Reemergence of Oropouche virus between 2023 and 2024 in Brazil.

Background: Oropouche virus (OROV; species Orthobunyavirus oropoucheense) is an arthropod-borne virus that has caused outbreaks of Oropouche fever in Central and South America since the 1950s. This study investigates virological factors contributing to the reemergence of Oropouche fever in Brazil between 2023 and 2024. Methods: In this study, we combined OROV genomic, molecular, and serological data from Brazil from 1 January 2015 to 29 June 2024, along with in vitro and in vivo characterization. Molecular screening data included 93 patients with febrile illness between January 2023 and February 2024 from the Amazonas State. Genomic data comprised two genomic OROV sequences from patients. Serological data were obtained from neutralizing antibody tests comparing the prototype OROV strain BeAn 19991 and the 2024 epidemic strain. Epidemiological data included aggregated cases reported to the Brazilian Ministry of Health from 1 January 2014 to 29 June 2024. Findings: In 2024, autochthonous OROV infections were detected in previously non-endemic areas across all five Brazilian regions. Cases were reported in 19 of 27 federal units, with 83.2% (6,895 of 8,284) of infections in Northern Brazil and a nearly 200-fold increase in incidence compared to reported cases over the last decade. We detected OROV RNA in 10.8% (10 of 93) of patients with febrile illness between December 2023 and May 2024 in Amazonas. We demonstrate that the 2023-2024 epidemic was caused by a novel OROV reassortant that replicated approximately 100-fold higher titers in mammalian cells compared to the prototype strain. The 2023-2024 OROV reassortant displayed plaques earlier than the prototype, produced 1.7 times more plaques, and plaque sizes were 2.5 larger compared to the prototype. Furthermore, serum collected in 2016 from previously OROV-infected individuals showed at least a 32-fold reduction in neutralizing capacity against the reassortment strain compared to the prototype. Interpretation: These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to a better understanding of the 2023-2024 OROV reemergence. The recent increased incidence may be related to a higher replication efficiency of a new reassortant virus that also evades previous immunity.

Coccidia of Guinea fowls: Validity of recorded Eimeria spp. (Apicomplexa: Eimeriidae) and first molecular identification of Eimeria grenieri Yvoré & Aycardi, 1967.

Guinea fowls, Numida meleagris (L., 1758), are galliform birds native to sub-Saharan Africa, but introduced in several countries around the world for domestic breeding and/or animal production. This species is considered more resistant to disease by Eimeria spp. than other domestic galliform birds. Here we review the Eimeria spp. known to infect species of Numididae and provide the first molecular identification of an Eimeria sp. from Guinea fowls. There are currently 3 named eimerians from Guinea fowls; Eimeria numidae Pellerdy, 1962; Eimeria grenieri Yvoré and Aycardi, 1967; and Eimeria gorakhpuri Bhatia & Pande, 1967. We reviewed each of these species descriptions and documented their taxonomic shortcomings. From that, we suggest that E. gorakhpuri is a junior synonym of E. numidae. In conclusion, we have morphologically redescribed in detail E. grenieri from N. meleagris from Rio de Janeiro and provided molecular supplementation through sequencing of three non-overlapping loci in cox1 and cox3 genes and fragments of small and large subunit mitochondrial rDNA.

FHIR Implementation Guide for Stroke: A dual focus on the patient's clinical pathway and value-based healthcare.

BACKGROUND: Stroke management requires a coordinated strategy, adhering to clinical pathways (CP) and value-based healthcare (VBHC) principles from onset to rehabilitation. However, the discrepancies between these pathways and actual patient experiences highlight the need for ongoing monitoring and addressing interoperability issues across multiple institutions in stroke care. To address this, the Fast Healthcare Interoperability Resource (FHIR) Implementation Guide (IG) standardizes the information exchange among these systems, considering a specific context of use. OBJECTIVE: Develop an FHIR IG for stroke care rooted in established stroke CP and VBHC principles. METHOD: We represented the stroke patient journey by considering the core stroke CP, the International Consortium for Health Outcomes Measurement (ICHOM) dataset for stroke, and a Brazilian case study using the Business Process Model and Notation (BPMN). Next, we developed a data dictionary that aligns variables with existing FHIR resources and adapts profiling from the Brazilian National Health Data Network (BNHDN). RESULTS: Our BPMN model encompassed three critical phases that represent the entire patient journey from symptom onset to rehabilitation. The stroke data dictionary included 81 variables, which were expressed as questionnaires, profiles, and extensions. The FHIR IG comprised nine pages: Home, Stroke-CP, Data Dictionary, FHIR, ICHOM, Artifacts, Examples, Downloads, and Security. We developed 96 artifacts, including 7 questionnaires, 27 profiles with corresponding example instances, 3 extensions, 18 value sets, and 14 code systems pertinent to ICHOM outcome measures. CONCLUSION: The FHIR IG for stroke in this study represents a significant advancement in healthcare interoperability, streamlining the tracking of patient outcomes for quality enhancement, facilitating informed treatment choices, and enabling the development of dashboards to promote collaborative excellence in patient care.

Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome.

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.

Hydrolysis of Casein by Pepsin Immobilized on Heterofunctional Supports to Produce Antioxidant Peptides.

A study was carried out on the immobilization of pepsin in activated carbon functionalized by different techniques (glutaraldehyde, genipin, and metallization) aiming at its application in obtaining bioactive peptides through casein hydrolysis. Studies of the immobilized derivatives were carried out in addition to the evaluation of the antioxidant potential of the peptides. Among the pH range studied, pH 3.0 was selected due to the higher activity of the derivatives at this pH. The support modification by metallization was the method with the best results, providing a 121% increase in enzymatic activity compared to other immobilization methods. In addition, this derivative provided activity closer to the soluble enzyme activity (3.30 U) and better storage stability, and allows reuse for more than 8 cycles. In turn, the peptides from casein hydrolysis showed potential as antioxidant agents, with a DPPH radical scavenging activity higher than 70%, maximum protection against ß-carotene oxidation close to 70%, and a maximum reducing power of Fe(III) into Fe(II) of 400 uM by the FRAP assay. The results showed that the new techniques for modification of activated carbon can be a promising approach for pepsin immobilization.

Isocycloseram: A new active ingredient for leaf-cutting ants control.

Leaf-cutting ants are the most important pests in several cropping systems in the Neotropics. Granulated baits containing active ingredients, considered hazardous by the Stockholm Convention, are the usual method to control these ants. Isocycloseram is a new insecticide molecule with high safety margin for mammals, but without registration for the ants in general. Thus, this study investigated the effectiveness of granulated baits with isocycloseram in leaf-cutting ants control under laboratory and field conditions. Initially, the mortality of Atta sexdens workers, fed with dehydrated citrus pulp paste containing different concentrations of isocycloseram was evaluated in the laboratory for 21 days, for toxicological classification. Subsequently, the loading, devolution, and incorporation of baits with different concentrations of isocycloseram and the mortality of A. sexdens colonies were evaluated in the laboratory. After that, the percentages of loading and devolution of baits, foraging activity, and colony mortality treated with 0.05, 0.1, 0.2, and 0.3% of isocycloseram were evaluated for the species A. sexdens, A. laevigata, and Acromyrmex lundii in field conditions. All concentrations of isocycloseram killed more than 15% of ants in 24 h and more than 90% in 21 days in the laboratory, being classified as a fast-acting and highly effective active ingredient. Baits with 0.001 to 0.03% of isocycloseram were highly loaded and exhibited low rate of devolution. The mortality of A. sexdens colony was higher at concentrations between 0.075 and 0.3%, in the laboratory. Baits containing isocycloseram at concentrations of 0.2 and 0.3% were highly loaded, presented low devolution rates, and were highly efficient in controlling A. sexdens, A. laevigata, and A. lundii in the field, at dosages of 6, 10, and 12 g/m² of nest. This is the first report of the use of isocycloseram against leaf-cutting ants, contributing to the development of efficient and toxicologically safer ant baits.

Biochemical changes, metal content, and spectroscopic analysis in sewage sludge composted with lignocellulosic residue using FTIR-MIR and FTIR-NIR.

