Exploring the BSA- and DNA-binding, cytotoxicity, and cell cycle evaluation of ternary copper(II)/diimine complexes with N,N-dibenzyl-N'-benzoylthiourea as promising metallodrug candidates.

Four new copper(II) complexes were synthesized and characterized with the general formula [Cu(N-N)(Th)(NO3)], where N-N corresponds to the N-heterocyclic ligands 1,10-phenanthroline (phen), 2,2'-bipyridine (bipy), 4,7-diphenyl-1,10-phenanthroline (dpp), and 4,4-dimethyl-2,2'-bipyridine (dmbp) and Th represents the N,N-dibenzyl-N'-benzoylthiourea. Cytotoxic activities of the complexes against HCT116 (human colon carcinoma), HepG2 (human hepatocellular carcinoma), and non-tumor MRC-5 (human lung fibroblast) cells were investigated. The copper(II) complexes 1-4 were characterized by spectroscopic techniques while complexes 1 and 2 were studied using single-crystal X-ray diffraction as well. The complexes possessed a five-coordinated structure with one nitrate ligand as a monodentate at the axial position and two bidentate ligands N-heterocyclic and N,N-dibenzyl-N'-benzoylthiourea. The complexes showed promising IC50 values, ranging from 0.3 to 9.0 µM. Furthermore, interaction studies with biomolecules such as calf thymus DNA (ct-DNA) and Bovine Serum Albumin (BSA), which can act as possible biological targets of the complexes, were carried out. The studies suggested that the compounds interact moderately with ct-DNA and BSA. Complexes 1, 2, and 4 did not lead to cell accumulation at any stage of the cell cycle but caused a significant increase in internucleosomal DNA fragmentation. Whereas, compound 3 caused cell cycle arrest in the S phase while doxorubicin caused cell cycle arrest in the G2/M phase. The effect of structural modifications on the metal compounds was correlated with their biological properties and it was concluded that an increase in biological activity occurred with increasing the extension of the diimine ligands. Thus, complex 3 was the most promising one.

Facilitating active learning of sectional anatomy with technology-enhanced small-group tasks: Assessment of knowledge gains, technology usability, and students' perceptions.

Learning 2D sectional anatomy facilitates the comprehension of 3D anatomical structures, anatomical relationships, and radiological anatomy. However, the efficacy of technology-enhanced collaborative instructional activities in sectional anatomy remains unclear, especially if theoretical frameworks, namely the Cognitive Theory of Multimedia Learning (CTML), are applied in instructional design. Thus, this study compared the educational impact of distinct 45-min-long technology-enhanced collaborative learning tasks in sectional anatomy. A sample of 115 first-year medical students was randomly divided into three experimental groups that used different supporting technologies to learn the sectional anatomy of the chest: IMAIOS e-learning platform and Microsoft Surface Hub (n = 37); anatomage table (n = 38); anatomage table with CTML-based presets (n = 40). Prelearning and postlearning tests revealed that significant knowledge gains in sectional anatomy were obtained by all groups even though no inter-group differences were found. Moreover, a five-point Likert scale questionnaire showed that the learning session was highly valued by all participants and that users of the anatomage with CTML-based presets reported higher enjoyment than users of the IMAIOS system (mean difference = 0.400; p = 0.037). In addition, students using the IMAIOS system and the anatomage with CTML-based presets provided System Usability Scale (SUS) scores of 67.64 and 67.69, respectively, reaching the benchmark of usability. By contrast, students using the anatomage table without presets awarded a SUS score of 64.14. These results suggest that the integration of multimedia technologies in anatomy teaching and learning should be grounded on CTML principles of instructional design. Otherwise, students' perceptions of ed-tech usability are potentially hindered.

Diagnosis in Bytes: Comparing the Diagnostic Accuracy of Google and ChatGPT 3.5 as an Educational Support Tool.

