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Four functionalized BODIPY derivatives (BDP1 to BDP4) were synthesized and their optical properties investigated both in solution and when incorporated into a solid matrix. Recognizing the versatility of BODIPY derivatives and the increasing interest in developing new luminescent organic dyes embedded in polymers, the BODIPY derivatives were dispersed into two types of polymeric matrices: Poly(methyl methacrylate) (PMMA) and Thermoplastic Polyurethane (TPU), both as films and microparticles. This resulted in eight new BODIPY-doped polymer films and eight types of BODIPY-doped polymeric microparticles for use in aqueous solutions. The integration of the BODIPY dyes into the polymeric matrices combines the unique properties of the polymer films, such as porosity, flexibility, and elasticity, with the excellent photophysical characteristics of the BODIPYs. Importantly, the dispersion minimized issues such as aggregation-caused quenching commonly observed in solid-state luminescent materials. The thermometric responses of all polymer films were evaluated by studying their solid-state emission spectra in the 25-200 °C temperature range. The reversibility of these temperature-induced changes was also assessed, revealing excellent recovery of luminescence. These promising results suggest these materials could have applications as fluorescent thermometric sensors. Furthermore, we explored the potential of the brominated (BDP3) and chalcogenated (BDP4) BODIPY derivatives as ammonia sensors. The two derivatives produced yellow fluorescent products upon interaction with the analyte. Kinetic studies using solid-state emission spectra of BDP4@TPU and BDP4@PMMA showed significant differences in reaction rates (minutes for BDP4@TPU and hours in the case of BDP4@PMMA) attributable to the higher permeability of TPU when compared with PMMA. Detection and quantification of ammonia concentration were conducted by means of simple photographic analysis, measuring the "R" (red) and "G" (green) components of RGB color parameters. The results from the photographic method correlated well with the results from fluorimetric spectroscopy studies. The photographic analysis is straightforward, portable, and does not require expensive equipment. Finally, we successfully applied polymeric microparticles doped with BODIPYs to detect ammonia in water, demonstrating their effectiveness without the need for organic solvents. This highlights their potential for environmental monitoring and other applications requiring sensitive and selective detection methods., Competing Interests: Declarations Ethical approval No ethical approval was necessary. Confllict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Biothiols, such as cysteine (Cys), glutathione (GSH), and homocysteine (Hcy), play crucial roles in various physiological processes and serve as biomarkers for oxidative stress and redox homeostasis. Their structural similarities, however, pose significant challenges in selective detection and quantification, limiting the availability of suitable probes. Here, we report the design and synthesis of a novel ratiometric fluorescent sensor based on a seleno-BODIPY (Se-BODIPY) derivative, enabling rapid discrimination and quantification of Cys, Hcy, and GSH with low detection limits (Cys = 0.8 μM, Hcy = 20.4 μM, and GSH = 35.9 μM) via fluorescence. The probe exhibits high selectivity towards these biothiols over 11 amino acids, operating through dual-mode detection (absorption and emission spectra) with a visible color change from blue to orange (Cys/Hcy) or pink (GSH) in a turn-on fluorescence process. Notably, the distinct reaction mechanisms between Se-BODIPY and GSH versus Cys/Hcy lead to a more prominent blue shift for Cys/Hcy, facilitating their differentiation. Kinetic studies further differentiate Cys from Hcy, with the BODIPY reacting much faster with Cys than the latter. The effectiveness of the sensor was demonstrated in quantifying biothiols in urine samples, providing a non-invasive method with high recovery rates. Additionally, its incorporation into paper strips allows detection of biothiols in water samples via visible and UV light-induced color changes, indicating its potential for solid-state detection without organic solvents.

The synthetic nitro-alcohol 2-nitro-1-phenyl-1-propanol (NPP) has endothelium-independent relaxing properties in isolated preparations of rat aorta and mesenteric artery. In this study, we investigated whether the vasodilator effects occur in coronary vessels and explored whether hyperpolarization is involved in the underlying mechanism of NPP-induced smooth muscle relaxation. The relaxing responses were studied in isolated preparations of the left anterior descending coronary (ADC) and the septal coronary (SC) arteries, which had been previously maintained under sustained contraction induced by the thromboxane A 2 analogue U-46619. Administered cumulatively, NPP elicited concentration-dependent vasorelaxation with similar potency in both vessels. The relaxant effect remained unaffected by the nitric oxide synthase inhibitor L-NAME, the protein kinase C inhibitor bisindolylmaleimide IV and the Rho-associated protein kinase inhibitor Y-27632. However, it was significantly diminished by the adenylyl cyclase inhibitor MDL-12,330A, the guanylyl cyclase inhibitor ODQ, as well as the K + channel inhibitors tetraethylammonium and CsCl. In ADC preparations impaled with intracellular micropipettes, NPP hyperpolarized the vascular preparation. When the isolated preparation was precontracted by 5-hydroxytryptamine or 80 mM KCl, NPP-induced relaxation with lower pharmacological potency compared to the vessels contracted by U-46619. In conclusion, NPP exhibits vasorelaxant effects on rat coronary arteries, likely involving pathways that include cyclic nucleotide production and membrane hyperpolarization., (© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Cancer, the second leading global cause of death, impacts both physically and emotionally. Conventional treatments such as surgeries, chemotherapy, and radiotherapy have adverse effects, driving the need for more precise approaches. Precision medicine enables more targeted treatments. Genetic mapping, alongside other molecular biology approaches, identifies specific genes, contributing to accurate prognoses. The review addresses, in clinical use, a molecular perspective on treatment. Biomarkers like alpha-fetoprotein, beta-human chorionic gonadotropin, 5-hydroxyindoleacetic acid, programmed death-1, and cytotoxic T lymphocyte-associated protein 4 are explored, providing valuable information. Bioinformatics, with an emphasis on artificial intelligence, revolutionizes the analysis of biological data, offering more accurate diagnoses. Techniques like liquid biopsy are emphasized for early detection. Precision medicine guides therapeutic strategies based on the molecular characteristics of the tumor, as evidenced in the molecular subtypes of breast cancer. Classifications allow personalized treatments, highlighting the role of trastuzumab and endocrine therapies. Despite the benefits, challenges persist, including high costs, tumor heterogeneity, and ethical issues. Overcoming obstacles requires collaboration, ensuring that advances in molecular biology translate into accessible benefits for all., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Engagement is an important component in the advancement of gene-drive vector control research programs as developers look to transition the technology from the laboratory to the field. As research advances and engagement surrounding this novel technology is put into practice, knowledge can be gained from practical experiences and applications in the field. A relationship-based model (RBM) provides a framework for end-user development of engagement programs and strategies. The model places end users at the center of the engagement decision-making processes rather than as recipients of predetermined strategies, methods, and definitions. Successful RBM application for healthcare delivery has previously been demonstrated, and the University of California Malaria Initiative (UCMI) has applied this model to its gene-drive program in the Democratic Republic of São Tomé and Príncipe. The model emphasizes the importance of local leadership in the planning, development, and implementation of all phases of project engagement. The primary aim of this paper is to translate the model from paper to practice and provide a transparent description, using practical examples, of the UCMI program implementation of RBM at its field site. End-user development of the UCMI engagement program provides a unique approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs. This paper may also serve as a reference and example for projects looking to establish an engagement program model that integrates end-user groups in the decision-making processes surrounding engagement.

