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Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is vital for bone formation, and its dysfunction is linked to osteoporosis (OP). In this work, we explored the function of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) in regulating osteogenic differentiation of hBMSCs. In the present study, the expression of SNHG14 in hBMSCs obtained from OP patients was measured by quantitative real-time polymerase chain reaction (qRT-PCR). SNHG14 was over-expressed or knocked down in hBMSCs, and the expression levels of OP-related genes (ALP, OCN, and OPN) in hBMSCs were detected by qRT-PCR and Western blot. StarBase database and miRanda database were used to predict the binding sites between SNHG14 and miR-185-5p, and between miR-185-5p and 3'UTR of WNT1 inducible signaling pathway protein 2 (WISP2), respectively. Luciferase reporter gene assay was used to validate the binding relationship between SNHG14 and miR-185-5p, and miR-185-5p and 3'UTR of WISP2, respectively. Here, we report that SNHG14 was significantly down-regulated in hBMSCs obtained from patients with OP. Overexpression of SNHG14 promoted osteogenic differentiation, while knockdown of SNHG14 worked oppositely. Mechanistically, miR-185-5p was demonstrated to be a target of SNHG14, and could reverse the function of SNHG14. Additionally, WISP2 was identified as a target gene of miR-185-5p in hBMSCs and could be indirectly regulated by SNHG14. Taken together, down-regulation of SNHG14 in hBMSCs accelerated the progression of OP via regulating miR-185-5p/WISP2 axis.
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Células Madre Mesenquimatosas , MicroARNs , ARN Largo no Codificante , Médula Ósea , Diferenciación Celular , Células Cultivadas , Humanos , MicroARNs/genética , Osteogénesis/genética , ARN Largo no Codificante/genéticaRESUMEN
We investigate the electronic properties and valley physics of Janus monolayer WSSe on a CrI3 substrate layer based on first-principles calculations. It is shown that the K and K' valley degeneracy can be lifted which leads to valley polarization (VP) in the WSSe due to the magnetic proximity coupling to a magnetic substrate. The magnitude of VP is highly sensitive to the interfacial electronic properties and can be tuned by varying the stacking configurations of the heterostructure. Interestingly, the direction of VP can be altered by manipulating the layer alignment without reversing the magnetism orientation of the magnetic substrate CrI3. We suggest that the hybridization between the bands of WSSe and the substrate plays an important role. Meanwhile, the charge distributions have been mapped out to uncover the microscopic origin of the direction variable VP. In addition, large VP can be achieved by adjusting the interlayer spacing. Our investigations may have potential applications in the design of valleytronic devices.
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Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.
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Infarto del Miocardio , Infarto del Miocardio con Elevación del ST , Femenino , Fibrinolíticos/uso terapéutico , Mortalidad Hospitalaria , Humanos , Infarto del Miocardio/tratamiento farmacológico , Proteínas Recombinantes , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno , Resultado del Tratamiento , Activador de Plasminógeno de Tipo UroquinasaRESUMEN
Objective: To explore the differential protein expressions in papillary thyroid carcinoma (PTC) with or without Hashimoto's thyroiditis (HT). Methods: Tissue microarray was prepared and the protein expression levels of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), vascular endothelial growth factor (VEGF), cyclinD1, mesothelial cell (MC) , CD56 and Galectin3 in the PTC tissues with or without HT were detected by immunohistochemical staining. Results: The positive expression rates of BRAF protein in the PTC tissues with or without HT groups were 55.4% (36/65) and 63.6% (42/66), respectively, without significant difference (P=0.336). The positive expression rates of VEGF protein in the PTC tissues with or without HT groups were 25.7% (19/74) and 25.8%(17/66), respectively, without significant difference (P=0.991). The positive expression rates of cyclin D1 protein in the PTC tissues with or without HT groups were 93.4% (71/76) and 97.6% (80/82), without significant difference (P=0.206). The positive expression rates of MC protein in the PTC tissues with or without HT groups were 86.1% (62/72) and 83.5%(71/85), without significant difference (P=0.654). The positive expression rates of Galectin3 protein in the PTC tissues with or without HT groups were 98.7% (76/77) and 97.5% (78/80), without significant difference (P=0.583). The positive expression rates of CD56 in the PTC tissues and adjacent thyroid follicular epithelial cells were 27.4% (32/117) and 65.0% (76/117), respectively, and the difference was statistically significant (P=0.001). The positive expression rates of CD56 in PTC tissues with or without HT were 35.5% (24/68) and 16.5% (13/79), respectively, and the difference was statistically significant (P=0.009). Conclusions: There are no significant differences in the expressions of BRAF, VEGF, CyclinD1, MC and Galectin3 between the PTC tissues with or without HT. However, the significantly differential expression of CD56 between the two group suggests that CD56 may be related to the pathogenesis of PTC with HT. CD56 may be used as a potential molecular marker in PTC diagnosis.