The use of lignocellulosic residues, originating from sawdust, in composting sewage sludge for organic fertilizer production, is a practice of growing interest. However, few studies have explored the effect of the proportion of sawdust and sewage sludge raw materials on composting performance in the humification process. This study assessed the addition of sawdust in the sewage sludge composting process, regarding carbon content, presence of heavy metals, and humification of the organic compost. The experimental design employed was a randomized complete block design with five treatments featuring different proportions of organic residues to achieve C/N ratios between 30-1 (T1: 100% sewage sludge and 0% sawdust, T2: 86% sewage sludge and 14.0% sawdust, T3: 67% sewage sludge and 33% sawdust, T4: 55% sewage sludge and 45% sawdust, and T5: 46.5% sewage sludge and 53.5% sawdust) and five replications, totaling 25 experimental units. The addition of lignocellulosic residue in sewage sludge composting increased the levels of TOC and the C/N ratio, reduced the levels of pH, P, N, Na, Ba, and Cr, and did not interfere with the levels of K, Ca, Mg, S, CEC, labile carbon, and metals Fe, Zn, Cu, Mn, Ni, and Pb. The increase in the proportion of sawdust residue favored the degradation of aliphatic groups, increasing the presence of aromatic structures and reducing humification at the end of composting. The use of sawdust as a lignocellulosic residue in sewage sludge composting is a viable and efficient alternative to produce high-quality organomineral fertilizers.

Role of the molecular structure of humified organic matter in rice plant response to environmental lead pollution.

Humified organic matter has been shown to decrease Pb toxicity in plants. However, there are still gaps in our understanding of the mechanism by which this phenomenon occurs. In this study, we aimed to assess the ability of humic substances (HSs), humic acids (HAs), and fulvic acids (FAs) to enhance defense mechanisms in rice plants under lead (Pb)-stressed conditions. HS fractions were isolated from vermicompost using the chemical fractionation methodology established by the International Humic Substances Society. These fractions were characterized by solid-state NMR and FTIR. Chemometric analysis was used to compare humic structures and correlate them with bioactivity. Three treatments were tested to evaluate the protective effect of humic fractions on rice plants. The first experiment involved the application of humic fractions along with Pb. The second comprised pretreatment with humic fractions followed by subsequent exposure to Pb stress. The third experiment involved Pb stress and subsequent treatment with humic fractions. The root morphology and components of the antioxidative defense system were evaluated and quantified. The results showed that HS + Pb, HA + Pb, and FA + Pb treatment preserved root growth and reduced the levels of O2- and malondialdehyde (MDA) in the roots by up to 5% and 2%, respectively. Pretreatment of the plants with humic fractions promoted the maintenance of root growth and reduced the contents of O2-, H2O2, and MDA by up to 48%, 22%, and 20%, respectively. Combined application of humic fractions and Pb reduced the Pb content in plant tissues by up to 60%, while pretreatment reduced it by up to 80%. The protective capacity of humic fractions is related to the presence of peptides, lignin, and carbohydrate fragments in their molecular structures. These results suggest that products could be developed that can mitigate the adverse effects of heavy metals on agricultural crops.

Purification of pineapple bromelain by IMAC chromatography using chlorophyll-activated macroporous matrices.

This study investigated the purification of bromelain obtained from pineapple fruit using a new adsorbent for immobilized metal ion affinity chromatography (IMAC), with chlorophyll obtained from plant leaves as a chelating agent. The purification of bromelain was evaluated in batches from the crude extract of pineapple pulp (EXT), and the extract precipitated with 50 % ammonium sulfate (EXT.PR), the imidazole buffer (200 mM, pH 7.2) being analyzed and sodium acetate buffer, pH 5.0 + 1.0 NaCl as elution solutions. All methods tested could separate forms of bromelain with molecular weights between ±21 to 25 kDa. Although the technique using EXT.PR stood out in terms of purity, presenting a purification factor of around 3.09 ± 0.31 for elution with imidazole and 4.23 ± 0.12 for acetate buffer solution. In contrast, the EXT methods obtained values between 2.44 ± 0.23 and 3.21 ± 0.74 for elution with imidazole and acetate buffer, respectively, for purification from EXT.PR has lower yield values (around 5 %) than EXT (around 15 %). The number of steps tends to reduce yield and increase process costs, so the purification process in a monolithic bed coupled to the chromatographic system using the crude extract was evaluated. The final product obtained had a purification factor of 6, with a specific enzymatic activity of 59.61 ± 0.00 U·mg-1 and a yield of around 39 %, with only one band observed in the SDS-PAGE electrophoresis analysis, indicating that the matrix produced can separate specific proteins from the total fraction in the raw material. The IMAC matrix immobilized with chlorophyll proved promising and viable for application in protease purification processes.

