic Potential of Rho Kinase Inhibitor Fasudil Derivative FaD-1 in Experimental Autoimmune Encephalomyelitis.
J. Mol. Neurosci.
PUBLISHED: 07-14-2014
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Although therapeutic potential of fasudil in EAE is promising, action mechanism and clinical limitations are still not fully understood and resolved. In this study, we observed the therapeutic potential of a novel Rho kinase (ROCK) inhibitor FaD-1, a fasudil derivative, and explored possible mechanism in MOG35-55-induced EAE. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG35-55) immunization. The pathology of spinal cord was measured by immunohistochemistry and neurological impairment was evaluated using clinical scores. FaD-1, as a novel ROCK inhibitor, inhibited the expression of ROCK II that is mainly expressed in the CNS. We show here that FaD-1 ameliorates the neurological defects and the severity of MOG-induced EAE in mice, accompanied by the protection of demyelination and the inhibition of neuroinflammation in spinal cord of EAE. In addition, FaD-1 dampened TLR2 and TLR4 signaling as well as Th1 (IFN-?) and Th17 (IL-17) responses in spinal cord of EAE. FaD-1 also prevented the expression of iNOS and production of inflammatory cytokine IL-1?, IL-6, and TNF-? which are specific markers for M1 inflammatory microglia/macrophages. This study highlights the therapeutic potential of FaD-1 as a ROCK inhibitor for the treatment of human autoimmune diseases with both inflammatory and autoimmune components.
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Incidence and Mortality Prognosis of Dysnatremias in Neurologic Critically Ill Patients.
Eur. Neurol.
PUBLISHED: 07-03-2014
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Background: Dysnatremia, which is associated with increased mortality in general intensive care units (ICU), has not been thoroughly studied in neurologic ICU (NICU). Methods: Prevalence of dysnatremia was retrospectively assessed. The multivariable binary logistic regression model was used to determine the influence of dysnatremia on mortality. Results: Of 519 patients, 106 (20.4%) were admitted with hyponatremia and 177 (34.10%) with hypernatremia. Hypernatremia was detected in 69 (13.29%) patients on admission to NICU and in 108 patients (20.81%) during the ICU stay. However, the incidence of dysnatremia did not differ across the neurological categories (p = 0.4690). ICU stay in patients with acquired hypernatremia (22.3 ± 25.35 days) was longer than those with admission hypernatremia (13.5 ± 12.8 days) or with consistent normonatremia (16.16 ± 20.06 days). The other indicators such as Acute Physiology and Chronic Health Evaluation II, Glasgow Coma Scale score, urinary catheterization, and incidence of pneumonia were also associated with the serum sodium concentrations. Hypernatremia both on admission and acquired in NICU could significantly differentiate between survivors and nonsurvivors (p = 0.002 and <0.0001). However, only NICU-acquired hypernatremia was the independent risk factor for mortality with high sensitivity (p = 0.000). Conclusions: Dysnatremia is more common in NICU, whereas only acquired-hypernatremia was independently associated with outcome. © 2014 S. Karger AG, Basel.
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Incidence and risk of severe infections associated with anti-epidermal growth factor receptor monoclonal antibodies in cancer patients: a systematic review and meta-analysis.