Objectives: To critically analyse and discuss oral hygiene protocols in the hospital environment in patients admitted to the ICU, through a systematic review of the literature., Methods: The electronic search was performed on Pubmed, Cochrane, Web of Science and Google Scholar databases. The indexing keywords according to the PRISMA protocol were: 'hospital dentistry', 'oral health', 'oral care' and 'intensive care unit'., Results: The initial search resulted in a total of 2671 articles. Pre-selection based on titles led to the exclusion of 2510 articles and the remaining 36 were selected for abstract reading. After analysing the eligibility of the articles, eight studies were included in the review and submitted to qualitative analysis., Conclusion: It can be concluded that cleaning with a soft bristle brush, use of chlorhexidine and lip moisturizing are methods commonly used in dental care actions in patients hospitalized in intensive care units., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

Background: Complementary feeding is critical in establishing undernutrition. However, experimental undernourished diets do not represent the amount of nutrients in the complementary diets of undernourished children., Objectives: To develop, validate, and evaluate the impact of a new murine model of undernutrition on the intestinal epithelium, based on the complementary diet of undernourished children from 7 countries with low-socioeconomic power belonging to the Malnutrition-Enteric Diseases (MAL-ED) cohort study., Methods: We used the difference in the percentage of energy, macronutrients, fiber and zinc in the complementary diet of children without undernutrition compared with stunting (height-for-age Z-score < -2) for the MAL-ED diet formulation. Subsequently, C57BL/6 mice were fed a control diet (AIN-93M diet) or MAL-ED diet for 28 d. Weight was measured daily; body composition was measured every 7 d; lactulose:mannitol ratio (LM) and morphometry were evaluated on days 7 and 28; the cotransport test and analysis of intestinal transporters and tight junctions were performed on day 7., Results: The MAL-ED diet presented -8.03% energy, -37.46% protein, -24.20% lipid, -10.83% zinc, +5.93% carbohydrate, and +45.17% fiber compared with the control diet. This diet rapidly reduced weight gain and compromised body growth and energy reserves during the chronic period (P < 0.05). In the intestinal epithelial barrier, this diet caused an increase in the LM (P < 0.001) and reduced (P < 0.001) the villous area associated with an increase in FAT/CD36 in the acute period and increased (P < 0.001) mannitol excretion in the chronic period., Conclusions: The MAL-ED diet induced undernutrition in mice, resulting in acute damage to the integrity of the intestinal epithelial barrier and a subsequent increase in the intestinal area during the chronic period. This study introduces the first murine model of undernutrition for the complementary feeding phase, based on data from undernourished children in 7 different countries., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Eucalyptus covers approximately 7.5 million hectares in Brazil and serves as the primary woody species cultivated for commercial purposes. However, native insects and invasive pests pose a significant threat to eucalyptus trees, resulting in substantial economic losses and reduced forest productivity. One of the primary lepidopteran pests affecting eucalyptus is Thyrinteina arnobia (Stoll, 1782) (Lepidoptera: Geometridae), commonly referred to as the brown looper caterpillar. To address this issue, FuturaGene, the biotech division of Suzano S.A., has developed an insect-resistant (IR) eucalyptus variety, which expresses Cry pesticidal proteins (Cry1Ab, Cry1Bb, and Cry2Aa), derived from Bacillus thuringiensis (Bt). Following extensive safety assessments, including field trials across various biomes in Brazil, the Brazilian National Technical Commission of Biosafety (CTNBio) recently approved the commercialization of IR eucalyptus. The biosafety assessments involved the analysis of molecular genomics, digestibility, thermostability, non-target organism exposure, degradability in the field, and effects on soil microbial communities and arthropod communities. In addition, in silico studies were conducted to evaluate allergenicity and toxicity. Results from both laboratory and field studies indicated that Bt eucalyptus is as safe as the conventional eucalyptus clone for humans, animals, and the environment, ensuring the secure use of this insect-resistant trait in wood production., Competing Interests: Authors DA, SA, and SL were employed by FuturaGene Israel Ltd. Authors AM, AAS, ACMP, CSR, ERG, JMWG, LB, MPG, RNG, TBD, TRD, and ACP were employed by Suzano S.A. (FuturaGene—Biotech Division). Author EZ, ES, MMD, and RM were employed by Suzano S.A. Author WJS was employed by W. J. Silva Agricultural Consulting Company., (Copyright © 2024 Avisar, Manoeli, dos Santos, Porto, Rocha, Zauza, Gonzalez, Soliman, Gonsalves, Bombonato, Galan, Domingues, Candelaria, Mafia, Graça, Azulay, Livne, Dias, Drezza, Silva and Pinheiro.)

Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the in vitro and in vivo anti-inflammatory activity of a novel diselenide named as dibenzyl[diselanediyIbis(propane-3-1diyl)] dicarbamate (DD). DD reacted with HOCl ( k  = 9.2 x 10 7 M -1 s -1 ), like glutathione ( k  = 1.2 x 10 8 M -1 s -1 ), yielding seleninic and selenonic acid derivatives, and it also decreased HOCl formation by activated human neutrophils (IC 50 =4.6 μM) and purified myeloperoxidase (MPO) (IC 50 =3.8 μM). However, tyrosine, MPO-I and MPO-II substrates, did not restore HOCl formation in presence of DD. DD inhibited the oxidative burst in d HL-60 cells with no toxicity up to 25 µM for 48h. Next, an intraperitoneal administration of 25, 50, and 75 mg/kg DD decreased total leukocyte, neutrophil chemotaxis, and inflammation markers (MPO activity, lipid peroxidation, albumin exudation, nitrite, TNF-α, IL-1β, CXCL1/KC, and CXCL2/MIP-2) on a murine model of carrageenan-induced peritonitis. Likewise, 50 mg/kg DD (i.p.) decreased carrageenan-induced paw edema over 5h. Histological and immunohistochemistry analyses of the paw tissue showed decreased neutrophil count, edema area, and MPO, carbonylated, and nitrated protein staining. Furthermore, DD treatment decreased the fMLP-induced chemotaxis of human neutrophils (IC 50 =3.7 μM) in vitro with no toxicity. Lastly, DD presented no toxicity in a single-dose model using mice (50 mg/kg, i.p.) over 15 days and in Artemia salina bioassay (50 to 2000 µM), corroborating findings from in silico toxicological study. Altogether, these results demonstrate that DD attenuates carrageenan-induced inflammation mainly by reducing neutrophil migration and the resulting damage from MPO-mediated oxidative burst.

The establishment of a virus infection is the result of the pathogen's ability to replicate in a hostile environment generated by the host's immune system. Here, we found that ISG15 restricts Dengue and Zika viruses' replication through the stabilization of its binding partner USP18. ISG15 expression was necessary to control DV replication driven by both autocrine and paracrine type one interferon (IFN-I) signaling. Moreover, USP18 competes with NS5-mediated STAT2 degradation, a major mechanism for establishment of flavivirus infection. Strikingly, reconstitution of USP18 in ISG15-deficient cells was sufficient to restore the STAT2's stability and restrict virus growth, suggesting that the IFNAR-mediated ISG15 activity is also antiviral. Our results add a novel layer of complexity in the virus/host interaction interface and suggest that NS5 has a narrow window of opportunity to degrade STAT2, therefore suppressing host's IFN-I mediated response and promoting virus replication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Espada, da Rocha, Ricciardi-Jorge, dos Santos, Soares, Malaquias, Patrício, Gonzalez Kozlova, dos Santos, Bordignon, Sanford, Fajardo, Sweeney, Báfica and Mansur.)

The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.

The α7 subtype of nicotinic receptors (α7 nAChRs) is one of the most abundant nicotinic receptor subtypes in the central nervous system (CNS) and both neurons and nonneuronal cells express α7 nAChRs. When activated, α7 nAChRs become permeable to cations and promote cellular responses such as anti-apoptotic signaling by modulating the caspases and proteins of the Bcl-2 family. Neuroprotection is an important function of these receptors, promoting neuronal survival under pathological conditions, including situations of stress and neuronal degeneration. Studies have demonstrated the relationship between the activation of these receptors and the reduction of neuronal or glial cell injury, by controlling apoptotic processes in different models, including neurodegenerative diseases such as Alzheimer's disease. Therefore, one of the most important signaling pathways activated by α7 nAChRs is the PI3K/Akt signaling cascade, which promotes the stimulation of anti-apoptotic molecules of the Bcl-2 family, Bcl-2 and Bcl-xl, and reduces the expression of caspases and proapoptotic molecules, resulting in cell survival. In Alzheimer's models, the literature shows that α7 nAChR activation attenuates Aβ-induced neurotoxicity through modulation of different intrinsic apoptotic pathways via PI3K/Akt and mitogen-activated protein kinase (MAPK). In this review, we provide an up-to-date summary of the current evidence on the relationship between the activation of α7 nAChRs, a subtype of nicotinic acetylcholine receptor, and its role in neuroprotection by modulating apoptotic pathways., (© 2023 Wiley Periodicals LLC.)

Eucalyptus comprises the largest planted area of cultivated production forest in Brazil. Genetic modification of eucalyptus can provide additional characteristics for increasing productivity, protecting plant yield, and potentially altering fiber for various industrial uses. With this objective, a transgenic eucalyptus variety, event H421, received regulatory approval for commercial release after 6 years of approved risk assessment studies by the Brazilian National Technical Biosafety Commission (CTNBio) in 2015, becoming the first approved genetically modified (GM) eucalyptus in the world. GM event H421 enables increased plant biomass accumulation through overexpression of the Arabidopsis 1,4-β-endoglucanase Cel1, which remodels the xyloglucan-cellulose matrix of the cell wall during development to promote cell expansion and growth. As required, in that time, by the current normative from CTNBio, a post-commercial release monitoring plan for H421 was submitted, incorporating general surveillance for five consecutive years with the submission of annual reports. The monitoring plan was conducted on fields of H421 progenies, with conventional clones as comparators, cultivated in representative regions where eucalyptus is cultivated in the states of São Paulo, Bahia, and Maranhão, representing Southeast, Northeast, and Northern Brazil. Over the course of the five-year general surveillance monitoring plan for the approved GM eucalyptus H421, no adverse effect that could impact the biosafety of the commercially approved event was identified. Additionally, the GM eucalyptus exhibited behavior highly consistent with that of conventional commercial clones. Therefore, there was no need for an extra risk assessment study of a case-specific monitoring plan. The results show the importance of continuously updating the regulation norms of governmental agencies to align with scientific advances., Competing Interests: During the development of activities, the authors were working at Suzano S/A, FuturaGene or were third-party contractors of Suzano S/A, which develops genetically modified (GM) eucalyptus. Authors TRD, RNG, JMG, ACP, AAS and MPG are employed by Suzano S.A. Author OA was employed by Suzano S.A and DBNBC Brazil Ltda. Authors DA, MA and NB are employed by FuturaGene. Author WS is a third party contracted by Suzano S.A and W J Silva Consultoria Agrícola S/C LTDA., (Copyright © 2023 Pinheiro, dos Santos, Avisar, Gonsalves, Galan, Abramson, Barimboim, Abrahão, Graça, Drezza and Silva.)