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Adenocarcinoma Papilar/genética , Antígeno CD56/metabolismo , Carcinoma Papilar/patología , Enfermedad de Hashimoto/genética , Proteínas Proto-Oncogénicas B-raf/genética , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/patología , Animales , Biomarcadores/análisis , Carcinoma Papilar/metabolismo , Ciclina D1/genética , Galectinas , Enfermedad de Hashimoto/metabolismo , Enfermedad de Hashimoto/patología , Humanos , Ratones , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas B-raf/metabolismo , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/patología , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Análisis de Matrices Tisulares , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Objective: To investigate the clinicopathological and immunohistochemistrical features of secretory carcinoma of the breast (SCB), as well as its diagnosis and prognosis. Methods: Five cases of SCB were collected and specimens were fully drawn. Microscopic pathology examinations and immunohistochemistry(SP method)were performed. Results: Five cases were all female patients aged from 31 to 54 years old (with an average age of 38 years), and all patients initially presented with the painless breast lump, often near the areola. Macroscopically, all the tumors were relatively circumscribed, with a mean diameter of 2.1 cm(1.2-3.0 cm). Histologically, the tumors revealed different patterns (microcystic, solid, ductal, and so forth) and appeared large amounts of intracellular and extracellular eosinophilic PAS- and AB-PAS- positive secretory materials, as well as the granular eosinophilic cytoplasm. Immunohistochemistrically, the tumor cells were strongly positive for epithelial membrane antigen (EMA) and S-100. Three cases had negative expression for estrogen receptor (ER) and progesterone (PR), and two cases had weakly focal expression. Human epidermal growth factor receptor 2 (HER2) and P53 were negative, while only one case had weakly focal expression. The tumors were positive for CK7, CK5/6, CD10, but they were negative for CEA, smooth muscle actin (SMA) and P63 . The proliferation index of Ki-67 was 5%-8%. There was no patient with metastasis of the tumor in axillary lymph node. Except 1 case lost follow-up, and the rest had no recurrence or distant metastasis. Conclusions: SCB is very rare, with low malignancy, and has better prognosis, but it is usually classified as triple-negative breast cancer because of the immune phenotype. The correct diagnosis of this lesion depends on clinical characteristics, morphology and immunohistochemistry.
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Neoplasias de la Mama , Mama , Carcinoma , Recurrencia Local de Neoplasia , Adulto , Axila , Femenino , Humanos , Inmunohistoquímica , Ganglios Linfáticos , Persona de Mediana Edad , Mucina-1 , Pronóstico , Receptor ErbB-2RESUMEN
We evaluated the effect of feeding soy flour-containing milk replacer (MR) with a lower than normal pH on growth, nutrient digestibility, digesta pH, and gastrointestinal development of preweaned calves. The study consisted of 48 neonatal calves, allocated to 8 treatments in a 2-factor 4×2 randomized design. The calves received 2 types of MR containing soy flour. The proportion of soy crude protein (CP) to total CP (SP/CP) in MR was 50% (MR50 treatment) or 80% (MR80 treatment), respectively. The pH of the reconstituted MR was decreased by 1 N HCl from to 6.2 to 5.5, 5.0, or 4.5. We measured body weight and dry matter intake and calculated feed conversion rate in the MR50 treatment. We monitored urinary and fecal pH consecutively for 5h when calves were 25d old. We also conducted a digestion trial to determine nutrient digestibility from 49 to 55d of age. At 63d old, calves were slaughtered, and gastrointestinal pH, mass index, and morphology were evaluated. Reducing the pH of MR containing soy flour improved average daily gain and feed conversion rate, increased Ca digestibility, and reduced urinary, fecal, and digesta pH in the rumen, reticulum, and omasum. Although treatments had no effect on gastrointestinal mass index, the pH 5.0 treatment led to favorable ruminal epithelium growth, and the pH 5.5 treatment led to better intestinal epithelium growth. Increasing SP/CP from 50 to 80% decreased P digestibility and fecal and digesta pH in rumen, reticulum, and omasum. Moreover, the MR80 treatment reduced the mass index of the abomasums and jejunum. In conclusion, decreasing the pH of MR containing soy flour to a pH of 5.0 to 5.5 improved the digestive tract of preweaned calves. A pH reduction to 4.5 had adverse effects on intestinal epithelium growth.
