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Morphological characterization of nanoparticle assemblies and hybrid nanomaterials is critical in determining their structure-property relationships as well as in the development of structures with desired properties. Electron tomography has become a widely utilized technique for the three-dimensional characterization of nanoparticle assemblies. However, the extraction of quantitative morphological parameters from the reconstructed volume can be a complex and labor-intensive task. In this study, we aim to overcome this challenge by automating the volumetric segmentation process applied to three-dimensional reconstructions of nanoparticle assemblies. The key to enabling automated characterization is to assess the performance of different volumetric segmentation methods in accurately extracting predefined quantitative descriptors for morphological characterization. In our methodology, we compare the quantitative descriptors obtained through manual segmentation with those obtained through automated segmentation methods, to evaluate their accuracy and effectiveness. To show generality, our study focuses on the characterization of assemblies of CdSe/CdS quantum dots, gold nanospheres and CdSe/CdS encapsulated in polymeric micelles, and silica-coated gold nanorods decorated with both CdSe/CdS or PbS quantum dots. We use two unsupervised segmentation algorithms: the watershed transform and the spherical Hough transform. Our results demonstrate that the choice of automated segmentation method is crucial for accurately extracting the predefined quantitative descriptors. Specifically, the spherical Hough transform exhibits superior performance in accurately extracting quantitative descriptors, such as particle size and interparticle distance, thereby allowing for an objective, efficient, and reliable volumetric segmentation of complex nanoparticle assemblies.

Spinal cord injury (SCI) affects an estimated three million persons worldwide, with ∼180,000 new cases reported each year leading to severe motor and sensory functional impairments that affect personal and social behaviors. To date, no effective treatment has been made available to promote neurological recovery after SCI. Deficits in motor function is the most visible consequence of SCI; however, other secondary complications produce a significant impact on the welfare of patients with SCI. Spasticity is a neurological impairment that affects the control of muscle tone as a consequence of an insult, trauma, or injury to the central nervous system, such as SCI. The management of spasticity can be achieved through the combination of both nonpharmacological and pharmacological approaches. Baclofen is the most effective drug for spasticity treatment, and it can be administered both orally and intrathecally, depending on spasticity location and severity. Interestingly, recent data are revealing that baclofen can also play a role in neuroprotection after SCI. This new function of baclofen in the SCI scope is promising for the prospect of developing new pharmacological strategies to promote functional recovery in patients with SCI.

Until recently, the cyanobacterial phylum only included oxygenic photosynthesizer members. The discovery of Melainabacteria as a group of supposed non-photosynthetic cyanobacteria asked to revisit such scenario. From metagenomic data, we were able to identify sequences encoding putative ADP-glucose pyrophosphorylases (ADP-GlcPPase) from free-living and intestinal Melainabacteria. The respective genes were de novo synthesized and over-expressed in Escherichia coli. The purified recombinant proteins from both Melainabacteria species were active as ADP-GlcPPases, exhibiting Vmax values of 2.3 (free-living) and 7.1 U/mg (intestinal). The enzymes showed similar S0.5 values (∼0.3 mM) for ATP, while the one from the intestinal source exhibited a 6-fold higher affinity toward glucose-1P. Both recombinant ADP-GlcPPases were sensitive to glucose-6P activation (A0.5 ∼0.3 mM) and Pi and ADP inhibition (I0.5 between 0.2 and 3 mM). Interestingly, the enzymes from Melainabacteria were insensitive to 3-phosphoglycerate, which is the principal activator of ADP-GlcPPases from photosynthetic cyanobacteria. As far as we know, this is the first biochemical characterization of an active enzyme from Melainabacteria. This work contributes to a better understanding of the evolution of allosteric regulation in the ADP-GlcPPase family, which is critical for synthesizing the main reserve polysaccharide in prokaryotes (glycogen) and plants (starch). In addition, our results offer further information to discussions regarding the phylogenetic position of Melainabacteria.

BackgroundThere are clinically relevant sex differences in acute and chronic pain mechanisms, but we are only beginning to understand their mechanistic basis. Transcriptome analyses of rodent whole dorsal root ganglion (DRG) have revealed sex differences, mostly in immune cells. We examined the transcriptome and translatome of the mouse DRG with the goal of identifying sex differences.MethodsWe used Translating Ribosome Affinity Purification (TRAP) sequencing and behavioral pharmacology to test the hypothesis that nociceptor (Nav1.8 expressing neurons) translatomes would differ by sex.ResultsWe found 66 genes whose mRNA were sex-differentially bound to nociceptor ribosomes. Many of these genes have known neuronal functions but have not been explored in sex differences in pain. We focused on Ptgds, which was increased in female mice. The mRNA encodes the prostaglandin D2 (PGD2) synthesizing enzyme. We observed increased Ptgds protein and PGD2 in female mouse DRG. The Ptgds inhibitor AT-56 caused intense pain behaviors in male mice but was only effective at high doses in females. Conversely, female mice responded more robustly to another major prostaglandin, PGE2, than did male mice. Ptgds protein expression was also higher in female cortical neurons, suggesting DRG findings may be generalizable to other nervous system structures.ConclusionsNociceptor TRAP sequencing (TRAP-seq) reveals unexpected sex differences in one of the oldest known nociceptive signaling molecule families, the prostaglandins. Our results demonstrate that translatome analysis reveals physiologically relevant sex differences important for fundamental protective behaviors driven by nociceptors.

The production of volatile fatty acids (VFA) is gaining momentum due to their central role in the emerging carboxylate platform. Particularly, the production of the longest VFA (from butyrate to caproate) is desired due to their increased economic value and easier downstream processing. While the use of undefined microbial cultures is usually preferred with organic waste streams, the use of defined microbial co-culture processes could tackle some of their drawbacks such as poor control over the process outcome, which often leads to low selectivity for the desired products. However, the extensive experimentation needed to design a co-culture system hinders the use of this technology. In this work, a workflow based on the combined use of mathematical models and wet experimentation is proposed to accelerate the design of novel bioprocesses. In particular, a co-culture consisting of Pediococcus pentosaceus and Megaphaera cerevisiae is used to target the production of high-value odd- and even‑carbon VFA. An unstructured kinetic model was developed, calibrated and used to design experiments with the goal of increasing the selectivity for the desired VFA, which were experimentally validated. In the case of even‑carbon VFA, the experimental validation showed an increase of 38 % in caproate yield and, in the case of enhanced odd‑carbon VFA experiments, the yield of butyrate and caproate diminished by 62 % and 94 %, respectively, while propionate became one of the main end products and valerate yield value increased from 0.007 to 0.085 gvalearte per gconsumed sugar. The workflow followed in this work proved to be a sound tool for bioprocess design due to its capacity to explore and design new experiments in silico in a fast way and ability to quickly adapt to new scenarios This work was financially supported by the project BIOCHEM (ERA-IB-2 7th call, ERA-IB-16-056) funded by MINECO (PCIN 2016-102) and Academy of Finland (311738). A. Regueira would like to acknowledge the support of the Xunta de Galicia through a postdoctoral fellowship (ED481B-2021-012). A. Regueira, M. Carballa and M. Mauricio-Iglesias belong to the Galician Competitive Research Group ED431C-2021/37, co-funded by Xunta de Galicia and ERDF (EU) SI

The present work aimed at investigating Zn alterations as a response to an inflammatory process in an in vitro human retinal pigment epithelial (RPE) cell model mimicking aging process. Cells were subjected to acute inflammatory stress with and without Zn supplementation and the effects of such exposure were evaluated by studying alterations at the transcriptome level and in the Zn concentration and its isotopic composition using single-collector and multi-collector ICP-mass spectrometry, respectively. The in vitro RPE model strongly responded to pro-inflammatory events (caused using 100 U/mL Interleukin-1α) at the RNA level by inducing immune and cytokine responses, while Zn supplementation (100 µM Zn) partially attenuated the aforementioned inflammatory effects. Interestingly, the Zn isotope ratios were correlated with the transcriptome, as inflammation was demonstrated to lead to a lighter Zn isotopic composition. This change in the isotopic composition of Zn signaling inflammation, which could also be avoided by short-term zinc supplementation, is probably indicating the modulation of the cellular immune function via cytokine signaling., This work was financially supported through project PID2019- 107838RB-I00/Agencia Estatal de Investigaci´on (AEI)/10.13039/ 501100011033) in Spain. M.A. acknowledges the University of Oviedo for the Ph.D. grant ref. PAPI-21-PF-05. F.V acknowledges the Flemish Research Foundation (FWO) for providing the funding for the acquisition of the MC-ICP-MS instrumentation (ZW15-02 – G0H6216N). M.C.R. thanks FWO for her senior postdoctoral grant.

