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Dynamics of epigenetic modifications such as acetylation and deacetylation of histone proteins have been shown to be crucial for the life cycle development and survival of Plasmodium falciparum, the deadliest malaria parasite. In this study, we present a novel series of peptoid-based histone deacetylase (HDAC) inhibitors incorporating nitrogen-containing bicyclic heteroaryl residues as a new generation of antiplasmodial peptoid-based HDAC inhibitors. We synthesized the HDAC inhibitors by an efficient multicomponent protocol based on the Ugi four-component reaction. The subsequent screening of 16 compounds from our mini-library identified 6i as the most promising candidate, demonstrating potent activity against asexual blood-stage parasites (IC 50 Pf3D7 = 30 nM; IC 50 PfDd2 = 98 nM), low submicromolar activity against liver-stage parasites (IC 50 PbEEF = 0.25 μM), excellent microsomal stability (t 1/2  > 60 min), and low cytotoxicity to HEK293 cells (IC 50  = 136 μM)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Ruthenium(II) tetraamine nitrosyl complexes with N-heterocyclic ligands are known for their potential as nitric oxide (NO • ) donors, capable of releasing NO • through either direct photodissociation or one-electron reduction of the Ru(II)NO + center. This study delivers a novel insight into the one-electron reduction mechanism for the model complex trans -[Ru II (NO)(NH 3 ) 4 (py)] 3+ (RuNOpy, py = pyridine) in phosphate buffer solution (pH 7.4). In situ FT-IR spectroelectrochemistry reveals that the pyridine ligand is readily released upon one-electron reduction of the nitrosyl complex, a finding supported by nuclear magnetic resonance spectroscopy ( 1 H NMR) and electrochemistry coupled to mass spectrometry (EC-MS), which detect free pyridine in solution. However, direct evidence of NO • release from RuNOpy as the primary step following reduction was not observed. Interestingly, FT-IR results indicate that the isomers of the nitrosyl complex, cis -[Ru(NO)(NH 3 ) 4 (OH)] + and trans -[Ru(NO)(NH 3 ) 4 (OH)] + , are formed following reduction and pyridine labilization, initiating an outer-sphere electron transfer process that triggers a chain electron transfer reaction. Finally, nitric oxide is liberated as an end product, arising from the reduction of the hydroxyl isomer complexes cis -[Ru(NO)(NH 3 ) 4 (OH)] 2+ and trans -[Ru(NO)(NH 3 ) 4 (OH)] 2+ . This study provides new insights into the reduction mechanism and transformation pathways of ruthenium nitrosyl complexes, contributing to our understanding of their potential as NO • donors.

Decision makers are often confronted with inadequate information to predict nutrient loads and yields in freshwater ecosystems at large spatial scales. We evaluate the potential of using data mapped at large spatial scales (regional to global) and often coarse resolution to predict nitrogen yields at varying smaller scales (e.g., at the catchment and stream reach level). We applied the SPAtially Referenced Regression On Watershed attributes (SPARROW) model in three regions: the Upper Midwest part of the United States, New Zealand, and the Grande River Basin in southeastern Brazil. For each region, we compared predictions of nitrogen delivery between models developed using novel large-scale datasets and those developed using local-scale datasets. Large-scale models tended to underperform the local-scale models in poorly monitored areas. Despite this, large-scale models are well suited to generate hypotheses about relative effects of different nutrient source categories (point and urban, agricultural, native vegetation) and to identify knowledge gaps across spatial scales when data are scarce. Regardless of the spatial resolution of the predictors used in the models, a representative network of water quality monitoring stations is key to improve the performance of large-scale models used to estimate loads and yields. We discuss avenues of research to understand how this large-scale modelling approach can improve decision making for managing catchments at local scales, particularly in data poor regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Hybrid nanocomposites combining biopolymer fibers incorporated with nanoparticles (NPs) have received increasing attention due to their remarkable characteristics. Inorganic NPs are typically chosen for their properties, such as magnetism and thermal or electrical conductivity, for example. Meanwhile, the biopolymer fiber component is a backbone, and could act as a support structure for the NPs. This shift towards biopolymers over traditional synthetic polymers is motivated by their sustainability, compatibility with biological systems, non-toxic nature, and natural decomposition. This study employed the solution blow spinning (SBS) method to obtain a nanocomposite comprising poly(vinyl pyrrolidone), PVA, and gelatin biodegradable polymer fibers incorporated with magnetic iron oxide nanoparticles coated with poly(acrylic acid), PAA 2k , coded as γ-Fe 2 O 3 -NPs-PAA 2k . The fiber production process entailed a preliminary investigation to determine suitable solvents, polymer concentrations, and spinning parameters. γ-Fe 2 O 3 -NPs were synthesized via chemical co-precipitation as maghemite and coated with PAA 2k through the precipitation-redispersion protocol in order to prepare γ-Fe 2 O 3 -NPs-PAA 2k . Biopolymeric fibers containing coated NPs with sub-micrometer diameters were obtained, with NP concentrations ranging from 1.0 to 1.7% wt. The synthesized NPs underwent characterization via dynamic light scattering, zeta potential analysis, and infrared spectroscopy, while the biopolymer fibers were characterized through scanning electron microscopy, infrared spectroscopy, and thermogravimetric analysis. Overall, this study demonstrates the successful implementation of SBS for producing biopolymeric fibers incorporating iron oxide NPs, where the amalgamation of materials demonstrated superior thermal behavior to the plain polymers. The thorough characterization of the NPs and fibers provided valuable insights into their properties, paving the way for their potential applications in various fields such as biomedical engineering, environmental remediation, and functional materials.

