COVID-19 and Lung Mast Cells: The Kallikrein–Kinin Activation Pathway

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE⁺ MCs, tryptase⁺ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.     

Composites based on high-density polyethylene,polylactide and calcium carbonate: effect of calcium carbonate nanoparticles as co-compatibilizers

Polymer Bulletin - Investigating the compatibility mechanism of hybrid composites based on two polymers and one mineral nanofiller is a challenge that needs to be better understood. This study...     

Salivary Glands after Prolonged Aluminum Exposure: Proteomic Approach Underlying Biochemical and Morphological Impairments in Rats

Aluminum (Al) is one of the most abundant elements on Earth, and its high extraction rate and industrial use make human exposure very common. As Al may be a human toxicant, it is important to investigate the effects of Al exposure, mainly at low doses and for prolonged periods, by simulating human exposure. This work aimed to study the effects of low-dose exposure to chloride aluminum (AlCl₃) on the oxidative biochemistry, proteomic profile, and morphology of the major salivary glands. Wistar male rats were exposed to 8.3 mg/kg/day of AlCl₃ via intragastric gavage for 60 days. Then, the parotid and submandibular glands were subjected to biochemical assays, proteomic evaluation, and histological analysis. Al caused oxidative imbalance in both salivary glands. Dysregulation of protein expression, mainly of those related to cytoarchitecture, energy metabolism and glandular function, was detected in both salivary glands. Al also promoted histological alterations, such as acinar atrophy and an increase in parenchymal tissue. Prolonged exposure to Al, even at low doses, was able to modulate molecular alterations associated with morphological impairments in the salivary glands of rats. From this perspective, prolonged Al exposure may be a risk to exposed populations and their oral health.     

Influence of low friction coatings on the scuffing load capacity and efficiency of gears

The influence of multilayer composite surface coatings on gear scuffing load carrying capacity, gear friction coefficient and gearbox efficiency is discussed in this work.The deposition procedures of molybdenum disulphide/titanium (MoS₂/Ti) and carbon/chromium (C/Cr) composite coatings are described.Tests reported in the literature, such as Rockwell indentations, ball cratering, pin-on-disc and reciprocating wear, confirm the excellent adhesion to the substrate and the tribological performance of these coatings, suggesting they can be applied with success in heavy loaded rolling–sliding contacts, such as those found in gears.FZG gear scuffing tests were performed in order to evaluate the coatings anti-scuffing performance, which both improved very significantly in comparison to uncoated gears. These results in conjunction with the friction power intensity (FPI) scuffing criterion allowed the determination of a friction coefficient factor X_SC to include the coating influence on the friction coefficient expression.The composite coatings were also applied to the gears of a transfer gearbox and its efficiency was measured and compared at different input speeds and torques with the uncoated carburized steel gears. Significant efficiency improvement was found with the MoS₂/Ti coating.     

Strongly Photosensitive and Fluorescent F8T2 Electrospun Fibers

Electrospun fibers of poly[(9,9‐dioctylfluorenyl‐2,7‐diyl)‐co‐bithiophene] (F8T2) with exceptional electro‐optical performance are obtained. The I/T characteristics measured in fibers with 7–15 µm diameter and 1 mm length show a semiconductor behavior; their thermal activation energy is 0.5 eV and the dark conductivity at RT is 5 × 10^?9 (Ω cm)^?1. Besides exhibiting a photosensitivity of about 60 under white light illumination with a light power intensity of 25 mW · cm^?2, the fibers also attain RT photoluminescence in the cyan, yellow, and red wavelength range under ultraviolet, blue, and green light excitation, respectively. Optical microscope images of F8T2 reveal homogeneous electrospun fibers, which are in good agreement with the uniformly radial fluorescence observed.

     

A simple but sound approach for processing crystal growth kinetic data

The effects of common data smoothing techniques, on the estimating of the kinetic and thermodynamic parameters of the crystal growth process, were discussed in the light of birth and spread model. Adoption of the moving average, and filtration caused a noticeable misunderstanding of the real ruling growth mechanism, especially, during the early period of the crystal growth.In this work, a MATLAB routine was developed with standard, and reliable method to treat the prolonged concentration-time data sets, as obtained from continuous recording of refractometric °Brix readings of pure sucrose solutions in laboratory batch crystallization process. The method consists of finding the median of the residence time for every °Brix concentration, with and without interference of previous and post readings. In addition to 30% reduction in the evaluated interfacial free energies, up to 5-folds of increase in the estimates of the overall kinetic coefficients were reported using the common smoothing techniques instead of the proposed routine.     