BMC Med
PUBLISHED: 06-18-2014
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BackgroundAnti-epidermal growth factor receptor (EGFR)-monoclonal antibodies (MoAbs) have been widely used in a variety of malignancies. Severe infections (¿grade 3) are potentially life-threatening adverse events with these drugs. However, the contribution of anti-EGFR MoAbs to infections is still unknown. We performed this meta-analysis to determine the overall incidence and risk of severe infections in cancer patients treated with these drugs.MethodsThe databases of PubMed and abstracts presented at oncology conferences and published in the proceedings were searched for relevant studies from January 2000 to May 2014. Summary incidences, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies.ResultsA total of 14,066 patients from 26 randomized controlled trials (RCTs) were included. The use of anti-EGFR-MoAbs significantly increased the risk of developing severe infections (RR 1.34, 95%CI: 1.10 to 1.62, P =0.003) in cancer patients, but not for fatal infections (RR 1.62, 95%CI: 0.81 to 3.26, P =0.18). Meta-regression indicated the infections might possibly occur early in the treatment with anti-EGFR MoAbs. On sub-group analysis, the risk of severe infections significantly varied with tumor type (P =0.001). When stratified by specific anti-EGFR MoAbs, a significantly increased risk of infections with cetuximab was observed (P <0.001), but not for panitumumab (P =0.98). Additionally, the use of anti-EGFR MoAbs significantly increased the risk of severe infections when used in conjunction with cisplatin (RR 1.48, 95% CI 1.22 to 1.79, P <0.001) or irinotecan (RR 1.53, 95% CI 1.12 to 2.10, P =0.008).When stratified by specific infectious events, anti-EGFR-MoAbs significantly increased the risk of developing severe sepsis (RR 4.30, 95%CI: 1.80 to 10.27; P =0.001).ConclusionsAnti-EGFR MoAbs treatment significantly increases the risk of developing severe infectious events in cancer patients. The risk may vary with tumor types. Clinicians should be aware of the risks of severe infections with the administration of these drugs in cancer patients.
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DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotype.
J. Autoimmun.
PUBLISHED: 06-12-2014
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Systemic lupus erythematosus (SLE) is an autoimmune disease well known for its clinical heterogeneity, and its etiology secondary to a cross-talk involving genetic predisposition and environmental stimuli. Although genome-wide analysis has contributed greatly to our understanding of the genetic basis of SLE, there is increasing evidence for a role of epigenetics. Indeed, recent data have demonstrated that in patients with SLE, there are striking alterations of DNA methylation, histone modifications, and deregulated microRNA expression, the sum of which contribute to over-expression of select autoimmune-related genes and loss of tolerance. To address this issue at the level of clinical phenotype, we performed DNA methylation, mRNA and microRNA expression screening using high-throughput sequencing of purified CD4+ T cells from patients with SLE, compared to age and sex matched controls. In particular, we studied 42 patients with SLE and divided this group into three clinical phenotypes: a) the presence of skin lesions without signs of systemic pathology; b) skin lesions but also chronic renal pathology; and c) skin lesions, chronic renal pathology and polyarticular disease. Interestingly, and as expected, sequencing data revealed changes in DNA methylation in SLE compared to controls. However, and more importantly, although there were common methylation changes found in all groups of SLE compared to controls, there was specific DNA methylation changes that correlated with clinical phenotype. These included changes in the novel key target genes NLRP2, CD300LB and S1PR3, as well as changes in the critical pathways, including the adherens junction and leukocyte transendothelial migration. We also noted that a significant proportion of genes undergoing DNA methylation changes were inversely correlated with gene expression and that miRNA screening revealed the existence of subsets with changes in expression. Integrated analysis of this data highlights specific sets of miRNAs controlled by DNA methylation, and genes that are altered by methylation and targeted by miRNAs. In conclusion, our findings suggest select epigenetic mechanisms that contribute to clinical phenotypes and further shed light on a new venue for basic SLE research.
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Stereoselective degradation of flutriafol and tebuconazole in grape.
Environ Sci Pollut Res Int
PUBLISHED: 06-08-2014
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The stereoselective dissipation of flutriafol and tebuconazole in grape had been studied. A simple and sensitive method for determination of flutriafol and tebuconazole enantiomers in grape was developed by high-performance liquid chromatography on a cellulose tris(3-chloro-4-methylphenylcarbamate) column. The limits of quantification for flutriafol and tebuconazole in grape were 0.033 and 0.043 mg kg(-1), respectively. The dissipations of flutriafol and tebuconazole stereoisomers in grape followed first-order kinetics (R (2)?>?0.93). The stereoisomers of flutriafol and tebuconazole were enantioselectively degraded in grape, and tebuconazole was more enantioselective than flutriafol. The half-life of (-)-tebuconazole was 5.2 days and shorter than (+)-tebuconazole with half-life of 6.4 days. The (-)-flutriafol was also preferentially degraded in grape, the half-lives of which were 6.59 and 6.98 days for (-) and (+)-flutriafol, respectively. The enantiomeric ratio value of the two fungicides was nearly 1.0 at the 1st day and increased to 1.143 for flutriafol and 2.015 for tebuconazole at the 28th day. The stereoselective dissipations could provide a reference to fully evaluate the risks of two important chiral triazole fungicides.
