Green CO2 technology for the preparation of aerogel dry powder loaded with beclomethasone dipropionate

Dry powder inhalers (DPIs) have gained increasing clinical acceptance in the local treatment of lung diseases due to their ability to meet the evolving needs of patients while avoiding environmental concerns. However, some formulations for DPIs still encounter performance limitations in terms of aerodynamic properties and achievement of therapeutic doses. Innovative aerogel powder formulations for DPIs processed using combined supercritical CO2 (scCO2)-based technologies can overcome these limitations, especially in the case of poorly water-soluble drugs. The loading of hydrophobic drugs into aerogels can be optimized through a thorough understanding of the physicochemical properties of the formulation and the scCO2 processing conditions. In this study, drug-loaded alginate aerogel particles were prepared by combining gelation-emulsification techniques and scCO2-based technologies. Beclomethasone dipropionate (BDP), a hydrophobic corticosteroid, was incorporated into the aerogel matrix by scCO2 impregnation. The influence of contact time, initial amount of drug, and use of co-solvents on the efficiency of scCO2 impregnation were studied. The kinetics of the BDP adsorption process was modelled to elucidate the time required for the drug to attain equilibrium concentration under specific operating conditions. Nitrogen adsorption-desorption and helium pycnometry revealed particles with large surface area (>200 m2/g) and porosity (ca. 90%). The resulting aerogels had excellent aerodynamic properties at relevant BDP doses, as confirmed by in vitro lung deposition tests. Ex vivo permeability tests with porcine lung tissues evidenced that BDP released from the inhaled formulation could penetrate the bronchial tissueWork supported by MICINN [PID2020–120010RB-I00/AEI/10.13039/501100011033], Agencia Estatal de Investigación [AEI] and FEDER funds. This publication is based upon work from ECO-AERoGELS COST Innovation Grant (ref. IG18125) supported by the European Commission. Th. D. acknowledges the support of Diputación Provincial de A Coruña for research in health science 2022–2023 (BINV-CS/2022) and of AERoGELS COST Action (ref. CA18125) for a Short Term Scientific Missions (STSM) grant to undergo the in vitro aerodynamic drug deposition tests of aerogels in the University of Parma (Italy). Clara López-Iglesias acknowledges Xunta de Galicia for her Postdoctoral contract (ED481B 2021/008). The authors would like to thank Ezequiel Vázquez Fernández, Carlos Illanes-Bordomás and Miguel Pereira-Silva (University of Santiago de Compostela, Spain) for their valuable support and technical help with Raman spectroscopy, analysis of SEM images and dialysis method in in vitro drug release studies, respectivelyS

Post-treatment of anaerobically digested sewage for nutrient removal

Although modern anaerobic sewage treatment systems and in particular the upflow anaerobic sludge blanket reactor (UASB) have demonstrated remarkable performance in tropical and subtropical regions, the effluent quality is generally not compatible with discharge standards in many countries, so post-treatment becomes necessary. In practice, the most widely applied post-treatment options are polishing ponds (PPs) and other aerobic treatment bioreactors. PPs are treatment units treating anaerobically pre-treated wastewater, which distinguishes them from conventional waste treatment ponds, wherein normally raw wastewater is treated. Anaerobic pre-treatment has a very profound influence on the configuration and operation of PPs, as will be shown in this chapter. Other aerobic post-treatments can be realized with conventional activated sludge systems, or more complex technological solutions including membrane bioreactors (MBRs) or trickling filters. The anaerobic–aerobic treatment has important advantages compared to the purely aerobic treatment: the volume and sludge production is much smaller, there is a possibility that the anaerobic–aerobic system operates with energetic self-sufficiency and the concentration of excess sludge is much higher facilitating its processing. An important problem of anaerobic–aerobic treatment is the difficulty of producing a final effluent with low nutrient concentration. Anaerobic sewage treatment reduces the content of biodegradable organic matter in the effluent, limiting in practice the removal of phosphorus to the use of chemical precipitation systems. For the case of nitrogen, the alternatives only go through new processes, which complement the poor capacity of conventional denitrification due to the limited concentration of biodegradable organic matter. This limits in practice, the nitrogen elimination capacity of activated sludge systems or trickling f ilters treating effluents from UASB reactors. A notable breakthrough could occur if reliable partial nitrification anammox processes for the water line were developed, as these are still under development, or systems in which the dissolved methane present in the anaerobic effluents was used to denitrify, as it has already been observed in some MBRs

