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Find video protocols related to scientific articles indexed in Pubmed.
A Chemical Tuned Strategy to Develop Novel Irreversible EGFR-TK Inhibitors with Improved Safety and Pharmacokinetic Profiles.
J. Med. Chem.
PUBLISHED: 11-20-2014
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Gatekeeper T790M mutation in EGFR is the most prevalent factor underlying acquired resistance. Acrylamide-bearing quinazoline derivatives are powerful irreversible inhibitors for overcoming resistance. Nevertheless, concerns about the risk of non-specific covalent modification have motivated the development of novel cysteine-targeting inhibitors. In this paper, we demonstrate that fluoro-substituted olefins can be tuned to alter Michael addition reactivity. Incorporation of these olefins into the quinazoline templates produced potent EGFR inhibitors with improved safety and pharmacokinetic properties. A lead compound 5a was validated against EGFRWT, EGFR T790M as well as A431 and H1975 cancer cell lines. Additionally, compound 5a displayed a weaker inhibition against the EGFR-independent cancer cell line SW620 when compared withafatinib. Oral administration of 5a at a dose of 30mg/kg induced tumor regression in a murine-EGFRL858R/T790M driven H1975 xenograft model. Also, 5a exhibited improved oral bioavailability and safety, as well as favorable tissue distribution properties and enhanced brain uptake. These findings provide the basis of a promising strategy toward the treatment of NSCLC patients with drug resistance.
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Dose-response for Starting and Stopping HIV Pre-Exposure Prophylaxis (PrEP) for MSM.
Clin. Infect. Dis.
PUBLISHED: 11-20-2014
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?This study estimated the number of daily tenofovir disoproxil fumarate/ emtricitabine (TDF/FTC) doses required to achieve and maintain (after discontinuation) intracellular drug concentrations that protect against HIV infection for men who have sex with men (MSM).
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Improving the carrier balance of light-emitting electrochemical cells based on ionic transition metal complexes.
Dalton Trans
PUBLISHED: 11-20-2014
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Recently, solid-state light-emitting electrochemical cells (LECs) based on ionic transition metal complexes (iTMCs) have attracted much research interest since they have the advantages of a simple device structure, a low operation voltage and compatibility with air-stable electrodes. These properties enable LECs to be cost-effective, versatile and power-efficient organic light-emitting sources. However, it is generally not easy to modify the molecular structure to achieve balanced carrier mobilities without altering the photoluminescence quantum yield of the iTMC. Furthermore, the carrier balance and the consequent device efficiency of single-layered LECs would not be easy to optimize since no carrier injection and transport layers can be used. In this perspective, some reported techniques to improve carrier balance of LECs based on iTMCs are described and reviewed. The importance and impact of these studies are highlighted. The effects on device lifetime and turn-on time because of employing these techniques to improve the carrier balance are also discussed. This perspective concludes that even with electrochemically doped layers, improving the carrier balance of LECs would be required for realizing efficient electroluminescent emission from simple-structure organic light-emitting sources.
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Self-powered ultrafast broadband photodetector based on p-n heterojunctions of CuO/Si nanowire array.
ACS Appl Mater Interfaces
PUBLISHED: 11-11-2014
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A new self-powered broadband photodetector was fabricated by coating an n-silicon nanowire (n-Si NW) array with a layer of p-cupric oxide (CuO) nanoflakes through a new simple solution synthesis method. The p-n heterojunction shows excellent rectification characteristics in the dark and distinctive photovoltaic behavior under broadband light illumination. The photoresponse of the detector at zero bias voltage shows that this self-powered photodetector is highly sensitive to visible and near-infrared light illuminations, with excellent stability and reproducibility. Ultrafast response rise and recovery times of 60 µs and 80 µs, respectively, are shown by the CuO based nano-photodetector. In addition, the broadband photodetector can also provide a rapid binary response, with current changing from positive to negative upon illumination under a small bias. The binary response arises from the photovoltaic behavior and the low turn-on voltage of the CuO/Si NW device. These properties make the CuO/Si NW broadband photodetector suitable for applications that require high response speeds and self-sufficient functionality.
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Tenofovir Diphosphate in Dried Blood Spots As an Objective Measure of Adherence in HIV-Infected Women.
AIDS Res. Hum. Retroviruses
PUBLISHED: 10-21-2014
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Abstract Simple and reproducible tools to assess antiretroviral adherence are needed. A level of tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) <1,250?fmol/punch is predicted to identify imperfect adherence. Herein we evaluated TFV-DP in DBS as a measure of adherence among HIV-infected women. DBS and peripheral blood mononuclear cells (PBMCs) were collected twice (?1 week apart) in 35 well-controlled HIV-infected women [median age 42 years, 14 African American/black (AA)] receiving daily coformulated tenofovir/emtricitabine and either atazanavir/ritonavir (n=20) or raltegravir (n=16). TFV-DP in DBS and PBMCs was quantified by LC-MS/MS. Six-month adherence was measured as average days between monthly pharmacy refills. Data were loge transformed for analysis and presented as median (range); the correlation between continuous variables was analyzed using the Pearson correlation coefficient. The average TFV-DP between the two visits (aTFV-DP) in DBS and PBMCs was 1,874 (706-3,776) fmol/punch and 125 (1-278) fmol/10(6) cells, respectively. AA women had lower levels of aTFV-DP in DBS compared to whites (1,660 vs. 1,970?fmol/punch; p=0.04), with a viremic patient having the lowest drug levels (706?fmol/punch). Days between pharmacy refills were 34 (30-54) vs. 30 (26-40) in women with TFV-DP in DBS <1,250 vs. ?1,250?fmol/punch (p=0.006). TFV-DP in DBS was negatively correlated with an increasing number of days between refills (r=-0.56, p=0.002). TFV-DP DBS was a reliable and objective measure of adherence in HIV-infected women based on a strong inverse relationship with pharmacy refill adherence.
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Biological Network Module-Based Model for the Analysis of Differential Expression in Shotgun Proteomics.
J. Proteome Res.
PUBLISHED: 10-21-2014
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Protein differential expression analysis plays an important role in the understanding of molecular mechanisms as well as the pathogenesis of complex diseases. With the rapid development of mass spectrometry, shotgun proteomics using spectral counts has become a prevailing method for the quantitative analysis of complex protein mixtures. Existing methods in differential proteomics expression typically carry out analysis at the single-protein level. However, it is well-known that proteins interact with each other when they function in biological processes. In this study, focusing on biological network modules, we proposed a negative binomial generalized linear model for differential expression analysis of spectral count data in shotgun proteomics. In order to show the efficacy of the model in protein expression analysis at the level of protein modules, we conducted two simulation studies using synthetic data sets generated from theoretical distribution of count data and a real data set with shuffled counts. Then, we applied our method to a colorectal cancer data set and a nonsmall cell lung cancer data set. When compared with single-protein analysis methods, the results showed that module-based statistical model which takes account of the interactions among proteins led to more effective identification of subtle but coordinated changes at the systems level.
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Mesenchymal Stem Cells with Increased Stromal Cell-Derived Factor 1 Expression Enhanced Fracture Healing.
Tissue Eng Part A
PUBLISHED: 09-25-2014
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Treatment of critical size bone defects pose a challenge in orthopedics. Stem cell therapy together with cytokines has the potential to improve bone repair as they cause the migration and homing of stem cells to the defect site. However, the engraftment, participation, and recruitment of other cells within the regenerating tissue are important. To enhance stem cell involvement, this study investigated overexpression of stem cells with stromal cell-derived factor 1 (SDF-1) using an adenovirus. We hypothesized that these engineered cells would effectively increase the migration of native cells to the site of fracture, enhancing bone repair. Before implantation, we showed that SDF-1 secreted by transfected cells increased the migration of nontransfected cells. In a rat defect bone model, bone marrow mesenchymal stem cells overexpressing SDF-1 showed significantly (p=0.003) more new bone formation within the gap and less bone mineral loss at the area adjacent to the defect site during the early bone healing stage. In conclusion, SDF-1 was shown to play an important role in accelerating fracture repair and contributing to bone repair in rat models, by recruiting more host stem cells to the defect site and encouraging osteogenic differentiation and production of bone.
