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Find video protocols related to scientific articles indexed in Pubmed.
[Dynamic changes of intestinal 16S rDNA metagenome in 5 infants.]
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 11-20-2014
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To investigate the dynamic changes of intestinal 16S rDNA metagenome in healthy infants.
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Enhanced four-wave mixing efficiency in four-subband semiconductor quantum wells via Fano-type interference.
Opt Express
PUBLISHED: 11-18-2014
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We propose and analyze an efficient way to enhance four-wave mixing (FWM) signals in a four-subband semiconductor quantum well via Fano-type interference. By using Schrödinger-Maxwell formalism, we derive explicitly analytical expressions for the input probe pulse and the generated FWM field in linear regime under the steady-state condition. With the aid of interference between two excited subbands tunneling to the common continuum, the efficiency to generate FWM field is found to be significantly enhanced, up to 35%. More interestingly, a linear growth rate in the FWM efficiency is demonstrated as the strength of Fano-type interference increases in presence of the continuum states, which can be maintained for a certain propagation distance (i.e., 50?m).
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[Advances of Driver Gene and Targeted Therapy of Non-small Cell Lung Cancer].
Zhongguo Fei Ai Za Zhi
PUBLISHED: 10-25-2014
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Lung cancer is the leading cause of cancer-related mortality in the worldwide. The discovery of drive gene makes tumor treatment is no longer "one-size-fits-all". Targeted therapy to change the present situation of cancer drugs become "bullet" with eyes, the effect is visible and bring a revolution in the treatment of lung cancer. The diver gene and targeted therapy have became the new cedule of non-small cell lung cancer (NSCLC). Society of Clinical Oncology (ASCO) has showed 11 kinds of diver genes. Here, we review the functional and structural characteristics and the targeted therapy in the 11 kinds of driver gene mutations.
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Serum Metabolomics Study and Eicosanoid Analysis of Childhood Atopic Dermatitis Based on Liquid Chromatography-Mass Spectrometry.
J. Proteome Res.
PUBLISHED: 10-16-2014
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Atopic dermatitis (AD) is the most common inflammatory skin disease in children. In the study, ultra high performance liquid chromatography-mass spectrometry was used to investigate serum metabolic abnormalities of AD children. Two batch fasting sera were collected from AD children and healthy control; one of them was for nontargeted metabolomics analysis, the other for targeted eicosanoids analysis. AD children were divided into high immunoglobulin E (IgE) group and normal IgE group. On the basis of the two analysis approaches, it was found that the differential metabolites of AD, leukotriene B4, prostaglandins, conjugated bile acids, etc., were associated with inflammatory response and bile acids metabolism. Carnitines, free fatty acids, lactic acid, etc., increased in the AD group with high IgE, which revealed energy metabolism disorder. Amino acid metabolic abnormalities and increased levels of Cytochrome P450 epoxygenase metabolites were found in the AD group with normal IgE. The results provided a new perspective to understand the mechanism and find potential biomarkers of AD and may provide a new reference for personalized treatment.
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Proton-insertion-enhanced pseudocapacitance based on the assembly structure of tungsten oxide.
ACS Appl Mater Interfaces
PUBLISHED: 10-14-2014
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The capacitances of supercapacitors with carbon and metal oxides as electrodes are usually associated with the available surface areas of the electrode materials. However, in this paper, we report that proton insertion, an unusual capacitive mechanism, may effectively enhance the capacitance of metal oxides with low surface area but specific structures. Tungsten trioxide (WO3) as the electrode material for supercapacitors has always suffered from low capacitance. Nevertheless, enhanced by the proton insertion mechanism, we demonstrate that electrodes fabricated by an assembly structure of hexagonal-phase WO3 (h-WO3) nanopillars achieve a high capacitance of up to 421.8 F g(-1) under the current density of 0.5 A g(-1), which is the highest capacitance achieved with pure WO3 as the electrodes so far, to the best of our knowledge. Detailed analyses indicate that proton insertion dominates the electrochemical behavior of h-WO3 and plays the key role in reaching high capacitance by excluding other mechanisms. In addition, a thorough investigation on the temperature-dependent electrochemical performance reveals excellent performance stability at different temperatures. This study provides a new approach to achieving high capacitance by effective proton insertion into ordered tunnels in crystallized metal oxides, which is primarily important for the fabrication of compact high-performance energy storage devices.
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[Effect and clinical significance of glucocorticoid on CD4+CD25+ regulatory T cells in patients with hepatitis B virus-related pre-liver failure].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-23-2014
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To investigate the effect and clinical significance of glucocorticoid on CD4+CD25+ regulatory T cells (Tregs) in patients with hepatitis B virus (HBV)-related pre-liver failure.
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[Function of CD4(+) CD25(+) regulatory T cells in Henoch-Schonlein purpura nephritis in children].
Zhonghua Er Ke Za Zhi
PUBLISHED: 09-17-2014
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To investigate the levels and functions of CD4(+)CD25(+) regulatory T cells and specific transcription factor Foxp3 and Th17 cells related cytokine in peripheral blood mononuclear cells (PBMC) and renal tissues, and explore their roles in pathogenesis of Henoch-Schonlein purpura nephropathy (HSPN) in children.
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[Preparation of elastic porous cell scaffold fabricated with combined polydimethylsiloxane (PDMS) and hydroxyapatite (HA)].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 09-16-2014
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Polydimethylsiloxane (PDMS) and hydroxyapatite (HA) were combined in our laboratory to fabricate an elastic porous cell scaffold with pore-forming agent, and then the scaffold was used as culture media for rat bone marrow derived mesenchymal stem cells (rBMSCs). Different porous materials (square and circular in shape) were prepared by different pore-forming agents (NaCl or paraffin spheres) with adjustable porosity (62%-76%). The HA crystals grew on the wall of hole when the material was exposed to SBF solutions, showing its biocompatibility and ability to support the cells to attach on the materials.
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Discrimination of Chinese teas with different fermentation degrees by stepwise linear discriminant analysis (S-LDA) of the chemical compounds.
J. Agric. Food Chem.
PUBLISHED: 09-11-2014
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This study aimed to construct objective and accurate analytical models of tea categories based on their polyphenols and caffeine. A total of 522 tea samples of 4 commonly consumed teas with different fermentation degrees (green tea, white tea, oolong tea, and black tea) were analyzed by high-performance liquid chromatography (HPLC) coupled with spectrophotometry, utilizing ISO 14502, as analytical tools. The content of polyphenols and caffeine varied significantly according to differently fermented teas, indicating that these active constituents may discriminate fermentation degrees effectively. By principal component analysis (PCA) and stepwise linear discriminant analysis (S-LDA), the vast majority of tea samples could be successfully differentiated according to their chemical markers. This study yielded three discriminant functions with the capacity to simultaneously discriminate the four tea categories with a 97.8% correct rate. In classification of oolong and other teas, there were one discriminant function and two equations with best discriminant capacity. Furthermore, the classification of different degrees of fermentation of oolong and external validation achieved the desired results. It is suggested that polyphenols and caffeine are the distinct variables to establish internationally recognized models of teas.
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Piecing the puzzle together: a revisit to transcript reconstruction problem in RNA-seq.
BMC Bioinformatics
PUBLISHED: 09-10-2014
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The advancement of RNA sequencing (RNA-seq) has provided an unprecedented opportunity to assess both the diversity and quantity of transcript isoforms in an mRNA transcriptome. In this paper, we revisit the computational problem of transcript reconstruction and quantification. Unlike existing methods which focus on how to explain the exons and splice variants detected by the reads with a set of isoforms, we aim at reconstructing transcripts by piecing the reads into individual effective transcript copies. Simultaneously, the quantity of each isoform is explicitly measured by the number of assembled effective copies, instead of estimated solely based on the collective read count. We have developed a novel method named Astroid that solves the problem of effective copy reconstruction on the basis of a flow network. The RNA-seq reads are represented as vertices in the flow network and are connected by weighted edges that evaluate the likelihood of two reads originating from the same effective copy. A maximum likelihood set of transcript copies is then reconstructed by solving a minimum-cost flow problem on the flow network. Simulation studies on the human transcriptome have demonstrated the superior sensitivity and specificity of Astroid in transcript reconstruction as well as improved accuracy in transcript quantification over several existing approaches. The application of Astroid on two real RNA-seq datasets has further demonstrated its accuracy through high correlation between the estimated isoform abundance and the qRT-PCR validations.
