Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story.

This study presents a new approach for identifying myeloperoxidase (MPO) inhibitors with strong in vivo efficacy. By combining inhibitor-like rules and structure-based virtual screening, the pipeline achieved a 70% success rate in discovering diverse, nanomolar-potency reversible inhibitors and hypochlorous acid (HOCl) scavengers. Mechanistic analysis identified RL6 as a genuine MPO inhibitor and RL7 as a potent HOCl scavenger. Both compounds effectively suppressed HOCl production in cells and neutrophils, with RL6 showing a superior inhibition of neutrophil extracellular trap release (NETosis). In a gout arthritis mouse model, intraperitoneal RL6 administration reduced edema, peroxidase activity, and IL-1ß levels. RL6 also exhibited oral bioavailability, significantly reducing paw edema when administered orally. This study highlights the efficacy of integrating diverse screening methods to enhance virtual screening success, validating the anti-inflammatory potential of potent inhibitors, and advancing the MPO inhibitor research.

A pilot-scale study of a novel system for simultaneous nitrogen and carbon removal: technological advancement of a structured bed reactor with intermittent aeration (SBRIA) in real domestic sewage treatment.

This study outlines the development of an effective pilot-scale simultaneous denitrification and nitrification (SDN) system using intermittent aeration for the removal of carbon and nitrogen from real domestic sewage. Given the limited research in this area, the main objective was to evaluate the overall performance of the SBRIA system on a pilot scale and show its benefits in domestic wastewater treatment. The structured bed reactor with intermittent aeration (SBRIA) notably achieved 57% efficiency in removing total nitrogen without requiring external carbon sources. It also demonstrated impressive removal rates of 56% for total chemical oxygen demand (CODT) and 82% for biochemical oxygen demand (BOD5), indicating its effectiveness in degrading organic matter. In addition, the SBRIA showed high pH control and managed the consumption of alkalinity without the need for an alkalizer, maintaining consistent mean values of 7.7 ± 0.8 for pH and 166.8 ± 79.8 mg·L-1 for alkalinity. The system also proved resilient against toxic shocks caused by significant variations in influent characteristics. This study offers valuable insights and compelling results into a cost-effective and efficient treatment approach using an innovative technology not previously applied at the pilot scale. Its potential to remediate polluted water is substantial.

Biofilm stratification and autotrophic-heterotrophic interactions in a structured bed reactor (SBRIA) for carbon and nitrogen removal.

The structured-bed reactor with intermittent aeration (SBRIA) is a promising technology for simultaneous carbon and nitrogen removal from wastewater. An in depth understanding of the microbiological in the reactor is crucial for its optimization. In this research, biofilm samples from the aerobic and anoxic zones of an SBRIA were analyzed through 16S rRNA sequencing to evaluate the bacterial community shift with variations in the airflow and aeration time. The control of the airflow and aeration time were essential to guarantee reactor performances to nitrogen removal close to 80%, as it interfered in nitrifying and denitrifying communities. The aeration time of 1.75 h led to establishment of different nitrogen removal pathways by syntrophic relationships between nitrifier, denitrifier and anammox species. Additionally, the predominance of these different species in the internal and external parts of the biofilm varied according to the airflow.

Optimization of airflow and aeration cycles in a new structured bed reactor configuration for carbon and nitrogen removal.

The Structured Bed Reactor with Recirculation and Intermittent Aeration (SBRRIA) is a reactor configuration that presents high efficiency of organic matter and nitrogen removal, besides low sludge production. However, operational parameters, as the recirculation rate, aeration time, and airflow, are not fully established. A bench-scale structured bed reactor with intermittent aeration was fed with synthetic effluent simulating the characteristics of sanitary sewage. The reactor was operated for 280 days with an operational hydraulic retention time (HRT) of 10 h. The reactor was operated without effluent recirculation for the first time since this approach was not yet reported, and was named Structured Bed Reactor with Intermittent Aeration (SBRIA). The COD removal was higher than 81% for all operational conditions, and the total nitrogen removal ranged from 10 to 80%. The highest efficiencies were obtained with an aeration time of 1 h 45 min (total cycle of 3 h) and an airflow rate of 4.5 L.min-1. Different nitrification and denitrification behaviours were observed, resulting in nitrification efficiencies over 90% when the reactor was submitted to higher aeration times and denitrification efficiencies above 90% when the reactor was submitted to low aeration times. The airflow ranges tested in this study affected the nitrification and the total nitrogen efficiencies. Even without effluent recirculation, the temporal profile showed that there were no peaks in the concentration of the nitrogen forms in the reactor effluent, saving electrical energy up to 75% due to pumping.

Catalogue of living crinoids (Echinodermata: Crinoidea) from Brazil.

Knowledge of living crinoids from Brazil is chiefly restricted to the contributions of Dr Luis Roberto Tommasi between the decades of 1950 and 1970. Herein we present an updated catalogue of the crinoids occurring along the Brazilian coast, including data on synonyms, type localities, type material, geographical distribution, bathymetric ranges, and occurrences of species along the coast. The data is based on an extensive revision of the literature and on a survey of several databases. A total of 20 species were catalogued, of which two are endemic (Phrixometra longipinna var. brasiliensis and Thaumatometra minutissima). According to information from the literature, P. longipinna var. brasiliensis represents an undescribed taxon. Although Brazil supports the greatest number of crinoid species in the Southwestern Atlantic, its crinoid fauna remains understudied and likely underestimated. Research on crinoids remains a subject of great potential, not only for taxonomy but also for other areas of knowledge.

Alpha thalassemia, but not ßS-globin haplotypes, influence sickle cell anemia clinical outcome in a large, single-center Brazilian cohort.

