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Find video protocols related to scientific articles indexed in Pubmed.
A Phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy in patients with advanced solid malignancies and peritoneal carcinomatosis.
Clin. Cancer Res.
PUBLISHED: 10-31-2014
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Background: Combined low-dose radiation therapy with poly (ADP-ribose) polymerase (PARP) inhibition has been shown to enhance anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with escalating doses of veliparib (ABT-888),a small molecule PARP inhibitor, in patients with peritoneal carcinomatosis from advanced solid tumors. Methods: Patients were treated with veliparib (80mg-320mg daily) for a total of 3 cycles. LDFWAR consisted of 21.6 Gy in 36 fractions, 0.6 Gy twice daily on days 1 and 5 for weeks 1-3 of each cycle. Circulating tumor cells (CTCs) were collected and evaluated for ?-H2AX. Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire. Results: Twenty-two patients were treated. Treatment-related grade 3/4 toxicites included lymphopenia (68%), anemia (9%), thrombocytopenia (14%), neutropenia (4%), leukopenia (9%), ascites (4%), vomiting (4%) and dyspnea (4%). No objective responses were observed. Disease stabilization (?24 wks) was observed in 7 patients (33%). Median PFS was 4.47 months and mOS was 13.04 months. In the subset of 8 ovarian and fallopian cancers (OV), mPFS was 6.77 months and mOS was 17.54 months compared to mPFS 2.71 months and mOS 13.01 months in others. Patients with OV had better QoL over time than those with other cancers. An increased percentage of ?-H2AX-positive CTCs was observed in a subset of patients (3/6 with >2 CTCs at baseline). Conclusions: Combined veliparib and LDFWAR is a well-tolerated regimen that resulted in prolonged disease stability for some patients with advanced solid tumors and carcinomatosis, particularly in the OV subpopulation.
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Constructing Higher-Order DNA Nanoarchitectures with Highly Purified DNA Nanocages.
ACS Appl Mater Interfaces
PUBLISHED: 10-28-2014
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DNA nanostructures have attracted great attention due to their precisely controllable geometry and great potential in various areas including bottom-up self-assembly. However, construction of higher-order DNA nanoarchitectures with individual DNA nanostructures is often hampered with the purity and quantity of these "bricks". Here, we introduced size exclusion chromatography (SEC) to prepare highly purified tetrahedral DNA nanocages in large scale and demonstrated that precise quantification of DNA nanocages was the key to the formation of higher-order DNA nanoarchitectures. We successfully purified a series of DNA nanocages with different sizes, including seven DNA tetrahedra with different edge lengths (7, 10, 13, 17, 20, 26, 30 bp) and one trigonal bipyramid with a 20-bp edge. These highly purified and aggregation-free DNA nanocages could be self-assembled into higher-order DNA nanoarchitectures with extraordinarily high yields (98% for dimer and 95% for trimer). As a comparison, unpurified DNA nanocages resulted in low yield of 14% for dimer and 12% for trimer, respectively. AFM images cleraly presented the characteristic structure of monomer, dimer and trimer, impling the purified DNA nanocages well-formed the designed nanoarchitectures. Therefore, we have demonstrated that highly purified DNA nanocages are excellent "bricks" for DNA nanotechnology and show great potential in various applications of DNA nanomaterials.
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[Comparison of serum lipid and protein oxidation products levels in patients with different types of dyslipidemia].
Wei Sheng Yan Jiu
PUBLISHED: 09-10-2014
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To explore serum redox status differences among different types of dyslipidemia patients.
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Adjusting Family Relatedness in Data-driven Burden Test of Rare Variants.
Genet. Epidemiol.
PUBLISHED: 08-28-2014
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Family data represent a rich resource for detecting association between rare variants (RVs) and human traits. However, most RV association analysis methods developed in recent years are data-driven burden tests which can adaptively learn weights from data but require permutation to evaluate significance, thus are not readily applicable to family data, because random permutation will destroy family structure. Direct application of these methods to family data may result in a significant inflation of false positives. To overcome this issue, we have developed a generalized, weighted sum mixed model (WSMM), and corresponding computational techniques that can incorporate family information into data-driven burden tests, and allow adaptive and efficient permutation test in family data. Using simulated and real datasets, we demonstrate that the WSMM method can be used to appropriately adjust for genetic relatedness among family members and has a good control for the inflation of false positives. We compare WSMM with a nondata-driven, family-based Sequence Kernel Association Test (famSKAT), showing that WSMM has significantly higher power in some cases. WSMM provides a generalized, flexible framework for adapting different data-driven burden tests to analyze data with any family structures, and it can be extended to binary and time-to-onset traits, with or without covariates.
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[Etiology analysis of incident hemodialysis patients in Shanxi province during 2010 and 2013].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-26-2014
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To retrieve the epidemiological literature of end stage renal hemodialysis patients.
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Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia.
Neurosci. Lett.
PUBLISHED: 08-22-2014
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Global cerebral ischemia (GCI) causes energy deficiency results in excessive release of glutamate from neurons. Astrocytic glutamate transporters play a predominant role in keeping extracellular glutamate concentrations below excitotoxic levels. Glutamate transporter 1 (GLT-1) may account for more than 90% of glutamate uptake in adult forebrain. Preclinical findings implicate that Harmine present neuroprotection effects in a rat model of amyotrophic lateral sclerosis disease, and the beneficial effects were specifically due to up-regulation of GLT-1. However, no experiments have explored the potential of Harmine to provide neuroprotection in the setting of GCI. The current study was designed to determine whether Harmine could attenuate cerebral infarction as well as improve neuronal survival after GCI. Furthermore, to test whether the mechanisms were associated with up-regulating of GLT-1, we used a GLT-1 specific inhibitor dihydrokainate (DHK) and analysis the expression of GLT-1 mRNA and protein in cortex of brain. We also examined whether Harmine treatment affected astrocytes activation via immunofluorescence. Our results showed that post-GCI administration of Harmine could attenuate cerebral infarct volume and decrease neurons death. It also caused significantly elevation of GLT-1 mRNA and protein and remarkably attenuation of astrocyte activation. We provide novel clues in understanding the mechanisms of which Harmine exerts its neuroprotective activity in neurological disorders.
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Correlation analysis between central corneal thickness and intraocular pressure in juveniles in Northern China: the Jinan city eye study.
PLoS ONE
PUBLISHED: 08-22-2014
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To determine the distributions and relation of central corneal thickness (CCT) and intraocular pressure (IOP) by NT-530P in Chinese juveniles, and the effect of gender, age, height, weight and refractive errors on the CTT and IOP.
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TAT-RhoGDI2, a novel tumor metastasis suppressor fusion protein: expression, purification and functional evaluation.
Appl. Microbiol. Biotechnol.
PUBLISHED: 08-22-2014
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Rho GDP dissociation inhibitor 2 (RhoGDI2) was identified as a functional metastasis suppressor in human bladder cancer, suggesting that increasing the RhoGDI2 level may represent a promising therapeutic strategy. It has been shown that the transactivator of transcription (TAT) protein from HIV-1 is able to efficiently deliver various biological molecules into several cell types. In this study, TAT peptide was fused with the N-terminus of RhoGDI2, and the resulting TAT-RhoGDI2 fragment was inserted into the pGEX-6p-1 plasmid and expressed as a glutathione S-transferase (GST)/TAT-RhoGDI2 fusion protein in Escherichia coli BL21(DE3) cells. A two-step purification strategy involving glutathione sepharose chromatography and PreScission protease cleavage was developed to purify TAT-RhoGDI2; subsequently, the identification of the involved macromolecules was achieved by Western blot. The final product, TAT-RhoGDI2, was obtained at a concentration of 112 mg/L. This is the first report on the efficient production of bioactive TAT-RhoGDI2 through a gene-engineering approach in E. coli. Using flow cytometry, we found that the TAT-RhoGDI2 fusion proteins could penetrate into bladder cancer cells with an extremely high efficiency. In vitro scratch and transwell assay and the migration/invasion behavior of UMUC3 cells were strongly reduced by the treatment with TAT-RhoGDI2. These studies support the use of the TAT-RhoGDI2 protein in tumor metastasis therapy.
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Identifying a polymorphic 'switch' that influences miRNAs' regulation of a myasthenia gravis risk pathway.