Evaluation of blastocyst re-expansion, quality in relation to storage temperature, and sexing using blastocoel fluid after manual perforation with a hand-held needle involving in vivo produced equine embryos.

The present study was designed to evaluate equine blastocyst re-expansion rate, quality, and sex following perforation of the blastocoel, collection of blastocoel fluid (BF), and PCR amplification of free DNA. Experiment 1 tested the feasibility of the BF sample collection with a hand-held, small-gauged needle (26g) and subsequent PCR amplification of the TSP-Y gene for males and AMEL-Y gene for males and AMEL-X gene for females. Experiment 2 tested the application of the technique. Equine embryos were collected via uterine flushes 8d after ovulation. Thereafter, embryos (n = 19) were initially assessed and transferred to a 50 µL droplet of holding medium in which the blastocoel was manually perforated as in Experiment 1. Within 1 min of detecting a diameter decrease or collapse, the entire volume of each droplet of medium was collected and stored at -20 °C until PCR. In Experiment 1, amplification of the TSP-Y gene was positive for males at 60% (9/15) and negative for females at 40% (6/15). In Experiment 2, a total of 42 embryos were randomly assigned to a collapsed embryo (CE) or intact embryo (IE) groups and stored at room temperature (RT, 25 °C) or cold temperature (CT, 5 °C) for 24h as follows: 1) CERT, n = 11; 2) CECT n = 11; 3) IERT, n = 10; and 4) IECT, n = 10. After 24h, embryo diameter and quality were reassessed. For all collapsed embryos (n = 19), blastocoel fluid was subjected to double PCR amplification of the TSPY gene with blood from adult male and female horses as controls. Positive gene amplification indicated 57.9% (11/19) of embryos were male and negative amplification indicated 31.6% (6/19) of embryos were female. Relative to the least diameter (0%) after perforation of collapsed embryos or fullest diameter (100%) of intact embryos at T0, percentage change in diameter and quality Grade 1 or 2 embryos after 24h of storage for all groups were, respectively: 31.2% and 54% for CERT group, 28.2% and 0% for CECT group, 25.9% and 100% for IERT group, 4.3% and 80% for IECT group, respectively. Thus, needle-induced leakage and collapse of the blastocoel at T0 resulted in a high rate of blastocyst re-expansion (69%) with many embryos (54%) achieving good quality at T24 with potential for transfer as either male or female embryos. For both collapsed and intact embryos, it was observed that storage for 24h at room temperature (25 °C) was associated with improved embryo growth and morphological quality compared to storage at cold temperature (5 °C).

Baseline metal and metalloid contamination in two marine sponge species, Hymeniacidon heliophila and Desmapsamma anchorata, from southeastern Brazil.

Sponges are not routinely employed as metal bioindicators in Brazil. In this sense, this study reports baseline metal and metalloid concentrations, determined by inductively coupled plasma mass spectrometry, for two Demospongiae sponge species, Hymeniacidon heliophila and Desmapsamma anchorata, sampled from two Southeastern Brazil areas. Sponges from Ilha Grande Bay, an Environmental Protection Area, exhibited higher Al, As, Cd, Co, Cr, Fe, and Ni levels compared to Vermelha Beach, a metropolitan area in the Rio de Janeiro city. Several strong correlations were noted between elemental pairs, indicating common contamination sources and/or similar metabolic detoxification routes. Comparisons of the means determined herein for each study site to other reports indicate mostly lower Ag, As, Co, Cd, and Cu levels, while Al levels were higher than other studies, and Cr, Ni, and Fe were within reported ranges. These baseline data further knowledge on metal pollution in Desmspongiae members, which are still limited.

Influences of plant organ, genotype, and cultivation site on the endophytic bacteriome of maize (Zea mays L.) in the semi-arid region of Pernambuco, Brazil.