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Harina , Leche , Alimentación Animal , Animales , Bovinos , Dieta/veterinaria , Digestión , Concentración de Iones de HidrógenoRESUMEN
Horizontal transfer (HT), the exchange of genetic material between species, plays important roles in transposon biology and genome evolution. In this study, we provide the first documented example of a new Academ transposon involved in recent and distant HTs into the genomes of species belonging to seven different orders of insects: Lepidoptera, Hymenoptera, Neuroptera, Embioptera, Dermaptera, Trichoptera and Zoraptera. These results suggest that HT of DNA transposons amongst insects has occurred on a broader scale than previously appreciated. The Academ transposon discovered in the Lepidoptera and parasitic wasps is of particular interest because the intimate association between wasps and their lepidopteran hosts might provide an opportunity for HT of transposons.
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Elementos Transponibles de ADN , Transferencia de Gen Horizontal , Insectos/genética , Animales , Interacciones Huésped-Parásitos , Insectos/parasitologíaRESUMEN
A combination of synchrotron-based x-ray spectroscopy and contact potential difference measurements have been used to examine the electronic structure of the (3 × 1) silicon terminated (100) diamond surface under ultra high vacuum conditions. An occupied surface state which sits 1.75 eV below the valence band maximum has been identified, and indications of mid-gap unoccupied surface states have been found. Additionally, the pristine silicon terminated surface is shown to possess a negative electron affinity of -0.86 ± 0.1 eV.
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Objective: To evaluate the efficacy and safety of intravenous thrombolytic therapy using reteplase in patients with acute ST-segment elevation myocardial infarction (STEMI). Method: A total of 73 hospitals from Henan province took part in this clinical trials during October 2012 to October 2014, 1 226 cases (1 014 male (82.7%), mean age 59.0 (51.0, 66.0) years) with acute STEMI received reteplase as thrombolytic agent.Reperfusion rate was judged according to the clinical symptoms, electrocardiogram, myocardial enzymes and heart rhythm, and the rate of cardiovascular events and bleeding events during hospitalization was also observed.Bleeding events were evaluated with global utilization of streptokinase and tissues plasminogen activator for occluded coronary arteries (GUSTO) criteria.Subgroup analysis was performed to compare the effects of various thrombolysis timing (time from onset to thrombolysis≤6 h or 6-12 h) on reperfusion rate, cardiovascular events and bleeding events rate. Results: The reperfusion rate was 89.3% (1 089/1 219) at 120 minutes after the thrombolysis, average recanalization time was (59.96±26.86) minutes.The reperfusion rate of ≤6 h thrombolysis group was significantly higher than in 6-12 hours group (90.3% (988/1094) vs. 80.8% (101/125), P=0.001), while in-hospital mortality (2.6%(28/1 094) and 0.8% (1/125), P=0.352) and rate of bleeding (5.9%(64/1 094) and 5.6%(7/125), P=0.910) were similar between the two groups. The total in-hospital mortality after thrombolysis was 2.4% (29/1219), which was significantly higher in failed recanalization group than in recanalization group (10.8%(14/130) vs. 1.4%(15/1089), P< 0.001). The total rate of bleeding after thrombolysis was 5.8% (71/1219), there were 3 severe bleeding cases according to GUSTO classification (0.2%), all of them were cerebral hemorrhage, and 2 out of 3 cases died. Conclusions: Reteplase use is related to high recanalization rate and low cardiovascular events and bleeding rate and our results thus show that reteplase is a safe and effective thrombolytic agent for STEMI patients.
