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Aims: Considering the need to identify new compounds with antifungal action, the activity of five 3-phenacylideneoxindoles compounds was evaluated. Materials & methods: The compounds were synthesized, and their antifungal activity was elucidated through minimum inhibitory concentration tests and interaction assay with other antifungals. Potential targets of compounds were predicted in silico. Results: 3-phenacylideneoxindoles compounds inhibited fungal growth with minimum inhibitory concentration and minimum fungicidal concentration ranging from 3.05 to 12.26 μM. The compounds demonstrated high selectivity index and presented a synergistic effect with itraconazole. In silico prediction revealed the pentafunctional AROM polypeptide, enolase, superoxide dismutase, catalase and kinases as proteins targets of the compound 4a. Conclusion: The results demonstrate that 3-phenacylideneoxindoles is a potential new class of antifungal compounds for paracoccidioidomycosis treatment.

A biofilm is a clump of bacteria living in a self-produced matrix of extracellular polymeric substances (EPS) linked to a biotic or abiotic surface, indicating that biofilms can exist on a variety of biotic and abiotic surfaces. Abiotic surfaces include floors, walls, drains, equipment, and food-contact surfaces, as well as biotic surfaces like meat, the oral cavity, the intestine, the urogenital tract, and the skin. Humans are a good source of biotic microenvironments for biofilm and bacterial growth, which leads to infectious diseases in most cases. The optimum biotic environment for bacteria to thrive requires a supply of nutrients, humidity, and the right temperature. Biofilms originate on inert surfaces or dead tissue, and they're frequent on medical devices and dead tissue fragments, but they can also form on living tissues. Biofilms' tolerance to harsh environments provides a favorable habitat for microbial populations, allowing for a more efficient flow of chemicals and information amongst microorganisms. As a result, biofilm resistance is a self-protective strategy for microbial development. Bacterial biofilms are detectable by direct and indirect methods and they could be controlled. Bacterial biofilm is a major cause of antimicrobial-resistant bacteria's development and spread, causing severe infections and increased mortality rates.

Virgin olive oil (VOO) is the main fat consumed by populations in the Mediterranean basin, and phenolic compounds, minor components of this fat, are known to be responsible for diverse health benefits when consumed in a regular diet. According to numerous investigations, these benefits are mostly related to phenols such as tyrosol and hydroxytyrosol and secoiridoid derivatives such as ligstroside, oleuropein, oleocanthal and oleacein. These compounds are present in low concentrations, and for some of them, standards are not commercially available, hampering studies on the mechanisms underlying their biological activity. In order to contribute to a better knowledge of the bioactivity of these compounds and their metabolites, they must be available with high purity and in sufficient amounts for the assays. Chemical synthesis has been considered a convenient way to obtain these compounds. This Review will focus on the synthesis of representative VOO compounds, namely, ligstroside, oleuropein, oleocanthal, oleacein and analogues.

Rivers suffer from multiple stressors acting simultaneously on their biota, but the consequences are poorly quantified at the global scale. We evaluated the biological condition of rivers globally, including the largest proportion of countries from the Global South published to date. We gathered macroinvertebrate- and fish-based assessments from 72,275 and 37,676 sites, respectively, from 64 study regions across six continents and 45 nations. Because assessments were based on differing methods, different systems were consolidated into a 3-class system: Good, Impaired, or Severely Impaired, following common guidelines. The proportion of sites in each class by study area was calculated and each region was assigned a Köppen-Geiger climate type, Human Footprint score (addressing landscape alterations), Human Development Index (HDI) score (addressing social welfare), % rivers with good ambient water quality, % protected freshwater key biodiversity areas; and % of forest area net change rate. We found that 50% of macroinvertebrate sites and 42% of fish sites were in Good condition, whereas 21% and 29% were Severely Impaired, respectively. The poorest biological conditions occurred in Arid and Equatorial climates and the best conditions occurred in Snow climates. Severely Impaired conditions were associated (Pearson correlation coefficient) with higher HDI scores, poorer physico-chemical water quality, and lower proportions of protected freshwater areas. Good biological conditions were associated with good water quality and increased forested areas. It is essential to implement statutory bioassessment programs in Asian, African, and South American countries, and continue them in Oceania, Europe, and North America. There is a need to invest in assessments based on fish, as there is less information globally and fish were strong indicators of degradation. Our study highlights a need to increase the extent and number of protected river catchments, preserve and restore natural forested areas in the catchments, treat wastewater discharges, and improve river connectivity.

