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Find video protocols related to scientific articles indexed in Pubmed.
[Construct validity of the life transition scale for parents of children with autism].
J Korean Acad Nurs
PUBLISHED: 11-11-2014
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The study was done to identify the construct validity and reliability of the life transition scale (LTS) for parents who have children with autism.
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Five-Year Results of Laparoscopic Sleeve Gastrectomy in Korean Patients with Lower Body Mass Index (30-35 kg/m(2)).
Obes Surg
PUBLISHED: 11-10-2014
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In Asia, laparoscopic sleeve gastrectomy (LSG) is the leading weight loss procedure for treating morbid obesity. However, long-term results of isolated LSG performed in patients with lower body mass index (BMI) (30-35 kg/m(2)) are scarce.
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[A novel vegetation index (MPRI) of corn canopy by vehicle-borne dynamic prediction].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 11-01-2014
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Ground-based remote sensing system is a significant way to understand the growth of corn and provide accurate and scientific data for precision agriculture. The vehicle-borne system is one of the most important tools for corn canopy monitoring. However, the vehicle-borne growth monitoring system cannot maintain steady operations due to the row spacing of corn. The reflectance of corn canopy, which was used to construct the model for the chlorophyll content, was disturbed by the reflectance of soil background. The background interference with the reflectance could not be removed effectively, which would result in a deviation in the growth monitoring. In order to overcome this problem, a novel vegetation index named MPRI was developed in the present paper. The tests were carried out by the vehicle-borne system on the cornfield. The sensors which configured the vehicle-borne system had 4 bands, being respectively 550, 650, 766 and 850 nm. It would obtain the spectral data while the vehicle moved along the row direction. The sampling rate was about 1 point per second. The GPS receiver obtained the location information at the same rate. MPRI was made up by the reflectance ratio of 660 and 550 nm. It was very effective to analyze the information about the reflectance of the canopy. The results of experiments showed that the MPRI of soil was the positive value and the MPRI of canopy was the negative value. So it is easier to distinguish the spectral information about soil and corn canopy by MPRI. The results indicated that: it had satisfactory forecasting accuracy for the chlorophyll content by using the MPRI on the moving monitoring. The R2 of the prediction model was about 0.72. The R2 Of the model of NDVI, which was used to represent the chlorophyll content, was only 0.24. It indicates that MPRI had good measurement results for the dynamic measurement process. It provided the novel measurement way to get the canopy reflectance spectra and the better vegetation index to construct the prediction model of the contents of chlorophyll.
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Follicle-Stimulating Hormone Induced Epithelial-Mesenchymal Transition of Epithelial Ovarian Cancer Cells Through Follicle-Stimulating Hormone Receptor PI3K/Akt-Snail Signaling Pathway.
Int. J. Gynecol. Cancer
PUBLISHED: 10-24-2014
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It has previously been shown that follicle-stimulating hormone (FSH) and its receptor contribute to epithelial ovarian cancer (EOC) development. Epithelial-mesenchymal transition (EMT) is the early event of metastasis in cancer. Therefore, the aim of this study was to investigate the roles of FSH and the FSH receptor (FSHR) in EMT of EOC.
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[Prevention and treatment of aromatase inhibitor-associated bone loss by shugan jiangu recipe in postmenopausal women with breast cancer: a clinical study].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 10-23-2014
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To study the effect of Shugan Jiangu Recipe (SJR) on bone mineral density (BMD) and serum bone metabolic biochemical markers in postmenopausal breast cancer patients with osteopenia.
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Effect of lead pollution control on environmental and childhood blood lead level in nantong, china: an interventional study.
Environ. Sci. Technol.
PUBLISHED: 10-23-2014
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Children's blood lead levels and prevalence of lead poisoning in China are significantly higher than in developed countries, though a substantial decrease has been observed. Since 2011, strict lead control policies in lead-related industries have been implemented in China, but the success of these policies is unknown. In this study, we collected environmental samples, questionnaire data, and blood samples from 106 children from 1 to 14 years old, before and after implementation of lead-usage control policy in wire rope factories by local government in Zhuhang, Nantong in 2012. Results showed that, one year after the lead control, lead concentrations sharply decreased in both environmental and biological samples with a decrease of 0.43 ?g/m(3) (-84.3%) in ambient air samples, 0.22 mg/kg (-36.1%) in vegetable samples, 441.1 mg/kg (-43.7%) in dust samples, and 6.24 ?g/dL (-51.5%) in childhood blood lead levels (BLL). This study demonstrates the success of lead control policies in promoting the prevention and control of childhood lead poisoning in Nantong, China.
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[Estrogen reduced myocardial damage by regulating G?s-cAMP pathway in isoprenaline injured rats].
Sheng Li Xue Bao
PUBLISHED: 10-22-2014
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The aim of the present study is to explore the mechanism of estrogen on regulating cardiac function disorder by adjusting the stimulating adenylate cyclase G ? protein (G?s)-cycle adenosine monophosphate (cAMP) signal pathway. Adult female rats were randomly divided into five groups: sham group, ovariectomized group (OVX), OVX and 17?-estradiol given group (OVX+E2), OVX and isoprenaline injected group (OVX+ISO), OVX and 17?-estradiol, isoprenaline injected group (OVX+E2+ISO). Rats were ovariectomized, and two weeks later, OVX+E2 group was injected with E2, OVX+ISO group was injected with ISO, OVX+E2+ISO group was injected with E2 and ISO. Another four weeks later, the hemodynamic parameters were monitored by carotid artery intubation: left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal differentials of left ventricular developed pressure (+dp/dtmax), and minimal differentials of left ventricular developed pressure (-dp/dtmax). Brain natriuretic peptide (BNP) and cAMP concentration in plasma were determined; G?s protein expression in myocardium was determined. The results showed that the hemodynamic parameters, the concentration of BNP and cAMP in plasma had no significant changes after ovariectomy compared with sham group. But after isoprenaline injection in ovariectomized rats, LVSP and +dp/dtmax declined (P < 0.01), LVEDP and -dp/dtmax elevated (P < 0.01); plasma BNP concentration increased (P < 0.01); plasma cAMP concentration decreased (P < 0.01), compared with OVX group. Further estrogen supplements improved the heart function treated by isoprenaline: LVSP and +dp/dtmax elevated (P < 0.01), LVEDP and -dp/dtmax declined (P < 0.05, P < 0.01); the plasma BNP concentration decreased (P < 0.01); the plasma cAMP concentration increased (P < 0.01). Estrogen had no significant influence on G?s protein expression. The results suggest that estrogen can alleviate myocardial injury and regulate cardiac function disorder by increasing cAMP level, finally improved the excessive suppression of myocardium.
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[Danshensu delays the senescence of rat aortic endothelial cells via activation of SIRT1-SOD pathway].
Sheng Li Xue Bao
PUBLISHED: 10-22-2014
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The present study was aimed to investigate the effect of pretreatment with Danshensu (DSS) on rat aortic endothelial cells (RAECs) senescence and the underlying mechanisms. Cultured RAECs at fourth and twelfth passages were taken as young and old groups, respectively. DSS and DSS+nicotinamide (DSS+N) groups were incubated with DSS and DSS in combination with nicotinamide, an inhibitor of silent information regulator 1 (SIRT1), from the fourth to twelfth passage, respectively. The cell status of senescence was determined by the senescence-associated ?-galactosidase (SA ?-gal) staining, and 4,6-diamino-2-phenyl indole (DAPI) fluorescent dye was used to detect senescence associated heterochromatin foci (SAHF) formation; Thiobarbituric acid (TBA) and colorimetric methods were used to evaluate malondialdehyde (MDA) and H2O2 contents; Western blot was employed to analysis the expressions of xanthine oxidase (XOD), SIRT1 and superoxide dismutase 2 (SOD2) in the RAECs. The results showed that, in comparison with young group, the old group exhibited higher SA ?-gal positive and SAHF formation rates, as well as higher MDA and H2O2 levels (P < 0.05 or P < 0.01), whereas DSS pretreatment reduced SA ?-gal positive and SAHF formation rates, decreased MDA and H2O2 contents (P < 0.05 or P < 0.01). The protection of DSS was reversed by nicotinamide. Compared with the young group, the old group showed higher expression levels of XOD, but lower SIRT1 and SOD2 expression levels (P < 0.05 or P < 0.01). With the pretreatment of DSS, the expression of XOD was declined, and the expression levels of SIRT1 and SOD2 were elevated, while nicotinamide reversed the effects of DSS. These results suggest that DSS delays senescence of RAECs via up-regulation of SIRT1.
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Optimized Preparation of a (99m)Tc-Radiolabeled Probe for Tracing MicroRNA.
Cell Biochem. Biophys.