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Infarto del Miocardio , Enfermedad Aguda , Anciano , Infarto de la Pared Anterior del Miocardio , Oclusión Coronaria , Electrocardiografía , Femenino , Fibrinolíticos , Hemorragia , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Terapia Trombolítica , Activador de Tejido PlasminógenoRESUMEN
We explore an analogue of optical frequency combs in driven nonlinear phononic systems, and present a mechanism for generating phononic frequency combs through nonlinear resonances. In the underlying process, a set of phonon modes is simultaneously excited by the external driving which yields frequency combs with an array of discrete and equidistant spectral lines of each nonlinearly excited phonon mode. Frequency combs through nonlinear resonance of different orders are investigated, and in particular the possibility of correlation tailoring in higher-order cases is revealed. We suggest that our results can be applied in various nonlinear acoustic processes, such as phonon harvesting, and can also be generalized to other nonlinear systems.
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Microarray data were collected from bile duct samples from subjects with malignant biliary strictures by endoscopic retrograde cholangiopancreatography to screen for key genes associated with this disease. A predicted interaction network was constructed for these genes to interpret their functions. The gene expression dataset GSE34166 (10 samples: 6 malignant and 4 benign control samples) was downloaded from the Gene Expression Omnibus database. R package scripts were used to process the data and screen for differentially expressed genes. Genes identified were uploaded to the analysis tool String 8.3 to generate a gene interaction network. A hub gene was identified by calculating the node degree. The interaction network of the hub gene with other genes in the human genome was constructed and screened (score >0.9), and pathway-enrichment analysis was performed to elucidate the hub gene function. In total, 377 differentially expressed genes were identified and a network comprising 209 pairs of interactions was constructed. The most critical hub gene was identified as GSTA1, and a GSTA1-based interaction network was constructed consisting of 25 genes (containing the differentially expressed gene GSTA3). The cytochrome P450 (CYP450)-metabolic pathway displayed the most significant enrichment. Additionally, 4 transcription factors and their binding sites were also identified. In conclusion, we have identified the differentially expressed genes GSTA1 (a hub gene) and GSTA3, which may cause abnormal gene expression and tumorigenesis through CYP450-metabolic pathways. The transcription factors and their binding sites in the promoter of the hub gene provide potential directions for future drug design.
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Neoplasias de los Conductos Biliares/genética , Proteínas ELAV/biosíntesis , Glutatión Transferasa/biosíntesis , Redes y Vías Metabólicas , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Biología Computacional , Proteína 2 Similar a ELAV , Regulación Neoplásica de la Expresión Génica , Glutatión Transferasa/genética , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Mapas de Interacción de Proteínas/genéticaRESUMEN
In this work, we theoretically investigate the spin-split energy bands of electrons and spin-polarized transport in two-dimensional (2D) spin-orbit lateral superlattices (SOLSLs), where the square rods with Rashba spin-orbit coupling (SOC) are distributed periodically by applying gate voltages on the semiconductor. Within the Landauer framework of ballistic transport, the energy bands, the electrical conductance, the spin polarization and the spin-dependent electronic charge distributions have been calculated. It is found that the energy minibands are formed and the energy levels are split up by the Rashba SOC. As a result, the spin-polarized conductance is obtained even in the absence of external magnetic fields and magnetic materials. Meanwhile, the spin polarization can approach high values in the SOLSLs by manipulating the strength of SOC. Furthermore, the spin-dependent electronic charge distributions have been obtained, which present a clear picture of spin-polarized conductance. Our investigations have the potential applications in spin-based quantum devices and semiconductor spintronics.
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The compressed ultrafast photography (CUP) can capture non-repetitive time-evolving events at 7 × 1013 fps, which is anticipated to find a diverse range of applications in physics, biomedical imaging, and materials science. The feasibility of diagnosing ultrafast phenomenon of Z-pinch by using the CUP has been analyzed in this article. Specifically, a dual-channel CUP design has been adopted for acquiring high quality reconstructed images and the strategies of identical masks, uncorrelated masks, and complementary masks have been compared. Furthermore, the image of the first channel was rotated by 90° to balance the spatial resolution between the sweep direction and the non-sweep direction. Both five synthetic videos and two simulated Z-pinch videos were chosen as the ground truth to validate this approach. The average peak signal to noise ratio of the reconstruction results is 50.55 dB for the self-emission visible light video and 32.53 dB for the laser shadowgraph video with unrelated masks (rotated channel 1). The simulation results show that the time-space-evolving process of plasma distribution can be well retold, and the phenomenon of plasma instability can be accurately diagnosed by the dual-channel CUP with unrelated masks (rotated channel 1). This study may promote the practical applications of the CUP in the field of accelerator physics.