Diphenylalanine is an amyloidogenic building block that can form a versatile array of supramolecular materials. Its shortcomings, however, include the uncontrolled hierarchical assembly into microtubes of heterogeneous size distribution and well-known cytotoxicity. This study rationalized heterochirality as a successful strategy to address both of these pitfalls and it provided an unprotected heterochiral dipeptide that self-organized into a homogeneous and optically clear hydrogel with excellent ability to sustain fibroblast cell proliferation and viability. Substitution of one l-amino acid with its d-enantiomer preserved the ability of the dipeptide to self-organize into nanotubes, as shown by single-crystal XRD analysis, whereby the pattern of electrostatic and hydrogen bonding interactions of the backbone was unaltered. The effect of heterochirality was manifested in subtle changes in the positioning of the aromatic side chains, which resulted in weaker intermolecular interactions between nanotubes. As a result, d-Phe-l-Phe self-organized into homogeneous nanofibrils with a diameter of 4 nm, corresponding to two layers of peptides around a water channel, and yielded a transparent hydrogel. In contrast with homochiral Phe-Phe stereoisomer, it formed stable hydrogels thermoreversibly. d-Phe-l-Phe displayed no amyloid toxicity in cell cultures with fibroblast cells proliferating in high numbers and viability on this biomaterial, marking it as a preferred substrate over tissue-culture plastic. Halogenation also enabled the tailoring of d-Phe-l-Phe self-organization. Fluorination allowed analogous supramolecular packing as confirmed by XRD, thus nanotube formation, and gave intermediate levels of bundling. In contrast, iodination was the most effective strategy to augment the stability of the resulting hydrogel, although at the expense of optical transparency and biocompatibility. Interestingly, iodine presence hindered the supramolecular packing into nanotubes, resulting instead into amphipathic layers of stacked peptides without the occurrence of halogen bonding. By unravelling fine details to control these materials at the meso- and macro-scale, this study significantly advanced our understanding of these systems.

Aim To determine in the adult population the crude and the sex- and age-adjusted prevalence rates of hypertriglyceridaemia (HTG) and to assess its association with cardiovascular risk factors, chronic kidney disease, cardiovascular and cardiometabolic diseases. Methods Cross-sectional observational study conducted in Primary Care, with 6,588 adult study subjects, randomly selected on base-population. Patients had HTG if the triglyceride level was ≥150 mg/dL (≥1.7 mmol/L), or were on lipid-lowering therapy to lower triglyceride. Associations were assessed by univariate and multivariate analysis, and crude and sex- and age-adjusted prevalence rates were determined. Results The arithmetic and geometric means of triglyceride levels were respectively 120.5 and 104.2 mg/dL in global population, 135.7 and 116.0 mg/dL in men, and 108.6 and 95.7 mg/dL in women. The crude HTG prevalence rates were 29.6% in global population, 36.9% in men and 23.8% in women. The sex- and age-adjusted HTG prevalence rates were 27.0% in global population, 34.6% in men and 21.4% in women. The independent variables that were most associated with HTG were hypercholesterolemia (OR: 4.6), low HDL-C (OR: 4.1), hepatic steatosis (OR: 2.8), diabetes (OR: 2.0), and obesity. (OR: 1.9). Conclusions The means of triglyceride levels and HTG prevalence rates are intermediate between those of other national and international studies. A fifth of the female adult population and more than a third of the male population had HTG. The independent factors associated with HTG were hypercholesterolemia and low HDL-C, and the cardiometabolic variables diabetes, hepatic steatosis and obesity.

Porphyrins are differentiated π-conjugated compounds with unique photochemical and redox properties. The tetrapyrrole macrocycle core of porphyrins is extremely favorable for the complexation of metal ions, resulting in hybrid metal–organic molecules with good photocatalytic properties. Over the years, porphyrins have been extensively tested as photocatalysts in advanced oxidative processes for the degradation of various organic contaminants in water. Recently, the use of porphyrins supported on solid materials is viewed as one of the most effective strategies to obtain photocatalytic systems with superior properties and applicability. Supported porphyrins can form highly organized hybrid materials, with high electron conductivity and great photoreaction properties. Here we review concepts, development, and application of supported porphyrins/metalloporphyrins. The first sections present an overview of the water contamination problem, the fundamentals of the photocatalytic treatment of water, and the main properties of porphyrins. The following sections focus on the application of supported porphyrins in the photodegradation of common organic contaminants in water. The last two sections discuss the main mechanisms and limitations.

Awareness of the adverse effects of exposure to pollutant mixtures, possibly much more severe than individual chemicals, has drawn attention towards the necessity of using multi-residue methods to obtain the most possible comprehensive information on exposome. Among the different biological matrices used for exposure assessment, hair enables to detect the largest number of chemicals, including many classes such as persistent pollutants, hydrophilic metabolites and metals. Most biomonitoring studies are however focused on a limited number of pollutants and only give a partial information on exposure. Combining several multi-residue methods, the present study aimed at assessing the exposure of a population to an extensive variety of chemicals by hair analysis. One hair sample was collected from each participant (55 children and 134 adults). Samples were analysed with three different multi-residue methods, targeting, respectively, 152 organic pollutants (pesticides, PCBs, bisphenols, PBDEs), 62 polycyclic aromatic hydrocarbons (PAHs) and metabolites, nicotine and cotinine and 36 metals. From 33 to 70 organic chemicals were detected in each child’s hair sample, and from 34 up to 74 in adults. From 7 to 26 PAH were detected per child, and 7 to 21 in adults. Twenty-three to 27 metals were detected per child and 21 to 28 per adult. The highest median concentration were observed for zinc (143 μg /mg in children; 164 μg /mg in adults), bisphenol A (95.9 pg/mg in children; 64.7 pg/mg in adults) and nicotine (66.4 pg/mg in children; 51.9 pg/mg in adults). The present study provides the most comprehensive exposure assessment ever and highlights the simultaneous exposure to multiple classes of pollutants in the general population. The results support the use of multi-residue methods for future studies on exposure-associated effects, to document exposome and better consider the effect of chemical mixtures.