Background & Aims: Changes in dietary habits including increased intake of refined sugars and fats and decreased intake of fiber have been suggested as potential risk factors for the development of inflammatory bowel diseases (IBD). Bioelectrical impedance analysis-derived phase angle (PhA) has been gaining attention in the clinical evaluation of nutritional status. In this study, we for the first time investigated the relationship of PhA and ultra-processed food intake with oxidative stress, body composition and biochemical parameters in adult patients with IBD., Methods: Body composition and PhA were evaluated through electrical bioimpedance. Nitrite (Nox), myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined in both groups. Food consumption was obtained by a food frequency questionnaire (FFQ)., Results: In comparison with the control group, the IBD group had increased (p < 0.05) concentrations of Nox (19.95 ± 1.4 vs. 35.43 ± 7.7 μM), MDA (0.70 ± 0.31 vs. 4.56 ± 0.62 nmol/L), and GSH (9.35 ± 0.38 vs. 10.74 ± 0.51 mg NPSH/μL plasma). PhA was positively correlated with GSH (R 2 :0.22; p:0.02) and SOD (R 2 :0.25; p:0.01). IBD patients ingested higher amounts of ultra-processed foods (IBD:17.04 ± 2.76 vs. Control:24.88 ± 2.30%). However, IBD patients had better consumption of unprocessed or minimally processed foods (IBD:79.06 ± 3.07 vs. Control:67.83 ± 2.32%). We found a positive correlation between ultra-processed food consumption and MDA (R 2 0.43; p:0.01)., Conclusions: PhA may be a practical and effective measure in clinical follow-up of IBD patients, being associated with bilirubin levels and antioxidant enzymes. Also, we recommend evaluating consumption of ultra-processed foods, since this was related with increasing oxidative stress markers in clinical follow-up of IBD patients., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest, financial or otherwise., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The literature is full of studies reporting environmental and health issues related to using traditional pesticides in food production and storage. Fortunately, alternatives have arisen in the last few decades, showing that organic agriculture is possible and economically feasible. And in this scenario, fungi may be helpful. In the natural environment, when associated with plants, these microorganisms offer plant-growth-promoting molecules, facilitate plant nutrient uptake, and antagonize phytopathogens. It is true that fungi can also be phytopathogenic, but even they can benefit agriculture in some way-since pathogenicity is species-specific, these fungi are shown to be useful against weeds (as bioherbicides). Finally, plant-associated yeasts and molds are natural biofactories, and the metabolites they produce while dwelling in leaves, flowers, roots, or the rhizosphere have the potential to be employed in different industrial activities. By addressing all these subjects, this manuscript comprehensively reviews the biotechnological uses of plant-associated fungi and, in addition, aims to sensitize academics, researchers, and investors to new alternatives for healthier and more environmentally friendly production processes.

Aim: Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder in women. We investigate the effect of physical exercise on body composition, nutritional parameters, and oxidative stress in rats with PCOS., Methods: Female rats were into three groups: Control, PCOS, and PCOS + Exercise. PCOS was induced by letrozole (1 mg/kg via p.o.) for 21 days consecutively. Physical exercise was swimming, for 21 consecutive days, 1 h/day with 5 % load. In all groups, we assessed the nutritional and murinometric parameters, body composition, thermography, and oxidative stress in brown adipose tissue (BAT) and peri-ovarian adipose tissue (POAT)., Key Findings: In PCOS we observed an increase (P < 0.05) in body weight vs. the Control group. But, the PCOS + Exercise group prevent this weight gain (P < 0.05). The temperature in BAT, decrease (P < 0.05) in the PCOS group vs. Control group. PCOS + Exercise prevented this reduction (P < 0.05) in BAT temperature vs. PCOS groups. We observed decreases (P < 0.05) in Lee Index and BMI in POS + Exercise vs. PCOS group. In PCOS rats, we observed an increase (P < 0.05) in murinometric (SRWG, EI, and FE) and body composition parameters (TWB, ECF, ICF, and FFM) vs. the Control group. The PCOS + Exercise prevents (P < 0.05) these changes in all groups, compared with PCOS. Regarding the BAT, we observe an increase (P < 0.05) in MPO and MDA levels in the PCOS vs. Control group. PCOS + Exercise prevents (P < 0.05) these increases vs. the PCOS group., Significance: PCOS modifies body composition, and nutritional parameters, and induces changes in oxidative stress in BAT. Physical exercise prevented these alterations., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest, financial or otherwise., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Agronomic biofortification with selenium (Se) effectively reduces hidden hunger and increases the nutritional intake of Se in people and animals. Because sorghum is a staple diet for millions of people and is used in animal feed, it becomes a crop with biofortification potential. Consequently, this study aimed to compare organoselenium compounds with selenate, which is effective in numerous crops, and to assess grain yield, the effect in the antioxidant system, and macronutrient/micronutrient contents of different sorghum genotypes treated with Se, via foliar spray. The trials used a 4 × 8 factorial design, with four Se sources (control-without Se supply, sodium selenate, potassium hydroxy-selenide, acetylselenide) and eight genotypes (BM737, BRS310, Enforcer, K200, Nugrain320, Nugrain420, Nugrain430, and SHS410). The Se rate used was 0.125 mg plant -1 . All genotypes reacted effectively to foliar fertilization with Se through sodium selenate. In this experiment, potassium hydroxy-selenide and acetylselenide showed low Se levels and lower Se uptake and absorption efficiency than selenate. Selenium fertilization increased grain yield and altered lipid peroxidation by malondialdehyde content, hydrogen peroxide content, catalase activity, ascorbate peroxidase, superoxide dismutase, and macronutrients and micronutrients content of the studied genotypes. In sum, biofortification with selenium led to an overall yield increase of sorghum plants and supplementation with selenium through sodium selenate was more efficient than organoselenium compounds, yet acetylselenide had a positive effect on the antioxidant system. Sorghum can be effectively biofortified through the foliar application of sodium selenate; however, studying the interaction between organic and inorganic Se compounds in plants is necessary.

