Search

Background: Auranofin is an approved anti-rheumatic drug that has a broad-range inhibitory action against several microorganisms, including human pathogenic fungi. The auranofin activity against Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, has not been properly addressed. Since there are few therapeutic options for this life-threatening systemic mycosis, this study evaluated the effects of auranofin on H. capsulatum growth and expression of virulence factors. Methodology/principal findings: Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) of auranofin against 15 H. capsulatum strains with distinct genetic backgrounds were determined using the yeast form of the fungus and a microdilution protocol. Auranofin activity was also assessed on a macrophage model of infection and on a Tenebrio molitor invertebrate animal model. Expression of virulence-related genes was compared between auranofin treated and untreated H. capsulatum yeast cells using a quantitative PCR assay. Auranofin affected the growth of different strains of H. capsulatum, with MIC and MFC values ranging from 1.25 to 5.0 μM and from 2.5 to >10 μM, respectively. Auranofin was able to kill intracellular H. capsulatum yeast cells and conferred protection against the fungus in the experimental animal model of infection. Moreover, the expression of catalase A, HSP70, superoxide dismutase, thioredoxin reductase, serine proteinase, cytochrome C peroxidase, histone 2B, formamidase, metallopeptidase, Y20 and YPS3 proteins were reduced after six hours of auranofin treatment. CONCLUSIONS/SIGNIFICANCE: Auranofin is fungicidal against H. capsulatum and reduces the expression of several virulence-related genes, which makes this anti-rheumatic drug a good candidate for new medicines against histoplasmosis. Author summary: Histoplasmosis is a serious disease caused by the fungus Histoplasma capsulatum, which can be life-threatening and has limited treatment options. In this study, we investigated the potential of auranofin, a drug originally approved for treating rheumatoid arthritis, to combat H. capsulatum. We tested auranofin against different strains of the fungus and found that it effectively inhibited fungal growth. This drug was also effective in killing the fungus within cells from the immune system and provided protection in an experimental animal model. Furthermore, auranofin reduced the expression of several genes associated with the fungus's ability to cause disease. These genes are involved in critical functions such as detoxifying harmful substances and maintaining cellular structures. By suppressing these genes, auranofin hampers the fungus's ability to survive and cause infection. These findings suggest that auranofin could be repurposed as a treatment for histoplasmosis, offering a new avenue for therapy against this challenging infection. This research is significant because it highlights the potential of existing drugs to treat other diseases, broadening our arsenal of available treatments and contributing to better healthcare solutions. [ABSTRACT FROM AUTHOR]

Finding strategies to enhance catalysts' electrochemical activity is based on controlling the material design. Bidimensional materials (2DM) such as MoS2 are explored as catalysts for the hydrogen evolution reaction (HER). A comprehensive study of the effects of doping 2D materials with transition metals based on theoretical predictions in tandem with experimental investigation correlates the doping type to the changes in the electronic and electrochemical activity. Localized electrochemical maps obtained by scanning electrochemical cell microscopy (SECCM) reveal that Ti‐doping induces a heterogeneous increase in 2H‐MoS2 basal plane electrochemical activity, while Ni‐doping induces a homogeneous decrease. Additionally, Kelvin probe microscopy provides insight into Ti‐doping, showcasing a decline in the 2H‐MoS2 work function, therefore confirming the predictions from density functional theory simulations. In essence, the findings underscore the potential of transition metal coordination on the 2H‐MoS2 surface as an attractive method for locally doping 2D materials with minimal damage to the crystalline lattice, consequently enhancing the electrochemical activity on the material's basal plane. [ABSTRACT FROM AUTHOR]

Renewable hydrogen obtained from renewable energy sources, especially when produced through water electrolysis, is gaining attention as a promising energy vector to deal with the challenges of climate change and the intermittent nature of renewable energy sources. In this context, this work analyzes a pilot plant that uses this technology, installed in the Itumbiara Hydropower Plant located between the states of Goiás and Minas Gerais, Brazil, from technical and economic perspectives. The plant utilizes an alkaline electrolyzer synergistically powered by solar photovoltaic and hydro sources. Cost data for 2019, when the equipment was purchased, and 2020–2023, when the plant began continuous operation, are considered. The economic analysis includes annualized capital, maintenance, and variable costs, which determines the levelized cost of hydrogen (LCOH). The results obtained for the pilot plant's LCOH were USD 13.00 per kilogram of H2, with an efficiency loss of 2.65% for the two-year period. Sensitivity analysis identified the capacity factor (CF) as the main determinant of the LCOH. Even though the analysis specifically applies to the Itumbiara Hydropower Plant, the CF can be extrapolated to larger plants as it directly influences hydrogen production regardless of plant size or capacity. [ABSTRACT FROM AUTHOR]

There is an urgent need for new antifungal drugs to treat invasive fungal diseases. Unfortunately, the echinocandin drugs that are fungicidal against other important fungal pathogens are ineffective against Cryptococcus neoformans, the causative agent of life-threatening meningoencephalitis in immunocompromised people. Contributing mechanisms for echinocandin tolerance are emerging with connections to calcineurin signaling, the cell wall, and membrane composition. In this context, we discovered that a defect in phosphate uptake impairs the tolerance of C. neoformans to the echinocandin caspofungin. Our previous analysis of mutants lacking three high affinity phosphate transporters revealed reduced elaboration of the polysaccharide capsule and attenuated virulence in mice. We investigated the underlying mechanisms and found that loss of the transporters and altered phosphate availability influences the cell wall and membrane composition. These changes contribute to the shedding of capsule polysaccharide thus explaining the reduced size of capsules onmutants lacking the phosphate transporters. We also found an influence of the calcineurin pathway including calcium sensitivity and an involvement of the endoplasmic reticulum in the response to phosphate limitation. Furthermore, we identified membrane and lipid composition changes consistent with the role of phosphate in phospholipid biosynthesis and with previous studies implicating membrane integrity in caspofungin tolerance. Finally, we discovered a contribution of phosphate to titan cell formation, a cell type that displays modified cell wall and capsule composition. Overall, our analysis reinforces the importance of phosphate as a regulator of cell wall and membrane composition with implications for capsule attachment and antifungal drug susceptibility. [ABSTRACT FROM AUTHOR]

