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m-Xylene is a volatile organic compound that is extensively used in various industrial processes. It is toxic, posing significant risks to human health and the environment. Therefore, developing gas sensors with high sensitivity and selectivity for m-xylene detection is critical. In this work, we demonstrated the synthesis of NiO-yolk double-shell (NiO-YDS) and NiO-yolk triple-shell (NiO-YTS) derived from NiO/Ni-BTC and NiO/Ni-PTA composites, respectively, using the microwave-assisted solvothermal method from Ni-BTC-derived NiO spheres. The NiO/Ni-BTC composite has trimesic acid (H3BTC) as an organic linker, while NiO/Ni-PTA has p-terephthalic acid (PTA). We investigated the sensing properties of these materials for 2-butanone, 2-nonanone, 3-methyl-1-butanol, acetone, benzene, ethanol, methanol, and m-xylene. These composites exhibited excellent sensitivity and selectivity for detecting m-xylene under dry conditions. Specifically, the NiO-YTS sensor showed a sensitivity of 217.5% to m-xylene, while the NiO-YDS sensor demonstrated a sensitivity of 179.8% at 350 °C in dry air. We emphasize the NiO-YTS composite due to its superior sensitivity and selectivity in detecting m-xylene compared with the NiO-YDS composite. The NiO-YTS sensor exhibited stable and reproducible sensing performance for 100 ppm of m-xylene under optimum working conditions, with a theoretical detection limit of 5.43 ppb and relatively fast response time (89 s) and recovery time (191 s). This work describes an easy method for synthesizing NiO-YDS and NiO-YTS derived from NiO/Ni-BTC and NiO/Ni-PTA composites. It demonstrates that these composites represent a new class of materials that can potentially enhance the sensitivity and selectivity of m-xylene gas sensors.
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Silver nanoparticles (AgNPs) synthesized through green synthesis routes are widely used as antimicrobial agents due to their advantages such as biocompatibility, stability, sustainability, speed and cost-effectiveness. Although AgNPs appear to be more potent than silver ions, the mechanisms related to their antibacterial activity are not yet fully understood. The most common proposed mechanism of AgNPs' toxicity so far is the release of silver ions and/or specific functions of the particles. In this context, the present study aimed to investigate the mechanisms of action of AgNPs synthesized using noni fruit peels (Morinda citrifolia) against the phytopathogen Xanthomonas campestris pv. campestris (Xcc) through proteomics. Xcc was treated with AgNPs (32 µM), AgNO3 (32 µM), or received no treatment (Ctrl - control condition), and its proteomic response was comprehensively characterized to elucidate the antimicrobial mechanisms of AgNPs in the phytopathogenic microorganism. A total of 352 differentially abundant proteins were identified. Most proteins were regulated in the AgNPs × Ctrl and AgNPs × AgNO3 comparisons/conditions. When Xcc treated with 32 µM AgNPs were compared to controls, the results showed 134 differentially abundant proteins, including 107 increased and 27 decreased proteins. In contrast, when Xcc treated with 32 µM AgNO3 were compared to Ctrl, the results showed only 14 differentially abundant proteins, including 10 increased proteins and 4 decreased proteins. Finally, when Xcc treated with 32 µM AgNPs were compared to Xcc treated with 32 µM AgNO3, the results showed 204 differentially abundant proteins, including 75 increased proteins and 129 decreased proteins. Gene ontology enrichment analysis revealed that most of the increased proteins were involved in important biological processes such as metal ion homeostasis, detoxification, membrane organization, metabolic processes related to amino acids and carbohydrates, lipid metabolic processes, proteolysis, transmembrane transport, and others. The AgNPs used in this study demonstrated effective antimicrobial activity against the phytopathogenic bacteria Xcc. Furthermore, the obtained results contribute to a better understanding of the mechanisms of action of AgNPs in Xcc and may aid in the development of strategies to control Xcc in brassica.