Among iron oxide phases, magnetite Fe3O4 is often the preferred one for nanotechnological and biomedical applications because of its high saturation magnetization and low toxicity. Although there are several synthetic routes that attempt to reach magnetite nanoparticles NPs , they are usually referred as IONPs iron oxide NPs due to the great difficulty in obtaining the monophasic and stoichiometric Fe3O4 phase. Added to this problem is the common increase of size shape polydispersity when larger NPs D gt; 20 nm are synthesized. An unequivocal correlation between a nanomaterial and its properties can only be achieved by the production of highly homogeneous systems, which, in turn, is only possible by the continuous improvement of synthesis methods. There is no doubt that solving the compositional heterogeneity of IONPs while keeping them monodisperse remains a challenge for synthetic chemistry. Herein, we present a methodical optimization of the iron oleate decomposition method to obtain Fe3O4 single nanocrystals without any trace of secondary phases and with no need of postsynthetic treatment. The average dimension of the NPs, ranging from 20 to 40 nm, has been tailored by adjusting the total volume and the boiling point of the reaction mixture. Mössbauer spectroscopy and DC magnetometry have revealed that the NPs present a perfectly stoichiometric Fe3O4 phase. The high saturation magnetization 93 2 A m2 kg at RT and the extremely sharp Verwey transition at around 120 K shown by these NPs have no precedent. Moreover, the synthesis method has been refined to obtain NPs with octahedral morphology and suitable magnetic anisotropy, which significantly improves the magnetic hyperthemia performance. The heating power of properly PEGylated nano octahedrons has been investigated by AC magnetometry, confirming that the NPs present negligible dipolar interactions, which leads to an outstanding magnetothermal efficiency that does not change when the NPs are dispersed in environments with high viscosity and ionic strength. Additionally, the heat production of the NPs within physiological media has been directly measured by calorimetry under clinically safe conditions, reasserting the excellent adequacy of the system for hyperthermia therapies. To the best of our knowledge, this is the first time that such bulklike magnetite NPs with minimal size shape polydispersity, minor agglomeration, and exceptional heating power are chemically synthesized

Current pharmacological therapies for treating obesity are of limited efficacy. Genetic ablation or loss of function of AMP-activated protein kinase alpha 1 (AMPKα1) in steroidogenic factor 1 (SF1) neurons of the ventromedial nucleus of the hypothalamus (VMH) induces feeding-independent resistance to obesity due to sympathetic activation of brown adipose tissue (BAT) thermogenesis. Here, we show that body weight of obese mice can be reduced by intravenous injection of small extracellular vesicles (sEVs) delivering a plasmid encoding an AMPKα1 dominant negative mutant (AMPKα1-DN) targeted to VMH-SF1 neurons. The beneficial effect of SF1-AMPKα1-DN-loaded sEVs is feeding-independent and involves sympathetic nerve activation and increased UCP1-dependent thermogenesis in BAT. Our results underscore the potential of sEVs to specifically target AMPK in hypothalamic neurons and introduce a broader strategy to manipulate body weight and reduce obesity.

The design of new strategies to increase the effectiveness of the antibacterial treatments is a main goal in public health. So, the aim of the study was to achieve a local antibacterial directed therapy as novel alternative allowing both, the delivery of the drug at the target, while minimizing undesirable side effects, thus anticipating an enhanced effectiveness. Hence, we have developed an innovative nanoformulation composed by biomimetic magnetic nanoparticles functionalized with the antimicrobial peptide AS-48 and its potential against Gram-positive and Gram-negative bacteria, either by itself or combined with magnetic hyperthermia has been investigated. Besides, the physical properties, binding efficiency, stability and mechanism of action of this nanoassembly are analyzed. Remarkably, the nanoassembly has a strong bactericidal effect on Gram-positive bacteria, but surprisingly also on E. coli and, finally, when combined with magnetic hyperthermia, on P. aeruginosa and K. pneumoniae. The results obtained represent a breakthrough since it allows a local treatment of infections, reducing and concentrating the dose of antimicrobial compounds, avoiding secondary effects, including the resistance generation and particularly because the combination with magnetic hyperthermia helps sensitizing resistant bacteria to the bactericidal effect of AS-48. Thus, this new formulation should be considered a promising tool in the antibacterial fight.

Investigating the relaxation of water 1H nuclei induced by paramagnetic Mn(II) complexes is important to understand the mechanisms that control the efficiency of contrast agents used in diagnostic magnetic resonance imaging (MRI). Herein, a series of potentially hexadentate triazacyclononane (TACN) derivatives containing different pendant arms were designed to explore the relaxation of the electron spin in the corresponding Mn(II) complexes by using a combination of 1H NMR relaxometry and theoretical calculations. These ligands include 1,4,7-triazacyclononane-1,4,7-triacetic acid (H3NOTA) and three derivatives in which an acetate group is replaced by sulfonamide (H3NO2ASAm), amide (H2NO2AM), or pyridyl (H2NO2APy) pendants. The analogue of H3NOTA containing three propionate pendant arms (H3NOTPrA) was also investigated. The X-ray structure of the derivative containing two acetate groups and a sulfonamide pendant arm [Mn(NO2ASAm)]− evidenced six-coordination of the ligand to the metal ion, with the coordination polyhedron being close to a trigonal prism. The relaxivities of all complexes at 20 MHz and 25 °C (1.1–1.3 mM–1 s–1) are typical of systems that lack water molecules coordinated to the metal ion. The nuclear magnetic relaxation profiles evidence significant differences in the relaxivities of the complexes at low fields (, The nature of the donor atoms and particularly the coordination polyhedron affect dramatically the zero field splitting in six-coordinate Mn(II) complexes, which has a strong impact in the relaxivities measured at low magnetic fields.

Allostery is a central mechanism for the regulation of multi-enzyme complexes. The mechanistic basis that drives allosteric regulation is poorly understood but harbors key information for enzyme engineering. In the present study, we focus on the tryptophan synthase complex that is composed of TrpA and TrpB subunits, which allosterically activate each other. Specifically, we develop a rational approach for identifying key amino acid residues of TrpB distal from the active site. Those residues are predicted to be crucial for shifting the inefficient conformational ensemble of the isolated TrpB to a productive ensemble through intra-subunit allosteric effects. The experimental validation of the conformationally driven TrpB design demonstrates its superior stand-alone activity in the absence of TrpA, comparable to those enhancements obtained after multiple rounds of experimental laboratory evolution. Our work evidences that the current challenge of distal active site prediction for enhanced function in computational enzyme design has become within reach We thank the Generalitat de Catalunya for the emerging group CompBioLab (2017 SGR-1707) and Spanish MINECO for project PGC2018-102192-B-I00. M.A.M.S. was supported by the Spanish MINECO for a PhD fellowship (BES-2015- 074964) and the National Research Foundation of Korea (NRF) under the Brain Pool Program (NRF2021H1D3A2A02038434), J. I. F. was supported by the European Community for Marie Curie fellowship (H2020- MSCA-IF-2016-753045) and Juan de la Cierva-Incorporación fellowship (IJCI-2017-34129). S.O. is grateful to the funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC-2015-StG-679001) and the Human Frontier Science Program (HFSP) for project grant RGP0054/2020

The synthesis of six dimeric spiroketals bearing an estradiol half fused to the 5α- or 5β-epimers of androstane, cholestane, and spirostane nuclei is described. The synthetic procedure comprises the Sonogashira­ coupling of different steroid alkynes with 2-iodoestradiol 17-monoacetate, followed by Pd-catalyzed spiroketalization. The structural characterization of the obtained hybrid dimers was performed using a combination of 1D and 2D NMR techniques, and was assisted by DFT calculations. Single crystal X-ray diffraction of one of the obtained compounds confirmed the proposed structures.