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miR-126 inhibits cell growth, invasion, and migration of osteosarcoma cells by downregulating ADAM-9.
Tumour Biol.
PUBLISHED: 05-17-2014
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Osteosarcoma (OS) has become one of the most common primary malignant tumors in the children and adolescents with a poor prognosis mainly due to high metastasis. A disintegrin and metalloprotease 9 (ADAM-9) plays a role in tumorigenesis, invasion, and metastasis in several tumors. miR-126 has been reported to be downregulated in OS tumor. However, the involvement of ADAM-9 in the pathology of OS and the relationship between miR-126 and ADAM-9 in OS cells remain unclear. In this study, using quantitative reverse-transcribed PCR (qRT-PCR) analysis on 37 pairs of OS tumors and matched adjacent normal bone tissues, we found that ADAM-9 is significantly upregulated, while miR-126 is downregulated in human OS tumors. Association analysis revealed that upregulation of ADAM-9 and downregulation of miR-126 are significantly involved in advanced clinical stage development and distant metastasis. Luciferase reporter assay revealed that miR-126 could directly target ADAM-9 3' untranslated region (UTR) and inhibit its expression in U2OS and MG-63 cells. Functional experiments revealed that downregulating ADAM-9 by miR-126 inhibited cellular growth, invasion, and migration in U2OS and MG-63 cells. In rescue experiments, restored ADAM-9 expression attenuated miR-126-mediated suppression, while knockdown of ADAM-9 by small interfering RNA (siRNA) represented similar results with miR-126-mediated tumor suppression in U2OS cells. Taken together, our data indicated that miR-126 inhibits cell growth, invasion, and migration of OS cells by downregulating ADAM-9.
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Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor.
Cancer Cell
PUBLISHED: 05-09-2014
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Oncoproteins and tumor suppressors antagonistically converge on critical nodes governing neoplastic growth, invasion, and metastasis. We discovered that phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific serine or threonine residues creates binding sites for the COP1 tumor suppressor protein, which is an ubiquitin ligase component, leading to their destruction. In the case of ETS1, however, phosphorylation of a neighboring tyrosine residue by Src family kinases disrupts COP1 binding, thereby stabilizing ETS1. Src-dependent accumulation of ETS1 in breast cancer cells promotes anchorage-independent growth in vitro and tumor growth in vivo. These findings expand the list of potential COP1 substrates to include proteins whose COP1-binding sites are subject to regulatory phosphorylation and provide insights into transformation by Src family kinases.
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Adding peginterferon to entecavir for HBeAg-positive chronic hepatitis B: A multicentre randomized trial (ARES study).