BACKGROUND: Adopting advanced digital technologies as diagnostic support tools in healthcare is an unquestionable trend accelerated by the COVID-19 pandemic. However, their accuracy in suggesting diagnoses remains controversial and needs to be explored. We aimed to evaluate and compare the diagnostic accuracy of two free accessible internet search tools: Google and ChatGPT 3.5. METHODS: To assess the effectiveness of both medical platforms, we conducted evaluations using a sample of 60 clinical cases related to urological pathologies. We organized the urological cases into two distinct categories for our analysis: (i) prevalent conditions, which were compiled using the most common symptoms, as outlined by EAU and UpToDate guidelines, and (ii) unusual disorders, identified through case reports published in the 'Urology Case Reports' journal from 2022 to 2023. The outcomes were meticulously classified into three categories to determine the accuracy of each platform: "correct diagnosis", "likely differential diagnosis", and "incorrect diagnosis". A group of experts evaluated the responses blindly and randomly. RESULTS: For commonly encountered urological conditions, Google's accuracy was 53.3%, with an additional 23.3% of its results falling within a plausible range of differential diagnoses, and the remaining outcomes were incorrect. ChatGPT 3.5 outperformed Google with an accuracy of 86.6%, provided a likely differential diagnosis in 13.3% of cases, and made no unsuitable diagnosis. In evaluating unusual disorders, Google failed to deliver any correct diagnoses but proposed a likely differential diagnosis in 20% of cases. ChatGPT 3.5 identified the proper diagnosis in 16.6% of rare cases and offered a reasonable differential diagnosis in half of the cases. CONCLUSION: ChatGPT 3.5 demonstrated higher diagnostic accuracy than Google in both contexts. The platform showed satisfactory accuracy when diagnosing common cases, yet its performance in identifying rare conditions remains limited.

Exploring self-care practices and health beliefs among men in the context of emerging infectious diseases: Lessons from the Mpox pandemic in Brazil.

Our goal was to explore self-care practices among men who have sex with men in the context of Mpox in Brazil. This study used qualitative research methods, including interviews and thematic analysis, to collect and analyze data from male participants across the Brazilian territory. The narratives unveil men's perspectives on self-care, risk reduction, and health beliefs during the Mpox pandemic. Our findings highlight a multifaceted approach to self-care among men, encompassing hygiene, physical contact management, mask usage, skin lesion vigilance, and adherence to official guidelines. Men's attitudes toward sexual behaviors emphasize the importance of reducing sexual partners, practicing safe sex, and combating misinformation through accurate information dissemination. The development of these behaviors and self-care practices can be facilitated by nurses guided by Dorothea Orem's Self-Care Theory, supported by patient-centered care, with strategies to address and confront the stigma associated with the disease and provide emotional support. Thus, the study underscores the pivotal role of self-care in mitigating infection risks, especially in the context of emerging infectious diseases. It acknowledges the impact of socio-cultural factors and healthcare policies on men's preventive measures. However, it also recognizes limitations, such as potential bias due to stigma concerns and a nonrepresentative sample. Ultimately, the research advocates for tailored education, promotion of gender equity, and healthcare empowerment to effectively manage health risks in such contexts.

Second booster dose improves antibody neutralization against BA.1, BA.5 and BQ.1.1 in individuals previously immunized with CoronaVac plus BNT162B2 booster protocol.