PUBLISHED: 10-16-2014
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Antisense oligonucleotides have been used for a variety of purposes in microRNA (miRNA) research including functional evaluation, target recognition, and gene studies. Although several (99m)Tc-radiolabeled oligonucleotides have been reported in antisense imaging, none of those were related to miRNA tracing. Moreover, separation after labeling was always required to achieve acceptable radiochemical purity. In this study, we prepared a (99m)Tc-radiolabeled oligonucleotide under optimized conditions for the purpose of tracing miRNA. A 22mer anti-miRNA oligonucleotide (AMO) was designed completely complementary to the sequence of mature miR-21. AMO probe modified with 2'-O-Methyl and phosphorothioate backbone was designed and synthesized. This probe was conjugated with a bifunctional chelator S-acetylmercaptoacetyltriglycine (NHS-MAG3) via a primary amine on 5'-end. Furthermore, it was radiolabeled and its optimization labeling conditions were performed by varying the amount of stannous ion, (99m)Tc-pertecnetate, and reaction time, respectively. Finally, the labeled product was identified by gel electrophoresis and evaluated for its serum stability. The AMO was synthesized with partial 2'-OMe and phosphorothioate modification to improve its stability. Excess of MAG3 impurity was removed by precipitation of tin and MAG3 after the conjugation. The labeling efficiency reached 97 % under the optimal reaction conditions of 2 ?g/?L SnCl2·2H2O addition, (99m)Tc solution with high specific activity, and 90-min reaction at room temperature. Gel electrophoresis confirmed that the peak of radioactivity located the same position of oligomer, which identified the successful radiolabeling. After incubated with human fresh serum for 12 h, labeled AMO showed good stability with high radiochemical purity and no significant degradation. A (99m)Tc-labeled AMO targeting miR-21 can be prepared with high labeling efficiency under optimized conditions, which provides a good support for the future use of miRNA-targeted tracing and imaging.
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[Zoledronate inhibits TRPV5 and NFATc1 expression during differentiation of osteoclasts].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 09-30-2014
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To explore the effect of zoledronate (ZOL) on osteoclast differentiation and expressions of transient receptor potential vanilloid 5 channel (TRPV5) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1).
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Arsenic Induces Polyadenylation of Canonical Histone mRNA by Down-regulating Stem-Loop-binding Protein Gene Expression.
J. Biol. Chem.
PUBLISHED: 09-28-2014
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The replication-dependent histone genes are the only metazoan genes whose messenger RNA (mRNA) does not terminate with a poly(A) tail at the 3'-end. Instead, the histone mRNAs display a stem-loop structure at their 3'-end. Stem-loop-binding protein (SLBP) binds the stem-loop and regulates canonical histone mRNA metabolism. Here we report that exposure to arsenic, a carcinogenic metal, decreased cellular levels of SLBP by inducing its proteasomal degradation and inhibiting SLBP transcription via epigenetic mechanisms. Notably, arsenic exposure dramatically increased polyadenylation of canonical histone H3.1 mRNA possibly through down-regulation of SLBP expression. The polyadenylated H3.1 mRNA induced by arsenic was not susceptible to normal degradation that occurs at the end of S phase, resulting in continued presence into mitosis, increased total H3.1 mRNA, and increased H3 protein levels. Excess expression of canonical histones have been shown to increase sensitivity to DNA damage as well as increase the frequency of missing chromosomes and induce genomic instability. Thus, polyadenylation of canonical histone mRNA following arsenic exposure may contribute to arsenic-induced carcinogenesis.
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[Efficacy of albendazole chitosan microspheres against Echinococcus granulosus infection in mice].
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi
PUBLISHED: 09-17-2014
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To observe the therapeutic effect of albendazole chitosan microspheres (ABZ-CS-MPs) on cystic echinococcosis in mice.
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Effect of siRNA with an asymmetric RNA/dTdT overhang on RNA interference activity.
Nucleic Acid Ther
PUBLISHED: 09-12-2014
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Small interfering RNAs (siRNAs) guide RNA-induced silencing complexes (RISC) to target mRNAs for sequence-specific silencing. A fundamental aspect of this highly coordinated process is a guide strand-specific loading of the siRNA duplex into the RISC for the accurate target recognition, which is currently dictated by certain duplex parameters such as thermodynamics. Here, we show that minor changes in the overhang structure have profound effects on the extent to which the individual strands of the siRNA duplex participate in RNAi activity. We demonstrate that the two strands of the siRNA are similarly eligible for assembly into RISC for the siRNAs with symmetric overhangs, whereas those with asymmetric RNA/deoxythymidine dinucleotide (dTdT) overhangs exhibit a distinct preference in favor of a strand with an RNA overhang that drives a mature RISC affinity to the desired target. We believe that this additional determinant provides a plausible and simple approach for improving the strand selection, thereby considerably increasing a specificity of target silencing.
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Systematic review of traditional chinese medicine for depression in Parkinson's disease.
Am. J. Chin. Med.
PUBLISHED: 09-03-2014
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Depression is the most common non-motor symptom of Parkinson's disease (PD). Recent clinical trials have evaluated the effectiveness of traditional Chinese medicine (TCM) in the treatment of depression in PD (dPD). However, the results are conflicting rather than conclusive. To investigate the effectiveness of TCM for the treatment of dPD, a systematic review was conducted. Literature searches and collections were performed to identify studies addressing the treatment of TCM for dPD. The methodological quality and risk of bias in all studies included were evaluated. Weighted mean difference (WMD) with 95% confidence interval (CI) was used as the effect measure. Finally, a total of 10 studies involving 582 patients were identified. The pooled results revealed that TCM combined with conventional drugs significantly improved the total scores of the unified Parkinson's disease rating scale (WMD = -7.35, 95% CI: -11.24 to -3.47) and the score of the Hamilton rating scale for depression (HAM-D) (WMD = -4.19, 95% CI: -5.14 to -3.24) compared with conventional drug, respectively. Conclusively, there is evidence that TCM may be beneficial to the treatment of dPD in spite of the methodological weakness of the included studies.
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Surface Plasmon-Polariton Mediated Red Emission from Organic Light-Emitting Devices Based on Metallic Electrodes Integrated with Dual-Periodic Corrugation.
Sci Rep
PUBLISHED: 09-01-2014
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We demonstrate an effective approach to realize excitation and outcoupling of the SPP modes associated with both cathode/organic and anode/organic interfaces in OLEDs by integrating dual-periodic corrugation. The dual-periodic corrugation consists of two set gratings with different periods. The light trapped in the SPP modes associated with both top and bottom electrode/organic interfaces are efficiently extracted from the OLEDs by adjusting appropriate periods of two set corrugations, and a 29% enhancement in the current efficiency has been obtained.
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A framework for evaluating and utilizing medical terminology mappings.
Stud Health Technol Inform
PUBLISHED: 08-28-2014
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Use of medical terminologies and mappings across them are considered to be crucial pre-requisites for achieving interoperable eHealth applications. Built upon the outcomes of several research projects, we introduce a framework for evaluating and utilizing terminology mappings that offers a platform for i) performing various mappings strategies, ii) representing terminology mappings together with their provenance information, and iii) enabling terminology reasoning for inferring both new and erroneous mappings. We present the results of the introduced framework from SALUS project where we evaluated the quality of both existing and inferred terminology mappings among standard terminologies.
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[Activation of TNF-? and signaling pathway in the hypothalamus of the rats subjected to chronic unpredictable mild stressors after middle cerebral artery occlusion].
Sheng Li Xue Bao
PUBLISHED: 08-19-2014
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This study was aimed to investigate the changes of the hypothalamic-pituitary-adrenal axis (HPAA) activity and the cytokines system in the hypothalamus of the depressive rats which were exposed to chronic unpredictable mild stressors (CUMS) after middle cerebral artery occlusion (MCAO). By means of qRT-PCR, ELISA and Western blot, mRNA and/or protein expressions of corticotropin releasing factor (CRF), tumor necrosis factors-? (TNF-?), suppressor of cytokines signaling 3 (SOCS3), phosphorylation of signal transducers and activators of transcription 3 (pSTAT3) were measured in the hypothalamus of rats. The results showed that, compared with control group, CUMS+MCAO group exhibited increased mRNA levels of CRF, TNF-?, SOCS3, as well as up-regulated CRF, TNF-?, SOCS3 and pSTAT3 protein expressions. Furthermore, there were correlations between CRF and TNF-?, TNF-? and SOCS3, SOCS3 and pSTAT3, respectively. These observations indicated the CRF system was activated in the post stroke depression (PSD) status. The TNF-? and its signaling pathway, STAT3/SOCS3, were up-regulated in mRNA and protein levels. In conclusion, this study presents the evidence which supports the hypothesis of signaling cross-talk between the CRF system and TNF-? signaling pathway after ischemic stroke and CUMS.
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The effect of full/partial UV-irradiation of TiO2 films on altering the behavior of fibrinogen and platelets.