PURPOSE: This study investigated the effects of both an active warm-up and the time-of-day variation on repeated-sprint performance. A second objective was to compare the post-exercise recovery between the experimental conditions. METHODS: Eleven male participants performed ten maximal cycling sprints (6 s each, with a 30-s interval between them) in the morning and late afternoon, either after a warm-up or control condition. The warm-up consisted of cycling for 10 min at 50% of the peak aerobic power. RESULTS: Rest measurements of rectal, muscle, and skin temperatures were higher in the afternoon compared to the morning (p

Visceral leishmaniasis (VL) in the Americas is a chronic systemic disease caused by infection with Leishmania infantum parasites. The toxicity of antileishmanial drugs, long treatment course and limited efficacy are significant concerns that hamper adequate treatment against the disease. Studies have shown the promise of an immunotherapeutics approach, combining antileishmanial drugs to reduce the parasitism and vaccine immunogens to activate the host immune system. In the current study, we developed an immunotherapy using a recombinant T cell epitope-based chimeric protein, ChimT, previously shown to be protective against Leishmania infantum, with the adjuvant monophosphoryl lipid A (MPLA) and amphotericin B (AmpB) as the antileishmanial drug. BALB/c mice were infected with L. infantum stationary promastigotes and later they received saline or were treated with AmpB, MPLA, ChimT/Amp, ChimT/MPLA or ChimT/MPLA/AmpB. The combination of ChimT/MPLA/AmpB significantly reduced the parasite load in mouse organs (p < 0.05) and induced a Th1-type immune response, which was characterized by higher ratios of anti-ChimT and anti-parasite IgG2a:IgG1 antibodies, increased IFN-γ mRNA and IFN-γ and IL-12 cytokines and accompanied by lower levels of IL-4 and IL-10 cytokines, when compared to other treatments and controls (all p < 0.05). Organ toxicity was also lower with the ChimT/MPLA/AmpB immunotherapy, suggesting that the inclusion of the vaccine and adjuvant ameliorated the toxicity of AmpB to some degree. In addition, the ChimT vaccine alone stimulated in vitro murine macrophages to significantly kill three different internalized species of Leishmania parasites and to produce Th1-type cytokines into the culture supernatants. To conclude, our data suggest that the combination of ChimT/MPLA/AmpB could be considered for further studies as an immunotherapy for L. infantum infection.

The collaborative federal–provincial Southern Indian Lake project in north-central Manitoba covered an area of more than 3500 km2 of the Trans-Hudson orogen. Regional-scale geological mapping, sampling, and lithogeochemical, isotopic, and geochronological studies resulted in the identification of distinct assemblages of supracrustal rocks and varied episodes of plutonism. A granodiorite gneiss dated at ca. 2520 Ma is interpreted to represent the basement of the Southern Indian domain and is considered a separate crustal domain, named the Partridge Breast block. The Churchill River assemblage is composed of juvenile pillow basalt with intervening clastic sedimentary rocks, possibly a reflection of plume magmatism related to initial rifting of the Hearne craton margin. The Pukatawakan Bay assemblage consists mainly of massive to pillowed, juvenile metabasaltic rocks and associated basinal metasedimentary rocks. The Partridge Breast Lake assemblage is dominated by continental-arc volcanic and volcaniclastic rocks associated with basinal metasedimentary rocks. The Strawberry Island assemblage, consisting of arenite and polymictic conglomerate, is interpreted to have been deposited in a foreland-basin basin or intra-orogen pull-apart basin environment. The Whyme Bay assemblage is characterized by fluvial-alluvial orogenic sediments and is temporally linked to the Sickle Group rocks in the Lynn Lake greenstone belt. Granitoid rocks, dominantly monzogranite and granodiorite, range in age from ca. 1890 to 1830 Ma and occur throughout the Southern Indian domain, and intermediate and mafic intrusions of similar ages are also present. In this paper, we integrate these new data into a tectonic framework for the Southern Indian domain of the Trans-Hudson orogen in Manitoba.

Introduction Cocaine use disorder is a significant public health issue without a current specific approved treatment. Among different approaches to this disorder, it is possible to highlight a promising immunologic strategy in which an immunogenic agent may reduce the reinforcing effects of the drug if they are able to yield sufficient specific antibodies capable to bind cocaine and/or its psychoactive metabolites before entering into the brain. Several carriers have been investigated in the anti-cocaine vaccine development; however, they generally present a very complex chemical structure, which potentially hampers the proper assessment of the coupling efficiency between the hapten units and the protein structure. Objectives The present study reports the design, synthesis and preclinical evaluation of two novel calix[n]arene-based anti-cocaine immunogens (herein named as V4N2 and V8N2) by the tethering of the hydrolysis-tolerant hapten GNE (15) on calix[4]arene and calix[8]arene moieties. Methods The preclinical assessment corresponded to the immunogenicity and dose–response evaluation of V4N2 and V8N2. The potential of the produced antibodies to reduce the passage of cocaine analogue through the blood–brain-barrier (BBB), modifying its biodistribution was also investigated. Results Both calix[n]arene-based immunogens elicited high titers of cocaine antibodies that modified the biodistribution of a cocaine radiolabeled analogue (99mTc-TRODAT-1) and decreased cocaine-induced behavior, according to an animal model. Conclusion The present results demonstrate the potential of V4N2 and V8N2 as immunogens for the treatment of cocaine use disorder.