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Stochastic bifurcation characteristics of SMA intravascular stent subjected to radial and axial excitations.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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A kind of shape memory alloy (SMA) hysteretic nonlinear model is developed, and the stochastic bifurcation characteristics of SMA intravascular stents subjected to radial and axial excitations are studied in this paper. A new nonlinear differential item is introduced to interpret the hysteretic phenomena of SMA strain-stress curves, and the dynamic model of SMA intravascular stent subjected to radial and axial stochastic excitations is established. The conditions of the system's stochastic stability are determined, and the probability density function of the system response is obtained. Finally, the stochastic Hopf bifurcation characteristics of the system are analyzed. Theoretical analysis and numerical simulation show that the system stability varies with bifurcation parameters, and stochastic Hopf bifurcation occurs in the process; there are two limit cycles in the stationary probability density of the system response in some cases, which means that there are two vibration amplitudes whose probability are both very high; jumping phenomena between the two vibration amplitudes appears with the change of conditions, which may cause stent fracture or loss. The results of this paper are helpful for application of SMA intravascular stent in biomedical engineering fields.
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The relationship between the plant-encoded RNA-dependent RNA polymerase 1 and alternative oxidase in tomato basal defense against Tobacco mosaic virus.
Planta
PUBLISHED: 09-05-2014
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Salicylic acid (SA) plays a critical role in plant defense against pathogen attack. The SA-induced viral defense in plants is distinct from the pathways mediating bacterial and fungal defense, which is pathogenesis-related protein-independent but involves an RNA-dependent RNA polymerase 1 (RDR1)-mediated RNA silencing mechanism and/or an alternative oxidase (AOX)-associated defense pathway. However, the relationship between these two viral defense-related pathways remains unclear. In this study, Tobacco mosaic virus (TMV) inoculation onto Solanum lycopersicum (tomato) leaves induced a rapid induction of the SlAOX1a transcript level as well as the total and CN-resistant respiration at 0.5 dpi, followed by an increase in SlRDR1 gene expression at 1 dpi in the upper uninoculated leaves. Silencing SlRDR1 using virus-induced gene silencing system significantly reduced SlRDR1 expression and tomato defense against TMV but had no evident effect on SlAOX1a transcription. Conversely, silencing SlAOX1a not only effectively reduced the AOX1a transcript level, but also blocked the TMV-induced SlRDR1 expression and decreased the basal defense against TMV. Furthermore, the application of an exogenous AOX activator on empty vector-silenced control plants greatly induced the accumulation of SlRDR1 and SlAOX1a transcript and reduced TMV viral RNA accumulation, but failed to have such effects on SlRDR1-silenced plants. Moreover, RDR1-overexpressed transgenic Nicotiana benthamiana plants enhanced defense against TMV than the empty vector-transformed plants, but these effects were not affected by the exogenous AOX activator or inhibitor. These results indicate that RDR1 is involved in the AOX-mediated defense pathway against TMV infection and plays a crucial role in enhancing RNA silencing to limit virus systemic spread.
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Overexpression of PSF1 is correlated with poor prognosis in hepatocellular carcinoma patients.
Int. J. Biol. Markers
PUBLISHED: 09-05-2014
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PSF1 is a subunit of the GINS complex which is essential for establishment of DNA replication forks, and the progression of the replisome. Previous studies have shown a close relationship between PSF1 and cell cycle in the proliferation of immature cells as well as tumors. The purpose of this study was to measure PSF1 expression in hepatocellular carcinoma (HCC) tissues, and determine the effects of down-regulation of PSF1 expression on growth of cancer cells, the cell cycle, apoptosis and cell invasiveness.
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Down-regulation of ether-a-go-go-related gene potassium channel protein through sustained stimulation of AT1 receptor by angiotensin II.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-28-2014
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We investigated the effects of AT1 receptor stimulation by angiotensin II (Ang II) on human ether-a-go-go-related gene (hERG) potassium channel protein in a heterogeneous expression system with the human embryonic kidney (HEK) 293 cells which stably expressed hERG channel protein and were transiently transfected with the human AT1 receptors (HEK293/hERG). Western-blot analysis showed that Ang II significantly decreased the expression of mature hERG channel protein (155-kDa band) in a time- and dose-dependent manner without affecting the level of immature hERG channel protein (135-kDa band). The relative intensity of 155-kDa band was 64.7±6.8% of control (P<0.01) after treatment of Ang II at 100nM for 24h. To investigate the effect of Ang II on the degradation of mature hERG channel protein, we blocked forward trafficking from ER to Golgi with a Golgi transit inhibitor brefeldin A (10?M). Ang II significantly enhanced the time-dependent reduction of mature hERG channel protein. In addition, the proteasomal inhibitor lactacystin (5?M) inhibited Ang II-mediated the reduction of mature hERG channel protein, but the lysosomal inhibitor bafilomycin A1 (1?M) had no effect on the protein. The protein kinase C (PKC) inhibitor bisindolylmaleimide 1 (1?M) antagonized the reduction of mature hERG channel protein induced by Ang II. The results indicate that sustained stimulation of AT1 receptors by Ang II reduces the mature hERG channel protein via accelerating channel proteasomal degradation involving the PKC pathway.
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Elevation in circulating YKL-40 concentration in patients with cerebrovascular disease.
Bosn J Basic Med Sci
PUBLISHED: 08-14-2014
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YKL-40 is a novel inflammatory protein. Elevated serum levels of YKL-40 have been reported in patients with atherosclerosis and other cardiovascular diseases, but the circulating profile of YKL-40 in patients with cerebrovascular disease has been less investigated. This prospective observational study aimed to determine serum levels of YKL-40 in patients with different subtypes and severities of cerebrovascular disease. Eighty patients with acute ischemic stroke, 30 patients with acute hemorrhagic stroke, 15 patients with transient ischemic attack (TIA) and 18 age- and gender-matched healthy control subjects were recruited. Blood was sampled. Serum levels of YKL-40 were measured by ELISA. In healthy control subjects, serum levels of YKL-40 were 45.09 ± 31.41 ng/ml, significantly lower than those in patients with acute ischemic stroke (178.58 ± 127.78 ng/ml), hemorrhagic stroke (105.32 ± 87.35 ng/ml) and TIA (148.09 ± 108 ng/ml) respectively (P<0.05). When the 80 acute ischemic stroke cases were stratified into four Oxfordshire Community Stroke subtypes, serum levels of YKL-40 were significantly higher in patients with total anterior (n=16), partial anterior (n=25) and posterior (n=12) circulation infarctions respectively than those with lacunar (n=27) infarction (P<0.05). Moreover, 63 of 80 patients with acute ischemic stroke survived. Circulating levels of YKL-40 in these stroke survivors were associated with the United States National Institutes of Health Stroke Scale (NIHSS) scores of neurological deficit. In summary, serum levels of YKL-40 were elevated in patients with cerebrovascular disease in lesion subtype- and severity-dependent manners. These observations suggest a potential for YKL-40 as a diagnostic/prognostic biomarker for cerebrovascular disease.
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Intravoxel incoherent motion diffusion-weighted MR imaging of breast cancer at 3.0 tesla: Comparison of different curve-fitting methods.
J Magn Reson Imaging
PUBLISHED: 07-21-2014
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To compare three different curve-fitting methods for intravoxel incoherent motion (IVIM) analysis in breast cancer.
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Nonlinear dynamic characteristics of SMA intravascular stent under radial stochastic loads.
Biomed Mater Eng
PUBLISHED: 06-24-2014
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Nonlinear dynamic characteristics of shape memory alloy (SMA) intravascular stent under radial stochastic loads were studied in this paper. Von de Pol item was improved to interpret the hysteretic phenomena of SMA, and the nonlinear dynamic model of SMA intravascular stent under radial stochastic loads was developed. The conditions of stochastic stability of the system were obtained in singular boundary theory. The steady-state probability density function of the dynamic response of the system was given, and the stochastic Hopf bifurcation characteristics of the system were analyzed. Theoretical analysis and numerical simulation show that the stability of the trivial solution varies with bifurcation parameters, and stochastic Hopf bifurcation appears in the process, which can cause stent fracture or loss. The results of this paper are helpful to application of SMA intravascular stent in biomedical engineering fields.
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Treatment protocols for growth hormone-secreting pituitary adenomas combined with craniofacial fibrous dysplasia: A case report of atypical McCune-Albright syndrome.
Exp Ther Med
PUBLISHED: 06-19-2014
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McCune-Albright syndrome (MAS) is a rare, post-zygotic (non-germline) disorder, characterized by hypersecretory endocrinopathies, fibrous dysplasia of the bone and café-au-lait macules. The most common endocrine dysfunction is gonadal hyperfunction; thus, hypersecretion of growth hormones (GHs) as a manifestation of endocrine hyperfunction in MAS is rarely reported. MAS affects both genders, although the majority of cases have been reported in young females. Atypical presentations of MAS, with only one or two of the classic symptoms, have been previously described, but remain particularly challenging due to the lack of a diagnostic phenotype. In patients with atypical MAS, analysis of mutations in the gene of the ?-subunit of the stimulatory G-protein is limited; thus, diagnosis is based on clinical judgment. In the present study, a male with polyostotic fibrous dysplasia and GH-secreting pituitary adenomas, diagnosed with atypical MAS, was reported. The pituitary adenoma was effectively treated with radiotherapy and the patient underwent surgery for the polyostotic fibrous dysplasia, with marked improvements observed in appearance.