The precise mode of action of ganaplacide (KAF156), a phase III antimalarial candidate, remains elusive. Here we employ omics-based methods with the closely related chemical analog, GNF179, to search for potential Plasmodium targets. Ranking potential targets derived from chemical genetics and proteomic affinity chromatography methodologies identifies SEY1 , or Synthetic Enhancement of YOP1, which is predicted to encode an essential dynamin-like GTPase implicated in homotypic fusion of endoplasmic reticulum (ER) membranes. We demonstrate that GNF179 decreases Plasmodium SEY1 melting temperature. We further show that GNF179 binds to recombinant Plasmodium SEY1 and subsequently inhibits its GTPase activity, which is required for maintaining ER architecture. Using ultrastructure expansion microscopy, we find GNF179 treatment changes parasite ER and Golgi morphology. We also confirm that SEY1 is an essential gene in P. falciparum . These data suggest that SEY1 may contribute to the mechanism of action of imidazolopiperazines and is a new and attractive druggable target.

This study shows the development of a software for calculating the number of nursing team members required for providing care during the coronavirus disease 2019 pandemic. Study about the development of a technology based on the literature about data and indicators. The indicators were systematized in the following dimensions: institutional, professional, and occupational structure, all with a focus on coronavirus disease 2019. The software was created to be used on the Web, client-server, in browsers such as Internet Chrome, Explorer, and/or Mozilla Firefox, accessing via an Internet address and also allowing access by Windows, Android, and Linux operating systems, with MySQL database used for data storage. The data and indicators related to the institutional structure for coronavirus disease 2019 were systematized with 10 dimensions and indicators, and the professional and occupational structure, with 14 dimensions and indicators. The construction of computer requirements followed the precepts of software engineering, with theoretical support from the area. In the evaluation of the software, data simulation revealed points that had to be adjusted to ensure security, data confidentiality, and easy handling. The software provides to calculate the size and quality of the team, nursing sizing required due to the needs generated by the coronavirus disease 2019 pandemic., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Acute pancreatitis following surgical or endoscopic procedures on the pancreas can compromise the outcome and lead to severe complications and even death. The aim of this study was to determine whether prolonged fasting affects the severity of acute pancreatitis (AP)., Methods: Male mice were divided into 4 groups: Group CF (n=5) control animals that fasted for 24 hours; Group CNF (n=5) control animals that did not fast; Group APF (n=7) that fasted for 24 hours and underwent induction of acute pancreatitis (AP) and Group APNF (n=7) that did not fast and underwent AP. Eight hours after AP blood was collected for evaluation of cytokines: IL-1β, IL-6, IL-10, TNF-α and MCP-1. Liver tissue was collected for determination of Malondialdehyde, pancreatic tissue for determination of enzyme content and lung tissue for determination of myeloperoxidase., Results: Significant increase in pancreatic amylase content was observed in group CF and increased serum levels of IL -6, Il-10 and MCP-1 were in group APF. Liver malondialdehyde was also increased in APF animals. APF group showed much more necrosis of the pancreatic acinar cells., Conclusion: In the present study, we observed an increase in the severity of acute pancreatitis with prolonged fasting in a severe acute pancreatitis model. These results suggest that in clinical practice, the preoperative fasting time should be shortened before pancreatic procedures.

Background: Neglected Tropical Diseases (NTD) are chronic infectious conditions that primarily affect marginalized populations. The chemotherapeutic arsenal available for treating NTD is limited and outdated, which poses a challenge in controlling and eradicating these diseases. This is exacerbated by the pharmaceutical industry's lack of interest in funding the development of new therapeutic alternatives. In addition, a considerable number of drugs used in NTD therapy have low aqueous solubility. To address this issue, solubility enhancement strategies, such as the use of inclusion complexes with cyclodextrins (CD) can be employed., Objective: Therefore, this systematic review aims to present the application of CD in complexing with drugs and chemotherapeutic compounds used in the therapy of some of the most prevalent NTD worldwide and how these complexes can enhance the treatment of these diseases., Methods: Two bibliographic databases, Science Direct and PubMed, were used to conduct the search. The selection of studies and the writing of this systematic review followed the criteria outlined by the PRISMA guidelines., Results: From a total of 978 articles, 23 were selected after applying the exclusion criteria. All the studies selected were consistent with the use of CD as a strategy to increase the solubility of therapeutic agents used in NTD., Conclusion: The results indicate that CD can enhance the solubility of chemotherapeutic agents for the treatment of Neglected Tropical Diseases (NTD). This review presents data that clearly highlights the potential use of CD in the development of new treatments for neglected tropical diseases. It can assist in the formulation of future treatments that are more effective and safer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Benznidazole, the drug of choice for treating Chagas Disease (CD), has significant limitations, such as poor cure efficacy, mainly in the chronic phase of CD, association with side effects, and parasite resistance. Understanding parasite resistance to benznidazole is crucial for developing new drugs to treat CD., Areas Covered: Here, the authors review the current understanding of the molecular basis of benznidazole resistance. Furthermore, they discuss the state-of-the-art methods and critical outcomes employed to evaluate the efficacy of potential drugs against T. cruzi , aiming to select better compounds likely to succeed in the clinic. Finally, the authors describe the different strategies employed to overcome resistance to benznidazole and find effective new treatments for CD., Expert Opinion: Resistance to benznidazole is a complex phenomenon that occurs naturally among T. cruzi strains. The combination of compounds that inhibit different metabolic pathways of the parasite is an important strategy for developing a new chemotherapeutic protocol.

Controlling malaria requires new drugs against Plasmodium falciparum . The P. falciparum cGMP-dependent protein kinase (PfPKG) is a validated target whose inhibitors could block multiple steps of the parasite's life cycle. We defined the structure-activity relationship (SAR) of a pyrrole series for PfPKG inhibition. Key pharmacophores were modified to enable full exploration of chemical diversity and to gain knowledge about an ideal core scaffold. In vitro potency against recombinant PfPKG and human PKG were used to determine compound selectivity for the parasite enzyme. P. berghei sporozoites and P. falciparum asexual blood stages were used to assay multistage antiparasitic activity. Cellular specificity of compounds was evaluated using transgenic parasites expressing PfPKG carrying a substituted "gatekeeper" residue. The structure of PfPKG bound to an inhibitor was solved, and modeling using this structure together with computational tools was utilized to understand SAR and establish a rational strategy for subsequent lead optimization.