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Sarcopenia is characterized by a decline in muscle strength, generalized loss of skeletal muscle mass, and impaired physical performance, which are common outcomes used to screen, diagnose, and determine severity of sarcopenia in older adults. These outcomes are associated with poor quality of life, increased risk of falls, hospitalization, and mortality in this population. The development of sarcopenia is underpinned by aging, but other factors can lead to sarcopenia, such as chronic diseases, physical inactivity, inadequate dietary energy intake, and reduced protein intake (nutrition-related sarcopenia), leading to an imbalance between muscle protein synthesis and muscle protein breakdown. Protein digestion and absorption are also modified with age, as well as the reduced capacity of metabolizing protein, hindering older adults from achieving ideal protein consumption (i.e., 1-1.5 g/kg/day). Nutritional supplement strategies, like animal (i.e., whey protein) and plant-based protein, leucine, and creatine have been shown to play a significant role in improving outcomes related to sarcopenia. However, the impact of other supplements (e.g., branched-chain amino acids, isolated amino acids, and omega-3) on sarcopenia and related outcomes remain unclear. This narrative review will discuss the evidence of the impact of these nutritional strategies on sarcopenia outcomes in older adults.
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Suplementos Dietéticos , Sarcopenia , Humanos , Sarcopenia/dietoterapia , Sarcopenia/prevención & control , Sarcopenia/metabolismo , Anciano , Músculo Esquelético/metabolismo , Envejecimiento/fisiología , Proteínas en la Dieta/administración & dosificación , Fuerza Muscular , Calidad de Vida , Anciano de 80 o más Años , Proteínas Musculares/metabolismoRESUMEN
Background: Gaucher's disease (GD), a lysosomal storage disorder, poses significant treatment challenges. This 23-year study assesses survival rates and treatment efficacy in Brazilian GD patients, integrating data from a 16-year cohort (2000-2015) and the TABNET/DATASUS medicines distribution data (1999-2022). Objective: To investigate the survival of GD patients in Brazil, identifying key risk factors and evaluating the impact of treatments funded by the Brazilian National Health System (SUS). Methodology: A 16-year retrospective cohort study was conducted using the National Database of SUS. Patients diagnosed with GD and treated with Enzyme Replacement Therapy (ERT) or Substrate Synthesis Inhibition (SSI) from 2000 to 2015 were included. Survival analysis was performed using Kaplan-Meier method and Cox proportional hazards model. The data from TABNET/DATASUS system from 1999 to 2022 was used to assess the trend in drug distribution beyond the main cohort. Results: The study included 1,234 patients. Survival rates at 5 and 10 years were 93.2% and 88.5%, respectively, with age and comorbidities like diabetes, cardiovascular diseases, and Parkinson's disease significantly affecting survival. Patients who received doses lower than DDD (n = 880) demonstrated a survival probability of 91.8%. In contrast, those with doses equal to the DDD (n = 15) showed a 100% survival probability, as no events were observed in this group. The greater than DDD group (n = 339) exhibited a survival probability of 81%. A log-rank test indicated a borderline statistical significance (p = 0.058) in the survival distributions among the different DDD adherence, with the lower dose group showing a favorable trend. Conclusion: This study provides insights into the survival rates and associated risk factors for GD patients in Brazil, contributing to the global understanding of GD and its management. While we acknowledge the inherent limitations of relying largely on electronic medical records and categorical codes, our findings underscore the need for early diagnosis, timely initiation of treatment, effective management of comorbidities, and personalized dosing strategies to improve patient outcomes. Future studies should aim to incorporate clinical verification of electronic data to further enhance the reliability and applicability of these findings.
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The integration of multicomponent reactions (MCRs), which offer a rapid and efficient approach to synthesize complex molecular scaffolds, with continuous flow platforms is an increasingly recognized strategy in green synthesis. This association enables precise control over reaction parameters, including improved kinetics and selectivity, reduced reaction times, enhanced yields and scalabilities, while aligning with sustainable and green chemistry principles through resource utilization, minimized waste, and reduced environmental impact. This review presents a critical analysis of recent studies covering the MCR-continuous flow association, with a focus on achieving greener and more sustainable synthesis practices.