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Primary spleen extranodal NK/T cell lymphoma, nasal type, with bone marrow involvement and CD30 positive expression: a case report and literature review.
Diagn Pathol
PUBLISHED: 09-03-2014
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Primay spleen NK/T cell lymphoma is very rare. We report a case of 39-years-old male of primary splenic NK/T cell lymphoma with bone marrow involvement and CD30 positive expression.
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[Efficacy and safety of Stronger Neo-Minophagen C for treatment of chronic hepatitis B: a meta-analysis of randomized controlled trials].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 09-02-2014
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To compare the efficacy and safety of Stronger Neo-Minophagen C (SNMC) in the treatment of chronic hepatitis B.
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Transcriptional regulation of cell cycle genes in response to abiotic stresses correlates with dynamic changes in histone modifications in maize.
PLoS ONE
PUBLISHED: 08-29-2014
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The histone modification level has been shown to be related with gene activation and repression in stress-responsive process, but there is little information on the relationship between histone modification and cell cycle gene expression responsive to environmental cues. In this study, the function of histone modifications in mediating the transcriptional regulation of cell cycle genes under various types of stress was investigated in maize (Zea mays L.). Abiotic stresses all inhibit the growth of maize seedlings, and induce total acetylation level increase compared with the control group in maize roots. The positive and negative regulation of the expression of some cell cycle genes leads to perturbation of cell cycle progression in response to abiotic stresses. Chromatin immunoprecipitation analysis reveals that dynamic histone acetylation change in the promoter region of cell cycle genes is involved in the control of gene expression in response to external stress and different cell cycle genes have their own characteristic patterns for histone acetylation. The data also showed that the combinations of hyperacetylation and hypoacetylation states of specific lysine sites on the H3 and H4 tails on the promoter regions of cell cycle genes regulate specific cell cycle gene expression under abiotic stress conditions, thus resulting in prolonged cell cycle duration and an inhibitory effect on growth and development in maize seedlings.
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Expression profiles of glyceraldehyde-3-phosphate dehydrogenase from Clonorchis sinensis: a glycolytic enzyme with plasminogen binding capacity.
Parasitol. Res.
PUBLISHED: 08-28-2014
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Globally, 15-20 million people are infected with Clonorchis sinensis (C. sinensis) which results in clonorchiasis. In China, clonorchiasis is considered to be one of the fastest-growing food-borne parasitic diseases. That more key molecules of C. sinensis are characterized will be helpful to understand biology and pathogenesis of the carcinogenic liver fluke. Glyceraldehyde-3-phosphate dehydrogenases (GAPDHs) from many species have functions other than their catalytic role in glycolysis. In the present study, we analyzed the sequence and structure of GAPDH from C. sinensis (CsGAPDH) by using bioinformatics tools and obtained its recombinant protein by prokaryotic expression system, to learn its expression profiles and molecular property. CsGAPDH could bind to human intrahepatic biliary epithelial cell in vivo and in vitro by the method of immunofluorescence assays. CsGAPDH also disturbed in lumen of biliary tract near to the parasite in the liver of infected rat. Western blotting analysis together with immunofluorescence assay indicated that CsGAPDH was a component of excretory/secretory proteins (CsESPs) and a surface-localized protein of C. sinensis. Quantitative real-time PCR (Q-PCR) and Western blotting demonstrated that CsGAPDHs are expressed at the life stages of adult worm, metacercaria, and egg, but the expression levels were different from each other. Recombinant CsGAPDH (rCsGAPDH) was confirmed to have the capacity to catalyze the conversion of glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate which was inhibited by AMP in a dose-dependent manner. In addition, rCsGAPDH was able to interact with human plasminogen in a dose-dependent manner by ELISA. The interaction could be inhibited by lysine. The plasminogen binding capacity of rCsGAPDH along with the distribution of CsGAPDH in vivo and in the liver of C. sinensis-infected rat hinted that surface-localized CsGAPDH might play an important role in host invasion of the worm besides its glycolytic activity. Our work will be a cornerstone for getting more messages about CsGAPDH and its role in biology and parasitism of C. sinensis.
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[Primary headache associated with sexual activity: 15 new cases and therapeutic outcomes].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-27-2014
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To explore the clinical manifestations, diagnosis, treatment and prognostic features of primary headache associated with sexual activity (PHASA) .
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Nanoscale structural modulation and enhanced room-temperature multiferroic properties.
Nanoscale
PUBLISHED: 08-23-2014
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Availability of a single-phase multiferroic material functional at room temperature poses a big challenge, although it is very important to both fundamental physics and application development. Recently, layered Aurivillius oxide materials, one of the most promising candidates, have attracted considerable interest. In this work, we investigated the nanoscale structural evolution of the six-layer Bi7Fe3-xCoxTi3O21 when substituting excessive Co. Nanoscale structural modulation (NSM) occurred at the boundaries when changing the material gradually from the originally designed six-layer nanoscale architecture down to five and then four, when increasing the Co content, inducing a previously unidentified analogous morphotropic transformation (AMT) effect. The AMT's net contribution to the enhanced intrinsic multiferroic properties at room temperature was confirmed by quantifying and deducting the contribution from the existing impurity phase using derivative thermo-magneto-gravimetry measurements (DTMG). Significantly, this new AMT effect may be caused by a possible coupling contribution from co-existing NSM phases, indicating a potential method for realizing multiferroic materials that function at room temperature.
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Identification, immunolocalization, and characterization analyses of an exopeptidase of papain superfamily, (cathepsin C) from Clonorchis sinensis.
Parasitol. Res.
PUBLISHED: 08-21-2014
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Cathepsin C is an important exopeptidase of papain superfamily and plays a number of great important roles during the parasitic life cycle. The amino acid sequence of cathepsin C from Clonorchis sinensis (C. sinensis) showed 54, 53, and 49% identities to that of Schistosoma japonicum, Schistosoma mansoni, and Homo sapiens, respectively. Phylogenetic analysis utilizing the sequences of papain superfamily of C. sinensis demonstrated that cathepsin C and cathepsin Bs came from a common ancestry. Cathepsin C of C. sinensis (Cscathepsin C) was identified as an excretory/secretory product by Western blot analysis. The results of transcriptional level and translational level of Cscathepsin C at metacercaria stage were higher than that at adult worms. Immunolocalization analysis indicated that Cscathepsin C was specifically distributed in the suckers (oral sucker and ventral sucker), eggs, vitellarium, intestines, and testis of adult worms. In the metacercaria, it was mainly detected on the cyst wall and excretory bladder. Combining with the results mentioned above, it implies that Cscathepsin C may be an essential proteolytic enzyme for proteins digestion of hosts, nutrition assimilation, and immune invasion of C. sinensis. Furthermore, it may be a potential diagnostic antigen and drug target against C. sinensis infection.
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Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer.
J Transl Med
PUBLISHED: 08-16-2014
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BackgroundHuman replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC).MethodsThe mRNA levels of RFC4 were assessed in 30 paired primary CRC tissues and matched normal colonic tissues by quantitative PCR. The protein expression levels of RFC4 were evaluated by western blotting (n =16) and immunohistochemistry (IHC; n =49), respectively. Clinicopathological features and survival data were correlated with the expression of RFC4 by IHC analysis in a tissue microarray comprising 331 surgically resected CRC. The impact of RFC4 on cell proliferation and the cell cycle was assessed using CRC cell lines.Results RFC4 expression was significantly increased in CRC specimens as compared to adjacent normal colonic tissues (P <0.05). High levels of RFC4, determined on a tissue microarray, were significantly associated with differentiation, an advanced stage by the Tumor-Node-Metastasis (TNM) staging system, and a poor prognosis, as compared to low levels of expression (P <0.05). However, in multivariate analysis, RFC4 was not an independent predictor of poor survival for CRC. In vitro studies, the loss of RFC4 suppressed CRC cell proliferation and induced S-phase cell cycle arrest.Conclusion RFC4 is frequently overexpressed in CRC, and is associated with tumor progression and worse survival outcome. This might be attributed to the regulation of CRC cell proliferation and cell cycle arrest by RFC4.
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Torque-stiffness-controlled dynamic walking with central pattern generators.