PLoS ONE
PUBLISHED: 08-12-2014
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The significant roles of genetic variants in myasthenia gravis (MG) pathogenesis have been demonstrated in many studies, and recently it has been revealed that aberrant level/regulation of microRNAs (miRNAs) might contribute to the initiation and progression of MG. However, the dysfunction of miRNA associated with single nucleotide polymorphisms (miRSNPs) has not been well investigated in MG. In this study, we created a contemporary catalog of 89 MG risk genes via manual literature-mining. Based on this risk gene catalog, we obtained 18 MG risk pathways. Furthermore, we identified 93 miRNAs that target MG risk pathways and revealed the miRSNPs 'switches' in miRNA regulation in the MG risk pathways by integrating the database information of miRSNPs. We also constructed a miRNA-mediated SNP switching pathway network (MSSPN) to intuitively analyze miRNA regulation of MG risk pathways and the relationship of the polymorphism 'switch' with these changes in regulation. Moreover, we carried out in-depth dissection on the correlation between hsa05200 (pathway in cancer) and MG development, and elaborated the significance of 4 high-risk genes. By network analysis and literature mining, we proposed a potential mechanism of miRSNPs?gene?pathway effects on MG pathogenesis, especially for rs28457673 (miR-15/16/195/424/497 family)?IGF1R?hsa05200 (pathway in cancer). Therefore, our studies have revealed a functional role for genetic modulators in MG pathogenesis at a systemic level, which could be informative for further miRNA and miRSNPs studies in MG.
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Oolong, black and pu-erh tea suppresses adiposity in mice via activation of AMP-activated protein kinase.
Food Funct
PUBLISHED: 08-07-2014
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It is well known that tea has a variety of beneficial impacts on human health, including anti-obesity effects. It is well documented that green tea and its constituent catechins suppress obesity, but the effects of other types of tea on obesity and the potential mechanisms involved are not yet fully understood. In this study, we investigated the suppression of adiposity by oolong, black and pu-erh tea and characterized the underlying molecular mechanism in vivo. We found that the consumption of oolong, black or pu-erh tea for a period of one week significantly decreased visceral fat without affecting body weight in male ICR mice. On a mechanistic level, the consumption of tea enhanced the phosphorylation of AMP-activated protein kinase (AMPK) in white adipose tissue (WAT). This was accompanied by the induction of WAT protein levels of uncoupling protein 1 and insulin-like growth factor binding protein 1. Our results indicate that oolong, black and pu-erh tea, and in particular, black tea, suppresses adiposity via phosphorylation of the key metabolic regulator AMPK and increases browning of WAT.
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Differential protein expression profiling of Arabidopsis thaliana callus under microgravity on board the Chinese SZ-8 spacecraft.
Planta
PUBLISHED: 07-31-2014
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Exposure of Arabidopsis callus to microgravity has a significant impact on the expression of proteins involved in stress responses, carbohydrate metabolism, protein synthesis, intracellular trafficking, signaling, and cell wall biosynthesis. Microgravity is among the main environmental stress factors that affect plant growth and development in space. Understanding how plants acclimate to space microgravity is important to develop bioregenerative life-support systems for long-term space missions. To evaluate the spaceflight-associated stress and identify molecular events important for acquired microgravity tolerance, we compared proteomic profiles of Arabidopsis thaliana callus grown under microgravity on board the Chinese spacecraft SZ-8 with callus grown under 1g centrifugation (1g control) in space. Alterations in the proteome induced by microgravity were analyzed by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry with isobaric tags for relative and absolute quantitation labeling. Forty-five proteins showed significant (p < 0.05) and reproducible quantitative differences in expression between the microgravity and 1g control conditions. Of these proteins, the expression level of 24 proteins was significantly up-regulated and that of 21 proteins was significantly down-regulated. The functions of these proteins were involved in a wide range of cellular processes, including general stress responses, carbohydrate metabolism, protein synthesis/degradation, intracellular trafficking/transportation, signaling, and cell wall biosynthesis. Several proteins not previously known to be involved in the response to microgravity or gravitational stimuli, such as pathogenesis-related thaumatin-like protein, leucine-rich repeat extension-like protein, and temperature-induce lipocalin, were significantly up- or down-regulated by microgravity. The results imply that either the normal gravity-response signaling is affected by microgravity exposure or that microgravity might inappropriately induce altered responses to other environmental stresses.
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Effect of a residue after evaporation from industrial vitamin C fermentation on chemical and microbial properties of alkali-saline soil.
Pak J Pharm Sci
PUBLISHED: 07-13-2014
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Residue after evaporation (RAE) from industrial vitamin C fermentation is emitted as a waste product at an amount of 60,000 tons per year in China. The disposal of RAE is difficult because of its high chemical oxygen demand (1.17×10(6) mg/l) and low pH (0.27). We hypothesized that RAE could be used as an ameliorant for alkali-saline soils, and tried to verify it by carrying out a pot experiment of pakchoi cultivation and to explore its effect on soil chemical and microbial properties. The results showed that pakchoi yield was increased by 28.13% and pakchoi quality was also enhanced under RAE treatment. The improved chemical and microbial properties of treated soil were also observed: soil pH was decreased from 9.19 to 9.03; total organic carbon, available phosphorus and available potassium were increased by 49.15%, 34.91% and 42.02%, respectively; number of culturable bacteria, actinomycetes and fungi, microbial biomass carbon and enzyme activity number were improved by 52.97%, 104.05%, 79.09%, 57.82% and 31.16%, respectively. These results suggested the residue application led to an improved soil quality and subsequently a higher yield and quality of pakchoi. This study provided a strong evidence for the feasibility of RAE as an ameliorant for alkali-saline soil.
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Electronic effect of terminal acceptor groups on different organic donor-acceptor small-molecule based memory devices.
Phys Chem Chem Phys
PUBLISHED: 07-11-2014
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In this work, three new organic donor–acceptor small-molecules, in which bicarbazole served as the electron donor, and benzothiazole, nitryl or 1,1?-dicyanovinyl were used as the electron acceptor, were designed and synthesized in order to fabricate sandwiched memory devices. Acceptors with a variable electron-delocalized extent and electron-withdrawing strength were attached to the molecular backbone in order to investigate the effect on the devices switching behavior. The bi-n-butylcarbazole benzothiazole (BCZ-BT) based memory device exhibited volatile static random access memory (SRAM) switching behaviour, while the devices based on bi-n-butylcarbazole nitryl (BCZ-NO2) was found to exhibit stable nonvolatile write-once-read-many-times (WORM) data storage characteristics and the bi-n-butylcarbazole dicyanovinyl (BCZ-CN) device acted as rewritable flash memory with a higher ON/OFF current ratio of about 104. Therefore, tunable data storage devices synthesized by adjusting the terminal acceptor groups offer feasible guidance for the rational design of organic molecules to achieve superior memory performance.
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Grain rotation mediated by grain boundary dislocations in nanocrystalline platinum.
Nat Commun
PUBLISHED: 06-14-2014
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Grain rotation is a well-known phenomenon during high (homologous) temperature deformation and recrystallization of polycrystalline materials. In recent years, grain rotation has also been proposed as a plasticity mechanism at low temperatures (for example, room temperature for metals), especially for nanocrystalline grains with diameter d less than ~15?nm. Here, in tensile-loaded Pt thin films under a high-resolution transmission electron microscope, we show that the plasticity mechanism transitions from cross-grain dislocation glide in larger grains (d>6?nm) to a mode of coordinated rotation of multiple grains for grains with d<6?nm. The mechanism underlying the grain rotation is dislocation climb at the grain boundary, rather than grain boundary sliding or diffusional creep. Our atomic-scale images demonstrate directly that the evolution of the misorientation angle between neighbouring grains can be quantitatively accounted for by the change of the Frank-Bilby dislocation content in the grain boundary.
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Prevalence and risk factors for pterygium in rural older adults in Shandong Province of China: a cross-sectional study.
Biomed Res Int
PUBLISHED: 06-12-2014
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To investigate the prevalence and risk factors for pterygium in rural older adults in Shandong Province, eastern China, a population-based, cross-sectional study was performed from April to July 2008. By means of cluster random sampling methods, a total of 19,583 people aged 50 years or above were randomly selected from four rural counties. Out of 19,583 people, 1,767 residents were excluded mainly because they were migrant workers when this study was performed. Finally, 17,816 (90.98%) people were included as eligible subjects. They received a comprehensive eye examination and a structured questionnaire voluntarily. Patients with pterygium were defined as having pterygium at the time of survey or pterygium surgery had been performed. 1,876 people were diagnosed as pterygium, either unilateral (1,083) or bilateral (793), which is equivalent to a prevalence of 10.53% (95% CI, 10.08-10.98). The multivariate logistic regression analysis showed that pterygium was independently associated with older age, areas, outdoor time, educational level, and use of hat and/or sunglasses. The prevalence of pterygium increased with age and hours spent under sunshine per day. Meanwhile, the higher the educational level and the more use of hat and/or sunglasses, the lower the pterygium prevalence.
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Gender differences in the relationship between plasma lipids and fasting plasma glucose in non-diabetic urban Chinese population: a cross-section study.