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Understanding ATP formation is essential for learning metabolism and is central to grasping metabolic processes as a whole. However, due to the high level of abstraction, the number of intermediate substrates, the connections, and integrated regulation, its comprehension often poses a challenge. This and the fact that traditional teaching methods struggle when dealing with highly abstract concepts, game-based strategies present a more concrete and dynamic alternative, which led to the creation of E!Canasta (card game). Developed based on Canasta and adapted in order to improve the learning of concepts, including some of pathway's regulation and integration, E!Canasta motivates students and promotes engagement in a fun activity. Students assemble a sequence of cards representing the glycolysis, acetyl-CoA, Krebs cycle, and electron transport chain, which correspond to the card suits. Strategically, some of the cards hold special feats that simulate some aspects of metabolic regulation and integration (to give or take away points). At the end of the game, points are added up for sequences and cards with positive or negative effects. The game was played with two classes of students enrolled in biochemistry as part of their graduations (86 players). Student perception on gameplay, motivation and understanding was measured through an anonymous Likert scale questionnaire, with very positive results in all questions. Statistically significant correlations were observed regarding the perceived comprehension of pathways and their regulation, and in linking motivation with a positive gaming experience, showcasing that E!Canasta demonstrates considerable educational potential, along with an enjoyable experience for learning ATP synthesis.
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Aim: This work describes the synthesis and antimicrobial evaluation of 6-aminated 1,4-benzoquinones (6-AQs) against seven resistant pathogens.Materials & methods: The 6-AQs, synthesized via a Michael addition reaction between bromoquinone and p-substituted anilines, were assessed for their antimicrobial activity through both in vitro and in silico analyses.Results: Bromoquinone and 6-AQs with electron-withdrawing groups demonstrated activity against Pseudomonas aeruginosa, with minimum inhibitory concentrations ranging from 16 to 128 µg/ml, comparable to standard antimicrobials. Two derivatives exhibited minimum inhibitory concentrations values against methicillin-resistant Staphylococcus aureus ranging from 64 to 128 µg/ml. These compounds demonstrated both bacteriostatic and bactericidal effects, and antibiofilm features.Conclusion: The 6-AQs 19g and 19f showed a promising antimicrobial profile, indicating their potential as new therapeutic options.
[Box: see text].
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Multidrug Resistance (MDR) can be considered one of the most frightening adaptation types in bacteria, fungi, protozoa, and eukaryotic cells. It allows the organisms to survive the attack of many drugs used in the daily basis. This force the development of new and more complex, highly specific drugs to fight diseases. Given the high usage of medicaments, poor variation in active chemical cores, and self-medication, the appearance of MDR is more frequent each time, and has been established as a serious medical and social problem. Over the years it has been possible the identification of several genes and proteins responsible for MDR and with that the development of blockers of them to reach MDR reversion and try to avoid a global problem. These mechanisms also have been observed in cancer cells, and several calcium channel blockers have been successful in MDR reversion, and the maleimide can be found included in them. In this review we explore the history, mechanisms, reversion efforts, and we specifically focused on the maleimide synthesis as MDR-reversers in co-administration, as well as their biological applications in a urge to expand the available information and explore a very plausible MDR reversion source.