Biol Cybern
PUBLISHED: 08-16-2014
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Walking behavior is modulated by controlling joint torques in most existing passivity-based bipeds. Controlled Passive Walking with adaptable stiffness exhibits controllable natural motions and energy efficient gaits. In this paper, we propose torque-stiffness-controlled dynamic bipedal walking, which extends the concept of Controlled Passive Walking by introducing structured control parameters and a bio-inspired control method with central pattern generators. The proposed walking paradigm is beneficial in clarifying the respective effects of the external actuation and the internal natural dynamics. We present a seven-link biped model to validate the presented walking. Effects of joint torque and joint stiffness on gait selection, walking performance and walking pattern transitions are studied in simulations. The work in this paper develops a new solution of motion control of bipedal robots with adaptable stiffness and provides insights of efficient and sophisticated walking gaits of humans.
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[Abnormal effect of absolute ethanol sclerotherapy for arteriovenous malformations on hemodynamics].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 08-09-2014
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To observe and analyze the abnormal effect of ethanol sclerotherapy for arteriovenous malformations on hemodynamics.
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Numerical analysis of an end-pumped Yb:YAG thin disk laser with variation of a fractional thermal load.
Appl Opt
PUBLISHED: 08-05-2014
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An analytical model is developed to describe the dynamic behavior of an end-pumped Yb:YAG thin disk laser. Within the model, the rate equations, including the nonradiative relaxation process, are calculated taking into account the dependence of the fractional thermal load on the temperature of the thin disk crystal and intracavity laser intensity. The fractional thermal load is analyzed, or can be evaluated clearly, under lasing or nonlasing conditions. The stable temperature and fractional thermal load in a thin disk crystal for different radiative quantum efficiencies are obtained using the numerical iterative method. Furthermore, the dependence of the laser output intensity on variables such as pumping intensity, coupler reflectivity, radiative quantum efficiency, and the temperature of thin disk crystal is discussed.
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Sleep disorders in multiple sclerosis in China: clinical, polysomnography study, and review of the literature.
J Clin Neurophysiol
PUBLISHED: 08-02-2014
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Sleep disorders are common in multiple sclerosis (MS). The aim of this study was to assess the subjective and objective sleep disturbances in patients with MS and to investigate their relationships with fatigue and excessive daytime sleepiness. All participants completed standardized questionnaires and underwent nocturnal polysomnography. English literature regarding MS and sleep disorders was systematically reviewed through PubMed searches. Eleven patients with MS with fatigue, 10 patients with MS without fatigue, and 11 controls were included in the study. According to the Pittsburg sleep quality index, 61.9% of the patients with MS were poor sleepers and based on the Epworth sleepiness scale, 38.1% of the patients with MS met the criteria of excessive daytime sleepiness. Additionally, patients with MS had more disturbed sleep with higher total arousal index (P < 0.01) and periodic limb movement arousal index (P < 0.001) than controls. None of the patients or controls had an apnea/hypopnea index greater than five. One patient had restless legs syndrome and four had rapid eye movement sleep behavior disorder. Our study shows that sleep disorders and excessive daytime sleepiness are frequent in MS.
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Response surface optimization of enzymatic hydrolysis of duck blood corpuscle using commercial proteases.
Poult. Sci.
PUBLISHED: 08-01-2014
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With the rapid development in livestock and poultry husbandry and increasing shortage of protein sources, recycling of wastes from agricultural and food processing such as blood corpuscles has been regarded as an important industrial procedure to obtain protein sources. This study aimed to find an appropriate method for recycling the considerable amounts of blood corpuscle so as to improve its nutritional value and organoleptic quality. An effective production process for enzymatic hydrolysis of duck blood corpuscle was successfully developed and optimized by response surface methodology. Optimal conditions based on achieving a high value of trichloroacetic acid solubility index were substrate concentration of 14 g/100 mL, temperature 51°C, initial pH 7.0, and time 7.5 h. The electrophoretic patterns of the protein hydrolysate were investigated, and a large diffuse band was observed in the vicinity of 5 kDa. The organoleptic quality of spray-dried blood corpuscle hydrolysate was also evaluated, indicating that enzymatic hydrolysis and decoloration methods were feasible and cost-effective to achieve the desirable bright yellow product without bitterness. In vitro protein digestibility of blood corpuscle hydrolysate was 96.32 ± 0.50%, which was better than that of soybean, fish meal, and casein. Based on the amino acid composition and nutritional parameters, we found that the spray-dried blood corpuscle hydrolysate had abundant nutritional value and high potential for application as an ingredient in nonruminant animal feed.
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A systemic inflammation-based prognostic scores (mGPS) predicts overall survival of patients with small-cell lung cancer.
Tumour Biol.
PUBLISHED: 07-25-2014
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Recent studies have shown the combination of C-reactive protein (CRP) and albumin (The modified Glasgow Prognostic Score, mGPS) had prognostic value in some solid tumors. However, no studies have examined its prognostic role in small-cell lung cancer (SCLC) patients. In this retrospective study, 460 consecutive SCLC patients were screened. Eligible patient was assigned a mGPS of 0, 1, or 2 based on pre-treatment plasma CRP and albumin (0: CRP???10 mg/L; 1: CRP >10 mg/L and albumin???35 g/L; 2: CRP?>?10 mg/L and albumin?
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Phosphorylated p38, a negative prognostic biomarker, complements TNM staging prognostication in colorectal cancer.
Tumour Biol.
PUBLISHED: 07-24-2014
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Phosphorylated p38 (p-p38) played a pivotal role in the regulation of disease progression and correlated with tumor prognosis. Here, we characterized the prognostic effect of p-p38 in colorectal cancer (CRC). Three hundred and sixteen CRC patients in stages I-III were recruited in this study. P-p38 expression was semi-quantitatively evaluated using tissue microarrays and immunohistochemistry staining. Overall survival (OS), disease-free survival (DFS), local failure-free survival (LFFS), and distant metastasis-free survival (DMFS) of patient subgroups, segregated by p-p38 expression level and clinical stage, were compared using Kaplan-Meier analysis. We found that p-p38 was overexpressed in 48.1 % (152/316) CRC tissues, whereas low or deficiently expressed in normal adjacent epithelia. Overexpression of p-p38 predicted poor OS (P?
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EBV-driven LMP1 and IFN-? up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy.
Oncotarget
PUBLISHED: 07-20-2014
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PD-L1 expression is a feature of Epstein-Barr virus (EBV) associated malignancies such as nasopharyngeal carcinoma (NPC). Here, we found that EBV-induced latent membrane protein 1 (LMP1) and IFN-? pathways cooperate to regulate programmed cell death protein 1 ligand (PD-L1). Expression of PD-L1 was higher in EBV positive NPC cell lines compared with EBV negative cell lines. PD-L1 expression could be increased by exogenous and endogenous induction of LMP1 induced PD-L1. In agreement, expression of PD-L1 was suppressed by knocking down LMP1 in EBV positive cell lines. We further demonstrated that LMP1 up-regulated PD-L1 through STAT3, AP-1, and NF-?B pathways. Besides, IFN-? was independent of but synergetic with LMP1 in up-regulating PD-L1 in  NPC. Furthermore, we showed that PD-L1 was associated with worse disease-free survival in NPC patients. These results imply that blocking both the LMP1 oncogenic pathway and PD-1/PD-L1 checkpoints may be a promising therapeutic approach for EBV positive NPC patients.
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Prognostic significance of thymidylate synthase in postoperative non-small cell lung cancer patients.
Onco Targets Ther
PUBLISHED: 07-16-2014
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The aim of the present study was to investigate the clinicopathologic/prognostic significance of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), and thymidine phosphorylase (TP) proteins in postoperative non-small cell lung cancer (NSCLC) patients. Microarray slides from a set of 178 NSCLC patients were used for the detection of TS, OPRT, and TP expression by immunohistochemistry. The correlation between clinicopathologic factors and protein expression of three proteins was analyzed. Ninety seven carcinomas (57.4%) were TS-positive, 90 carcinomas (53.9%) were OPRT-positive, and 102 carcinomas (69.4%) were TP-positive. Compared with the TS-positive patients, the overall survival (OS) was significantly lower in the TS-negative patients (hazard ratio [HR] =1.766, 95% confidence interval [CI] =1.212-2.573, P=0.003). Significant differences between TS-positive and TS-negative patients was also observed in the following stratified analyses: 1) adenocarcinoma subgroup (HR =2.079, 95% CI =1.235-3.500, P=0.006); 2) less than 60-year-old subgroup (HR =1.890, 95% CI =1.061-3.366, P=0.031); 3) stage II/III subgroup (HR =1.594, 95% CI =1.036-2.453, P=0.034); and 4) surgery plus adjuvant therapy subgroup (HR =1.976, 95% CI =1.226-3.185, P=0.005). However, the OS was not significantly correlated with OPRT or TP protein expression. This study demonstrates that the TS level in tumor tissues may be a useful marker to predict the postoperative OS in NSCLC patients.
