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Nature-based solutions (NBSs) offer environmentally rational, socially acceptable, and economically viable alternatives for solving diverse water issues. Therefore, the involvement of local communities is crucial, as their participation in developing shared knowledgewithin their territories is essential for building and sustaining resilient ecosystems. This study highlights a co-created, nature-based initiative that led to the construction of a vegetated vermifilter for greywater reuse and monitoring in a small community at the Nonguén School Community, located in the Biobío region, central Chile. The project was initiated in 2019, but not completed until 2022 due to the COVID-19 pandemic. The vermifilter was based on green filters and was used to recover white greywater (dishwater and handwash water) for irrigation use. The circular biofilter, built by the community and directly connected to the kitchen, consisted of four distinct layers: rock, sand, topsoil, and sawdust. It also included populations of earthworms and wetland plants, all primarily collected by the community. Water analysis (i.e., pH, temperature, BOD5, TSS, nitrate, phosphate, turbidity, dissolved oxygen, and total and fecal coliforms) demonstrated a moderate effectiveness during a measured period in 2022. We highlight and discuss the fundamental role of the participation of the local community in the whole co-work process and key lessons and barriers to further optimize a vermifilter design.
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Ciência do Cidadão , Chile , COVID-19 , Áreas Alagadas , Monitoramento Ambiental/métodos , HumanosRESUMO
Toxoplasma gondii is a protozoan parasite causing toxoplasmosis, a principal concern for public health and livestock industries. Effective vaccination strategies are crucial for controlling toxoplasmosis, particularly in the lamb, which are significant reservoirs of T. gondii. In addition, ovine toxoplasmosis also causes economic losses due to abortions and reproductive complications. In this study, we evaluated two immunization strategies to elucidate the immune protective potential of T. gondi major surface protein SAG1 fused to the plant heat shock proteins 90-kDa (pHsp90) adjuvant against experimental toxoplasmosis in lambs. We performed an oral administration of fresh leaves homogenate infiltrated with a B- and T-cell antigenic epitope-containing surface protein SAG1 (SAG1HC) fused to Arabidopsis thaliana Hsp90 (AtHsp81.2-SAG1HC) (Plant Vaccine) and a subcutaneous administration of recombinant SAG1HC fused to Nicotiana benthamiana Hsp90 (NbHsp90.3-SAG1HC) produced in Escherichia coli (Recombinant Vaccine). Our results showed that only the Recombinant Vaccine significantly increased anti-rSAG1 total IgG values (⼠4-fold more than the Vehicle and Control groups). In addition, only lambs immunized with the Plant Vaccine showed a significant increase (⼠3-fold more than the Vehicle and Control groups) in IFN-γ serum levels after the experimental infection (evaluated 8 days post-challenge). On the other hand, we also observed a statistically significant decrease (⼠80 % less) in histopathological lesions (injury score) in challenged vaccinated lambs compared to challenged but not vaccinated animals (Vehicle and Control groups). Previously, we showed that the chimera recombinant Gra4-Gra7 protein is an acute marker of human infection. Since Gra4-Gra7 is not connected to the SAG1 immunogen, this chimera allows us to monitor infection in challenged lambs early. All lambs from the Control and Vehicle groups showed higher rates of serological reactivity than lambs from the vaccinated groups, concurrently with increased severity of lesions. These results suggest that the Plant-based and Recombinant Vaccines are promising candidates for controlling T. gondii infection in lambs, with potential benefits for enhancing public health and animal welfare.