The diagnosis of attention-deficit hyperactivity disorder (ADHD) is based on the health history and on the evaluation of questionnaires to identify symptoms. This evaluation can be subjective and lengthy, especially in children. Therefore, a biomarker would be of great value to assist mental health professionals in the process of diagnosing ADHD. Event-related potential (ERP) is one of the most informative and dynamic methods of monitoring cognitive processes. Previous works suggested that specific sets of ERP-microstates are selectively affected by ADHD. This paper proposes a new methodology for the ERP-microstate analysis and identification of ADHD patients based on complex networks to model the microstate topographic maps. The analysis of global and local features of ERP-microstate networks revealed topological differences between ADHD and healthy control. The classification using a neural network with a single hidden layer resulted in an average accuracy of 99.72% in binary classification and 99.31% in the classification of ADHD subtypes. The results were compared to the power band spectral densities and the energy of wavelet coefficients. The temporal features of ERP-microstates, such as frequency of occurrence, duration, coverage, and transition probabilities, were also evaluated for comparison proposes. Overall, the selected topological features of ERP-microstate networks derived from the proposed method performed significantly better classification results. The results suggest that topological features of ERP-microstate networks are promising to identify ADHD and its subtypes with a neural network model compared to power band spectrum density, wavelet transform, and temporal features of ERP-microstates., (© 2023. International Federation for Medical and Biological Engineering.)

Background: Chagas disease is caused by the parasite Trypanosoma cruzi , and the lack of effective and safe treatments makes identifying new classes of compounds with anti- T. cruzi activity of paramount importance. Methods: Hit-to-lead exploration of a metabolically stable N -imidazoylpiperazine was performed. Results: Compound 2 , a piperazine derivative active against T. cruzi , was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives. Conclusion: Compounds 6e and 10a were identified as optimized compounds with low micromolar in vitro activity, low cytotoxicity and suitable preliminary absorption, distribution, metabolism and excretion and physicochemical properties. Both compounds reduced parasitemia in mouse models of Chagas disease, providing a promising opportunity for further exploration of new antichagasic compounds.

This study investigates the interaction between sakuranetin, a versatile pharmaceutical flavonoid, and monolayers composed of unsaturated phospholipids, serving as a surrogate for cell membranes. The phospholipids were 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE). We conducted a series of experiments to comprehensively investigate this interaction, including surface pressure assessments, Brewster angle microscopy (BAM), and polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). Our findings unequivocally demonstrate that sakuranetin interacts with these phospholipids, expanding the monomolecular films. Notably, regarding POPC, the presence of sakuranetin led to a reduction in stability and a decline in surface elasticity, which can likely be attributed to intricate molecular rearrangements at the interface. The visual evidence of aggregations in BAM images reinforces the interactions substantiated by PM-IRRAS, highlighting sakuranetin's interaction with the polar and nonpolar regions of POPC. However, it is worth noting that these aggregations do not appear to contribute significantly to the viscosity of the mixed film, and our investigations did not reveal any substantial hysteresis. In contrast, when examining POPE, we observed a minor reduction in thermodynamic stability, indicative of fewer rearrangements within the monolayer. This notion was further reinforced by the limited presence of aggregations in the BAM images. Sakuranetin also increased the rigidity of the lipid monolayer; nevertheless, the monolayer remained predominantly elastic, facilitating easy re-spreading on the surface, especially for the first lipid. PM-IRRAS analysis unveiled interactions between sakuranetin and POPE's polar and nonpolar segments, compellingly explaining the observed monolayer expansion. Taken together, our data suggest that sakuranetin was more effectively incorporated into the monomolecular layer of POPE, indicating that membranes comprised of POPC might exhibit a greater degree of interaction in the presence of this pharmacologically active compound., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism., (© 2024. The Author(s).)

Background: Morus nigra L. is a plant with significant potential for drug development due to the presence of numerous bioactive compounds in its various parts., Objectives: This article aims to compile the technological perspectives of Morus nigra L. towards drug development and therapeutic indications based on registered patents in databases., Methods: The study analyzed patents published within the last five years, focusing on products derived from different parts of the Morus nigra L. plant. Patent databases such as the European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), the World Intellectual Property Organization (WIPO), and the National Institute of Industrial Property Databases (INPI) were examined., Results: A total of 45 patents were categorized by country of origin, type of applicant, extraction method, and therapeutic indications. China had the highest number of patent filings (43.48%), and private companies were the primary technology patent holders (38.64%). Noteworthy extraction methods included ultrasound-assisted extraction, decoction, infusion, and maceration. The most utilized plant parts were leaves (44.44%), followed by fruits (35.56%), root bark (15.56%), and stems (4.44%). The main therapeutic indications identified were the treatment of hyperglycemia and dyslipidemia (43.33%), along with digestive problems, cosmetics, nutrition, and cleaning applications., Conclusion: The study of patents covers discoveries and advancements often absent in scientific articles, making a review focused on this advanced information crucial for expanding existing scientific knowledge. Even if some therapies have been explored previously, patents can reveal innovative approaches and fresh perspectives that contribute to sustained scientific progress., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the gastrointestinal tract. The etiology is not fully understood, but environmental, microbial, and immunologic factors, as well as a genetic predisposition, play a role. UC is characterized by episodes of abdominal pain, diarrhea, bloody stools, weight loss, severe colonic inflammation, and ulceration. Despite the increase in the frequency of UC and the deterioration of the quality of life, there are still patients who do not respond well to available treatment options. Against this background, natural products such as polysaccharides are becoming increasingly important as they protect the intestinal mucosa, promote wound healing, relieve inflammation and pain, and restore intestinal motility. In this study, we investigated the effect of a polysaccharide isolated from the biomass of Campomanesia adamantium and Campomanesia pubescens (here referred to as CPW) in an experimental model of acute and chronic ulcerative colitis induced by dextran sulfate sodium (DSS). CPW reversed weight loss, increased disease activity index (DAI), bloody diarrhea, and colon shortening. In addition, CPW reduced visceral mechanical hypersensitivity, controlled oxidative stress and inflammation, and protected the mucosal barrier. CPW is not absorbed in the intestine, does not inhibit cytochrome P450 proteins, and does not exhibit AMES toxicity. These results suggest that CPW attenuates DSS-induced acute and chronic colitis in mice and may be a potential alternative treatment for UC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Spodoptera frugiperda (fall armyworm) is one of the most important maize pests in the world and the baculovirus Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV), a natural pathogen of this pest, has been used as a biopesticide for its control. At present, in vivo strategies at the commercial scale are employed by multiplying the virus in the host insect in biofactory facilities; however, in vitro large-scale production is an interesting alternative to overcome the limitations of baculoviruses massal production. This study aimed to develop the process of the SfMNPV in vitro production by evaluating the effects of different multiplicities of infection (MOI) and nutritional supplements, morphological and molecular analysis of the infection on the growth of Sf9 cells and virus production. The Bioreactor Stirred Tank Reactor (STR) approach with glutamine-supplemented Sf-900 III serum free culture medium, combined with the MOI of 1.0, showed the best viral production performance, with a specific productivity above 300 occlusion bodies (OBs)/cell and volumetric productivity of 9.0 × 10 11 OBs/L.