The synthesis of a new family of pentacoordinated spiro[4.4]phosphoranes stabilized by the ortho-benzamide bidentate ligand (oBA, -C6H4-2-C(O)NH-) through reaction of Cα,C ortho -dilithiated phosphazenes with oxiranes is reported. Mixtures of epimers that differ in configuration at the phosphorus atom were obtained with moderate to high yields and diastereoselectivities. C3-Disubstituted derivatives could be separated, which provided access to enantiopure products arising from the reaction with (R)-2-phenyloxirane. Stereomutation was observed by heating the spirophosphoranes at 100 °C. Directed ortho-lithiation of spirophoshoranes followed by electrophilic quench reactions including carbon-based and heteroatom-based electrophiles afforded derivatives functionalized in a remote position with respect to the phosphorus atom. Benzoic acid catalyzed hydrolysis of spirophosphoranes furnished ortho-(γ-hydroxyalkylphosphoryl)benzamides by cleavage of the P–O and P–N bonds with retention of the phosphorus configuration. In contrast, alkaline hydrolysis led to the formation of γ-hydroxyphosphinic acids and benzamide.

Background and purpose Translational controls pervade neurobiology. Nociceptors play an integral role in the detection and propagation of pain signals. Nociceptors can undergo persistent changes in their intrinsic excitability. Pharmacological disruption of nascent protein synthesis diminishes acute and chronic forms of pain-associated behaviours. However, the targets of translational controls that facilitate plasticity in nociceptors are unclear. Experimental approach We used ribosome profiling to probe the translational landscape in dorsal root ganglion (DRG) neurons from male Swiss-Webster mice, after treatment with nerve growth factor and IL-6. Expression dynamics of c-Fos were followed with immunoblotting and immunohistochemistry. The involvement of ribosomal protein S6 kinase 1 (S6K1), a downstream component of mTOR signalling, in the control of c-Fos levels was assessed with low MW inhibitors of S6K1 (DG2) or c-Fos (T-5224), studying their effects on nociceptor activity in vitro using multielectrode arrays (MEAs) and pain behaviour in vivo in Swiss-Webster mice using the hyperalgesic priming model. Key results c-Fos was expressed in sensory neurons. Inflammatory mediators that promote pain in both humans and rodents promote c-Fos translation. The mTOR effector S6K1 is essential for c-Fos biosynthesis. Inhibition of S6K1 or c-Fos with low MW compounds diminished mechanical and thermal hypersensitivity in response to inflammatory cues. Additionally, both inhibitors reduced evoked nociceptor activity. Conclusion and implications Our data show a novel role of S6K1 in modulating the rapid response to inflammatory mediators, with c-Fos being one key downstream target. Targeting the S6 kinase pathway or c-Fos is an exciting new avenue for pain-modulating compounds.

Domingo A Pascual-Figal,1– 3 Aychel E Roura-Piloto,4 Encarnación Moral-Escudero,4 Enrique Bernal,5 Helena Albendín-Iglesias,4 M Teresa Pérez-Martínez,1 Jose Antonio Noguera-Velasco,6 Iria Cebreiros-López,6 Álvaro Hernández-Vicente,1 David Vázquez-Andrés,1 Carmen Sánchez-Pérez,2 Amjad Khan,7 Fátima Sánchez-Cabo,3 Elisa García-Vázquez4 On behalf of the COL-COVID Investigators1Cardiology Department, Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain; 2Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, (CIBERCV), Madrid, Spain; 3Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; 4Infectious Diseases and Internal Medicine Department, Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain; 5Infectious Diseases and Internal Medicine Department, Hospital Universitario Reina Sofia, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain; 6Clinical Biochemistry Department, Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain; 7Department of Chemistry, University of Oxford, Oxford, UKCorrespondence: Domingo A Pascual-FigalLAIB, Despacho 2.52, Av. Buenavista s/n, Murcia, 30120, SpainTel +34-868888163Email dpascual@um.esBackground: Colchicine has been proposed as a potential therapy in coronavirus disease 2019 (COVID-19) due to their anti-inflammatory actions.Methods: The COL-COVID study was a prospective, randomized, controlled and open-label clinical trial that compared colchicine added to standard treatment vs standard treatment in hospitalized COVID-19 patients that do not need mechanical ventilatory support. Colchicine was initiated within the first 48 hours of admission at a 1.5 mg loading dose, followed by 0.5 mg b.i.d. for one week and 0.5 mg per day for 28 days. The study endpoints were clinical status (7-points WHO ordinal scale) and inflammatory biomarkers (IL-6 and CRP).Results: A total of 103 patients (51± 12 years, 52% male) were randomly allocated to colchicine arm (n=52) and control arm (n=51). At day 28, all patients in the colchicine group were alive and discharged, whereas in the control group, two patients died in-hospital and one patient remained hospitalized. Clinical improvement in terms of changes on WHO scale at day 14 and 28 and time to 1-point clinical improvement did not differ between the two groups. Clinical deterioration (increase of at least 1-point in WHO scale) was observed in a higher proportion of cases in colchicine group (13.8%) vs control group (5.8%) (p=0.303); after adjustment by baseline risk factors and concomitant therapies, colchicine therapy was associated with a lower risk of clinical deterioration (p=0.030). Inflammatory biomarkers CRP and IL-6 concentrations course did not differ between the two arms.Conclusion: In hospitalized COVID-19 patients, colchicine treatment neither improved the clinical status, nor the inflammatory response, over the standard treatment. Nevertheless, a preventive effect for further clinical deterioration might be possible.Trial Registration: NCT04350320.Keywords: colchicine, COVID-19, inflammation

Penicillium digitatum is a widespread pathogen responsible for the postharvest decay of citrus, one of the most economically important crops worldwide. Currently, chemical fungicides are still the main strategy to control the green mould disease caused by the fungus. However, the increasing selection and proliferation of fungicide-resistant strains require more efforts to explore new alternatives acting via new or unexplored mechanisms for postharvest disease management. To date, several non-chemical compounds have been investigated for the control of fungal pathogens. In this scenario, understanding the molecular determinants underlying P. digitatum’s response to biological and chemical antifungals may help in the development of safer and more effective non-chemical control methods. In this work, a proteomic approach based on isobaric labelling and a nanoLC tandem mass spectrometry approach was used to investigate molecular changes associated with P. digitatum’s response to treatments with α-sarcin and beetin 27 (BE27), two proteins endowed with antifungal activity. The outcomes of treatments with these biological agents were then compared with those triggered by the commonly used chemical fungicide thiabendazole (TBZ). Our results showed that differentially expressed proteins mainly include cell wall-degrading enzymes, proteins involved in stress response, antioxidant and detoxification mechanisms and metabolic processes such as thiamine biosynthesis. Interestingly, specific modulations in response to protein toxins treatments were observed for a subset of proteins. Deciphering the inhibitory mechanisms of biofungicides and chemical compounds, together with understanding their effects on the fungal physiology, will provide a new direction for improving the efficacy of novel antifungal formulations and developing new control strategies.

In 2011, a new type of hyper-cross-linked polymers (HCPs) arose, known as knitting aromatic polymers (KAPs), characterized by their extraordinary chemical and thermal stability, by their porosity p...