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A low bandgap asymmetrical squaraine for high-performance solution-processed small molecule organic solar cells.
Chem. Commun. (Camb.)
PUBLISHED: 07-09-2014
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A novel asymmetrical squaraine ASQ-5 bearing indoline as an end capper exhibits a low bandgap of 1.43 eV and a broad absorption band in the Vis-NIR region of 550-850 nm in thin films, hence renders solution-processed organic solar cells with an impressive Jsc of up to 11.03 mA cm(-2) and an excellent PCE of 4.29%.
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Sensory innervation around immediately vs. delayed loaded implants: a pilot study.
Int J Oral Sci
PUBLISHED: 07-07-2014
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Although neurophysiological and psychophysical proof of osseoperception is accumulating, histomorphometric evidence for the neural mechanisms of functional compensation following immediate and delayed implant loading is still lacking. For this randomized split-mouth study, six mongrel dogs randomly received one of four treatment protocols at 36 implant-recipient sites over 16 weeks (third maxillary incisor, third and fourth mandibular premolar): immediate implant placement and immediate loading (IIP+IL); delayed implant placement and delayed loading (DIP+DL); delayed implant placement and immediate loading (DIP+IL); and natural extraction socket healing (control). Histomorphometry was performed in the peri-implant bone and soft tissues within 300?µm around the implants. Immunocytochemistry and transmission electron microscopy were used to confirm the presence of neural structures and to reveal their ultrastructural characteristics, respectively. Myelinated nerve fibres densely populated the peri-implant crestal gingival and apical regions, although they were also identified in the woven bone and in the osteons near the implant threads. Compared with the control group in the mandible, the group that received IIP+IL showed a higher innervation (in N?mm(-2), 5.94±1.12 vs. 3.15±0.63, P<0.001) and smaller fibre diameter (in µm, 1.37±0.05 vs. 1.64±0.13, P=0.016), smaller axon diameter (in µm, 0.89±0.05 vs. 1.24±0.10, P=0.009) and g-ratio (0.64±0.04 vs. 0.76±0.05, P<0.001) in the middle region around the implants. Compared with DIP+IL in the mandible, IIP+IL had a higher nerve density (in N?mm(-2), 13.23±2.54 vs. 9.64±1.86, P=0.027), greater fibre diameter (in µm, 1.32±0.02 vs. 1.20±0.04, P=0.021), greater axon diameter (in µm, 0.92±0.01 vs. 0.89±0.03, P=0.035) and lower g-ratio (0.69±0.01 vs. 0.74±0.01, P=0.033) in the apical region around the implants. It may be assumed that the treatment protocol with IIP+IL is the preferred method to allow optimized peri-implant re-innervation, but further functional measurements are still required.International Journal of Oral Science advance online publication, 12 September 2014; doi:10.1038/ijos.2014.53.
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The timing of surgical treatment of knee dislocations: a systematic review.
Knee Surg Sports Traumatol Arthrosc
PUBLISHED: 07-04-2014
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Traumatic knee dislocations (KDs) are unusual yet limb-threatening injuries; the timing of surgical intervention is still debated. A systematic review was performed to determine the optimal timing of surgery with respect to injury pattern.
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Arabidopsis DELLA protein degradation is controlled by a type-one protein phosphatase, TOPP4.
PLoS Genet.
PUBLISHED: 07-01-2014
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Gibberellins (GAs) are a class of important phytohormones regulating a variety of physiological processes during normal plant growth and development. One of the major events during GA-mediated growth is the degradation of DELLA proteins, key negative regulators of GA signaling pathway. The stability of DELLA proteins is thought to be controlled by protein phosphorylation and dephosphorylation. Up to date, no phosphatase involved in this process has been identified. We have identified a dwarfed dominant-negative Arabidopsis mutant, named topp4-1. Reduced expression of TOPP4 using an artificial microRNA strategy also resulted in a dwarfed phenotype. Genetic and biochemical analyses indicated that TOPP4 regulates GA signal transduction mainly via promoting DELLA protein degradation. The severely dwarfed topp4-1 phenotypes were partially rescued by the DELLA deficient mutants rga-t2 and gai-t6, suggesting that the DELLA proteins RGA and GAI are required for the biological function of TOPP4. Both RGA and GAI were greatly accumulated in topp4-1 but significantly decreased in 35S-TOPP4 transgenic plants compared to wild-type plants. Further analyses demonstrated that TOPP4 is able to directly bind and dephosphorylate RGA and GAI, confirming that the TOPP4-controlled phosphorylation status of DELLAs is associated with their stability. These studies provide direct evidence for a crucial role of protein dephosphorylation mediated by TOPP4 in the GA signaling pathway.
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Expression of astrocyte elevated gene-1 (AEG-1) as a biomarker for aggressive pancreatic ductal adenocarcinoma.
BMC Cancer
PUBLISHED: 06-30-2014
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Altered expression of astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression. The present study aimed to investigate the clinical and prognostic significance of AEG-1 expression in pancreatic ductal adenocarcinoma (PDAC).
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Electro-acupuncture at Neiguan pretreatment alters genome-wide gene expressions and protects rat myocardium against ischemia-reperfusion.
Molecules
PUBLISHED: 06-21-2014
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This study investigated genome-wide gene expressions and the cardioprotective effects of electro-acupuncture pretreatment at the PC6 Neiguan acupoint on myocardial ischemia reperfusion (I/R) injury. Male SD rats were randomly divided into four groups: sham operation (SO), I/R, electro-acupuncture at the PC6 Neiguan acupoint pretreatment (EA) and electro-acupuncture at non-acupoint pretreatment (NA). Compared with the I/R group, the survival rate of the EA group was significantly increased, the arrhythmia score, infarction area, serum concentrations of CK, LDH and CK-Mb and plasma level of cTnT were significantly decreased. RNA-seq results showed that 725 genes were up-regulated and 861 genes were down-regulated under I/R conditions compared to the SO group; both EA and NA reversed some of these gene expression levels (592 in EA and 238 in NA group). KEGG pathway analysis indicated that these genes were involved in multiple pathways, including ECM, MAPK signaling, apoptosis, cytokine and leukocyte pathways. In addition, some pathways were uniquely regulated by EA, but not NA pretreatment, such as oxidative stress, cardiac muscle contraction, gap junction, vascular smooth muscle contraction, hypertrophic, NOD-like receptor, and P53 and B-cell receptor pathways. This study was first to reveal the gene expression signatures of acute myocardial I/R injury and electro-acupuncture pretreatment in rats.
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Neuroprotective effect of the traditional Chinese herbal formula Tongxinluo: a PET imaging study in rats.
Neural Regen Res
PUBLISHED: 06-18-2014
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Tongxinluo has been widely used in China for the treatment of acute stroke and for neuroprotection. However, there are few positron emission tomography (PET) studies on the neuroprotective effect of Tongxinluo on cerebral ischemia/reperfusion in small animals. In the present study, Tongxinluo superfine powder suspension or its vehicle was administered intragastrically to rats for 5 successive days before middle cerebral artery occlusion. (18)F-fluorodeoxyglucose (FDG) small animal PET imaging showed that at 1 and 2 weeks after cerebral ischemia/reperfusion, glucose metabolism in the ischemic area was greater in rats that had received Tongxinluo than in those that had received the vehicle. Nissl staining showed that 2 weeks after cerebral ischemia/reperfusion, there was less neuronal loss in the prefrontal cortex in Tongxinluo-treated rats than in controls. In addition, Tongxinluo-treated animals showed better neurologic function and lower cerebral infarct volume than rats that received the vehicle. These findings suggest that Tongxinluo exhibits neuroprotective effects in cerebral ischemia/reperfusion injury and demonstrates that (18)F-FDG small animal PET imaging is a useful tool with which to study the molecular pharmacology of traditional Chinese medicine.
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Neuronal nitric oxide synthase, as a downstream signaling molecule of c?jun, regulates the survival of differentiated PC12 cells.