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Anticorpos Antiprotozoários , Antígenos de Protozoários , Proteínas de Choque Térmico HSP90 , Nicotiana , Proteínas de Protozoários , Vacinas Protozoárias , Doenças dos Ovinos , Toxoplasma , Toxoplasmose Animal , Animais , Ovinos , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/genética , Toxoplasma/imunologia , Toxoplasma/genética , Toxoplasmose Animal/prevenção & controle , Toxoplasmose Animal/imunologia , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/genética , Anticorpos Antiprotozoários/sangue , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/imunologia , Proteínas de Choque Térmico HSP90/imunologia , Proteínas de Choque Térmico HSP90/genética , Vacinas Protozoárias/imunologia , Vacinas Protozoárias/administração & dosagem , Vacinas Protozoárias/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Imunoglobulina G/sangue , Plantas Geneticamente Modificadas , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , ImunizaçãoRESUMO
BACKGROUND: The circadian clock, which governs periodic physiological changes, is influenced by various environmental factors, and its disruptions can lead to non-communicable chronic diseases (NCDs). Among the genes that control the circadian clock are ARNTL, CLOCK, CRY1, PER1, PER2, NR1D2, and MTNR1B, with several polymorphisms associated with diseases such as diabetes and hypertension. Therefore, this study aimed to determine the association between SNPs in the aforementioned genes and markers of non-communicable chronic diseases (NCDs) in a young population, stratified by gender. METHODS: A sample of 346 individuals of both sexes aged 18 to 27 underwent clinical and nutritional evaluations to determine clinical markers associated with NCDs. Using isothermal PCR, 119 polymorphisms in the ARNTL, CLOCK, CRY1, PER1, PER2, NR1D2, and MTNR1B genes were determined. Subsequently, binary logistic regression analyses and mean comparisons using Student's t-test and one-way ANOVA with Bonferroni adjustment were performed. RESULTS: Polymorphisms were associated with risk factors such as elevated waist circumference, BMI, insulin, and lipid imbalances, while some acted protectively. Notable SNPs included rs6486122, rs77486964, rs11022756, rs72869158 from ARNTL; rs7309618, rs10778528 from CRY1; rs2304911 from PER1; rs72620839, rs58574366 from PER2; rs6832769, rs1056547 from CLOCK; and rs4858095, rs11922577 from NR1D2, providing insights into the associations of genetic markers with clinically relevant markers for NCDs. CONCLUSION: Clock gene polymorphisms exhibit associations with clinical markers of NCDs, emphasizing the intricate interaction between the biological clock and risk factors. This underscores the importance of genetic testing and personalized clinical approaches for prevention and treatment. Further research is needed to understand the underlying mechanisms and long-term health impacts of these genetic variations.
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Collagen is an abundant component in the human body and plays a fundamental role in the integrity and function of various tissues, including skin, bones, joints, and connective tissues. This natural polymer also contributes to physiological balance and individual health. Within this context, this article reviews the structure of collagen, describing intrinsic characteristics that range from its molecular composition to its organization into bundles. Additionally, the review highlights some of the applications of collagen in tissue engineering, particularly its mimicry of the skin's extracellular matrix. For this review, searches were performed in PubMed, Scopus, and Web of Sciences. The inclusion criteria were established based on the relevance of the studies for the objectives of the review and methodological quality. After selection of the articles, a critical analysis of their content was conducted and the information was synthesized and presented concisely. Analysis of the properties of collagen revealed its key importance for the design of bioactive materials in regenerative applications. However, challenges such as the need for improvement of the integration of implanted materials and a better understanding of the underlying biological processes remain.
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Biofilms are a virulence factor for Candida albicans, a common pathogen in human fungal infections, making them resistant to many commercial antifungals. Therefore, the discovery of compounds that inhibit and eradicate biofilms is a priority. As thiosemicarbazones have had their effect on Candida biofilms little explored, this study investigated the inhibitory and eradication activity of 30 thiosemicarbazones and analogues against C. albicans biofilms. After initial screening, four compounds were selected and compound 28 emerged as the most potent with BIC50 at 31.55 ± 1.18 µM. By scanning electron microscopy analysis, blastoconidia adhered to the reduced surface and reduced formation of pseudohyphae and hyphae was revealed. Despite the inhibitory activity, the four compounds failed to eradicate the biofilm by more than 50%. Thus, the results suggest that the compounds evaluated are very promising for the development of effective antibiofilm compounds and open up new perspectives for elucidating the mechanism of action.