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INTRODUCTION: High-frequency chest wall oscillation (HFCWO) devices are used to improve airway clearance in various respiratory conditions. This study comprehensively assesses the evidence on efficacy and safety and identifies trends in scientific publications and patents across geographic regions. METHODS: This study utilized an integrated approach, combining bibliographic and bibliometric research with artificial intelligence (AI) tools. Four databases - PubMed, Europe Pubmed Central, Cochrane Database of Systematic Reviews, and CINAHL - were searched for systematic reviews on the effectiveness of treatment options for HFCWO. The AMSTAR-2 tool was used to evaluate the risk of bias in systematic reviews. Bibliographic research synthesized the evidence following PRISMA and Cochrane guidelines. The Dimensions platform was used for bibliometric analysis to provide insights into the global landscape. AI tools with prompt engineering tools Chain-of-Thoughts (CoT) and Tree of Thoughts (ToT) were used to enhance data extraction capabilities. RESULTS: The umbrella review identified 12 systematic reviews supporting the effectiveness of HFCWO in improving pulmonary function parameters, sputum characteristics, dyspnea, health scores, and quality of life in conditions including cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease (COPD), or neuromuscular diseases, with varying evidence of certainty. Eight of the twelve reviews had a moderate to high AMSTAR-2 confidence level, while several studies lacked sufficient descriptions of methods, treatment regimens, outcome measures, and adverse effects. Despite the absence of adverse events, the overall evidence quality between studies is evaluated as low to very low. Bibliometric analysis found a significant increase in global interest over the past two decades, with 230 research publications, 137 patents, and 56 clinical trials. CONCLUSIONS: The study highlights the potential of HFCWO devices in respiratory care but demands more robust evidence. The increasing interest in airway clearance devices highlights the necessity for HFCWO mechanism and safety research, underlining its therapeutic relevance in respiratory medicine. The interdisciplinary integration of AI tools and prompt engineering contributes to a nuanced understanding of the available evidence.
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Advanced oxidation processes (AOP) stood out as an efficient alternative for the treatment of organic contaminants. In this work, there were proposed syntheses of mixed catalysts of pyrite and graphene oxide and pyrite and zinc oxide to treat a mixture of the drugs atenolol and propranolol in aqueous solution through the photo-Fenton process with ultraviolet radiation. The efficiency of the methodologies used in the syntheses was confirmed through different characterization analyses. It was verified that the pyrite and zinc oxide catalyst led to the best contaminant degradation percentages with values equal to 88 and 84% for the groups monitored at the wavelengths (λ) of 217 and 281 nm. The degradation kinetics presented a good fit to the kinetic model proposed by Chan and Chu (2003) with R2 equal to 0.99, indicating a pseudo-first-order degradation profile. Finally, toxicity tests were carried out with two types of seeds, watercress and cabbage, for the solution before and after treatment. The cabbage seeds showed a reduction in germination percentages for the samples after treatments, while no toxicity was observed for watercress ones. This highlights the importance of evaluating the implications caused by products in relation to different organisms representing the biota.
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Grafito , Oxidación-Reducción , Óxido de Zinc , Grafito/química , Catálisis , Óxido de Zinc/química , Sulfuros/química , Contaminantes Químicos del Agua/química , Hierro/química , CinéticaRESUMEN
Many studies have demonstrated the excellent performance of 10-MDP (10-methacryloyloxydecyl dihydrogen phosphate) as a functional monomer for dental adhesive materials and as a primer for ceramic surfaces. Although adhesive performance is affected by the purity level of 10-MDP, this parameter is rarely described, and possible byproducts have been suggested in the literature, but have not been identified to date. The present study aims to present an accessible 10-MDP synthesis strategy with easily handled reagents and address the characterization challenges, especially in identifying byproducts. 10-MDP was synthesized from 10-hydroxydecyl methacrylate and phosphorus pentoxide in acetone. The final product was characterized by nuclear magnetic resonance (NMR), infrared spectroscopy (FTIR) and mass spectrometry MALDITOF/TOF. The main chemical groups associated with 10-MDP were identified by 1H, 31P, and 13C NMR analyses. Only mass spectrometry analyses (MALDITOF/TOF) could identify the presence of dimers as byproducts. Its proposed chemical structure indicates that the dimers were formed by the reaction between the phosphate ester groups and others formed by the reaction of the methacrylic group of 10-MDP molecules. Careful adjustment of the synthesis conditions to reduce the formation of these byproducts is also described. The results indicate that the characterization of 10-MDP batches as raw materials is an important task because, depending on the byproduct present, its ability to polymerize or acid etching capacity may be compromised.