Colloids Surf B Biointerfaces
PUBLISHED: 08-15-2014
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Titanium oxide (TiO2) thin film is a potential candidate for the surface modification of blood-contacting devices. It has previously been reported that ultraviolet light (UV) irradiation could alter the biocompatibility of TiO2 films. However, the effect of UV-irradiated TiO2 films on blood compatibility has rarely been reported. This study attempts to determine: (1) whether UV-irradiation of TiO2 films enhances their blood compatibility, (2) the interaction between UV-irradiated TiO2 films, fibrinogen (Fgn), and platelets, especially how Fgn and platelets respond to the geometry of the partially UV-irradiated TiO2 film surface. Anatase TiO2 films were subjected to full and partial UV-irradiation. Full UV-irradiation improved the blood compatibility of TiO2 films by almost completely inhibiting the adhesion and activation of platelets, strongly suppressing the adsorption and conformational change of Fgn, and preventing the formation of fibrin fibers. Additionally, hemolysis was not observed. After partial UV-irradiation, the regions where Fgn adsorption was reduced (Fgn-dark regions) were formed at regions where UV-irradiation had occurred, but were extended in comparison with the UV-irradiated regions, which could be related to the generation and diffusion of reactive oxygen species (ROS) on the UV-irradiated TiO2 surface. It is worthwhile to study how ROS altered the nature of TiO2 films, thereby enhancing their blood compatibility. Furthermore, platelets were found adhering to the Fgn-adsorbed regions (Fgn-bright regions) selectively, suggesting that the inhibition of platelet adhesion could be related to the suppression of Fgn adsorption on the UV-irradiated TiO2 surface. It was also noted that platelet surface coverage (Sp) was not linearly correlated with Fgn-bright region surface coverage (Sf), which indicated that the adhesion and spreading of platelets were regulated by both Sf and the geometry of Fgn.
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Moisture-Responsive Graphene Paper Prepared by Self-Controlled Photoreduction.
Adv. Mater. Weinheim
PUBLISHED: 08-06-2014
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A facile and cost-effective preparation of moisture-responsive graphene bilayer paper by focused sunlight irradiation is reported. The smart graphene paper shows moisture-responsive properties due to selective adsorption of water molecules, leading to controllable actuation under humid conditions. In this way, graphene-based moisture-responsive actuators including a smart claw, an orientable transporter, and a crawler paper robot have been successfully developed.
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BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones.
Nat. Struct. Mol. Biol.
PUBLISHED: 07-24-2014
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Small-molecule BET inhibitors interfere with the epigenetic interactions between acetylated histones and the bromodomains of the BET family proteins, including BRD4, and they potently inhibit growth of malignant cells by targeting cancer-promoting genes. BRD4 interacts with the pause-release factor P-TEFb and has been proposed to release RNA polymerase II (Pol II) from promoter-proximal pausing. We show that BRD4 occupies widespread genomic regions in mouse cells and directly stimulates elongation of both protein-coding transcripts and noncoding enhancer RNAs (eRNAs), in a manner dependent on bromodomain function. BRD4 interacts with elongating Pol II complexes and assists Pol II in progression through hyperacetylated nucleosomes by interacting with acetylated histones via bromodomains. On active enhancers, the BET inhibitor JQ1 antagonizes BRD4-associated eRNA synthesis. Thus, BRD4 is involved in multiple steps of the transcription hierarchy, primarily by facilitating transcript elongation both at enhancers and on gene bodies independently of P-TEFb.
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LC-MS/MS Determination and Pharmacokinetic Study of Dehydrocorydaline in Rat Plasma after Oral Administration of Dehydrocorydaline and Corydalis yanhusuo Extract.
Molecules
PUBLISHED: 07-09-2014
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A rapid, sensitive and selective liquid chromatography/tandem mass spectrometry method (LC-MS/MS) was developed and validated for determination of dehydrocorydaline (DHC) in rat plasma using nitidine chloride as an internal standard. The analytes were solid-phase extracted and eluted on a C18 chromatography column using a mobile phase of acetonitrile and water (containing 0.8% formic acid and 10 mM ammonium acetate) (28:72, v/v). Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range 0.625-250 ng/mL with a quantification limit of 0.625 ng/mL. The precision was <13.7%, the accuracy >93.1%, and extraction recovery ranged from 92.1% to 107%. The validated method was successfully applied to the pharmacokinetics and excretion study of DHC in rat plasma after oral administration of pure DHC and an effective fraction of Corydalis yanhusuo (EFY). The pharmacokinetic parameters showed that DHC from EFY was absorbed more rapidly and eliminated more slowly than pure DHC. The result suggests that the differences might be due to the presence of P-glycoprotein (P-gp) inhibitors and that other alkaloids co-existing in the EFY may compete with DHC for transportation by P-gp, metabolization by P450, and binding to plasma proteins.
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Effects of Treg cells and IDO on human epithelial ovarian cancer cells under hypoxic conditions.
Mol Med Rep
PUBLISHED: 06-18-2014
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The aim of the present study was to explore the effect of hypoxia on ovarian cancer. A total of 6 samples were analyzed: SKOV3?IP cells (ovarian cancer cell line); SKOV3?IP and regulatory T (Treg) cells; SKOV3?IP and cytotoxic T lymphocytes (CTLs); SKOV3?IP and natural killer (NK) cells; SKOV3?IP co-cultured with CTLs and Treg cells; and SKOV3?IP co-cultured with Treg cells and NK cells. The expression of indoleamine 2,3?dioxygenase (IDO) was detected by reverse transcription-polymerase chain reaction (RT?PCR) and western blot analysis. An enzyme?linked immunosorbent assay (ELISA) was used to detect the concentration of transforming growth factor?? (TGF??), interferon?? (IFN??), interleukin?2 (IL?2), interleukin?10 (IL?10), and perforin. Moreover, ovarian cancer cell apoptosis and invasive ability were examined using flow cytometry and a Transwell chamber assay. IDO expression was significantly reduced in hypoxia and enhanced by Treg cells. Treg cells inhibited the IL?2, IFN?? and perforin secretion, and significantly (P<0.05) increased the IL?10 and TGF?? levels. The effects of Treg cells were enhanced with prolongation of the cell exposure to hypoxic conditions. In addition, Treg cells attenuated the promotive effect of CTLs and NK cells on cancer cell apoptosis. In addition, Treg cells significantly increased the SKOV3?IP invasive ability (P=0.00109) under hypoxic conditions. Our results suggest that IDO and Treg cells may serve as important therapeutic targets for patients with ovarian cancer.
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Proliferation conditions promote intrinsic changes in NK cells for an IL-10 response.
J. Immunol.
PUBLISHED: 06-06-2014
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Constitutively found at high frequencies, the role for NK cell proliferation remains unclear. In this study, a shift in NK cell function from predominantly producing IFN-?, a cytokine with proinflammatory and antimicrobial functions, to producing the immunoregulatory cytokine IL-10 was defined during extended murine CMV infection. The response occurred at times subsequent to IL-12 production, but the NK cells elicited acquired responsiveness to IL-12 and IL-21 for IL-10 production. Because neither IL-12 nor IL-21 was required in vivo, however, additional pathways appeared to be available to promote NK cell IL-10 expression. In vitro studies with IL-2 to support proliferation and in vivo adoptive transfers into murine CMV-infected mice demonstrated that NK cell proliferation and further division enhanced the change. In contrast to the sustained open profile of the IFN-? gene, NK cells responding to infection acquired histone modifications in the IL-10 gene indicative of changing from a closed to an open state. The IL-10 response to IL-12 was proliferation dependent ex vivo if the NK cells had not yet expanded in vivo but independent if they had. Thus, a novel role for proliferation in supporting changing innate cell function is reported.
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Surface-plasmon-mediated programmable optical nanofabrication of an oriented silver nanoplate.
ACS Nano
PUBLISHED: 06-05-2014
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We report polarized femtosecond laser-light-mediated growth and programmable assembly of photoreduced silver nanoparticles into triply hierarchical micropatterns. Formation of erected arrays of nanoplates with a thickness as small as ?/27 (?, the writing laser wavelength) level is demonstrated. The growth mechanism of nanoplates has been clarified: (i) the excited surface plasmons enhance the local electric field and lead to spatially selective growth of silver atoms at the opposite ends of dipoles induced on early created silver seeds; (ii) the optical attractive force overcomes electrostatic repulsion in the enhanced local electric field to assemble the silver nanoparticles directly. The triply hierarchical micropattern shape and location, the nanoplate orientation, and thickness are all attained in controlled fashion.
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Cutoff value of pharyngeal residue in prognosis prediction after neuromuscular electrical stimulation therapy for Dysphagia in subacute stroke patients.
Ann Rehabil Med
PUBLISHED: 05-22-2014
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To determine the cutoff value of the pharyngeal residue for predicting reduction of aspiration, by measuring the residue of valleculae and pyriformis sinuses through videofluoroscopic swallowing studies (VFSS) after treatment with neuromuscular electrical stimulator (VitalStim) in stroke patients with dysphagia.
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Large indentation strain-stiffening in nanotwinned cubic boron nitride.
Nat Commun
PUBLISHED: 05-14-2014
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Recent experiments reported a substantial strengthening of cubic boron nitride by nanotwinning. This discovery raises fundamental questions about new atomistic mechanisms governing incipient plasticity in nanostructured strong covalent solids. Here we reveal an unusual twin-boundary dominated indentation strain-stiffening mechanism that produces a large strength enhancement at nanometer-scale twinning size where a strength reduction is normally expected due to the reverse Hall-Petch effect. First-principles calculations unveil significantly enhanced indentation shear strength in nanotwinned cubic boron nitride by bond rearrangement at the twin boundary under indentation compression and shear strains that produces especially strong stress response. This remarkable strain-stiffening mechanism offers fundamental insights for understanding the stress response of nanotwinned covalent solids under indentation.