Introduction: SARS-CoV-2 vaccines production and distribution enabled the return to normalcy worldwide, but it was not fast enough to avoid the emergence of variants capable of evading immune response induced by prior infections and vaccination. This study evaluated, against Omicron sublineages BA.1, BA.5 and BQ.1.1, the antibody response of a cohort vaccinated with a two doses CoronaVac protocol and followed by two heterologous booster doses. Methods: To assess vaccination effectiveness, serum samples were collected from 160 individuals, in 3 different time points (9, 12 and 18 months after CoronaVac protocol). For each time point, individuals were divided into 3 subgroups, based on the number of additional doses received (No booster, 1 booster and 2 boosters), and a viral microneutralization assay was performed to evaluate neutralization titers and seroconvertion rate. Results: The findings presented here show that, despite the first booster, at 9m time point, improved neutralization level against omicron ancestor BA.1 (133.1 to 663.3), this trend was significantly lower for BQ.1.1 and BA.5 (132.4 to 199.1, 63.2 to 100.2, respectively). However, at 18m time point, the administration of a second booster dose considerably improved the antibody neutralization, and this was observed not only against BA.1 (2361.5), but also against subvariants BQ.1.1 (726.1) and BA.5 (659.1). Additionally, our data showed that, after first booster, seroconvertion rate for BA.5 decayed over time (93.3% at 12m to 68.4% at 18m), but after the second booster, seroconvertion was completely recovered (95% at 18m). Discussion: Our study reinforces the concerns about immunity evasion of the SARS-CoV-2 omicron subvariants, where BA.5 and BQ.1.1 were less neutralized by vaccine induced antibodies than BA.1. On the other hand, the administration of a second booster significantly enhanced antibody neutralization capacity against these subvariants. It is likely that, as new SARS-CoV-2 subvariants continue to emerge, additional immunizations will be needed over time.

Multi-trait selection for nutritional and physiological quality of cacao genotypes in irrigated and non-irrigated environments.

Water is a scarce, strategic resource and the most important input for economic development, especially in agricultural countries such as Brazil. Cocoa production is directly related to water availability, and, as climate changes, selecting drought-tolerant genotypes is vital to keep cacao crops sustainable. Here, we evaluated cacao genotypes under irrigated and water-stressed conditions and selected drought-tolerant ones based on nutritional and physiological traits. Thirty-nine genotypes were monitored for three years for agronomic traits and higher fruit yield. After this evaluation, the 18 most promising genotypes were evaluated in a randomized block design, under a 2 (with and without irrigation)  ×  18 (genotypes) factorial arrangement, with three replicates and five plants per plot. We evaluated seven physiological and 11 nutritional traits, selecting genotypes based on the Genotype-by-Trait Biplot approach. Significant effects (p < 0.05) were observed for the nutritional traits N, P, Mg, S, Zn, Cu, Mn and for the physiological traits CO2 assimilation rate (A), stomatal conductance (gs), transpiration (E), intercellular and atmospheric CO2 concentrations (Ci/Ca), intrinsic water use efficiency (A/gs), instantaneous water use efficiency (A/E), and instantaneous carboxylation efficiency (A/Ci), as determined by analysis of variance. The genotype  ×  irrigation treatment interaction was significant (p < 0.05) for the traits A, gs, and E. Genotypes CP 41, CP 43, and CCN 51 exhibited superior performance for both nutritional and physiological traits (A, gs, and E). In the irrigated environment, CP 41 showed superiority in traits such as P, A/E, A/gs, Mn, S, and Zn. Conversely, under non-irrigated conditions, CP 43 exhibited better performance in nutritional properties, specifically Mn, Mg, and Zn. Notably, in both irrigated and non-irrigated environments, CCN 51 excelled in key physiological traits, including A/Ci, A/E, and A/gs. This robust performance across diverse conditions suggests that these three genotypes possess physiological mechanisms to endure water-stressed conditions. Our research can generate valuable insights into these genotypes informing suitable choices for cocoa cultivation, especially in the context of global climate change.

GIS-FA: an approach to integrating thematic maps, factor-analytic, and envirotyping for cultivar targeting.

KEY MESSAGE: We propose an "enviromics" prediction model for recommending cultivars based on thematic maps aimed at decision-makers. Parsimonious methods that capture genotype-by-environment interaction (GEI) in multi-environment trials (MET) are important in breeding programs. Understanding the causes and factors of GEI allows the utilization of genotype adaptations in the target population of environments through environmental features and factor-analytic (FA) models. Here, we present a novel predictive breeding approach called GIS-FA, which integrates geographic information systems (GIS) techniques, FA models, partial least squares (PLS) regression, and enviromics to predict phenotypic performance in untested environments. The GIS-FA approach enables: (i) the prediction of the phenotypic performance of tested genotypes in untested environments, (ii) the selection of the best-ranking genotypes based on their overall performance and stability using the FA selection tools, and (iii) the creation of thematic maps showing overall or pairwise performance and stability for decision-making. We exemplify the usage of the GIS-FA approach using two datasets of rice [Oryza sativa (L.)] and soybean [Glycine max (L.) Merr.] in MET spread over tropical areas. In summary, our novel predictive method allows the identification of new breeding scenarios by pinpointing groups of environments where genotypes demonstrate superior predicted performance. It also facilitates and optimizes cultivar recommendations by utilizing thematic maps.