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Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula.
ISME J
PUBLISHED: 06-18-2014
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The gut microbiota is hypothesized to have a critical role in metabolic diseases, including type 2 diabetes (T2D). A traditional Chinese herbal formula, Gegen Qinlian Decoction (GQD), can alleviate T2D. To find out whether GQD modulates the composition of the gut microbiota during T2D treatment, 187 T2D patients were randomly allocated to receive high (HD, n=44), moderate (MD, n=52), low dose GQD (LD, n=50) or the placebo (n=41) for 12 weeks in a double-blinded trial. Patients who received the HD or MD demonstrated significant reductions in adjusted mean changes from baseline of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) compared with the placebo and LD groups. Pyrosequencing of the V3 regions of 16S rRNA genes revealed a dose-dependent deviation of gut microbiota in response to GQD treatment. This deviation occurred before significant improvement of T2D symptoms was observed. Redundancy analysis identified 47 GQD-enriched species level phylotypes, 17 of which were negatively correlated with FBG and 9 with HbA1c. Real-time quantitative PCR confirmed that GQD significantly enriched Faecalibacterium prausnitzii, which was negatively correlated with FBG, HbA1c and 2-h postprandial blood glucose levels and positively correlated with homeostasis model assessment of ?-cell function. Therefore, these data indicate that structural changes of gut microbiota are induced by Chinese herbal formula GQD. Specifically, GQD treatment may enrich the amounts of beneficial bacteria, such as Faecalibacterium spp. In conclusion, changes in the gut microbiota are associated with the anti-diabetic effects of GQD.
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Chest X-ray and CT findings of early H7N9 avian influenza cases.
Acta Radiol
PUBLISHED: 06-12-2014
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The H7N9 strain of bird flu is a new type of avian flu that was identified at the end of March 2013. The disease is concerning because most patients have become severely ill.
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Long-term changes in the masseter muscle following reduction gonioplasty.
J Craniofac Surg
PUBLISHED: 06-06-2014
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Many plastic surgeons use mandibular osteotomy (reduction gonioplasty) without masseter resection to correct a square face. However, there is not enough long-term observation of the masseter after reduction gonioplasty, although some researches have already confirmed that the volume of masseter muscle does decrease shortly after reduction gonioplasty.
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Increased expression of native cytosolic Cu/Zn superoxide dismutase and ascorbate peroxidase improves tolerance to oxidative and chilling stresses in cassava (Manihot esculenta Crantz).
BMC Plant Biol.
PUBLISHED: 05-30-2014
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Cassava (Manihot esculenta Crantz) is a tropical root crop, and is therefore, extremely sensitive to low temperature; its antioxidative response is pivotal for its survival under stress. Timely turnover of reactive oxygen species (ROS) in plant cells generated by chilling-induced oxidative damages, and scavenging can be achieved by non-enzymatic and enzymatic reactions in order to maintain ROS homeostasis.
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MyD88 and TRIF mediate divergent inflammatory and regenerative responses to skeletal muscle ischemia.
Physiol Rep
PUBLISHED: 05-01-2014
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We have previously shown that MyD88 KO mice appear protected from ischemic muscle injury while TRIF KO mice exhibit sustained necrosis after femoral artery ligation (FAL). However, our previous data did not differentiate whether the protective effect of absent MyD88 signaling was secondary to attenuated injury after FAL or quicker recovery from the insult. The purpose of this study was to delineate these different possibilities. On the basis of previous findings, we hypothesized that MyD88 signaling promotes enhanced inflammation while TRIF mediates regeneration after skeletal muscle ischemia. Our results show that after FAL, both MyD88 KO mice and TRIF KO mice have evidence of ischemia, as do their control counterparts. However, MyD88 KO mice had lower levels of serum IL-6 24 h after FAL, while TRIF KO mice demonstrated sustained serum IL-6 up to 1 week after injury. Additionally, MyD88 KO mice had higher nuclear content and larger myofibers than control animals 1 week after injury. IL-6 is known to have differential effects in myoblast function, and can inhibit proliferation and differentiation. In tibialis anterior muscle harvested from injured animals, IL-6 levels were higher and the proliferative marker MyoD was lower in TRIF KO mice by PCR. Furthermore, expression of MyD88 appeared to be higher in skeletal muscle of TRIF KO mice. In vitro, we showed that myoblast differentiation and proliferation were attenuated in response to IL-6 treatment giving credence to the finding that low IL-6 in MyD88 KO mice may be responsible for larger myocyte sizes 1 week after FAL. We conclude that MyD88 and TRIF work in concert to mediate a balanced response to ischemic injury.
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[Retrospective clinical analysis of heterotopic pancreas misdiagnosed as gastrointestinal stromal tumors].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 04-25-2014
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To improve the differential diagnosis and treatment between heterotopic pancreas and gastrointestinal stromal tumor.
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Molecular identification of adulteration in mutton based on mitochondrial 16S rRNA gene.
Mitochondrial DNA
PUBLISHED: 04-18-2014
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Abstract The aim of this study is to set up a protocol for identification of the adulteration in mutton based on mitochondrial 16S rRNA gene. The multiplex polymerase chain reaction (multi-PCR) assay was carried out to trace the impure DNA in mutton. A universal primer pair yielded an approximate 610?bp fragment in mutton, pork, duck, chicken, horse and cat meats. The amplicons of multi-PCR assay represented the species-specific products, which could be discriminated by the size ranging from 106?bp to 532?bp. Subsequently, the authentication of each fragment was also confirmed by sequencing. Random analyses of adulterants with various meats yielded the identical results to their components, showing the suitability of the multi-PCR assay for tracing of adulterant meats with high-accuracy and precision. This assay was sensitive to detect the species-specific DNA in different proportional mixtures of mutton and duck/pork (9.1%-90.9%). In conclusion, this multi-PCR assay successfully discriminated the double-, triple-, quadruple-, and quintuple-mixtures containing variant counterparts. This method will be particularly useful in the detection of mutton adulteration in processed foods further.
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An enriched environment reduces the stress level and locomotor activity induced by acute morphine treatment and by saline after chronic morphine treatment in mice.
Neuroreport
PUBLISHED: 04-09-2014
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This study investigated the relationships among an enriched environment, stress levels, and drug addiction. Mice were divided randomly into four treatment groups (n=12 each): enriched environment without restraint stress (EN), standard environment without restraint stress (SN), enriched environment with restraint stress (ES), and standard environment with restraint stress (SS). Mice were reared in the respective environment for 45 days. Then, the ES and SS groups were subjected to restraint stress daily (2 h/day) for 14 days, whereas the EN and SN groups were not subjected to restraint stress during this stage. The stress levels of all mice were tested in the elevated plus maze immediately after exposure to restraint stress. After the 2-week stress testing period, mice were administered acute or chronic morphine (5 mg/kg) treatment for 7 days. Then, after a 7-day withdrawal period, the mice were injected with saline (1 ml/kg) or morphine (5 mg/kg) daily for 2 days to observe locomotor activity. The results indicated that the enriched environment reduced the stress and locomotor activity induced by acute morphine administration or saline after chronic morphine treatment. However, the enriched environment did not significantly inhibit locomotor activity induced by morphine challenge. In addition, the stress level did not mediate the effect of the enriched environment on drug-induced locomotor activity after acute or chronic morphine treatment.
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Residential indoor and personal PM10 exposures of ambient origin based on chemical components.
J Expo Sci Environ Epidemiol
PUBLISHED: 03-06-2014
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Many studies have focused on the relationships of particulate matter between indoor, outdoor and personal exposure; however, considerable uncertainties remain regarding the portion of indoor particles and personal exposure of ambient origin. As part of the Particle Exposure Assessment for Community Elderly (PEACE) study in Tianjin, China, we have further interpreted the relationships between personal, residential indoor, outdoor and community PM10 (particulate matter with aerodynamic diameters of less than 10??m). Comparisons of the chemical compositions of PM10 samples were performed using the coefficient of divergence (COD). A robust regression method, least-trimmed squared (LTS) regression, was used to estimate the infiltration factors of PM10 from residential outdoor to indoor environments based on the particulate component concentrations. Personal exposures of ambient origin were also estimated. A relatively good correlation was found between the personal and indoor PM10 samples with respect to chemical composition. The infiltration factors (Finf) of the residential indoor-outdoor PM10 were 0.74±0.31 (mean±SD) in summer and 0.44±0.22 in winter, with medians of 0.98 and 0.48, respectively. The residential outdoor contributions to the indoor environments were 87±55??g/m(3) in summer and 80±54??g/m(3) in winter, with medians of 75??g/m(3) and 61??g/m(3), respectively. The personal exposures of ambient origin were 92±44??g/m(3) in summer and 89±47??g/m(3) in winter, with medians of 81??g/m(3) and 80??g/m(3), respectively. This study indicated that the infiltrations in an urbanized area in North China exhibited a seasonal difference: the residential outdoor contributions to residential indoor environments were larger in summer due to the higher use of natural ventilation. The personal exposures of ambient origin were comparable during the different seasons, whereas those of non-ambient origin were higher in summer than in winter.
