Enhancing anticancer cytotoxicity through bimodal drug delivery from ultrasmall Zr MOF nanoparticles

Dual delivery of dichloroacetate and 5-fluorouracil from Zr MOFs into cancer cells is found to enhance in vitro cytotoxicity. Tuning particle size and, more significantly, surface chemistry, further improves cytotoxicity by promoting caveolae-mediated endocytosis and cytosolic cargo delivery

Application of zirconium MOFs in drug delivery and biomedicine

Nanoparticulate metal-organic frameworks (MOFs) have the requisite high storage capacities, tailorable structures, ease of functionalisation, and excellent biocompatibilities for application as nanoscale drug delivery devices (DDSs). Zirconium MOFs in particular combine optimal stability towards hydrolysis and postsynthetic modification with low toxicity, and so are particularly suited for biological applications. This review covers the use of Zr MOFs as DDSs with focus on the different physical properties that makes them attractive for use. The various methods for modifying the surfaces of Zr MOFs are described with pertinent examples of the resulting enhancements in aqueous stability, colloidal dispersion, and stimuli-responsive drug release. The in vitro and in vivo application of Zr MOFs for photodynamic therapy and drug delivery are discussed with respect to the structural features of the MOFs and their surface functionality, and perspectives on their future applications and analogous hafnium MOFs are given

Solvent and substituent effects on the thermolysis of antimalarial fluorophenyl substituted 1,2.4-trioxanes

The kinetics and mechanism of the thermal decomposition reaction of cis-6-(4-fluoropheny1)-5,6-[2-(4-fluorophenyl)-propylidene]-3, 3-tetramethylene-1,2,4-trioxacyclo-hexane (I) were investigated separately in n-hexane and in methanol solutions over the temperature and concentration ranges of 393.2-443.2 K and 2.7-54 × 10-5 M, respectively. The values of the activation parameters for both reactions were compared with the corresponding ones for the thermolysis of cis-6-(4-fluorophenyl-5,6-[2-(4- fluorophenyl)-3-hydroxypropylidene]-3,3-tetramethylene-1,2,4-trioxacyclohexane (II), investigated in the same solvents and temperature range. Substituent and solvent effects on the initial homolytic rupture of the O-O peroxydic bonds of those molecules were evaluated.Facultad de Ciencias Exacta

Solvent and substituent effects on the thermolysis of antimalarial fluorophenyl substituted 1,2.4-trioxanes

The kinetics and mechanism of the thermal decomposition reaction of cis-6-(4-fluoropheny1)-5,6-[2-(4-fluorophenyl)-propylidene]-3, 3-tetramethylene-1,2,4-trioxacyclo-hexane (I) were investigated separately in n-hexane and in methanol solutions over the temperature and concentration ranges of 393.2-443.2 K and 2.7-54 × 10-5 M, respectively. The values of the activation parameters for both reactions were compared with the corresponding ones for the thermolysis of cis-6-(4-fluorophenyl-5,6-[2-(4- fluorophenyl)-3-hydroxypropylidene]-3,3-tetramethylene-1,2,4-trioxacyclohexane (II), investigated in the same solvents and temperature range. Substituent and solvent effects on the initial homolytic rupture of the O-O peroxydic bonds of those molecules were evaluated.Facultad de Ciencias Exacta

Climate Change: Risky Business?