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Effect of the guide strand 3'-end structure on the gene-silencing potency of asymmetric siRNA.
Biochem. J.
PUBLISHED: 05-08-2014
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siRNAs are short dsRNAs that mediate efficient target gene silencing in a sequence-specific manner. We previously developed a novel siRNA structure, called asiRNA (asymmetric siRNA), which alleviates the off-target effects associated with conventional siRNA structures without decreasing target gene silencing potency. In the present study, we explored the effect of the guide strand 3'-end structure on the gene silencing potency of asiRNA. Interestingly, asiRNAs with a 21 nt guide strand solely composed of RNA resulted in gene silencing that was more than 6-fold more efficient compared with the corresponding asiRNA guide strand harbouring a dTdT (deoxythymidine dinucleotide) at its 3'-end. We demonstrated that the molecular basis of potency of the asiRNA with a 21 nt guide strand composed solely of RNA was due to the enhanced formation of the RISC (RNA-induced silencing complex) and increased affinity towards hAgo2 (human Argonaute2). Our observations may assist researchers in designing new asiRNAs with high on-target silencing efficiency with low off-target effects, which is critical for applications in both basic research and therapeutic development.
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Role of the nano amorphous interface in the crystallization of Sb2Te3 towards non-volatile phase change memory: insights from first principles.
Phys Chem Chem Phys
PUBLISHED: 04-25-2014
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The nano amorphous interface is important as it controls the phase transition for data storage. Yet, atomic scale insights into such kinds of systems are still rare. By first-principles calculations, we obtain the atomic interface between amorphous Si and amorphous Sb2Te3, which prevails in the series of Si-Sb-Te phase change materials. This interface model reproduces the experiment-consistent phenomena, i.e. the amorphous stability of Sb2Te3, which defines the data retention in phase change memory, and is greatly enhanced by the nano interface. More importantly, this method offers a direct platform to explore the intrinsic mechanism to understand the material function: (1) by steric effects through the atomic "channel" of the amorphous interface, the arrangement of the Te network is significantly distorted and is separated from the p-orbital bond angle in the conventional phase-change material; and (2) through the electronic "channel" of the amorphous interface, high localized electrons in the form of a lone pair are "projected" to Sb2Te3 from amorphous Si by a proximity effect. These factors set an effective barrier for crystallization and improve the amorphous stability, and thus data retention. The present research and scheme sheds new light on the engineering and manipulation of other key amorphous interfaces, such as Si3N4/Ge2Sb2Te5 and C/Sb2Te3, through first-principles calculations towards non-volatile phase change memory.
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[Study on long-term stability of biological nitrogen removal via nitrite from real landfill leachate].
Huan Jing Ke Xue
PUBLISHED: 04-12-2014
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The long-term stability of nitrogen removal from municipal landfill with high ammonia nitrogen (NH(4+)-N) content was investigated by using a biological system consisting of a first-stage up-flow anaerobic sludge bed (UASB) and sequencing batch reactor (SBR) under normal and low temperature conditions. The 623 days experimental results clearly showed: the efficient denitrification and methanogenesis were conducted in a same UASB reactor, and almost 100% of denitrification was obtained, when feed COD concentration ranged from 1,000 mg x L(-1) to 13 800 mg x L(-1), effluent COD concentration was between 150 mg x L(-1) and 1,234 mg x L(-1), and when the influent ammonia nitrogen (NH(4+)-N) changed from 574 mg x L(-1) to 2,360 mg-L(-1), the effluent NH:-N was below 10 mg x L(-1), the removal efficiency reached 90% and 98%, respectively. Especially, above 99.2% removal efficiency of TN was obtained, and effluent TN concentration was below 30 mg L(-1)), advanced and efficient nitrogen and organic removal were achieved in the biological system. Furthermore, stable nitrification and denitrification were achieved during the entire experiment period, especially, were maintained successfully for 171 days at the temperature below 15 degrees C and the lowest temperature of 10. 2 degrees C during two winters.
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Changes of Flavor Compounds of Hydrolyzed Chicken Bone Extracts during Maillard Reaction.
J. Food Sci.
PUBLISHED: 04-02-2014
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Flavor quality, including non-volatile and volatile compounds, of hydrolyzed chicken bone extracts (HCBE) during Maillard reaction (MR) was evaluated with HPLC, tasting sensory system, Electronic-Nose (E-nose), and GC-MS. Results showed that flavor amino acids (AA) accounted for 72% to 74% of total free AA in HCBE. Taste of umami increased first and then decreased during MR, while equivalent umami concentration remained at a stable level. Results of taste sensing system and bitter AA showed that MR could reduce the bitter taste of HCBE significantly. E-Nose test showed there are great changes of volatile flavor during MR. And total of 59 volatile compounds were identified in HCBE during MR, which should responsible for the increase of flavor in HCBE. Our results indicated that MR could be used as an effective way to change the flavor compounds in HCBE, and therefore provide a strategy for preparation of meaty flavor enhancer from bone residue as a byproduct of meat industry.
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Efficient intracellular delivery and multiple-target gene silencing triggered by tripodal RNA based nanoparticles: A promising approach in liver-specific RNAi delivery.
J Control Release
PUBLISHED: 03-26-2014
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RNA interference (RNAi) triggering oligonucleotides in unconventional structural format can offer advantages over conventional small interfering RNA (siRNA), enhanced cellular delivery and improved target gene silencing. With this concept, we present a well-defined tripodal-interfering RNA (tiRNA) structure that can induce simultaneous silencing of multiple target genes with improved potency. The tiRNA structure, formed by the complementary association of three single-stranded RNA units, was optimized for improved gene silencing efficacy. When combined with cationic polymers such as linear polyethyleneimine (PEI), tiRNA assembled to form a stable nano-structured complex through electrostatic interactions and induced stronger RNAi response over conventional siRNA-PEI complex. In combination with a liver-targeting delivery system, tripodal nucleic acid structure demonstrated enhanced fluorescent accumulation in mouse liver compared to standard duplex nucleic acid format. Tripodal RNA structure complexed with galactose-modified PEI could generate effective RNAi-mediated gene silencing effect on experimental mice models. Our studies demonstrate that optimized tiRNA structural format with appropriate polymeric carriers have immense potential to become an RNAi-based platform suitable for multi-target gene silencing.
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Expression analysis of genes encoding mitogen-activated protein kinases in maize provides a key link between abiotic stress signaling and plant reproduction.
Funct. Integr. Genomics
PUBLISHED: 03-24-2014
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Mitogen-activated protein kinases (MAPKs) play important roles in stress responses and development in plants. Maize (Zea mays), an important cereal crop, is a model plant species for molecular studies. In the last decade, several MAPKs have been identified in maize; however, their functions have not been studied extensively. Genome-wide identification and expression analysis of maize MAPK genes could provide valuable information for understanding their functions. In this study, 20 non-redundant maize MAPK genes (ZmMPKs) were identified via a genome-wide survey. Phylogenetic analysis of MAPKs from maize, rice (Oryza sativa), Arabidopsis (Arabidopsis thaliana), poplar (Populus trichocarpa), and tomato (Solanum lycopersicum) classified them into four major classes. ZmMPKs in the same class had similar domains, motifs, and genomic structures. Gene duplication investigations suggested that segmental duplications made a large contribution to the expansion of ZmMPKs. A number of cis-acting elements related to plant development and response to stress and hormones were identified in the promoter regions of ZmMPKs. Furthermore, transcript profile analysis in eight tissues and organs at various developmental stages demonstrated that most ZmMPKs were preferentially expressed in reproductive tissues and organs. The transcript abundance of most ZmMPKs changed significantly under salt, drought, cold, or abscisic acid (ABA) treatments, implying that they might participate in abiotic stress and ABA signaling. These expression analyses indicated that ZmMPKs might serve as linkers between abiotic stress signaling and plant reproduction. Our data will deepen our understanding of the complexity of the maize MAPK gene family and provide new clues to investigate their functions.
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A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3.
Blood
PUBLISHED: 03-14-2014
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Mutations of STAT3 underlie the autosomal dominant form of hyperimmunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in nonhematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and nonhematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild-type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.
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Circulating hematopoietic stem and progenitor cells are myeloid-biased in cancer patients.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-03-2014
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Cancer is associated with a profound perturbation in myelopoiesis that results in the accumulation of myeloid-derived suppressor cells (MDSCs) to promote disease progression. Recent studies in mice suggest that tumor-derived factors could regulate the differentiation of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow and subsequently contribute to dysregulation of hematopoiesis. However, the nature and role of HPSCs in patients with cancer remain unknown. Here we show, in detailed studies of the peripheral blood from 133 untreated patients with seven different types of tumors, that the composition of circulating HSPCs was significantly altered in patients with solid tumors. The frequencies of circulating granulocyte-monocyte progenitors (GMPs) were increased four to seven fold in all types of tumors examined, and the circulating hematopoietic precursors exhibited myeloid bias with a skew toward granulocytic differentiation in patients with solid tumors. These myeloid precursors are selectively enriched in tumor tissues, and the high levels of circulating GMPs were positively correlated with disease progression. By using cord blood-derived CD34(+) cells, we developed an in vitro short-term culture model to effectively induce the rapid generation of MDSCs. We found that, among the factors produced by various tumors, GM-CSF, granulocyte colony-stimulating factor, and IL-6 could not only promote the myeloid-biased differentiation, but also induce the differentiation of myeloid precursors into functional MDSCs. These findings suggest that the altered circulating HSPCs may serve as an important link between dysregulated bone marrow hematopoiesis and accumulated MDSCs in patients with cancer.