Front Med
PUBLISHED: 06-12-2014
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The association between dyslipidemia and elevated fasting glucose in type 2 diabetes is well known. In non-diabetes, whether this association still exists, and whether dyslipidemia is an independent risk factor for high fasting plasma glucose (FPG) levels are not clear. This cross-sectional study recruited 3460 non-diabetic Chinese subjects (1027 men, and 2433 women, aged 35-75 years old) who participated in a health survey. Men and women were classified into tertiles by levels of plasma lipids respectively. In women, the prevalence of impaired fasting glucose (IFG) was decreased with increased HDL-C. A stepwise increase in HDL-C was associated with decreasing FPG levels (lowest tertiles, FPG: 5.376 ± 0.018; middle tertiles, 5.324 ± 0.018; highest tertiles, 5.276 ± 0.018 mmol/L; P = 0.001). Reversely, FPG levels increased from lowest tertiles to highest tertiles of LDL-C, TC, and TG. we found that women in the first tertile with lower HDL-C level had a 1.75-fold increase in risk of IFG compared with non-diabetic women in the third tertile with higher HDL-C level (OR: 1.75; 95% CI: 1.20-2.56). In men, no significant association was found. We took age, BMI, waist/hip ratio, education, smoking, alcohol drinking, and physical exercise as adjusted variables. In Chinese non-diabetic women, dyslipidemia is independently associated with high levels of FPG; TG, HDL-C, and LDL-C are predictors of IFG independent of BMI and waist/hip ratio.
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Mice deficient in the gene for cytochrome P450 (CYP)1A1 are more susceptible than wild-type to hyperoxic lung injury: evidence for protective role of CYP1A1 against oxidative stress.
Toxicol. Sci.
PUBLISHED: 06-03-2014
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Hyperoxia contributes to acute lung injury in diseases such as acute respiratory distress syndrome in adults and bronchopulmonary dysplasia in premature infants. Cytochrome P450 (CYP)1A1 has been shown to modulate hyperoxic lung injury. The mechanistic role(s) of CYP1A1 in hyperoxic lung injury in vivo is not known. In this investigation, we hypothesized that Cyp1a1(-/-) mice would be more susceptible to hyperoxic lung injury than wild-type (WT) mice, and that the protective role of CYP1A1 is in part due to CYP1A1-mediated decrease in the levels of reactive oxygen species-mediated lipid hydroperoxides, e.g., F2-isoprostanes/isofurans, leading to attenuation of oxidative damage. Eight- to ten-week-old male WT (C57BL/6J) or Cyp1a1(-/-) mice were exposed to hyperoxia (>95% O2) or room air for 24-72 h. The Cyp1a1(-/-) mice were more susceptible to oxygen-mediated lung damage and inflammation than WT mice, as evidenced by increased lung weight/body weight ratio, lung injury, neutrophil infiltration, and augmented expression of IL-6. Hyperoxia for 24-48 h induced CYP1A expression at the mRNA, protein, and enzyme levels in liver and lung of WT mice. Pulmonary F2-isoprostane and isofuran levels were elevated in WT mice after hyperoxia for 24 h. On the other hand, Cyp1a1(-/-) mice showed higher levels after 48-72 h of hyperoxia exposure compared to WT mice. Our results support the hypothesis that CYP1A1 protects against hyperoxic lung injury by decreasing oxidative stress. Future research could lead to the development of novel strategies for prevention and/or treatment of acute lung injury.
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Comparison of different surgery procedures for convergence insufficiency-type intermittent exotropia in children.
Br J Ophthalmol
PUBLISHED: 05-19-2014
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To compare prospectively the surgical outcomes of different surgery procedures for convergence insufficiency (CI)-type intermittent exotropia (IXT) in children.
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Implementation of validated pharmacodynamic assays in multiple laboratories: challenges, successes, and limitations.
Clin. Cancer Res.
PUBLISHED: 05-17-2014
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There is a "life cycle" of pharmacodynamic (PD) biomarker assays that guides the development and clinical implementation in our laboratories. The well-recognized elements of analytical assay validation and demonstration of fitness-for-purpose of the biomarker, specimen collection, handling, and assay methods are only a part of the required activities. Assay transfer across laboratories and testing on actual human clinical specimens are vital for understanding assay performance and robustness. In our experience, this patient specimen-centered approach has required assay method modifications, some unexpected, but which were critical to successful implementation in clinical trials. In addition, dispersing assays throughout the National Cancer Institute's clinical trials network has required the development of calibrator and control materials as well as formal training courses for smooth implementation. One measure of success of this approach has been that a number of the assays developed at NCI's Frederick National Laboratory have ultimately reached the stage of commercialization, enabling wide accessibility of the PD biomarker assays by the research community. See all articles in this ccr focus section, "Progress in pharmacodynamic endpoints."
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Colouration mechanism of underglaze copper-red decoration porcelain (AD 13th-14th century), China.
J Synchrotron Radiat
PUBLISHED: 04-25-2014
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Underglaze copper-red decoration, i.e. the copper colourant used to paint diversified patterns on the surface of a body and then covered by transparent glaze and fired at high temperature in a reductive firing environment, is famous all over the world. However, the red colouration mechanism generated by underglaze copper remains unclear. In particular, the fact that the edges of the red patterns are orange has been ignored in previous research. Here, non-destructive analysis has been carried out on a precious fragment of early underglaze red porcelain using synchrotron radiation X-ray fluorescence, X-ray absorption near-edge spectroscopy (XANES) and reflection spectrometry techniques. The results suggest that the copper content in the red region is higher than that in the orange region, and other colour generation elements do not have obvious content difference, indicating that the colour generation effect of the underglaze red product is related to the copper content. XANES analysis shows that the valence states of copper in the red and orange regions are similar and metal copper contributes to their hues. The results of reflection spectrometry demonstrate that tiny orange hues could be attributed to the Mie scatting effect. Therefore, light-scattering effects should be considered when researching the colouration mechanism of underglaze red.
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E2F1 renders prostate cancer cell resistant to ICAM-1 mediated antitumor immunity by NF-?B modulation.
Mol. Cancer
PUBLISHED: 04-08-2014
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E2F1 is the gatekeeper of the cell cycle controlling an analogous balance between proliferation and cell death. E2F1 expression is elevated in advanced prostate cancer. However, it is still unclear that the roles and mechanisms of E2F1 on prostate cancers.
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Corneal collagen cross-linking with hypoosmolar riboflavin solution in keratoconic corneas.
Biomed Res Int
PUBLISHED: 03-24-2014
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To report the 12-month outcomes of corneal collagen cross-linking (CXL) with a hypoosmolar riboflavin and ultraviolet-A (UVA) irradiation in thin corneas.
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Rabies and rabies virus in wildlife in mainland China, 1990-2013.
Int. J. Infect. Dis.
PUBLISHED: 03-06-2014
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The number of wildlife rabies and wildlife-associated human and livestock rabies cases has increased in recent years, particularly in the southeast and northeast regions of mainland China. To better understand wildlife rabies and its role in human and livestock rabies, we reviewed what is known about wildlife rabies from the 1990s to 2013 in mainland China. In addition, the genetic diversity and phylogeny of available wildlife-originated rabies viruses (RABVs) were analyzed. Several wildlife species carry rabies including the bat, Chinese ferret badger, raccoon dog, rat, fox, and wolf. RABVs have been isolated or detected in the bat, Chinese ferret badger, raccoon dog, Apodemus, deer, and vole. Among them, the bat, Chinese ferret badger, and raccoon dog may play a role in the ecology of lyssaviruses in mainland China. All wildlife-originated RABVs were found to belong to genotype 1 RABV except for a bat-originated Irkut virus isolated in 2012. Several substitutions were found between the glycoprotein of wildlife-originated RABVs and vaccine strains. Whether these substitutions could affect the efficacy of currently used vaccines against infections caused by these wildlife-originated RABVs needs to be investigated further. Phylogenetic analysis showed that RABVs in the bat, Chinese ferret badger, and raccoon dog were distinct from local dog-originated RABVs, and almost all collected wildlife-originated isolates were associated with older China clades II to V, suggesting the possibility of wildlife reservoirs in mainland China through the ages.
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Umbilical cord-derived mesenchymal stem cells regulate thymic epithelial cell development and function in Foxn1(-/-) mice.
Cell. Mol. Immunol.
PUBLISHED: 02-24-2014
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Thymic microenvironments are essential for the maturation of thymocytes, which can be anatomically compartmentalized into cortical and medullar regions. The absence of the gene encoding the transcription factor forkhead box n1 (Foxn1) causes epithelial differentiation to stall in the precursor stage, resulting in the formation of an abnormal thymus. In this study, we used human umbilical cord-derived mesenchymal stem cells (UC-MSCs) to treat Foxn1(-/-) mice, and then analyzed the maturation and distribution of thymic epithelial cells in the Foxn1(-/-) thymic rudiment and the thymopoiesis of this newly developed rudiment. Our data showed a well-organized cortex-medulla architecture and an obvious improvement in the maturation of thymic epithelial cells along with the appearance of UEA-1(+)MHCII(hi) thymic epithelial cells in the rudiment. We further demonstrated improved thymopoiesis and the enhanced export of mature T cells with increased numbers of regulatory T cells into the peripheral blood. Furthermore, we observed that MSCs can engraft into thymic tissue and express many cytokines or proteins, particularly keratinocyte growth factor (KGF) and CD248, which are essential for thymic development. Collectively, our data identified a new mechanism for MSCs, which may provide a proper microenvironment for the reconstitution and functional maturation of the thymus in Foxn1(-/-) mice. Additionally, we elicited additional insights into the therapeutic efficacy of MSCs in several autoimmune diseases.