Hepatology
PUBLISHED: 05-01-2014
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Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long-term therapy may be required. We investigated whether adding-on peginterferon (PEG-IFN) to ETV therapy enhances serologic response rates. In this global investigator-initiated, open-label, multicentre randomized trial, HBeAg-positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5mg/day) and were randomized in a 1:1 ratio to either PEG-IFN add-on therapy (180µg/week) from week 24 to 48 (n=85), or to continue ETV monotherapy (n=90). Response was defined as HBeAg loss with HBV DNA <200 IU/mL at week 48. Responders discontinued ETV at week 72. All patients were followed until week 96. Response was achieved in 16/85 (19%) patients allocated to the add-on arm versus 9/90 (10%) in the monotherapy arm (p=0.095). Adjusted for HBV DNA levels prior to randomized therapy, PEG-IFN add-on was significantly associated with response (OR 4.8, 95%CI: 1.6 - 14.0, p=0.004). Eleven (13%) of add-on treated patients achieved disease remission after ETV cessation, versus 2/90 (2%) of patients treated with monotherapy (p=0.007), which was 79% (11/14) versus 25% (2/8) of those who discontinued ETV (p=0.014). At week 96, 22 (26%) patients assigned add-on versus 12 (13%) assigned monotherapy achieved HBeAg seroconversion (p=0.036). PEG-IFN add-on led to significantly more decline in HBsAg, HBeAg and HBV DNA (all p<0.001). Combination therapy was well-tolerated. Conclusion: Although the primary endpoint was not reached, 24 weeks of PEG-IFN add-on therapy led to a higher proportion of HBeAg response compared to ETV monotherapy. Add-on therapy resulted in more viral decline and appeared to prevent relapse after stopping ETV. Hence PEG-IFN add-on therapy may facilitate the discontinuation of nucleos(t)ide analogues. http://www.Clinicaltrials.gov number: NCT00877760. (Hepatology 2014;).
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A four-long non-coding RNA signature in predicting breast cancer survival.
J. Exp. Clin. Cancer Res.
PUBLISHED: 04-27-2014
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BackgroundMany long non-coding RNAs(lncRNAs) have been found to be a good marker for several tumors. Using lncRNA-mining approach, we aimed to identify lncRNA expression signature that can predict breast cancer patient survival.MethodsWe performed LncRNA expression profiling in 887 breast cancer patients from Gene Expression Omnibus (GEO) datasets. The association between lncRNA signature and clinical survival was analyzed using the training set(n = 327,from GSE 20685). The validation for the association was performed in another three independent testing sets(252 from GSE21653, 204 from GSE12276, and 104 from GSE42568).ResultsA set of four lncRNA genes (U79277, AK024118, BC040204, AK000974) have been identified by the random survival forest algorithm. Using a risk score based on the expression signature of these lncRNAs, we separated the patients into low-risk and high-risk groups with significantly different survival times in the training set. This signature was validated in the other three cohorts. Further study revealed that the four-lncRNA expression signature was independent of age and subtype. Gene Set Enrichment Analysis (GSEA) suggested that gene sets were involved in several cancer metastasis related pathways.ConclusionsThese findings indicate that lncRNAs may be implicated in breast cancer pathogenesis. The four-lncRNA signature may have clinical implications in the selection of high-risk patients for adjuvant therapy.
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Enantioselective Degradation of Metalaxyl in Grape, Tomato, and Rice Plants.
Chirality
PUBLISHED: 04-26-2014
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Enantioselective biodegradation of chiral pesticide metalaxyl in grape, tomato, and rice plants under field conditions were studied. Metalaxyl enantiomers were completely separated with a resolution (Rs) of 5.01 by high-performance liquid chromatography (HPLC) based on a cellulose tris (3-chloro-4-methyl phenyl carbamate) chiral column (Lux Cellulose-2). Metalaxyl enantiomers from matrixes were extracted by acetonitrile and purged using Cleanert Alumina-A solid phase extraction (SPE). The linearity, recovery, precision, sensitivity, and matrix effect of the method were assessed. The result showed that significant stereoselectivity occurred in grape, tomato, and rice plants. In grape, (+)-S-metalaxyl with a half-life of 5.5 d degraded faster than (-)-R-metalaxyl with that of 6.9 d, and the enantiomer fraction (EF) value reached 0.37 at 21 d. The same enantioselectivity was observed in tomato, and the half-life was 2.2 d for the S-enantiomer and 3.0 d for the R-enantiomer. The EF values decreased from 0.49 of 0 d to 0.26 of 14 d. On the other hand, a preferential degradation of the R-form was found in rice plants, with an EF value of 0.70 at 14 d, and the corresponding half-life was 2.3 d for the R-form and 2.8 d for the S-form. Chirality 00:000-000, 2014. © 2014 Wiley Periodicals, Inc.