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Slide fastener reduction of graphene-oxide edges by calcium: insight from ab initio molecular dynamics.
Chemphyschem
PUBLISHED: 02-20-2014
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The reduction of graphene oxide can be used as a simple way to produce graphene on a large scale. However, the numerous edges produced by the oxidation of graphite seriously degrade the quality of the graphene and its carrier transport property. In this work, the reduction of oxygen-passivated graphene edges and the subsequent linking of separated graphene sheets by calcium are investigated by using first-principles calculations. The calculations show that calcium can effectively remove the oxygen groups from two adjacent edges. The joining point of the edges serves as the starting point of the reduction and facilitates the reaction. Once the oxygen groups are removed, the crack is sutured. If the joining point is lacking, it becomes difficult to zip the separated fragments. A general electron-reduction model and a random atom-reduction model are suggested for these two situations. The present study sheds light on the reduction of graphene-oxide edges by using reactive metals to give large-sized graphene through a simple chemical reaction.
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Long dsRNA-mediated RNA interference and immunostimulation: a targeted delivery approach using polyethyleneimine based nano-carriers.
Mol. Pharm.
PUBLISHED: 02-20-2014
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RNA oligonucleotides capable of inducing controlled immunostimulation combined with specific oncogene silencing via an RNA interference (RNAi) mechanism provide synergistic inhibition of cancer cell growth. With this concept, we previously designed a potent immunostimulatory long double stranded RNA, referred to as liRNA, capable of executing RNAi mediated specific target gene silencing. In this study, we developed a highly effective liRNA based targeted delivery system to apply in the treatment of glioblastoma multiforme. A stable nanocomplex was fabricated by complexing multimerized liRNA structures with cross-linked branched poly(ethylene imine) (bPEI) via electrostatic interactions. We show clear evidence that the cross-linked bPEI was quite effective in enhancing the cellular uptake of liRNA on U87MG cells. Moreover, the liRNA-PEI nanocomplex provided strong RNAi mediated target gene silencing compared to that of the conventional siRNA-PEI complex. Further, the bPEI modification strategy with specific ligand attachment assisted the uptake of the liRNA-PEI complex on the mouse brain endothelial cell line (b.End3). Such delivery systems combining the beneficial elements of targeted delivery, controlled immunostimulation, and RNAi mediated target silencing have immense potential in anticancer therapy.
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Abnormal ?-catenin immunohistochemical expression as a prognostic factor in gastric cancer: a meta-analysis.
World J. Gastroenterol.
PUBLISHED: 02-18-2014
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To evaluate the effect of ?-catenin immunohistochemical expression on the prognosis of gastric cancer (GC).
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Common origin of green luminescence in carbon nanodots and graphene quantum dots.
ACS Nano
PUBLISHED: 02-17-2014
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Carbon nanodots (C-dots) synthesized by electrochemical ablation and small molecule carbonization, as well as graphene quantum dots (GQDs) fabricated by solvothermally cutting graphene oxide, are three kinds of typical green fluorescence carbon nanomaterials. Insight into the photoluminescence origin in these fluorescent carbon nanomaterials is one of the important matters of current debates. Here, a common origin of green luminescence in these C-dots and GQDs is unraveled by ultrafast spectroscopy. According to the change of surface functional groups during surface chemical reduction experiments, which are also accompanied by obvious emission-type transform, these common green luminescence emission centers that emerge in these C-dots and GQDs synthesized by bottom-up and top-down methods are unambiguously assigned to special edge states consisting of several carbon atoms on the edge of carbon backbone and functional groups with C?O (carbonyl and carboxyl groups). Our findings further suggest that the competition among various emission centers (bright edge states) and traps dominates the optical properties of these fluorescent carbon nanomaterials.
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Target gene abundance contributes to the efficiency of siRNA-mediated gene silencing.
Nucleic Acid Ther
PUBLISHED: 02-14-2014
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The gene-silencing activity of a small interfering RNA (siRNA) is determined by various factors. Considering that RNA interference (RNAi) is an unparalleled technology in both basic research and therapeutic applications, thorough understanding of the factors determining RNAi activity is critical. This report presents observations that siRNAs targeting KRT7 show cell-line-dependent activity, which correlates with the expression level of KRT7 mRNA. By modulating the target mRNA level, it was confirmed that highly expressed genes are more susceptible to siRNA-mediated gene silencing. Finally, several genes that show different expression levels in a cell-line dependent manner were tested, which verified the expression-level-dependent siRNA activities. These results strongly suggest that the abundance of target mRNA is a critical factor that determines the efficiency of the siRNA-mediated gene silencing in a given cellular context. This report should provide practical guidelines for designing RNAi experiments and for selecting targetable genes in RNAi therapeutics studies.
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Development of a novel method for hot-pressure extraction of protein from chicken bone and the effect of enzymatic hydrolysis on the extracts.
Food Chem
PUBLISHED: 02-12-2014
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To investigate the hot-pressure extraction of protein from chicken bone (CB), chicken bone extracts (CBE) was prepared from CB by heating at 130±0.5 °C for 120 min, followed by filtration, standing, defatting, and concentration. Effects of enzymatic hydrolysis on the properties of hydrolysates were examined. Results showed CBE contained 25.59% of protein, and showed a desirable value of protein digestibility-corrected amino acid score for adult. The total amino acid (AA) content of CBE is 21.99%, among which 40.62% and 54.66% are essential and fresh AA, respectively. Forty kinds of volatile compounds were identified after 24 h of hydrolysis, with 2,3,5-trimethylpyrazine as the key flavor compound. After 8 h of hydrolysis of CBE, the content of small MW of peptides (400-1000 Da) increased by 74 times compared with that of 1 h. CBE and its hydrolysates demonstrate a new kind of potential suitable nutritional supplement in various foods.
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Type I IFN induces binding of STAT1 to Bcl6: divergent roles of STAT family transcription factors in the T follicular helper cell genetic program.
J. Immunol.
PUBLISHED: 01-31-2014
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CD4(+) T follicular helper cells (TFH) are critical for the formation and function of B cell responses to infection or immunization, but also play an important role in autoimmunity. The factors that contribute to the differentiation of this helper cell subset are incompletely understood, although several cytokines including IL-6, IL-21, and IL-12 can promote TFH cell formation. Yet, none of these factors, nor their downstream cognate STATs, have emerged as nonredundant, essential drivers of TFH cells. This suggests a model in which multiple factors can contribute to the phenotypic characteristics of TFH cells. Because type I IFNs are often generated in immune responses, we set out to investigate whether these factors are relevant to TFH cell differentiation. Type I IFNs promote Th1 responses, thus one possibility was these factors antagonized TFH-expressed genes. However, we show that type I IFNs (IFN-?/?) induced B cell lymphoma 6 (Bcl6) expression, the master regulator transcription factor for TFH cells, and CXCR5 and programmed cell death-1 (encoded by Pdcd1), key surface molecules expressed by TFH cells. In contrast, type I IFNs failed to induce IL-21, the signature cytokine for TFH cells. The induction of Bcl6 was regulated directly by STAT1, which bound to the Bcl6, Cxcr5, and Pdcd1 loci. These data suggest that type I IFNs (IFN-?/?) and STAT1 can contribute to some features of TFH cells but are inadequate in inducing complete programming of this subset.
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The synthesis, characterization and optical properties of novel 5-(3-aryl-1H-pyrazol-5-yl)-2-(3-butyl-1-chloroimidazo[1,5-a]pyridin-7-yl)-1,3,4-oxadiazole.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 01-14-2014
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A series of novel 5-(3-aryl-1H-pyrazol-5-yl)-2-(3-butyl-1-chloroimidazo[1,5-a]- pyridin-7-yl)-1,3,4-oxadiazole derivatives has been synthesized from 3-butyl-1-chloroimidazo[1,5-a]pyridine-7-carboxylic acid and ethyl 3-aryl-1H-pyrazole-5-carboxylate. The compounds were characterized using IR, (1)H NMR, HRMS and UV-vis absorption. The fluorescence spectral characteristics of the compounds in dichloromethane were investigated. The results showed that absorption ?max and emission ?max was less correlated with substituent groups on N-1 position of pyrazole moiety and para position of benzene moiety. The calculated molecular orbital correlates well with their absorption.
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Pyrethroid and their metabolite, 3-phenoxybenzoic acid showed similar (anti)estrogenic activity in human and rat estrogen receptor ?-mediated reporter gene assays.
Environ. Toxicol. Pharmacol.