Two series of chlorine or fluorine derivatives containing monooxamato ligands result in diamagnetic complexes of Y3+ and La3+ and paramagnetic complexes of Nd3+ and Ho3+ that behave as single-ion magnets at lower temperatures.

Ecological and safe packaging solutions arise as pivotal points in the development of an integrated system for sustainable meat production. The aim of this study was to assess the effect of a combined chitosan (Ch) + green tea extract (GTE) + essential oil (thyme oil, TO; flaxseed oil, FO; or oregano oil, OO) coating on the safety and quality of vacuum-packaged beef during storage at 4 °C. An optimized bio-based coating formulation was selected (2% Ch + 2% GTE + 0.1% FO) to be applied to three fresh beef cuts (shoulder, Sh; knuckle, Kn; Striploin, St) based on its pH (5.8 ± 0.1), contact angle (22.3 ± 0.4°) and rheological parameters (viscosity=0.05 Pa.s at shear rate > 20 s−1). Shelf-life analysis showed that the Ch–GTE–FO coating delayed lipid oxidation and reduced total viable counts (TVC) and Enterobacteriaceae growth compared with uncoated beef samples over five days. In addition, Ch–GTE–FO coating decreased total color changes of beef samples (e.g., ∆E*=9.84 and 3.94, for non-coated and coated Kn samples, respectively) for up to five days. The original textural parameters (hardness, adhesiveness and springiness) of beef cuts were maintained during storage when Ch–GTE–FO coating was applied. Based on the physicochemical and microbial characterization results, the combination of the Ch–GTE–FO coating developed was effective in preserving the quality of fresh beef cuts during refrigerated storage along with vacuum packaging., This research was funded by ETHICAL MEAT—Integrated System for Sustainable Meat Production project (POCI-01-0247-FEDER-072254), co-financed by the European Regional Development Fund (ERDF) through Compete 2020–Competitiveness and Internationalisation Operational Programme (POCI). This work was also financially supported by FCT under the scope of the strategic funding of UIDB/04469/2020 unit, and by LABBELS—Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020., info:eu-repo/semantics/publishedVersion

Serological assays have been widely used to detect anti-SARS-CoV-2 antibodies, which are generated from previous exposure to the virus or after vaccination. The presence of anti-SARS-CoV-2 Nucleocapsid antibodies was recently reported in patients´ urine using an in-house urine-based ELISA-platform, allowing a non-invasive way to collect clinical samples and assess immune conversion. In the current study, we evaluated and validated another in-house urine-based ELISA for the detection of anti-SARS-CoV-2 Spike antibodies. Three partial recombinant SARS-CoV-2 Spike proteins comprising the Receptor Binding Domain, expressed in eukaryotic or prokaryotic systems, were tested in an ELISA platform against a panel of over 140 urine and paired serum samples collected from 106 patients confirmed positive for SARS-CoV-2 by qRT-PCR. The key findings from our study were that anti-SARS-CoV-2 Spike antibodies could be detected in urine samples and that the prokaryotic expression of the rSARS-CoV-2 Spike protein was not a barrier to obtain relatively high serology efficiency for the urine-based assay. Thus, use of a urine-based ELISA assay with partial rSARS-CoV-2 Spike proteins, expressed in a prokaryotic system, could be considered as a convenient tool for screening for the presence of anti-SARS-CoV-2 Spike antibodies, and overcome the difficulties arising from sample collection and the need for recombinant proteins produced with eukaryotic expression systems.

The transport of drugs by efflux transporters in biomembranes limits their bioavailability and is a major determinant of drug resistance development by cancer cells and pathogens. A large number of chemically dissimilar drugs are transported, and despite extensive studies, the molecular determinants of substrate specificity are still not well understood. In this work, we explore the role of polar and non-polar interactions on the interaction of a homologous series of fluorescent amphiphiles with the efflux transporter P-glycoprotein. The interaction of the amphiphiles with P-glycoprotein is evaluated through effects on ATPase activity, efficiency in inhibition of [125I]-IAAP binding, and partition to the whole native membranes containing the transporter. The results were complemented with partition to model membranes with a representative lipid composition, and details on the interactions established were obtained from MD simulations. We show that when the total concentration of amphiphile is considered, the binding parameters obtained are apparent and do not reflect the affinity for P–gp. A new formalism is proposed that includes sequestration of the amphiphiles in the lipid bilayer and the possible binding of several molecules in P–gp’s substrate-binding pocket. The intrinsic binding affinity thus obtained is essentially independent of amphiphile hydrophobicity, highlighting the importance of polar interactions. An increase in the lipophilicity and amphiphilicity led to a more efficient association with the lipid bilayer, which maintains the non-polar groups of the amphiphiles in the bilayer, while the polar groups interact with P–gp’s binding pocket. The presence of several amphiphiles in this orientation is proposed as a mechanism for inhibition of P-pg function.