Alpha thalassemia and beta-globin haplotype are considered classical genetic disease modifiers in sickle cell anemia (SCA) causing clinical heterogeneity. Nevertheless, their functional impact on SCA disease emergence and progression remains elusive. To better understand the role of alpha thalassemia and beta-globin haplotype in SCA, we performed a retrospective study evaluating the clinical manifestations of 614 patients. The univariate analysis showed that the presence of alpha-thalassemia -3.7-kb mutation (αα/-α and -α/-α) decreased the risk of stroke development (p = 0.046), priapism (p = 0.033), and cholelithiasis (p = 0.021). Furthermore, the cumulative incidence of stroke (p = 0.023) and cholelithiasis (p = 0.006) was also significantly lower for patients carrying the alpha thalassemia -3.7-kb mutation. No clinical effects were associated with the beta-globin haplotype analysis, which could be explained by the relatively homogeneous haplotype composition in our cohort. Our results reinforce that alpha thalassemia can provide protective functions against hemolysis-related symptoms in SCA. Although, several genetic modifiers can impact the inflammatory state of SCA patients, the alpha thalassemia mutation remains one of the most recurrent genetic aberration and should therefore always be considered first.

Taxonomic guide and historical review of echinoids (Echinodermata: Echinoidea) from northeastern Brazil.

The class Echinoidea contains among the best-known echinoderms. The group has left the most complete fossil record of this phylum, and contains about 1000 living species, of which 51 are recorded along the Brazilian coast. Although the first record of echinoids in Brazil was made 369 years ago, the knowledge of this fauna remains quite unsatisfactory from a taxonomic and ecological point of view, particularly in the north and northeastern regions of the country. This study provides the first annotated list of echinoids from northeastern Brazil. The studied material largely belongs to collections of the Federal University of Paraíba (CIPY), Federal University of Sergipe (LABIMAR-UFS), Federal University of Bahia (MZUFBA), University of São Paulo (MZUSP), and National Museum of the Federal University of Rio de Janeiro (MNRJ). Thirty-two species from 29 genera, 18 families, and 10 orders were identified. Descriptions of species are provided. Highest diversities of Echinoidea were encountered for the states of Bahia (19 spp.), Alagoas (11 spp.), Paraíba (10 spp.), Ceará (7 spp.), Rio Grande do Norte (7 spp.), and Pernambuco (6 spp.). On the basis of the data analysed, Maranhão (2 spp.), Piauí (2 spp.), and Sergipe (3 spp.) have the lowest diversity. Sandy substrates and depths below 10 m were the least sampled areas over the continental shelf. Although the studied species are common, some taxonomic problems were encountered and discussed. We also provide ecological information and comments on status of the species from the studied region. As a result of this inventory, we were able to provide the first assessment of the echinoid fauna of northeastern Brazil.

Behavior of Pigs Reared in Enriched Environment: Alternatives to Extend Pigs Attention.

Three trials were carried out in a completely randomized design aiming to assess the behavior of pigs in growth phase in enriched environments. Trial 1 evaluated the effects of frequency of availability of environmental enrichment. The animals were assigned to four treatments: 1) control with no enrichment object; 2) objects provided for six consecutive days uninterruptedly; 3) objects provided on alternate days, and 4) objects provided for six consecutive days taken away by the end of the afternoon and replaced at dawn. Trial 2 assessed the effects of scent on animals' acceptance and maintenance of interest in objects. Animals were assigned to four treatments: 1) unscented object; 2) object with banana scent; 3) object with rum scent; 4) object with scents alternated every other day. Trial 3 aimed to assess the influence of environmental enrichment based on providing rewards at different difficulty levels. Animals were assigned to three treatments: 1) object with no reward; 2) object with a reward at an easy level; 3) object with a reward at a difficult level. Each trial had six days of behavioral observations every ten minutes for eight hours each day using images from video cameras. Enrichment objects stimulated the animals' natural behavior of nuzzling and exploring the environment. The way the objects were available did not impact the success of their use. Offering enrichment on alternate days or removing the objects by the end of the day was not an effective strategy to extend the animals' interest. The olfactory stimulus in environmental enrichment objects had no positive effect on extending the animals' interest on them, nor did alternating the aromas. The tactile stimulus was a key factor for object attractiveness. Providing environmental enrichment objects with rewards stimulated the exploratory behavior of pigs. The level of difficulty to obtain the reward may discourage the animals.

Antibiotic-modifying activity of riachin, a non-cyanogenic cyanoglycoside extracted from Bauhinia pentandra.

BACKGROUND: The search for new active compounds from the Brazilian flora has intensified in recent years, especially for new drugs with antibiotic potential. Accordingly, the aim of this study was to determine whether riachin has antibiotic activity in itself or is able to modulate the activity of conventional antibiotics. METHODS: A non-cyanogenic cyanoglycoside known as riachin was isolated from Bauhinia pentandra, and was tested alone and in combination with three antibiotics (clindamycin, amikacin, and gentamicin) against multiresistant bacterial strains (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). RESULTS: Riachin did not show significant antibiotic activity when tested alone against any strain (P>0.05). However, when combined with conventional antibiotics, it showed drug-modifying activity against strains of S. aureus exposed to clindamycin (P<0.001) as well as against P. aeruginosa exposed to amikacin (P<0.001). Although riachin did not show direct antibiotic activity, it had synergistic activity when combined with amikacin or clindamycin. The mechanism of action of this synergism is under investigation. CONCLUSION: The results of this work demonstrate that some substances of natural origin can enhance the effectiveness of certain antibiotics, which means a substantial reduction in the drug dose required and possibly in consequent adverse events for patients.