Double-edged lipid nanoparticles combining liposome-bound TRAIL and encapsulated doxorubicin showing an extraordinary synergistic pro-apoptotic potential

Although TRAIL (TNF-related apoptosis-inducing ligand, also known as Apo2L) was described as capable of inducing apoptosis in transformed cells while sparing normal cells, limited results obtained in clinical trials has limited its use as an anti-tumor agent. Consequently, novel TRAIL formulations with enhanced bioactivity are necessary for overcoming resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumors. Our group has generated artificial liposomes with sTRAIL anchored on their surface (large unilamellar vesicle (LUV)-TRAIL), which have shown a greater cytotoxic activity both in vitro and in vivo when compared to sTRAIL against distinct hematologic and epithelial carcinoma cells. In this study, we have improved LUV-TRAIL by loading doxorubicin (DOX) in its liposomal lumen (LUVDOX-TRAIL) in order to improve their cytotoxic potential. LUVDOX-TRAIL killed not only to a higher extent, but also with a much faster kinetic than LUV-TRAIL. In addition, the concerted action of the liposomal DOX and TRAIL was specific of the liposomal DOX and was not observed when with soluble DOX. The cytotoxicity induced by LUVDOX-TRAIL was proven to rely on two processes due to different molecular mechanisms: a dynamin-mediated internalization of the doxorubicin-loaded particle, and the strong activation of caspase-8 exerted by the liposomal TRAIL. Finally, greater cytotoxic activity of LUVDOX-TRAIL was also observed in vivo in a tumor xenograft model. Therefore, we developed a novel double-edged nanoparticle combining the cytotoxic potential of DOX and TRAIL, showing an exceptional and remarkable synergistic effect between both agents

Design of the electric propulsion system for dumper trucks

This article designs a high-efficiency electric propulsion system for industrial trucks, such as dumper trucks. This design proposes using an alternative energy storage system of green H2 hydrogen to reduce emissions. This design determines the propulsion systems' technical and power requirements, starting with each vehicle's driving and duty cycles. For this analysis, a longitudinal dynamic model is created, with which the behavior of the energy conversion chain of the propulsion system is established. The evolutionary methodology analyzes the dynamic forces of vehicle interaction to size the propulsion system's components and the storage system. Using green H2 as fuel allows an energy yield three times higher than diesel. In addition, using this green hydrogen prevents the emission of 264,172 kg of CO₂, which the dumper emits when consuming 1,000 daily gallons of diesel within its working day

Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK

Copyright © 2014 Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

Micro Push-out Bond Strength and Bioactivity Analysis of a Bioceramic Root Canal Sealer

Introduction: Bioactive endodontic sealers have been developed to improve the quality of root canal obturation. EndoSequence Bioceramic (BC) Sealer is amongst calcium silicate-based materials recently developed for permanent root canal filling. The objective of this study was to evaluate the bioactivity of BC Sealer and its micro push-out bond strength to dentin compared to AH-Plus (AH) sealer. Methods and Materials: To perform the micro push-out test, 24 root canals of mandibular premolars were instrumented and divided into two groups (n=12). Each root was cut into 4 slices and lumens of the canals were filled with the sealers and submitted to micro push-out test. Failure mode was assessed using scanning electron microscopy (SEM). Bioactivity of BC sealer was investigated with scanning electron microscopy/energy-dispersive X-ray (SEM/EDS) and X-ray diffraction (XRD). Bioactivity assessments were reported descriptively. Bond strength data were analyzed by parametric t-test (α=5%). Results: In micro push-out test AH had higher bond strength mean values (16.29 MPa) than BC sealer (9.48 MPa) (P<0.05). Both groups had low amount of adhesive failure. SEM showed the presence of a mineral precipitate after 30 days and EDS analysis showed that those precipitates have high proportion of Ca. XRD showed peaks of crystalline phases of calcium carbonate compatible with the bioactivity. Conclusion: BC sealer showed indications of bioactivity and lower bond strength to dentine compared to AH.Keywords: Bioactivity; Bioceramic; Dentine; Micro Push-Out Bond Strength; Root Canal Seale

Data preprocessing workflow for exhaled breath analysis by GC/MS using open sources