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T-cell-associated cellular immunotherapy for lung cancer.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 04-22-2014
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The aim of the present study was to discuss recent findings on the role of T cells in lung cancer to provide information on their potential application, especially in cellular immunotherapy.
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Effects of Uric Acid on Hearts of Rats with Chronic Kidney Disease.
Am. J. Nephrol.
PUBLISHED: 04-22-2014
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Aims: To study the effects of uric acid on cardiac lesions and its possible mechanism by establishing an early-stage CKD animal model with hyperuricemia. Allopurinol was used to see whether it could reduce cardiac lesions. Methods: The experimental rats were randomly divided into 4 groups (n = 15): Group A (sham-operative group), Group B (CKD group), Group C (CKD with hyperuricemia group), Group D (CKD with hyperuricemia + allopurinol group). After 16 weeks, the rats were sacrificed and blood samples were collected for detection of Scr, SUA, hs-CRP and IL-6. Kidney and heart tissues were pathologically examined. The collagen I of heart tissues was examined by immunohistochemistrical methods. Results: Obvious pathological changes could be observed in Group C. However, compared to Group C, the pathological changes in Group D were lighter. The proportion of collagen I positive area (PCIPA) in Group C was significantly higher than that in Group A, B and D. Univariate analysis showed that the SUA level had a significant positive correlation with PCIPA in myocardium. IL-6 and hs-CRP levels in Group C were significantly higher than in Group A, B and D. Univariate analysis showed that the SUA level had a significant positive correlation with IL-6 and hs-CRP, and PCIPA in myocardium had a significant positive correlation with hs-CRP and IL-6 levels. Conclusions: There were obvious cardiac lesions in early-stage CKD rats with hyperuricemia, and the severity of cardiac lesions was positively related to the level of SUA. Micro-inflammation might be one mechanism causing cardiac lesions. Allopurinol could alleviate cardiac lesions in early-stage CKD rats by lowering the SUA level, which, in turn, could reduce the severity of micro-inflammation. © 2014 S. Karger AG, Basel.
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Macrophage activation syndrome in Kawasaki Disease: More common than we thought?
Semin. Arthritis Rheum.
PUBLISHED: 04-11-2014
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To analyze the clinical characteristics, treatment, and outcomes of Kawasaki Disease (KD) patients associated with macrophage activation syndrome (MAS) and to compare two diagnostic standards (the HLH 2009 and Ravelli?s criteria).
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Homologous recombination efficiency enhanced by inhibition of MEK and GSK3?
Genesis
PUBLISHED: 02-10-2014
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Homologous recombination in embryonic stem cells (ESCs) is widely utilized in genome engineering, particularly in the generation of gene targeted mice. However, genome engineering is often plagued by the problem of low homologous recombination efficiency. In this study, we developed a novel method to increase the efficiency of homologous recombination in ESCs by changing its culture conditions. By comparing the efficiency of different ESCs in various culture conditions, we determined that chemicals that inhibit the MEK and GSK3? pathways (2i condition) enhance homologous recombination and eliminate differences in efficiencies among cell lines. Analysis of gene expression patterns in ESCs maintained in different culture conditions has identified several homologous recombination-related candidates, including the pluripotent markers Eras and Tbx3. The results of this study suggest that homologous recombination is associated with ESC pluripotency. genesis 00:1-8, 2014. © 2014 Wiley Periodicals, Inc.
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Methotrexate intercalated layered double hydroxides with different particle sizes: structural study and controlled release properties.