Endophytic bacteria play a crucial role in plant development and adaptation, and the knowledge of how endophytic bacteria assemblage is influenced by cultivation site and plant genotype is an important step to achieve microbiome manipulation. This work aimed to study the roots and stems of endophytic bacteriome of four maize genotypes cultivated in two regions of the semi-arid region of Pernambuco - Brazil. Our hypothesis is that the endophytic community assemblage will be influenced by plant genotypes and cultivation region. Metabarcoding sequencing data revealed significant differences in alfa diversity in function of both factors, genotypes, and maize organs. Beta diversity analysis showed that the bacterial communities differ mainly in function of the plant organ. The most abundant genera found in the samples were Leifsonia, Bacillus, Klebsiella, Streptomyces, and Bradyrhizobium. To understand ecological interactions within each compartment, we constructed co-occurrence network for each organ. This analysis revealed important differences in network structure and complexity and suggested that Leifsonia (the main genera found) had distinct ecological roles depending on the plant organ. Our data showed that root endophytic maize bacteria would be influenced by cultivation site, but not by genotype. We believe that, collectively, our data not only characterize the bacteriome associated with this plant and how different factors shape it, but also increase the knowledge to select potential bacteria for bioinoculant production.

Sensitivity and specificity of a syphilis rapid diagnostic test in blood donors' samples.

Rapid Diagnostic Tests (RDT) are useful to identify syphilis cases, particularly for hard-to-reach populations and if laboratory services are scarce. However, RDT performance may be suboptimal. We aimed to assess the sensitivity and specificity of a syphilis RDT using well-characterized blood donors' samples. We categorized samples from 811 blood donors into five groups: 1 - Samples with reactive Chemiluminescence (QML), FTA-Abs, and VDRL; 2 - Samples with reactive QML and FTA-Abs, and nonreactive VDRL; 3 - Samples with reactive QML, and nonreactive for other markers (false-positives); 4 - Controls with nonreactive QML; and 5 - Samples reactive for HIV, with nonreactive QML. Sensitivity was tested in groups 1 (overall and according to VDRL titers) and 2; specificity was tested in groups 3‒5. The RDT had high specificity, even in samples reactive for HIV. The sensitivity was high (91.9%) in samples with reactive VDRL but varied between 75.0%‒100% according to VDRL titers. The overall sensitivity was lower (81.3%) in samples with reactive FTA-Abs and nonreactive VDRL. The RDT is a useful tool to detect active syphilis but may be more limited for cases with very early or remote infection, or those with prior treatment. When higher sensitivity is needed, additional strategies including recurrent testing or laboratory-based tests may be required.

Expression of Endothelin-1, Endothelin Receptor-A, and Endothelin Receptor-B in facial melasma compared to adjacent skin.

Background/Objectives: Although melasma is highly prevalent, its pathogenesis is not yet fully understood. In the skin, endothelin-1 (ET-1) is primarily produced by keratinocytes in response to UVB exposure, which is mediated by an increase in IL-1α or reactive oxygen species. ET-1 plays a role in melanogenesis by binding to specific receptor B (ERB) or receptor A (ERA). However, the expression of ET-1, ERA, and ERB in melasma has not been systematically investigated. The objective of this study was to evaluate the expression of ET-1, ERA, and ERB in facial melasma compared to the adjacent unaffected skin. Methods: Cross-sectional study, with 40 skin samples (20: facial melasma; 20: adjacent unaffected skin) from women with facial melasma without treatment for 30 days except for sunscreen. A triple staining immunofluorescence technique was performed for anti-vimentin, DAPI, plus one of the following antibodies: (a) anti-ET1, (b) anti-ERA; (c) anti-ERB. Interfollicular areas on the slides of each topography (melasma; unaffected skin) were photographed in triplicate under confocal laser microscopy. The mean staining intensities of the image histograms (0-255 pixels intensity) were estimated for different types of cells (suprabasal keratinocytes, basal layer, and upper dermis) and were blindly compared between topographies. Results: The mean (SD) age of the participants was 44.9 (9.2). The expression of ET-1 was increased in the whole epidermis with melasma when compared to the adjacent skin, being 32.8% (CI95% 14.7%-52.6%) higher in the spinous layer (p=0.013), 30.4% (CI95% 13.7%-47.9%) higher in the basal layer (p=0.014), and 29.7% (CI95% 11.4%-49.7%) higher in the melanocytes (p=0.006). There was no noticeable expression of ET-1 within the cells on the upper dermis. Neither ERA nor ERB resulted in differential epidermal expression between melasma and unaffected skin (p≥0.1). Conclusion: ET-1 is expressed more intensely on the epidermis from the skin with facial melasma compared to the unaffected adjacent skin.