Milk provisioning in oviparous caecilian amphibians.

Among vertebrates, the yolk is commonly the only form of nutritional investment offered by the female to the embryo. Some species, however, have developed parental care behaviors associated with specialized food provisioning essential for offspring survival, such as the production of lipidic-rich parental milk in mammals. Here, we show that females of the egg-laying caecilian amphibian Siphonops annulatus provide similarly lipid-rich milk to altricial hatchlings during parental care. We observed that for 2 months, S. annulatus babies ingested milk released through the maternal vent seemingly in response to tactile and acoustic stimulation by the babies. The milk, composed mainly of lipids and carbohydrates, originates from the maternal oviduct epithelium's hypertrophied glands. Our data suggest lactation in this oviparous nonmammalian species and expand the knowledge of parental care and communication in caecilians.

Wireless Sensor for Meat Freshness Assessment Based on Radio Frequency Communication.

Wireless communication technologies, particularly radio frequency (RF), have been widely explored for wearable electronics with secure and user-friendly information transmission. By exploiting the operational principle of chemically actuated resonant devices (CARDs) and the electrical response observed in chemiresistive materials, we propose a simple and hands-on alternative to design and manufacture RF tags that function as CARDs for wireless sensing of meat freshness. Specifically, the RF antennas were meticulously designed and fabricated by lithography onto a flexible substrate with conductive tape, and the RF signal was characterized in terms of amplitude and peak resonant frequency. Subsequently, a single-walled carbon nanotube (SWCNT)/MoS2/In2O3 chemiresistive composite was incorporated into the RF tag to convey it as CARDs. The RF signal was then utilized to establish a correlation between the sensor's electrical response and the RF attenuation signal (reflection coefficient) in the presence of volatile amines and seafood (shrimp) samples. The freshness of the seafood samples was systematically assessed throughout the storage time by utilizing the CARDs, thereby underscoring their effective potential for monitoring food quality. Specifically, the developed wireless tags provide cumulative amine exposure data within the food package, demonstrating a gradual decrease in radio frequency signals. This study illustrates the versatility of RF tags integrated with chemiresistors as a promising pathway toward scalable, affordable, and portable wireless chemical sensors.

Quantitative thermodynamic exposure assessment of PCBs available to sandworms (Alitta virens) in activated carbon remediated sediment during ongoing sediment deposition.

Marine mesoscale studies with sandworms (Alitta virens) were conducted to isolate important processes governing the exposure and bioaccumulation of polychlorinated biphenyls (PCBs) at contaminated sediment sites. Ex situ equilibrium sampling with silicone-coated jars, and in situ passive sampling with low-density polyethylene (LDPE) were used to determine the performance of an activated carbon (AC) amendment remedy applied to the bed sediment. A quantitative thermodynamic exposure assessment ('QTEA') was performed, showing that PCB concentrations in polymers at equilibrium with the surficial sediment were suited to measure and assess the remedy effectiveness with regard to PCB bioaccumulation in worms. In practice, monitoring the performance of sediment remedies should utilize a consistent and predictive form of polymeric sampling of the sediment. The present study found that ex situ equilibrium sampling of the surficial sediment was the most useful for understanding changes in bioaccumulation potential as a result of the applied remedy, during bioturbation and ongoing sediment and contaminant influx processes. The ultrathin silicone coatings of the ex situ sampling provided fast equilibration of PCBs between the sediment interstitial water and the polymer, and the multiple coating thicknesses were applied to confirm equilibrium and the absence of surface sorption artifacts. Overall, ex situ equilibrium sampling of surficial sediment could fit into existing frameworks as a robust and cost-effective tool for contaminated sediment site assessment.