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Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene.
Toxicol. Lett.
PUBLISHED: 02-11-2014
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Maternal smoking is one of the risk factors for preterm birth and for the development of bronchopulmonary dysplasia (BPD). In this study, we tested the hypothesis that prenatal exposure of rats to benzo[a]pyrene (BP), a component of cigarette smoke, will result in increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification, and that cytochrome P450 (CYP)1A and 1B1 enzymes and oxidative stress mechanistically contribute to this phenomenon. Timed pregnant Fisher 344 rats were administered BP (25 mg/kg) or the vehicle corn oil (CO) on gestational days 18, 19 and 20, and newborn rats were either maintained in room air or exposed to hyperoxia (85% O2) for 7 or 14 days. Hyperoxic newborn rats prenatally exposed to the vehicle CO showed lung injury and alveolar simplification, and inflammation, and these effects were potentiated in rats that were prenatally exposed to BP. Prenatal exposure to BP, followed by hyperoxia, also resulted in significant modulation of hepatic and pulmonary cytochrome P450 (CYP)1A and 1B1 enzymes at PND 7-14. These rats displayed significant oxidative stress in lungs at postnatal day (PND) 14, as evidenced by increased levels of the F2-isoprostane 8-iso-PGF2?. Furthermore, these animals showed BP-derived DNA adducts and oxidative DNA adducts in the lung. In conclusion, our results show increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification following maternal exposure to BP, and our results suggest that modulation of CYP1A/1B1 enzymes, increases in oxidative stress, and BP-DNA adducts contributed to this phenomenon.
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Nanoscale optical probes for cellular imaging.
Chem Soc Rev
PUBLISHED: 01-06-2014
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Nanomaterials with unique optical properties have shown great promise as probes for cellular imaging. Based on these properties, a wide range of plasmonic, fluorescent and Raman probes have been designed and prepared. Nanomaterials of different sizes and shapes have also been functionalized with various types of biomolecules, such as antibodies, DNA or RNA, which are actively exploited to realize targeted imaging. In this review, we will summarize recent advances in using functional nanomaterials for imaging, primarily cellular imaging. These nanomaterials are categorized based on their conducting properties, i.e. conductors, semiconductors and insulators.
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Analysis on tank truck accidents involved in road hazardous materials transportation in china.
Traffic Inj Prev
PUBLISHED: 01-02-2014
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Due to the sheer size and capacity of the tanker and the properties of cargo transported in the tank, hazmat tanker accidents are more disastrous than other types of vehicle accidents. The aim of this study was to provide a current survey on the situation of accidents involving tankers transporting hazardous materials in China.
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SNP@lincTFBS: an integrated database of polymorphisms in human LincRNA transcription factor binding sites.
PLoS ONE
PUBLISHED: 01-01-2014
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Large intergenic non-coding RNAs (lincRNAs) are a new class of functional transcripts, and aberrant expression of lincRNAs was associated with several human diseases. The genetic variants in lincRNA transcription factor binding sites (TFBSs) can change lincRNA expression, thereby affecting the susceptibility to human diseases. To identify and annotate these functional candidates, we have developed a database SNP@lincTFBS, which is devoted to the exploration and annotation of single nucleotide polymorphisms (SNPs) in potential TFBSs of human lincRNAs. We identified 6,665 SNPs in 6,614 conserved TFBSs of 2,423 human lincRNAs. In addition, with ChIPSeq dataset, we identified 139,576 SNPs in 304,517 transcription factor peaks of 4,813 lincRNAs. We also performed comprehensive annotation for these SNPs using 1000 Genomes Project datasets across 11 populations. Moreover, one of the distinctive features of SNP@lincTFBS is the collection of disease-associated SNPs in the lincRNA TFBSs and SNPs in the TFBSs of disease-associated lincRNAs. The web interface enables both flexible data searches and downloads. Quick search can be query of lincRNA name, SNP identifier, or transcription factor name. SNP@lincTFBS provides significant advances in identification of disease-associated lincRNA variants and improved convenience to interpret the discrepant expression of lincRNAs. The SNP@lincTFBS database is available at http://bioinfo.hrbmu.edu.cn/SNP_lincTFBS.
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Analysis of the transcriptome in hyperoxic lung injury and sex-specific alterations in gene expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Exposure to high concentration of oxygen (hyperoxia) leads to lung injury in experimental animal models and plays a role in the pathogenesis of diseases such as Acute Respiratory Distress Syndrome (ARDS) and Bronchopulmonary dysplasia (BPD) in humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. The major goal of this study was to characterize the changes in the pulmonary transcriptome following hyperoxia exposure and further elucidate the sex-specific changes. Male and female (8-10 wk) wild type (WT) (C57BL/6J) mice were exposed to hyperoxia (FiO2>0.95) and gene expression in lung tissues was studied at 48 h. A combination of fold change ?1.4 and false discovery rate (FDR)<5% was used to define differentially expressed genes (DEGs). Overrepresentation of gene ontology terms representing biological processes and signaling pathway impact analysis (SPIA) was performed. Comparison of DEG profiles identified 327 genes unique to females, 585 unique to males and 1882 common genes. The major new findings of this study are the identification of new candidate genes of interest and the sex-specific transcriptomic changes in hyperoxic lung injury. We also identified DEGs involved in signaling pathways like MAP kinase and NF-kappa B which may explain the differences in sex-specific susceptibility to hyperoxic lung injury. These findings highlight changes in the pulmonary transcriptome and sex-specific differences in hyperoxic lung injury, and suggest new pathways, whose components could serve as sex-specific biomarkers and possible therapeutic targets for acute lung injury (ALI)/acute respiratory distress (ARDS) in humans.
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Human fibroblast reprogramming to pluripotent stem cells regulated by the miR19a/b-PTEN axis.
PLoS ONE
PUBLISHED: 01-01-2014
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Induction of pluripotent stem cells (iPSC) by defined transcription factors is the recognized canonical means for somatic reprogramming, however, it remains incompletely understood how individual transcription factors affect cell fate decisions during the reprogramming process. Here, we report induction of fibroblast reprogramming by various transcriptional factors is mediated by a miR19a/b-PTEN axis. cMyc, one of the four Yamanaka factors known to stimulate both somatic cell reprogramming and tumorigenesis, induced the expression of multiple mircoRNAs, miR-17 ? 92 cluster in particular, in the early stage of reprogramming of human fibroblasts. Importantly, miR-17 ? 92 cluster could greatly enhance human fibroblast reprogramming induced by either the four Yamanaka factors (Oct4, Sox2, Klf4, and cMyc, or 4F) or the first three transcriptional factors (Oct4, Sox2, and Klf4, or 3F). Among members of this microRNA cluster, miR-19a/b exhibited the most potent effect on stimulating fibroblst reprogramming to iPSCs. Additional studies revealed that miR-19a/b enhanced iPSC induction efficiency by targeted inhibition of phosphatase and tensin homolog (PTEN), a renowned tumor suppressor whose loss-of-function mutations were found in multiple human malignancies. Our results thus demonstrate an important role of miR-19a/b-PTEN axis in the reprogramming of human fibroblasts, illustrating that the somatic reprogramming process and its underlying regulation pathways are intertwined with oncogenic signaling in human malignancies.
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Effect of mixed transplantation of autologous and allogeneic microskin grafts on wound healing in a rat model of acute skin defect.
PLoS ONE
PUBLISHED: 01-01-2014
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The treatment of extensive thermal injuries with insufficient autologous skin remains a great challenge to burn surgeons. In this study, we investigated the influence of the ratio of autologous and allogeneic tissue in mixed microskin grafts on wound healing in order to develop an effective method for using limited donor skin to cover a large open wound. Four different mixtures were tested: autologous microskin at an area expansion ratio of 10?1 with allogeneic microskin at an area expansion ratio of 10?1 or 10?3 and autologous microskin at an expansion ratio of 20?1 with allogeneic microskin at an expansion ratio of 20?3 or 20?6. Wound healing, wound contraction, and integrin ?1 expression were measured. Mixed microskin grafting facilitated wound healing substantially. The mixture of autologous microskin at an expansion ratio of 10?1 with the same amount of allogeneic microskin achieved the most satisfactory wound healing among the 4 tested mixtures. Histological examination revealed the presence of obviously thickened epidermis and ectopic integrin ?1 expression. Keratinocytes expressing integrin ?1 were scattered in the suprabasal layer. Higher levels of integrin ?1 expression were associated with faster wound healing, implying that ectopic expression of integrin ?1 in keratinocytes may play a pivotal role in wound healing. In conclusion, this study proves that this new skin grafting technique may improve wound healing.