This study aimed to evaluate Attalea funifera seed oil with or without resveratrol entrapped in organogel nanoparticles in vitro against A375 human melanoma tumor cells. Organogel nanoparticles with seed oil (SON) or with resveratrol entrapped in the seed oil (RSON) formed functional organogel nanoparticles that showed a particle size <100 nm, polydispersity index <0.3, negative zeta potential, and maintenance of electrical conductivity. The resveratrol entrapment efficiency in RSON was 99 ± 1%. The seed oil and SON showed no cytotoxicity against human non-tumor cells or tumor cells. Resveratrol at 50 μg/mL was cytotoxic for non-tumor cells, and was cytotoxic for tumor cells at 25 μg/mL. Resveratrol entrapped in RSON showed a decrease in cytotoxicity against non-tumor cells and cytotoxic against tumor cells at 50 μg/mL. Thus, SON is a potential new platform for the delivery of resveratrol with selective cytotoxic activity in the treatment of melanoma.

Diet composition has a great impact on body composition. Several studies have suggested a beneficial effect of adding olive oil to a calorie-restricted diet as a weight loss strategy. However, there is no clear direction regarding the effect of olive oil on body fat distribution. This systematic review with meta -analysis aims to investigate the effect of olive oil consumption (for cooking or as a supplement) on body fat distribution in adults. The present study was conducted following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and was registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42021234652). All randomized clinical trials of parallel or crossover design found in PubMed ( via MEDLINE), EMBASE, Web of Science and Scopus databases that compared the effects of olive oil with other oils on body fat distribution in adults were included. 52 articles were included. The results indicate that the consumption of olive oil does not seem to alter the distribution of body fat, despite a small indication that supplementation in capsules can increase adipose mass (Mean Difference = 0.28 kg, 95% CI [-0.27, 0.83]; between-groups difference p = 0.59) and waist circumference (mean difference = 1.74 kg, 95% CI [0.86, 1.62]; between-groups difference p < 0.01) and decrease its auxiliary culinary use (mean difference = -0.32 kg, 95% CI [-0.90, 0.26]). Lean mass responds negatively to OO the higher the dose (slope = -0.61, 95% CI [-1.01, -0.21], p = 0.003) and time offered (slope = -0.8822, 95% CI [-1.44, -0.33], p = 0.002). In conclusion, this systematic review showed that OO ingestion in different delivery vehicles, dosages, and durations can interfere body composition. It is important to emphasize that some other aspects of the population and the intervention, that were not possible to be explored in the analysis, could confound the real effects of OO on body composition.

Fungi, yeasts and bacteria produce volatile compounds during their metabolism. In this study, the volatile compounds produced by yeast strains (Saccharomyces cerevisiae and Rhodotorula mucilaginosa) and fungal strains (Aspergillus carbonarius and Aspergillus ochraceus) during competitive interactions were investigated by solid-phase microextraction coupled with gas chromatography-mass spectrometry. Fifty-six volatile compounds were identified representing alcohols, aldehydes, esters, ketones, aromatic compounds, acids, furans, phenols, and nitrogen compounds, being the largest amount in the class of esters and alcohols. Eight compounds were identified only in interactive culture conditions such as 2-amino-1-propanol, isopropylamine, dimethylamine, pentyl propanoate, ethyl-2-aminopropanoate, acetone, oxalic acid, and β-elemene and five of these were produced in cocultures including A. carbonarius. These will be developed for future biotechnological applications such as in the pharmaceutical and biological industry to produce drugs. Antimicrobial and antifungal activities; Solvent and herbicide; flavoring ingredient; solvent, plastic synthesis, nail polish remover and thinner, pesticide and herbicide; important in the complexation of minerals in the soil; and plant-environment interactions, defending predators, pathogens, and competitors., (© 2023 Wiley-VCH GmbH.)