Colloids Surf B Biointerfaces
PUBLISHED: 02-08-2014
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To study the influence of particle size on release properties, drug efficacy and other properties, a series of methotrexate intercalated layered double hydroxides (MTX/LDHs) nanohybrids with different particle sizes were synthesized through traditional coprecipitation method, by using the mixture of water and polyethylene glycol (volume ratio is 3:1) as solvent. The relationship between particle size and hydrothermal treatment conditions (i.e., time and temperature) had been systematically investigated, and the results indicate that the particle size can be precisely controlled between 70 and 300 nm. Elemental C/H/N and inductive coupled plasma (ICP) analysis indicated that different hydrothermal treatment almost has no effect on compositions of the nanohybrids. X-ray diffraction (XRD) patterns and fourier transform infrared spectroscopy (FTIR) investigations manifested the successful intercalation of MTX anions. MTX/LDHs particles exhibited hexagonal platelet morphology with round corner, due to the adsorption of MTX anions on positively charged LDHs surface. In addition, the crystallinity of MTX/LDHs increased with the particle diameters and the thermal stability of MTX anions was enhanced by holding together with LDHs layers. The in vitro release showed that bigger particles have much longer release duration, and the bioassay tests indicated that bigger particles are more efficient in the suppression of the tumor cells.
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Benign prostatic hyperplasia: prostatic arterial embolization versus transurethral resection of the prostate--a prospective, randomized, and controlled clinical trial.
Radiology
PUBLISHED: 01-31-2014
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To compare prostatic arterial embolization (PAE) and transurethral resection of the prostate (TURP) in the care of patients with benign prostatic hyperplasia (BPH).
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Higher blood pressure control rate in a real life management program provided by the community health service center in China.
BMC Public Health
PUBLISHED: 01-29-2014
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Community health service center (CHSC) in China is always regarded as a good facility of primary care, which plays an important role in chronic non-communicable disease management. This study aimed to investigate the blood pressure (BP) control rate in a real life CHSC-based management program and its determinants.
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Role of mitofusin-2 in high mobility group box-1 protein-mediated apoptosis of T cells in vitro.
Cell. Physiol. Biochem.
PUBLISHED: 01-29-2014
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Background: High mobility group box-1 protein (HMGB1), a ubiquitous nuclear protein, which is recognized as a danger-associated molecular pattern (DAMP) triggering activation of the innate immune system. Previous studies have shown that HMGB1 also plays a role in T cell-mediated immunity, but the effect of HMGB1 on apoptosis of T cells and its precise mechanism remain to be determined. Methods: Two kinds of apoptosis assay techniques were used, i.e., Annexin V-FITC conjunction with PI to identify early apoptotic cells, Hoechst 33342 staining for double-stranded DNA to observe nuclear fragmentation or apoptotic body. The activation status of caspase-3, caspase-8, as well as caspase-9 was examined by colorimetric assay. The dynamic changes in intracellular calcium concentration ([Ca(2+)]i) was monitored by flow cytometry. Overexpression of Mfn2 was preformed by lentiviral vector transfection. The mRNA and protein levels of Mfn2 were determined by RT-PCR and Western-blotting. Results: Treatment of Jurkat T cells with recombinant human HMGB1 (rhHMGB1) causes a significant dose-dependent increase in percentage of apoptotic cells. When T cells are incubated with HMGB1 they express decreased mitochondria fusion-related protein mitofusin-2 (Mfn2) and activate mitochondrial apoptotic pathway via elevation of [Ca(2+)]i, Bax insertion, and activation of caspase. Furthermore, overexpression of Mfn2 ameliorates the apoptosis of T cells induced by HMGB1. This occurs at least partly through Mfn2 keeps Ca(2+) homeostasis in T cells evidenced by monitoring [Ca(2+)]i dynamics. Conclusion: HMGB1 can trigger apoptosis of T lymphocytes through mitochondrial death pathway associated with [Ca(2+)]i elevation. Mfn2 plays a pivotal role in this process, and it might be a novel therapeutic target in T cell apoptosis related disorders. © 2014 S. Karger AG, Basel.
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Sick sinus syndrome associated with hypopituitarism: a case report and literature review.
J Biomed Res
PUBLISHED: 01-16-2014
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Though an association between autoimmune diseases and sick sinus syndrome has been reported, there has been no report on the association of hypopituitarism and sick sinus syndrome. Herein, we provide the first case report of hypopituitarism accompanying sick sinus syndrome in a 51-year-old woman presented to our hospital with syncope due to cardiac arrest. The patient was successfully managed by pacemaker installation and hormone replacement therapy.