The recently released IPCC report states that climate change is unequivocal, unprecedented and anthropogenic in origin. Climate change is a three-pronged global externality with environmental, socio-economic and political consequences.. It may unleash ‘catastrophic’ losses in welfare if tipping points are crossed. Actions to avert catastrophic outcomes should arguably resemble insurance decisions rather than investment decisions. Early recommendations from the economics community on a climate policy ramp have been partially upended by stronger calls for action based, inter alia, on severe tail events. Efforts by the international community to respond to more urgent calls for action have so far failed to materialise. Future research on severe tail events, environmentally sound technologies and the establishment of more acceptable burden sharing agreements may improve the current grim prospects for effective and efficient climate action.El quinto informe del IPCC, recientemente publicado, afirma que el cambio climático es inequívoco, sin precedentes y antropogénico en origen. El cambio climático como externalidad global tiene consecuencias para el medio ambiente, la economía, la sociedad y la política. Dichas consecuencias podrían desencadenar pérdidas ‘catastróficas’ de bienestar si se sobrepasan determinados puntos críticos. Es posible argumentar que las acciones para evitar dichos resultados catastróficos deberían asemejarse a las decisiones relativas a la adquisición de seguros, que evitan las peores consecuencias de eventos catastróficos, más que a decisiones sobre inversiones. Las recomendaciones históricas de seguir una política de mitigación gradual han sido parcialmente desbancadas por llamadas más contundentes a la acción debido a la existencia de eventos extremos. Los esfuerzos de la comunidad internacional hasta la fecha han sido insuficientes para responder a las llamadas urgentes a la acción. La investigación de eventos extremos, el desarrollo de tecnologías respetuosas con el entorno y los acuerdos de reparto de carga aceptables para los distintos países, podrían favorecer una acción climática efectiva y eficiente

Design of affordable sustainable energy supply systems for residential buildings: A case study

The residential sector plays an important role to mitigate climate change due to its high energy consumption. Polygeneration systems are a suitable alternative enabling efficient use of natural resources with low environmental impact. However, their deployment depends, among other factors, on the economic cost and the legal restrictions. This work analyses the potential reduction of greenhouse gases emissions, expressed in CO2 -equivalent emissions (CO2eq), in residential buildings installing polygeneration systems and considering the current Spanish self-consumption regulation. This is achieved through a multiobjective optimization, applying a Mixed Integer Linear Programming model, considering economic, environmental and legal aspects. Obtained results provide interesting replicable lessons, and show the interest of collective installations, in which remarkable CO2eq emissions reductions, above 65% with respect to conventional systems, can be achieved at an affordable cost. Technologies such as photovoltaic, reversible heat pumps, biomass and thermal energy storage are competitive when properly integrated. Furthermore, the sale of renewable electricity to the grid under a net-billing scheme, with suitable electricity sale prices, is an appropriate approach, aligned with the European climate and energy policy. Nevertheless, the current Spanish self-consumption regulation is mostly appropriate for small-medium size residential buildings

Overlapping Mixtures of Gaussian Processes for the data association problem

In this work we introduce a mixture of GPs to address the data association problem, i.e. to label a group of observations according to the sources that generated them. Unlike several previously proposed GP mixtures, the novel mixture has the distinct characteristic of using no gating function to determine the association of samples and mixture components. Instead, all the GPs in the mixture are global and samples are clustered following "trajectories" across input space. We use a non-standard variational Bayesian algorithm to efficiently recover sample labels and learn the hyperparameters. We show how multi-object tracking problems can be disambiguated and also explore the characteristics of the model in traditional regression settings

Occurrence of pesticide residues in Spanish honey measured by QuEChERS method followed by liquid and gas chromatography–Tandem mass spectrometry

In the current study, the QuEChERS extraction method with slight modifications, followed by liquid and gas chromatography–tandem mass spectrometry, was applied for the determination of 399 pesticide residues in 91 raw honey samples from northeastern Spain. The quality control proce-dure established in Document No. SANTE/12682/2019 was successfully followed: the responses in reagent blank and blank honey samples were below 30% of the reporting limit (0.01 mg kg-1) for all analysed compounds, the correlation coefficients (R2) were higher than 0.99 in most calibration curves, the deviation of back-calculated concentration from the true concentration was below ±20% (using the standard of 50 µg L-1 concentration), and the recoveries of spiked samples on matrix were within the range of 70–120% for almost all analytes. Only chlorfenvinphos (2–7.8 ng/g) and coumaphos (8.8–37 ng/g) were detected in 13 samples, and neither were observed to exceed their maximum residue limits (MRLs). Dietary risk assessment for pesticide residues in honey above their lowest calibrated level (LCL) was performed, and two different age groups, adults and infants, were considered as populations at risk. The contribution of honey lay far below the acceptable daily intake (ADI) for both pesticide residues. Therefore, according to our results, honey is unlikely to pose concerns for consumer health in terms of its contribution to dietary long-term exposure. However, to maintain the level of compliance, pesticide residues in honey should be continuously monitored. © 2021 by the authors. Licensee MDPI, Basel, Switzerland