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) Fundacao de Apoio a Pesquisa do Distrito Federal (FAPDF), Fundacao de Amparo a Pesquisa do Estado do Amazonas (FAPEAM), BIODIVERSA/FAPEAM, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ), Bundesministerium fuer Bildung und Forschung, Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), FAPEAM-Program POSGRAD, Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), INPA/MCTI 465540/2014-7, Leibniz Competition 0621187/2017, Leibniz-Gemeinschaft R20F0002, Instituto Nacional de Pesquisas da Amazpnia, unidade de~pesquisa Ministerio da Ciencia, Tecnologia e Inovacoes (INPA/MCTI) 403758/2021-1, Programa Peixe Vivo of the Companhia Energetica de Minas Gerais 033W034A, Royal Society of New Zealand, Tertiary Education Commission, Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Foundation for Science and Technology, Associate LaboratoryARNET J45/2018, CEEC

A nutrição é um dos pilares para o desenvolvimento da cadeia produtiva de suínos, aves e peixes, isso, devido seu impacto no desempenho e na saúde animal. A procura por alimentos alternativos que ofereçam qualidade nutracêutica é crescente nos dias atuais, principalmente pelos custos elevados e ingredientes limitados que afetam a produção comercial. Nesse cenário, o uso de farinha de insetos promove pesquisas pelo mundo todo a fim de elucidar suas potencialidades, embora já seja conhecido que a farinha de insetos é rica em proteínas, lipídios e fonte de minerais e vitaminas, é importante conhecer seus efeitos no organismo, por exemplo, o papel que a quitina exerce na digestibilidade e imunidade. A quantidade e qualidade dos nutrientes presentes na farinha de insetos é dependente da espécie utilizada e o seu processamento. As espécies mais utilizadas são a Black soldier fly (BSF) e Tenebrio molitor, além da mosca doméstica, tenébrio gigantes, grilos e gafanhotos. No Brasil, ainda não existe nenhuma legislação que orienta e normatize a produção e comercialização de insetos para o consumo. Com isso, objetivou-se com essa revisão, abordar o uso da farinha de insetos na dieta de suínos, aves e peixes, visando melhorias na produtividade dessas culturas de maneira sustentável e lucrativa.

Visceral leishmaniasis (VL) is a neglected tropical disease of global importance caused by parasites of the genus Leishmania, and coinfection with human immunodeficiency virus (HIV) is common in countries where both diseases are endemic. In particular, widely used immunological tests for VL diagnosis have impaired sensitivity (Se) and specificity (Sp) in VL/HIV coinfected patients and there is also cross-reactivity with other endemic diseases, e.g., Chagas disease, malaria, and tuberculosis. To develop new antigens to improve the diagnosis of VL and VL/HIV coinfection, we predicted eight specific B-cell epitopes of four Leishmania infantum antigens and constructed a recombinant polypeptide chimera antigen called ChimLeish. A serological panel of 195 serum samples was used to compare the diagnostic capabilities of ChimLeish alongside the individual synthetic peptides. ChimLeish reacted with sera from all VL and VL/HIV coinfected patients [Se = 100%; Sp = 100%; area under the curve (AUC) = 1.0]. Peptides showed lower reactivities (Se = 76.8 to 99.2%; Sp = 67.1 to 95.7%; AUC between 0.87 and 0.98) as did a L. infantum antigenic preparation used as an antigen control (Se = 56.8%; Sp = 69.5%: AUC = 0.45). Notably, ChimLeish demonstrated a significant reduction (p < 0.05) of anti-ChimLeish antibodies after treatment and cure of a small number of patients. Although only a limited serological panel was tested, preliminary data suggest that ChimLeish should be evaluated in larger sample studies for the diagnosis of VL and VL/HIV coinfection.

Background Patients with heart failure (HF) often have altered renal function. Urinary sodium is a marker of diuretic resistance and is associated with a worse prognosis in HF. Growth differentiation factor-15 (GDF-15) is a marker of oxidative stress and inflammation and is a prognostic predictor in HF. Objectives We sought to assess the relationship of GDF-15 with renal function parameters and with urinary sodium in patients with chronic HF. Methods We undertook a cross-sectional study of patients with HF from specialized outpatient clinic. Patients with signs and symptoms of HF and LVEF Results Sixty-seven patients were included. The etiologies of HF were hypertension, diabetes mellitus, alcoholic cardiomyopathy and idiopathic cardiomyopathy. Forty-one (61.2%) individuals were male, with a mean age of 61±13 years. Median GDF-15 values were 1413 pg/mL (interquartile range 1044–2554). Patients with GDF-15 values above the median had lower urinary sodium values (88 mEq/L [53–121] vs 112 [76–171], p=0.06), lower glomerular filtration rate (GFR) (63.9±29.1 vs 91.2±25 mL/min/1.73 m2, p=0.001) and higher creatinine levels (1.32 mg/dL [0.85–1.71] vs 0.91 [0.78–1.08], p Conclusion GDF-15 correlated with lower urinary sodium levels and worse kidney function in patients with chronic HF. Future studies should address whether GDF-15 is a predictor of worsening renal function overtime. Funding Acknowledgement Type of funding sources: None.