Toxoplasmosis is a worldwide disease caused by Toxoplasma gondii, which can infect diverse hosts, including dogs. Although T. gondii infection in dogs is usually subclinical, they are susceptible to infection and develop a specific immune response to the parasite. In 2018, the largest outbreak of human toxoplasmosis in the world occurred in Santa Maria, in southern Brazil; however, the impact of this outbreak on other hosts was not investigated at the time. Considering that dogs often share the same environmental sources of infection as humans, mainly water sources, and that in Brazil, the detection rates of anti-T. gondii immunoglobulin G (IgG) in dogs is very high, this study investigated the frequency of anti-T. gondii IgG in dogs in Santa Maria before and after the outbreak. A total of 2.245 serum samples were analyzed, 1159 collected before the outbreak and 1086 collected after the outbreak. Serum samples were tested for anti-T. gondii antibodies using an indirect immunofluorescence antibody test (IFAT). The infection detection of T. gondii was 16% (185/1159) before the outbreak and 43% (466/1086) after the outbreak. These results showed the infection of dogs with T. gondii and the high frequency of anti-T. gondii antibodies in dogs after the outbreak in humans in 2018, reinforcing water as a possible source of infection and the importance of including toxoplasmosis in the differential diagnosis of dogs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The production of fish flour is an alternative for better use of the raw material, although it is rarely used in instant food. Thus, the aimed of this study was to evaluate Oreochromis niloticus (Nile tilapia) and Cynoscion virescens (croaker) fillets and the elaboration of flour with filleting by-products for inclusion in food products. Carcasses and heads of the two fish species were cooked, pressed, ground, subjected to drying and re-grinding to obtain standardized flours. These carcass flours were seasoned (sweet and salted). This study was organized into two experimental tests: Test 1: Yield, physicochemical and microbiological analyzes of fillets and flours made from carcass and head of Nile tilapia and croaker; Test 2: Seasoned flours made from Nile tilapia carcasses. There was a difference in fillets yield, where the croaker demonstrated 46.56% and the Nile tilapia 32.60%. Nile tilapia fillets had higher protein content (17.08%) and lower lipid content (0.89%) compared to croaker fillets (14.21 and 4.45%). Nile tilapia backbone flour had the highest protein content (55.41%) and the croaker the highest ash (45.55%) and the lowest Nile tilapia (28.38%). The head flours had lower protein contents (39.86%). Flours produced with croaker backbone had higher levels of calcium and phosphorus (9.34 and 9.27%). However, Nile tilapia backbone flour showed higher contents of essential amino acids. These flours demonstrated a fine granulometry (0.23 to 0.56 mm). Seasoned flours demonstrated interaction between fish species and flavors for moisture, ash, carbohydrates, calcium and phosphorus. The highest protein content (29.70%) was for Nile tilapia flour sweet flours (31.28%) had higher protein content, while salted lipids (8.06%). Nile tilapia has a lower fillet yield, although with a high protein content and low lipid content. Comparing the flours made from filleting by-products, the backbone flour has better nutritional quality, with Nile tilapia being superior to that of croaker, especially in terms of protein and amino acids., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Santos Corrêa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The encapsulation of fisetin into S. cerevisiae cells through sonoporation coupled with drying is reported for the first time in the literature. To establish the best conditions to maximize the amount of internalized fisetin, the cell density (5-10% w/v), fisetin concentration (1-3 mg/mL), acoustic energy density (0-333.3 W/L), and drying method (freeze-drying and spray drying) were analyzed through a Box-Behnken experimental design (BBD) coupled with response surface methodology (RSM). Higher encapsulation efficiency (EE) was achieved with a cell density of 10% w/v, while fisetin concentration of 3 mg/mL favored the encapsulation yield (EY) and antioxidant activity (AA). Higher EE (67.7%), EY (25.7 mg/g), and AA (90%) were registered when an acoustic density of 333.3 W/L was used. Furthermore, both drying protocols promoted fisetin encapsulation, but through spray drying, the EE, EY, and AA were 11.5%, 11.1%, and 26.6% higher than via freeze-drying, respectively. This work proved that fully filled biocapsules were produced through sonoprocessing, and their morphology was influenced by the acoustic energy and drying process. Overall, these results open new perspectives for the application of sonoprocessing-assisted encapsulation, paving the way for developing innovative yeast-based delivery systems for lipophilic compounds such as fisetin. KEY POINTS: • Sonoprocessing improves the encapsulation of fisetin into S. cerevisiae cells • Spray drying promotes fisetin loading into yeasts' intracellular space and cavities • Fisetin binding with yeast extracellular agents are favored by freeze-drying., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In Brazil, visceral leishmaniasis (VL) has been expanding and urbanizing, mainly in non-endemic areas such as the State of Rio Grande do Sul. Considering that infected dogs are the main reservoirs of VL in urban areas, the present study aimed to evaluate the propagation of canine visceral leishmaniasis (CVL) infection from an unaffected region in transition to a VL transmission area. For this, 1159 and 1087 samples of canine serum from 2015 and 2021, respectively, were analyzed, using the indirect immunofluorescence test. In addition, necropsy reports between 2007 and 2021 were evaluated. The results showed a prevalence of anti-Leishmania spp. antibodies of 7.5% in the samples from 2015, while in 2021 samples, it was 23.5%, with an incidence of 0.4 cases per 100 dogs. It is noteworthy that in 2007, there was no record of CVL as the cause of death in the pathological reports, and in 2021, 41 diagnoses were made with the protozoan being a determinant of the death of the animal. These values indicate an increasing trend in the prevalence and incidence coefficients of CVL. The results of this study allowed us to verify the spread of the disease from an unaffected region to a transmission area of the agent, as well as provide subsidies for health authorities to implement improvements in the CVL control program in the municipality, to mitigate the emergence of human cases of the disease., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to compare the resistance of the Oryctolagus cuniculus L. (rabbit) and Oreochromis niloticus L. (Nile tilapia) skins, as well as to observe the design of the flower of these skins and the morphology of the dermis. Tilapia and rabbit skins were placed inside the same equipment (tannery machine) for the chromium salt tanning process. The flower design of the fish leather distinguishes it from the rabbit leather, the latter being constituted by the opening of the hair follicles and pores, while the fish leather is constituted by the presence of protective lamellae and insertion of the scales. The dermis of rabbit skin consists of thick bundles of collagen fibers arranged in all directions, which differs from the morphology observed in the dermis of fish skin. However, in the Nile tilapia skin dermis, overlapping and parallel layers of longitudinal collagen fiber bundles are observed, these layers are interspersed with fiber bundles crossing the sking surface (transversely), tying the fibers together and providing greater strength, which can be proven by the strength test. The fish leathers, despite having less thickness (1.0 mm), demonstrated significantly greater tensile strength (13.52 ± 1.86 N mm -2 ) and tear strength (53.85 ± 6.66 N mm -2 ) than rabbit leathers, that is, (8.98 ± 2.67 N mm -2 ) and (24.25 ± 4.34 N mm -2 ). However, rabbit leather demonstrated higher elasticity (109.97 ± 13.52%) compared to Nile tilapia leather (78.97 ± 8.40%). It can be concluded that although the rabbit leather is thicker due to the histological architecture of the dermis (thick bundles of collagen fibers arranged in all directions with no pattern of organization of collagen fibers), it shows less resistance than Nile tilapia leather, which demonstrates an organization of overlapping and parallel layers and intercalating collagen fiber bundles transversally to the surface, functioning as tendons for the swimming process. It is recommended to use a piece of fabric (lining) together with the fleshy side of the rabbit leather, to increase resistance when used in clothing and footwear, as these products require greater tensile strength. Thus, it minimizes this restriction for the use of rabbit leather in the aforementioned purposes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Gislaine Gonçalves Oliveira et al.)