Few studies have focused on nutrient-deficient diets and associated pathobiological dynamics of body composition and intestinal barrier function. This study evaluated the impact of a nutrient-deficient diet on physical development and intestinal morphofunctional barrier in mice. C57BL/6 (21 days of age) mice were fed a Northeastern Brazil regional basic diet (RBD) or a control diet for 21 d. The animals were subjected to bioimpedance analysis, lactulose test, morphometric analysis and quantitative reverse transcription-PCR to evaluate tight junctions and intestinal transporters. RBD feeding significantly reduced weight ( P < 0·05) from day 5, weight gain from day 3 and tail length from day 14. The intake of RBD reduced total body water, extracellular fluid, fat mass and fat-free mass from day 7 ( P < 0·05). RBD induced changes in the jejunum, with an increase in the villus:crypt ratio on day 7, followed by reduction on days 14 and 21 ( P < 0·05). Lactulose:mannitol ratio increased on day 14 ( P < 0·05). Changes in intestinal barrier function on day 14 were associated with reductions in claudin-1 and occludin, and on day 21, there was a reduction in the levels of claudin-2 and occludin. SGLT-1 levels decreased on day 21. RBD compromises body composition and physical development with dynamic changes in intestinal barrier morphofunctional. RBD is associated with damage to intestinal permeability, reduced levels of claudin-1 and occludin transcripts and return of bowel function in a chronic period.

Organochloride (OC) and polychlorinated biphenyl (PCB) concentrations were determined in the muscle tissue of fifty sardine samples (Sardinella brasiliensis) sampled off the south-east Brazilian shelf. The aim herein was to investigate OCs and PCBs composition profile, bioaccumulation potential and human risks. The concentrations of 18 organochlorine pesticides (OCPs) were below the method limit of quantification in most samples (ca. 94%), with few detected, namely δ -HCH, γ -HCH, Endosulfan I and II, Endosulfan Sulphate, DDE, Dieldrin, Endrin, Endrin Aldeide, Endrin Cetone and Metoxyclor. The median concentration for the Σ41 PCBs was 2.32 ng g -1 , ranging from values below the limit of quantification (-1 . Based on the analyzed samples, the concentrations reported herein do not represent a risk for human consumption according to both national and international guidelines, nor do OC and PCB bioaccumulation in sardines appear to be a concern at the moment. These findings, although preliminary, represent a baseline for future comparisons of the quality of an important source of protein available to the poorest Brazilian population strata.

Background: Hypertension is a chronic, multifactorial clinical condition characterized by sustained high blood pressure levels. It is often associated with functional-structural alterations of target organs, which include heart, brain, kidneys, and vasculature., Objective: This study highlights the recent correlation between the immune system and hypertension and its repercussions on target-organ damage., Methods: The descriptors used for the search of the study were "hypertension", "immunity", and "target organs". The methodology of the study followed the main recommendations of the PRISMA statement., Results: The damage to the vasculature arises mainly from the migration of T cells and monocytes that become pro-inflammatory in the adventitia, releasing TNF-α, IFN-γ, and IL-17, which induce endothelial damage and hinder vascular relaxation. In the renal context, the inflammatory process associated with hypertension culminates in renal invasion by leukocytes, which contribute to the injury of this organ by mechanisms of intense sympathetic stimulation, activation of the reninangiotensin system, sodium retention, and aggravation of oxidative stress. In the cardiac context, hypertension increases the expression of pro-inflammatory elements, such as B, T, and NK cells, in addition to the secretion of IFN-γ, IL-17, IL-23, and TNF-α from angiotensin II, reactive oxygen species, and aldosterone. This pro-inflammatory action is also involved in brain damage through SphK1. In view of the above, the participation of the immune system in hypertension-induced injuries seems to be unequivocal., Conclusion: Therefore, understanding the multifactorial mechanisms related to hypertension will certainly allow for more efficient interventions in this condition, preventing target organ damage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Insulin-like growth factor-1 (IGF-1) plays critical roles in the development of the central nervous system (CNS), including the retina, regulating cell proliferation, differentiation, and survival. Here, we investigated the role of IGF-1 on retinal cell proliferation using primary cultures from rat neural retina. Our data show that IGF-1 stimulates retinal cell proliferation and regulates the expression of neurotrophic factors, such as interleukin-4 and brain-derived neurotrophic factor. In addition, our results indicates that IGF-1-induced retinal cell proliferation requires activation of multiple signaling pathways, including phosphatidylinositol 3-kinase, protein kinase Src, phospholipase-C, protein kinase C delta, and mitogen-activated protein kinase pathways. We further show that activation of matrix metalloproteinases and epidermal growth factor receptor is also necessary for IGF-1 enhancing retinal cell proliferation. Overall, these results unveil potential mechanisms by which IGF-1 ensures retinal cell proliferation and support the notion that manipulation of IGF-1 signaling may be beneficial in CNS disorders associated with abnormal cell proliferation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