Mol Med Rep
PUBLISHED: 05-09-2014
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The high expression of c-jun and neuronal nitric oxide synthase (nNOS) generally occurs in neurons following the generation of various animal models of central neuronal diseases. However, the mechanism between them in neuronal disease remains to be elucidated. Our previous studies demonstrated that the expression of c?jun always occurs prior to expression of nNOS in motoneuron injuries and suppression of c?jun expression by c?jun siRNA decreased nNOS expression in differentiated PC12 cells. The present study aimed to examine whether there was an association of up and downstream regulation or crosstalk between c?jun and nNOS in neurons. Using a culture of differentiated PC12 cells in vitro, the expression of nNOS and c-jun in cells was investigated by immunofluorescence. The nNOS inhibitor 7?nitroindazole (7?NI) was used in differentiated PC12 cells to downregulate the expression of nNOS. The optimal concentration of 7?NI on the viability and survival of cultured differentiated PC12 cells was selected using a 3?(4,5-dimethylthiazol-2-yl)?2,5-diphenyltetrazolium assay and the effects of 7?NI on the activity of constitutive nitric oxide synthase (cNOS) in differentiated PC12 cells were determined using a NOS Activity Detection kit. The effects of 7?NI on the gene expression of nNOS and c?jun were detected by western blot analysis. The results from the immunofluorescence demonstrated that the c?jun and nNOS protein were constantly expressed in PC12 cells. The cell viability of differentiated PC12 cells were significantly inhibited by treatment with 200 and 400 µmol/l 7?NI, and the expression levels of the nNOS protein were significantly inhibited by treatment with 200 µmol/l 7?NI. However, 7?NI had no significant effect on the protein expression level of c?jun and the total activities of cNOS. Based on our previous studies, which revealed that the nNOS gene was a downstream signaling molecule of the JNK/c?jun signaling pathway in cultured neurons, the expression of nNOS downstream was able to be regulated by c?jun which was the upstream molecule. Therefore, these results indicated that the association between them involved up and downregulation instead of crosstalk.
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Connexin 31.1 degradation requires the Clathrin-mediated autophagy in NSCLC cell H1299.
J. Cell. Mol. Med.
PUBLISHED: 05-08-2014
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Connexins have relative short half-lives. Connexin 31.1 (Cx31.1) was newly reported to be down-regulated in non-small cell lung cancer cell lines, and displayed tumour-suppressive properties. However, no reports describing how a cell regulates Cx31.1 level were found. In this study, Cx31.1 was suggested to be degraded through both ubiquitin-proteasome system (UPS) and autophagy. Blockage of UPS with MG-132 increased Cx31.1 level, but could not inhibit the degradation of Cx31.1 completely. In H1299 cells stably expressing Cx31.1, Cx31.1 reduced when autophagy was induced through starvation or Brefeldin A treatment. Knockdown of autophagy-related protein ATG5 could increase the cellular level of Cx31.1 both under normal growth condition and starvation-induced autophagy. Colocalization of Cx31.1 and autophagy marker light chain 3 (LC3) was revealed by immunofluorescence analysis. Coimmunoprecipitation and immunofluorescence showed that Cx31.1 might interact with clathrin heavy chain which was newly reported to regulate autophagic lysosome reformation (ALR) and controls lysosome homoeostasis. When clathrin expression was knockdown by siRNA treatment, the level of Cx31.1 increased prominently both under normal growth condition and starvation-induced autophagy. Under starvation-induced autophagy, LC3-II levels were slightly accumulated with siCla. treatment compared to that of siNC, which could be ascribed to that clathrin knockdown impaired the late stage of autophagy, ALR. Taken together, we found autophagy contributed to Cx31.1 degradation, and clathrin might be involved in the autophagy of Cx31.1.
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Rapid carbonation for calcite from a solid-liquid-gas system with an imidazolium-based ionic liquid.
Int J Mol Sci
PUBLISHED: 05-08-2014
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Aqueous carbonation of Ca(OH)2 is a complex process that produces calcite with scalenohedral calcite phases and characterized by inadequate carbonate species for effective carbonation due to the poor dissolution of CO2 in water. Consequently, we report a solid-liquid-gas carbonation system with an ionic liquid (IL), 1-butyl-3-methylimidazolium bromide, in view of enhancing the reaction of CO2 with Ca(OH)2. The use of the IL increased the solubility of CO2 in the aqueous environment and enhanced the transport of the reactive species (Ca2+ and CO32-) and products. The presence of the IL also avoided the formation of the CaCO3 protective and passivation layer and ensured high carbonation yields, as well as the production of stoichiometric rhombohedral calcite phases in a short time.
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An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome.
Nat. Genet.
PUBLISHED: 05-05-2014
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Inflammasomes are innate immune sensors that respond to pathogen- and damage-associated signals with caspase-1 activation, interleukin (IL)-1? and IL-18 secretion, and macrophage pyroptosis. The discovery that dominant gain-of-function mutations in NLRP3 cause the cryopyrin-associated periodic syndromes (CAPS) and trigger spontaneous inflammasome activation and IL-1? oversecretion led to successful treatment with IL-1-blocking agents. Herein we report a de novo missense mutation (c.1009A > T, encoding p.Thr337Ser) affecting the nucleotide-binding domain of the inflammasome component NLRC4 that causes early-onset recurrent fever flares and macrophage activation syndrome (MAS). Functional analyses demonstrated spontaneous inflammasome formation and production of the inflammasome-dependent cytokines IL-1? and IL-18, with the latter exceeding the levels seen in CAPS. The NLRC4 mutation caused constitutive caspase-1 cleavage in cells transduced with mutant NLRC4 and increased production of IL-18 in both patient-derived and mutant NLRC4-transduced macrophages. Thus, we describe a new monoallelic inflammasome defect that expands the monogenic autoinflammatory disease spectrum to include MAS and suggests new targets for therapy.
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Characterization of the secreted cathepsin B cysteine proteases family of the carcinogenic liver fluke Clonorchis sinensis.
Parasitol. Res.
PUBLISHED: 05-02-2014
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Clonorchis sinensis excretory/secretory products (ESP) have gained high attentions because of their potential to be vaccine candidates and drug targets in C. sinensis prevention. In this study, we extensively profiled the characteristics of four C. sinensis cathepsin B cysteine proteases (CsCB1, CsCB2, CsCB3, and CsCB4). Bioinformatics analysis showed all CsCBs contained signal peptides at the N-terminal. Functional domains and residues were found in CsCB sequences. We expressed four CsCBs and profiled immune responses followed by vaccine trials. Recombinant CsCBs could induce high IgG titers, indicating high immunogenicity of CsCB family. Additionally, ELISA results showed that both IgG1 and IgG2a levels apparently increased post-immunization with all four CsCBs, showing that combined Th1/Th2 immune responses were triggered by CsCB family. Both Real-time polymerase chain reaction (RT-PCR) and Western blotting confirmed that four CsCBs have distinct expression patterns in C. sinensis life stages. More importantly, we validated our hypothesis that CsCBs were C. sinensis excretory/secretory products. CsCBs could be recognized by C. sinensis-infected sera throughout the infection period, indicating that secreted CsCBs are immune triggers during C. sinensis infection. The protective effect was assessed by comparing the worm burden and egg per gram (EPG) between CsCB group and control group, showing that worm burden (P?
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Fractional Reactive Extraction for Symmetrical Separation of 4-Nitro-D,L-Phenylalanine in Centrifugal Contactor Separators: Experiments and Modeling.
Chirality
PUBLISHED: 03-26-2014
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The enantioselective liquid-liquid extraction of 4-nitro-D,L-phenylalanine (D,L-Nphy) using PdCl2 {(s)-BINAP} as extractant in dichloroethane was studied experimentally in a countercurrent cascade of 10 centrifugal contactor separators (CCSs) at 5°C, involving flow ratio, extractant concentration, and Cl(-) concentration. The steady-state enantiomeric excess (ee) in both stream exits was 90.86% at a 93.29% yield. The predicted value was modeled using an equilibrium stage approach. The correlation between model and experiment was satisfactory. The model was applied to optimize the production of both enantiomers in >97% ee and >99% ee. 14 stages and 16 stages are required for 97% ee and 99% ee for both enantiomers, respectively. Chirality 00:000-000, 2014. © 2014 Wiley Periodicals, Inc.
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A mix-and-read fluorescence strategy for the switch-on probing of kinase activity based on an aptameric-peptide/graphene-oxide platform.