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Constructing and characterizing a bioactive small molecule and microRNA association network for Alzheimers disease.
J R Soc Interface
PUBLISHED: 12-20-2013
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Alzheimers disease (AD) is an incurable neurodegenerative disorder. Much effort has been devoted to developing effective therapeutic agents. Recently, targeting microRNAs (miRNAs) with small molecules has become a novel therapy for human diseases. In this study, we present a systematic computational approach to construct a bioactive Small molecule and miRNA association Network in AD (SmiRN-AD), which is based on the gene expression signatures of bioactive small molecule perturbation and AD-related miRNA regulation. We also performed topological and functional analysis of the SmiRN-AD from multiple perspectives. At the significance level of p ? 0.01, 496 small molecule-miRNA associations, including 25 AD-related miRNAs and 275 small molecules, were recognized and used to construct the SmiRN-AD. The drugs that were connected with the same miRNA tended to share common drug targets (p = 1.72 × 10(-4)) and belong to the same therapeutic category (p = 4.22 × 10(-8)). The miRNAs that were linked to the same small molecule regulated more common miRNA targets (p = 6.07 × 10(-3)). Further analysis of the positive connections (quinostatin and miR-148b, amantadine and miR-15a) and the negative connections (melatonin and miR-30e-5p) indicated that our large-scale predictions afforded specific biological insights into AD pathogenesis and therapy. This study proposes a holistic strategy for deciphering the associations between small molecules and miRNAs in AD, which may be helpful for developing a novel effective miRNA-associated therapeutic strategy for AD. A comprehensive database for the SmiRN-AD and the differential expression patterns of the miRNA targets in AD is freely available at http://bioinfo.hrbmu.edu.cn/SmiRN-AD/.
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Adjustment of ON-State Retention Ability Based on New Donor-Acceptor Imides through Structural Tailoring for Volatile Device Applications.
ACS Appl Mater Interfaces
PUBLISHED: 12-20-2013
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In this study, two D-A molecules NACANA and CANACA, based on carbazole (CA) donor and naphthalimide (NA) acceptor, with different D-A arrangement (A-D-A and D-A-D) were synthesized. The photophysical and electrochemical properties, microstructure and memory behaviors of both A-D-A and D-A-D molecules were systematically investigated. The fabricated devices ITO/NACANA or CANACA layer/Al with a simple sandwich configuration both exhibited volatile nature after shutting off the external electric field. Interestingly, NACANA showed ON-state retention time of ca. 12 min, longer than that of CANACA (ca. 6 min). The difference in retention ability of the programmed states could be assigned to the difference of the D-A arrangement. This type of retention ability adjustment by varying the arrangement of donor and acceptor segments may provide a guide of structure design for future organic-based specific memory devices with tunable volatile property.
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Role of the blood-brain barrier in rabies virus infection and protection.
Protein Cell
PUBLISHED: 11-23-2013
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Rabies is an acute, progressive encephalitis caused by infection with rabies virus (RABV). It is one of the most important zoonotic infections and causes more than 70,000 human deaths annually ( http://www.rabiescontrol.net ). It has long been held that a rabies infection is lethal in humans once the causative RABV reaches the central nervous system (CNS); however, this concept was challenged by the recent recovery of a small number of rabies patients. An analysis of these patients revealed that the bloodbrain barrier (BBB) played a major role in protection against the virus. The main reason for the survival of these patients was enhanced BBB permeability after infection with the causative agent (usually bat-originated RABV showing reduced pathogenicity), which allowed immune cells to enter the tissues of the CNS and clear the infection (Willoughby et al., 2005). These findings have been confirmed in animal infection experiments (Wang et al., 2005; Roy and Hooper, 2007, 2008; Faber et al., 2009). Thus, the BBB has attracted the attention of scientists interested in the pathogenesis of, and therapeutic approaches, for rabies. This paper introduces the role of the BBB in rabies infections and protection of the CNS and provides insight into future treatments for patients with clinical rabies.
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Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy.
Stem Cells Dev.
PUBLISHED: 10-04-2013
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This study was designed to assess the safety and efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs) in the treatment of rheumatoid arthritis (RA). In this ongoing cohort, 172 patients with active RA who had inadequate responses to traditional medication were enrolled. Patients were divided into two groups for different treatment: disease-modifying anti-rheumatic drugs (DMARDs) plus medium without UC-MSCs, or DMARDs plus UC-MSCs group (4×10(7) cells per time) via intravenous injection. Adverse events and the clinical information were recorded. Tests for serological markers to assess safety and disease activity were conducted. Serum levels of inflammatory chemokines/cytokines were measured, and lymphocyte subsets in peripheral blood were analyzed. No serious adverse effects were observed during or after infusion. The serum levels of tumor necrosis factor-alpha and interleukin-6 decreased after the first UC-MSCs treatment (P<0.05). The percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells of peripheral blood was increased (P<0.05). The treatment induced a significant remission of disease according to the American College of Rheumatology improvement criteria, the 28-joint disease activity score, and the Health Assessment Questionnaire. The therapeutic effects maintained for 3-6 months without continuous administration, correlating with the increased percentage of regulatory T cells of peripheral blood. Repeated infusion after this period can enhance the therapeutic efficacy. In comparison, there were no such benefits observed in control group of DMARDS plus medium without UC-MSCs. Thus, our data indicate that treatment with DMARDs plus UC-MSCs may provide safe, significant, and persistent clinical benefits for patients with active RA.
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Dehydroepiandrosterone-sulfate (DHEAS) promotes MIN6 cells insulin secretion via inhibition of AMP-activated protein kinase.
Biochem. Biophys. Res. Commun.
PUBLISHED: 09-20-2013
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Derived from adrenal cortical, dehydroepiandrosterone-sulfate (DHEAS) is a precursor to androgens and estrogens, with various bioactivities. Although it has the property of anti-diabetes, the long-term effect of DHEAS on insulin secretion in beta-cells is still unclear. In this study, the effect of DHEAS on the insulin secretion activity in MIN6 cell lines in vitro was assessed. Insulin biosynthesis and secretion were stimulated by DHEAS for 24h. DHEAS inhibited the AMPK activation and upregulated the expression of ACC-1. These findings indicate that DHEAS may exert prominent stimulatory effects on insulin secretion partly via AMPK inhibition and ACC-1 upregulation.
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MicroRNA-21 in the pathogenesis of acute kidney injury.
Protein Cell
PUBLISHED: 09-13-2013
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Acute kidney injury (AKI), associated with significant morbidity and mortality, is widely known to involve epithelial apoptosis, excessive inflammation, and fibrosis in response to ischemia or reperfusion injury, which results in either chronic pathological changes or death. Therefore, it is imperative that investigations are conducted in order to find effective, early diagnoses, and therapeutic targets needed to help prevent and treat AKI. However, the mechanisms modulating the pathogenesis of AKI still remain largely undetermined. MicroRNAs (miRNAs), small non-coding RNA molecules, play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene expression. MicroRNA-21 (miR-21) is a recently identified, typical miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fibrotic signaling pathways in AKI. As a result, miR-21 is now considered a novel biomarker when diagnosing and treating AKI. This article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI.
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Effect of a ?-spacer between a donor and an acceptor on small molecule-based data-storage device performance.
Chem. Commun. (Camb.)
PUBLISHED: 09-10-2013
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We demonstrate that replacing the hydrazone linkage by a linear ?-spacer bridging a carbazole donor and a naphthalimide acceptor induces a critical change in molecular organization and electron density distribution in the conjugation backbone that correlates with a remarkable variation of memory performance from DRAM to WORM types.
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Interactive effect of galanin-like peptide (GALP) and spontaneous exercise on energy metabolism.
Peptides
PUBLISHED: 09-03-2013
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Galanin-like peptide (GALP) is a neuropeptide involved in energy metabolism. The interactive effect of GALP and exercise on energy metabolism has not been investigated. The aim of this study was to determine if energy metabolism in spontaneously exercising mice could be promoted by intracerebroventricular (ICV) GALP administration. Changes in respiratory exchange ratio in response to GALP ICV administration indicated that lipids were primarily consumed followed by a continuous consumption of glucose throughout the dark period in non-exercising mice. In mice permitted to spontaneously exercise on a running-wheel, GALP ICV administration increased the consumed oxygen volume and heat production level from 5 to 11h after administration. These effects occurred independently from the total running distance. The interaction between GALP ICV administration and spontaneous exercise decreased body weight within 24h (F(1,16)=5.772, p<0.05), with no significant interaction observed regarding food and water intake or total distance. Energy metabolism-related enzymes were assessed in liver and skeletal muscle samples, with a significant interaction on mRNA expression between GALP ICV administration and spontaneous exercise observed in phosphoenolpyruvate carboxykinase (F(1,16)=18.602, p<0.001) that regulates gluconeogenesis and glucose transporter-4 (F(1,16)=21.092, p<0.001). GALP significantly decreased the mRNA expression of sterol regulatory element-binding protein-1c (p<0.05) that regulates fatty acid synthesis regardless of spontaneous exercise with no changes to acetyl-CoA carboxylase a and fatty acid synthetase. These results indicate the GALP ICV administration can further promote energy metabolism when administered to spontaneously exercising mice.