Green propolis is an attractive natural source of antioxidant and antimicrobial compounds. In this paper, pectin (P) films incorporated with green propolis extract (PE) (i.e., P/PE films) were prepared by casting. The effect of different PE concentrations (13% w/w) on films' physicochemical properties was investigated for the first time. Regardless of the PE concentration added, no significant morphological and structural changes of the P-based films were identified using scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FT-IR) analysis. However, a reduction in the crystallinity of the P films was observed through the X-ray diffraction (XRD) analysis, which was correlated to film tensile strength (TS) reduction from 19.0 (P film) to 14.8 MPa (P/PE3% film). The other mechanical and water vapor barrier properties did not change significantly. However, the incorporation of PE improved UV-light barrier properties of the P films. Additionally, antioxidant activity of the P films (12.6%) considerably increased to 54.8% (P/PE3% film), suggesting the potential of P/PE film to be used as active food packaging., The authors acknowledge the National Council for Scientific and Technological Development (CNPq), grant number 403595/2021-5, and the São Paulo Research Foundation (FAPESP) for the post-doctoral fellowship of L. Marangoni Júnior (2021/04043-2). This study was partly financed by the Coordination for the Improvement of Higher Education Personnel – Brazil (CAPES) – Financial Code 001. This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit., info:eu-repo/semantics/publishedVersion

O vínculo é uma das formas de se demonstrar a afetividade e permite um desenvolvimento psíquico mais saudável. Esta pesquisa teve o objetivo compreender a importância do cuidado e acolhimento realizado por parte das cuidadoras na construção do vínculo, visando reduzir o sofrimento de crianças institucionalizadas. Foi realizada uma entrevista semiestruturada com nove cuidadoras de uma Associação localizada numa cidade do interior do estado de São Paulo. Os resultados mostraram que as cuidadoras desenvolvem vínculo afetivo com as crianças, e contribuem na amenização dos impactos da institucionalização, uma vez que realizam o papel de figura materna. Em contrapartida, as cuidadoras demonstraram um descontentamento com a instituição referente ao número reduzido de funcionárias, destacando a alta rotatividade como um fator que prejudica o cuidado das crianças. Além disso, apresentaram dificuldades em compreender o limite de envolvimento afetivo com as crianças, para que seja uma relação saudável para ambas as partes. Espera-se que os resultados desta pesquisa forneçam conhecimento às cuidadoras, referente à importância no processo de cuidar, e o papel do vínculo no desenvolvimento psíquico ao longo do processo de abrigamento. Palavras-chave: desenvolvimento psíquico; cuidadoras; vínculo.

Os acidentes com animais peçonhentos têm importância na saúde pública, sendo fundamental ações educativas para prevenção, diagnóstico e tratamentos. No Brasil, os soros hiperimunes são preconizados para o tratamento dos acidentados. Esses produtos são produzidos por laboratórios oficiais seguindo requisitos das Boas Práticas de Fabricação (BPF) e distribuídos gratuitamente pelo Sistema Único de Saúde. Buscando atender uma demanda da sociedade, o projeto de extensão “Kaizen: Formação de recursos humanos e o aperfeiçoamento contínuo profissional, institucional e social sobre animais peçonhentos e a produção de soros na saúde pública” estabeleceu uma parceria entre o Instituto Vital Brazil (IVB) e o Curso de Farmácia da Universidade Federal do Rio de Janeiro (UFRJ-Macaé) para o desenvolvimento de ciclos de ações educativas para diferentes públicos. O primeiro ciclo foi realizado pela universidade e direcionado aos colaboradores do IVB envolvendo conteúdos das BPF. O segundo ciclo foi realizado pelo IVB para o público de Macaé e municípios limítrofes com a participação de estudantes de ensino fundamental, médio e superior, além de agentes de combate de endemias, exército brasileiro, defesa civil, centro de zoonoses e guarda ambiental. Após a realização das ações, formulários de avaliação foram fornecidos aos participantes, observando-se alto grau de satisfação. Dessa forma, as ações contribuíram para o aprimoramento do conhecimento das BPF, além de ampliar os espaços de construção do conhecimento e aprendizagem para evitar os acidentes com animais peçonhentos, assim como nos tratamentos e produção dos soros hiperimunes e distribuição na saúde pública.