Chem Asian J
PUBLISHED: 03-12-2014
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Protein kinase plays a vital role in regulating signal-transduction pathways and its simple and quick detection is highly desirable because traditional kinase assays typically rely on a time-consuming kinase-phosphorylation process (ca. 1?h). Herein, we report a new and rapid fluorescence-based sensing platform for probing the activity of protein kinase that is based on the super-quenching capacity of graphene oxide (GO) nanosheets and specific recognition of the aptameric peptide (FITC-IP20). On the GO/peptide platform, the fluorescence quenching of FITC-IP20 that is adsorbed onto GO can be restored by selective binding of active protein kinase to the aptameric peptide, thereby resulting in the fast switch-on detection of kinase activity (ca. 15?min). The feasibility of this method has been demonstrated by the sensitive measurement of the activity of cAMP-dependent protein kinase (PKA), with a detection limit of 0.053?mU??L(-1). This assay technique was also successfully applied to the detection of kinase activation in cell lysate.
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MicroRNA-152 modulates the canonical Wnt pathway activation by targeting DNA methyltransferase 1 in arthritic rat model.
Biochimie
PUBLISHED: 03-11-2014
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Rheumatoid arthritis (RA) is an autoimmune and progressive systemic disease of unknown etiology. Research shows that fibroblast-like synoviocytes (FLS) participate in the cartilage erosion, synovial hyperplasia, inflammatory cytokine secretion and suggests that fibroblast-like synoviocytes (FLS) display a crucial role in RA pathogenesis. Recent studies have suggested the role of the Wnt signaling pathway in the pathogenesis of RA. In previous study, we identified that increased methyl-CpG-binding protein 2 (MeCP2) reduced the secreted frizzled-related protein 4 (SFRP4) expression in FLS in Arthritic rat model and the DNA methyltransferase (DNMT) inhibitor 5-Aza-2'-deoxycytidine (5-azadC) could induce the SFRP4 expression, indicating that DNMT has a key role in the differential expression of SFRP4. MicroRNAs (MiRNAs), which are small non-coding RNAs, are involved in diverse biological functions, regulation of gene expression, pathogenesis of autoimmune disease and carcinogenesis. In light of the directly down-regulation of miR-152 on DNMT1 expression by targeting the 3' untranslated regions of its transcript in nickel sulfide (NiS)-transformed human bronchial epithelial cells, we investigated whether miR-152 is aberrantly expressed and targets DNMT1 in FLS in Arthritic rat model. Our results demonstrated that the expression of miR-152 was specifically down-regulated in Arthritic rat model, whereas up-regulation of miR-152 in FLS resulted in a marked reduction of DNMT1 expression. Further experiments revealed that increased miR-152 indirectly up-regulated the SFRP4 expression, a negative regulator of WNT signaling pathway, by targeting the DNMT1. Moreover, activation of miR-152 expression in FLS could inhibit the canonical Wnt pathway activation and result in a significant decrease of FLS proliferation. MiR-152 and DNA methylation may provide molecular mechanisms for the activation of canonical Wnt pathway in RA. Combination of miR-152 and DNMT1 may be a promising treatment strategy for RA patients in which SFRP4 is inactivated.
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ERCC6 dysfunction presenting as progressive neurological decline with brain hypomyelination.
Am. J. Med. Genet. A
PUBLISHED: 03-10-2014
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Mutations in ERCC6 are associated with growth failure, intellectual disability, neurological dysfunction and deterioration, premature aging, and photosensitivity. We describe siblings with biallelic ERCC6 mutations (NM_000124.2:c. [543?+?4delA];[2008C?>?T]) and brain hypomyelination, microcephaly, cognitive decline, and skill regression but without photosensitivity or progeria. DNA repair assays on cultured skin fibroblasts confirmed a defect of transcription-coupled nucleotide excision repair and increased ultraviolet light sensitivity. This report expands the disease spectrum associated with ERCC6 mutations. © 2014 Wiley Periodicals, Inc.
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A universal lateral flow biosensor for proteins and DNAs based on the conformational change of hairpin oligonucleotide and its use for logic gate operations.
Biosens Bioelectron
PUBLISHED: 02-25-2014
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A universal lateral flow biosensor for proteins and DNAs was designed on the base of target-induced conformational changes of hairpin oligonucleotide (HO). CEA (carcinoembryonic antigen) protein and c-DNA were detected both with the naked eye and a strip reader. The scheme of detecting proteins and DNAs were based on the unique molecular recognition properties of HO to the targets to form different quantities of "active" biotin groups on the surface of gold nanoparticles (AuNPs). The output of the strip is the color of the test line, which inspired us to combine strip biosensor with logic gate. Two strip logic gates ("OR" and "INH") were designed in our paper and the combinatorial logic gates in our paper could be used to make high-throughput judgment about what targets were present in the input samples according to the output results. The biosensor facilitates a portable analysis at ambient temperature as it is simple to be conducted and no requirement of training is needed. The strip logic system is proved an excellent selection and can operate effectively as well as in human serum samples. Therefore, we indicate that such logic strips a foreseeable promise in application of intelligent point-of-care and in-field diagnostics.
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Fluorescent detection of protein kinase based on positively charged gold nanoparticles.
Talanta
PUBLISHED: 02-14-2014
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Herein, we report a fluorometric method for monitoring the activity and inhibition of protein kinase based on positively charged gold nanoparticles, (+)AuNPs. In this assay, when the cationic substrate peptide (S-peptide) is phosphorylated by protein kinase, the resulting negatively charged product peptide (P-peptide) will be adsorbed onto (+)AuNPs through electrostatic interaction, and the fluorescence of fluorescein isothiocyanate (FITC) on the peptide will be quenched by (+)AuNPs. Thus, the fluorescence of solution can respond to the activity of protein kinase. The feasibility of this (+)AuNPs-based method has been demonstrated by sensitive measurement of the activity of cAMP-dependent protein kinase (PKA) with a low detection limit (0.5 mU ?L(-1)). Furthermore, the system is successfully applied to estimate the IC50 value of PKA inhibitor H-89. The fast mix-and-readout detection process as well as the simple synthesis of the unmodified (+)AuNPs makes this proposed method a promising candidate for simple and cost-effective kinase activity detection and a good potential in high-throughput screening of kinase-related drugs.
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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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microRNA-103a functions as a mechno-sensitive microRNA to inhibit bone formation through targeting Runx2.
J. Bone Miner. Res.
PUBLISHED: 01-24-2014
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Emerging evidence indicates that microRNAs (miRNAs) play essential roles in regulating osteoblastogenesis and bone formation. However, the role of miRNA in osteoblast mechanotransduction remains to be defined. In this study, we aimed to investigate if miRNAs regulate mechanical stimulation-triggered osteoblast differentiation and bone formation through modulation of Runx2, the master transcription factor for osteogenesis. We first investigated the role of mechanical loading both in a mouse model and in an osteoblasts culture system and the outcomes clearly demonstrated that mechanical stimuli can regulate osteogenesis and bone formation both in vivo and in vitro. Using bioinformatic analyses and subsequently confirmed by quantitative Real-Time PCR (qRT-PCR), we found that multiple miRNAs were responding to in vitro mechanical stimulation that potentially target Runx2. Among which miR-103a was fully characterized. miR-103a and its host gene PANK3 were both downregulated during cyclic mechanical stretch-induced (CMS) osteoblast differentiation, whereas Runx2 protein expression was upregulated. Overexpression of miR-103a significantly decreased and inhibition of miR-103a increased Runx2 protein level, suggesting that miR-103a acts as an endogenous attenuator of Runx2 in osteoblasts. Mutation of putative miR-103a binding sites in Runx2 mRNA abolishes miR-103a-mediated repression of the Runx2 3'UTR luciferase reporter activity, suggesting that miR-103a binds to Runx2 3'UTR. Osteoblast marker genes profiling and osteogenic phenotype assays demonstrated that miR-103a negatively correlates with CMS-induced osteogenesis. Further, the perturbation of miR-103a also has a significant effect on osteoblast activity and matrix mineralization. More importantly, we found an inhibitory role of miR-103a in regulating bone formation in hindlimb unloading mice, and pretreatment with antagomir-103a partly rescued the osteoporosis caused by mechanical unloading. Taken together, our data suggest that miR-103a is the first identified mechano-sensitive miRNA that regulates osteoblast differentiation via directly targeting Runx2, and therapeutic inhibition of miR-103a may be an efficient anabolic strategy for skeletal disorders caused by pathological mechanical loading. © 2014 American Society for Bone and Mineral Research.
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Efficacy and safety of dexmedetomidine versus propofol for the sedation of tube-retention after oral maxillofacial surgery.
J. Oral Maxillofac. Surg.
PUBLISHED: 01-21-2014
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To compare the safety and efficacy of sedation induced by dexmedetomidine and propofol after oral and maxillofacial surgery.