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Antifúngicos , Biofilmes , Candida albicans , Tiossemicarbazonas , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Antifúngicos/farmacologia , Antifúngicos/química , Tiossemicarbazonas/farmacologia , Tiossemicarbazonas/química , Testes de Sensibilidade Microbiana , Hifas/efeitos dos fármacos , Microscopia Eletrônica de VarreduraRESUMO
The Crotalus molossus complex consists of five to seven phylogenetically related lineages of black-tailed rattlesnakes widely distributed in Mexico. While previous studies have noted venom variation within specific lineages of the Crotalus molossus complex, a comprehensive characterization of interspecific and ontogenetic venom variations, their functional implications, and the neutralizing ability of the Mexican antivenom against these variants remains largely unexamined. Herein, using two proteomic approaches for five lineages (C. basiliscus, C. m. molossus, C. m. nigrescens, C. m. oaxacus, and C. ornatus) of the C. molossus complex we characterized the number of toxins and their relative abundance in the venom of individuals of varying sizes. All five lineages undergo ontogenetic venom composition shifts associated with snake length. However, the pattern of ontogenetic shifts varied among lineages. In some lineages, these shifts led to significant differences in proteolytic, phospholipase A2, and fibrinogenolytic activities. Venom in smaller C. basiliscus, C. m. nigrescens, and C. m. oaxacus individuals had lower LD50 values (more lethal) in mice. Whereas the venom lethality of C. m. nigrescens (both juvenile and adult) and C. m. oaxacus (adult) was several times higher in a mammalian (mouse) model than in a reptilian (iguana) model. Antivipmyn® showed different neutralizing potencies toward venom pools. Overall, our results indicated that even among closely related rattlesnake lineages, venom phenotypes may vary greatly, impacting their function and the efficacy of antivenom neutralization.
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In this work, we performed an investigation on the structures and ionization potentials (IPs) of the H2COâ¯HNO dimer. The ground-state properties of six conformations were explored using the coupled-cluster with single, double, and perturbative triple excitations, CCSD(T), approach with large correlation consistent basis sets. Conformation III presented the strongest hydrogen-bonding interaction (with the NHâ¯O distance being 2.016 Å) and was assigned as the most stable among the conformations. In addition, twelve lowest-lying IPs of all the H2COâ¯HNO conformations were determined using the equation-of-motion ionization potential coupled-cluster with single and double excitations method (EOMIP-CCSD) combined with correlation consistent basis sets, extrapolation to the complete basis set limit, and consideration of core correlation effects. The first IP of conformation III was determined to be 10.46 eV, while the corresponding values for conformations I and II were found as being lower than the value obtained for conformation III by 0.41 eV and 0.24 eV, respectively. These differences (that were also noticed for other low-lying IPs) may be helpful for the assignments of experimental results and, thus, it is expected that the outcomes from this work may serve as motivation for other experimental and theoretical investigations involving H2COâ¯HNO dimers (particularly studies that rely on the quantities obtained here).
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RNA interference (RNAi) mediated by the small interfering RNA (siRNA) pathway is a major antiviral mechanism in insects. This pathway is triggered when double-stranded RNA (dsRNA) produced during virus replication is recognized by Dicer-2, leading to the formation of virus-derived siRNA duplexes. These siRNAs are loaded onto the programmable nuclease Argonaute-2 (AGO2), with one strand serving as a guide to target and cleave fully complementary sequences of viral RNAs. While siRNAs are generated from viral dsRNA, the specific viral RNA species targeted for silencing during RNA virus replication remains unclear. In this study, we characterized the primary viral RNA targets of the Drosophila siRNA pathway during infections caused by negative and positive RNA viruses, namely Vesicular stomatitis virus (VSV) and Sindbis virus (SINV). Our findings reveal that polyadenylated transcripts of VSV and SINV are the major targets of silencing by the siRNA pathway during infection, likely when they are poised for translation. Consistent with earlier findings, we show that AGO2 is associated with ribosomes in control and virus infected cells. Therefore, we propose that the inhibition of the replication of RNA viruses in Drosophila results from the silencing of incoming viral transcripts, facilitated by the association of AGO2 with ribosomes.