Colloidal synthesis of Au nanoparticles using polyelectrolytes with 1,3,4-thiadiazole as reducing agents

Heterocyclic compounds are well known for their biological activity and coordination properties. Some heterocyclic compounds have been employed in the stabilization against coalescence of metallic nanoparticles in colloidal solutions, for example, tetrazole, triazole, and pyrazole. The aim of this work is to design new polyelectrolytes with heterocyclic pendant groups useful as reducing agents of Au³⁺ and as stabilizing agents for the synthesis of colloidal Au nanoparticles. Thus, polyelectrolytes with thiosemicarbazone and 1,3,4-thiadiazole pendant groups were used as reducing agents of Au³⁺ ions and stabilizing agents of Au nanoparticles. The voltammetry study of the polyelectrolytes showed that one with thiosemicarbazone pendant groups is the better reducing agent than polyelectrolytes with heterocyclic pendant groups. The polyelectrolytes can control the growth of the nanoparticles, obtaining structures with an average size of 9 nm. In this study, it was concluded that the nature of the heterocyclic group does not have an effect on the shape of nanoparticles and quasi-spherical nanoparticles were obtained with all polyelectrolytes. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47790.     

Enhancements in sugar immobilization in polymeric macroporous matrices for affinity capture

The use of macroporous monolithic matrices in the purification of biocompounds is constantly growing and developing. In this work, the objective was to optimize the quantity of N-acetyl-D-glucosamine (D-GlcNAc) immobilized on the surface of macroporous polymeric cryogels for capture of lectins from less clarified solutions. Surface response methodology was applied and it was observed that the immobilization temperature of the glutaraldehyde (GLU) and the D-GlcNAc concentration influenced the amount of sugar immobilized. The matrices produced with 1.1% of allyl glycidyl ether were functionalized by GLU. Optimal maximum condition was obtained with mean value of 160.39 ± 26.38 mg of D-GlcNAc immobilized per gram of dry cryogel. Characterization analyses of the matrices showed that the activation process was effective, maintaining the macroporous structure and physical characteristics. The adsorbents produced were tested for capture of lectins from a crude protein solution of barley. At tested conditions, adsorbent capture around 11% of protein in solution but reduce the hemaglutinating capacity in 40%, demonstrating its selectivity. The cryogels functionalized with D-GlcNAc present potential for use in capture compounds by affinity with carbohydrates, such as lectins. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47956.     

Asymmetric synthesis and conformational analysis by NMR spectroscopy and MD of Aba- and α-MeAba-containing dermorphin analogues

Dermorphin analogues, containing a (S)‐ and (R)‐4‐amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐one scaffold (Aba) and the α‐methylated analogues as conformationally constrained phenylalanines, were prepared. Asymmetric phase‐transfer catalysis was unable to provide the (S)‐α‐Me‐o‐cyanophenylalanine precursor for (S)‐α‐MeAba in acceptable enantiomeric purity. However, by using a Schöllkopf chiral auxiliary, this intermediate was obtained in 88 % ee. [(S)‐Aba 3‐Gly 4]dermorphin retained μ‐opioid affinity but displayed an increased δ‐affinity. The corresponding R epimer was considerably less potent. In contrast, the [(R)‐α‐MeAba 3‐Gly 4]dermorphin isomer was more potent than its S epimer. Tar‐MD simulations of both non‐methylated [Aba 3‐Gly 4]dermorphin analogues showed a degree of folding at the C‐terminal residues toward the N terminus of the peptide, without however, adopting a stabilized β‐turn conformation. The α‐methylated analogues, on the other hand, exhibited a type I/I′ β‐turn conformation over the α‐MeAba 3 and Gly 4 residues, which was stabilized by a hydrogen bond involving Tyr 5‐H_N and D ‐Ala 2‐CO.     

Synthesis and Evaluation of the Anticancer and Trypanocidal Activities of Boronic Tyrphostins

Molecules containing an (cyanovinyl)arene moiety are known as tyrphostins because of their ability to inhibit proteins from the tyrosine kinase family, an interesting target for the development of anticancer and trypanocidal drugs. In the present work, (E)‐(cyanovinyl)benzeneboronic acids were synthesized by Knoevenagel condensations without the use of any catalysts in water through a simple protocol that completely avoided the use of organic solvents in the synthesis and workup process. The in vitro anticancer and trypanocidal activities of the synthesized boronic acids were also evaluated, and it was discovered that the introduction of the boronic acid functionality improved the activity of the boronic tyrphostins. In silico target fishing with the use of a chemogenomic approach suggested that tyrosine‐phosphorylation‐regulated kinase 1a (DYRK1A) was a potential target for some of the designed compounds.