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Endoplasmic reticulum stress is the crossroads of autophagy, inflammation, and apoptosis signaling pathways and participates in liver fibrosis.
Inflamm. Res.
PUBLISHED: 01-09-2014
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The objective of the review is to examine the crossroads of autophagy, inflammation, and apoptosis signaling pathways and their participation in liver fibrosis.
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DJ-1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway.
Oncol. Rep.
PUBLISHED: 01-09-2014
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Peritoneal metastasis is a major cause of death in patients with advanced gastric carcinoma. DJ-1 is now considered to play an important role in the metastasis of various malignancies. However, it remains largely unclear whether DJ-1 is involved in the development of peritoneal metastasis by gastric carcinoma. In the present study, we showed that the expression of DJ-1 was significantly upregulated in gastric cancer specimens with peritoneal metastasis compared to those without peritoneal metastasis. Knockdown of DJ-1 expression significantly inhibited invasion and migration, in vitro and the in vivo peritoneal metastatic abilities of SGC7901 gastric cancer cells. Moreover, knockdown of DJ-1 also diminished the expression of matrix metallopeptidase (MMP)-2 and MMP-9. All of these effects were reversed by restoration of DJ-1 expression. Following investigation of the pathway through which DJ-1 regulates cell invasion and migration, DJ-1 was found to cause phosphorylation of Akt in SGC7901 gastric cancer cells. Inhibition of the Akt pathway in SGC7901 cells mimicked the effects of DJ-1 knockdown on cell migration, invasion, MMP-2 and MMP-9 expression, and abolished the effects of DJ-1 in promoting SGC7901 cell invasion and migration. Taken together, the present study revealed that DJ-1 plays an important role in the development of peritoneal carcinomatosis from gastric carcinoma, at least partially through activation of the Akt pathway and consequent upregulation of MMP-2 and MMP-9 expression. Thus, DJ-1 may be a potential therapeutic target for peritoneal carcinomatosis of gastric carcinoma.
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Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice.
World J. Gastroenterol.
PUBLISHED: 01-07-2014
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To test the role of mast cells in gut inflammation and colitis using interleukin (IL)-10-deficient mice as an experimental model.
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The Prognostic Value of Plasma Soluble ST2 in Hospitalized Chinese Patients with Heart Failure.
PLoS ONE
PUBLISHED: 01-01-2014
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sST2 has been shown to be a risk predictor in heart failure (HF). Our aim was to explore the characteristics and prognostic value of soluble ST2 (sST2) in hospitalized Chinese patients with HF.
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Prevalence and Molecular Characterization of Cryptosporidium in Goats across Four Provincial Level Areas in China.
PLoS ONE
PUBLISHED: 01-01-2014
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This study assessed the prevalence, species and subtypes of Cryptosporidium in goats from Guangdong Province, Hubei Province, Shandong Province, and Shanghai City of China. Six hundred and four fecal samples were collected from twelve goat farms, and the overall infection rate was 11.4% (69/604). Goats infected with Cryptosporidium were found in eleven farms across four provincial areas, and the infection rate ranged from 2.9% (1/35) to 25.0% (9/36). Three Cryptosporidium species were identified. Cryptosporidium xiaoi (45/69, 65.2%) was the dominant species, followed by C. parvum (14/69, 20.3%) and C. ubiquitum (10/69, 14.5%). The infection rate of Cryptosporidium spp. was varied with host age and goat kids were more susceptible to be infected than adult goats. Subtyping C. parvum and C. ubiquitum positive samples revealed C. parvum subtype IIdA19G1 and C. ubiquitum subtype XIIa were the most common subtypes. Other C. parvum subtypes were detected as well, such as IIaA14G2R1, IIaA15G1R1, IIaA15G2R1 and IIaA17G2R1. All of these subtypes have also been detected in humans, suggesting goats may be a potential source of zoonotic cryptosporidiosis. This was the first report of C. parvum subtypes IIaA14G2R1, IIaA15G1R1 and IIaA17G2R1 infecting in goats and the first molecular identification of C. parvum and its subtypes in Chinese goats.
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Risk of treatment-related deaths with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis of 41 randomized controlled trials.
Onco Targets Ther
PUBLISHED: 01-01-2014
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Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have widely been used in advanced cancer. However, these drugs may also lead to serious adverse events. The present meta-analysis aimed to determine the overall incidence and risk of deaths due to VEGFR-TKIs with more detailed subgroup analysis.
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Effects of an oral allosteric AKT inhibitor (MK-2206) on human nasopharyngeal cancer in vitro and in vivo.
Drug Des Devel Ther
PUBLISHED: 01-01-2014
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Protein kinase B (AKT) signaling frequently is deregulated in human cancers and plays an important role in nasopharyngeal carcinoma (NPC). This preclinical study investigated the effect of MK-2206, a potent allosteric AKT inhibitor, on human NPC cells in vitro and in vivo.
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Multi-targeted antiangiogenic tyrosine kinase inhibitors in advanced non-small cell lung cancer: meta-analyses of 20 randomized controlled trials and subgroup analyses.
PLoS ONE
PUBLISHED: 01-01-2014
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Multi-targeted antiangiogenic tyrosine kinase inhibitors (MATKIs) have been studied in many randomized controlled trials (RCTs) for treatment of advanced non-small cell lung cancer (NSCLC). We seek to summarize the most up-to-date evidences and perform a timely meta-analysis.
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Sequence analysis and molecular characterization of Clonorchis sinensis hexokinase, an unusual trimeric 50-kDa glucose-6-phosphate-sensitive allosteric enzyme.
PLoS ONE
PUBLISHED: 01-01-2014
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Clonorchiasis, which is induced by the infection of Clonorchis sinensis (C. sinensis), is highly associated with cholangiocarcinoma. Because the available examination, treatment and interrupting transmission provide limited opportunities to prevent infection, it is urgent to develop integrated strategies to prevent and control clonorchiasis. Glycolytic enzymes are crucial molecules for trematode survival and have been targeted for drug development. Hexokinase of C. sinensis (CsHK), the first key regulatory enzyme of the glycolytic pathway, was characterized in this study. The calculated molecular mass (Mr) of CsHK was 50.0 kDa. The obtained recombinant CsHK (rCsHK) was a homotrimer with an Mr of approximately 164 kDa, as determined using native PAGE and gel filtration. The highest activity was obtained with 50 mM glycine-NaOH at pH 10 and 100 mM Tris-HCl at pH 8.5 and 10. The kinetics of rCsHK has a moderate thermal stability. Compared to that of the corresponding negative control, the enzymatic activity was significantly inhibited by praziquantel (PZQ) and anti-rCsHK serum. rCsHK was homotropically and allosterically activated by its substrates, including glucose, mannose, fructose, and ATP. ADP exhibited mixed allosteric effect on rCsHK with respect to ATP, while inorganic pyrophosphate (PPi) displayed net allosteric activation with various allosteric systems. Fructose behaved as a dose-dependent V activator with the substrate glucose. Glucose-6-phosphate (G6P) displayed net allosteric inhibition on rCsHK with respect to ATP or glucose with various allosteric systems in a dose-independent manner. There were differences in both mRNA and protein levels of CsHK among the life stages of adult worm, metacercaria, excysted metacercaria and egg of C. sinensis, suggesting different energy requirements during different development stages. Our study furthers the understanding of the biological functions of CsHK and supports the need to screen for small molecule inhibitors of CsHK to interfere with glycolysis in C. sinensis.
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[A survey on knowledge of recommended heart failure guidelines among Chinese physicians].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 12-17-2013
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To obtain the knowledge status on recommended heart failure (HF) guidelines among Chinese physicians.
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Activation of hypoxia-inducible factor-2 in adipocytes results in pathological cardiac hypertrophy.
J Am Heart Assoc
PUBLISHED: 12-12-2013
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Obesity can cause structural and functional abnormalities of the heart via complex but largely undefined mechanisms. Emerging evidence has shown that obesity results in reduced oxygen concentrations, or hypoxia, in adipose tissue. We hypothesized that the adipocyte hypoxia-signaling pathway plays an essential role in the development of obesity-associated cardiomyopathy.