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Proteínas Argonautas , Proteínas de Drosophila , Interferência de RNA , RNA Interferente Pequeno , RNA Viral , Animais , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , RNA Interferente Pequeno/genética , Vírus de RNA/genética , Sindbis virus/genética , Replicação Viral , Drosophila melanogaster/virologia , Genoma Viral , Vesiculovirus/genética , Drosophila/virologia , Drosophila/genéticaRESUMO
This study investigated the late effects of maternal protein restriction (MPR) and early postnatal sugar consumption on liver health in male Sprague-Dawley rat offspring, focusing on changes observed throughout the aging process. The animals were divided into the following groups: Control (CTR): Male offspring whose dams consumed a normal protein diet (NPD, 17% protein) and water ad libitum during gestation and lactation, and then fed a NPD and water until PND 540; Control + Sugar (CTR + SUG): The same treatment as CTR, but consuming a sugar solution (10% diluted in water) from postnatal day (PND) 21-90, and then fed a NPD and water until PND 540; Gestational and Lactational Low Protein (GLLP): Male offspring whose dams consumed a low-protein diet (LPD, 6% protein) during gestation and lactation and, then fed a NPD and water ad libitum until PND 540; Gestational and Lactational Low Protein + Sugar (GLLP + SUG): male offspring whose dams consumed a LPD during gestation and lactation, and then fed a NPD and a sugar solution (10% diluted in water) ad libitum from PND 21 to 90. On PND 540, the animals were anesthetized, weighed, and euthanized, and their livers were collected for morphological and molecular analyses. The GLLP and GLLP + SUG groups showed lower body weight and lower retroperitoneal fat weight compared to the CTR and CTR + SUG groups. Morphological analysis revealed inflammatory foci in the liver from the CTR + SUG, GLLP, and GLLP + SUG groups, compared to the CTR group. Hepatic activities of CAT, SOD, and GSH-Px were increased in the GLLP + SUG group and decreased in the GLLP group, compared to the CTR group. Immunohistochemistry showed a significant increase in occupied area per foci de hepatocytes positive for GSTpi (placental form) in the CTR + SUG, GLLP, and GLLP + SUG groups, compared to the CTR group. Proteomic analysis of the groups revealed significant changes in hepatic metabolic and inflammatory pathways. In the CTR + SUG group, upregulated pathways associated with non-alcoholic fatty liver disease (NAFLD) and downregulated pathways related to autophagy were observed. In the GLLP and GLLP + SUG groups, there was a significant impact on metabolic pathways, including glucose metabolism, gluconeogenesis, glycogenesis, and cellular stress responses. An upregulation of pathways associated with chemokine- and cytokine-mediated inflammatory processes was also identified, indicating activation of the immune system in the liver during aging. Therefore, MPR, with or without postnatal sugar consumption, resulted in hepatic changes in metabolism and the antioxidant defense in old male offspring.
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Furofuran lignans are important chiral secondary metabolites widely distributed in the plant kingdom. Despite extensive biological potential, their absolute configuration assignments are mostly based on empirical comparisons of OR values and ECD spectra obtained for structurally related molecules. Since the main structural differences among furofuran lignans reside on the substitution patterns of the chromophoric aromatic moieties, as well as their relative orientations, this approach is risky and the reported stereochemical assignments require independent verification. Herein, a combination of experimental and theoretical vibrational circular dichroism (VCD) spectroscopy was used to investigate the stereochemistry of furofuran lignans isolated from Aristolochiaceae species. Besides providing unambiguous assignments of the absolute configurations of the target lignans, the combination of VCD, molecular dynamics (MD) and QM/MM calculations revealed that key spectral features in acetonitrile solution were reproduced only in the presence of explicit solvent molecules. While that would be expected for molecules containing H-bond donor groups, such as phillygenin (1), the same trend was observed for compounds devoid of H-bond interactions with the solvent (epieudesmin 2 and eudesmin 3). The inclusion of explicit solvation was found to be critical for the stabilization of dihedral angles that allow for proper normal mode coupling and correct reproduction of experimental data. Given that the IR and VCD spectra of the lignans obtained in chloroform solutions were almost superimposable to those recorded in acetonitrile, the conformational stabilization described above and the requirement for explicit solvation would not be restricted to acetonitrile.