© 2020 The Authors. This document is made available under the CC-BY 4.0 license. http://creativecommons.org/licenses/by /4.0/ This document is the Accepted version of a Published Work that appeared in final form in Scientifc Reports. To access the final edited and published work see https://doi.org/10.1038/s41598-020-79014-

Exploring the HIV-1 Rev Recognition Element (RRE)-Rev Inhibitory Capacity and Antiretroviral Action of Benfluron Analogs

Human immunodeficiency virus-type 1 (HIV-1) remains one of the leading contributors to the global burden of disease, and novel antiretroviral agents with alternative mechanisms are needed to cure this infection. Here, we describe an exploratory attempt to optimize the antiretroviral properties of benfluron, a cytostatic agent previously reported to exhibit strong anti-HIV activity likely based on inhibitory actions on virus transcription and Rev-mediated viral RNA export. After obtaining six analogs designed to modify the benzo[c]fluorenone system of the parent molecule, we examined their antiretroviral and toxicity properties together with their capacity to recognize the Rev Recognition Element (RRE) of the virus RNA and inhibit the RRE-Rev interaction. The results indicated that both the benzo[c] and cyclopentanone components of benfluron are required for strong RRE-Rev target engagement and antiretroviral activity and revealed the relative impact of these moieties on RRE affinity, RRE-Rev inhibition, antiviral action and cellular toxicity. These data provide insights into the biological properties of the benzo[c]fluorenone scaffold and contribute to facilitating the design of new anti-HIV agents based on the inhibition of Rev function.This research was funded by Generalitat Valenciana of Spain (PROMETEO 2021/036 grant to J.G. and GRISOLIAP/2020/026 contract to M.P.S.), MCIN/AEI/10.13039/501100011033 of Spain and “ERDF A way of making Europe” (grants PID2020-117508RB-I00 to V.M., RTI2021-093935-B-I00 to J.G., PID2021-125978OB-C2 to J.A. and PID2019-109870RB-I00 and CB21/13/00063 to J.M.-P.).S

Logística de distribución de productos perecederos: estudio de caso Fuente de Oro ( Meta) Viotá ( Cundinamarca)

En el siguiente trabajo se realizará una análisis sobre el caso Logística de distribución de productos perecederos: Fuente de Oro (Meta) y Viotá (Cundinamarca)”, teniendo en cuenta que se debe diseñar la red estructural, así como detallar los factores incidentes del entorno en cada uno de los nodos de la red propuesta, luego realizar un diagrama de flujo de proceso por responsabilidades, siguiendo con la evaluación de la vulnerabilidad del sistema logístico desde el componente de inventarios y almacenamiento, de transporte y distribución, el componente tecnológico, en la red diseñada. Después de lo anterior se hará una exploración acerca del sistema logístico de los mercados campesinos en Colombia y proponer una ruta para mejorar dicho sistema teniendo en cuenta algunos subprocesos.In the following work an analysis will be carried out on the Logistics case of distribution of perishable products: Source of Gold (Meta) and Viotá (Cundinamarca) ”, taking into account that the structural network must be designed, as well as detailing the incident factors of the environment in each of the nodes of the proposed network, then carry out a process flow diagram for responsibilities, following with the evaluation of the vulnerability of the logistics system from the inventory and storage component, transport and distribution, the technological component, in The designed network. After the above, an exploration will be made about the logistics system of the peasant markets in Colombia and propose a route to improve said system taking into account some threads

Aprovechamiento de vertientes en las nacientes del arroyo Valcheta

El paraje de Chipauquil se encuentra ubicado a 60 km al sur de la localidad de Valcheta, en el sureste de la provincia de Río Negro. Se accede al mismo por la ruta provincial Nº 60. La meseta de Somuncura, a cuyos pies se encuentran las nacientes del arroyo en tres diferentes cañadones, funciona como un gran reservorio de agua dulce que proveniente de las escasas precipitaciones de la región (220 mm/año) penetran a través de las fisuras del basalto que la constituyen y luego de recorrer km en su interior, aflora en numerosas vertientes de agua de variable caudal.EEA Valle InferiorFil: Bueno, Jorge Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgentinaFil: Gallego, Juan José. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgentinaFil: Martinez, Roberto Simon. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; Argentina. Universidad Nacional de Rio Negro; ArgentinaFil: Zelmer, Hernán. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgentinaFil: D`Onofrio, Mariano Sebastián. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgentinaFil: Saber, Ciro Adrián. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgentinaFil: Llampa, Julio Argentino. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior. Agencia de Extensión Rural Valcheta; Argentin