Damage measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in antiphospholipid antibody-positive patients included in the APS ACTION registry.

OBJECTIVES: Our primary objective was to quantify damage burden measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in aPL-positive patients with or without a history of thrombosis in an international cohort (the APS ACTION cohort). Secondly, we aimed to identify clinical and laboratory characteristics associated with damage in aPL-positive patients. METHODS: In this cross-sectional study, we analysed the baseline damage in aPL-positive patients with or without APS classification. We excluded patients with other autoimmune diseases. We analysed the demographic, clinical and laboratory characteristics based on two subgroups: (i) thrombotic APS patients with high vs low damage; and (ii) non-thrombotic aPL-positive patients with vs without damage. RESULTS: Of the 826 aPL-positive patients included in the registry as of April 2020, 586 with no other systemic autoimmune diseases were included in the analysis (412 thrombotic and 174 non-thrombotic). In the thrombotic group, hyperlipidaemia (odds ratio [OR] 1.82; 95% CI 1.05, 3.15; adjusted P = 0.032), obesity (OR 2.14; 95% CI 1.23, 3.71; adjusted P = 0.007), aß2GPI high titres (OR 2.33; 95% CI 1.36, 4.02; adjusted P = 0.002) and corticosteroid use (ever) (OR 3.73; 95% CI 1.80, 7.75; adjusted P < 0.001) were independently associated with high damage at baseline. In the non-thrombotic group, hypertension (OR 4.55; 95% CI 1.82, 11.35; adjusted P = 0.001) and hyperlipidaemia (OR 4.32; 95% CI 1.37, 13.65; adjusted P = 0.013) were independent predictors of damage at baseline; conversely, single aPL positivity was inversely correlated with damage (OR 0.24; 95% CI 0.075, 0.77; adjusted P = 0.016). CONCLUSIONS: DIAPS indicates substantial damage in aPL-positive patients in the APS ACTION cohort. Selected traditional cardiovascular risk factors, steroids use and specific aPL profiles may help to identify patients more prone to present with a higher damage burden.

The long-lasting Ascaris suum antigens in the lungs shapes the tissue adaptation modifying the pulmonary architecture and immune response after infection in mice.

Ascariasis is the most prevalent helminth affecting approximately 819 million people worldwide. The acute phase of Ascariasis is characterized by larval migration of Ascaris spp., through the intestinal wall, carried to the liver and lungs of the host by the circulatory system. Most of the larvae subsequently transverse the lung parenchyma leading to tissue injury, reaching the airways and pharynx, where they can be expectorated and swallowed back to the gastrointestinal tract, where they develop into adult worms. However, some larvae are trapped in the lung parenchyma inciting an inflammatory response that causes persistent pulmonary tissue damage long after the resolution of infection, which returns to tissue homeostasis. However, the mechanism by which chronic lung disease develops and resolves remains unknown. Here, using immunohistochemistry, we demonstrate that small fragments and larval antigens of Ascaris suum are deposited and retained chronically in the lung parenchyma of mice following a single Ascaris infection. Our results reveal that the prolonged presence of Ascaris larval antigens in the lung parenchyma contributes to the persistent immune stimulation inducing histopathological changes observed chronically following infection, and clearly demonstrate that larval antigens are related to all phases of tissue adaptation after infection: lung injury, chronic inflammation, resolution, and tissue remodeling, in parallel to increased specific humoral immunity and the recovery of lung function in mice. Additional insight is needed into the mechanisms of Ascaris antigen to induce chronic immune responses and resolution in the host lungs following larval migration.

Ornithogenesis and soil-landscape interplays at northern Harmony Point, Nelson Island, Maritime Antarctica.

