Synthesis and Structure-Activity Relationship of Covalent Inhibitors of SARS-CoV-2 Papain-Like Protease with Antiviral Potency.

The papain-like protease (PLpro) is a highly conserved domain encoded by the coronavirus (CoV) genome and it plays an essential role in the replication and maturation of the virus in addition to weakening host immune response. Due to the virus's reliance on PLpro for survival and propagation, small-molecule inhibitors of PLpro serve as an attractive model for direct-acting antiviral therapeutic agents against SARS-CoV-2. Building upon existing work aimed at designing covalent inhibitors against PLpro, we report the synthesis and structure-activity relationship of analogs based on the known covalent inhibitor 1 (Sanders, et al.

A Computational Pipeline for Accurate Prioritization of Protein-Protein Binding Candidates in High-Throughput Protein Libraries.

Identifying the interactome for a protein of interest is challenging due to the large number of possible binders. High-throughput experimental approaches narrow down possible binding partners but often include false positives. Furthermore, they provide no information about what the binding region is (e.

The effect of temperature on the synthesis of magnetite nanoparticles by the coprecipitation method.

Magnetic nanoparticles, such as magnetite (FeO), exhibit superparamagnetic properties below 15 nm at room temperature. They are being explored for medical applications, and the coprecipitation technique is preferred for cost-effective production. This study investigates the impact of synthesis temperature on the nanoparticles' physicochemical characteristics.

Cardiotoxicity and ROS Protection Assessment of three Structure-Related N-Acylhydrazones with Potential for the Treatment of Neurodegenerative Diseases.

The senescence process is associated with accumulated oxidative damage and increased metal concentration in the heart and brain. Besides, abnormal metal-protein interactions have also been linked with the development of several conditions, including Alzheimer's and Parkinson's diseases. Over the years we have described a series of structure-related compounds with different activities towards models of such diseases.

Sifting Through the Noise: A Computational Pipeline for Accurate Prioritization of Protein-Protein Binding Candidates in High-Throughput Protein Libraries.

Identifying the interactome for a protein of interest is challenging due to the large number of possible binders. High-throughput experimental approaches narrow down possible binding partners, but often include false positives. Furthermore, they provide no information about what the binding region is (e.

Toxicological Effects of Fine Particulate Matter (PM): Health Risks and Associated Systemic Injuries-Systematic Review.

Previous studies focused on investigating particulate matter with aerodynamic diameter ≤ 2.5 µm (PM) have shown the risk of disease development, and association with increased morbidity and mortality rates. The current review investigate epidemiological and experimental findings from 2016 to 2021, which enabled the systemic overview of PM's toxic impacts on human health.

Protocol for production and purification of SARS-CoV-2 3CL.

3CL protease from SARS-CoV-2 is a primary target for COVID-19 antiviral drug development. Here, we present a protocol for 3CL production in Escherichia coli. We describe steps to purify 3CL, expressed as a fusion with the Saccharomyces cerevisiae SUMO protein, with yields up to 120 mg L following cleavage.

Silver-modified nitrogen-doped graphene quantum dots as a sensor for formaldehyde in milk using headspace micro-extraction on a single-drop of aqueous nanoparticles dispersion.

Background: Fraudulent practices used to distort the quality of milk and derivatives include the addition of formaldehyde.

Results: A formaldehyde sensor was developed based on the luminescence of newly proposed N-doped graphene quantum dots modified with silver (N-GQDs-Ag) that were prepared using a simple method. A microdroplet of the nanoparticle dispersion was used to collect formaldehyde vapor by headspace single-drop micro-extraction (HS-SDME).

Use of selective quenching of a photoluminescent probe based on a Eu(III) β-diketonate complex for determination of methylmercury in produced water after liquid-liquid extraction.

An Eu(III) β-diketonate complex was produced and employed as a photoluminescent probe to determine methylmercury (CHHg). To establish its molecular structure, the Eu(III) complex was characterized by elemental (CHNS) and thermogravimetric analyses and infrared spectroscopy. After establishing robust conditions to use the Eu(III) complex as an analytical probe, it was employed for the analysis of produced water (PW) samples with the analytical response based on the luminescence suppression proportional to the concentration of CHHg (a linear model after normalization of the response within the concentration range from 0.

Assessment of air quality changes during COVID-19 partial lockdown in a Brazilian metropolis: from lockdown to economic opening of Rio de Janeiro, Brazil.

Abstract: During the COVID-19 pandemic, restrictive measures are taken by several cities around the world, as well as Rio de Janeiro, reducing routine activities in large urban centers and primary pollutant emissions. This study aims to assess air quality during this partial lockdown through O, CO, and PM concentrations and meteorological data collected in five air quality monitoring stations spread over the whole city, considering the substantial changes in city routine. The period evaluated starts in March 2020, when the partial lockdown was decreed, and ends in September 2020, when economic opening ended.

Assessment of the effects of seasonality on the ecotoxicity induced by the particulate matter using the animal model Caenorhabditis elegans.

The present work aimed to establish potential changes in the ecotoxicological effects on C. elegans induced by the exposure of coarse (PM) and fine (PM) particulate matter collected during dry and rainy periods. We also analyzed the probable influence on the change of a city's activities as the mega-events result in air quality.