In the developing retina, precise coordination of cell proliferation, differentiation, and survival is essential for proper retinal maturation and function. We have previously reported evidence that interleukin-4 (IL-4) plays critical roles in neuronal differentiation and survival during retinal development. However, little is known about the role of IL-4 on retinal cell proliferation. In the current study, we investigated if IL-4 regulates cell proliferation induced by epidermal growth factor (EGF) and by fibroblast growth factor 2 (FGF2) in primary retinal cell cultures obtained from newborn rats. First, we show that EGF and FGF2 act as mitogens for glial cells, increasing proliferation of these cells in the retina. EGF- and FGF2-induced mitogenesis requires activation of distinct cell-intrinsic signals. In retinal cells exposed to FGF2, IL-4 downregulates p53 levels (a protein whose activation induces cell-cycle arrest) and increases mitogenic responsiveness to FGF2 through activation of protein kinase A (PKA) pathway. Conversely, in retinal cells exposed to EGF, IL-4 downregulates cyclin D1 levels (a protein required for cell-cycle progression), upregulates p53 levels, and decreases mitogenic responsiveness to EGF. The inhibitory effect induced by IL-4 on retinal cells exposed to EGF requires activation of Janus kinase 3 (JAK3), but not activation of PKA. Based on previous and current findings, we propose that IL-4 serves as a node of signal divergence, modulating multiple cell-intrinsic signals (e.g., cyclin D1, p53, JAK3, and PKA) and mitogenic responsiveness to cell-extrinsic signals (e.g., FGF2 and EGF) to control cell proliferation, differentiation, and survival during retinal development., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Infertility is a worldwide concern, affecting one in six couples throughout their reproductive period. Therefore, enhancing the clinical tools available to identify the causes of infertility may save time, money, and emotional distress for the involved parties. This study aims to annotate potential biomarkers in follicular fluid that are negatively affecting pregnancy outcomes in women suffering infertility-related diseases such as endometriosis, tuboperitoneal factor, uterine factor, and unexplained infertility, using a metabolomics approach through high-resolution mass spectrometry. Follicular fluid samples collected from women who have the abovementioned diseases and managed to become pregnant after in vitro fertilization procedures [control group (CT)] were metabolically compared with those from women who suffer from the same diseases and could not get pregnant after the same treatment [infertile group (IF)]. Mass spectrometry analysis indicated 10 statistically relevant differential metabolites in the IF group, including phosphatidic acids, phosphatidylethanolamines, phosphatidylcholines, phosphatidylinositol, glucosylceramides, and 1-hydroxyvitamin D3 3-D-glucopyranoside. These metabolites are associated with cell signaling, cell proliferation, inflammation, oncogenesis, and apoptosis, and linked to infertility problems. Our results indicate that understanding the IF's metabolic profile may result in a faster and more assertive female infertility diagnosis, lowering the costs, and increasing the probability of a positive pregnancy outcome., (© 2022. The Author(s).)

Aim: To evaluate the influence of swimming training on calcium responsiveness of the myocardium of rats with different infarction sizes (MI). Method: female Wistar rats, sedentary sham (SS = 14), sedentary moderate MI (SMI = 8) and sedentary large MI (SLI = 10) were compared to trained sham (TS = 16), trained moderate MI (TMI = 9) and trained large MI (TLI = 10). After 4 weeks of MI, the animals swam for 60 min/day, 5 days/week, for additional 8 weeks. Papillary muscles of the left ventricle were subjected to different concentrations of extracellular calcium. Inotropism was evaluated through the developed tension (DT), the maximum positive value of the first temporal derivation (+Td/td) and the time to peak tension (TPT). Lusitropism was evaluated by the maximum negative value of the first temporal derivation (-Td/td) and time to 50% relaxation (50%TR). Statistical significance was determined using multivariate analysis of variance and a Hotelling T2 test for the absolute power values of all four extracellular calcium concentrations ( p < 0.05). Results: MI depressed inotropism (from 17% to 51%) and lusitropism (from 22% to 54%) of the sedentary rats, but exercise attenuated the losses, especially regarding + dT/dt, TPT, -dT/dt and 50%TR. Exercise attenuated the decrease in myocardial responsiveness, proportionally to the size of the MI. Conclusion: Myocardial calcium responsiveness is favorably affected in animals with moderate and large MI after swimming exercise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Portes, dos Santos, Padovani, Oliveira, Serra and Tucci.)

To compare in magnetic resonance imaging the anatomical risk factors for anterior cruciate ligament (ACL) injury and patellar dislocation among patients who suffered acute knee injury, 105 patients with acute knee injury resulting in 38 patellar dislocations (patella group), 35 ACL injuries (ACL group), and 32 meniscus or medial collateral ligament injuries (control group) were included. These groups were compared for risk factors for patellar dislocation (patellar height, trochlear dysplasia, and quadriceps angle of action) and for ACL injury (intercondylar width, posterior inclination of tibial plateaus, and depth of the medial plateau). Univariate analysis found statistically significant differences ( p  < 0.05) between the patella and ACL groups in patellar height (Caton-Deschamps [CD] 1.23 vs. 1.07), trochlear facet asymmetry (55 vs. 68%), PTTG (13.08 vs. 8.01 mm), and the patellar tip and trochlear groove (PTTG) angle (29.5 vs. 13.71 degrees). The patella group also differed from control in medial plateau inclination (4.8 vs. 1.87 degrees), patellar height (CD 1.23 vs 1.08), trochlear facet asymmetry (55 vs. 69%), lateral trochlear inclination (17.11 vs. 20.65 degrees), trochlear depth (4.1 vs. 6.05 mm), PTTG (13.08 vs. 9.85 mm), and the PTTG angle (29.5 vs. 17.88 degrees). The ACL and control groups were similar in all measures. Multivariate analysis found the following significant determinants between the Patella and Control groups: patellar height (CD index, odds ratio [OR]: 80.13, p  = 0.015), trochlear anatomy (asymmetry of facets M/L, OR: 1.06, p  = 0.031) and quadriceps action angle (PTTG angle, OR: 1.09, p  = 0.016); between the ACL and control groups: PTTG angle (OR: 0.936, p  = 0.04) and female gender (OR: 3.876, p  = 0.032); and between the patella and ACL groups, the CD index (OR: 67.62, p  = 0.026), asymmetry of the M/L facets (OR: 1.07, p  = 0.011) and PTTG angle (OR: 1.16, p  < 0.001). In conclusion, in patients with acute knee injury, the anatomical factors patellar height, trochlear dysplasia, and quadriceps angle of action were related to the occurrence of patellar dislocation. None of the anatomical factors studied was related to the occurrence of anterior cruciate ligament injury., Competing Interests: None declared., (Thieme. All rights reserved.)