Imazethapyr is an herbicide that is used in a variety of crops worldwide, including soybean and corn. The aim of the present study was to evaluate the biomarkers responses of adult Leptodactylus latinasus exposed to the formulation Pivot® H (10.59% imazethapyr) in the laboratory at concentrations and under conditions that simulate two potential field exposure scenarios: an immersion in field runoff (Scenario 1: 10 mg/L) and a direct exposure to the droplets emitted by spray noozles (Scenario 2: 1000 mg/L). In both scenarios, the experimental procedure involved completely immersing the frogs over a period of 15 s. Different endpoints were evaluated at several ecotoxicological levels 48 and 96 h after the herbicide exposure. These included individual (biometric indices and behavior alterations), histological (liver pigments and lesions), biochemical (catalase, glutathione system and cholinesterase activities) and genotoxic effects (micronuclei induction and nuclear abnormalities). Forty-eight hours after imazethapyr exposure, frogs submitted to Scenario 1 presented an inhibition of liver glutathione-S-transferase activity, whereas histological alterations and increased hepatic cholinesterase levels were observed in frogs exposed under Scenario 2. Ninety-six hours after exposure to the imazethapyr formulation, frogs from the Scenario 1 treatment presented a decrease in liver melanin and hemosiderin, increased hepatic catalase activity and micronuclei induction. For their part, frogs exposed to Scenario 2 presented a decrease in the hepatosomatic index, an increase in liver alterations, melanin reduction and micronuclei induction. The multivariate analysis enables correlations to be made between biomarkers of different organizational level in exposed anurans. Our result indicates that real exposure to imazethapyr formulations under field conditions may pose a risk to Leptodactylus latinasus populations living in the agroecosystems., Facultad de Ciencias Naturales y Museo

This study documents the first validation of the suitability of the most common parameters and protocols used in marine ecophysiology to characterise photosynthesis by means of chlorophyll a fluorescence tools. We demonstrate that the effective yield of PSII (ΔF/Fm′) is significantly underestimated when using short inductions times (≤1 min) following the rapid light curve protocol (RLC). The consequent electron transport rates (ETR) underestimations are species-specific and highly variable with irradiance and the photoacclimatory condition of the sample. Our analysis also questions the use of relative descriptors (relETR), as they not only overestimate photosynthesis, but overlook one of the fundamental components of the photosynthetic response: light absorption regulation. Absorptance determinations were fundamental to characterise the ETR response of low-pigmented seagrass leaves, and also uncovered relevant differences between two coral species and the accclimatory response of a cultured dinoflagellate to temperature. ETR and oxygen evolution determinations showed close correlations for all organisms tested with the expected slope of 4 e– per O2 molecule evolved, when correct photosynthesis inductions and light absorption determinations were applied. However, ETR curves cannot be equated to conventional photosynthetic response to irradiance (P vs E) curves, and caution is needed when using ETR to characterise photosynthesis rates above photosynthesis saturation (Ek). This validation strongly supports the utility of fluorescence tools, underlining the need to correct two decades of propagation of erroneous concepts, protocols and parameters in marine eco-physiology. We aim also to emphasise the importance of optical descriptions for understanding photosynthesis, and for interpreting fluorescence measurements. In combination with conventional gross photosynthesis (GPS) approaches, optical characterisations open an extraordinary opportunity to determine two central parameters of photosynthesis performance: the quantum yield (φmax) of the process and its minimum quantum requirements (1/φmax). The combination of both approaches potentiates the possibilities of chlorophyll a fluorescence tools to characterise marine photosynthesis biodiversity.

Intraoral fixed appliances remain in the potentially corrosive environment of the mouth for an average of two years. Over time, corrosion causes the release of metal ions, such as nickel and chromium. These metals can become allergenic and cytotoxic, causing different conditions in the human body. The aim of this study therefore is to carry out a systematic review of the available scientific evidence on the accumulation of metal ions, and the genotoxic and cytotoxic effects in oral mucosa cells deriving from short- and long-term exposure to them. The systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome (quantification of metal ion deposits and assessment of their genotoxic and/or cytotoxic effects) and secondary outcome (complementary analysis of cytotoxic and genotoxic effects) were examined. The Cochrane Collaboration tool and Toxicological data Reliability Assessment Tool (ToxRTool) were used for quality assessment. Once the search was performed, a total of seven articles met the inclusion criteria and were included in this study. Two main techniques were used to assess genotoxic effects: alkaline comet assay (6/7) and micronucleus method (1/7). Cytotoxicity was evaluated (4/7) using the trypan blue dye test. Accumulations of nickel (7/7), chromium (5/7), and other metals (zinc, cobalt, iron, manganese, molybdenum, titanium) were also quantified. The results allowed us to conclude that release of metal ions and acute cell and DNA damage in oral mucosa cells takes place in the early stages of treatment. However, more long-term studies are needed to evaluate chronic exposure to metals and DNA damage, as well as cellular capacity to recover DNA integrity.

We describe the synthesis of 1,4-disubstituted 5-triazenyl-1,2,3-triazoles bearing diethoxy arylphosphoryl moieties via a domino reaction between ortho-azidophosphonates and premade copper(I) alkynides involving chelation-assisted [3+2] cycloaddition followed by interception of the copper(I) triazolide generated by the azide. A resulting dicopper(I) triazoletriazenide complex has been characterized through X-ray diffraction.

p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis., p53 regulates signalling pathways involved in metabolic homeostasis. Here the authors show that O-GlcNAcylation of p53 in the liver plays a key role in the physiological regulation of glucose homeostasis, potentially via controlling the expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase.

Background and Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). Methods and Results We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein > 88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia < 1,000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. Conclusion Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.

Centro de Investigación en Sanidad Animal (CISA), Research on immunotherapeutic agents has become a focus for the treatment of fish diseases. The ability of algae to produce secondary metabolites of potential interest as immunotherapeutics has been documented. The present research intended to assess antiviral and antibacterial activities of macro- and microalgae extracts against viral and bacterial pathogens and explore their immunomodulatory potential using zebrafish (Danio rerio) larvae as a model organism. The cytotoxicity and antiviral activity of eight methanolic and ethanolic extracts from two macroalgae (Fucus vesiculosus, Ulva rigida) and two microalgae (Nannochloropsis gaditana, Chlorella sp.) were analyzed in established fish cell lines. Six extracts were selected to evaluate antibacterial activity by disk diffusion and growth inhibition assays. The three most promising extracts were characterized in terms of fatty acid composition, incorporated at 1% into a plant-based diet, and evaluated their effect on zebrafish immune response and intestinal morphology in a short-term feeding trial. All extracts exhibited in vitro antiviral activity against viral hemorrhagic septicemia and/or infectious pancreatic necrosis viruses. Methanolic extracts from F. vesiculosus and U. rigida were richer in saturated fatty acids and exhibited in vitro antibacterial action against several bacteria. Most promising results were obtained in vivo with F. vesiculosus methanol extract, which exerted an anti-inflammatory action when incorporated alone into diets and induced pro-inflammatory cytokine expression, when combined with the other extracts. Moreover, dietary inclusion of the extracts improved intestinal morphology. In summary, the results obtained in this study support the potential of algae as natural sources of bioactive compounds for the aquaculture industry., M. Monteiro, A. S. Lavrador, R. A. Santos, and F. Rangel were supported by grants SFRH/BD/114995/2016, ZEBRALGRE_BM_2019-003, SFRH/BD/131069/2017, and SFRH/BD/138375/2018, respectively, from FCT — Foundation for Science and Technology, under the POCI program. A. Couto C. Serra and P. Enes have a scientific employment contract supported by national funds through FCT. E. da Costa and M. R. Domingues are financially supported by FCT/MCTES (Portugal) through CESAM (UIDB/50017/2020 + UIDP/50017/2020), QOPNA (FCT UID/QUI/00062/2019), LAQV/REQUIMTE (UIDB/50006/2020), and RNEM (LISBOA-01–0145-FEDER-402–022125). This research was partially supported by the Strategic Funding to UID/Multi/04423/2019 (POCI-01–0145-FEDER-007621) through national funds provided by FCT under the project PTDC/CVT-WEL/5207/2014.