PUBLISHED: 01-07-2014
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Pyrethroids are commonly used as pesticides which are suspected as endocrine disruptors in many studies; however, still we do not know their effects on different species. To compare their effects on human estrogen receptor (hER?) and rat estrogen receptor (rER?), we developed a hER? and rER? mediated luciferase reporter assay to investigate the (anti)estrogenic activities of three frequently used pyrethroids (fenvalerate, cypermethrin, permethrin) and their metabolite 3-phenoxybenzoic acid (3-PBA). All three pyrethroids significantly induced expression of the luciferase, while none of them were antagonistic to 1 nM E? mediated induction. Interestingly, 3-PBA, showed antagonist activity by decreasing the effect of 1 nM E? to 55.12% in hER? assay and to 45.12% in rER? assay. Our results firstly demonstrated that pyrethroids and 3-PBA showed similar response in the hER? and rER? mediated reporter gene assay, which indicated that data derived from reporter gene assay or other receptor mediated assay systems with rat ER system might be used to predict to estrogenic or anti-estrogenic effects to human systems.
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Quantitative dynamic modelling of the gene regulatory network controlling adipogenesis.
PLoS ONE
PUBLISHED: 01-01-2014
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Gene regulatory networks (GRNs) coherently coordinate the expressions of genes and control the behaviors of cellular systems. The complexity in modeling a quantitative GRN usually results from inaccurate parameter estimation, which is mostly due to small sample sizes. For better modeling of GRNs, we have designed a small-sample iterative optimization algorithm (SSIO) to quantitatively model GRNs with nonlinear regulatory relationships. The algorithm utilizes gene expression data as the primary input and it can be applied in case of small-sized samples. Using SSIO, we have quantitatively constructed the dynamic models for the GRNs controlling human and mouse adipogenesis. Compared with two other commonly-used methods, SSIO shows better performance with relatively lower residual errors, and it generates rational predictions on the adipocyte responses to external signals and steady-states. Sensitivity analysis further indicates the validity of our method. Several differences are observed between the GRNs of human and mouse adipocyte differentiations, suggesting the differences in regulatory efficiencies of the transcription factors between the two species. In addition, we use SSIO to quantitatively determine the strengths of the regulatory interactions as well as to optimize regulatory models. The results indicate that SSIO facilitates better investigation and understanding of gene regulatory processes.
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[Introspection of oxidant/antioxidant imbalance in the inner ear].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 12-24-2013
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Free radicals are atoms, molecules or ions with unpaired electrons. In biological systems, free radicals can have a dual role, being beneficial in some situations and deleterious in others. Free radicals are required for normal cellular metabolism, but they lead to cellular degeneration if overproduced. To prevent the excessive buildup of free radicals, cells have developed an elaborate series of antioxidant enzymes that counteract oxidative stress and protect cells by maintaining the proper balance of oxidation and anti-oxidation. Therefore, when there is an oxidant/anti-oxidant imbalance, no matter what direction, cells are likely to be damaged. Numerous reports in the literature indicate that free radicals play important roles in diseases of the inner ear as a result of noise exposure, ototoxic drugs, aging, and other pathological conditions. Therefore, there have been many attempts to employ antioxidants treat inner ear damage. However, antioxidant therapy could be harmful if the improper compound or dose is employed. Effective antioxidant therapy requires prior knowledge of the type(s) of oxidative stress occurring in real time in the inner ear. Since most techniques for detecting free radicals in the inner ear are not clinically feasible, systemic anti-oxidant therapy is generally performed "blindly" and therefore likely to disrupt normal antioxidant levels in the inner ear or elsewhere in the body. If only a single anti-oxidant is used to treat a disease, it may disturb subsequent steps the oxidative/anti-oxidative chain reaction. An alternative approach, hydrogen therapy represents a promising therapeutic tool because it can selectively scavenge the strongest oxidant species, the hydroxyl radical and peroxynitrite anion, without disturbing normal oxidant/anti-oxidant cellular processes. In addition, hydrogen has no cytotoxic effects to cells so that it provides a near ideal therapy to eliminate toxic free radicals.
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Beam shaping of edge-emitting diode lasers using a single double-axial hyperboloidal micro-lens.
Opt Lett
PUBLISHED: 12-18-2013
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We report an innovative approach for beam shaping of edge-emitting semiconductor diode lasers using a single double-axial hyperboloidal micro-lens fabricated with femtosecond laser direct writing technology. The two hyperboloids of different axial lengths focus the light from fast and slow axes to an identical focal spot. The divergence angles were shaped from 60° and 9° to 6.9 and 32.3 mrad, respectively, and the single-end fiber coupling efficiency is measured higher than 80%. The device is simple in fabrication, robust in structure, and easy for operation, by which multiple reflections and absorptions at interfaces are reduced, and assembly errors are minimized.
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Spectral engineering by flexible tunings of optical Tamm states and Fabry-Perot cavity resonance.
Opt Lett
PUBLISHED: 11-02-2013
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We present a design for spectral engineering in a metal dual distributed Bragg reflector (DBR)-based structure. Optical Tamm states and Fabry-Perot cavity mode, dual windows for light-matter interaction enhancement, can be excited simultaneously and tuned flexibly, including their respective bandwidth and resonant wavelength, due to the variable reflection phase from the outer DBRs internal surface. The design can find applications in solar cells for light trappings. Via calculations of overall absorptivity, the proposed simpler dual-states-based scheme is demonstrated to be almost as effective as the coherent-light-trapping scheme, owing to the dual-states-induced broader-band absorption enhancement.
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[Dynamics of Cry1ab protein content in the rhizosphere soil and straw debris of transgenic Bt corn].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 11-02-2013
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By using ELISA test kits, a field investigation was conducted on the degradation dynamics of CrylAb protein in the rhizosphere soil of Bt corn MON810 at its different growth stages and in the MON810 straws returned into field after harvest. Three models (shift-log model, exponential model, and bi-exponential model) were used to fit the degradation dynamics of the Cry1 Ab protein from the straw debris, and the DT50 and DT90, values were estimated. There existed great differences in the CrylAb protein content in the rhizosphere soil of MON810 at its different growth stages, but overall, the CrylAb protein content was decreased remarkably with the growth of MON810. The degradation of Cry1 Ab protein from the straws covered on soil surface and buried in soil showed the same two-stage pattern, i.e., more rapid at early stage and slow-stable in later period. Within the first week after straw return, the degradation rate of the CrylAb protein from the straws covered on soil surface was significantly higher than that from the straws buried in soil. At 10 d, the degradation rate of the CrylAb protein from the straws covered on soil surface and buried in soil was basically the same, being 88.8% and 88.6%, respectively. After 20 days, the degradation of CrylAb protein entered slow-stable stage. Till at 180 d, a small amount of Cry1Ab protein could still be detected in the straw debris. All of the three models used in this study could fit the decay pattern of the CrylAb protein from the straw debris in field. By comparing the correlation coefficient (r) and the consistency between the measured and calculated DT90, bi-exponential model was considered to be the best.
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Efficient cross-coupling of aryl Grignard reagents with alkyl halides by recyclable ionic iron(III) complexes bearing a bis(phenol)-functionalized benzimidazolium cation.
Org. Biomol. Chem.
PUBLISHED: 10-23-2013
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A novel bis(phenol)-functionalized benzimidazolium salt, 1,3-bis(3,5-di-tert-butyl-2-hydroxybenzyl)benzimidazolium chloride (H3LCl, 1), was designed and used to prepare ionic iron(III) complexes of the type [H3L][FeX4] (X = Cl, 2; X = Br, 3). Both 2 and 3 were characterized by elemental analysis, Raman spectroscopy, electrospray ionization mass spectrometry and X-ray crystallography. The catalytic performances of 2 and 3 in cross-coupling reactions using aryl Grignard reagents with primary and secondary alkyl halides bearing ?-hydrogens were studied. This analysis shows that complex 2 has good potential for alkyl chloride-mediated coupling. In comparison, complex 3 showed slightly lower catalytic activity. After decanting the product contained in the ethereal layer, complex 2 could be recycled at least eight times without significant loss of catalytic activity.
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Monolithic bifocal zone-plate lenses for confocal collimation of laser diodes.
Opt Lett
PUBLISHED: 10-02-2013
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An elliptical monolithic bifocal zone plate as a collimating lens, whose two focal lengths in the orthogonal directions match the different beam waist positions of the fast and slow axes light from edge-emitting laser diodes, is proposed and experimentally demonstrated by employing femtosecond laser direct writing technology. The high-quality eight-level zone plate exhibits a diffraction efficiency of 92.9%, which is much higher than those ever reported. Shaped by the elliptical lens, the laser diodes divergence angles are simultaneously reduced from 65° (1134 mrad, fast axis) and 24° (418 mrad, slow axis) to 7.7 and 136.5 mrad, respectively.
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Fabrication and characterization of Ag film with sub-nanometer surface roughness as a flexible cathode for inverted top-emitting organic light-emitting devices.