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Effect of iodine excess on Th1, Th2, Th17, and Treg cell subpopulations in the thyroid of NOD.H-2h4 mice.
Biol Trace Elem Res
PUBLISHED: 03-04-2014
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Iodine is an indispensable micronutrient for thyroid hormone synthesis and metabolism. Iodine excess may trigger and exacerbate autoimmune thyroiditis (AIT). The pathogenetic mechanism of iodine excess-induced AIT is partly regarded as T helper type 1 (Th1) cell and/or T helper type 17 (Th17) cell dominant autoimmune disease. It is still unknown whether other cluster of differentiation 4+ T (CD4+T) cell subpopulations are involved. Therefore, we studied the profile of all the CD4+T cell subpopulations of the thyroid in iodine excess-induced nonobese diabetic-H2h4 (NOD.H-2h4) mice to explore the potential immunologic mechanism of iodine excess-induced AIT. A total of 40 healthy 8-week-old NOD.H-2h4 mice were randomly allocated into the normal group (NG, n=20) and the test group (TG, n=20), which were fed with double-distilled water and 0.05% sodium iodine (NaI) for 8 weeks, respectively. Compared to the NG, in the TG, the incidence of AIT was significantly higher, the expressions of interleukin-17 (IL-17), interleukin-23 (IL-23), interleukin-6 (IL-6), and transforming growth factor-? (TGF-?) remarkably increased by immunohistochemistry, which were further verified by reverse transcription polymerase chain reaction (RT-PCR), while the protein and mRNA expressions of interleukin-4 (IL-4) and interferon-? (INF-?) decreased markedly. In the AIT mice, the expressions of retinoic acid-related orphan receptor gamma t (ROR?t), retinoic acid-related orphan receptor alpha (ROR?), and signal transducer and activator of transcription 3 (STAT3) were much higher, the expression of forkhead/winged helix transcription factor p3 (Foxp3) significantly lower by western blot, and the proportion of Th17 cells by flow cytometry method (FCM) much larger compared to those of the NG group. In conclusion, Th17 cells may promote an inflammatory reaction in the development of iodine-excess-induced AIT, which is negatively regulated by Th1, T helper type 2 (Th2), and regulatory T (Treg) cells.
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Protective role of hydrogen-rich water on aspirin-induced gastric mucosal damage in rats.
World J. Gastroenterol.
PUBLISHED: 03-04-2014
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To investigate the role of the hydrogen-rich water (HRW) in the prevention of aspirin-induced gastric mucosal injury in rats.
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The PPAR?-FGF21 hormone axis contributes to metabolic regulation by the hepatic JNK signaling pathway.
Cell Metab.
PUBLISHED: 03-03-2014
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The cJun NH2-terminal kinase (JNK) stress signaling pathway is implicated in the metabolic response to the consumption of a high-fat diet, including the development of obesity and insulin resistance. These metabolic adaptations involve altered liver function. Here, we demonstrate that hepatic JNK potently represses the nuclear hormone receptor peroxisome proliferator-activated receptor ? (PPAR?). Therefore, JNK causes decreased expression of PPAR? target genes that increase fatty acid oxidation and ketogenesis and promote the development of insulin resistance. We show that the PPAR? target gene fibroblast growth factor 21 (Fgf21) plays a key role in this response because disruption of the hepatic PPAR?-FGF21 hormone axis suppresses the metabolic effects of JNK deficiency. This analysis identifies the hepatokine FGF21 as a critical mediator of JNK signaling in the liver.
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Role of testis-specific high-mobility-group protein in transcriptional regulation of inducible nitric oxide synthase expression in the liver of endotoxic shock mice.
FEBS J.
PUBLISHED: 02-24-2014
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Inducible nitric oxide synthase (iNOS) plays a central role in tissue damage during endotoxic shock. However, the underlying mechanisms that control transcription of iNOS are not completely defined. A screening strategy with DNA pull-down technology and two-dimensional difference in gel electrophorcsis (2D-DIGE) analysis was used to identify regulators that interact with the iNOS promoter. We found 14 proteins that bind to the iNOS promoter in the liver of endotoxic shock mice. After matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis, one of these proteins was identified as testis-specific high-mobility-group protein (tsHMG), an alternative splicing isoform encoded by the mitochondrial transcription factor A gene. We identified the binding sites of tsHMG on the iNOS promoter using a LiquiChip system, and further confirmed interactions between tsHMG and iNOS by RT-PCR, western blotting and immunofluorescence. Functional analysis by over-expression and RNA interference of tsHMG revealed that tsHMG regulates lipopolysaccharide-stimulated iNOS expression. These results indicate that tsHMG participates in modulation of iNOS expression in the early stage of endotoxic shock.
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Evaluation of high-risk clinicopathological indicators in gastrointestinal stromal tumors for prognosis and imatinib treatment outcome.
BMC Gastroenterol
PUBLISHED: 02-23-2014
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Although the clinical benefit of imatinib adjuvant therapy for high-risk patients with gastrointestinal stromal tumor (GIST) has been proven, the recurrence rate still remains high. This study aimed to sub-divide high-risk GIST patients with some "very high-risk" factors for more precise prognostic indicator, and possible association with efficiency of imatinib adjuvant therapy.
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A Multicenter Randomized Controlled Trial of a Nutrition Intervention Program in a Multiethnic Adult Population in the Corporate Setting Reduces Depression and Anxiety and Improves Quality of Life: The GEICO Study.
Am J Health Promot
PUBLISHED: 02-15-2014
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Abstract Purpose . To determine whether a plant-based nutrition program in a multicenter, corporate setting improves depression, anxiety, and productivity. Design . A quasi-experimental study examined the impact of diet on emotional well-being and productivity. Setting . The study was conducted in 10 corporate sites of a major U.S. insurance company. Subjects . There were 292 participants (79.8% women, 20.2% men), with body mass index ?25 kg/m(2) and/or previous diagnosis of type 2 diabetes. Intervention . Either weekly instruction in following a vegan diet or no instruction was given for 18 weeks. Measures . Depression and anxiety were measured using the Short Form-36 questionnaire. Work productivity was measured using the Work Productivity and Activity Impairment questionnaire. Analysis . Baseline characteristics were examined by t-test for continuous variables and ?(2) test for categorical variables. Analysis of covariance models were adjusted for baseline covariates. Paired t-tests were used to determine within-group changes and t-tests for between-group differences. Results . In an intention-to-treat analysis, improvements in impairment because of health (p < .001), overall work impairment because of health (p = .02), non-work-related activity impairment because of health (p < .001), depression (p = .02), anxiety (p = .04), fatigue (p < .001), emotional well-being (p = .01), daily functioning because of physical health (p = .01), and general health (p = 0.02) in the intervention group were significantly greater than in the control group. Results were similar for study completers. Conclusion . A dietary intervention improves depression, anxiety, and productivity in a multicenter, corporate setting.
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An optimized HPLC/MS/MS method for quantification of excitatory amino acids in rat hippocampus and its application in brain ischemia/reperfusion research.
Biomed. Chromatogr.
PUBLISHED: 02-10-2014
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An optimized HPLC/MS/MS method was established to quantify glutamate (Glu) and aspartic acid (Asp) in rat hippocampus with glutamate-d5 (Glu-d5) as internal standard. The mass spectrometry was operated under the multiple reaction monitoring mode using electrospray ionization in the positive ion mode for Glu and negative ion mode for Asp. The retention times of Glu, Asp and Glu-d5 were 1.53, 2.07 and 1.52?min, respectively. The linearity of calibration curves was good, with r(2) ?>?0.99 and a lower limit of quantitation of 10?ng/mL. The intra-day precisions (relative standard deviation, RSD) of Glu and Asp were in the range of 3.61-8.17 and 4.22-10.09%, respectively; the inter-day precisions (RSD) of Glu and Asp were in the range of 3.57-5.19 and 2.49-5.04%, respectively. The accuracies of Glu and Asp were in the range of -2.10-6.20 and -0.90-10.00%, respectively. The recovery rates of 10, 100 and 1000?ng/mL were found to be 0.89?±?0.24, 1.01?±?0.10 and 0.90?±?0.12 for Glu and 0.99?±?0.26, 0.93?±?0.07 and 1.13?±?0.13 for Asp, respectively. This optimized method was successfully applied to quantify the concentration of Glu and Asp in rat hippocampus in brain ischemia/reperfusion research. Copyright © 2014 John Wiley & Sons, Ltd.