Papel de la nedilación de PCK1 en la gluconeogénesis hepática

La nedilación es un mecanismo postraduccional que agrega una proteína similar a la ubiquitina, a saber, la proteína 8 regulada negativamente durante el desarrollo expresada por células precursoras neurales (NEDD8). En este trabajo mostramos en ratones que la nedilación en el hígado está modulada por la disponibilidad de nutrientes. La inhibición de la nedilación en el hígado de ratón reduce la capacidad gluconeogénica y las acciones hiperglucémicas de las hormonas contrarreguladoras. Además, las personas con diabetes tipo 2 presentan niveles elevados de nedilación hepática. A nivel mecanístico, el ayuno o la restricción calórica de ratones conduce a la nedilación de la fosfoenolpiruvato carboxiquinasa 1 (PCK1) en tres residuos de lisina: K278, K342 y K387. Encontramos que la mutación de las tres lisinas PCK1 que están nediladas reduce su tasa de actividad gluconeogénica. Las simulaciones de dinámica molecular muestran que la nedilación de PCK1 podría reposicionar dos bucles que rodean el centro catalítico en una configuración abierta, haciendo que el centro catalítico sea más accesible. Nuestro estudio revela que la nedilación de PCK1 proporciona un mecanismo preciso para controlar el metabolismo de la glucosa al vincular la disponibilidad total de nutrientes con la homeostasis metabólica

Boosting Oxygen Reduction Reaction Selectivity in Metal Nanoparticles with Polyoxometalates

The lack of selectivity toward the oxygen reduction reaction (ORR) in metal nanoparticles can be linked to the generation of intermediates. This constitutes a crucial constraint on the performance of specific electrochemical devices, such as fuel cells and metal–air batteries. To boost selectivity of metal nanoparticles, a novel methodology that harnesses the unique electrocatalytic properties of polyoxometalates (POM) to scavenge undesired intermediates of the ORR (such as HO2−) promoting selectivity is proposed. It involves the covalent functionalization of metal nanoparticle's surface with an electrochemically active capping layer containing a new sulfur-functionalized vanadium-based POM (AuNP@POM). To demonstrate this approach, preformed thiolate Au(111) nanoparticles with a relatively poor ORR selectivity are chosen. The dispersion of AuNP@POM on the surface of carbon nanofibers (CNF) enhances oxygen diffusion, and therefore the ORR activity. The resulting electrocatalyst (AuNP@POM/CNF) exhibits superior stability against impurities like methanol and a higher pH tolerance range compared to the standard commercial Pt/C. The work demonstrates for the first time, the use of a POM-based electrochemically active capping layer to switch on the selectivity of poorly selective gold nanoparticles, offering a promising avenue for the preparation of electrocatalyst materials with improved selectivity, performance, and stability for ORR-based devices.This work has received financial support from the Ministry of Science of Spain (RYC-2016-20258, CNS2023-145421, PID2021-127341OB-I00, TED2021-131451BC21 and PDC2022-133925-I00 for M.d.C.G.-L., IJC2020-044369-I for J.M.V.-F. and FPU20/01072 for L.V.-A.), the European Research Council (ERC) (Starting Grant (NANOCOMP-679124) and ZABCAT (966743) for M.d.C.G.-L.), the Xunta de Galicia (for Predoctoral Fellowship (ED481A-2020/155) for E.P.Q.-D. and Centro singular de investigación de Galicia accreditation 2019–2022, ED431G 2019/03), and the European Union (European Regional Development Fund─ERDF).S

Magnetic-driven Interleukin-4 internalization promotes magnetic nanoparticle morphology and size-dependent macrophage polarization

Macrophages are known to depict two major phenotypes: classically activated macrophages (M1), associated with high production of pro-inflammatory cytokines, and alternatively activated macrophages (M2), which present an anti-inflammatory function. A precise control over M1-M2 polarization is a promising strategy in therapeutics to modulate both tissue regeneration and tumor progression processes. However, this is not a simple task as macrophages behave differently depending on the microenvironment. In agreement with this, non-consistent data have been reported regarding macrophages response to magnetic iron oxide nanoparticles (MNPs). To investigate the impact of both tissue microenvironment and MNPs properties on the obtained macrophage responses, single-core (SC) and multi core (MC) citrate coated MNPs, are synthesized and, afterwards, loaded with a macrophage polarization trigger, IL-4. The developed MNPs are then tested in macrophages subjected to different stimuli. We demonstrate that macrophages treated with low concentrations of MNPs behave differently depending on the polarization stage independently of the concentration of iron. Moreover, we find out that MNPs size and morphology determines the effect of the IL-4 loaded MNPs on M1 macrophages, since IL-4 loaded SC MNPs favor the polarization of M1 macrophages towards M2 phenotype, while IL-4 loaded MC MNPs further stimulate the secretion of pro-inflammatory cytokinesThis work was supported by the Programa de Axudas de apoio á etapa predoutoral 2020 of Xunta de Galicia, by the European Commission under the BOW project (FETPROACT-EIC-05-2019, Grant 952183), CARTsol project (PLEC2022-009217 funded by MICINN/AEI /10.13039/501100011033 and NextGenerationEU/ PRTR) and partially supported by the Spanish Ministry of Science and Innovation (ref PID2020-112626RB-C21), Modalities «Research Challenges» and «Knowledge Generation» and the Regional Consellería de Innovación Program for the Grupos de Referencia Competitiva 2021 —GRC2021 project of Xunta de GaliciaS