Effects of raw material and chemical composition were considered relative to the intrinsic properties and the rheological behavior of nanofibrillated cellulose aqueous suspensions (CNFs). Atomic force microscopy, Fourier-transform infrared spectroscopy, surface chemistry analysis, thermal gravimetrical analysis, and zeta-potential were used to study the morphology, chemical composition, charge density, as well as thermal and colloidal stability of the different CNFs. Regarding the rheological properties of the samples, steady-state and oscillation studies of the CNF aqueous suspensions obtained from wood and soybean hulls were performed. An interesting correlation was found between the rheological behavior of CNF suspensions and their intrinsic properties. Soybean CNF presented lower viscosities than wood samples, which could be related to their morphology and charge density. Additionally, unbleached soybean CNF (sb-LCNF) showed yield stress compared with the other samples, which could be attributed to the presence of pectin. Furthermore, the different chemical compositions between the samples affected their thermal properties, as well as on their crystallinity.

The wide range of optical and magnetic properties of lanthanide(III) ions is associated with their intricate electronic structures which, in contrast to lighter elements, is characterized by strong relativistic effects and spin-orbit coupling. Nevertheless, computational methods are now capable of describing the ladder of electronic energy levels of the simpler trivalent lanthanide ions, as well as the lowest energy term of most of the series. The electronic energy levels result from electron configurations that are first split by spin-orbit coupling into groups of energy levels denoted by the corresponding Russell-Saunders terms. Each of these groups are then split by the ligand field into the actual electronic energy levels known as microstates or sometimes mJ levels. The ligand-field splitting directly informs on the coordination geometry and is a valuable tool for determining the structure and thus correlating the structure and properties of metal complexes in solution. The issue with lanthanide complexes is that the determination of complex structures from ligand-field splitting remains a very challenging task. In this paper, the optical spectra-absorption, luminescence excitation, and luminescence emission-of ytterbium(III) solvates were recorded in water, methanol, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF). The electronic energy levels, that is, the microstates, were resolved experimentally. Subsequently, density functional theory calculations were used to model the structures of the solvates, and ab initio relativistic complete active space self-consistent field calculations (CASSCF) were employed to obtain the microstates of the possible structures of each solvate. By comparing the experimental and theoretical data, it was possible to determine both the coordination number and solution structure of each solvate. In water, methanol, and N,N-dimethylformamide, the solvates were found to be eight-coordinated and have a square antiprismatic coordination geometry. In DMSO, the speciation was found to be more complicated. The robust methodology developed for comparing experimental spectra and computational results allows the solution structures of homoleptic lanthanide complexes to be determined.

Euglena gracilis is a eukaryotic single-celled and photosynthetic organism grouped under the kingdom Protista. This phytoflagellate can accumulate the carbon photoassimilate as a linear β-1,3-glucan chain called paramylon. This storage polysaccharide can undergo degradation to provide glucose units to obtain ATP and reducing power both in aerobic and anaerobic growth conditions. Our group has recently characterized an essential enzyme for accumulating the polysaccharide, the UDP-glucose pyrophosphorylase (Biochimie vol 154, 2018, 176–186), which catalyzes the synthesis of UDP-glucose (the substrate for paramylon synthase). Additionally, the identification of nucleotide sequences coding for putative UDP-sugar pyrophosphorylases suggests the occurrence of an alternative source of UDP-glucose. In this study, we demonstrate the active involvement of both pyrophosphorylases in paramylon accumulation. Using techniques of single and combined knockdown of transcripts coding for these proteins, we evidenced a substantial decrease in the polysaccharide synthesis from 39 ± 7 μg/106 cells determined in the control at day 21st of growth. Thus, the paramylon accumulation in Euglena gracilis cells decreased by 60% and 30% after a single knockdown of the expression of genes coding for UDP-glucose pyrophosphorylase and UDP-sugar pyrophosphorylase, respectively. Besides, the combined knockdown of both genes resulted in a ca. 65% reduction in the level of the storage polysaccharide. Our findings indicate the existence of a physiological dependence between paramylon accumulation and the partitioning of sugar nucleotides into other metabolic routes, including the Leloir pathway’s functionality in Euglena gracilis.

The direct one-pot transformation of glucose into γ-valerolactone (GVL) can be accomplished by means of a cascade of reactions in which Bronsted acid-catalyzed transformations are combined with catalytic transfer hydrogenation (CTH) by using 2-propanol as sacrificial alcohol, avoiding the use of high-pressure hydrogen. Catalysts containing Zr Lewis acid sites have been successfully applied in CTH reactions while the acid-driven transformations can be preferentially promoted by Bronsted Al-related acidity. Here, we present the combination of Zr and Al as active sites within a BEA zeolite structure as catalyst, with the possibility of adjusting the Al/Zr ratio from ∞ (commercial H-Beta) to 0 (aluminium-free Zr-Beta), which show a scale of Bronsted/Lewis acid sites ratios. The Al/Zr ratio has a strong impact on the products distribution. As the Zr content increases, higher amount of GVL is obtained, leading to a maximum over the catalyst with high amount of Zr and low content of Al acid sites (Al/Zr = 0.2). An increase of reaction temperature, as well as reaction time, allows an enhancement of yields towards the desired products, leading to a maximum yield towards GVL of 24 mol% over Zr-Al-Beta (2.0), and a maximum yield towards isopropyl lactate of 26 mol% over Zr-Beta at 190 °C.

The challenge for synthesizing magnetic nanoparticle chains may be achieved under the application of fixation fields, which are the externally applied fields, enhancing collective magnetic features due to adequate control of dipolar interactions among magnetic nanoparticles. However, relatively little attention has been devoted to how size, concentration of magnetic nanoparticles, and intensity of an external magnetic field affect the evolution of chain structures and collective magnetic features. Here, iron oxide nanoparticles are developed by the coprecipitation method at diameters below (10 and 20 nm) and above (50 and 80 nm) their superparamagnetic limit (at about 25 nm) and then are subjected to a tunable fixation field (40-400 mT). Eventually, the fixation field dictates smaller particles to form chain structures in two steps, first forming clusters and then guiding chain formation via "cluster-cluster" interactions, whereas larger particles readily form chains via "particle-particle" interactions. In both cases, dipolar interactions between the neighboring nanoparticles augment, leading to a substantial increase in their collective magnetic features which in turn results in magnetic particle hyperthermia efficiency enhancement of up to one order of magnitude. This study provides new perspectives for magnetic nanoparticles by arranging them in chain formulations as enhanced performance magnetic actors in magnetically driven magnetic applications.

Selenium is an essential element in human and animal metabolism integrated into the catalytic site of glutathione peroxidase (GPX1), an antioxidant enzyme that protects cells from damage caused by reactive oxygen species (ROS). Oxidative stress refers the imbalance between ROS and antioxidant defense systems. It generates alterations of DNA, proteins and lipid peroxidation. The imbalance occurs particularly during ischemia and lack of postmortem perfusion. This mechanism is of relevance in transplant organs, affecting their survival. The aim of this research is to evaluate the effect of seleno-methionine (SeMet) as a protective agent against postmortem ischemia injury in transplant organs. Wistar rats were orally administered with SeMet. After sacrifice, liver, heart and kidney samples were collected at different postmortem intervals (PMIs). SeMet administration produced a significant increase of Se concentration in the liver (65%, p < 0.001), heart (40%, p < 0.01) and kidneys (45%, p < 0.05). Levels of the oxidative stress marker malondialdehyde (MDA) decreased significantly compared to control in the heart (0.21 ± 0.04 vs. 0.12 ± 0.02 mmol g−1) and kidneys (0.41 ± 0.02 vs. 0.24 ± 0.03 mmol g−1) in a PMI of 1–12 h (p < 0.01). After SeMet administration for 21 days, a significant increase in GPX1 activity was observed in the liver (80%, p < 0.001), kidneys (74%, p < 0.01) and heart (35%, p < 0.05). SeMet administration to rats significantly decreased the oxidative stress in the heart, liver and kidneys of rats generated by postmortem ischemia. Fil: Hasuoka, Paul Emir. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentina Fil: Pérez Iglesias, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentina Fil: Teves, Mauricio Roberto. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina Fil: Kaplan, Marcos Manuel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ferrúa, Nelson Hugo. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina Fil: Pacheco, Pablo Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentina

Layered double hydroxides (LDH) are anionic clays, mainly used as adsorbents, ion exchange material, and catalysts. Generally, they present high specific surface areas, alkaline character, high metallic dispersion, and high thermal stability. If they contain a transitional element in their structure, the solid may present redox properties. LDH were synthesized with the following combinations: MgAl, MgFe, and ZnMgFe, aiming to determine the effect of cationic nature in the structure and the functionality of the synthesized clay as adsorbents in polluted aqueous effluents. The textural properties were determined by nitrogen adsorption isotherms. Crystalline structure was studied by XRD and the presence of the anions of the interlayer was determined by FTIR spectroscopy. The studies of removal of As(III) and As(V) from aqueous solutions, using the LDH, show that after 24 h the solids reach a high removal efficiency. ZnMgFe solid removed both species of arsenic with values of 95 and 98% for As(II) and As(V), respectively. The MgFe solid showed some selectivity to the uptake of As(V), while the MgAl only removed As(V). This selective behaviour can be beneficial in studies of arsenic speciation. HIGHLIGHTS Al and Fe present different electrostatic interactions which modify the LDH activity.; The different chemical behaviour of the constituent metals has influenced the morphology.; The solids present more than 88% of removal of As(V) in less than 24 h.; MgAl mostly removed As(V).; ZnMgFe had an excellent performance for both arsenic species.

Glutamate oxaloacetate transaminase 1 (GOT1) enzyme plays a critical role in the cell metabolism by participating in the carbohydrate and amino acid metabolism. In ischemic stroke, we have demonstrated that recombinant GOT1 acts as a novel neuroprotective treatment against the excess of extracellular glutamate that accumulates in the brain following ischemic stroke. In this study, we investigated the inhibitory effect of GOT1 on brain metabolism and on the ischemic damage in a rat model of ischemic stroke by means of a specific antibody developed against this enzyme. Inhibition of GOT1 caused higher brain glutamate and lactate levels and this response was associated with larger ischemic lesion. This study represents the first demonstration that the inhibition of the blood GOT1 activity leads to more severe ischemic damage and poorer outcome and supports the protective role of GOT1 against ischemic insults.

Soil salinity is one of the most critical environmental stresses that affects crop productivity. In a context in which world demand for food is growing continuously, this problem requires urgent attention. Actions that go beyond traditional agricultural practices are needed. The objective of the current study was to develop a bioactive, economic, and sustainable compound that can increase the tolerance of cultivated plants in saline-stress situations by combining the hosting capacity of natural bentonite nanoclay (Bent) with a phytoactive osmoprotective compound, L-Proline (Pro). The Bent-Pro nanocomposite synthesis method, its final chemical structure, and in vitro bioactivity were addressed here. The results indicated that Bent can retain a maximum of 14.4% (w/w) of Pro. The (001) X-ray diffraction (XRD) peak of Bent shifted to smaller angles in the pattern of Bent-Pro, indicating that Pro has a monolayer arrangement between the Bent layers. The results of transmission electron microscopy (TEM) also supported this result. Pro was also retained on the edges or external surfaces of Bent, as indicated by thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). In addition, Pro functional groups identified by Fourier-transform infrared (FTIR) spectroscopy indicated that it was present in its zwitterionic form. The role of Bent-Pro as a protector against plant saline stress was assayed using Arabidopsis thaliana (A. thaliana) as a model, demonstrating that it mitigates the detrimental effects of NaCl-mediated salt stress on seed germination and the leaf chlorophyll level, thus highlighting the relevance of this contribution and the versatility and broad applicability of clays.

The brain extracellular matrix (ECM) is involved in crucial processes of neural support, neuronal and synaptic plasticity, extrasynaptic transmission, and neurotransmission. ECM is a tridimensional fibrillary meshwork composed of macromolecules that determine its bioactivity and give it unique characteristics. The characterization of the brain ECM is critical to understand its dynamic in SZ. Thus, a comparative study was developed with 71 patients with schizophrenia (SZ) and 70 healthy controls. Plasma of participants was analysed by label-free liquid chromatography–tandem mass spectrometry, and the results were validated using the classical western blot method. Lastly, immunostaining of post-mortem human brain tissue was performed to analyse the distribution of the brain ECM proteins by confocal microscopy. The analysis identified four proteins: fibronectin, lumican, nidogen-1, and secreted protein acidic and rich in cysteine (SPARC) as components of the brain ECM. Statistical significance was found for fibronectin (P = 0.0166), SPARC (P = 0.0003), lumican (P = 0.0012), and nidogen-1 (P

Understanding the thermal stability of bimetallic nanoparticles is of vital importance to preserve their functionalities during their use in a variety of applications. In contrast to well-studied bimetallic systems such as Au@Ag, heat-induced morphological and compositional changes in Au@Pt nanoparticles are insufficiently understood, even though Au@Pt is an important material for catalysis. To investigate the thermal instability of Au@Pt nanorods at temperatures below their bulk melting point, we combined in situ heating with two- and three-dimensional electron microscopy techniques, including three-dimensional energy-dispersive X-ray spectroscopy. The experimental results were used as input for molecular dynamics simulations, to unravel the mechanisms behind the morphological transformation of Au@Pt core–shell nanorods. We conclude that thermal stability is influenced not only by the degree of coverage of Pt on Au but also by structural details of the Pt shell.

25 pags., 14 figs., 2 tabs., Tropospheric ozone ((Formula presented.)) is an important greenhouse gas and a surface pollutant. The future evolution of (Formula presented.) abundances and chemical processing are uncertain due to a changing climate, socioeconomic developments, and missing chemistry in global models. Here, we use an Earth System Model with natural halogen chemistry to investigate the changes in the (Formula presented.) budget over the 21st century following Representative Concentration Pathway (RCP)6.0 and RCP8.5 climate scenarios. Our results indicate that the global tropospheric (Formula presented.) net chemical change (NCC, chemical gross production minus destruction) will decrease (Formula presented.), notwithstanding increasing or decreasing trends in ozone production and loss. However, a wide range of surface NCC variations (from −60 (Formula presented.) to 150 (Formula presented.)) are projected over polluted regions with stringent abatements in (Formula presented.) precursor emissions. Water vapor and iodine are found to be key drivers of future tropospheric (Formula presented.) destruction, while the largest changes in (Formula presented.) production are determined by the future evolution of peroxy radicals. We show that natural halogens, currently not considered in climate models, significantly impact on the present-day and future global (Formula presented.) burden reducing (Formula presented.) 30–35 Tg (11–15 (Formula presented.)) of tropospheric ozone throughout the 21st century regardless of the RCP scenario considered. This highlights the importance of including natural halogen chemistry in climate model projections of future tropospheric ozone., EC, H2020, H2020 Priority Excellent Science, H2020 European Research Council (ERC). Grant Number: ERC-2016-COG726349; NSF, Office of Science of the US Department of Energy, PICT-2016-0714 (ANPCyT) i-COOP-B20331 (CSIC + CONICET)