The focus on building energy efficiency using alternative materials in structures, especially concrete, and the main technical and environmental challenges therein, aligns with Sustainable Development Goals (SDG). This study proposes a review that analyzes structures made with recycled concrete, relating to the energy efficiency of buildings. A classification structure was proposed, addressing the following questions: (i) What are the various dimensions in which research into energy-efficient recycled concrete is concentrated? (ii) What are the themes and classes of research associated with these dimensions? (iii) What are the main shortcomings of current approaches, and what would be a good research agenda for the future development of energy-efficient recycled concrete? A bibliometric analysis was carried out, presenting geographical and cluster maps to understand different research trends and refine future research. This was followed by a bibliographic analysis, reviewing the most relevant studies from the last five years (2019–2024). The results showed some residual alternative materials (around 45 types from five different industries) used in the production of energy-efficient concrete. And, as a negative effect, as substitution rates increase, porosity is the property with the greatest impact on energy efficiency. The greater the number of pores and the greater their interconnection, the lower the material's thermal insulation. [ABSTRACT FROM AUTHOR]

Objectives: This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced peripheral neuropathy (VIPN) in mice. Methods: The inhibitory activity of myeloperoxidase was assessed by measuring HOCl formation. Formalin and hot plate tests were used to study the acute antinociceptive effect of DMAC. VIPN was induced through the administration of vincristine sulphate (0.1 mg/kg, i.p., 14 days). Then, DMSO, DMAC (10 or 30 mg/kg; i.p.), or pregabalin (10 mg/kg, i.p.) were administered for 14 consecutive days. Thermal hyperalgesia and mechanical allodynia were evaluated before and after VIPN induction and on days 1, 3, 7, and 14 of treatment. Neurodegeneration and neuroinflammation were assessed through immunohistochemistry for NF200, iNOS, and arginase-1 within the sciatic nerve. Key findings: DMAC inhibited myeloperoxidase activity in vitro and presented an acute antinociceptive effect in both formalin and hot plate tests, with the involvement of muscarinic and opioid receptors. Treatment with 30 mg/kg of DMAC significantly attenuated thermal hyperalgesia and mechanical allodynia and prevented macrophage proinflammatory polarisation in VIPN mice. Conclusions: Our results show that DMAC, acting through different mechanisms, effectively attenuates VIPN. [ABSTRACT FROM AUTHOR]

Como construir processos de cidades inteligentes que superem as desigualdades socioespaciais, em especial as desigualdades que se refletem na saúde? Esta é uma das questões que inicia este artigo no formato de ensaio crítico-reflexivo que não tem a pretensão de trazer respostas absolutas e prontas para os assuntos que se entrecruzam no questionamento elencado. Apoia-se metodologicamente na revisão narrativa da literatura com base no referencial teórico da determinação social do processo saúde-doença e na compreensão da informação em saúde como um direito. Este texto traz alguns tópicos sobre a temática das cidades inteligentes no contexto brasileiro, acrescido da discussão da saúde como direito social, democraticamente conquistado no Brasil e as interfaces necessárias com temáticas relevantes para o campo da informação em saúde. São feitas reflexões e apontamentos necessários para que a incorporação da tecnologia digital nas cidades se dê no sentido de diminuir as desigualdades territoriais e não insivibilizá-las ou agudizá-las. Para a análise reflexiva foram trazidas situações exemplos que pudessem elucidar a discussão. É necessário avançar em processos e metodologias que identifiquem as desigualdades territoriais, em especial, as que incidem na saúde, pensar em formas de uso, incorporação e adaptação das tecnologias de informação e comunicação de acordo com as heterogeneidades e necessidades locais. Fortalecendo a informação em saúde como um direito humano e a construção de saúde digital e cidades digitais inclusivas e não como barreiras de acesso.

A transição nutricional no Brasil traçou um caminho singular refletindo-se em adoecimentos e óbitos, principalmente nas morbidades como a desnutrição e a obesidade. Dessa forma, esse estudo descreveu análise temporal da internação e mortalidade por desnutrição e obesidade no Brasil de 2000 a 2016, de forma a investigar o comportamento e a tendência nacional. Trata-se de um estudo epidemiológico quantitativo descritivo de caráter exploratório cujo objetivo foi descrever a distribuição dos casos de óbitos e internações hospitalares por desnutrição e obesidade no Brasil. Para a análise dos dados, foi realizada a estratificação etária, para compreender o comportamento epidemiológico dentro dos diferentes grupos etários. Em linhas gerais, a desnutrição no Brasil apresenta uma tendência de declínio, ao longo dos anos, enquanto a obesidade segue uma tendência de aumento da sua incidência pelos próximos anos, mudando então o padrão nutricional brasileiro. Tanto a desnutrição quando obesidade, no Brasil, apresentaram comportamentos peculiares em seus extremos etários – menores de um ano de idade e os maiores de sessenta anos, pois são grupos que apresentam uma vulnerabilidade em relação às condições nutricionais abordadas.