The use of deep eutectic solvents (DESs) that act as all‐in‐one solvent–template–reactant systems offers an interesting green alternative to conventional syntheses in materials science. This Review ...aims to provide a comprehensive overview to emphasize the similarities and discrepancies between DES‐assisted and conventional syntheses and rationalize certain green features that are common for the three DES‐assisted syntheses described herein: one case of radical polymerization and two cases of polycondensations. For instance, DESs contain the precursor itself and some additional components that either provide certain functionality (e.g., drug delivery and controlled release, or electrical conductivity) to the resulting materials or direct their formation with a particular structure (e.g., hierarchical‐type). Moreover, DESs provide a reaction medium, so polymerizations are ultimately carried out in a solventless fashion. This means that DES‐assisted syntheses match green chemistry principles 2 and 5 because of the economy of reagents and solvents, whereas the functionality incorporated by the second component allows the need for any post‐synthesis derivatization to be minimized or even fully avoided (principle 8). DESs also provide new precursors that favor more efficient polymerization (principle 6) by decreasing the energy input required for reaction progress. Finally, the use of mild reaction conditions in combination with the compositional versatility of DESs, which allows low‐toxic components to be selected, is also of interest from the viewpoint of green chemistry because it opens up the way to design biocompatible and/or eco‐friendly synthetic methods (principle 3).
Chain reaction: Deep eutectic solvent (DES)‐assisted polymerizations, which exhibit greener features (reagent and solvent economy, mild reaction conditions, waste reduction, high reaction yields, etc.) than those of conventional ones, are described (see picture).
Cadmium (Cd) toxicity has been widely studied in different plant species; however, the mechanism involved in its toxicity as well as the cell response against the metal have not been well ...established. In this work, using pea (Pisum sativum) plants, we studied the effect of Cd on antioxidants, reactive oxygen species (ROS), and nitric oxide (NO) metabolism of leaves using different cellular, molecular, and biochemical approaches. The growth of pea plants with 50 μM CdCl₂ affected differentially the expression of superoxide dismutase (SOD) isozymes at both transcriptional and posttranscriptional levels, giving rise to a SOD activity reduction. The copper/zinc-SOD down-regulation was apparently due to the calcium (Ca) deficiency induced by the heavy metal. In these circumstances, the overproduction of the ROS hydrogen peroxide and superoxide could be observed in vivo by confocal laser microscopy, mainly associated with vascular tissue, epidermis, and mesophyll cells, and the production of superoxide radicals was prevented by exogenous Ca. On the other hand, the NO synthase-dependent NO production was strongly depressed by Cd, and treatment with Ca prevented this effect. Under these conditions, the pathogen-related proteins PrP4A and chitinase and the heat shock protein 71.2, were up-regulated, probably to protect cells against damages induced by Cd. The regulation of these proteins could be mediated by jasmonic acid and ethylene, whose contents increased by Cd treatment. A model is proposed for the cellular response to long-term Cd exposure consisting of cross talk between Ca, ROS, and NO.
•Mild neonatal resveratrol supplementation prevent lipid accumulation in skeletal muscle induced by a high-fat diet later in life.•Mild neonatal resveratrol supplementation enhanced muscular ...capacities for fat oxidation and mitochondria activity in adulthood.•Mild neonatal resveratrol supplementation increased fat oxidation capacities and a decreased capacity for lipogenesis in liver in adulthood.•SIRT1 and AMPK pathways being more active in skeletal muscle (and liver) of adult mice treated with resveratrol in early life.•Neonatal resveratrol supplementation could represent a multi-target-directed strategy to prevent obesity and metabolic disturbances related to ectopic fat accumulation in non-adipose tissues.
Metabolic programming by dietary chemicals consumed in early life stages is receiving increasing attention. We here studied long-term effects of mild resveratrol (RSV) supplementation during lactation on muscular and hepatic lipid metabolism in adulthood. Newborn male mice received RSV or vehicle from day 2–20 of age, were weaned onto a chow diet on day 21, and were assigned to either a high-fat diet (HFD) or a normal-fat diet on day 90 of age for 10 weeks. RSV-treated mice showed in adulthood protection against HFD-induced triacylglycerol accumulation in skeletal muscle, enhanced muscular capacities for fat oxidation and mitochondria activity, signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling in muscle, and increased fat oxidation capacities and a decreased capacity for lipogenesis in liver compared with controls. Thus, RSV supplementation in early postnatal life may help preventing later diet-related disorders linked to ectopic lipid accumulation in muscle and liver tissues.