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BACKGROUND: Liver transplantation is the treatment of choice in patients with chronic liver disease and acute liver failure of any etiology. Scales such as the Survival Outcome Following Transplantation (SOFT) score and the Balance of Risk (BAR) score can be used to predict survival. In this study, we compared these scales in the Mexican population. METHODS: A cross-sectional analytical study was carried out in a Mexican third-level transplant center. The MELD, SOFT, and BAR scales were adopted. The ROC curves of the three predictive scores were constructed, and the areas under the curve were obtained and compared. A bivariate analysis and Cox regression were performed. Finally, a survival analysis was performed using Kaplan-Meier curves. RESULTS: We analyzed 123 liver transplant (LT) recipients. The bivariate analysis and Cox regression indicated that portal thrombosis, with an HR of 3.36 (IC 1.069-10.59, p = 0.038), and the number of red blood cells transfused, with an HR of 1.084 (CI 1.039-1.130, p < 0.000), were significantly associated with mortality. The receiver height was a protective factor, with an HR of 0.001 (CI 0.000-0.761, p = 0.041). Regarding the Pearson correlation analysis, the BAR scale had a coefficient of 0.199 (p = 0.032) for transfusion, while the SOFT scale's correlation coefficients for cold ischemia and transfusion were 0.236 (p = 0.011) and 0.274 (p = 0.003), respectively, all indicating weak correlations. The areas under the curve (AUCs) of MELD, SOFT, and BAR in predicting 3-month mortality were 0.495 (P = 0.94), 0.608 (p = 0.129), and 0.502 (p = 0.97), respectively. Finally, in the survival analysis using Kaplan-Meier curves, an estimated mean survival period of 71.52 months was obtained, with a survival rate of 89.3 % at 30 days and 81.1 % at five years. CONCLUSION: In this study, it was found that all three scales were deficient in discriminating among the outcomes obtained in the Mexican population.
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BACKGROUND: In the 6 months following Hurricane Maria the number of people who died from the hurricane was much higher than was initially estimated from death certificates. Disruption of health care services and displacement led to the exacerbation of pre-existing chronic diseases. The objectives of this study were to (1) estimate the excess deaths in Puerto Rico in the 6 months following Maria, (2) identify geographical areas experiencing higher risk of chronic disease mortality following Maria and (3) identify community-level vulnerability characteristics associated with some communities being at higher risk of increased chronic disease mortality after Maria. METHODS: Death records were obtained from Puerto Rico's Department of Health Demographic Registry. Mortality risks per 100 000 were calculated for chronic disease categories and all-cause mortality for the 6 months following Maria and the same months in the year before. Geospatial analysis using Getis-Ord Gi* Statistic was used to determine if mortality clusters of 6 month mortality risk following hurricane Maria by census tract were statistically significant. Multinomial logistic regression was used to model the association between census tract level social vulnerability and being classified as higher or sustained risk of mortality in the 6 months following Hurricane Maria compared to the previous year's mortality risk. Odds ratios and 95% confidence intervals were estimated to measure associations between social vulnerability and mortality risk. RESULTS: In the 6 months following Maria there were increases in mortality risk for cardiovascular disease, Alzheimer's, diabetes, sepsis, chronic respiratory disease, hypertension and all-cause mortality. Examining community level characteristics associated with vulnerability to disasters, neighborhoods with higher proportion of people 65 and older, higher proportion of houses being multiunit structures and higher proportion of households with no vehicle, in comparison to other neighborhoods in Puerto Rico,were more likely to have sustained high risk for mortality before and after Maria or increased risk of being a hot spot for chronic disease mortality after Maria.
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OBJECTIVE: To analyze the retail food environment and identify the presence of food swamps around public and private higher education institutions (HEIs) in Belo Horizonte, Minas Gerais. METHODS: This is an ecological study with the analysis unit being a 500-meter buffer network around 81 in-person HEI units. The density and proximity between the HEIs and food purchasing establishments for immediate consumption were assessed according to the administrative category and per capita income of the census tract, as well as the presence of food swamps. RESULTS: In 98.76% of the buffers there was at least one establishment for immediate consumption. Snack bars, restaurants, and bars were the categories most available and closest to the HEIs. The density of establishments was higher around private HEIs and around HEIs located in higher income areas. It was found that 95.06% of HEIs were located in areas classified as food swamps. CONCLUSION: Thus, the HEIs evaluated were exposed to neighborhoods with an unhealthy food environment, which may predispose university students to food choices based on the consumption of ultra-processed foods and alcoholic beverages.