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A case report of acute myocardial infarction concomitant with Standford type B aortic dissection.
J Cardiovasc Dis Res
PUBLISHED: 02-07-2014
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Acute myocardial infarction (AMI) concomitant with aortic dissection (AD) is rare but a devastating situation if misdiagnosed as simply AMI, followed by anticoagulant or thrombolytic therapy. In such cases, Standford type B AD was extremely infrequent.
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Gastrointestinal stromal tumor: 15-years' experience in a single center.
BMC Surg
PUBLISHED: 01-20-2014
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Gastrointestinal stromal tumor (GIST) is known for its wide variability in biological behaviors and it is difficult to predict its malignant potential. The aim of this study is to explore the characteristics and prognostic factors of GIST.
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Maternal hypertension after a low-birth-weight delivery differs by race/ethnicity: evidence from the National Health and Nutrition Examination Survey (NHANES) 1999-2006.
PLoS ONE
PUBLISHED: 01-01-2014
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Studies have suggested an increase in maternal morbidity and mortality due to cardiovascular diseases in women with a prior low-birth-weight (LBW, <2,500 grams) delivery. This study evaluated blood pressure and hypertension in women who reported a prior preterm or small-for-gestational-age (SGA) LBW delivery in the National Health and Nutrition Examination Survey 1999-2006 (n?=?6,307). This study also aimed to explore if race/ethnicity, menopause status, and years since last pregnancy modified the above associations. A total of 3,239 white, 1,350 black, and 1,718 Hispanics were assessed. Linear regression models were used to evaluate blood pressure by birth characteristics (preterm-LBW, SGA-LBW, and birthweight ?2,500). Logistic regression models estimated the odds ratios (OR) of hypertension among women who reported a preterm-LBW or SGA-LBW delivery compared with women who reported an infant with birthweight ?2,500 at delivery. Overall, there was a positive association between a preterm-LBW delivery and hypertension (adjusted OR?=?1.39, 95% confidence interval (CI) 1.02-1.90). Prior SGA-LBW also increased the odds of hypertension, but the estimate did not reach statistical significance (adjusted OR?=?1.21, 95% CI 0.76-1.92). Race/ethnicity modified the above associations. Only black women had increased risk of hypertension following SGA-LBW delivery (adjusted OR?=?2.09, 95% CI 1.12-3.90). Black women were at marginally increased risk of hypertension after delivery of a preterm-LBW (adjusted OR?=?1.49, 95% CI 0.93-2.38). Whites and Hispanics had increased, but not statistically significant, risk of hypertension after a preterm-LBW (whites: adjusted OR?=?1.39, 95% CI 0.92-2.10; Hispanics: adjusted OR?=?1.22, 95% CI 0.62-2.38). Stratified analysis indicated that the associations were stronger among women who were premenopausal and whose last pregnancy were more recent. The current study suggests that in a representative United States population, women with a history of preterm- or SGA-LBW deliveries have increased odds of hypertension and this risk appears to be higher for black women and younger women.
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Prognostic value of Ki67 index in gastrointestinal stromal tumors.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Ki67 index is one of the most important immunocytochemical markers of proliferation in tumors, but the criterion of Ki67 index in GISTs was not well-defined yet. Our study aims to fully evaluate the prognostic value of Ki67 index in GIST patients and efficiency of imatinib adjuvant therapy.
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Calcium sensing receptor modulates extracellular calcium entry and proliferation via TRPC3/6 channels in cultured human mesangial cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Calcium-sensing receptor (CaSR) has been demonstrated to be present in several tissues and cells unrelated to systemic calcium homeostasis, where it regulates a series of diverse cellular functions. A previous study indicated that CaSR is expressed in mouse glomerular mesangial cells (MCs), and stimulation of CaSR induces cell proliferation. However, the signaling cascades initiated by CaSR activation in MCs are currently unknown. In this study, our data demonstrate that CaSR mRNA and protein are expressed in a human mesangial cell line. Activating CaSR with high extracellular Ca2+ concentration ([Ca2+]o) or spermine induces a phospholipase C (PLC)-dependent increase in intracellular Ca2+ concentration ([Ca2+]i). Interestingly, the CaSR activation-induced increase in [Ca2+]i results not only from intracellular Ca2+ release from internal stores but also from canonical transient receptor potential (TRPC)-dependent Ca2+ influx. This increase in Ca2+ was attenuated by treatment with a nonselective TRPC channel blocker but not by treatment with a voltage-gated calcium blocker or Na+/Ca2+ exchanger inhibitor. Furthermore, stimulation of CaSR by high [Ca2+]o enhanced the expression of TRPC3 and TRPC6 but not TRPC1 and TRPC4, and siRNA targeting TRPC3 and TRPC6 attenuated the CaSR activation-induced [Ca2+]i increase. Further experiments indicate that 1-oleoyl-2-acetyl-sn-glycerol (OAG), a known activator of receptor-operated calcium channels, significantly enhances the CaSR activation-induced [Ca2+]i increase. Moreover, under conditions in which intracellular stores were already depleted with thapsigargin (TG), CaSR agonists also induced an increase in [Ca2+]i, suggesting that calcium influx stimulated by CaSR agonists does not require the release of calcium stores. Finally, our data indicate that pharmacological inhibition and knock down of TRPC3 and TRPC6 attenuates the CaSR activation-induced cell proliferation in human MCs. With these data, we conclude that CaSR activation mediates Ca2+ influx and cell proliferation via TRPC3 and TRPC6 in human MCs.
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The use of functional chemical-protein associations to identify multi-pathway renoprotectants.
PLoS ONE
PUBLISHED: 01-01-2014
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Typically, most nephropathies can be categorized as complex human diseases in which the cumulative effect of multiple minor genes, combined with environmental and lifestyle factors, determines the disease phenotype. Thus, multi-target drugs would be more likely to facilitate comprehensive renoprotection than single-target agents. In this study, functional chemical-protein association analysis was performed to retrieve multi-target drugs of high pathway wideness from the STITCH 3.1 database. Pathway wideness of a drug evaluated the efficiency of regulation of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in quantity. We identified nine experimentally validated renoprotectants that exerted remarkable impact on KEGG pathways by targeting a limited number of proteins. We selected curcumin as an illustrative compound to display the advantage of multi-pathway drugs on renoprotection. We compared curcumin with hemin, an agonist of heme oxygenase-1 (HO-1), which significantly affects only one KEGG pathway, porphyrin and chlorophyll metabolism (adjusted p?=?1.5×10-5). At the same concentration (10 µM), both curcumin and hemin equivalently mitigated oxidative stress in H2O2-treated glomerular mesangial cells. The benefit of using hemin was derived from its agonistic effect on HO-1, providing relief from oxidative stress. Selective inhibition of HO-1 completely blocked the action of hemin but not that of curcumin, suggesting simultaneous multi-pathway intervention by curcumin. Curcumin also increased cellular autophagy levels, enhancing its protective effect; however, hemin had no effects. Based on the fact that the dysregulation of multiple pathways is implicated in the etiology of complex diseases, we proposed a feasible method for identifying multi-pathway drugs from compounds with validated targets. Our efforts will help identify multi-pathway agents capable of providing comprehensive protection against renal injuries.
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High average power picosecond pulse and supercontinuum generation from a thulium-doped, all-fiber amplifier.
Opt Lett
PUBLISHED: 12-11-2013
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We demonstrate a high-power, picosecond, thulium-doped, all-fiber master oscillator power amplifier with average power of 120.4 W. The compact fiber oscillator is carefully designed with high repetition rate for the purpose of overcoming the detrimental effects of fiber nonlinearity in the later fiber amplifiers. The pulse duration of 16 ps at 333.75 MHz repetition rate results in a peak power of 22.5 kW in the final fiber power amplifier. To the best of our knowledge, this is the first demonstration of average power exceeding 100 W from an ultrashort pulse laser at 2 ?m wavelength. On the other hand, by decreasing the fiber oscillator repetition rate and pulse duration for enhancing the fiber nonlinearity effects, we also demonstrate a high-power supercontinuum source with average power of 36 W from 1.95 ?m to beyond 2.4 ?m in the final fiber power amplifier.