Introduction: The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario., Patients and Methods: This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method., Results: One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p < 0.001)., Conclusions: Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier España, S.L.U.)

The effect of the addition of the prebiotic inulin and free and microencapsulated Bifidobacterium animalis subsp. Lactis (BB-12) strains to synbiotic dry coppa formulations was evaluated during 45 days of ripening. The following formulations were made: control C without probiotic and prebiotic; PROB with free probiotic; SYNB with free probiotic and inulin; ENPROB with microencapsulated probiotic, and ENSYNB with microencapsulated probiotic and inulin. The incorporation of BB-12 with inulin provided adequate physicochemical characteristics (proximate composition, weight loss, pH, water activity (a w ), and instrumental color). The treatments PRO and SYNB showed lower lipid and protein oxidation levels. The treatments PROB, SYNB, ENPROB, and ENSYNB had viable cell counts above 10 9 CFU/g and can be considered probiotic. In the in vitro gastrointestinal simulation, the BB-12 strain showed survival and growth capacity in saline solution and at low pH values for all treatments. The sample SYNB was the most accepted by the assessors in the sensory evaluation. Therefore, dry coppa can be used as a vehicle for the development of a synbiotic fermented meat product., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A novel baculovirus observed to infect Automeris liberia (Cramer) (bullseye moth) is here described. Caterpillars of A. liberia with symptoms of viral infection were collected from African oil palm plantations in Tailândia, PA, Brazil. Macerated caterpillars were then offered to caterpillars of Automeris cinctistriga (Felder & Rogenhoper), leading to viral symptoms and death before pupation. A transmission electron microscope was used for virus ultrastructural identification. The presence of viral occlusion bodies (OBs) containing multiple nucleocapsids was observed and such features are compatible with Alphabaculovirus (Baculoviridae). Molecular detection by PCR with primers for polyhedrin gene (polh) and for late expression factor-8 gene (lef-8), confirmed that this isolate belonged to Alphabaculovirus genus. To our knowledge, this is the first record of a baculovirus isolated from or associated to Automeris. The name Automeris liberia nucleopolyhedrovirus (AuliNPV) is proposed for the new virus., (© 2022. Sociedade Entomológica do Brasil.)

Objective: This study compared the clinical performance of large indirect restorations (IRs) versus direct restorations (DRs) in posterior teeth., Methods: Thirty subjects received two class II restorations (n = 60), one fabricated from a precured composite block (Grandio Blocs, VOCO) for the indirect technique (IT) and the other with light-cured composite (GrandioSO, VOCO) for the direct technique (DT). For IT, the restoration was created using the computer-aided design and computer-aided manufacturer (CAD/CAM) system. For DT, the material was applied light-cured by using a layering technique. All restorations were evaluated by using the World Dental Federation criteria., Results: Twenty-three subjects attended the 2-year recall, and 46 restorations were evaluated. No significant differences were detected between the techniques for most parameters analyzed (p > 0.05). For "color match" at 7 days and 6 months, better results were observed for the DT. In relation to the overall scores, all restorations were esthetically acceptable after 2 years, while 93.3% of DT and 90% of IT showed acceptable function. For biological scores, 96.67% of DRs and 100% of IRs was acceptable after 24 months. Considering all properties, the success rates were 93.3% for DRs and 90% for IRs., Conclusions: After 2 years, both restorations presented similar and good clinical behavior for all the properties analyzed., Clinical Significance: Light-cured direct posterior composite restorations may perform similarly to indirect composite restorations made with precured CAD/CAM composite blocks up to 2 years., (© 2021 Wiley Periodicals LLC.)

Background: This study aimed to investigate the effect of metabolic syndrome (MetS) on tooth loss in adults from a population-based sample., Methods: Cross-sectional analysis based on data from a cohort study (2009 to 2014) with adults from Southern Brazil. MetS (exposure), lack of functional dentition and number of lost teeth (outcomes) were assessed using self-reported, laboratory and clinical data. Possible confounders included sex, age, family income, education level, smoking status, and sugar consumption. The effect of MetS on the outcomes was estimated using conventional logistic or negative binomial regression models. Marginal structural modeling (MSM) with stabilized weights (a counterfactual analytical method) was also used to enhance group comparability and estimate causal effects., Results: A total of 1,283 participants had available information for the outcomes. Individuals with MetS were more likely to experience a lack of functional dentition than those without MetS (odds ratio [OR] from logistic regression, 1.7; 95% CI, 1.0 to 2.9; OR from MSM, 3.2; 95% CI, 2.3 to 4.6). Moreover, the number of teeth lost was 20% higher in participants with MetS compared with those without MetS in conventional analysis (mean ratio [MR], 1.2; 95% CI, 1.1 to 1.3). The MR increased to 1.7 (95% CI, 1.5 to 2.0) when using MSM., Conclusion: Our findings provide evidence on the effect of MetS on tooth loss., (© 2021 American Academy of Periodontology.)

Introduction: In minimally invasive mitral valve repair, right minithoracotomy is the most widely performed method, providing a good view of the mitral valve. But regarding other techniques and although it offers limited visualization, the periareolar access is a less traumatic alternative. This study's purpose is to compare in-hospital outcomes in patients who underwent video-assisted minimally invasive mitral valve repair via right minithoracotomy and periareolar access., Methods: This is a retrospective observational study including 37 patients (> 18 years old), without previous right thoracic surgery, who underwent their primary mitral valve repair, with indication for minimally invasive video-assisted approach (via right minithoracotomy or periareolar access), between January 2018 and August 2019. Patients' medical records were consulted to collect demographics data, operative details, and in-hospital outcomes., Results: Twenty-one patients underwent right minithoracotomy, and 16 were operated via periareolar access. The mean patients' age was 62±12 years in the right minithoracotomy group and 61±9 years in the periareolar access group (P=0.2). There are no significant differences in incision length, cardiopulmonary bypass time, aortic cross-clamping time, hematocrit, amount of chest tube drainage, and intensive care unit and in-hospital length of stay. Time to extubation presented significant differences between the right minithoracotomy and the periareolar access group (4.85 hours vs. 5.62 hours, respectively) (P=0.04)., Conclusion: In this study, we found similar results in the two applied surgical techniques, except for the time to extubation.