The present study evaluated the general welfare state of two strains of transgenic goats bred in a region with a hot and humid tropical climate. Nine females were used, being three transgenic for human lysozyme (hLZ group), three transgenic for human glucocerebrosidase (hGCase group), and three non-transgenic (control group). The temperature and humidity index (THI) were recorded during the morning, afternoon, and evening. The physiological parameters measured were respiratory rate, heart rate, and rectal and vaginal temperatures. Venous blood samples were collected using Vacutainer® tubes containing 10% ethylenediaminetetraacetic acid (EDTA). Also, analysis of erythrogram, leukogram, and some biochemical parameters of serum was performed. It was observed that the afternoon shift presented the largest THI, being potentially more impactful on the physiology of animals. In general, respiratory and heart rates were higher in transgenic animals, especially in the hLZ group compared to the control group (P

Chemical fixation of CO2 to produce cyclic carbonates can be a green and atomic efficient process. In this work, a series of porphyrazines (Pzs) containing electron-withdrawing groups and central MII ions (where M = Mg, Zn, Cu, and Co) were synthesized and investigated as catalysts for the cycloaddition of CO2 to epoxides. Then, the efficiency of the Pzs was tested by varying cocatalyst type and concentration, epoxide, temperature, and pressure. MgIIPz bearing trifluoromethyl groups (1) showed the best conversion, producing, selectively, 78% of propylene cyclic carbonate (PCC), indicating that a harder and stronger Lewis acid is more effective for epoxide activation. Moreover, cocatalyst variation showed a notable effect on the reaction yields. Spectrophotometric titrations, MALDI-TOF mass spectra, and theoretical calculations suggest poisoning of the catalyst when tetrabutylammonium chloride (TBAC) and large amounts of tetrabutylammonium bromide (TBAB) were used in the system. The same was not observed for tetrabutylammonium iodide (TBAI), indicating that the metal-cocatalyst interaction may govern the reaction rate. In addition, two rare examples of crystalline structures were obtained, proving the distorted square pyramidal geometry with water molecule as axial ligand. This is one of the first studies reporting Pzs as catalysts for the chemical fixation of CO2, and we believe that the intricate balance between cocatalyst concentration and conversion efficiency shown here may aid future studies in the area.

Water is the most important resource for all kind forms of live. It is a vital resource distributed unequally across different regions of the globe, with populations already living with water scarcity, a situation that is spreading due to the impact of climate change. The reversal of this tendency and the mitigation of its disastrous consequences is a global challenge posed to Humanity, with the scientific community assuming a major obligation for providing solutions based on scientific knowledge. This article reviews literature concerning the development of nanomaterials for water purification technologies, including collaborative scientific research carried out in our laboratory (nanoLAB@UA) framed by the general activities carried out at the CICECO-Aveiro Institute of Materials. Our research carried out in this specific context has been mainly focused on the synthesis and surface chemical modification of nanomaterials, typically of a colloidal nature, as well as on the evaluation of the relevant properties that arise from the envisaged applications of the materials. As such, the research reviewed here has been guided along three thematic lines: 1) magnetic nanosorbents for water treatment technologies, namely by using biocomposites and graphite-like nanoplatelets; 2) nanocomposites for photocatalysis (e.g., TiO2/Fe3O4 and POM supported graphene oxide photocatalysts; photoactive membranes) and 3) nanostructured substrates for contaminant detection using surface enhanced Raman scattering (SERS), namely polymers loaded with Ag/Au colloids and magneto-plasmonic nanostructures. This research is motivated by the firm believe that these nanomaterials have potential for contributing to the solution of environmental problems and, conversely, will not be part of the problem. Therefore, assessment of the impact of nanoengineered materials on eco-systems is important and research in this area has also been developed by collaborative projects involving experts in nanotoxicity. The above topics are reviewed here by presenting a brief conceptual framework together with illustrative case studies, in some cases with original research results, mainly focusing on the chemistry of the nanomaterials investigated for target applications. Finally, near-future developments in this research area are put in perspective, forecasting realistic solutions for the application of colloidal nanoparticles in water cleaning technologies.

This research work investigates the development of alginate-based films incorporating phenolic compounds extracted from Amaranthus cruentus grain using different solvents. Alginate, glycerol, and amaranth grain phenolic compounds at various concentrations were used to produce the films. An experimental Central Composite Rotatable Design (CCRD) was used to evaluate the effect of these variables on different film’s properties, i.e., water vapor permeability, hydrophobicity, moisture content, solubility, thermal, mechanical, and optical properties. This study demonstrated that high phenolic compound content and antioxidant capacity were obtained from amaranth grain using ethanol as the extraction solvent. Alginate films incorporating amaranth phenolic compounds were successfully manufactured, and this study can be used to tailor the formulation of alginate films containing amaranth phenolic compounds, depending on their final food application. For example, less flexible but more resistant and water-soluble films can be produced by increasing the alginate concentration, which was confirmed by a Principal Component Analysis (PCA) and Partial Least Squares (PLS) analysis. This study showed that active alginate films with amaranth phenolic compounds can be tailored to be used as food packaging material with potential antioxidant activity.