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Prognostic value of mutational characteristics in gastrointestinal stromal tumors: a single-center experience in 275 cases.
Med. Oncol.
PUBLISHED: 11-22-2013
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The objective of this study was to investigate the impact of KIT/PDGFRA mutations on the prognosis of gastrointestinal stromal tumors (GISTs). In the present study, genotype analyses were performed based on GIST samples from 275 patients. The relationship between mutation and clinicopathological characteristics were explored. All factors were evaluated for their impacts on relapse-free survival (RFS). Briefly, the results of genotype analyses showed that mutations were identified in 258 (93.8 %) patients, and deletion was the most frequent type of mutation accounting for 47.3 % (122/258) of all mutation cases, followed by substitution (87/258, 33.7 %) and duplication (49/258, 19.0 %). Moreover, for KIT exon 11 mutation, the most frequently involved area was from codon 557 to 560. Deep analyses showed that the mutation types were correlated with tumor location (P = 0.005), tumor size (P = 0.022), mitosis rate (P < 0.001), risk grade (P < 0.001), and relapse (P = 0.004). Furthermore, delW557-K558 correlated with mitosis rate (P = 0.042) and relapse (P = 0.036), and delTyr568/570 correlated with tumor origin (P = 0.018). Most importantly, mitotic rate [HR = 2.901 (95 % CI 1.094-7.695), P = 0.032] and risk grade [HR = 9.629 (95 % CI 1.997-46.416), P = 0.005] would be the representative traditional prognostic factors, and deletion with >3 codons would be an novel independent predictor of poor outcome for RFS in GIST patients with deletion mutation of KIT exon 11 [HR = 7.970 (95 % CI 1.774-35.803), P = 0.007]. All results indicated that mutation determined clinicopathological features and prognosis of GISTs, and more than three codons involvement may be a novel adverse indicator.
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Schistosoma japonicum tegumental protein 20.8, role in reproduction through its calcium binding ability.
Parasitol. Res.
PUBLISHED: 10-31-2013
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Schistosomiasis threatens thousands of millions of peoples health every year in the world. Schistosoma japonicum, a pathogen of schistosomiasis, is covered by a lipid bilayer membrane which plays an important role in nutrient transport, signal transduction, interaction with hosts immune system, etc. Thus, molecules in the tegumental membrane have gained more and more interest for understanding biological and pathological processes of schistosoma. In this study, we found a protein from S. japonicum cDNA library which has a 20.8 KDa molecular weight (SjTP20.8). Recombinant SjTP20.8 was produced and purified from Escherichia coli. The recombinant protein could be detected by S. japonicum-infected mice and human sera, and it had been found localizing in the tegumental membrane of S. japonicum in the section using immunofluorescence assay. In electrophoretic mobility shift assay, the protein could bind calcium iron in neutral condition. Result of cercariae challenge experiment indicates antibody against this protein can protect mice from chronic hepatic fibrosis. Our results indicate the S. japonicum tegumental protein 20.8 is crucial for the parasites calcium absorbing and reproduction.
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Diagnostic efficacy of contrast-enhanced sonography by combined qualitative and quantitative analysis in breast lesions: a comparative study with magnetic resonance imaging.
J Ultrasound Med
PUBLISHED: 09-26-2013
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The purpose of this study was to evaluate the diagnostic efficacy of contrast-enhanced sonography for differentiation of breast lesions by combined qualitative and quantitative analyses in comparison to magnetic resonance imaging (MRI).
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[Risk assessment of schistosomiasis transmission in earthquake-stricken areas after the Lushan Earthquake in Sichuan Province on April 20, 2013].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 09-13-2013
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To assess the impact of the "4 x 20" Lushan Earthquake on the risk of schistosomiasis transmission in Lushan and Tianquan counties, so as to provide the evidence for formulating appropriate measures for schistosomiasis prevention and control.
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On the Utility of Quantitative Diffusion-Weighted MR Imaging as a Tool in Differentiation between Malignant and Benign Thyroid Nodules.
Acad Radiol
PUBLISHED: 08-28-2013
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To evaluate the ability of diffusion-weighted magnetic resonance imaging (DWI) in differentiating malignant thyroid nodules from benign lesions with a meta-analysis.
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Incubation of selected fermentable fibres with feline faecal inoculum: correlations between in vitro fermentation characteristics and end products.
Arch Anim Nutr
PUBLISHED: 08-19-2013
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This study aimed to evaluate correlations between fermentation characteristics and end products of selected fermentable fibres (three types of fructans, citrus pectin, guar gum), incubated with faecal inocula from donor cats fed two diets, differing in fibre and protein sources and concentrations. Cumulative gas production was measured over 72 h, fermentation end products were analysed at 4, 8, 12, 24, 48 and 72 h post-incubation, and quantification of lactobacilli, bifidobacteria and bacteroides in fermentation liquids were performed at 4 and 48 h of incubation. Partial Pearson correlations, corrected for inoculum, were calculated to assess the interdependency of the fermentation characteristics of the soluble fibre substrates. Butyric and valeric acid concentrations increased with higher fermentation rates, whereas acetic acid declined. Concentrations of butyric acid (highest in fructans) and propionic acid were inversely correlated with protein fermentation end products at several time points, whereas concentrations of acetic acid (highest in citrus pectin) were positively correlated with these products at most time points. Remarkably, a lack of clear relationship between the counts of bacterial groups and their typically associated products after 4 h of incubation was observed. Data from this experiment suggest that differences in fibre fermentation rate in feline faecal inocula coincide with typical changes in the profile of bacterial fermentation products. The observed higher concentrations of propionic and butyric acid as a result of fibre fermentation could possibly have beneficial effects on intestinal health, and may be confounded with a concurrent decrease in the production of putrefactive compounds. In conclusion, supplementing guar gum or fructans to a feline diet might be more advantageous compared with citrus pectin. However, in vivo research is warranted to confirm these conclusions in domestic cats.
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Development and validation of a dried blood spot assay for the quantification of ribavirin using liquid chromatography coupled to mass spectrometry.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 08-15-2013
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Efficient, inexpensive and sensitive assays for the measurement of drugs are of interest for pharmacokinetic and pharmacodynamics (PK-PD) analysis. Dried blood spots (DBS) are a unique bioanaltyical matrix with the potential to fulfill this interest for the measurement of numerous analytes. Here we describe the development and validation of a reversed-phase high performance liquid chromatographic (LC), tandem mass spectrometry (MS/MS) assay for the determination of ribavirin (RBV) in DBS. A 3mm punch from spotted and dried whole blood was extracted in methanol utilizing isotopically labeled internal standard for LC-MS/MS analysis. Validation was performed over a range of 0.05?g/mL to 10.0?g/mL and the method was shown to be precise (coefficient of variation ?15%) and accurate (within ±15% of control). These acceptance criteria were met for hematocrit ranges of 20-54%, for center versus edge punches and for spot volumes from 10 to 60?L. RBV was stable for up to 140 days at room temperature and -20°C as well as for three freeze/thaw cycles. Correlation of RBV in DBS versus in plasma yielded r(2)?0.98 demonstrating that DBS can be used as an alternative to plasma for PK-PD studies in human subjects.
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Midface Contour Change after Reduction Malarplasty with a Modified L-shaped Osteotomy: A Surgical Outcomes Study.
Aesthetic Plast Surg
PUBLISHED: 07-16-2013
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The zygomatic bone, which is located on both sides of the midface, significantly contributes to the overall facial form. Asian people usually have a wide midface and prominent zygoma. Reduction malarplasty is one of the most frequently performed facial contouring surgeries in Asian countries. This study aimed to evaluate the surgical outcomes of reduction malarplasty with a modified L-shaped osteotomy.
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[Study on process conditions of Forsytiae Fructus].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 07-16-2013
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To study the effect of different processing methods on the content and biological activity of main chemical constituents of Forsytiae Fructus, in order to provide the basis for rational processing of Forsytiae Fructus.
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[Research of DNA barcode of Teseudinis Carapax et Planstrum and its adulterants based on COI gene sequence].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 07-16-2013
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To use COI gene on the Mauremys reevesii and its adulterants by molecular identification. Search a rapid, accurate method of identification of Teseudinis Carapax et Planstrum and its adulterants.
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Quantitation of tenofovir and emtricitabine in dried blood spots (DBS) with LC-MS/MS.