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Peroxisomes are highly dynamic and metabolically active organelles that play an important role in cellular functions, including reactive oxygen species (ROS) metabolism. Peroxisomal dynamics, such as ...the proliferation, movement, and production of dynamic extensions called peroxules, have been associated with ROS in plant cells. However, the function and regulation of peroxules are largely unknown. Using confocal microscopy, we have shown that treatment of Arabidopsis leaves with the heavy metal cadmium produces time course-dependent changes in peroxisomal dynamics, starting with peroxule formation, followed by peroxisome proliferation, and finally returning to the normal morphology and number. These changes during Cd treatment were regulated by NADPH oxidase (C and F)-related ROS production. Peroxule formation is a general response to stimuli such as arsenic and is regulated by peroxin 11a (PEX11a), as Arabidopsis pex11a RNAi lines are unable to produce peroxules under stress conditions. The pex11a line showed higher levels of lipid peroxidation content and lower expression of genes involved in antioxidative defenses and signaling, suggesting that these extensions are involved in regulating ROS accumulation and ROS-dependent gene expression in response to stress. Our results demonstrate that PEX11a and peroxule formation play a key role in regulating stress perception and fast cell responses to environmental cues.
Nicotinamide riboside, an NAD
precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders ...related to NAD
decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.
Anionic carbosilane dendrons decorated with sulfonate functions and one thiol moiety at the focal point have been used to synthesize water‐soluble gold nanoparticles (AuNPs) through the direct ...reaction of dendrons, gold precursor, and reducing agent in water, and also through a place‐exchange reaction. These nanoparticles have been characterized by NMR spectroscopy, TEM, thermogravimetric analysis, X‐ray photoelectron spectroscopy (XPS), UV/Vis spectroscopy, elemental analysis, and zeta‐potential measurements. The interacting ability of the anionic sulfonate functions was investigated by EPR spectroscopy with copper(II) as a probe. Different structures and conformations of the AuNPs modulate the availability of sulfonate and thiol groups for complexation by copper(II). Toxicity assays of AuNPs showed that those produced through direct reaction were less toxic than those obtained by ligand exchange. Inhibition of HIV‐1 infection was higher in the case of dendronized AuNPs than in dendrons.
Capturing gold: Water‐soluble gold nanoparticles (AuNPs) have been isolated with pendant anionic sulfonate carbosilane dendrons. The antiviral properties of dendronized AuNPs are higher than that of the free dendrons (see figure).
Characterization of the tumor microenvironment through immunoprofiling has become an essential resource for the understanding of the complex immune cell interactions and the assessment of biomarkers ...for prognosis and prediction of immunotherapy response; however, these studies are often limited by tissue heterogeneity and sample size. The nanoString GeoMx
®
Digital Spatial Profiler (DSP) is a platform that allows high-plex profiling at the protein and RNA level, providing spatial and temporal assessment of tumors in frozen or formalin-fixed paraffin-embedded limited tissue sample. Recently, high-impact studies have shown the feasibility of using this technology to identify biomarkers in different settings, including predictive biomarkers for immunotherapy in different tumor types. These studies showed that compared to other multiplex and high-plex platforms, the DSP can interrogate a higher number of biomarkers with higher throughput; however, it does not provide single-cell resolution, including co-expression of biomarker or spatial information at the single-cell level. In this review, we will describe the technical overview of the platform, present current evidence of the advantages and limitations of the applications of this technology, and provide important considerations for the experimental design for translational immune-oncology research using this tissue-based high-plex profiling approach.