Exhaled volatilome analysis as a useful tool to discriminate asthma with other coexisting atopic diseases in women of childbearing age

©2021. The authors. This document is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is published version of a Published Work that appeared in final form in Scientifc Reports. To access the final edited and published work see https://doi.org/10.1038/s41598-021-92933-2The prevalence of asthma is considerably high among women of childbearing age. Most asthmatic women also often have other atopic disorders. Therefore, the diferentiation between patients with atopic diseases without asthma and asthmatics with coexisting diseases is essential to avoid underdiagnosis of asthma and to design strategies to reduce symptom severity and improve quality of life of patients. Hence, we aimed for the frst time to conduct an analysis of volatile organic compounds in exhaled breath of women of childbearing age as a new approach to discriminate between asthmatics with other coexisting atopic diseases and non-asthmatics (with or without atopic diseases), which could be a helpful tool for more accurate asthma detection and monitoring using a noninvasive technique in the near future. In this study, exhaled air samples of 336 women (training set (n= 211) and validation set (n= 125)) were collected and analyzed by thermal desorption coupled with gas chromatography-mass spectrometry. ASCA (ANOVA (analysis of variance) simultaneous component analysis) and LASSO+LS (least absolute shrinkage and selection operator+ logistic regression) were employed for data analysis. Fifteen statistically signifcant models (p-value< 0.05 in permutation tests) that discriminated asthma with other coexisting atopic diseases in women of childbearing age were generated. Acetone, 2-ethyl-1-hexanol and a tetrahydroisoquinoline derivative were selected as discriminants of asthma with other coexisting atopic diseases. In addition, carbon disulfde, a tetrahydroisoquinoline derivative, 2-ethyl-1-hexanol and decane discriminated asthma disease among patients with other atopic disorders. Results of this study indicate that refned metabolomic analysis of exhaled breath allows asthma with other coexisting atopic diseases discrimination in women of reproductive ag

A school- and community-based intervention to promote healthy lifestyle and prevent type 2 diabetes in vulnerable families across Europe : design and implementation of the Feel4Diabetes-study

Objective: To describe the design of the Feel4Diabetes-intervention and the baseline characteristics of the study sample. Design: School- and community-based intervention with cluster-randomized design, aiming to promote healthy lifestyle and tackle obesity and obesity-related metabolic risk factors for the prevention of type 2 diabetes among families from vulnerable population groups. The intervention was implemented in 2016-2018 and included: (i) the 'all-families' component, provided to all children and their families via a school- and community-based intervention; and (ii) an additional component, the 'high-risk families' component, provided to high-risk families for diabetes as identified with a discrete manner by the FINDRISC questionnaire, which comprised seven counselling sessions (2016-2017) and a text-messaging intervention (2017-2018) delivered by trained health professionals in out-of-school settings. Although the intervention was adjusted to local needs and contextual circumstances, standardized protocols and procedures were used across all countries for the process, impact, outcome and cost-effectiveness evaluation of the intervention. Setting: Primary schools and municipalities in six European countries. Subjects: Families (primary-school children, their parents and grandparents) were recruited from the overall population in low/middle-income countries (Bulgaria, Hungary), from low socio-economic areas in high-income countries (Belgium, Finland) and from countries under austerity measures (Greece, Spain). Results: The Feel4Diabetes-intervention reached 30 309 families from 236 primary schools. In total, 20 442 families were screened and 12 193 'all families' and 2230 'high-risk families' were measured at baseline. Conclusions: The Feel4Diabetes-intervention is expected to provide evidence-based results and key learnings that could guide the design and scaling-up of affordable and potentially cost-effective population-based interventions for the prevention of type 2 diabetes