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Características de Residência , Brasil , Humanos , Universidades/estatística & dados numéricos , Abastecimento de Alimentos/estatística & dados numéricos , Comércio/estatística & dados numéricos , Fatores Socioeconômicos , Alimentos/estatística & dados numéricos , Restaurantes/estatística & dados numéricos , CidadesRESUMO
This study evaluates the ability of the GFN2-xTB method and Conceptual Density Functional Theory-derived tools to predict local reactivity in large systems. Carbon-based systems such as C60, C70, Li+@C70, C240, C360, C648, and C720 have been used as test sets, and the orbital-weighted dual descriptor was employed to identify nucleophilic and electrophilic regions, providing a comprehensive analysis of their reactivity patterns. The results confirm that the GFN2-xTB method accurately reproduces reactivity profiles observed experimentally and at the DFT level, particularly in well-known fullerenes like C60 and C70. The addition of an endohedral Li+ cation to C70 demonstrated enhanced electrophilicity and reduced unfavorable nucleophilic regions, consistent with previous studies. For larger and less-studied systems, such as C240, C360, C648, and C720, the analysis revealed distinct reactivity features, including the localization of nucleophilic regions in -C≡C- units of C240/C648, the nucleophilic regions at the ends of the C360 nanoparticle model, and the emergence of electrophilic zones due to the reduction in aromaticity of the benzenoid rings in C720. These findings validate the GFN2-xTB method as a computationally efficient alternative for exploring the reactivity of large structures and contribute valuable insights into their potential applications in molecular design for material science and nanotechnology.
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A 0.5 molal solution of NaCl in water confined within charged graphene nanoslits represents an intriguing system for molecular dynamics simulation, functioning as a model for a nanocapacitor. This charged configuration not only holds practical significance for the advancement of nanoscale capacitors but also offers valuable insights into how the charged walls and applied electric field influence the structure of water, the movement of ions within the solution, and how these alterations in water impact the overall fluid behavior. The behavior of the solution under nanoconfinement diverges markedly from that observed in bulk conditions, exhibiting distinct structural, dynamic, and dielectric properties. The charging of the graphene nanoslits generates an electric field within the nanopore, which plays a critical role in modulating molecular interactions. Key properties, including the static dielectric constant, polarization, and density of the 0.5 molal solution, are systematically examined through the molecular structure of the confined system. The models employed in this study include the flexible FAB/ϵ model of water, which effectively reproduces various experimental properties of water under different pressure and temperature conditions. Additionally, the NaCl/ϵ model is used, which also captures a range of experimental characteristics associated with sodium chloride solutions. Together, these models facilitate a comprehensive understanding of the complex behavior of water and ions under the influence of nanoconfinement and electric fields, providing insights that are essential for both fundamental science and practical applications in nanotechnology.
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Atrazine (ATZ) is an herbicide that can persist in terrestrial and aquatic environments and potentially cause significant harm to amphibian health. Therefore, the Brazilian National Environment Council (CONAMA) sets the limit concentration of ATZ in waters at 2µg/L. Our study evaluated the genotoxic, mutagenic, and biochemical alterations in Dendropsophus minutus tadpoles in the 25 Gosner stage, to acute exposure (96h) of ATZ (T1 - 0.02µg/L, T2 - 0.04µg/L, T3 - 0.08µg/L, T4 - 2µg/L). The comet assay showed all concentrations caused DNA damage with an increase to T2, T3, and T4. In the micronucleus test (MN) and Erythrocyte Nuclear Abnormality test (ENA), T3 and T4 accumulated more anucleated (AN), binucleated cells (BC) and ENAs. Redox imbalance was not detected. Therefore, we conclude that the concentrations tested are not safe for the health and development of D. minutus tadpoles, and the CONAMA limit needs to be reviewed since all tadpoles presented DNA damage. More studies are necessary to identify other alterations that ATZ can cause in the tadpole health of tropical species. Therefore, implementing public policies aimed at safeguarding the lives of both adult and juvenile amphibians is imperative for the conservation of biodiversity and ecosystem stability.
