From Data to Discovery

Funding Information: The Article Processing Charge for the publication of this research was funded by the Coordination for the Improvement of Higher Education Personnel - CAPES (ROR identifier: 00x0ma614). The authors would like to thank the funding agencies CNPq (441038/2020-4), CAPES-STINT (88881.304811/2018-01), FAPEG (202010267000272), FAPESP (Grants 2017/18611-7, 2021/06769-0, and 2021/06769-0), Instituto Serrapilheira (grant G-1709-16618), the Swedish Research Council (grants 2016-05627 and 2021-03667). J.V.B.B., L.T.F., L.C.S.A., M.L.M., J.C. received FAPESP fellowships (grants 2019/21854-4, 2019/02171-3, 2021/13809-9, 2023/07805-6, 2020/11060-8, 2018/24878-9). L.C.S.A. also received CNPq fellowship (Grants 162117/2018-3). M.P. acknowledges funding from the \u201Cla Caixa Foundation, grant HR21-848, and the European Union Horizon Europe programme (grant 101080744). CHA thanks the \u201CL\u2019Ore\u0301al-UNESCO-ABC Para Mulheres na Cie\u0301ncia\u201D and \u201CL\u2019Ore\u0301al-UNESCO International Rising Talents\u201D for the awards and fellowships received, which partially funded this work. C.H.A. and F.T.M.C. are CNPq research fellows. Publisher Copyright: © 2024 The Authors. Published by American Chemical Society.Malaria presents a significant challenge to global public health, with around 247 million cases estimated to occur annually worldwide. The growing resistance of Plasmodium parasites to existing therapies underscores the urgent need for new and innovative antimalarial drugs. This study leveraged artificial intelligence (AI) to tackle this complex challenge. We developed multistage Machine Learning Quantitative Structure-Activity Relationship (ML-QSAR) models to effectively analyze large datasets and predict the efficacy of chemical compounds against multiple life cycle stages of Plasmodium parasites. We then selected 16 compounds for experimental evaluation, six of which showed at least dual-stage inhibitory activity and one inhibited all life cycle stages tested. Moreover, explainable AI (XAI) analysis provided insights into critical molecular features influencing model predictions, thereby enhancing our understanding of compound interactions. This study not only empowers the development of advanced predictive AI models but also accelerates the identification and optimization of potential antiplasmodial compounds.publishersversionpublishe

Fipronil and 2,4-D effects on tropical fish: Could avoidance response be explained by changes in swimming behavior and neurotransmission impairments?

Brazil is the largest producer of sugarcane, a crop largely dependent on chemical control for its maintenance. The insecticide fipronil and herbicide 2,4-D stand out among the most commonly used pesticides and, therefore, environmental consequences are a matter of concern. The present study aimed to investigate the toxicity mechanisms of Regent® 800 WG (a.i. fipronil) and DMA® 806 BR (a.i. 2,4-D) pesticides using forced and non-forced exposures through an integrative approach: firstly, to assess whether contamination by fipronil and 2,4-D can trigger the avoidance behavior of the fish Danio rerio (zebrafish) and Hyphessobrycon eques (serpae tetra or mato-grosso). Additionally, the effects on fish were analyzed considering the swimming behavior together with a biomarker of neurotoxicity, the activity of acetylcholinesterase (AChE). In avoidance tests with pesticide gradients, D. rerio avoided the highest concentrations of the two compounds and H. eques avoided only the highest concentration of 2,4-D. The swimming behavior (distance moved) was reduced and AChE was inhibited when D. rerio was exposed to fipronil. The 2,4-D affected the swimming (maximum speed) of H. eques, but AChE was not altered. Avoidance response seemed not to have been affected by possible effects of contaminants on swimming behavior and Ache activity. This study showed the importance of knowing the avoidance capacity, swimming behavior and neurotoxic effects of pesticides on fish in an integrated and realistic context of exposure in environments contaminated with pesticides and can be useful as ecologically relevant tools for ecological risk assessment.We would like to thank the São Paulo Research Foundation “Fundação de Amparo à Pesquisa do Estado de São Paulo” (FAPESP) for the post doctorate grant to the first author (Process number: 2017/24126-4). Financial support was also provided by FAPESP (2015/18790-3). CVM Araújo is grateful to the Spanish Ministry of Science and Innovation for the Ramón y Cajal contract (RYC-2017-22324).Peer reviewe

Whole-body bioconcentration and biochemical and morphological responses of gills of the neotropical fish Prochilodus lineatus exposed to 2,4-dichlorophenoxyacetic acid or fipronil individually or in a mixture