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A graphene oxide-based fluorescent biosensor for the analysis of peptide-receptor interactions and imaging in somatostatin receptor subtype 2 overexpressed tumor cells.
Anal. Chem.
PUBLISHED: 08-12-2013
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Analysis of peptide-receptor interactions provides insights for understanding functions of proteins in cells. In this work, we report the development of a fluorescent biosensor for the analysis of peptide-receptor interactions using graphene oxide (GO) and fluorescein isothiocyanate (FITC)-labeled octreotide (FOC). Octreotide is a synthesized cyclic peptide with somatostatin-like bioactivity that has been clinically employed. FOC exhibits high adsorption affinity for GO, and its binding results in efficient fluorescence quenching of FITC. Interestingly, the specific binding of the antibody anti-octreotide (AOC) with FOC competitively releases FOC from the GO surface, leading to the recovery of fluorescence. By using this GO-based fluorescent platform, we can detect AOC with a low detection limit of 2 ng/mL. As a step further, we employ this GO-FOC biosensor to image somatostatin receptor subtype 2 overexpressed AR42J tumor cells, which demonstrates high promise for molecular imaging in cancer diagnosis.
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Comparative evaluation of topical pranoprofen and fluorometholone in cases with chronic allergic conjunctivitis.
Cornea
PUBLISHED: 08-08-2013
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This study was conducted to compare the efficacy of 0.1% fluorometholone and 0.1% pranoprofen in cases with chronic allergic conjunctivitis.
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Spectroscopic and biological studies of phenanthroline compounds: selective recognition of gene-promoter G-quadruplex DNAs preferred over duplex DNA.
Chem. Biodivers.
PUBLISHED: 06-19-2013
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G-Quadruplex DNA formed in the promoter regions of proto-oncogenes would block the transcription process and eventually suppress the development of tumors, so compounds that stabilize G-quadruplex DNA are potential antitumor drugs. This article describes the interactions of three phenanthroline compounds, a-c, with proto-oncogene c-kit2 and c-myc G-quadruplex DNAs by means of polymerase chain reaction (PCR) stop assay, fluorescence resonance energy transfer melting (FRET melting) assay, fluorescence indicator displacement (FID) assay, UV/VIS absorption, fluorescence, and circular dichroism (CD) spectroscopies. All three compounds displayed selectivity for the G-quadruplex over duplex, with binding constants (Ka) for the both quadruplexes varying from 0.49×10? to 3.32×10? M?¹ (4.1- to 33.2-fold specificity). Compounds a, b, and c were potential stabilizers for the c-kit2 G-quadruplex with the melting-temperature increase (?Tm) values of 12-15°. CD Spectra indicated that a-c disrupted the structure of c-kit2 G-quadruplex, whereas no significant change was observed for c-myc G-quadruplex.
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Light emission in water-containing cocrystals: the influence of water molecules on the fluorescence properties of a schiff-base molecule.
Chem Asian J
PUBLISHED: 06-18-2013
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In the presence or absence of water, a Schiff-base compound, 4-amino-3-(2-(2-hydroxybenzylidene)hydrazinyl)-1H-1,2,4-triazole-5(4H)-thione (HATT), forms different crystalline states (HATT, HATT?2?H2 O, and a lamellar structure, m-HATT?n?H2 O), which show different luminescence emission properties. Herein, we investigate the emission of HATT and the role of water molecules. A water molecule, which acts as both a hydrogen-bond acceptor and -donor, enlarges the distance between adjacent HATT molecules and hinders non-radiative decay pathways.
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Cross-species protein interactome mapping reveals species-specific wiring of stress response pathways.
Sci Signal
PUBLISHED: 05-23-2013
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The fission yeast Schizosaccharomyces pombe has more metazoan-like features than the budding yeast Saccharomyces cerevisiae, yet it has similarly facile genetics. We present a large-scale verified binary protein-protein interactome network, "StressNet," based on high-throughput yeast two-hybrid screens of interacting proteins classified as part of stress response and signal transduction pathways in S. pombe. We performed systematic, cross-species interactome mapping using StressNet and a protein interactome network of orthologous proteins in S. cerevisiae. With cross-species comparative network studies, we detected a previously unidentified component (Snr1) of the S. pombe mitogen-activated protein kinase Sty1 pathway. Coimmunoprecipitation experiments showed that Snr1 interacted with Sty1 and that deletion of snr1 increased the sensitivity of S. pombe cells to stress. Comparison of StressNet with the interactome network of orthologous proteins in S. cerevisiae showed that most of the interactions among these stress response and signaling proteins are not conserved between species but are "rewired"; orthologous proteins have different binding partners in both species. In particular, transient interactions connecting proteins in different functional modules were more likely to be rewired than conserved. By directly testing interactions between proteins in one yeast species and their corresponding binding partners in the other yeast species with yeast two-hybrid assays, we found that about half of the interactions that are traditionally considered "conserved" form modified interaction interfaces that may potentially accommodate novel functions.
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MicroRNA expression analysis of rosette and folding leaves in Chinese cabbage using high-throughput Solexa sequencing.
Gene
PUBLISHED: 05-13-2013
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In this study, a global analysis of miRNA expression from rosette leaves (RLs) and folding leaves (FLs) of Chinese cabbage (Brassica rapa L. ssp. pekinensis) was conducted using high-throughput Solexa sequencing. In total, over 12 million clean reads were obtained from each library. Sequence analysis identified 64 conserved miRNA families in each leaf type and 104 and 95 novel miRNAs from RLs and FLs, respectively. Among these, 61 conserved miRNAs and 61 novel miRNAs were detected in both types of leaves. Furthermore, six conserved and 21 novel miRNAs were differentially expressed between the two libraries. Target gene annotation suggested that these differentially expressed miRNAs targeted transcription factors, F-box proteins, auxin and Ca(2+) signaling pathway proteins, protein kinases and other proteins that may function in governing leafy head formation. This study advanced our understanding of the important roles of miRNAs in regulating leafy head development in Chinese cabbage.
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Comparison of bilateral lateral rectus recession and unilateral recession resection for basic type intermittent exotropia in children.
Br J Ophthalmol
PUBLISHED: 05-04-2013
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To compare surgical outcome of bilateral lateral rectus recession (BLR-rec) and unilateral lateral rectus recession combined with medial rectus resection (R&R) for the basic type of intermittent exotropia (IXT) in children.
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Sorghum bmr6 mutant analysis demonstrates that a shared MYB1 transcription factor binding site in the promoter links the expression of genes in related pathways.
Funct. Integr. Genomics
PUBLISHED: 04-09-2013
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Sorghum is not only an important cereal crop but also a biofuel crop. The sorghum brown midrib mutant 6 (bmr6) has a reduced lignin content in the cell walls and vascular tissues, which could potentially be advantageous for cellulosic biofuel production. Meanwhile, both dry matter yield and plant height were decreased in the bmr6 mutant. To identify genes affected in the mutant, differential gene expression analysis was performed for bmr6 and the wild type. As a result, a total of 1,052 differentially expressed genes were detected between the two samples, of which 166 genes were downregulated and 886 genes were upregulated. Five hundred seventy-nine of the 1,052 differentially expressed genes could be assigned to 154 documented pathways. These pathways mainly included primary and secondary metabolism. Therefore, mutation of the bmr6 gene, which impaired the biosynthesis of lignin, ultimately affected the expression of these genes associated with the growth and development of sorghum. Except for the bmr6 gene, 11 key enzyme genes of monolignols biosynthesis were upregulated. Promoter analysis identified that these genes have common MYB sites. It revealed that a feedback mechanism existed in the pathway and a MYB1 transcription factor (Sb02g031190) could associate with the upregulation of these genes in sorghum. In this study, we investigated gene expressions at a global level in sorghum bmr6 mutant and provided valuable insights into the mechanisms of lignin biosynthesis.
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Sex-specific differences in hyperoxic lung injury in mice: implications for acute and chronic lung disease in humans.
Toxicol. Appl. Pharmacol.
PUBLISHED: 03-23-2013
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Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO2>0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF 2?) (LC-MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2? levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F>M) and VEGF (M>F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans.
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Identifying dysfunctional miRNA-mRNA regulatory modules by inverse activation, cofunction, and high interconnection of target genes: a case study of glioblastoma.