In the last 30 years a plethora of phylogeography studies have been published targeting Brazilian marine species. To date, several historical and extant physical and ecological processes have been identified as drivers of allopatric, sympatric and parapatric population genetic differentiation detected along the Brazilian coast. Examples of extant physical barriers include the split of the South Equatorial Current into the Brazil and North Brazil boundary currents, the mouth of major rivers (e.g., Amazon, São Francisco and Doce rivers) and coastal upwellings. Examples of historical barriers include the Vitória-Trindade seamount chain promoting genetic differentiation during periods of glacial maxima and lower sea levels. Examples of ecological speciation include adaptations to different substrata, resource use and reproductive biology. We used published data to build data sets and generalized additive models to identify patterns of spatial phylogeographical concordance across multiple taxa and markers. Our results identify Cape São Roque as the most dominant extant barrier to gene flow along the Brazilian coast, followed by the Vitória-Trindade seamount chain and Cape Santa Marta. Cape Santa Marta is the northern winter limit of the Rio da Plata plume and is intermittently influenced by the Malvinas Current. This study provides a novel explicit quantitative approach to comparative phylogeography that recognizes four Brazilian phylogeographical regions delimited by processes associated with barriers to gene flow.

Imidazoles constitute an important class of heterocyclic compounds with extensive potential use, from pharmaceuticals to optoelectronics. However, synthetic methodologies capable of producing novel nonsymmetric imidazoles are still scarce. In a combined synthesis, photophysical and computational investigation, we show that ruthenium(II) catalysis enables C−H/N−H alkyne annulation of nonsymmetric imidazoles derived from naturally occuring β-lapachone and nor-β-lapachone. This method provides an efficient and versatile tool for synthesizing fluorescent compounds with a broad application range.

This research work investigates the development of alginate-based films incorporating phenolic compounds extracted from

Currently, there is no licensed vaccine to protect against human visceral leishmaniasis (VL), a potentially fatal disease caused by infection with Leishmania parasites. In the current study, a recombinant chimeric protein ChimT was developed based on T-cell epitopes identified from the immunogenic Leishmania amastigote proteins LiHyp1, LiHyV, LiHyC and LiHyG. ChimT was associated with the adjuvants saponin (Sap) or monophosphoryl lipid A (MPLA) and used to immunize mice, and their immunogenicity and protective efficacy were evaluated. Both ChimT/Sap and ChimT/MPLA induced the development of a specific Th1-type immune response, with significantly high levels of IFN-γ, IL-2, IL-12, TNF-α and GM-CSF cytokines produced by CD4+ and CD8+ T cell subtypes (p < 0.05), with correspondingly low production of anti-leishmanial IL-4 and IL-10 cytokines. Significantly increased (p < 0.05) levels of nitrite, a proxy for nitric oxide, and IFN-γ expression (p < 0.05) were detected in stimulated spleen cell cultures from immunized and infected mice, as was significant production of parasite-specific IgG2a isotype antibodies. Significant reductions in the parasite load in the internal organs of the immunized and infected mice (p < 0.05) were quantified with a limiting dilution technique and quantitative PCR and correlated with the immunological findings. ChimT/MPLA showed marginally superior immunogenicity than ChimT/Sap, and although this was not statistically significant (p > 0.05), ChimT/MPLA was preferred since ChimT/Sap induced transient edema in the inoculation site. ChimT also induced high IFN-γ and low IL-10 levels from human PBMCs isolated from healthy individuals and from VL-treated patients. In conclusion, the experimental T-cell multi-epitope amastigote stage Leishmania vaccine administered with adjuvants appears to be a promising vaccine candidate to protect against VL.

Manganese-based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium-based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single-pot template synthetic strategy to develop a MnCA, MnL , and studied the most important physicochemical properties in vitro. MnL displays optimized r relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r =21.1 mM s (20 MHz, 298 K, pH 7.4) upon binding to BSA (K =4.2×10 M ). In vivo studies show that MnL is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCA Magnevist. MnL shows great promise as a novel MRI contrast agent. Me Me b −1 −1 3 −1 Me Me 1 1 a

Objective To map the evidence available in the literature on the health-related quality of life of women with breast cancer using hormone therapy. Data sources This review followed the Joanna Briggs Institute methodological recommendations and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines. Searches were performed in nine databases using descriptors, synonyms and keywords; grey literature was also included. The review protocol was registered with the Open Science Framework under doi: http://doi.org/10.17605/OSF.IO/347FM . Inclusion criteria were established according to the Population, Concept, and Context strategy. The selection of studies was performed by two independent reviewers with the aid of RAYYAN software and disagreements were resolved by a third reviewer. The main information from the included articles was grouped into textual categories and presented by means of a narrative synthesis. Data Summary A total of 5419 records were identified, of which 42 studies fully met the eligibility criteria. Most were multicenter studies (42.9%) and randomized controlled trials (62%). Most studies addressed anastrozole (39.5%), letrozole (34.2%), and tamoxifen (26.3%), which were studied alone or in combination. The most widely used health-related quality-of-life assessment tool was the EORTC-QLQ-C30. The concomitant use of hormone therapy and cyclin-dependent kinase inhibitors 4 and 6 showed improvement in health-related quality of life. Conclusion In recent years there has been an increase in studies focused on health-related quality of life, and the evidence pointed to relevant information on health-related quality of life and the use of endocrine therapy, tamoxifen in combination with aromatase inhibitors, as well as aromatase inhibitor alone and the use of cyclin-dependent kinase 4 and 6.