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Computational approaches for predicting biomedical research collaborations.
PLoS ONE
PUBLISHED: 01-01-2014
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Biomedical research is increasingly collaborative, and successful collaborations often produce high impact work. Computational approaches can be developed for automatically predicting biomedical research collaborations. Previous works of collaboration prediction mainly explored the topological structures of research collaboration networks, leaving out rich semantic information from the publications themselves. In this paper, we propose supervised machine learning approaches to predict research collaborations in the biomedical field. We explored both the semantic features extracted from author research interest profile and the author network topological features. We found that the most informative semantic features for author collaborations are related to research interest, including similarity of out-citing citations, similarity of abstracts. Of the four supervised machine learning models (naïve Bayes, naïve Bayes multinomial, SVMs, and logistic regression), the best performing model is logistic regression with an ROC ranging from 0.766 to 0.980 on different datasets. To our knowledge we are the first to study in depth how research interest and productivities can be used for collaboration prediction. Our approach is computationally efficient, scalable and yet simple to implement. The datasets of this study are available at https://github.com/qingzhanggithub/medline-collaboration-datasets.
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Functional short tandem repeat polymorphism of PTPN11 and susceptibility to hepatocellular carcinoma in Chinese populations.
PLoS ONE
PUBLISHED: 01-01-2014
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PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Loss of Shp2 promotes hepatocellular carcinoma (HCC), suggesting that PTPN11 functions as a tumor suppressor in HCC tumorgenesis. The aim of this study was to evaluate the effects of the short tandem repeat (STR) polymorphism (rs199618935) within 3'UTR of PTPN11 on HCC susceptibility in Chinese populations.
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Intratumor IL-17-positive mast cells are the major source of the IL-17 that is predictive of survival in gastric cancer patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Interleukin-17 (IL-17) is prevalent in tumor tissue and suppresses effective anti-tumor immune responses. However, the source of the increased tumor-infiltrating IL-17 and its contribution to tumor progression in human gastric cancer remain poorly understood. In this study, we enrolled 112 gastric cancer patients, immunofluorescence was used to evaluate the colocalization of CD3, CD4, CD56, CD20, CD68, and mast cell tryptase (MCT) with IL-17. Immunohistochemistry was used to evaluate the distribution of microvessel density (CD34), CD66b(+), CD68(+), and FoxP3(+) cells in different microanatomical areas. Prognostic value was determined by Kaplan-Meier analysis and a Cox regression model. The results showed that mast cells, but not T cells or macrophages, were the predominant cell type producing IL-17 in gastric cancer. Significant positive correlations were detected between densities of mast cell-derived IL-17 and microvessels, neutrophils, and regulatory T cells (Tregs). Furthermore, we found that the majority of vascular endothelial cells expressing Interleukin-17 receptor (IL-17R). Kaplan-Meier analysis revealed that increasing intratumor infiltrated mast cells and IL-17(+) cells, as well as MCT(+) IL-17(+) cells, were significantly associated with worse overall survival. These findings indicated that mast cells were the major source of IL-17 in gastric cancer, and intratumor IL-17 infiltration may have promoted tumor progression by enhancing angiogenesis in the tumor microenvironment through the axis of IL-17/IL-17R. IL-17-positive mast cells showed a prognostic factor in gastric cancer, indicating that immunotherapy targeting mast cells might be an effective strategy to control intratumor IL-17 infiltration, and consequently reverse immunosuppression in the tumor microenvironment, facilitating cancer immunotherapy.
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A genetic variant rs1801274 in FCGR2A as a potential risk marker for Kawasaki disease: a case-control study and meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent genome-wide association study found rs1801274, a functional single nucleotide polymorphism (SNP) in IgG receptor gene FCGR2A, was associated with increased risk of Kawasaki disease (KD). However, subsequent studies on the role of this SNP were limited and controversial.
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What is Visualize?

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

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