Identification of Entry Inhibitors against Delta and Omicron Variants of SARS-CoV-2

Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor in just 10 min. A drug library of 1068 approved compounds was used to screen for SARS-CoV2 entry inhibition, and 9 active drugs were identified as specific pseudovirus entry inhibitors. A plaque reduction neutralization test using authentic SARS-CoV-2 virus in Vero E6 cells confirmed that 2 of these drugs (Etravirine and Dolutegravir) significantly inhibited the infection of SARS-CoV-2. With molecular docking, we showed that both Etravirine and Dolutegravir are preferentially bound to primary ACE2-interacting residues on the RBD domain, implying that these two drug blocks may prohibit the viral attachment of SARS-CoV-2. We compared the neutralizing activities of these entry inhibitors against different pseudoviruses carrying spike proteins from alpha, beta, gamma, and delta variants. Both Etravirine and Dolutegravir showed similar neutralizing activities against different variants, with EC50 values between 4.5 to 5.8 nM for Etravirine and 10.2 to 22.9 nM for Dolutegravir. These data implied that Etravirine and Dolutegravir may serve as general spike inhibitors against dominant viral variants of SARS-CoV-2.     

Highly selective transport of transesterification reaction compounds through supported liquid membranes containing ionic liquids based on the tetrafluoroborate anion

We previously reported the selective simultaneous separation of the substrates and products of a transesterification reaction (vinyl butyrate, 1-butanol, butyl butyrate and butyric acid) through supported liquid membranes (SLMs) based on 1-n-alkyl-3-methylimidazolium cations combined with tetrafluoroborate, hexafluorophosphate and bis{(trifluoromethyl)sulfonyl}imide anions. The best results were obtained by the use of tetrafluoroborate based ionic liquids, which led us to further investigate the use of these new supported liquid membranes for the selective separation of different substrates and products of transesterification reactions. With this aim, the permeability of sixteen different organic compounds (vinyl esters, aliphatic esters, alcohols and carboxylic acids) through SLMs containing tetrafluoroborate based ionic liquids ([bmim⁺][BF₄⁻] and [omim⁺][BF₄⁻]) were evaluated. It was found that permeability increased as the alkyl chain length decreased for the same organic functional group. In addition, significant permeability differences were found between the different organic functional groups.As regards the operational stability of these SLMs, they were seen to be very stable when tested over eight continuous cycles of 48 h each.     

Simple and high-throughput method for the multimycotoxin analysis in cereals and related foods by ultra-high performance liquid chromatography/tandem mass spectrometry

A rapid, reliable and sensitive method was developed to determine 12 mycotoxins (deoxynivalenol, aflatoxins B1, B2, G1, G2 and M1, fumonisins B1 and B2, ochratoxin A, HT-2 and T-2 toxin and zearalenone) simultaneously in maize, walnuts, biscuits and breakfast cereals. The method is based on a single extraction step using acetonitrile/water mixture (80/20 v/v) followed by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS). The selectivity of the MS/MS detection allowed the elimination of further clean up steps. Extraction, chromatographic and detection conditions were optimised in order to increase sample throughput and sensitivity. Matrix-matched calibration was used for quantification and recoveries of the extraction process ranged from 70.0% and 108.4%, with relative standard deviations lower than 25% in all the cases, when samples were fortified at 5 and 50 μg/kg. Limits of detection ranged from 0.01 to 2.1 μg/kg and limits of quantification ranged from 0.03 to 6.30 μg/kg, which were always below the tolerance levels of mycotoxins set by European Union in the matrices evaluated. Several samples were analysed and aflatoxins B1, B2, G1, G2 and T-2 toxin were detected in one maize sample, with concentrations lower than 6.0 μg/kg and deoxynivalenol was detected in a breakfast cereal at 42.1 μg/kg.     

Evaluation of current techniques for isolation of chars as natural adsorbents

Chars in soils or sediments may potentially influence the soil/sediment sorption behavior. Current techniques for the isolation of black carbon including chars rely often on acid demineralization, base extraction, and chemical oxidation to remove salts and minerals, humic acid, and refractory kerogen, respectively. Little is known about the potential effects of these chemical processes on the char surface and adsorptive properties. This study examined the effects of acid demineralization, base extraction, and acidic Cr2O7 2- oxidation on the surface areas, surface acidity, and benzene adsorption characteristics of laboratory-produced pinewood and wheat-residue chars, pure or mixed with soils, and a commercial activated carbon. Demineralization resulted in a small reduction in the char surface area, whereas base extraction showed no obvious effect. Neither demineralization nor base extraction caused an appreciable variation in benzene adsorption and presumably the char surface properties. By contrast, the Cr2O7 2- oxidation caused a >31% reduction in char surface area. The Boehm titration, supplemented by FTIR spectra, indicated that the surface acidity of oxidized chars increased by a factor between 2.3 and 12 compared to non-oxidized chars. Benzene adsorption with the oxidized chars was lower than that with the non-oxidized chars by a factor of >8.9; both the decrease in char surface area and the increase in char surface acidity contributed to the reduction in char adsorptive power. Although the Cr2O7 2-oxidation effectively removes resistant kerogen, it is not well suited for the isolation of chars as contaminant adsorbents because of its destructive nature. Alternative nondestructive techniques that preserve the char surface properties and effectively remove kerogen must be sought.     