Understanding the influence of soil-forming factors and processes in ornithogenic soils is important to predict impacts of climate change on Antarctic ecosystems. Herein, we analyzed the soil-landscape interplays and development of ornithogenic soils at Harmony Point (HP), Nelson Island. We collected, described, and classified 24 soil profiles, combined with vegetation and landforms descriptions. Geoprocessing techniques were employed for mapping. Soil physical, chemical, geochemical, and mineralogical analyses were applied. Patterned ground, "Ornithogenic"/Typic Gelorthent, and moss carpets were the dominant landform, soil and vegetation classes, respectively. Soils from rocky outcrops were more structured, acidic, with higher organic carbon, organometallic complexes, and secondary phosphate minerals, due to former bird influence. Soils from cryoplanated platforms presented higher water pH, base saturation, clay content, and secondary silicate minerals. Soils from marine terraces presented high exchangeable bases, phosphorous, and amorphous phosphate minerals. Soil chemical weathering is enhanced by ornithogenesis and widespread in HP. Besides ornithogenesis, organic matter accumulation, cryoturbation, and cryoclastic processes are also important to pedogenesis of ornithogenic soils. The soils of the cryoplanated platforms exhibited a gradient of pedogenetic development corresponding to increasing biota influence and distance from glacier. In contrast, soils of rocky outcrops were more developed even close to the glacier, due to ornithogenesis.

Involved-Field Radiation Therapy for Patients With Unresectable Pancreatic Adenocarcinomas: Failure Pattern Analysis.

Introduction Unresectable pancreatic tumors are frequently diagnosed. Initial treatment is carried out with chemotherapy. Eventually, in selected cases, radiotherapy may be used to improve local control rates and relieve the symptoms. The volume of radiotherapy treatment fields is the subject of controversy in the literature. The use of involved fields with the gross tumor volume encompassing the primary tumor and lymph nodes considered clinically positive is associated with a lower rate of side effects, but can lead to a higher rate of regional loco failures, especially in regional lymph nodes. The purpose of this article is to analyze the failure pattern of chemotherapy and involved-field radiation therapy (IFRT) for treating patients with unresectable pancreatic adenocarcinomas. Methods Clinical records of thirty consecutive patients treated from March 2016 to June 2020 for unresectable pancreatic adenocarcinoma were analyzed. The patients were treated with initial systemic chemotherapy (median: 6 cycles) with regimens based on gemcitabine or oxaliplatin-irinotecan (folfirinox/folfox) followed by radiotherapy (total dose of 50-54 Gy/with fractionation of 2 Gy/day). The patients were treated with IFRT. Local failure (LF) was defined as an increase in radiographic abnormality within the planning target volume (PTV). Elective nodal failure (ENF) was defined as recurrence in any lymph node region outside the PTV. Any other failure was defined as distant failure (DF). Results The median age of the patients was 68 years (range: 44-80 years); 20 patients (66.7%) were men, and 11 (36.6%) and 19 (63.4%) patients presented with tumors of stage II and III, respectively. Most patients (63.3%) had tumors in the pancreatic head. The median survival was 17.2 months. Tumor recurrences were classified as LF, DF, LF and DF in 7 (23.3%), 17 (56.7%), and 5 (16.7%) patients, respectively. Only one patient (3.3%) had both LF and ENF. No severe side effects related to radiotherapy were reported. Conclusion The use of IFRT did not cause a significant amount of ENF, besides presenting low morbidity, which is of special importance for patients with locally advanced tumors or low performance status. The predominant failure pattern was distant metastases.

Modifying effects of 2,4-D and Glyphosate exposures on gut-liver-adipose tissue axis of diet-induced non-alcoholic fatty liver disease in mice.