Ammonia is a widely used toxic industrial chemical that can cause severe respiratory ailments. Therefore, understanding and developing materials for its efficient capture and controlled release is necessary. One such class of materials is 3D porous metal-organic frameworks (MOFs) with exceptional surface areas and robust structures, ideal for gas storage/transport applications. Herein, interactions between ammonia and UiO-67-X (X: H, NH 2 , CH 3 ) zirconium MOFs were studied under cryogenic, ultrahigh vacuum (UHV) conditions using temperature-programmed desorption mass spectrometry (TPD-MS) and in-situ temperature-programmed infrared (TP-IR) spectroscopy. Ammonia was observed to interact with μ 3 -OH groups present on the secondary building unit of UiO-67-X MOFs via hydrogen bonding. TP-IR studies revealed that under cryogenic UHV conditions, UiO-67-X MOFs are stable towards ammonia sorption. Interestingly, an increase in the intensity of the C-H stretching mode of the MOF linkers was detected upon ammonia exposure, attributed to NH-π interactions with linkers. These same binding interactions were observed in grand canonical Monte Carlo simulations. Based on TPD-MS, binding strength of ammonia to three MOFs was determined to be approximately 60 kJ mol -1 , suggesting physisorption of ammonia to UiO-67-X. In addition, missing linker defect sites, consisting of H 2 O coordinated to Zr 4+ sites, were detected through the formation of nNH 3 ⋅H 2 O clusters, characterized through in-situ IR spectroscopy. Structures consistent with these assignments were identified through density functional theory calculations. Tracking these bands through adsorption on thermally activated MOFs gave insight into the dehydroxylation process of UiO-67 MOFs. This highlights an advantage of using NH 3 for the structural analysis of MOFs and developing an understanding of interactions between ammonia and UiO-67-X zirconium MOFs, while also providing directions for the development of stable materials for efficient toxic gas sorption., (© 2021 Wiley-VCH GmbH.)

Cruzain, the main cysteine protease of Trypanosoma cruzi , plays key roles in all stages of the parasite's life cycle, including nutrition acquisition, differentiation, evasion of the host immune system, and invasion of host cells. Thus, inhibition of this validated target may lead to the development of novel drugs for the treatment of Chagas disease. In this study, a multiparameter optimization (MPO) approach, molecular modeling, and structure-activity relationships (SARs) were employed for the identification of new benzimidazole derivatives as potent competitive inhibitors of cruzain with trypanocidal activity and suitable pharmacokinetics. Extensive pharmacokinetic studies enabled the identification of metabolically stable and permeable compounds with high selectivity indices. CYP3A4 was found to be involved in the main metabolic pathway, and the identification of metabolic soft spots provided insights into molecular optimization. Compound 28 , which showed a promising trade-off between pharmacodynamics and pharmacokinetics, caused no acute toxicity and reduced parasite burden both in vitro and in vivo ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pauli, Rezende Jr., Slafer, Dessoy, de Souza, Ferreira, Adjanohun, Ferreira, Magalhães, Krogh, Michelan-Duarte, Del Pintor, da Silva, Cruz, Dias and Andricopulo.)

The present paper aims to establish different treatments for neglected tropical disease by a survey on drug conjugations and possible fixed-dose combinations (FDC) used to obtain alternative, safer and more effective treatments. The source databases used were Science Direct and PubMed/Medline, in the intervals between 2015 and 2021 with the drugs key-words or diseases, like "schistosomiasis", "praziquantel", "malaria", "artesunate", "Chagas' disease", "benznidazole", "filariasis", diethylcarbamazine", "ivermectin", " albendazole". 118 works were the object of intense analysis, other articles and documents were used to increase the quality of the studies, such as consensuses for harmonizing therapeutics and historical articles. As a result, an effective NTD control can be achieved when different public health approaches are combined with interventions guided by the epidemiology of each location and the availability of appropriate measures to detect, prevent and control disease. It was also possible to verify that the FDCs promote a simplification of the therapeutic regimen, which promotes better patient compliance and enables a reduction in the development of parasitic resistance, requiring further studies aimed at resistant strains, since the combined APIs usually act by different mechanisms or at different target sites. In addition to eliminating the process of developing a new drug based on the identification and validation of active compounds, which is a complex, long process and requires a strong long-term investment, other advantages that FDCs have are related to productive gain and gain from the industrial plant, which can favor and encourage the R&D of new FDCs not only for NTDs but also for other diseases that require the use of more than one drug., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dietary supplements composed by the combination of a calcium salt with cholecalciferol (vitamin D 3 ) are widely used for improving bone health in conditions caused by the deficiency of these compounds in the body. Historically, these supplements have been linked to quality and safety issues. In the case of calcium salts, the presence of potentially toxic contaminants such as lead (Pb) has already been alerted by health authorities from different countries. Meanwhile, cholecalciferol is very unstable under inadequate manufacturing and storage conditions. The content of both compounds in commercial dietary supplements is often found to be in disagreement with the label claims, which can lead to a deficient or excessive nutrient intake by consumers. In this scenario, analyzing these compounds is still a difficult and time-consuming task, which usually requires specific pretreatment procedures and multiple analytical methods due to the inorganic nature of calcium and the organic nature of cholecalciferol. Therefore, this article reviews the analytical methods, described in official compendia and scientific literature, for the determination of calcium salts and cholecalciferol in dietary supplement formulations. We also approached the sample preparation procedures highly required due to the matrix complexity of these materials.