Neuro-oncology
PUBLISHED: 03-20-2013
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Accumulating evidence demonstrates that complex diseases may arise from cooperative effects of multiple dysfunctional miRNAs. Thus, identifying abnormal functions cooperatively regulated by multiple miRNAs is useful for understanding the pathogenesis of complex diseases.
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A graphene-based platform for fluorescent detection of SNPs.
Analyst
PUBLISHED: 03-20-2013
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A novel fluorescent single nucleotide polymorphism (SNP) assay was developed by using Graphene Oxide (GO), which provides a fast, sensitive and simple method for SNP detection. The strategy was based on the single base extension reaction and different absorption capacity of fluorescein labeled dGTP (dGTP-Fl) and double-stranded DNA (dsDNA) to GO. dGTP-Fl is incorporated into the probe by extension reaction for the mutant target but not for the wild target, which leads to recovered fluorescence for the mutant target because of weak interaction between dsDNA and GO and weak fluorescence for the wild target because of the quenched fluorescence of dGTP-Fl by GO. The method shows a linear range for the mutant-type target from 3 nM to 50 nM and 3 nM is the detection limit. It was noted that as low as 10% mutant-type target could be detected in the presence of the wild-type target, in which the concentration is 9 times higher than that of the mutant-type target.
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The improvement of pelvic floor muscle function in POP patients after the Prolift procedure: results from surface electromyography.
Int Urogynecol J
PUBLISHED: 03-09-2013
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Patients with pelvic organ prolapse (POP) have lower pelvic floor muscle (PFM) function. We hypothesized that pelvic reconstructive surgery could improve PFM function and strength.
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A power-free microfluidic chip for SNP genotyping using graphene oxide and a DNA intercalating dye.
Chem. Commun. (Camb.)
PUBLISHED: 03-08-2013
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We herein report a power-free microfluidic chip for fluorescent DNA detection with high single-nucleotide polymorphism discrimination, using a DNA intercalator and graphene oxide.
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A microRNA miR-34a-regulated bimodal switch targets notch in colon cancer stem cells.
Cell Stem Cell
PUBLISHED: 03-04-2013
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microRNAs regulate developmental cell-fate decisions, tissue homeostasis, and oncogenesis in distinct ways relative to proteins. Here, we show that the tumor suppressor microRNA miR-34a is a cell-fate determinant in early-stage dividing colon cancer stem cells (CCSCs). In pair-cell assays, miR-34a distributes at high levels in differentiating progeny, whereas low levels of miR-34a demarcate self-renewing CCSCs. Moreover, miR-34a loss of function and gain of function alter the balance between self-renewal versus differentiation both in vitro and in vivo. Mechanistically, miR-34a sequesters Notch1 mRNA to generate a sharp threshold response where a bimodal Notch signal specifies the choice between self-renewal and differentiation. In contrast, the canonical cell-fate determinant Numb regulates Notch levels in a continuously graded manner. Altogether, our findings highlight a unique microRNA-regulated mechanism that converts noisy input into a toggle switch for robust cell-fate decisions in CCSCs.
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MicroRNA-124a is epigenetically regulated and acts as a tumor suppressor by controlling multiple targets in uveal melanoma.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 02-14-2013
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MicroRNA-124a (miR-124a), an abundant microRNA in the central neuron system, has been linked to tumor progression. Here, we investigated the role of miR-124a in uveal melanoma development.
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Highly sensitive and selective detection of silver(I) in aqueous solution with silver(I)-specific DNA and Sybr Green I.
Analyst
PUBLISHED: 02-11-2013
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We report a label-free fluorescence turn-on approach for the sensitive and selective sensing of silver ion Ag(+) based on Ag(+) induced conformational change of cytosine-rich single-stranded DNA. A silver specific oligonucleotide (SSO) undergoes a structural transition from single-stranded DNA (ssDNA) to a C-Ag(+)-C mediated hairpin structure, which can be recognized by a double-stranded DNA (dsDNA) intercalator Sybr Green I (SG). The linear response range for Ag(+) detection was from 1 nM to 100 nM. The method presented here is highly sensitive and a limit of detection of 1 nM was obtained. More importantly, this optical method was successfully used to identify complex sample mixtures.
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Xanthoceraside attenuates learning and memory deficits via improving insulin signaling in STZ-induced AD rats.
Neurosci. Lett.
PUBLISHED: 02-07-2013
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Xanthoceraside, a triterpenoid saponin extracted from the fruit husks of Xanthoceras sorbifolia Bunge, has been shown to reverse the cognitive deficits observed in several Alzheimers disease (AD) animal models. Increasing evidence suggests the involvement of the insulin signaling pathway in neurodegenerative disorders such as AD. Thus, we used an AD animal model of cognitive impairment induced by the intracerebroventricular (ICV) injection of streptozotocin (STZ) to test the effects of xanthoceraside on behavioral impairments and insulin signaling mechanisms. In our present study, memory impairment was assessed using the Morris water maze test. The expression of IR, IGF-1R and Raf-1/ERK/CREB was tested by western blotting. The STZ group showed memory deficits in the Morris water maze test and significant decreases in IR and IGF-1R protein levels in the hippocampus. Xanthoceraside treatment significantly rescued memory deficits, as well as IR and IGF-1R protein expression levels. STZ inhibited the Ras/ERK signaling cascade and decreased the phosphorylation of CREB; these effects were also attenuated by xanthoceraside treatment. These results suggest the potential use of xanthoceraside for the treatment of neurodegenerative disorders in which brain insulin signaling may be involved.
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Nondestructive analysis of dragonfly eye beads from the warring states period, excavated from a Chu tomb at the Shenmingpu site, Henan Province, China.
Microsc. Microanal.
PUBLISHED: 02-07-2013
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Dragonfly eye beads are considered to be the earliest types of glass objects in China, and in the past have been considered as evidence of culture interaction or trade between West and East Asia. In this article, synchrotron radiation microcomputed tomography and ?-probe energy dispersive X-ray fluorescence were used to determine the chemical composition, microstructure, and manufacturing technology of four dragonfly eye beads, excavated from a Chu tomb at the Shenmingpu site, Henan Province, China, dated stylistically to the Middle and Late Warring State Period (475 BC-221 BC). First, a nondestructive method was used to differentiate the material types including faience (glazed quartz), frit, glazed pottery (clay ceramic), and glass. Three beads were identified as faience and one bead as glazed pottery. The glaze recipe includes quartz, saltpeter, plant ash, and various copper, and is classified as belonging to the K2O-CaO-SiO2 glass system, which indicates that these beads were not imported from the West. Based on computed tomography slices, the manufacturing technology of the faience eye beads appears to include the use of an inner core, molding technology, and the direct application glazing method. These manufacturing features are consistent with the techniques used in China during this same time period for bronze mold-casting, proto-porcelain, and glass.
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Genetic diversity and molecular evolution of the rabies virus matrix protein gene in China.
Infect. Genet. Evol.
PUBLISHED: 02-02-2013
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To investigate the diversity of rabies virus (RABV) matrix protein (M) gene in the current Chinese rabies epidemic, we fully examined M gene of 63 street RABVs (Virus isolated from naturally infected animals), and performed phylogenetic and mutational analysis. Our results indicate that the Chinese RABV M gene is well conserved with 90.6% to 100% amino acid similarity. Analysis of the mutations indicates that the sequences can be divided into four groups with each group defined by distinct substitutions. The PPxY motif and residue E58, which are essential for efficient virus production and pathogenicity, were completely conserved. The estimated mean rate of nucleotide substitution was 4.6×10(-4) substitutions per site per year, and the estimated average time of the most recent common ancestor (TMRCA) was 265 years ago based on the M gene of Chinese street RABVs, which are similar to previously reported values for the glycoprotein (G) and nucleoprotein (N) gene. This indicates that the genomic RNA of RABVs circulating worldwide is stable; G, N and M genes are evolving at a similar rate. This study showed that although the Chinese RABV strains could be divided into distinct clades based on the phylogenetic analysis, their functional domains of M proteins were highly conserved.
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The oxidative damage and inflammatory response induced by lead sulfide nanoparticles in rat lung.
Food Chem. Toxicol.
PUBLISHED: 01-29-2013
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Lead sulfide nanoparticles (PbS NPs) are one important nanoparticle materials which is widely used in photoelectric production, but its potential health hazard to respiratory system is not clear. This study aimed to explore the possible mechanism of lung injury induced by PbS NPs. Male SD rats were treated with nanoparticles of 60 nm and 30 nm lead sulfide. The main methods were detecting the vigor of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) and the content of malondialdehyde (MDA) in both blood and lung tissues and observing the pathological changes in lung tissue. PbS NPs suppressed the activity of SOD and T-AOC, and increased serum MDA content (P<0.05); both effects were observed together in lung tissues of 30-nm group (P<0.05) accompanied by an obviously inflammatory response. PbS NPs induced oxidative damage and inflammatory response in lung tissue, which may be an underlying mechanism for its pulmonary toxicity. Additionally, the toxicity of PbS NPs was closely related with the size of nanoparticles.