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BACKGROUND: It has been generally accepted that spondylolysis will decrease the segmental stability of the lumbar spine, increase the load exerted on the disc at the spondylolytic level and the level above, accelerating disc degeneration. AIM: Here we describe the Buck's technique enhanced with pedical screw-rod-hook construct and discuss the indication of direct repair of pars defect with disc herniation at caudal level and disc degeneration at cranial level of spondylolysis. PATIENTS AND METHODS: A 19 year-old man had suffered low back trouble in the course of 5 years and unilateral sciatica of 7 months. To treat it the limited disc discectomy was performed first. RESULTS: Buck's screwing with modified angle of insertion enhanced with pedical screw-rod-hook construct and allograft surrounding the defect was finally accomplished. At the follow-up of one month after operation, he had no back pain or sciatica, and no disability in daily activities (VAS: 0), the modified Prolo Scale score was 8. CONCLUSIONS: Direct repair of spondylolysis with disc degeneration at cranial adjacent level combined with disc herniation at spondylolytic level may be debatable. We take it as an alternative to the established treatment.
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Discectomía/métodos , Desplazamiento del Disco Intervertebral/cirugía , Adulto , Tornillos Óseos , Humanos , Masculino , Espondilólisis/cirugíaRESUMEN
The aim of the present research was to determine the interactive effect of zearalenone (ZEA) and soybean isoflavone (ISO) on the growth performance, development of organs and serum parameters in prepubertal gilts. Ninety 75-day-old female pigs (Duroc × Landrace × Yorkshire, 26.5 ± 0.60 kg) were randomly allocated to nine diet treatments during the 21-day study. The experiment employed a 3 × 3 factorial design using a non-soybean meal diet with the addition of 0, 0.5 or 2.0 mg/kg ZEA and 0, 300 or 600 mg/kg ISO. The results indicated that simultaneous addition of ZEA and ISO had no significant influence on the growth performance in prepubertal gilts. Zearalenone with 2 mg/kg increased (p < 0.05) the relative weight of the reproductive organs (including uterus and vagina) but had no obvious effects (p > 0.05) on the relative weight of the heart, liver, lung, kidney and spleen. Isoflavone at 600 mg/kg could offset the increased weight of the reproductive organs induced by ZEA. Simultaneous addition of ZEA and ISO to prepubertal gilts increased the level of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in the serum (p < 0.05) at day 14 but their levels decreased (p < 0.05) over time. Zearalenone increased the level of malondialdehyde and decreased the concentrations of superoxide dismutase and glutathione peroxidase (p < 0.05) in the serum. The results suggested that ISO added to diets at 600 mg/kg could reduce the increase in the relative weight of reproductive organs and relieve the oxidative stress induced by ZEA added at 2 mg/kg during the growth phase in prepubertal gilts.
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Glycine max/química , Isoflavonas/farmacocinética , Porcinos/sangre , Porcinos/crecimiento & desarrollo , Zearalenona/farmacocinética , Animales , Peso Corporal/efectos de los fármacos , Interacciones Farmacológicas , Estrógenos no Esteroides/farmacocinética , Femenino , Genitales Femeninos/efectos de los fármacos , Glutatión Peroxidasa/sangre , Corazón/anatomía & histología , Corazón/efectos de los fármacos , Isoflavonas/efectos adversos , Isoflavonas/química , Riñón/anatomía & histología , Riñón/efectos de los fármacos , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Hígado/enzimología , Pulmón/anatomía & histología , Pulmón/efectos de los fármacos , Malondialdehído/sangre , Tamaño de los Órganos , Maduración Sexual/fisiología , Bazo/anatomía & histología , Bazo/efectos de los fármacos , Superóxido Dismutasa/sangre , Zearalenona/efectos adversosRESUMEN
AIMS/HYPOTHESIS: Amylin, a secretory protein mainly produced by pancreatic beta cells, is elevated in the circulation of patients with diseases related to acute and chronic inflammation, including acute pancreatitis, pancreas graft rejection, obesity and insulin resistance. TNF-α is involved in these disorders. We investigated the effect of TNF-α on amylin levels and the underlying mechanisms, using murine pancreatic beta cell line MIN6 and pancreatic islets. METHODS: Amylin, proinsulin and prohormone convertase 1/3, 2 (Pc1/3, Pc2 [also known as Pcsk1/3 and Pcsk2, respectively]) mRNA levels, and amylin promoter and nuclear factor κB (NF-κB) activation were examined by real-time PCR and luciferase reporter assay, respectively. Amylin protein level and mitogen-activated