Nitric oxide (NO) and nitrosylated derivatives are produced in peroxisomes, but the impact of NO metabolism on organelle functions remains largely uncharacterised. Double and triple NO‐related ...mutants expressing cyan florescent protein (CFP)‐SKL (nox1 × px‐ck and nia1 nia2 × px‐ck) were generated to determine whether NO regulates peroxisomal dynamics in response to cadmium (Cd) stress using confocal microscopy. Peroxule production was compromised in the nia1 nia2 mutants, which had lower NO levels than the wild‐type plants. These findings show that NO is produced early in the response to Cd stress and was involved in peroxule production. Cd‐induced peroxisomal proliferation was analysed using electron microscopy and by the accumulation of the peroxisomal marker PEX14. Peroxisomal proliferation was inhibited in the nia1 nia2 mutants. However, the phenotype was recovered by exogenous NO treatment. The number of peroxisomes and oxidative metabolism were changed in the NO‐related mutant cells. Furthermore, the pattern of oxidative modification and S‐nitrosylation of the catalase (CAT) protein was changed in the NO‐related mutants in both the absence and presence of Cd stress. Peroxisome‐dependent signalling was also affected in the NO‐related mutants. Taken together, these results show that NO metabolism plays an important role in peroxisome functions and signalling.
A tight regulation of NO is required for optimal peroxisomal function and dependent signalling. NO is essential for peroxule production and peroxisome proliferation occurring in plant response to Cd. Additionally, peroxisome number and distribution as well as the oxidative metabolism of the organelle are altered by different levels of NO under control and stress conditions.
One of the drawbacks in improving the aroma properties of tomato (Solanum lycopersicum) fruit is the complexity of this organoleptic trait, with a great variety of volatiles contributing to determine ...specific quality features. It is well established that the oxylipins hexanal and (Z)-hex-3-enal, synthesized through the lipoxygenase pathway, are among the most important aroma compounds and impart in a correct proportion some of the unique fresh notes in tomato. Here, we confirm that all enzymes responsible for the synthesis of these C6 compounds are present and active in tomato fruit. Moreover, due to the low odor threshold of (Z)-hex-3-enal, small changes in the concentration of this compound could modify the properties of the tomato fruit aroma. To address this possibility, we have overexpressed the ω-3 fatty acid desaturases FAD3 and FAD7 that catalyze the conversion of linoleic acid (18:2) to linolenic acid (18:3), the precursor of hexenals and its derived alcohols. Transgenic OE-FAD tomato plants exhibit altered fatty acid composition, with an increase in the 18:3/18:2 ratio in leaves and fruits. These changes provoke a clear variation in the C6 content that results in a significant alteration of the (Z)-hex-3-enal/hexanal ratio that is particularly important in ripe OE-FAD3FAD7 fruits. In addition to this effect on tomato volatile profile, OE-FAD tomato plants are more tolerant to chilling. However, the different behaviors of OE-FAD plants underscore the existence of separate fatty acid fluxes to ensure plant survival under adverse conditions.
Cadmium treatment induces transient peroxisome proliferation in Arabidopsis leaves. To determine whether this process is regulated by pexophagy and to identify the mechanisms involved, we analysed ...time course‐dependent changes in ATG8, an autophagy marker, and the accumulation of peroxisomal marker PEX14a. After 3 hr of Cd exposure, the transcript levels of ATG8h, ATG8c, a, and i were slightly up‐regulated and then returned to normal. ATG8 protein levels also increased after 3 hr of Cd treatment, although an opposite pattern was observed in PEX14. Arabidopsis lines expressing GFP‐ATG8a and CFP‐SKL enabled us to demonstrate the presence of pexophagic processes in leaves. The Cd‐dependent induction of pexophagy was demonstrated by the accumulation of peroxisomes in autophagy gene (ATG)‐related Arabidopsis knockout mutants atg5 and atg7. We show that ATG8a colocalizes with catalase and NBR1 in the electron‐dense peroxisomal core, thus suggesting that NBR1 may be an autophagic receptor for peroxisomes, with catalase being possibly involved in targeting pexophagy. Protein carbonylation and peroxisomal redox state suggest that protein oxidation may trigger pexophagy. Cathepsine B, legumain, and caspase 6 may also be involved in the regulation of pexophagy. Our results suggest that pexophagy could be an important step in rapid cell responses to cadmium.
The molecular mechanisms governing pexophagy have been elusive. The data presented in this study show that pexophagy takes place in response to Cd toxicity to regulate peroxisomal populations and quality and is regulated by H2O2 and peroxisomal oxidation. NBR1 may be an autophagic receptor for peroxisome, and cathepsin B, legumain, and caspase 6 could be involved in the regulation of pexophagy.
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