Nonalcoholic fatty liver disease (NAFLD), which is linked to western diet (WD) intake, affects 30% of the world's population and involves the crosstalk of liver steatosis, hypertrophy/inflammation of adipose tissue and deregulation of gut microbiome. Glyphosate and 2,4-D are some of the most applied herbicides worldwide, and their roles in NAFLD have not been investigated. Thus, the present study evaluated whether glyphosate and 2,4-D, in single or mixed exposure, alter WD-induced NAFLD in a mouse model. Male C57Bl/6 mice (n = 10/group) received a fat (30% lard, 0.02% cholesterol), and sucrose-rich diet (20%) and high sugar solution (23.1 and 18.9 g/L of fructose and glucose) for 6 months. Simultaneously, animals received glyphosate (0.05 or 5 mg/kg/day), 2,4-D (0.02 or 2 mg/kg/day), or their combination (0.05 +0.02 or 5 +2 mg/kg/day) by intragastrical administration (5 ×/week). Doses were based on the Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) levels. Herbicide exposures featured differential responses. WD-induced obesity, hypercholesterolemia, and hyperglycemia remained unaltered. Compared to the group receiving only WD, only the concomitant exposure to WD and 2,4-D (2 mg) enhanced the percentage of mice with moderate/severe hepatic inflammation, CD68 macrophage infiltration, and malondialdehyde levels in the liver. In line, this herbicide modulated immune response- (including Cd4, C8b, Cd28, Cxcr3, Cxcr6) and oxidative stress-related (such as Gsta1, Gsta2, Gsta4, Gstm1, Gstm2, Gstm3, Gstm4, Nqo1, Gpx2) genes in the hepatic transcriptome analysis. This exposure also enriched pro-inflammatory Deferribacteres phylum in fecal microbiome. In general, the herbicide mixtures did not feature the same effects attributed to 2,4-D isolated exposure. Our findings indicate that 2,4-D, at a dose within the toxicological limits, was able to induce disturbances in mainly at the liver and gut axes involved in NAFLD development in male mice.

Indole-3-carbinol and chlorogenic acid combination modulates gut microbiome and attenuates nonalcoholic steatohepatitis in a murine model.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, affecting almost 32% of the population and ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Recent findings indicate that the fast-growing prevalence of NAFLD might be linked to adherence to a Westernized diet (WD), mostly composed of fat/sugar-enriched foods. The WD has been reportedly targeted as a potential driver of gut-liver axis unbalance, suggesting a major role in NASH. On the other hand, bioactive food compounds feature as a potential chemopreventive strategy against NASH, due to their beneficial effects (i.e, anti-inflammatory/oxidant activity and modulation of gut microbiome). Brassicaceae vegetables are known for their high amount of isothiocyanates and polyphenols, as indole-3-carbinol (I3C) and chlorogenic acid (CGA). Thus, we sought to assess the effects of human relevant doses of I3C and CGA isolated or in combination (5/125 mg/Kg of body weight, respectively) on a diet/chemical-induced murine model of NASH. I3C + CGA oral treatment diminished NAFLD activity score (NAS) (p < 0.0001), as well as alleviated the hepatic lipid (p = 0.0011) accumulation, prevented hepatic stellate cell (HSC) activation (p < 0.0001), and subsequent fibrosis (p < 0.0001). The combination also reduced the number of both hepatic CD68-positive macrophages (p < 0.0001) and cleaved caspase-3 hepatocytes (p < 0.0001) and diminished the malondialdehyde levels (p = 0.0155). Additionally, the combination of I3C + CGA restored the relative abundance of Alistipes (p = 0.0299), Allobaculum (p = 0.0014), Bacteroides (p = 0.0046), and Odoribacter (p = 0.0030) bacteria genera on the gut microbiome. Taken together, these findings show that the combination of I3C + CGA at populational-relevant ingestion, rather than the I3C or CGA alone, was able to modulate gut microbiome and attenuate NASH in this hybrid model mouse.

Soil-vegetation relationship in savanic formations of the Jalapão, Brazil.

Understanding the influence of fine-scale abiotic filters on plant communities can provide important insights into floristic patterns of the Brazilian Cerrado. We aimed to evaluate the interactions of the soil and the plant community composition with their distribution in different sandy environments of Brazilian Cerrado, the Jalapão region. Eight environments were sampled, each with ten plots of 20 × 50 m. All woody individuals presenting circumference at soil height ≥ 10 cm were sampled. Subplots of 5 × 15 m were demarcated, where woody individuals with a circumference at soil height ≥ 5 and < 10 cm were sampled. Subplots of 2 × 2 m were also demarcated to sample herbaceous individuals. Soil samples varying from 0 to 20 cm of depth were collected for each plot (20 × 50 m). Overall, 20000 individuals that belong to 338 species and 76 families were sampled. The dominant family was Fabaceae. There were significant differences among the environments regarding species richness and soil. The analyzed soils are extremely poor and with a tendency to sandy texture, small chemical and/or physical variations imply differences in the distribution of vegetation. Our study revealed abiotic filters exerted crucial fine-scale effects on plant community in the Jalapão region.