Background: The oral route is the most frequently used and the most convenient route of drug administration since it has several advantages, such as ease of use, patient compliance, and better costeffectiveness. However, physicochemical and biopharmaceutical limitations of various active pharmaceutical ingredients (API) hinder suitability for this route, including degradation in the gastrointestinal tract, low intestinal permeability, and low bioavailability. To overcome these problems, while maintaining therapeutic efficacy, polymeric nanoparticles have attracted considerable attention for their ability to increase drug solubility, promote the controlled release, and improve stability. In addition, the functionalization of nanocarriers can increase uptake and accumulation at the target site of action, and intestinal absorption, making it possible to obtain more viable, safe and efficient treatments for oral administration., Objective: This systematic review aimed to seek recent advances in the literature on the use of polymeric nanoparticles functionalization to increase intestinal permeability of APIs that are intended for oral administration., Methods: Two bibliographic databases were consulted (PubMed and ScienceDirect). The selected publications and the writing of this systematic review were based on the guidelines mentioned in the PRISMA statement., Results: Out of a total of 3036 studies, 22 studies were included in this article based on our eligibility criteria. The results were consistent for the application of nanoparticle functionalization to increase intestinal permeability., Conclusion: The functionalized polymeric nanoparticles can be considered as carrier systems that improve the intestinal permeability and bioavailability of APIs, with the potential to result, in the future, in the development of oral medicines., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The World Health Organization (WHO) classifies leishmaniasis as a disease for which the development of new treatments is a priority. Available drugs are not fully effective in all cases; they have parenteral administration and exhibit serious and common adverse effects. The only oral drug available (miltefosine) has shown resistance, is expensive, and is not available in many endemic countries. Thus, the development of an oral medicine may solve many of these issues. Based on that, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs for the treatment of cutaneous leishmaniasis. A literature search for keywords "leishmania and oral" was performed in PubMed and ScienceDirect, considering articles published in the last 5 years. The articles were selected based on the objective of the review. The main problem in the current treatment of leishmaniasis is the administration of injectables, since it requires patients to travel to health centers, hospitalization, and professional administration, conditions that are not adapted to the socioeconomic reality of patients. Therefore, many research studies have evaluated oral alternatives for the treatment of cutaneous leishmaniasis. The main tested approaches were obtaining new molecules, repositioning drugs, and new formulations of old drugs. The prospects are encouraging but still require more in vivo bioavailability and clinical trials., (© 2021 the International Society of Dermatology.)

Baculoviruses have been applied for biocontrol of agricultural pests, such as velvetbean caterpillar (Anticarsia gemmatalis) and fall armyworm (Spodoptera frugiperda). Cell culture is an interesting approach for large-scale production of these viruses. Co-infection of a host cell with two distinct viruses can contribute to reduce costs due to saving cell culture media, bioreactor space and the resulting co-occluded polyhedra may help to reduce final biopesticide costs. The baculovirus Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) and Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) were chosen to test a model for in vitro co-infection in SF21 cells. Different proportions of SfMNPV/AgMNPV were evaluated along three in vitro passages by optical microscopy analysis of cells and real-time PCR (qPCR) of DNA obtained from budded viruses (BVs) and occlusion bodies (OBs). The kinetics of viral protein synthesis was carried out for analysis of the co-infection in first passage and bioassays with the resulting OBs were performed against A. gemmatalis and S. frugiperda larvae. The results demonstrated successful co-infection in these cells. The quantity of SfMNPV and AgMNPV in supernatants and sediments tends to be maintained stable during the three passages, although the amount of AgMNPV was higher than SfMPNV in most of the experiments. Analysis of the kinetics of radiolabed proteins showed that the cell protein synthesis was shut off and two distinct bands of about 30 kDa, regarded to be the polyhedrin of each virus, were strongly detected at 48 and 72 hp.i. Although the pathogenicity of the produced viruses was not completely satisfactory, the bioassays confirmed occurrence of co-infected larvae with disproportional amount of each virus., (© 2021. Sociedade Brasileira de Microbiologia.)

The discovery of new targets for the treatment of malaria, in particular those aimed at the pre-erythrocytic stage in the life cycle, advanced with the demonstration that orally administered inhibitors of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) could clear infection in a murine model. This enthusiasm was tempered by unsatisfactory safety and/or pharmacokinetic issues found with these chemotypes. To address the urgent need for new scaffolds, this paper presents initial structure-activity relationships in an imidazole scaffold at four positions, representative in vitro ADME, hERG characterization, and cell-based antiparasitic activity. This series of PfPKG inhibitors has good in vitro PfPKG potency, low hERG activity, and cell-based antiparasitic activity against multiple Plasmodium species that appears to be correlated with the in vitro potency., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Knowledge of plant responses to environmental heterogeneity during ontogeny is important to elucidate the changes that occur to promote resource capture in tropical forests. We tested the hypothesis that expression changes in leaf metamer traits of Brazilian rosewood (Dalbergia nigra), from seedlings to emergent canopy trees, occur as new microclimate environments are achieved. We also tested the hypothesis that increased light heterogeneity in the understorey leads to higher plasticity in leaf traits of seedlings and saplings than in sun-exposed metamers of emergent trees subject to stressful conditions. We compared leaf metamer traits of 53 individuals including seedlings, saplings and emergent trees. We also evaluated the light heterogeneity in vertical strata and the variations in leaf traits within individuals (among metamers of the same individual). These were associated with height of the individuals. Compared to understorey plants, emergent trees presented larger metamers, with lower specific leaf area (SLA), lower investment in leaf area per total dry mass of metamer (LAR m ), lower specific petiole length (SPL) and lower specific internode length (SIL). Higher phenotypic variation within individuals was observed in seedlings, which decreased as the trees grew taller. The results suggest the integration of ontogenetic changes in leaf traits under new microclimate conditions as the plants reach different vertical strata in the forest. Additionally, our results support the hypothesis that increased light heterogeneity in the understorey shaped higher phenotypic variation within individuals in juveniles and that stressful conditions in sun-exposed leaf metamers of emergent trees led to increased phenotypic stability., (© 2021 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)