Are more physical education classes related to less time in leisure-time sedentary behavior? An analysis including adolescents from 73 countries.

This study aimed to verify the association between the weekly frequency of physical education (PE) classes and leisure sitting time among adolescents. We analyzed data from 73 countries using the Global School-based Student Health Survey (283,233 adolescents between 11 and 18 years of age). Leisure sitting time and weekly frequency of PE classes were self-reported. Sex, age, and food insecurity were used as covariates and the analyses were stratified by world regions and country income level. Poisson regression models (random-effects meta-analysis) were used for the main analyses. In comparison with 1 PE class per week (reference group), those with no PE classes presented a lower prevalence of ≥ 3 h/d of leisure sitting time (PR [95%CI] = 0.94 [0.91; 0.98]). On the other hand, adolescents with 2 days (PR [95%CI] = 1.06 [1.02; 1.26]), 3-4 days (PR [95%CI] = 1.17 [1.12; 1.22]), and 5 days (PR [95%CI] = 1.08 [1.04; 1.11]) of PE classes presented a higher likelihood of ≥ 3 h/d of leisure sitting time. No clear differences were observed for the different world regions and country income levels. We conclude that a higher weekly frequency of PE classes is associated with increased leisure sitting time among adolescents worldwide.

Prospective cohort of parameters of glycemic and lipid metabolism after abdominoplasty in normal weight and formerly obese patiens.

Background: Obesity poses a major risk for cardiovascular diseases, while it is almost a consensus that intra-abdominal adiposity has a more deleterious effect for metabolic syndrome. In this sense, it is speculated that lipectomy or liposuction would be metabolically harmful, as it changes the abdominal-superficial adipose tissue ratio. However, the literature has shown conflicting evidence. Methods: In order to evaluate the possibility of metabolism alteration resulting from body coutouring surgery, a prospective cohort was implemented with 35 patients who underwent abdominoplasty, including some with a history of massive weight loss. Fasting blood glucose, fasting plasma insulin, triglycerides, total cholesterol and fractions were requested preoperatively and in the third postoperative month. The groups were also compared with each other. Results: No statistically significant variation between the exams collected in the preoperative period and those collected after abdominoplasty was found. There was a statistically significant difference in LDL (low-density lipoprotein; p = 0.033) and non-HDL (non-high-density lipoprotein) cholesterol (p = 0.020) between the two control tests of the groups surveyed. There were also differences in comorbidities (p = 0.006) and complications (p <0.001) between the groups. Conclusions: Abdominoplasty was not able of changing tests that assess glycemic and lipid metabolism three months after the operation. Our attention was drawn to the fact that patients who had massive weight loss had better control of LDL cholesterol (p = 0.033) and non-HDL cholesterol (p = 0.020), despite having higher weight and body mass index (p <0.001).

Current Fragment-to-lead Approaches Starting from the 7-azaindole: The Pharmacological Versatility of a Privileged Molecular Fragment.

Fragment-based drug discovery is one of the most powerful paradigms in the recent context of medicinal chemistry and is being widely practiced by academic and industrial researchers. Currently, azaindoles are among the most exploited molecular fragments in pharmaceutical innovation projects inspired by fragment-to-lead strategies. The 7-azaindole is the most prominent representative within this remarkable family of pyrrolopyridine fragments, as it is present in the chemical structure of several approved antitumor drugs and also of numerous therapeutic candidates. In this paper, a brief overview on existing proofs of concept in the literature will be presented, as well as some recent works that corroborate 7-azaindole as a privileged and pharmacologically versatile molecular fragment.

Fragment-based Drug Discovery Successful Contributions to Current Pharmacotherapeutic Agents Arsenal against Aggressive Cancers: A Mini-Review.