Ouabain is a classic Na + K + ATPase ligand and it has been described to have neuroprotective effects on neurons and glial cells at nanomolar concentrations. In the present work, the neuroprotective and immunomodulatory potential of ouabain was evaluated in neonatal rat retinal cells using an optic nerve axotomy model in vitro. After axotomy, cultured retinal cells were treated with ouabain (3 nM) at different periods. The levels of important inflammatory receptors in the retina such as TNFR1/2, TLR4, and CD14 were analyzed. We observed that TNFR1, TLR4, and CD14 were decreased in all tested periods (15 min, 45 min, 24 h, and 48 h). On the other hand, TNFR2 was increased after 24 h, suggesting an anti-inflammatory potential for ouabain. Moreover, we showed that ouabain also decreased Iba-1 (microglial marker) density. Subsequently, analyses of retrograde labeling of retinal ganglion cells (RGC) were performed after 48 h and showed that ouabain-induced RGC survival depends on autophagy. Using an autophagy inhibitor (3-methyladenine), we observed a complete blockage of the ouabain effect. Western blot analyses showed that ouabain increases the levels of autophagy proteins (LC3 and Beclin-1) coupled to p-CREB transcription factor and leads to autophagosome formation. Additionally, we found that the ratio of cleaved/pro-caspase-3 did not change after ouabain treatment; however, p-JNK density was enhanced. Also, ouabain decreased reactive oxygen species production immediately after axotomy. Taken together, our results suggest that ouabain controls neuroinflammation in the retina following optic nerve axotomy and promotes RGC neuroprotection through activation of the autophagy pathway., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In previous work, we developed a Saccharomyces cerevisiae strain (DLG-K1) lacking the main monosaccharide transporters ( hxt -null) and displaying high xylose reductase, xylitol dehydrogenase and xylulokinase activities. This strain proved to be a useful chassis strain to study new glucose/xylose transporters, as SsXUT1 from Scheffersomyces stipitis . Proteins with high amino acid sequence similarity (78-80%) to SsXUT1 were identified from Spathaspora passalidarum and Spathaspora arborariae genomes. The characterization of these putative transporter genes ( SpXUT1 and SaXUT1 , respectively) was performed in the same chassis strain. Surprisingly, the cloned genes could not restore the ability to grow in several monosaccharides tested (including glucose and xylose), but after being grown in maltose, the uptake of 14 C-glucose and 14 C-xylose was detected. While SsXUT1 lacks lysine residues with high ubiquitinylation potential in its N-terminal domain and displays only one in its C-terminal domain, both SpXUT1 and SaXUT1 transporters have several such residues in their C-terminal domains. A truncated version of SpXUT1 gene, deprived of the respective 3'-end, was cloned in DLG-K1 and allowed growth and fermentation in glucose or xylose. In another approach, two arrestins known to be involved in the ubiquitinylation and endocytosis of sugar transporters ( ROD1 and ROG3 ) were knocked out, but only the rog3 mutant allowed a significant improvement of growth and fermentation in glucose when either of the XUT permeases were expressed. Therefore, for the efficient heterologous expression of monosaccharide (e.g., glucose/xylose) transporters in S. cerevisiae , we propose either the removal of lysines involved in ubiquitinylation and endocytosis or the use of chassis strains hampered in the specific mechanism of membrane protein turnover.

The objective of this study was to evaluate the effects of adapting Nellore and ½ Angus/Nellore (AN) feedlot cattle over periods of 9 and 14 days to high-concentrate diets on performance, feeding behaviour, carcass traits and rumen morphometrics. Seventy-two yearling bulls (313.5 kg ± 24.5), 36 Nellore and 36 AN, were randomly allocated in 24 pens (3 animals/pen; 24 m 2 and 2.0 m of bunk space/animal) according to a randomized complete block design with a 2 × 2 factorial arrangement of treatments as follows: Nellore adapted for 9 days, Nellore adapted for 14 days, AN adapted for 9 days, and AN adapted for 14 days. Each treatment was composed by 6 pens (considered the experimental unit in this study). The adaptation lasted either 9 or 14 days and consisted of 3 step-up diets. Therefore, yearling bulls received the finishing diet containing 86% concentrate either on day 10 or 15 of the study, which lasted 89 days taking into account adaptation and finishing periods. Cattle were slaughtered in a commercial abattoir, and two 1-cm 2 -rumen fragments, one from cranial and another from ventral sac, were collected. The AN cattle outperformed Nellore in terms of average daily gain (1.71 kg/day vs. 1.27 kg/day, p < 0.01), gain:feed ratio (0.137 kg/kg vs. 0.127 kg/kg, p = 0.02) and hot carcass weight (243.64 kg vs. 228.98 kg, p < 0.01). No main effect of the adaptation period was observed for any of the feedlot performance and carcass traits variables evaluated. Compared to feedlot cattle adapted for 9 days, feedlot cattle adapted for 14 days sorted against long (0.68 vs. 0.91, p < 0.01) and for fine particles (1.04 vs. 1.00, p = 0.01). An interaction (p < 0.01) of genotype and adaptation period was observed for rumenitis, where Nellore bulls adapted for 14 days presented the highest scores. In conclusion, there was no evidence that either Nellore or AN cattle benefit from an adaptation period shorter than 14 days., (© 2021 Wiley-VCH GmbH.)