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[Effect of rehabilitation training on insulin-resistance and hippocampus amyloid-beta peptide in rats with vascular dementia].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 12-10-2013
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Objective: To investigate the effect of rehabilitation training on insulin-resistance and insulindegrading enzyme (IDE) in the hippocampus in rats with vascular dementia. Methods: A total of 45 female Sprague-Dawley rats were randomly assigned into a rehabilitation group (n=15), an immobilization group (n=15), and a sham-operation group (n=15). The rats in the former 2 groups were operated on to establish the experimental vascular dementia model by bilateral common carotid artery permanent ligation. The rats learning and memory were assessed 4 weeks after the operation. The plasma level of insulin was determined by ELISA at different time points after the operation. Immunohistochemical staining was used to detect the IDE expression in the hippocampus area. Results: The rats in the rehabilitation group showed significantly better learning ability than that in the immobilization group (P<0.05). The plasma level of insulin in the rehabilitation group was lower than that in the immobilization group (P<0.05), IDE expression in the rehabilitation group was higher than that in the immobilization group (P<0.05) at 7 d and 28 d after the operation. Conclusion: Rehabilitation can accelerate the recovery of learning and memory in rats with vascular dementia, and the mechanism is possibly related to the amelioration of insulin resistance and increase of IDE expression in the hippocampus.
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Molecular Characterization of Severin fromClonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells.
PLoS Negl Trop Dis
PUBLISHED: 12-01-2013
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Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC). It has been well known that the excretory/secretory products of C. sinensis (CsESPs) play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin), which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell.
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Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold Intolerance.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 11-27-2013
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Very long-chain acyl-CoA dehydrogenase (VLCAD) enzyme catalyzes the first step of mitochondrial ?-oxidation. Patients with VLCAD deficiency present with hypoketotic hypoglycemia and cardiomyopathy, which can be exacerbated by fasting and/or cold stress. Global VLCAD knockout mice recapitulate these phenotypes: mice develop cardiomyopathy, and cold exposure leads to rapid hypothermia and death. However, the contribution of different tissues to development of these phenotypes has not been studied. We generated cardiac-specific VLCAD-deficient (cVLCAD(-/-)) mice by Cre-mediated ablation of the VLCAD in cardiomyocytes. By 6 months of age, cVLCAD(-/-) mice demonstrated increased end-diastolic and end-systolic left ventricular dimensions and decreased fractional shortening. Surprisingly, selective VLCAD gene ablation in cardiomyocytes was sufficient to evoke severe cold-intolerance in mice who rapidly developed severe hypothermia, bradycardia and markedly depressed cardiac function in response to fasting and cold-exposure (+5o C). We conclude that cardiac-specific VLCAD deficiency is sufficient to induce cold-intolerance and cardiomyopathy and is associated with reduced ATP production. These results provide strong evidence that fatty acid oxidation in myocardium is essential for maintaining normal cardiac function under these stress conditions.
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[Establishment and identification of a C57B/6 mouse sarcoidosis granuloma model].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 11-21-2013
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To establish a C57BL/6 mouse sarcoidosis granuloma model elicited by mycobacterial superoxide dismutase A peptide (SodA).
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Preparation and characterization of chain-like and peanut-like Fe3O4@SiO2 core-shell structure.
J Nanosci Nanotechnol
PUBLISHED: 11-20-2013
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The size- and shape-controlled Fe3O4@SiO2 nanocomposites were successfully synthesized via the sol-gel method. The results showed that the size, shape, and property of the products were directly influenced by the amount of TEOS, and the concentration of water-based magnetic fluid in the coating process. The morphology and properties of the products were characterized by TEM, SEM, X-ray powder diffraction, IR and EDS. The Fe3O4@SiO2 composites with easily-controlled size arranged from 58 to 835 nm could be synthesized by adjusting the experimental parameters. When TEOS amount is 1 mL and the concentration of magnetic fluid were 30.0 and 10.0 mg/mL respectively, chain-like and peanuts-like well-dispersed Fe3O4@SiO2 particles with clear core-shell structure were obtained. These size- and shape-controlled Fe3O4@SiO2 composites may have potential application in the field of targeted drug delivery and MRI contrast agent.
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A label-free silicon quantum dots-based photoluminescence sensor for ultrasensitive detection of pesticides.
Anal. Chem.
PUBLISHED: 11-11-2013
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Sensitive, rapid, and simple detection methods for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents are in urgent demand. A novel label-free silicon quantum dots (SiQDs)-based sensor was designed for ultrasensitive detection of pesticides. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce betaine and H2O2 which can quench the photoluminescence (PL) of SiQDs. Upon the addition of pesticides, the activity of AChE is inhibited, leading to the decrease of the generated H2O2, and hence the PL of SiQDs increases. By measuring the increase in SiQDs PL, the inhibition efficiency of pesticide to AChE activity was evaluated. It was found that the inhibition efficiency was linearly dependent on the logarithm of the pesticides concentration. Consequently, pesticides, such as carbaryl, parathion, diazinon, and phorate, were determined with the SiQDs PL sensing method. The lowest detectable concentrations for carbaryl, parathion, diazinon, and phorate reached 7.25 × 10(-9), 3.25 × 10(-8), 6.76 × 10(-8), and 1.9 × 10(-7) g/L, respectively, which were much lower than those previously reported. The detecting results of pesticide residues in food samples via this method agree well with those from high-performance liquid chromatography. The simple strategy reported here should be suitable for on-site pesticides detection, especially in combination with other portable platforms.
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Intra-molecular G-quadruplex structure generated by DNA-templated click chemistry: "Turn-on" fluorescent probe for copper ions.
Biosens Bioelectron
PUBLISHED: 10-08-2013
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A novel homogenous fluorescent sensor for signal-on detection of Cu(2+) has been developed based on intra-molecular G-quadruplex formed by DNA-templated click reaction and crystal violet (CV) as label-free signal reporter. The clickable DNA probe consists of two G-rich strands (A and B) bearing azide and alkyne group, respectively, and a template strand (C) locating two proximate reactants by pairing with A and B. The sequences of A and B are derived from asymmetric split of the G-quadruplex sequence (TTAGGG)4. In the presence of Cu(2+), the whole G-quadruplex sequence A-B is generated by chemical ligation of A and B via copper ion-catalyzed alkyne-azide cycloaddition, then released from template by toehold strand displacement, and consequently forming a stable intra-molecular G-quadruplex, which binds with CV to generate a strong fluorescent signal. Oppositely, weak fluorescence was obtained without Cu(2+) because of unstable intermolecular G-quadruplex formed by A and B and lack of lateral loop connection. Therefore, the Cu(2+) can be sensitively and specifically detected by the fluorescence of the CV-stained G-quadruplex with a low detection limit of 65nM and a linear range of 0.1-3µM. This method rationally integrated the DNA-templated synthesis and G-quadruplex structure-switch, presenting a simple and promising approach for biosensor development.
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Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors for Chinese patients with squamous cell carcinoma of lung harboring EGFR mutation.
J Thorac Dis
PUBLISHED: 09-24-2013
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Epidermal growth factor receptor (EGFR) mutation mostly occurred in lung adenocarcinoma, rarely in squamous cell carcinoma (SQCC). EGFR mutation rate in SQCC varied in previous reports, and the efficacy of EGFR tyrosine kinase inhibitors (TKIs) in SQCC harboring EGFR mutation has not yet been fully evaluated. The aim of this study was to investigate the efficacy EGFR-TKIs for Chinese patients with SQCC of lung harboring EGFR mutation.
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Malate synthase gene AoMls in the nematode-trapping fungus Arthrobotrys oligospora contributes to conidiation, trap formation, and pathogenicity.
Appl. Microbiol. Biotechnol.
PUBLISHED: 09-23-2013
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Malate synthase (Mls), a key enzyme in the glyoxylate cycle, is required for virulence in microbial pathogens. In this study, we identified the AoMls gene from the nematode-trapping fungus Arthobotrys oligospora. The gene contains 4 introns and encodes a polypeptide of 540 amino acids. To characterize the function of AoMls in A. oligospora, we disrupted it by homologous recombination, and the ?AoMls mutants were confirmed by PCR and Southern blot analyses. The growth rate and colony morphology of the ?AoMls mutants showed no obvious difference from the wild-type strains on potato dextrose agar (PDA) plate. However, the disruption of gene AoMls led to a significant reduction in conidiation, failure to utilize fatty acids and sodium acetate for growth, and its conidia were unable to germinate on minimal medium supplemented with sodium oleate. In addition, the trap formation was retarded in the ?AoMls mutants, which only produced immature traps containing one or two rings. Moreover, the nematicidal activity of the ?AoMls mutants was significantly decreased. Our results suggest that the gene AoMls plays an important role in conidiation, trap formation and pathogenicity of A. oligospora.
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