After a decade of approval of the drug vemurafenib in 2011, the hopeless scenario imposed by some severe cancer types has been mitigated by the magic bullets developed through fragment-based drug discovery. Moreover, this recent approach to medicinal chemistry has been successfully practiced by academic laboratories and pharmaceutical industry workflows focused on drug design with an enhanced profile for chemotherapy of aggressive tumors. This mini-review highlights the successes achieved by these research campaigns in the fruitful field of the molecular fragment paradigm that resulted in the approval of six new anticancer drugs in the last decade (2011-2021), as well as several promising clinical candidates. It is a particularly encouraging opportunity for other researchers who want to become aware of the applicability and potency of this new paradigm applied to the design and development of powerful molecular weapons in the constant war against these merciless scourges of humanity.

The use of pracaxi oil collector in the selective flotation of xenotime from silicates.

Rare earth elements have played a key role in technological advancement, attracting great visibility in the global commodity market. Xenotime, a heavy rare earth resource (YPO4), can be found associated with granitic rocks, as in the Pitinga deposit, located in the Brazilian Amazon region, where the main gangue minerals are quartz, microcline and albite. This research investigates the application of a new collector produced from pracaxi oil, an Amazon oil abundant in Brazil, in the selective flotation between xenotime and its main gangue minerals. The study conducted the synthesis and characterization of the collector, the chemical, mineralogical and surface characterization of minerals, as well as the evaluation of collector adsorption and flotability via microflotation tests, zeta potential measurements, surface tension determination and XRD, WDXRF, ICP-MS, FTIR and XPS analyses. The pracaxi collector was found to be mainly composed of oleic acid (56.2%), linoleic acid (14.1%) and behenic acid (10.6%), in addition to exhibiting a critical micelle concentration (CMC) of approximately 150 mg/L. Microflotation tests indicated that the best condition for selective recovery of xenotime occur at alkaline condition (pH 9.0), presenting selectivity of approximately 90% with collector concentration of 10.0 mg/L. The zeta potential data confirmed a selective adsorption of pracaxi collector onto xenotime, with an increase in the surface charge from -30 mV to -68 mV, whereas no significant changes were detected in the silicates. The FTIR spectra showed the appearance of a band at 1545 cm-1 on the surface of the xenotime after collector adsorption, which indicates, along with the zeta potential data, the chemical nature of the adsorption. The presence of small amounts of iron in the lattice structure of silicate gangues can act as an activator, and therefore, may be responsible for the small flotability of these minerals. The performance of the pracaxi oil collector presented in this study indicates the great potential of this Amazonian oil for application in the selective flotation of xenotime ores found in the region.

In Vitro Transdifferentiation Potential of Equine Mesenchymal Stem Cells into Schwann-Like Cells.

Schwann cells (SCs) are essential for the regenerative processes of peripheral nerve injuries. However, their use in cell therapy is limited. In this context, several studies have demonstrated the ability of mesenchymal stem cells (MSCs) to transdifferentiate into Schwann-like cells (SLCs) using chemical protocols or co-culture with SCs. Here, we describe for the first time the in vitro transdifferentiation potential of MSCs derived from equine adipose tissue (AT) and equine bone marrow (BM) into SLCs using a practical method. In this study, the facial nerve of a horse was collected, cut into fragments, and incubated in cell culture medium for 48 h. This medium was used to transdifferentiate the MSCs into SLCs. Equine AT-MSCs and BM-MSCs were incubated with the induction medium for 5 days. After this period, the morphology, cell viability, metabolic activity, gene expression of glial markers glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), p75 and S100ß, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), and the protein expression of S100 and GFAP were evaluated in undifferentiated and differentiated cells. The MSCs from the two sources incubated with the induction medium exhibited similar morphology to the SCs and maintained cell viability and metabolic activity. There was a significant increase in the gene expression of BDNF, GDNF, GFAP, MBP, p75, and S100ß in equine AT-MSCs and GDNF, GFAP, MBP, p75, and S100ß in equine BM-MSCs post-differentiation. Immunofluorescence analysis revealed GFAP expression in undifferentiated and differentiated cells, with a significant increase in the integrated pixel density in differentiated cells and S100 was only expressed in differentiated cells from both sources. These findings indicate that equine AT-MSCs and BM-MSCs have great transdifferentiation potential into SLCs using this method, and they represent a promising strategy for cell-based therapy for peripheral nerve regeneration in horses.