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In situ atomic-scale observation of continuous and reversible lattice deformation beyond the elastic limit.
Nat Commun
PUBLISHED: 01-15-2013
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The elastic strain sustainable in crystal lattices is usually limited by the onset of inelastic yielding mediated by discrete dislocation activity, displacive deformation twinning and stress-induced phase transformations, or fracture associated with flaws. Here we report a continuous and gradual lattice deformation in bending nickel nanowires to a reversible shear strain as high as 34.6%, which is approximately four times that of the theoretical elastic strain limit for unconstrained loading. The functioning deformation mechanism was revealed on the atomic scale by an in situ nanowire bending experiments inside a transmission electron microscope. The complete continuous lattice straining process of crystals has been witnessed in its entirety for the straining path, which starts from the face-centred cubic lattice, transitions through the orthogonal path to reach a body-centred tetragonal structure and finally to a re-oriented face-centred cubic structure.
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A multi-histology trial of fostamatinib in patients with advanced colorectal, non-small cell lung, head and neck, thyroid, and renal cell carcinomas, and pheochromocytomas.
Cancer Chemother. Pharmacol.
PUBLISHED: 01-12-2013
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A multi-cohort phase II study of fostamatinib, an oral multi-kinase inhibitor, was conducted to determine the response rate in patients with advanced colorectal (CRC), thyroid, non-small cell lung, head and neck, and renal cell carcinomas, and pheochromocytomas.
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Genetic and evolutionary characterization of RABVs from China using the phosphoprotein gene.
Virol. J.
PUBLISHED: 01-07-2013
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While the function of the phosphoprotein (P) gene of the rabies virus (RABV) has been well studied in laboratory adapted RABVs, the genetic diversity and evolution characteristics of the P gene of street RABVs remain unclear. The objective of the present study was to investigate the mutation and evolution of P genes in Chinese street RABVs.
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Functional deficiency of aryl hydrocarbon receptor augments oxygen toxicity-induced alveolar simplification in newborn mice.
Toxicol. Appl. Pharmacol.
PUBLISHED: 01-02-2013
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Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. New BPD is characterized as having alveolar simplification. We reported previously that aryl hydrocarbon receptor (AhR) deficiency increased susceptibility to hyperoxic lung injury in adult mice, and this was associated with decreased expression of cytochrome P450 1A enzymes and increased lung inflammation. Whether AhR protects newborn mice against hyperoxia-induced alveolar simplification is unknown. Thus, we tested the hypothesis that decreased activation of the pulmonary AhR augments hyperoxia-induced alveolar simplification and lung inflammation in newborn mice. Experimental groups included one-day old wild type (WT) and AhR dysfunctional (AhRd) mice exposed to 21% O? (air) or 85% O? (hyperoxia) for 14 days. Exposure of newborn WT mice to hyperoxia resulted in increased protein, enzyme and mRNA expression of the AhR-regulated lung cytochrome P450 1A1, NAD(P)H quinone oxidoreductase-1, and microsomal glutathione S-transferase 1 enzymes, suggesting that hyperoxia increases activation of the pulmonary AhR. On the other hand, in the AhRd mice, hyperoxia induced the AhR-regulated enzymes to a lesser extent probably due to the dysfunctional AhR in these mice. Alveolar simplification and lung inflammation was increased in mice exposed to hyperoxia compared with those exposed to air, and AhRd mice were more susceptible to hyperoxia-induced alveolar simplification and lung inflammation compared with WT mice. These findings suggest that decreased activation of the pulmonary AhR in newborn AhRd mice augments hyperoxia-induced alveolar simplification and lung inflammation in these mice.
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Epigenetic inactivation of EFEMP1 is associated with tumor suppressive function in endometrial carcinoma.
PLoS ONE
PUBLISHED: 01-01-2013
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EFEMP1, the epidermal growth factor-containing fibulin-like extracellular matrix protein 1, functions as an oncogene or a tumor suppressor depending on the cancer types. In this study, we aim to determine whether EFEMP1 affects the tumorigenesis and progression of endometrial carcinoma.
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Functional metabotropic glutamate receptors 1 and 5 are expressed in murine podocytes.
Kidney Int.
PUBLISHED: 12-14-2011
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In non-neuronal cells, glutamate is an extracellular signaling mediator. Since podocytes have glutamate-containing vesicles, we sought to determine glutamate receptor presence and action in glomerular cells. The metabotropic glutamate receptors (mGluR) 1, 5, 6, and 8 were found to be expressed in mouse brain and glomeruli; predominantly in podocytes. In two models of proteinuria (BalB/C mice with puromycin aminonucleoside- and doxorubicin-induced podocyte injury) we found that the selective mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine (DHPG) attenuated albuminuria and improved the expression of the podocyte marker WT-1. TUNEL staining showed that the number of podocytes undergoing apoptosis was inversely correlated with the number of WT-1-positive cells in glomeruli. When podocytes were treated with DHPG in vitro, they generated cyclic AMP and activated CREB (cyclic AMP response element binding protein). The selective mGluR1/5 antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid, the adenylate cyclase inhibitor SQ22536, and RNA interference knockdown of mGluR1 or mGluR5 all prevented DHPG-induced cAMP generation and CREB activation. DHPG inhibited apoptosis and the decrease of aminonucleoside-induced mitochondrial membrane potential in podocytes but had no effect in the presence of SQ22536 with knockdown mGluR1 or mGluR5. Thus, functional mGluR1 and mGluR5 are expressed in podocytes and their activation protects against albuminuria and podocyte apoptosis, processes that are, at least in part, dependent on cAMP.
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Comparison between graded unilateral and bilateral medial rectus recession for esotropia.
Br J Ophthalmol
PUBLISHED: 11-17-2011
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To compare the postoperative surgical outcomes and the changes in deviation achieved per millimetre of recession in patients treated by graded unilateral medial rectus (UMR) or bilateral medial rectus (BMR) recession for small to large angle esotropia with a minimum follow-up of 6 months.
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[Effect of different light of LED light quality on growth and antioxidant enzyme activities of Ganoderma lucidum].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-01-2011
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To study the effect of light quality on growth, antioxidant enzyme activities of Ganoderma lucidum mycelium.
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A highly sensitive and selective competition assay for the detection of cysteine using mercury-specific DNA, Hg and Sybr Green I.
Sensors (Basel)
PUBLISHED: 09-03-2011
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We here report a rapid, sensitive, selective and label-free fluorescence detection method for cysteine (Cys). The conformation of mercury-specific DNA (MSD) changes from a random coil form to a hairpin structure in the presence of Hg2+ due to the formation of a thymine-Hg2+ -thymine (T-Hg2+ -T) complex. Cys can selectively coordinate with Hg2+ and extract it from the thymine-Hg2+ -thymine complex. The hairpin structure dehybridizes and the fluorescence intensity of Sybr Green I (SG) decreases upon addition of Cys because SG efficiently discriminates mercury-specific DNA and mercury-specific DNA/Hg2+ complex. The detection can be finished within 5 min with high sensitivity and selectivity. In addition, we can obtain variable dynamic ranges for Cys by changing the concentration of MSD/Hg2+.
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Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas.
Cancer Res.
PUBLISHED: 07-27-2011
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A phase I trial of ABT-888 (veliparib), a PARP inhibitor, in combination with topotecan, a topoisomerase I-targeted agent, was carried out to determine maximum tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of the combination in patients with refractory solid tumors and lymphomas. Varying schedules and doses of intravenous topotecan in combination with ABT-888 (10 mg) administered orally twice a day (BID) were evaluated. Plasma and urine pharmacokinetics were assessed and levels of poly(ADP-ribose) (PAR) and the DNA damage marker ?H2AX were measured in tumor and peripheral blood mononuclear cells (PBMC). Twenty-four patients were enrolled. Significant myelosuppression limited the ability to coadminister ABT-888 with standard doses of topotecan, necessitating dose reductions. Preclinical studies using athymic mice carrying human tumor xenografts also informed schedule changes. The MTD was established as topotecan 0.6 mg/m²/d and ABT-888 10 mg BID on days one to five of 21-day cycles. Topotecan did not alter the pharmacokinetics of ABT-888. A more than 75% reduction in PAR levels was observed in 3 paired tumor biopsy samples; a greater than 50% reduction was observed in PBMCs from 19 of 23 patients with measurable levels. Increases in ?H2AX response in circulating tumor cells (CTC) and PBMCs were observed in patients receiving ABT-888 with topotecan. We show a mechanistic interaction of a PARP inhibitor, ABT-888, with a topoisomerase I inhibitor, topotecan, in PBMCs, tumor, and CTCs. Results of this trial reveal that PARP inhibition can modulate the capacity to repair topoisomerase I-mediated DNA damage in the clinic.
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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.