This paper addresses the concept of Industry 4.0 from the perspective of the molds industry, a key industry in today’s industrial panorama. With its constant modernization, several technologies have been introduced, in particular regarding machining equipment. With each brand and model requiring different (proprietary) interfaces and communication protocols, this technological diversity renders the automatic interconnection with production management software extremely challenging. In this paper a methodology to build monitoring solutions for machining devices is defined, based on the main equipment and operations used by molds industry companies. For a standardized approach, OPC UA is used for high-level communication between the various systems. As a key result of this paper, and given the variety of monitoring systems and communication protocols, the developed approach combines various different machine interfaces on a single system, in order to cover a relevant subset of machining equipment currently in use by the molds industry. This kind of all-in-one approach will give production managers access to the information needed for a continuous monitoring and improvement of the entire production process.

pH is a critical parameter that has found unique application in magnetic resonance imaging (MRI) mapping acidity in tissues. This study reports a series of Dy-based MR probes that show innovative T2ex features, governed by proton catalyzed events. With an increase of pH from 5.5 to 8.0, the r2ex relaxivity increased dramatically, while the r1 relaxivity remained unchanged. The resulting r2ex/r1 allowed for concentration-independent and direct mapping of physiologically relevant pH ranges.

In this study, novel ruthenium(III) complexes with hydroxybenzophenones with the general formula cis-[RuCl2(HB)(dppb)] were obtained, where HB = 2-hydroxy-4-(octyloxy)benzophenone (C1), 2-hydroxy-4-methoxybenzophenone (C2), 2,2′-dihydroxy-4,4′-dimethoxybenzophenone (C3), 2,2′-dihydroxy-4-methoxybenzophenone (C4), 2,4-dihydroxybenzophenone (C5), and 2,4,4′-trihydroxybenzophenone (C6), and dppb = 1,4-bis(diphenylphosphine)butane. These compounds were characterized by elemental analysis, molar conductivity, cyclic voltammetry, infrared and UV-vis spectroscopy, and powder X-ray diffraction. The crystal structures of C2, C3, C4, and C5 were determined by single-crystal X-ray diffraction analysis which confirmed the bidentate coordination of the carbonyl and phenolate oxygens of HB with ruthenium(III). Additionally, the cis geometry and electronic transitions of C1–C6 were investigated using DFT calculations. Finally, the comparative activity against promastigote forms of L. amazonensis was made available for the ligands HB1–HB6 and C1–C6. The ligands significantly inhibited the proliferation of promastigote forms, confirming the results previously published by some of us. Unfortunately, their respective complexes showed no activity. It is important to emphasize that the leishmanicidal activity of 2,2′-dihydroxy-4,4′-dimethoxybenzophenone (HB3), 2,2′-dihydroxy-4-methoxybenzophenone (HB4), and 2,4,4′-trihydroxybenzophenone (HB6) ligands is reported here for the first time. Despite the fact that they were less active against promastigote forms when compared to amphotericin B, two of them (HB4 and HB6) were less cytotoxic to J774 macrophages.

Graphical abstract, Candida auris has emerged as a serious worldwide threat by causing opportunistic infections that are frequently resistant to one or more conventional antifungal medications resulting in high mortality rates. Against this backdrop, health warnings around the world have focused efforts on understanding C. auris fungal biology and effective prevention and treatment approaches to combat this fungus. To date, there is little information about the differentially expressed genes when this fungus is treated with conventional antifungals, and caspofungin is a standard echinocandin deployed in the therapy against C. auris. In this work, we treated two distinct strains of C. auris for 24 h with caspofungin, and the cellular responses were evaluated at the morphological, translational and transcriptional levels. We first observed that the echinocandin caused morphological alterations, aggregation of yeast cells, and modifications in the cell wall composition of C. auris. Transcriptomic analysis revealed an upregulation of genes related to the synthesis of the cell wall, ribosome, and cell cycle after exposure to caspofungin. Supporting these findings, the integrated proteomic analysis showed that caspofungin-treated cells were enriched in ribosome-related proteins and cell wall, especially mannoproteins. Altogether, these results provide further insights into the biology of C. auris and expands our understanding regarding the antifungal activity of caspofungin and reveal cellular targets, as the mannose metabolism, that can be further explored for the development of novel antifungals.