protein kinase phosphorylation were detected by western blot. Activator protein 1 (AP1) activation was examined by electrophoretic mobility shift assay (EMSA). RESULTS: TNF-α acutely induced amylin expression at the transcriptional level and increased proamylin and the intermediate form of amylin in MIN6 cells and islets. However, it had no effect on proinsulin, Pc1/3 and Pc2 expression. Studies with (1) MIN6 cells treated with inhibitors of MEK1/2, c-Jun-N-terminal kinase (JNK) or protein kinase Cζ (PKC(ζ)), (2) MIN6 cells expressing a c-Jun-dominant negative construct and (3) islets from Fos knockout mice demonstrated that TNF-α induced amylin expression through the PKC(ζ)-extracellular signal-regulated kinase (ERK)/JNK pathways. EMSA showed that (PKC(ζ)), JNK and ERK1/2 were involved in TNF-α-induced AP1 activation, suggesting that TNF-α induces murine amylin expression through the (PKC(ζ)) - ERK1/2 - AP and PKC(ζ) - JNK - AP1 pathways. Further studies showed that TNF-α also induced murine amylin expression through the phosphatidylinositol 3 kinase-NF-κB signalling pathway and enhanced human amylin promoter activation through NF-κB and AP1. CONCLUSIONS/INTERPRETATION: TNF-α acutely induces amylin gene expression in beta cells through multiple signalling pathways, possibly contributing to amylin elevation in acute inflammation-related pancreatic disorders.
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Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Animales , Western Blotting , Células Cultivadas , Ensayo de Cambio de Movilidad Electroforética , Polipéptido Amiloide de los Islotes Pancreáticos/genética , Ratones , Reacción en Cadena de la PolimerasaRESUMEN
We present a comprehensive study of gold nanoparticle embedding into polystyrene (PS) surfaces at temperatures ranging from T ( g ) + 8 K to T ( g ) - 83 K and times as long as 10(5) minutes. This range in times and temperatures allows the first concurrent observation of and differentiation between surface and bulk behavior in the 20 nm region nearest the free surface of the polymer film. Of particular importance is the temperature region near the bulk glass transition temperature where both surface and bulk processes can be measured. The results indicate that for the case of PS, enhanced surface mobility only exists at temperatures near or below the bulk T ( g ) value. The surface relaxation times are only weakly temperature dependent and near T ( g ), the enhanced mobility extends less than 10nm into the bulk of the film. The results suggest that both the concept of a "surface glass transition" and the use of glass transition temperatures to measure local mobility near interfaces may not universally apply to all polymers. The results can also be used to make a quantitative connection to molecular dynamics simulations of polymer films and surfaces.
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Oro/química , Modelos Químicos , Nanopartículas/química , Polímeros/química , Pesos y Medidas/instrumentación , Poliestirenos/química , Temperatura de TransiciónRESUMEN
An excitation at 201 meV is observed in the doped-hole ladder cuprate Sr14Cu24O41, using ultraviolet resonance Raman scattering with incident light at 3.7 eV polarized along the rungs. The excitation is of charge nature, with a temperature independent excitation energy, and can be understood via an intraladder pair-breaking process. The intensity tracks closely the order parameter of the charge density wave in the ladder CDW(L), but persists above its transition temperature T(CDW(L)), indicating a strong local pairing above the T(CDW(L)). The 201 meV excitation vanishes in La6Ca8Cu24O(41+δ), and La5Ca9Cu24O41 which are samples with no holes in the ladders. Our results suggest that the doped holes in the ladder are composite bosons consisting of paired holons that order below T(CDW).
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We report direct evidence of room-temperature ferromagnetic ordering in O-deficient ZnO:Cu films by using soft x-ray magnetic circular dichroism and x-ray absorption. Our measurements have revealed unambiguously two distinct features of Cu atoms associated with (i) magnetically ordered Cu ions present only in the oxygen-deficient samples and (ii) magnetically disordered regular Cu2+ ions present in all the samples. We find that a sufficient amount of both oxygen vacancies (V(O)) and Cu impurities is essential to the observed ferromagnetism, and a non-negligible portion of Cu impurities is uninvolved in the magnetic order. Based on first-principles calculations, we propose a microscopic "indirect double-exchange" model, in which alignments of localized large moments of Cu in the vicinity of the V(O) are mediated by the large-sized vacancy orbitals.