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BACKGROUND: Testicular macrophages (TM) have long been recognized for their role in immune response within the testicular environment. However, their involvement in steroid hormone synthesis, particularly testosterone, has not been fully elucidated. This study aims to explore the capability of TM to synthesize and secrete testosterone de novo and to investigate the regulatory mechanisms involved. RESULTS: Transcriptomic analysis revealed significant expression of Cyp11a1, Cyp17a1, Hsd3b1, and Hsd17b3 in TM, which are key enzymes in the testosterone synthesis pathway. qPCR analysis and immunofluorescence validation confirmed the autonomous capability of TM to synthesize testosterone. Ablation of TM in mice resulted in decreased physiological testosterone levels, underscoring the significance of TM in maintaining testicular testosterone levels. Additionally, the study also demonstrated that Cebpb regulates the expression of these crucial genes, thereby modulating testosterone synthesis. CONCLUSIONS: This research establishes that TM possess the autonomous capacity to synthesize and secrete testosterone, contributing significantly to testicular testosterone levels. The transcription factor Cebpb plays a crucial role in this process by regulating the expression of key genes involved in testosterone synthesis.
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Proteína beta Potenciadora de Unión a CCAAT , Macrófagos , Testículo , Testosterona , Animales , Masculino , Testosterona/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Testículo/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Perfilación de la Expresión GénicaRESUMEN
Nowadays, layered double hydroxides (LDH), sometimes referred as hydrotalcite-like compounds, have gained great attention since their composition and structure can be easily modified, so that they can be implemented in multiple fields. LDH-based composite materials based on LDH exhibit tremendously improved properties such as high specific surface area, which promotes the accessibility to a greater number of LDH active sites, considerably improving their catalytic, adsorbent and biological activities. Therefore, this review summarizes and discusses the synthesis methods of composites constituted by LDH with other inorganic compounds such as zeolites, cationic clays, hydroxyapatites, among many others, and describe the resulting characteristics of the resulting composites, emphasizing the morphology. Brief descriptions of their properties and applications are also included.
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BACKGROUND: Rare-earth sulfide nanoparticles (NPs) could harness the optical and magnetic features of rare-earth ions for applications in nanotechnology. However, reports of their synthesis are scarce and typically require high temperatures and long synthesis times. RESULTS: Here we present a biosynthesis of terbium sulfide (TbS) NPs using microorganisms, identifying conditions that allow Escherichia coli to extracellularly produce TbS NPs in aqueous media at 37 °C by controlling cellular sulfur metabolism to produce a high concentration of sulfide ions. Electron microscopy revealed ultrasmall spherical NPs with a mean diameter of 4.1 ± 1.3 nm. Electron diffraction indicated a high degree of crystallinity, while elemental mapping confirmed colocalization of terbium and sulfur. The NPs exhibit characteristic absorbance and luminescence of terbium, with downshifting quantum yield (QY) reaching 28.3% and an emission lifetime of ~ 2 ms. CONCLUSIONS: This high QY and long emission lifetime is unusual in a neat rare-earth compound; it is typically associated with rare-earth ions doped into another crystalline lattice to avoid non-radiative cross relaxation. This suggests a reduced role of nonradiative processes in these terbium-based NPs. This is, to our knowledge, the first report revealing the advantage of biosynthesis over chemical synthesis for Rare Earth Element (REE) based NPs, opening routes to new REE-based nanocrystals.