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and the insecticide fipronil have been used widely in agriculture and detected in aquatic ecosystems, where they threaten wildlife. This study evaluated the whole-body bioconcentration and the biochemical and morphological changes in the gills of the neotropical fish Prochilodus lineatus exposed for 96 h to 2,4-D or fipronil as single compounds or as a mixture (2,4-D + fipronil). Fish exposed to either compound alone bioconcentrated 2,4-D (77 ± 23 ng g −1 fish dry mass) and fipronil (789 ± 178 ng g −1 fish dry mass). Fish exposed to 2,4-D + fipronil bioconcentrated fipronil (683 ± 73 ng g −1 fish dry mass) but not 2,4-D. In the gills, catalase (CAT) and glutathione-S-transferase (GST) activities and the lipid peroxidation (LPO) level increased after exposure to 2,4-D. GST activity increased after exposure to fipronil. Conversely, no changes occurred in CAT and GST activities and LPO upon exposure to 2,4-D + fipronil. Histopathological changes such as hyperplasia, cellular hypertrophy, epithelial lifting, and vascular congestion were frequent in the gills of fish exposed to 2,4-D or fipronil individually or 2,4-D + fipronil. The mitochondria-rich cell (MRC) density increased on gill surface in fish exposed to fipronil or 2,4-D + fipronil. Only exposure to 2,4-D alone induced oxidative stress in the gills. Most morphological changes showed defense responses against the pesticides; however, hypertrophy and the change in MRC indicated compensatory responses to maintain the gill osmoregulatory function. The 2,4-D + fipronil mixture showed antagonistic interaction, except for the MRC fractional area at gill surface, which showed synergistic interaction. This is the first report showing antagonistic interaction of 2,4-D and fipronil in the gills after exposing fish to the mixture of both pesticides. The biochemical and morphological changes in gills endanger the gill functions, a phenomenon that implies an energy cost for fish.Fil: Portruneli, Natália. Universidade Federal do São Carlos; BrasilFil: Bonansea, Rocio Ines. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Valdés, María Eugenia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: da Silva, Laís Conceição Menezes. Universidade de Sao Paulo; BrasilFil: Viana, Natália Prudêncio. Universidade Federal do São Carlos; BrasilFil: Goulart, Bianca V.. Universidade Estadual de Campinas; BrasilFil: Souza, Iara da Costa. Universidade Federal do São Carlos; BrasilFil: Espíndola, Evaldo Luiz Gaeta. Universidade de Sao Paulo; BrasilFil: Montagner, Cassiana Carolina. Universidade Estadual de Campinas; BrasilFil: Wunderlin, Daniel Alberto. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: Fernandes, Marisa Narciso. Universidade Federal do São Carlos; Brasi

Desenvolvimento de estratégias inovadoras de imunização para viabilizar o uso de vacas como biofábricas de anticorpos neutralizantes produzidos a partir do colostro para tratamento e prevenção de doenças pandêmicas.

A Covid-19 é uma doença viral que causou graves problemas para a saúde pública e muitas mortes mundialmente. Anticorpos neutralizantes constituem uma estratégia de tratamento de casos graves dessa doença. Uma vez que o colostro bovino é rico em anticorpos e estes possuem alta homologia com IgG humana, o presente trabalho visa utilizar formulações vacinais contendo antígeno recombinante Spike (domínio RBD) do vírus SARS-CoV2 para viabilizar o uso de vacas como biofábricas. Para tal, vacas foram inoculadas, no período pré-parto, com o antígeno recombinante encapsulado em nanossistemas com direcionamento ativo para fagócitos (NIBDAF) ou em formulações contendo adjuvantes comerciais à base de sulfato de alumínio e saponina, além de uma vacina comercial contra o coronavírus bovino (BCoV). Foram coletados soro e colostro no dia do parto. A atividade neutralizante dos anticorpos foi medida por ELISA competitivo, demonstrando que todas as formulações utilizadas, com exceção da vacina contra BCoV, foram capazes de proporcionar neutralização do vírus SARS-CoV2. Testes deverão ser conduzidos em modelo murino para verificar efeito protetor de anticorpos purificados e do uso do colostro hiperimune como nutracêutico. A estratégia de uso de vacas como biofábricas de anticorpos neutralizantes pode constituir uma alternativa ao tratamento de doenças endêmicas ou patologias agudas em humanos e animais.Pibic/Fapemig

Desenvolvimento de estratégias inovadoras de imunização para viabilizar o uso de vacas como biofábricas de anticorpos neutralizantes produzidos a partir do colostro para tratamento e prevenção de doenças pandêmicas.

A Covid-19 é uma doença viral que causou graves problemas para a saúde pública e muitas mortes mundialmente. Anticorpos neutralizantes constituem uma estratégia de tratamento de casos graves dessa doença. Uma vez que o colostro bovino é rico em anticorpos e estes possuem alta homologia com IgG humana, o presente trabalho visa utilizar formulações vacinais contendo antígeno recombinante Spike (domínio RBD) do vírus SARS-CoV2 para viabilizar o uso de vacas como biofábricas. Para tal, vacas foram inoculadas, no período pré-parto, com o antígeno recombinante encapsulado em nanossistemas com direcionamento ativo para fagócitos (NIBDAF) ou em formulações contendo adjuvantes comerciais à base de sulfato de alumínio e saponina, além de uma vacina comercial contra o coronavírus bovino (BCoV). Foram coletados soro e colostro no dia do parto. A atividade neutralizante dos anticorpos foi medida por ELISA competitivo, demonstrando que todas as formulações utilizadas, com exceção da vacina contra BCoV, foram capazes de proporcionar neutralização do vírus SARS-CoV2. Testes deverão ser conduzidos em modelo murino para verificar efeito protetor de anticorpos purificados e do uso do colostro hiperimune como nutracêutico. A estratégia de uso de vacas como biofábricas de anticorpos neutralizantes pode constituir uma alternativa ao tratamento de doenças endêmicas ou patologias agudas em humanos e animais.Pibic/Fapemig