Magnetic Characterization by Scanning Microscopy of Functionalized Iron Oxide Nanoparticles.

This study aimed to systematically understand the magnetic properties of magnetite (FeO) nanoparticles functionalized with different Pluronic F-127 surfactant concentrations (FeO@Pluronic F-127) obtained by using an improved magnetic characterization method based on three-dimensional magnetic maps generated by scanning magnetic microscopy. Additionally, these FeO and FeO@Pluronic F-127 nanoparticles, as promising systems for biomedical applications, were prepared by a wet chemical reaction. The magnetization curve was obtained through these three-dimensional maps, confirming that both FeO and FeO@Pluronic F-127 nanoparticles have a superparamagnetic behavior.

Peripheral and lung resident memory T cell responses against SARS-CoV-2.

Resident memory T cells (T) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, T are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome.

The use of hedgerows to mitigate pesticide exposure of a population living in a rural area.

Farmer populations living in houses inside vegetable gardens are exposed to indoor pesticide pollution. The pulverization drift and volatile pesticides transported by wind are important sources of indoor pollution, which can be mitigated by hedgerows. This study was the first attempt in Brazil to investigate the efficiency of six different hedgerow species in reducing pesticide residues in air.

Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity.

Background: Global pandemic SARS-CoV-2 causes a prothrombotic state without fully elucidated effects. This study aims to analyse and quantify the possible retinal microvascular abnormalities.

Materials And Methods: Case-control study.

The aroylhydrazone INHHQ prevents memory impairment induced by Alzheimer's-linked amyloid-β oligomers in mice.

Converging evidence indicates that neurotoxicity and memory impairment in Alzheimer's disease is induced by brain accumulation of soluble amyloid-β oligomers (AβOs). Physiological metals are poorly distributed and concentrated in the senile plaques typical of Alzheimer's disease, where they may be coordinated to the amyloid-β peptide (Aβ). Indeed, zinc and copper increase Aβ oligomerization and toxicity.

Aroylhydrazones constitute a promising class of 'metal-protein attenuating compounds' for the treatment of Alzheimer's disease: a proof-of-concept based on the study of the interactions between zinc(II) and pyridine-2-carboxaldehyde isonicotinoyl hydrazone.

With the increasing life expectancy of the world's population, neurodegenerative diseases, such as Alzheimer's disease (AD), will become a much more relevant public health issue. This fact, coupled with the lack of efficacy of the available treatments, has been driving research directed to the development of new drugs for this pathology. Metal-protein attenuating compounds (MPACs) constitute a promising class of agents with potential application on the treatment of neurodegenerative diseases, such as AD.

Probing the Surface of a Laccase for Clues towards the Design of Chemo-Enzymatic Catalysts.

Systems featuring a multi-copper oxidase associated with transition-metal complexes can be used to perform oxidation reactions in mild conditions. Here, a strategy is presented for achieving a controlled orientation of a ruthenium-polypyridyl graft at the surface of a fungal laccase. Laccase variants are engineered with unique surface-accessible lysine residues.

A moderate metal-binding hydrazone meets the criteria for a bioinorganic approach towards Parkinson's disease: Therapeutic potential, blood-brain barrier crossing evaluation and preliminary toxicological studies.

Alzheimer's and Parkinson's diseases share similar amyloidogenic mechanisms, in which metal ions might play an important role. In this last neuropathy, misfolding and aggregation of α-synuclein (α-Syn) are crucial pathological events. A moderate metal-binding compound, namely, 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), which was previously reported as a potential 'Metal-Protein Attenuating Compound' for Alzheimer's treatment, is well-tolerated by healthy Wistar rats and does not alter their major organ weights, as well as the tissues' reduced glutathione and biometal levels, at a concentration of 200mgkg.

Structural Solutions for Low-Cost Bamboo Frames: Experimental Tests and Constructive Assessments.

Experimental tests and constructive assessments are presented for a simple bamboo framed structure with innovative low-cost and low technology joints, specifically conceived for small buildings in developing countries. Two full scale one-storey bamboo frames have been designed by using the simplest joints solution among three different tested typologies. The entire building process is based on low-technology and natural materials: bamboo canes, wooden cylinders, plywood plates and canapé rods.

Identifying Nursing Interventions in a Cancer Screening Program Using Nursing Interventions Classification Taxonomy.

Purpose: This study aimed to investigate which Nursing Interventions Classification (NIC) labels correspond to specific nursing interventions provided during cancer screening to establish a nursing documentation system.

Method: This descriptive study was conducted to identify and classify the interventions that cancer screening nurses perform based on an initial list.

Findings: The initial list was grouped into 15 interventions that corresponded to four domains and eight classes.

Reduction in parvalbumin-positive interneurons and inhibitory input in the cortex of mice with experimental autoimmune encephalomyelitis.

In multiple sclerosis (MS), inflammation leads to damage of central nervous system myelin and axons. Previous studies have postulated impaired GABA transmission in MS, and recent postmortem analysis has shown that GABAergic parvalbumin (PV)-positive interneurons are decreased in the primary motor cortex (M1) of patients with MS. In this report, we present evidence for the loss of a specific population of GABAergic interneurons in the experimental autoimmune encephalomyelitis mouse model of MS.