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Escherichia coli , Metales de Tierras Raras , Sulfuros , Terbio , Terbio/química , Terbio/metabolismo , Escherichia coli/metabolismo , Sulfuros/metabolismo , Sulfuros/química , Metales de Tierras Raras/metabolismo , Metales de Tierras Raras/química , Nanopartículas/química , Luminiscencia , Tecnología Química Verde/métodosRESUMEN
An extended library of hybrids that combined a penicillin derivative with a peptoid moiety was designed and synthetized using either a solid-phase or a mixed solid-phase/solution-phase strategy. The library was further evaluated for antiproliferative activity. While none of the different synthesized compounds showed significant cytotoxicity against a normal cell line, tumor cell results drew several conclusions, when comparing with our reference, the highly active triazolylpeptidyl penicillin derivative, TAF7f. Thus, when the 1,2,3-triazole group was exchanged by its "retro-inverse" analogue, no change was noted in the activity of the hybrids; however, better performance was generally obtained if the triazole is replaced by a glycine moiety. Additionally, the absence of hydrogen bond donor groups decreased the compounds activity, which could explain that, in general, this set of derivatives were less active than their peptide-containing analogues. From this study, is indisputable that, regardless of the type of chain (peptide, peptoid or mixture) attached to penicillin, an isobutyl side chain placed in the position closest to penicillin and a benzyl in the next position are determinant for the activity.
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The increasing threat from antibiotic-resistant bacteria has necessitated the development of novel methods to counter bacterial infections. In this context, the application of metallic nanoparticles (NPs), especially gold (Au) and silver (Ag), has emerged as a promising strategy due to their remarkable antibacterial properties. This review examines research published between 2006 and 2023, focusing on leading journals in nanotechnology, materials science, and biomedical research. The primary applications explored are the efficacy of Ag and Au NPs as antibacterial agents, their synthesis methods, morphological properties, and mechanisms of action. An extensive review of the literature on NPs synthesis, morphology, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and effectiveness against various Gram(+/-) bacteria confirms the antibacterial efficacy of Au and Ag NPs. The synthesis methods and characteristics of NPs, such as size, shape, and surface charge, are crucial in determining their antibacterial activity, as these factors influence their interactions with bacterial cells. Furthermore, this review underscores the urgent necessity of standardizing synthesis techniques, MICs, and reporting protocols to enhance the comparability and reproducibility of future studies. Standardization is essential for ensuring the reliability of research findings and accelerating the clinical application of NP-based antimicrobial approaches. This review aims to propel NP-based antimicrobial strategies by elucidating the properties that enhance the antibacterial activity of Ag and Au NPs. By highlighting their inhibitory effects against various bacterial strains and relatively low cytotoxicity, this work positions Ag and Au NPs as promising materials for developing antibacterial agents, making a significant contribution to global efforts to combat antibiotic-resistant pathogens.
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Surfactants can be used as nanoparticle stabilizing agents. However, since synthetic surfactants are not economically viable and environmentally friendly, biosurfactants are emerging as a green alternative for the synthesis and stabilization of nanoparticles. Nanoparticles have been applied in several areas of industry, such as the production of biomedical and therapeutic components, packaging coating, solar energy generation and transmission and distribution of electrical energy, among others. The aim of this study was to synthesize, in a simple and green way, silver nanoparticles (AgNPs) using the biosurfactant produced by Candida lipolytica UCP 0899 as a stabilizer. AgNPs were examined and morphologically characterized using the techniques of ultraviolet-visible spectroscopy (UV-visible), scanning electron microscopy (SEM), zeta potential and energy dispersive X-ray spectroscopy (EDS). Newly formed silver nanoparticles showed a maximum UV-visible absorption peak at 400 nm, while a shift to 410 nm was observed in those stored for 120 days. SEM micrograph confirmed the formation of nanoparticles with an average size of 20 nm and with a predominant spherical structure, while a zeta potential of -60 mV suggested that the use of the biosurfactant promoted their stability. Stabilized nanoparticles were tested for their antimicrobial activity against bacterial isolates of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Enterobacter sp., as well as fungal isolates of Candida albicans and Aspergillus niger. At a concentration of 16.50 µg/mL, AgNPs inhibited the growth of all target microorganisms according to the following decreasing order: E. coli (95%), S. aureus, C. albicans (90%), A. niger (85%), Enterobacter sp. (75%) and P. aeruginosa (71%). These results suggest the potential use of the biosurfactant as a stabilizer of silver nanoparticles as an antimicrobial agent in different industrial sectors. Furthermore, the in vivo toxicity potential of biosurfactants was evaluated using the Tenebrio molitor model. The larvae were treated with concentrations in the range of 2.5, 5.0 and 10 g/L, and no mortality was observed within the 24 to 72 h period, demonstrating non-toxicity within the tested concentration range. These findings support the safety, efficacy and non-toxicity of biosurfactant-stabilized nanoparticles.