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Anuros , Atrazina , Biomarcadores , Ensaio Cometa , Dano ao DNA , Herbicidas , Larva , Testes para Micronúcleos , Poluentes Químicos da Água , Atrazina/toxicidade , Animais , Larva/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Herbicidas/toxicidade , Dano ao DNA/efeitos dos fármacos , Biomarcadores/metabolismo , OxirreduçãoRESUMO
Neuroinflammation is a critical factor in the pathogenesis of various neurodegenerative and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder. Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), have demonstrated promising therapeutic effects on neuroinflammation, primarily through interactions with serotonin (5-HT) receptors, particularly the 5-HT2A receptor. Activation of these receptors by psychedelics modulates the production of pro-inflammatory cytokines, regulates microglial activity, and shifts the balance between neurotoxic and neuroprotective metabolites. Additionally, psychedelics affect critical signaling pathways, including the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and mechanistic target of rapamycin (mTOR) pathways, promoting neuroplasticity and exerting anti-inflammatory effects. Beyond the serotonergic system, other neurotransmitter systems-including the glutamatergic, dopaminergic, noradrenergic, gamma-aminobutyric acid (GABAergic), and cholinergic systems-also play significant roles in mediating the effects of psychedelics. This review examines the intricate mechanisms by which psychedelics modulate neuroinflammation and underscores their potential as innovative therapeutic agents for treating neuroinflammatory and neuropsychiatric disorders.
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Ovarian aging is associated with fibro-inflammation, contributing to the decline in oocyte count and quality. Given the immunomodulatory properties of the vasoactive intestinal peptide (VIP) in the reproductive tract, we investigated its role in maintaining ovarian immune homeostasis and preventing premature aging. We evaluated young VIP knockout (KO) mice, comparing them to young wild type (WT) females, for signs of premature aging. Histological staining revealed aberrant ovarian morphology in VIP KO mice, characterized by increased atretic follicles and decreased ovarian reserve compared to WT controls. Moreover, VIP KO ovaries showed reduced vascularization, increased collagen deposition and elevated ROS and IL-1ß levels. Foamy macrophages were significantly predominant, indicating premature aging in young VIP KO ovaries. To determine potential mechanisms behind these pathogenic changes, we conditioned peritoneal macrophages from young WT or VIP KO mice in vitro with ovarian-conditioned media from young WT or VIP KO mice to mimic the respective ovarian microenvironment. When WT or VIP KO peritoneal macrophages were conditioned with ovarian media from their respective genotypes, lipid droplet accumulation increased compared to control medium. In cross-genotype experiments, WT macrophages conditioned with media from VIP KO ovaries selectively accumulated higher levels of lipid droplets, whereas no differences were observed in VIP KO macrophages conditioned with WT ovarian media. This suggests that VIP KO macrophages are uniquely sensitized to the inflammatory environment of VIP KO ovaries, implicating both ovarian factors and macrophage status. These findings highlight the role of VIP in preventing fibro-inflammation, thereby preserving ovarian health and preventing premature aging.
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Membrane solubilization by detergents is routinely performed to separate membrane components, and to extract and purify membrane proteins. This process depends both on the characteristics of the detergent and properties of the membrane. Here we investigate the interaction of eight detergents with very distinct physicochemical features with model membranes in different biologically relevant phases. The detergents chosen were the non-ionic Triton X-100, Triton X-165, C10E5, octyl glucopyranoside (OG) and dodecyl maltoside (DDM) and the ionic sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium bromide (CTAB) and Chaps. Three lipid compositions were explored: pure palmitoyl oleoyl phosphatidylcholine (POPC), in the liquid-disordered (Ld) phase, sphingomyelin (SM)/cholesterol 7:3 (chol) in the liquid-ordered (Lo) phase and the biomimetic POPC/SM/chol 2:1:2, which might exhibit Lo/Ld phase separation. Turbidity measurements of small liposomes were performed along the titration with the detergents to obtain the overall solubilization profiles and optical microscopy of giant unilamellar vesicles (GUVs) was used to reveal the mechanism of interaction of the detergents. The presence of cholesterol renders the membranes partly/fully insoluble in all detergents, and the charged detergents are the least effective to solubilize POPC. The non-ionic detergents, with exception of DDM, with the bulkiest headgroup, caused a substantial increase in surface area of POPC, which was quantified directly on single GUVs. The other detergents induced mainly vesicle burst. Detergents that caused some increase in area induced Lo/Ld phase separation in the ternary mixture, with preferential solubilization of the latter. The insoluble area fraction left intact was quantified. Overall, the non-ionic detergents were the most effective in solubilizing lipid membranes.