Nanoscale
PUBLISHED: 09-23-2013
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An ultra-smooth Ag film with sub-nanometer surface roughness on a flexible substrate has been fabricated by a template-stripping process and its effect on the carrier injection and transport in organic light-emitting devices (OLEDs) has been investigated. The use of the ultra-smooth Ag film as an electrode results in both enhanced carried injection due to the improved contact between the electrode and the organic layer and enhanced carrier transport due to the larger grain size of the deposited organic layer on it. The ultra-smooth Ag film on the flexible substrate has been applied in inverted top-emitting OLEDs (ITOLEDs) as cathode, which exhibit improved efficiency due to the enhanced electron injection and transport. The maximum current efficiency of the ITOLEDs on the flexible substrate is 9.72 cd A(-1), whereas it is 6.03 cd A(-1) for the devices on the conventional Si substrate, which corresponds to about a 62% enhancement. Moreover, the flexible ITOLEDs keep their good performance under a small bending radius and after repeated bending.
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Compact fiber tip modal interferometer for high-temperature and transverse load measurements.
Opt Lett
PUBLISHED: 08-31-2013
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A compact fiber tip modal interferometer (FTMI) based on two-wave interference has been demonstrated. Its fabrication process is very simple, just involving fiber tapering by a fusion splicer. The effective sensing area of the FTMI has a small length of ~310 ?m. The interference spectra of the fiber tips with different size and profile have been analyzed. The FTMI has a good mechanical strength and high-temperature stability. It can be used for high-temperature and transverse load sensing simultaneously in a harsh environment when two different attenuation peaks are chosen to be monitored.
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Cholesterol Contributes to Diabetic Nephropathy through SCAP-SREBP-2 Pathway.
Int J Endocrinol
PUBLISHED: 08-17-2013
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Diabetic nephropathy (DN) has been associated with the presence of lipid deposition. We hypothesized that the disruption of intracellular cholesterol feedback may contribute to DN. Diabetes was induced by high fat/sucrose diet and low-dose intraperitoneal injection of streptozocin (STZ) in male Sprague-Dawley rats. Then diabetic rats were randomly divided into two groups: untreated diabetic group (DM) and atorvastatin-treated group (DM + AT). We found that the levels of serum blood urea nitrogen and creatinine, as well as 24-hour urine protein and urinary neutrophil gelatinase-associated lipocalin, were significantly increased in diabetic rats. This result indicated that the diabetic rats suffered from functional renal damage. We also observed lipid droplet accumulation and increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), low density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), and SREBP-cleavage activating protein (SCAP) in the kidneys of diabetic rats. However, atorvastatin ameliorated renal lipid accumulation and improved the renal function of diabetic rats despite an increase in mRNA and protein expressions of HMG-CoAR, LDLr, and SREBP-2. These results demonstrated that intracellular cholesterol feedback regulation is disrupted in rats with type 2 diabetes, thereby causing renal cholesterol accumulation. Atorvastatin ameliorated renal cholesterol accumulation by reducing renal cholesterol synthesis.
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Multifunctional superparamagnetic iron oxide nanoparticles: design, synthesis and biomedical photonic applications.
Nanoscale
PUBLISHED: 07-24-2013
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Superparamagnetic iron oxide nanoparticles (SPIONs) have shown great promise in biomedical applications. In this review, we summarize the recent advances in the design and fabrication of core-shell and hetero-structured SPIONs and further outline some exciting developments and progresses of these multifunctional SPIONs for diagnosis, multimodality imaging, therapy, and biophotonics.
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Internal structure-mediated ultrafast energy transfer in self-assembled polymer-blend dots.
Nanoscale
PUBLISHED: 07-03-2013
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Applications of polymeric semiconductors in organic electronics and biosensors depend critically on the nature of energy transfer in these materials. Important questions arise as to how this long-range transport degrades in amorphous condensed solids which are most amenable to low-cost optoelectronic devices and how fast energy transfer could occur. Here, we address these in disordered, densely packed nanoparticles made from green-light-harvesting host polymers (PFBT) and deep-red-emitting dopant polymers (PF-DBT5). By femtosecond selective excitation of donor (BT) units, we study in detail the internal structure-mediated energy transfer to uniformly distributed, seldom acceptor (DBT) units. It has been unambiguously demonstrated that the creation of interchain species is responsible for the limitation of bulk exciton diffusion length in polymer materials. This interchain Förster resonance energy transfer (FRET) becomes a preferred and dominant channel, and near 100% energy transfer efficiency could be achieved at high acceptor concentrations (>10 wt%). Side-chain carboxylic acid groups in functionalized polymer-blend dots slightly slow down the FRET rate, but it could not affect the Förster radius and FRET efficiency. These findings imply that a greater understanding of the role of interchain species could be an efficient approach to improve the cell efficiency.
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Direct observation of quantum-confined graphene-like States and novel hybrid States in graphene oxide by transient spectroscopy.
Adv. Mater. Weinheim
PUBLISHED: 06-27-2013
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Quantum-confined graphene-like electronic states are directly observed in graphene oxide and photothermally reduced graphene oxide via transient spectroscopy. An unexpected novel hybrid state arising from amorphous carbon-like peripheral structure with high sp(3) /sp(2) carbon ratio in close vicinity of confined graphene-like states is found commonly existent in various carbon nanomaterials, including graphene oxide, graphene quantum dots, and carbon dots.
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Broadband light extraction from white organic light-emitting devices by employing corrugated metallic electrodes with dual periodicity.
Adv. Mater. Weinheim
PUBLISHED: 05-24-2013
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A dual-periodic corrugation consisting of two sets of gratings with different periods to realize a broadband light extraction in white organic light-emitting diodes (WOLEDs) is shown. A 37 % enhancement in current efficiency and 48 % enhancement in the external quantum efficiency compared to those of the conventional planar devices have been obtained. Besides the much improved efficiency, the dual-periodic corrugated WOLEDs exhibit satisfying viewing characteristics.
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[Study on the risk assessment method of regional groundwater pollution].
Huan Jing Ke Xue
PUBLISHED: 05-15-2013
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Based on the boundary elements of system risk assessment, the regional groundwater pollution risk assessment index system was preliminarily established, which included: regional groundwater specific vulnerability assessment, the regional pollution sources characteristics assessment and the health risk assessment of regional featured pollutants. The three sub-evaluation systems were coupled with the multi-index comprehensive method, the risk was characterized with the Spatial Analysis of ArcMap, and a new method to evaluate regional groundwater pollution risk that suitable for different parts of natural conditions, different types of pollution was established. Take Changzhou as an example, the risk of shallow groundwater pollution was studied with the new method, and found that the vulnerability index of groundwater in Changzhou is high and distributes unevenly; The distribution of pollution sources is concentrated and has a great impact on groundwater pollution risks; Influenced by the pollutants and pollution sources, the values of health risks are high in the urban area of Changzhou. The pollution risk of shallow groundwater is high and distributes unevenly, and distributes in the north of the line of Anjia-Xuejia-Zhenglu, the center of the city and the southeast, where the human activities are more intense and the pollution sources are intensive.
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Complex three-dimensional polymer-metal core-shell structures towards emission control.
Phys Chem Chem Phys
PUBLISHED: 05-13-2013
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We report the fabrication of three-dimensional periodic metal nickel nanostructures achieved by the combination of femtosecond laser-induced two-photon polymerization and electroless plating technology. We can control the deposition speed of 10 nm per second by adjusting the reaction time. The thermal stability is good under 500 °C for the three-dimensional graphite-lattice polymer structure with 200 nm nickel film. Optical reflectivity and thermal emission measurements under 550 °C showed that the fabricated metallic structure was thermally excited and emitted light at ? = 4.50, 4.95 ?m. The emission peak wavelengths agree with the absorption peaks. These data demonstrate that creating metallic photonic crystals by incorporation of metals to laser-fabricated templates is a simple and cost-efficient method. The emitters can work at such low temperatures, which is more important for realistic operation in applications.
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Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-30-2013
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Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behçet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (IL10, IL23R, CCR1, STAT4, KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and ERAP1) and 11 genes selected for their role in innate immunity (IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene, IL23R (P = 6.9 × 10(-5)), and one gene involved in innate immunity, TLR4 (P = 8.0 × 10(-4)), were associated with BD. In addition, damaging or rare damaging NOD2 variants were nominally significant across all three burden tests applied (P = 0.0063-0.045). Furthermore, carriage of the familial Mediterranean fever gene (MEFV) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65; P = 1.8 × 10(-12)). The disease-associated NSVs in MEFV and TLR4 implicate innate immune and bacterial sensing mechanisms in BD pathogenesis.
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Ionic Ni(II) complexes containing a triphenylphosphine ligand and an imidazolium cation: synthesis, structures and catalysis for aryl Grignard cross-coupling of aryl halides.
Dalton Trans
PUBLISHED: 04-26-2013
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Novel ionic Ni(II) complexes of general formula [R2im][Ni(PPh3)Cl3] (R2im = 1,3-bis(2,6-diisopropylphenyl)imidazolium cation, IPrim, 1a; R2im = 1,3-diisopropylimidazolium cation, (i)Prim, 2a) were easily prepared in high yields by the direct reaction of Ni(PPh3)2Cl2 with 1 equiv. of N,N-dihydrocarbylimidazolium salt, [R2im]Cl. Their bromide analogs [R2im][Ni(PPh3)Br3] (R2im = IPrim, 1b; R2im = (i)Prim, 2b) were synthesized by the same reaction in the presence of excess NaBr. The reaction of Ni(DME)Cl2 (DME = 1,2-dimethoxyethane) with 2 equiv. of [IPrim]Cl led to the formation of the complex [IPrim]2[NiCl4] (3) in an almost quantitative yield. All these complexes were characterized by elemental analysis, electrospray ionization mass spectrometry (ESI-MS), and (1)H NMR spectroscopy; X-ray crystallography was performed for 1a, 1b, 2a, and 2b. A catalytic study of the cross-coupling reactions of aryl Grignard reagents with aryl halides revealed that complexes 1a and 1b possessed the highest activities. In comparison, complexes 2a, 2b, 3, and the related biscarbene Ni(II) complex Ni(IPr)2Cl2 [IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] exhibited moderate activities; the least active complexes were Ni(PPh3)2Cl2 and [NEt4][Ni(PPh3)Cl3].