Acuerdo del Consejo de Gobierno de 10 de junio de 2024 que aprobó la modificación del Acuerdo del Consejo de Gobierno de 28 de octubre de 2022, sobre el procedimiento de admisión y matrícula condicionada en los estudios de #máster universitario. Texto consolidado

Documento en Galego. Data de publicación no taboleiro electrónico da USC o 19/6/202

Nuevas estrategias de análisis en radiogenómica del cáncer de próstata

Aproximadamente el 50% de los pacientes con cáncer recibirán radioterapia como parte de su tratamiento. A pesar de que los avances tecnológicos en radioterapia permiten aplicar el tratamiento de forma cada vez más precisa en el tumor, parte del tejido sano será inevitablemente irradiado, lo que puede dar lugar al desarrollo de efectos adversos. Estos efectos impactarán negativamente en la calidad de vida del paciente. Se ha descrito que los factores genéticos desempeñan un papel muy importante en el desarrollo y severidad de los efectos adversos a la radioterapia. Así, el propósito de esta tesis es la identificación de marcadores genéticos asociados con el sangrado rectal, uno de los efectos adversos más relevantes en el tratamiento radioterápico de pacientes con cáncer de próstata.2025-01-2

Evaluating the performance of carbon-based adsorbents fabricated from renewable biomass precursors for post-combustion CO2 capture

The significant increase in atmospheric CO2 concentration originated mainly from fossil fuels combustion has encouraged the development and improvement of CO2 separation operations to reduce emissions and control climate change and global warming. Therefore, this work is focused on the separation of CO2 from N2 in flue gas streams under post-combustion conditions by developing low-cost adsorbents. Six carbons were fabricated from biomass resources (olive stones and almond shells) to assess their influence on CO2 adsorption capacity: One carbonized and two KOH-activated carbons with carbon/KOH ratio of 1:2 and 1:4 (w/w) for each precursor. The carbons were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), elemental analysis, nitrogen and carbon dioxide adsorption–desorption analysis, X-ray diffraction (XRD), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS) and point of zero charge determination. In addition, the equilibrium adsorption data of pure components for all adsorbents were measured at 0, 25 and 50 °C between 0 and 760 mmHg and CO2/N2 selectivity was determined. Activated carbons were found to have higher CO2 adsorption capacity but with a reduction in apparent selectivity. Dynamic binary adsorption simulations performed in a fixed-bed column demonstrated that the activated carbon produced from olive stones with a carbon/KOH ratio of 1:4 (w/w) can separate a mixture of 14 % CO2 and 86 % N2 at 25 and 50 °C with the highest selectivity, CO2 adsorption capacity, CO2 purity and N2 recovery factor. Reducing flow rate, the breakthrough time increased. Moreover, the breakthrough time was reduced by increasing the temperature from 25 to 50 °C owing to the exothermic nature of adsorption process.This work is part of I+D+i project Reference PID2021-122923NB-I00 financed by MCIN/AEI /10.13039/501100011033 / FEDER, UE. Authors would like to thank the use of RIAIDT-USC analytical facilities. Authors would also like to thank Dr. Carlos A. Pena and Dr. A. Gil for their helps in performing the kinetic experiments and determining the solid density of carbons, respectively.S

A consistent test of equality of distributions for Hilbert-valued random elements

Two independent random elements taking values in a separable Hilbert space are considered. The aim is to develop a test with bootstrap calibration to check whether they have the same distribution or not. A transformation of both random elements into a new separable Hilbert space is considered so that the equality of expectations of the transformed random elements is equivalent to the equality of distributions. Thus, a bootstrap test procedure to check the equality of means can be used in order to solve the original problem. It will be shown that both the asymptotic and bootstrap approaches proposed are asymptotically correct and consistent. The results can be applied, for example, in functional data analysis. In practice, the test can be solved with simple operations in the original space without applying the mentioned transformation, which is used only to guarantee the theoretical results. Empirical results and comparisons with related methods support and complement the theory.The research has been partially supported by Grants MTM2017-89632-P and PID2020-116587GB-I00 funded by MICIU/AEI/10.13039/501100011033 and the COST Action CA21163 from the European Cooperation in Science and Technology. The authors would like to express their gratitude to the referees and editors by their helpful comments and suggestions.S