A Novel Aptamer LL4A Specifically Targets Vemurafenib-Resistant Melanoma through Binding to the CD63 Protein.

Melanoma is a highly aggressive tumor with a poor prognosis, and half of all melanoma patients harbor BRAF mutations. A BRAF inhibitor, vemurafenib (PLX4032), has been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to treat advanced melanoma patients with BRAFV600E mutation. However, the efficacy of vemurafenib is impeded by adaptive resistance in almost all patients. In this study, using a cell-based SELEX (systematic evolution of ligands by exponential enrichment) strategy, we obtained a DNA aptamer (named LL4) with high affinity and specificity against vemurafenib-resistant melanoma cells. Optimized truncated form (LL4A) specifically binds to vemurafenib-resistant melanoma cells with dissociation constants in the nanomolar range and with excellent stability and low toxicity. Meanwhile, fluorescence imaging confirmed that LL4A significantly accumulated in tumors formed by vemurafenib-resistant melanoma cells, but not in control tumors formed by their corresponding parental cells in vivo. Further, a transmembrane protein CD63 was identified as the binding target of aptamer LL4A using a pull-down assay combined with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. CD63 formed a supramolecular complex with TIMP1 and β1-integrin, activated the nuclear factor кB (NF-кB) and mitogen-activated protein kinase (MAPK) signaling pathways, and contributed to vemurafenib resistance. Potentially, the aptamer LL4A may be used diagnostically and therapeutically in humans to treat targeted vemurafenib-resistant melanoma

Seguimiento online de la conductividad eléctrica del vino inducido por ultrasonido

We assessed the effects of ultrasonic frequency, power, temperature and exposure time on the electric conductivity (EC) of wine to evaluate the feasibility of the online EC monitoring as an indicator to reflect the changes of wine quality under the ultrasound irradiation. Results showed that the continuously monitored curve of EC was significantly different from the values recorded at the beginning and end of sonication. An abrupt rise and a rapid drop of wine EC were observed at the start and end points of sonication, respectively, in all working conditions. With regards to the assayed wine temperatures, the effect exerted by this parameter on EC before sonication was totally different from that observed when the samples were cooled down after ultrasound treatment. All in all, these results suggest that the online EC monitoring of wine may be used as an efficient indicator to control and reflect the real changes of wine under ultrasound treatment.Hemos estudiado los efectos de la frecuencia de ultrasonido, la potencia, la temperatura y el tiempo de exposición en la conductividad eléctrica (EC) del vino para evaluar la viabilidad del seguimiento EC online como indicador para reflejar los cambios en la calidad del vino bajo irradiación de ultrasonido. Los resultados mostraron que la curva de EC supervisada en continuo fue significativamente diferente de los valores registrados al principio y al final de la sonicación. Se observaron un aumento brusco y una rápida caída de EC del vino al principio y al final de la sonicación, respectivamente, para todas las condiciones estudiadas. En referencia a las temperaturas testadas del vino, el efecto ejercido por este parámetro en EC antes de la sonicación fue totalmente distinto de aquel observado cuando se enfriaron las muestras después del tratamiento de ultrasonido. En resumen, estos resultados sugieren que el seguimiento online de EC del vino podría ser utilizado como un indicador eficiente para controlar y reflejar los cambios reales en el vino con el uso de tratamiento de ultrasonido.National Natural Science Foundation of China [grant number 31101324]Natural Science Foundation of Shaanxi Province, China [grant number 2015JM3097]Technology Transfer Promotion Project of Xi’an, Shaanxi Province, China [grant number CXY1434(5)]Fundamental Research Funds for the Central Universities of China [grant number GK201302039], [grant number GK201404006], [grant number GK201505128

9-(4-Bromo­but­yl)-9H-carbazole

In the title compound, C16H16BrN, the bromo­butyl group lies on one side of the carbazole ring plane and has a zigzag shape. The dihedral angle between the two benzene rings is 0.55°. In the crystal, mol­ecules are connected by van der Waals inter­actions

Estudio preliminar sobre el efecto del ultrasonido en las propiedades fisicoquímicas del vino tinto

Ultrasound is regarded as a potential alternative method for improving the quality of some wines. This study was initiated with the objective of evaluating the effects of ultrasound on some important physicochemical properties of red wine such as chromatic characteristics (CC), electrical conductivity (EC), pH, titratable acidity (TA), total phenolic compounds (TPCs) and DPPH (1,1-diphenyl-2-picryl-hydrazyl) free radical scavenging activity (DFRSA). The operational parameters assessed were ultrasound power, ultrasound frequency, exposure time and bath temperature. Results illustrated that there were significant changes in CC, EC and TPC while pH and TA hardly changed except for samples treated at high temperatures. DFRSA was correlated to TPC during ultrasonic treatment. Application of principal component analysis to the experimental data suggested that exposure time was the factor with the greatest ability to induce changes on wine. Results suggested that ultrasound may be applied to improve some physicochemical properties of red wine.El ultrasonido se considera uno de los métodos alternativos potenciales para mejorar la calidad de algunos vinos. Se comenzó este estudio con el objetivo de evaluar los efectos del ultrasonido en algunas de la propiedades fisicoquímicas importantes del vino tinto como son: las características cromáticas (CC), la conductividad eléctrica (EC), el pH, la acidez (TA), los compuestos fenólicos totales (TPC) y el DPPH (1,1-difenil-2-picrilhidrazil) de actividad de eliminación de radicales libres (DFRSA). Los parámetros operacionales examinados fueron: la potencia de ultrasonido, la frecuencia de ultrasonido, el tiempo de exposición y la temperatura de baño. Los resultados ilustraron la existencia de cambios significativos en CC, EC y TPC, mientras que el pH y TA prácticamente no cambiaron excepto en las muestras tratadas con altas temperaturas. DFRSA tuvo correlación con TPC durante el tratamiento con ultrasonido. La aplicación de análisis de componentes principales a los datos experimentales sugirió que el tiempo de exposición era el factor con mayor habilidad para inducir cambios en el vino. Los resultados sugirieron que el ultrasonido podría aplicarse para mejorar algunas de las propiedades fisicoquímicas del vino tinto.National Natural Science Foundation of China [No. 31101324]Natural Science Foundation of Shaanxi Province, China [No. 2015JM3097]Technology Transfer Promotion Project of Xi’an, Shaanxi Province, China [No.CXY1434(5)]Fundamental Research Funds for the Central Universities of China [Nos. GK201302039, GK201404006