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Sensing combustion intermediates by femtosecond filament excitation.
Opt Lett
PUBLISHED: 04-19-2013
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Simultaneous monitoring of multiple combustion intermediates using femtosecond filament-induced nonlinear spectroscopy is demonstrated. Clean fluorescence emissions from free radicals CH, CN, NH, OH, and C(2), as well as atomic C and H, are observed when a femtosecond filament is formed in the laminar ethanol/air flame on an alcohol burner. The fluorescence signals of these species are found to vary as functions of the position of interaction of the filament with the flame along the vertical axis of the central combusting flow, opening up a possibility for remote combustion diagnostic in engines by the excitation of femtosecond laser filament.
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Ultrasensitive temperature sensor based on an isopropanol-sealed optical microfiber taper.
Opt Lett
PUBLISHED: 04-19-2013
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We demonstrate an ultrasensitive temperature sensor based on an isopropanol-sealed optical microfiber taper (OMT) in a capillary. The OMT is highly sensitive to ambient refractive index (RI) with a maximum sensitivity of 18989 nm/RI unit in the range of 1.3955-1.4008. The thermo-optic effect of isopropanol and the thermal expansions of the sealant and sealed liquid turn the OMT into an ultrasensitive temperature sensor with the maximum sensitivity of -3.88 nm/°C in the range of 20°C-50°C. The temperature sensitivity contributions from different mechanisms are also investigated theoretically and experimentally.
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Fabrication and multifunction integration of microfluidic chips by femtosecond laser direct writing.
Lab Chip
PUBLISHED: 03-16-2013
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In the pursuit of modern microfluidic chips with multifunction integration, micronanofabrication techniques play an increasingly important role. Despite the fact that conventional fabrication approaches such as lithography, imprinting and soft lithography have been widely used for the preparation of microfluidic chips, it is still challenging to achieve complex microfluidic chips with multifunction integration. Therefore, novel micronanofabrication approaches that could be used to achieve this end are highly desired. As a powerful 3D processing tool, femtosecond laser fabrication shows great potential to endow general microfluidic chips with multifunctional units. In this review, we briefly introduce the fundamental principles of femtosecond laser micronanofabrication. With the help of laser techniques, both the preparation and functionalization of advanced microfluidic chips are summarized. Finally, the current challenges and future perspective of this dynamic field are discussed based on our own opinion.
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RNA interference-mediated simultaneous silencing of four genes using cross-shaped RNA.
Mol. Cells
PUBLISHED: 03-06-2013
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The structural flexibility of RNA interference (RNAi)-triggering nucleic acids suggests that the design of unconventional RNAi trigger structures with novel features is possible. Here, we report a cross-shaped RNA duplex structure, termed quadruple interfering RNA (qiRNA), with multiple target gene silencing activity. qiRNA triggers the simultaneous down-regulation of four cellular target genes via an RNAi mechanism. In addition, qiRNA shows enhanced intracellular delivery and target gene silencing over conventional siRNA when complexed with jetPEI, a linear polyethyleneimine (PEI). We also show that the long antisense strand of qiRNA is incorporated intact into an RNA-induced silencing complex (RISC). This novel RNA scaffold further expands the repertoire of RNAi-triggering molecular structures and could be used in the development of therapeutics for various diseases including viral infections and cancer.
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The design, preparation, and evaluation of asymmetric small interfering RNA for specific gene silencing in mammalian cells.
Methods Mol. Biol.
PUBLISHED: 02-21-2013
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RNA interference (RNAi) is a highly efficient endogenous gene silencing mechanism mediated by short double-stranded RNAs termed small interfering RNAs (siRNAs). The current standard siRNA structure, which is used by most researchers to trigger sequence-specific target gene silencing, consists of a double strand region of 19 bp with 2 nt 3-overhangs at both ends. However, in addition to the desired target gene silencing, this conventional siRNA structure also exhibits several unintended effects that constitute obstacles to the use of siRNA in gene function studies and therapeutics development. Here, we provide protocols for designing and preparing an alternative structure for RNAi trigger, termed asymmetric shorter-duplex RNA (asiRNA). The asiRNA structure has a duplex region shorter than 19 bp and has an asymmetric 3-overhang structure. Importantly, the asiRNA structure not only triggers efficient target gene silencing comparable to that of the 19 bp standard siRNA structure but also significantly reduces nonspecific effects triggered by 19 bp siRNAs such as sense-strand-mediated off-target silencing and the saturation of RNAi machinery. Procedures are described for verifying that asiRNA activates gene silencing through an Ago2-dependent pathway and for assessing the miRNA pathway competition potency and specific and nonspecific silencing abilities of asiRNAs. We propose that asiRNA, an improved RNAi trigger that can overcome the nonspecific effects evoked by standard siRNA structures, can be developed as a precise and effective tool for both functional genomics and therapeutic applications.
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Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct STAT target gene.
PLoS ONE
PUBLISHED: 02-13-2013
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CD4(+) T helper (Th) cells differentiate into distinct effector subsets that are critical for host defense, but are also implicated in the pathogenesis of autoimmune disorders. Thelper17 (Th17) cells in particular are emerging as important drivers of multiple diseases including psoriasis, spondyloarthropathy and multiple sclerosis. To gain insight into the function of Th17 cells, we performed transcriptional profiling in hopes of elucidating products not previously recognized as being functionally relevant in these T cells. Herein, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted protein with pleiotropic effects on cellular growth, survival and integrity of the extracellular matrix, is preferentially produced by Th17 and Th1 cells. We further show that Th1 and Th17 cell TIMP1 regulation follows separate mechanisms with a requirement for STAT4 in the former and STAT3 in the latter. Finally, we demonstrate that when restricted to T cells, expression of TIMP1 promotes neuropathology in experimental allergic encephalomyelitis.
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A meta-analysis of the relationship of the Parkin p.Val380Leu polymorphism to Parkinsons disease.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 01-17-2013
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Parkinsons disease (PD) is one of the most common movement disorders. Parkin p.Val380Leu polymorphism (c.1239G > C) has been investigated as a potential genetic hallmark of PD, but studies examining the association between the polymorphism and PD have reported conflicting results. Therefore, we conducted a meta-analysis to assess the influence of Parkin p.Val380Leu polymorphism on the susceptibility of PD. Computer and hand searches of the literature were conducted using the MEDLINE, EMBASE, Cochrane Library, and China Academic Journals databases to identify studies addressing the association between the Parkin p.Val380Leu polymorphism and PD risk. We performed analyses of study characteristics, heterogeneity, and funnel plot asymmetry in analyses analogous to additive, dominant, recessive, homozygous, and heterozygous genetic models with the odds ratio (OR) as the measure of association. A total of 11 case-control studies involving 2,073 PD cases and 2,131 controls were included. When all 11 studies were pooled into the analysis, the presence of the Leu allele at the Parkin p.Val389Leu polymorphism was associated with decreased risk for PD in three genetic comparison models: OR in additive model: 0.79, 95% confidence interval (CI) = 0.64-0.98, P = 0.029; OR in recessive model: 0.55, 95% CI = 0.35-0.89, P = 0.014; OR in homozygous model: 0.51, 95% CI = 0.32-0.82, P = 0.005. Beggs funnel plot and Eggers test provided visual and statistical evidences for funnel plot symmetry, without evidence presence of publication bias. We conclude that the presence of the Leu allele at the Parkin p.Val380Leu polymorphism is associated decreased risk for PD.
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Identification of early replicating fragile sites that contribute to genome instability.
Cell
PUBLISHED: 01-02-2013
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DNA double-strand breaks (DSBs) in B lymphocytes arise stochastically during replication or as a result of targeted DNA damage by activation-induced cytidine deaminase (AID). Here we identify recurrent, early replicating, and AID-independent DNA lesions, termed early replication fragile sites (ERFSs), by genome-wide localization of DNA repair proteins in B cells subjected to replication stress. ERFSs colocalize with highly expressed gene clusters and are enriched for repetitive elements and CpG dinucleotides. Although distinct from late-replicating common fragile sites (CFS), the stability of ERFSs and CFSs is similarly dependent on the replication-stress response kinase ATR. ERFSs break spontaneously during replication, but their fragility is increased by hydroxyurea, ATR inhibition, or deregulated c-Myc expression. Moreover, greater than 50% of recurrent amplifications/deletions in human diffuse large B cell lymphoma map to ERFSs. In summary, we have identified a source of spontaneous DNA lesions that drives instability at preferred genomic sites.
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