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The aim of the present study was to report the remodeling of the basement membrane through physiological stimulus during the treatment of fibrosis in a lower limb with lymphedema. A clinical trial was conducted involving the evaluation of the basement membrane in skin biopsies before and after treatment for clinical stage II lower limb lymphedema using the Godoy method for the reversal of lymphedema and skin fibrosis. The samples were stained with Gomori's reticulin stain and evaluated using Weibel's multipoint morphometric method at the Godoy Clinic. Prior to treatment for lymphedema, rupture and important discontinuity of the basement membrane was found. After treatment, structural continuity and thickness had returned to the regions of previous rupture. The difference was statistically significant (P < 0.05, paired t-test). The present study reports that physiological stimuli targeting the lymphatic system led to the clinical reversal of fibrosis, as well as stimulate the synthesis of extracellular matrix proteins and the reconstruction of the basal lamina of the skin.
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Aim: This work aimed to synthesize a new pyrimidine PYB01 with potential application against antimicrobial resistance.Materials & methods: PYB01 was synthesized through condensation reaction between 3a and 3b. The antimicrobial evaluation was carried out using the microdilution method in Mueller-Hinton Agar and in silico predictions using different software.Results: PYB01 has moderate antibiotic activity and high capacity to efficiently modulate antibiotic resistance in Staphylococcus aureus. In silico evaluations demonstrated that PYB01 is probably an allosteric inhibitor of Protein Binding Penicilin 2a and modulates the action of oxacillin by decreasing the minimum inhibitory concentration by 64-times. PYB01 demonstrate a good pharmacokinetic profile and toxicological.Conclusion: PYB01 has great potential to go further in investigating its use against antimicrobial resistance.
[Box: see text].
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Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Oxacilina , Pirimidinas , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Pirimidinas/química , Pirimidinas/farmacología , Pirimidinas/síntesis química , Oxacilina/farmacología , Estructura Molecular , Sinergismo Farmacológico , Animales , HumanosRESUMEN
The Arctic is warming three times faster than the global average, imposing challenges to cold-adapted fish, such as Arctic char (Salvelinus alpinus). We evaluated stress and metabolic responses of Arctic char to different thermal acclimation scenarios to determine whether responses to thermal variation differed from those to stable exposures. Fish were exposed for 7â days to one of four treatments: (1) control (12°C); (2) mean (16°C), corresponding to the mean temperature of the diel thermal cycle; (3) constant high temperature (20°C); and (4) diel thermal cycling (12 to 20°C every 24â h). Exposure to 20°C causes increases plasma lactate and glucose, an imbalance in antioxidant systems, and oxidative stress in the liver. The 20°C treatment also elevated fractional rates of protein synthesis and caused oxidative stress in the heart. Stress responses were more pronounced in diel thermal cycling than in mean (16°C) fish, indicating that peak exposure temperatures or variation are physiologically important. Cortisol was highest in diel thermal cycling fish and oxidative stress was noted in the liver. Gill Na+/K+-ATPase activity was also significantly reduced in diel thermal cycling fish, suggesting gill remodeling in response to an osmoregulatory stress. Exposure to a constant 20°C was more challenging than a diel thermal cycle, demonstrating the importance of daily cooling to recovery. Arctic char inhabit a thermally variable environment and understanding how this impacts their physiology will be critical for informing conservation strategies in the context of a rapidly warming Arctic.