Two metal–organic frameworks (MOFs) made of indium and 1,3,5-tris(4-carboxyphenyl)benzene (H3btb) and having a layered structure have been synthesized under solvothermal conditions: [In(btb)(H2O)(DMF)]·L (InPF-50) and [In2(btb)2Cl2]2−·[(CH3)2NH2]22+·L (InPF-51). The structures of both materials have been determined by single crystal X-ray diffraction. The synthetic study which has been carried out demonstrates the influence of the selected indium salt in obtaining each MOF. The structure of both materials consists of pairs of catenated layers, where the metal atoms display coordinated solvent ligands that provide potential open metal sites. The accessibility to these sites along with the presence of Lewis basic sites in the form of uncoordinated oxygen atoms make InPF-50 and -51 efficient catalysts for the four-component Ugi reaction. We attribute this high activity not only to the presence of both acid and basic sites, but also to their convenient locations in the MOF structures. This is further supported by the comparison with [In3O(btb)2(HCO2)]·L, InPF-110, a highly porous indium MOF that only displays Lewis acid sites, and shows lower activity., This work has been supported by the Spanish Ministry of Ministry of Science, Innovation and Universities Project MAT2016-78465-R, MAT2017-82288-C2-2-P, and CTQ2017-87262-R. D. R.-F. acknowledges an FPU scholarship from the Spanish Ministry of Science, Innovation and Universities. F. G. acknowledges the Spanish Ministry for Science, Innovation and Universities, for funding through the “Ramón y Cajal” program., We acknowledge support of the publication fee by the CSIC Open Access Support Initiative through its Unit of Information Resources for Research (URICI)

Background Pot-pollen is a fermented product stored by stingless bees in cerumen pots and traditionally used as food or medicine by natives in tropical regions. The knowledge of pot-pollen composition from the Amazon region is important to strengthen the breeding of native bees and consequently contribute to sustainable development in this region. The aim of the present study was to determine the chemical composition of Melipona seminigra pot-pollen from Amazonas, Brazil. Results We report the identification of 21 phenolic compounds using UPLC-ESI-QToF-MS. Overall, the predominant constituents of pot-pollen were protein (333.8-470.7 g kg-1 ) and dietary fibers (247.6-353.3 g kg-1 ). The predominant fatty acids were polyunsaturated (44.95-59.57% of total fatty acid content) and the samples contained all essential amino acids. Total carotenoids content (TCC) ranged from 3.2-48.0 μg g-1 , total flavonoids content (TFC) from 1.9-4.5 mg CAE g-1 , total reducing capacity (TRC) from 7.0-15.0 mg GAE g-1 , ferric-reducing antioxidant power (FRAP) from 2.8-8.9 μmol TE g-1 and oxygen radical absorbance capacity (ORAC) from 224.9-1117.0 μmol TE g-1 . Conclusions This study reports for the first time a comprehensive chemical characterization of M. seminigra pot-pollen. The samples presented antioxidant activity, high values of nutrients and bioactive compounds such as polyphenols, carotenoids, insoluble dietary fibers, polyunsaturated fatty acids, and essential amino acids, comparable to other health foods. This article is protected by copyright. All rights reserved.

A series of hybrid dimers having orthogonal steroidal cores bridged by a chroman ketal moiety were obtained by Pd-catalyzed three-component reactions of steroid alkynols, 2-formylestradiol 17-monoacetate, and methyl orthoformate, via ortho-quinone methide intermediates. One of the obtained L-shaped scaffolds showed an inefficient crystal packing featuring large channels within the crystal array. Monte Carlo simulations indicate that these voids preferentially allocate n-hexane, opening the way to explore further applications of similar organic crystalline materials as selective hosts for small molecules.

Modern polymer bonded explosives (PBX) are often characterized by a sensitive response to external thermomechanical insult that in some cases lead to accidental detonation. Current strategies for desensitizing PBXs come at the expense of a significant reduction in performance. A possible method for desensitizing PBX without adverse performance effects is the multifunctional tailoring of mechanical properties through strategic incorporation of multi-walled carbon nanotubes (MWCNTs) directly into the binder phase. In this work, a fabrication method is presented that produces polymer bonded simulants (PBS) of PBX that incorporate MWCNTs into the binder phase, hydroxyl-terminated polybutadiene (HTPB). These materials were characterized via microscopy and unconfined quasi-static compression testing to determine the effects of MWCNTs. Quasi-static compression showed evidence of a MWCNT induced structural skeleton effect that provided the binder with an increased strength, load transfer, and a greater ability to resist strain localizations prior to failure. These enhancements demonstrate the potential of using MWCNTs to enhance energetic materials.

The organic fraction of municipal waste (OFMW), source-sorted (SS-OFMW) and non-sorted (NS-OFMW), was used as raw material for the sequential production of bioethanol and biogas. Non-isothermal and simultaneous saccharification and fermentation (NSSF) resulted in maximum ethanol concentrations of 51 g/L and 26 g/L for SS-OFMW and NS-OFMW samples, showing overall process yields of up to 80 % and 59 %, respectively, even without subjecting substrate to hydrothermal pretreatment. Subsequently, the solid residues resulting from the fermentation were further subjected to anaerobic digestion (AD), showing a methanogenic potential of 384 ± 6 mL CH4/g of volatile solids (VSin) and 322 ± 3 mL CH4/g VSin, respectively. These methane yields were similar or even higher to those obtained when using non-fermented OFMW substrates (SS-OFMW: 380 ± 18 mL CH4/g VSin and NS-OFMW: 239 ± 4 mL CH4/g VSin), highlighting NSSF as a beneficial step to enhance methane yields during AD. Overall, bioconversion of OFMW would benefit from coupling bioethanol and biogas production since the biogas produced might be further employed as bioenergy source to compensate operational costs.

We evaluated interleukin-6 (IL-6) receptor-α subunit (IL-6Rα) signaling inhibition with sarilumab and tocilizumab, the association between IL-6Rα receptor occupancy (RO) and C-reactive protein (CRP), and the potential clinical relevance of any differences. For this, we measured IL-6Rα binding and signaling inhibition with sarilumab and tocilizumab in vitro, simulated soluble IL-6Rα RO over time for approved sarilumab subcutaneous (SC) and tocilizumab intravenous (IV) and SC doses, and assessed associations between calculated RO and CRP reduction, 28-joint Disease Activity Score based on CRP, and 20%/50%/70% improvement in American College of Rheumatology responses from clinical data. Sarilumab binds IL-6Rα in vitro with 15- to 22-fold higher affinity than tocilizumab, and inhibits IL-6–mediated classical and trans signaling via membrane-bound and soluble IL-6Rα. Sarilumab 200 and 150 mg SC every 2 weeks achieved >90% RO after first and second doses, respectively, maintained throughout the treatment period. At steady-state trough, RO was greater with sarilumab 200 mg (98%) and 150 mg SC every 2 weeks (94%), and tocilizumab 162 mg SC weekly (>99%) and 8 mg/kg IV every 4 weeks (99%), vs tocilizumab 162 mg SC every 2 weeks (84%) and 4 mg/kg IV every 4 weeks (60%). Higher RO was associated with greater CRP reduction and 28-joint Disease Activity Score based on CRP reduction, and more sarilumab patients achieving 20%/50%/70% improvement in American College of Rheumatology responses. The greatest reduction in CRP levels was observed with sarilumab (both doses) and tocilizumab 8 mg/kg IV every 4 weeks (reductions proportionally smaller with 4 mg/kg IV every 4 weeks). Higher IL-6Rα binding affinity translated into higher RO with sarilumab vs tocilizumab 4 mg/kg every 4 weeks or 162 mg every 2 weeks; tocilizumab required the higher dose or increased frequency to maintain the same degree of RO and CRP reduction. Higher RO was associated with clinical parameter improvements.