J Pharm Biomed Anal
PUBLISHED: 06-14-2013
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A reversed-phase high performance liquid chromatographic (LC), tandem mass spectrometry (MS/MS) assay for the determination of tenofovir (TFV) and emtricitabine (FTC) in dried blood spots (DBS) from human whole blood was developed and validated. Whole blood samples were spotted, dried, and a 3mm punch was extracted with methanol for analysis by LC-MS/MS utilizing stable isotope labeled internal standards. The assay was validated over the range of 2.5-1000ng/mL for TFV and 2.5-5000ng/mL for FTC. The method was accurate (within ±15% of control) and precise (coefficient of variation ?15%) for hematocrit concentrations ranging from 25% to 76%; using edge punches vs. center punches; and spot volumes of 10-50?L. Analytes were stable for five freeze/thaw cycles and up to 6 days at room temperature, whereas long-term storage required -20°C or -80°C. Comparison of TFV and FTC in DBS vs. plasma yielded r(2)?0.96, indicating that DBS can be used as a plasma alternative for pharmacokinetic analyses in vivo.
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Desensitization of G-protein-coupled receptors induces vascular hypocontractility in response to norepinephrine in the mesenteric arteries of cirrhotic patients and rats.
HBPD INT
PUBLISHED: 06-08-2013
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The increased beta-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of alpha-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models.
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Potential therapeutic targets for the primary gallbladder carcinoma: estrogen receptors.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-04-2013
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Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, ER?, ER? and ER?. ER? and ER? appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.
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Electroacupuncture-Induced Neuroprotection against Cerebral Ischemia in Rats: Role of the Dopamine D2 Receptor.
Evid Based Complement Alternat Med
PUBLISHED: 06-03-2013
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Background. Cerebral ischemia is known to produce brain damage and related behavioural deficits, including memory deficits and motor disorders. Evidence shows that EA significantly promotes recovery of neurological function and thus improves quality of life. Objective. Evidence exists for the involvement of catecholamines in human neuroplasticity. A better understanding of dopaminergic (DAergic) modulation in this process will be important. Methods. A total of 72 adult male Sprague-Dawley (SD) rats were divided into 6 groups: normal, model, EA, spiperone group, EA + spiperone group, and pergolide. The middle cerebral artery occlusion (MCAO) model was used in all 6 groups except the normal group. A behavioural assessment was conducted at 1, 3, 5, and 7 days after MCAO. The percent of brain infarct area was also determined 7 days after MCAO. Tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP-43) fluorescence double labeling was performed in the striatum. Results. In this study, we found that EA at Fengchi (GB20) acupoints resulted in marked improvements based on a behavioural assessment. Both TTC staining and GAP-43 immunofluorescence labeling results showed that EA treatment reduced ischemia injury and promoted neuroplasticity compared with the model group. The D2R-selective agonist, pergolide, showed similar results, but these results were reversed by the D2R-selective antagonist, spiperone. We also found that there were more colocalization and expression of GAP-43 and TH in the EA and pergolide groups than those in the other groups. Conclusion. These results suggest that the neuroplasticity induced by EA was mediated by D2 autoreceptors in DAergic neurons.
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[Preliminary study on establishing an animal model of neuroschistosomiasis by direct injection of Schistosoma japonicum eggs through skull].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 05-22-2013
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To establish an experimental model of neuroschistosomiasis and investigate the model establishment factors.
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[The effects of tissue inhibitor of metalloproteinases on beta-dystroglycan in salivary adenoid cystic carcinoma].
Hua Xi Kou Qiang Yi Xue Za Zhi
PUBLISHED: 05-14-2013
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To investigate the expression of beta-dystroglycan (beta-DG) and the roles of tissue inhibitor of metalloproteinases (TIMPs) on beta-DG in salivary adenoid cystic carcinoma (SACC).
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A new method for detecting cerebral hemorrhage in rabbits by magnetic inductive phase shift.
Biosens Bioelectron
PUBLISHED: 05-09-2013
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Cerebral hemorrhage, which is an important clinical problem, is often monitored and studied using expensive devices, such as magnetic resonance imaging (MRI) and positron emission tomography (PET) that are unavailable in economically underdeveloped regions. Magnetic induction tomography (MIT) is a new type of non-contact, non-invasive, and low-cost detection technology, and exhibits prospects for wide application, especially for the detection of brain diseases. However, the previous studies on MIT have focused on laboratory models and rarely on in vivo applications because the induced signals produced by biological tissues are notably weak. Based on the symmetry between the two brain hemispheres and the fact that a local brain hemorrhage will not affect the contra-lateral hemisphere, a symmetric cancellation-type sensor detection system, which is characterized by one excitation coil and two receiving coils, was designed to improve the detection sensitivity of MIT. This method was subsequently used to detect the occurrence of cerebral hematomas in rabbits. The average phase drift induced by a 3-ml injection of autologous blood was 1.885°, which is a fivefold improvement compared with the traditional single excitation coil and single receiving coil method. The results indicate that this system has high sensitivity and anti-interference ability and high practical value.
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3D-image-guided high-dose-rate intracavitary brachytherapy for salvage treatment of locally persistent nasopharyngeal carcinoma.
Radiat Oncol
PUBLISHED: 05-08-2013
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To evaluate the therapeutic benefit of 3D-image-guided high-dose-rate intracavitary brachytherapy (3D-image-guided HDR-BT) used as a salvage treatment of intensity modulated radiation therapy (IMRT) in patients with locally persistent nasopharyngeal carcinoma (NPC).
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Coupled expression of Cu/Zn-superoxide dismutase and catalase in cassava improves tolerance against cold and drought stresses.
Plant Signal Behav
PUBLISHED: 04-19-2013
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Recently we reported that the joint expression of cassava Cu/Zn superoxide dismutase (MeCu/ZnSOD) and catalase (MeCAT1) prolonged the shelf life of cassava storage-roots by the stabilization of reactive oxygen species (ROS) homeostasis after harvest. Since oxidative damage is a major feature of plants exposed to environmental stresses, transgenic cassava showing increased expression of the cytosolic MeCu/ZnSOD and the peroxisomal MeCAT1 should have improved resistance against other abiotic stresses. After cold treatment, the transgenic cassava maintained higher SOD and CAT activities and lower malendialdehyde content than those of wild type plants (WT). Detached leaves of transgenic cassava also showed slower transpirational water loss than those of WT. When plants were not watered for 30 d, transgenic lines exhibited a significant increase in water retention ability, accumulated 13% more proline and 12% less malendialdehyde than WTs, and showed enhanced activity of SOD and CAT. These results imply that manipulation of the antioxidative mechanism allows the development of staple crops with improved tolerance to abiotic stresses.
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Mutation screening for the EXT1 and EXT2 genes in Chinese patients with multiple osteochondromas.
Arch. Med. Res.
PUBLISHED: 04-17-2013
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Multiple osteochondromas (MO), an autosomal dominant skeletal disease, is characterized by the presence of multiple cartilage-capped bone tumors (exostoses). Two genes with mutations that are most commonly associated with MO have been identified as EXT1 and EXT2, which are Exostosin-1 and Exostosin-2. In this study, a variety of EXT1 and EXT2 gene mutations were identified in ten Chinese families with MO.
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Chemical shift assignments of domain 4 from the phosphohexomutase from Pseudomonas aeruginosa suggest that freeing perturbs its coevolved domain interface.
Biomol NMR Assign
PUBLISHED: 04-16-2013
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A domain needed for the catalytic efficiency of an enzyme model of simple processivity and domain-domain interactions has been characterized by NMR. This domain 4 from phosphomannomutase/phosphoglucomutase (PMM/PGM) closes upon glucose phosphate and mannose phosphate ligands in the active site, and can modestly reconstitute activity of enzyme truncated to domains 1-3. This enzyme supports biosynthesis of the saccharide-derived virulence factors (rhamnolipids, lipopolysaccharides, and alginate) of the opportunistic bacterial pathogen Pseudomonas aeruginosa. (1)H, (13)C, and (15)N NMR chemical shift assignments of domain 4 of PMM/PGM suggest preservation and independence of its structure when separated from domains 1-3. The face of domain 4 that packs with domain 3 is perturbed in NMR spectra without disrupting this fold. The perturbed residues overlap both the most highly coevolved positions in the interface and residues lining a cavity at the domain interface.