Pig sire type and sex effects on carcass traits,meat quality and physicochemical and sensory characteristics of Serrano dry‐cured ham

This study demonstrates that improvements in animal line selection by breeding enterprises exert a strong effect on carcass traits, meat quality and sensory characteristics of Serrano dry‐cured ham. A total of 461 pigs from the offspring of a Duroc (DU) × Landrace (LD) sow mated with two DU boars and a DU × Large White (LW) boar from three breeding enterprises were evaluated. The two DU terminal sires were significantly different (P < 0.05) in carcass conformation, backfat thickness, ham and loin yields, raw ham traits, myoglobin concentration and total pigments formed during the curing process; in addition, the two lines provided different percentages of hams (54 vs 91%) with sufficient subcutaneous fat and weight to manufacture dry‐cured Serrano hams using a slow ripening process (11 months). The DU × LW sire had the best carcass and ham traits from an economic standpoint and obtained highest scores for sensory characteristics of Serrano ham evaluated by a trained panel test; furthermore, this line provided 84% of total hams suitable for manufacturing Serrano hams by a slow process. When the sex effect was analysed, carcass and ham traits of females were more favourable, but females presented a higher incidence of pale, soft and exudative (PSE) meat and a lower percentage of hams with sufficient subcutaneous fat and weight to produce Serrano hams using a slow ripening process (61% for females and 91% for castrates). On the other hand, castrates provided Serrano hams cured by a slow procedure with better organoleptic characteristics than females. Right and left hams were similar. Copyright © 2005 Society of Chemical Industry     

Alpha‐Synuclein Binds to the Inner Membrane of Mitochondria in an α‐Helical Conformation

The human alpha‐Synuclein (αS) protein is of significant interest because of its association with Parkinson's disease and related neurodegenerative disorders. The intrinsically disordered protein (140 amino acids) is characterized by the absence of a well‐defined structure in solution. It displays remarkable conformational flexibility upon macromolecular interactions, and can associate with mitochondrial membranes. Site‐directed spin‐labeling in combination with electron paramagnetic resonance spectroscopy enabled us to study the local binding properties of αS on artificial membranes (mimicking the inner and outer mitochondrial membranes), and to evaluate the importance of cardiolipin in this interaction. With pulsed, twofrequency, double‐electron electron paramagnetic resonance (DEER) approaches, we examined, to the best of our knowledge for the first time, the conformation of αS bound to isolated mitochondria.     

Effect of the drying process on the compressive strength and cell proliferation of hydroxyapatite‐derived scaffolds

The compressive strength and MC3T3 cell proliferation response of robocast hydroxyapatite‐derived scaffolds was evaluated for samples fabricated by conventional and freeze‐drying methods followed by sintering at 1100 or 1300°C. Both the sintering temperature and, especially, the drying method affected significantly the size and morphology of the residual microporosity within the robocast scaffold's struts. The freeze‐drying method generated a persistent large (1‐10 μm) microporosity of dendritic morphology that was found to improve the biological response of hydroxyapatite‐derived scaffolds. Conversely, conventional drying enhances the compressive strength of the structures. Strength was also increased at the higher sintering temperature, although at the expense of a poorer cell proliferation behavior. The results of this study suggest that the use of a freeze drying process after printing by robocasting provides a very appropriate method for enhancing the biological performance and reliability of bioceramic robocast scaffolds without severely reducing their compressive strength. And, thus, shows promise as an effective method to optimize the performance of robocast scaffolds for bone tissue regeneration.     

Neuroprotective Effect of Melatonin: A Novel Therapy against Perinatal Hypoxia-Ischemia

One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their lifetime. For this reason, new and more effective neuroprotective strategies are urgently required, in order to minimize as much as possible the neurological consequences of this encephalopathy. In this sense, interest has grown in the neuroprotective possibilities of melatonin, as this hormone may help to maintain cell survival through the modulation of a wide range of physiological functions. Although some of the mechanisms by which melatonin is neuroprotective after neonatal asphyxia remain a subject of investigation, this review tries to summarize some of the most recent advances related with its use as a therapeutic drug against perinatal hypoxic-ischemic brain injury, supporting the high interest in this indoleamine as a future feasible strategy for cerebral asphyctic events.     

Biobased adhesives,gums, emulsions,and binders: current trends and future prospects

Biopolymers derived from renewable resources are an emerging class of advanced materials that offer many useful properties for a wide range of food and nonfood applications. Current state of the art in research and development of renewable polymers as adhesives, gums, binders, and emulsions is the subject of this review. Much of the focus will be on major biopolymers such as starch, proteins, lignin, oils, and their derivatives found in both natural and modified forms, but other biopolymers of promising commercial interest will also be included where warranted. Polymers produced in nature are remarkably diverse in their chemistry, thermomechanical properties, rheology, plasticity, and chemical reactivity. In particular, their capacity to undergo a wide array of chemical modifications yields materials with tailored properties suitable for use as adhesives, gums, coatings, emulsions, and binders. Many such materials are now widely used in commercial products like building materials, lubricants, sealants, coatings, bonding aids, pharmaceuticals, paper, glues, flocculants, processed and frozen foods, as well as tissue engineering and bone repair products. This review provides a general overview of biobased polymers highlighting their source, availability, properties, and usage in industrial products along with the future prospects, challenges, and opportunities they offer.     

The high‐speed measurement of a partial area imaging system applied to photoresist development processing

Abstract

Among the parameters that affect photolithography, the most important are exposure and development time which affect the coating photoresist characteristics. This study further researches the relationship between the exposure and development time using a high speed image inspection system, and the relationship between the development time and photoresist depth using a Scanning Probe Microscope (SPM). A partial scan CCD camera and high speed frame capture card were used to obtain the photoresist development processing parameters. The experimental results verified that this imaging system provides an economical and effective method for producing a micro‐photo‐etched product. It is expected that these experiments can also offer some good references useful in the micro electro mechanical industrial field.