Effects of glyphosate exposure on western diet-induced non-alcoholic fatty liver disease in mice.

We evaluated whether glyphosate promotes western diet (WD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed WD and received intragastrical glyphosate (0.05, 5 or 50 mg/kg) for 6 months. Glyphosate did not promote WD-induced obesity, hypercholesterolemia, glucose intolerance, hepatic steatosis, and fibrosis. Nonetheless, the higher dose (50 mg) enhanced hepatic CD68+ macrophage density, p65, TNF-α, and IL-6 protein levels. Furthermore, this dose decreased hepatic Nrf2 levels, while enhancing lipid peroxidation in the liver and adipose tissue. Hepatic transcriptome revealed that glyphosate at 50 mg upregulated 212 genes and downregulated 731 genes. Genes associated with oxidative stress and inflammation were upregulated, while key cell cycle-related genes were downregulated. Our results indicate that glyphosate exposure - in a dose within the toxicological limits - impairs hepatic inflammation/redox dynamics in a NAFLD microenvironment.

Synergic vascular photodynamic activity by methylene blue-curcumin supramolecular assembly.

A supramolecular assembly was obtained by combining methylene blue (MB) with a natural plant extract, curcumin (Curc), in a stoichiometric ratio of 1:4 in aqueous solution (90% PBS + 10% ethanol) at room temperature. The MB-Curc supramolecular assembly was evidenced by absorption and fluorescence spectroscopies, and the stoichiometry and bonding constant were obtained using Cielens model. Its stability and photostability were evaluated by chromatographic analysis and UV-Vis absorption. The MB-Curc avoids the aggregation of both isolated compounds and efficiently produces singlet oxygen (ΦΔ= 0.52 ± 0.03). Its potential for photodynamic antiangiogenic treatments was evaluated through the vascular effect observed in chicken chorioallantoic membrane (CAM) assay. The results showed intense damage in CAM vascular network by MB-Curc after irradiation, which is higher than the effect of isolated compounds, indicating a synergistic vascular effect. This combination can be essential to prevent cancer revascularization after photodynamic application and improve the efficacy of this approach. The characteristics exhibited by MB-Curc make it a potential candidate for use in cancer treatments through photodynamic antiangiogenic therapy.

Identifying cellular markers of focal cortical dysplasia type II with cell-type deconvolution and single-cell signatures.

Focal cortical dysplasia (FCD) is a brain malformation that causes medically refractory epilepsy. FCD is classified into three categories based on structural and cellular abnormalities, with FCD type II being the most common and characterized by disrupted organization of the cortex and abnormal neuronal development. In this study, we employed cell-type deconvolution and single-cell signatures to analyze bulk RNA-seq from multiple transcriptomic studies, aiming to characterize the cellular composition of brain lesions in patients with FCD IIa and IIb subtypes. Our deconvolution analyses revealed specific cellular changes in FCD IIb, including neuronal loss and an increase in reactive astrocytes (astrogliosis) when compared to FCD IIa. Astrogliosis in FCD IIb was further supported by a gene signature analysis and histologically confirmed by glial fibrillary acidic protein (GFAP) immunostaining. Overall, our findings demonstrate that FCD II subtypes exhibit differential neuronal and glial compositions, with astrogliosis emerging as a hallmark of FCD IIb. These observations, validated in independent patient cohorts and confirmed using immunohistochemistry, offer novel insights into the involvement of glial cells in FCD type II pathophysiology and may contribute to the development of targeted therapies for this condition.