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[Molecular mechanism and therapeutic strategy for resistance to tyrosine kinase inhibitors in targeted treatment of gastrointestinal stromal tumors].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 03-29-2013
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Gastrointestinal stromal tumor(GIST) is the most common mesenchymal neoplasm of the GI tract. Aberrant activation of tyrosine kinase through mutated KIT or platelet-derived growth factor receptor(PDGFRA) is the key pathogenic factor in most cases. Tyrosine kinase inhibitors (TKI) such as imatinib and sunitinib can suppress activation of tyrosine kinaase receptor and has gained wide recognition as the first-line adjuvant therapy for advanced or high-risk GIST after surgery. It has become the classic model of treatment for solid tumor with molecular targeted therapy. However, the emergence of drug-resistance limits the long-term benefit of these drugs in most patients and has been a challenging clinical concern. Many factors are related to the resistance of TKI, of which KIT/PDGFRA mutation is the most important one. Genetic amplification of KIT, loss of heterozygosity, activation of an alternative downstream signaling pathways, and drug concentration are all possible factors. Therefore, reasonable individual treatment strategy and early resistance evaluation for imatinib- and sunitinib-resistant GISTs are important to patients with drug resistance in order to improve therapeutic efficacy and quality of life.
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[Clinicopathological features and management of gastrointestinal stromal tumors complicated with synchronous other alimentary malignant tumor].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 03-29-2013
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To explore the clinicopathologic features, treatment and prognosis of gastrointestinal stromal tumor(GIST) complicated with synchronous other alimentary malignant tumors.
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High glucose-induced apoptosis in cultured podocytes involves TRPC6-dependent calcium entry via the RhoA/ROCK pathway.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-27-2013
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Increasing evidence indicates that podocyte apoptosis is a key event in the development of diabetic nephrology. However, the underlying mechanism of this apoptosis remains poorly understood. In this study, we report that high levels of glucose enhanced the expression of TRPC6 and TRPC6-dependent Ca(2+) influx, but glucose levels did not affect TRPC1 and TRPC5 expression. TRPC6 knockdown by siRNA interference attenuated the observed increase in glucose-induced podocyte apoptosis. High glucose levels also increased the generation of ROS; inhibition of ROS activity by N-acetyl-l-cysteine attenuated the high glucose-induced increase in TRPC6 expression and Ca(2+) influx. Exogenous treatment with H2O2 mimicked the high glucose response, resulting in an increase in TRPC6 expression and Ca(2+) influx. Taken together, these data suggest that high glucose levels induce ROS, thereby mediating TRPC6 expression and Ca(2+) influx. Because RhoA activity is increased following TRPC6 activation, we investigated whether TRPC6 is involved in high glucose-induced apoptosis via the RhoA/ROCK pathway. We report that high glucose levels produced an increase in RhoA activity, and this effect was abolished by the knockdown of TRPC6. Moreover, inhibition of the RhoA/ROCK pathway by a ROCK inhibitor, Y27632, also attenuated high glucose-induced apoptosis. We conclude that TRPC6 is involved in high glucose-induced podocyte apoptosis through the RhoA/ROCK pathway.
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The effect of temperature on the viability of human mesenchymal stem cells.
Stem Cell Res Ther
PUBLISHED: 03-03-2013
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Impaction allograft with cement is a common technique used in revision hip surgeries for the last 20 years. However, its clinical results are inconsistent. Recent studies have shown that mesenchymal stem cells (MSCs) seeded onto allograft can enhance bone formation. This in vitro study investigates whether the increase in temperature related to the polymerisation of bone cement will affect the viability of human MSCs.
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Prognostic assessment of different metastatic lymph node staging methods for gastric cancer after D2 resection.
World J. Gastroenterol.
PUBLISHED: 02-21-2013
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To compare the prognostic assessment of lymph node ratio and absolute number based staging system for gastric cancer after D2 resection.
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How reliable are standard radiographic measures of the foot and ankle in children with achondroplasia?
Clin. Orthop. Relat. Res.
PUBLISHED: 01-25-2013
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Radiographic measurements are typically used in achondroplasia (ACH) during correction of lower limb alignment. However, reliabilities for the measurements on weightbearing radiographs of the foot and ankle in patients with ACH have not been described, and the differences between the ACH population and subjects without ACH likewise have not been well characterized; these issues limit the use of studies on this subject.
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Enhanced reactive oxygen species scavenging by overproduction of superoxide dismutase and catalase delays postharvest physiological deterioration of cassava storage roots.
Plant Physiol.
PUBLISHED: 01-23-2013
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Postharvest physiological deterioration (PPD) of cassava (Manihot esculenta) storage roots is the result of a rapid oxidative burst, which leads to discoloration of the vascular tissues due to the oxidation of phenolic compounds. In this study, coexpression of the reactive oxygen species (ROS)-scavenging enzymes copper/zinc superoxide dismutase (MeCu/ZnSOD) and catalase (MeCAT1) in transgenic cassava was used to explore the intrinsic relationship between ROS scavenging and PPD occurrence. Transgenic cassava plants integrated with the expression cassette p54::MeCu/ZnSOD-35S::MeCAT1 were confirmed by Southern-blot analysis. The expression of MeCu/ZnSOD and MeCAT1 was verified by quantitative reverse transcription-polymerase chain reaction and enzymatic activity analysis both in the leaves and storage roots. Under exposure to the ROS-generating reagent methyl viologen or to hydrogen peroxide (H2O2), the transgenic plants showed higher enzymatic activities of SOD and CAT than the wild-type plants. Levels of malondialdehyde, chlorophyll degradation, lipid peroxidation, and H2O2 accumulation were dramatically reduced in the transgenic lines compared with the wild type. After harvest, the storage roots of transgenic cassava lines show a delay in their PPD response of at least 10 d, accompanied by less mitochondrial oxidation and H2O2 accumulation, compared with those of the wild type. We hypothesize that this is due to the combined ectopic expression of Cu/ZnSOD and CAT leading to an improved synergistic ROS-scavenging capacity of the roots. Our study not only sheds light on the mechanism of the PPD process but also develops an effective approach for delaying the occurrence of PPD in cassava.
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An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes.
Mol. Cell
PUBLISHED: 01-17-2013
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Animal germ cells produce PIWI-interacting RNAs (piRNAs), small silencing RNAs that suppress transposons and enable gamete maturation. Mammalian transposon-silencing piRNAs accumulate early in spermatogenesis, whereas pachytene piRNAs are produced later during postnatal spermatogenesis and account for >95% of all piRNAs in the adult mouse testis. Mutants defective for pachytene piRNA pathway proteins fail to produce mature sperm, but neither the piRNA precursor transcripts nor the trigger for pachytene piRNA production is known. Here, we show that the transcription factor A-MYB initiates pachytene piRNA production. A-MYB drives transcription of both pachytene piRNA precursor RNAs and the mRNAs for core piRNA biogenesis factors including MIWI, the protein through which pachytene piRNAs function. A-MYB regulation of piRNA pathway proteins and piRNA genes creates a coherent feedforward loop that ensures the robust accumulation of pachytene piRNAs. This regulatory circuit, which can be detected in rooster testes, likely predates the divergence of birds and mammals.
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Expression of Cry1Aa in cassava improves its insect resistance against Helicoverpa armigera.
Plant Mol. Biol.
PUBLISHED: 01-17-2013
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Lepidopteran insects affect cassava production globally, especially in intercropping system. The expression of Cry toxins in transgenic crops has contributed to an efficient control of insect pests, leading to a significant reduction in chemical insecticide usage. Helicoverpa armigera is a Lepidopteran pest that feeds on a wide range of plants like cotton and cassava. In the present study, transgenic cassava plants over-expressing Cry1Aa, which we named as Bt cassava, were developed and used to evaluate its efficacy against H. armigera as a model. Insect feeding assays were carried out to test the effects of Bt cassava leaves on the development and survival of H. armigera. Significant reduction (P < 0.05) in the survival and weight were detected on larvae fed with Bt cassava leaves in comparison with those fed with wild-type cassava leaves. The higher expression of Cry1Aa in transgenic cassava caused the lethal effect in larvae, in contrast to the normal growth and development of adults and pupation observed when fed with wild-type leaves. Morphological observation on the larval midguts showed that the consumption of Bt cassava affected the gut integrity of H. armigera. The columnar cells of the midgut epithelium were dramatically damaged and showed loose or disordered structure. Their cytoplasms become highly vacuolated and contained disorganized microvilli. Our study demonstrated that the transgenic cassava expressing the Cry1Aa is effective in controlling H. armigera. Our Bt transgenic cassava plant would provide a long-term beneficial effect on all crops in intercropping system, which in-turn, will be profitable to the farmers.
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Enhanced external counterpulsation inhibits endothelial apoptosis via modulation of BIRC2 and Apaf-1 genes in porcine hypercholesterolemia.
Int. J. Cardiol.
PUBLISHED: 01-07-2013
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Enhanced external counterpulsation (EECP) could improve endothelium-dependent vasodilatation of carotid artery and restore imbalance of nitric oxide and endothein-1 in patients with coronary artery disease. Our study was designed to test the hypothesis that long-term EECP may protect vascular endothelial cells from apoptosis by modifying apoptosis-related gene expression.
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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.