An insult can trigger a protective response or even cell death depending on different factors that include the duration and magnitude of the event and the ability of the cell to activate protective intracellular signals, including inflammatory cytokines. Our previous work showed that the treatment of Lister Hooded rat retinal cell cultures with 50 ng/mL phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, increases the survival of retinal ganglion cells (RGCs) kept in culture for 48 h after axotomy. Here we aim to analyze how PMA modulates the levels of TNF-α and IL-1β (both key inflammatory mediators) and the impact of this modulation on RGCs survival. We hypothesize that the increase in RGCs survival mediated by PMA treatment depends upon modulation of the levels of IL-1β and TNF-α. The effect of PMA treatment was assayed on cell viability, caspase 3 activation, TNF-α and IL-1β release and TNF receptor type I (TNFRI) and TNF receptor type II (TNFRII) levels. PMA treatment increases IL-1β and TNF-α levels in 15 min in culture and increases the release of both cytokines after 30 min and 24 h, respectively. Both IL-1β and TNF-α levels decrease after 48 h of PMA treatment. PMA treatment also induces an increase in TNFRII levels while decreasing TNFRI after 24 h. PMA also inhibited caspase-3 activation, and decreased ROS production and EthD-1/calcein ratio in retinal cell cultures leading to an increase in cell viability. The neutralization of IL-1β (anti-IL1β 0,1ng/mL), the neutralization of TNF-α (anti-TNF-α 0,1ng/mL) and the TNF-α inhibition using a recombinant soluble TNFRII abolished PMA effect on RGCs survival. These data suggest that PMA treatment induces IL1β and TNF-α release and modulation of TNFRI/TNFRII expression promoting RGCs survival after axotomy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: In addition to the cardiovascular and renal systems, the gastrointestinal tract also contains angiotensin ATR 1a , ATR 1b , and ATR 2 . We previously observed that the 2Kidney-1Clip hypertension model elicits physical exercise and gastrointestinal dysmotility, which is prevented by renin-angiotensin system blockers. Here, we investigate the effect of physical exercise on inflammation, stress biomarkers, and angiotensin II receptors in the duodenum of 2K1C rats. Methods: Arterial hypertension was induced by the 2K1C surgical model. The rats were allocated in Sham, 2K1C, or 2K1C+Exercise groups. One week after surgery, they were submitted to a physical exercise protocol (running 5x/week, 60min/day). Next, we assessed their intestinal contractility, cytokine levels (TNF-α, IL-1β, and IL-6), oxidative stress levels (MPO, GSH, MDA, and SOD), and the gene expression of angiotensin receptors (ATR 1A , ATR 1B , and ATR 2 ). Results: In comparison with the Sham group, the 2K1C arterial hypertension decreased ( p <0.05) the intestinal contractility. In comparison with 2K1C, the 2K1C+Exercise group exhibited lower ( p <0.05) MPO activity (22.04±5.90 vs. 78.95±18.09 UMPO/mg tissue) and higher ( p <0.05) GSH concentrations in intestinal tissues (67.63±7.85 vs. 31.85±5.90mg NPSH/mg tissue). The 2K1C+Exercise group showed lower ( p <0.05) cytokine levels in the intestine than 2K1C rats. In comparison with the Sham group, the 2K1C+Exercise rats showed higher ( p <0.05) gene expression of ATR 2 in the duodenum. Conclusion: 2K-1C hypertension elicits an oxidative stress and inflammation process in the duodenum. Physical exercise modulates the expression twice as much of ATR2 receptors, suggesting possible anti-inflammatory and antioxidant effects induced by exercise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 da Silva, Severo, dos Santos, Mendes, Nobre, de Oliveira, Ferreira, Medeiros, Lima-Junior, Havt, Palheta-Junior, dos Santos and Tolentino.)

This study tested the effects of β-methylphenylethylamine (β-MPEA) and octopamine on contractile parameters of the gastrointestinal tract in rats. We hypothesized that some of their effects result from interactions with trace amine (TA)-associated receptors or serotoninergic 5-hydroxytryptamine (5-HT) receptors. β-MPEA-induced contractions in rat gastric fundus strips under resting tonus conditions, but induced relaxation in preparations that were previously contracted with carbachol. Octopamine relaxed gastric fundus strips maintained at resting tonus or contracted with carbachol. The contractile effect of β-MPEA was reduced by cyproheptadine and methiothepin, antagonists of excitatory 5-HT receptors. The relaxing effect of β-MPEA on gastric fundus was insensitive to pretreatment with N-(3-ethoxyphenyl)-4-(1-pyrrolidinyl)-3-(trifluoromethyl)benzamide (EPPTB) and tropisetron, antagonists of TA 1 and 5-HT 4 receptors, respectively. Both EPPTB and tropisetron inhibited the relaxant effects of octopamine on carbachol-contracted preparations. Contrarily, EPPTB did not reduce the relaxant effects of RO5263397 (TA 1 agonist) or zacopride (5-HT 4 agonist). Octopamine, but not β-MPEA, delayed the gastrointestinal transit of a liquid test meal in awaken rats. In isolated preparations of the small intestine under resting conditions, β-MPEA did not alter the basal tonus, but octopamine relaxed it. Intestinal preparations previously contracted with carbachol relaxed after the addition of octopamine and decreased the magnitude of their spontaneous rhythmic contractions in a tropisetron-dependent manner. Thus, β-MPEA and octopamine exerted pharmacological actions on the rat gastrointestinal tract. The excitatory effects of β-MPEA involved 5-HT receptors. Octopamine inhibited the rat gut contractility through the likely involvement of 5-HT 4 and TA receptors. Overall, octopamine effectively inhibited rat gastrointestinal transit., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Because of limited free diffusion in the cytoplasm, viruses must use active transport mechanisms to move intracellularly. Nevertheless, how the plant single-stranded DNA begomoviruses hijack the host intracytoplasmic transport machinery to move from the nucleus to the plasmodesmata remains enigmatic. Here, we identified nuclear shuttle protein (NSP)-interacting proteins from Arabidopsis (Arabidopsis thaliana) by probing a protein microarray and demonstrated that the cabbage leaf curl virus NSP, a facilitator of the nucleocytoplasmic trafficking of viral (v)DNA, interacts in planta with an endosomal vesicle-localized, plant-specific syntaxin-6 protein, designated NSP-interacting syntaxin domain-containing protein (NISP). NISP displays a proviral function, unlike the syntaxin-6 paralog AT2G18860 that failed to interact with NSP. Consistent with these findings, nisp-1 mutant plants were less susceptible to begomovirus infection, a phenotype reversed by NISP complementation. NISP-overexpressing lines accumulated higher levels of vDNA than wild-type. Furthermore, NISP interacted with an NSP-interacting GTPase (NIG) involved in NSP-vDNA nucleocytoplasmic translocation. The NISP-NIG interaction was enhanced by NSP. We also showed that endosomal NISP associates with vDNA. NISP may function as a docking site for recruiting NIG and NSP into endosomes, providing a mechanism for the intracytoplasmic translocation of the NSP-vDNA complex toward and from the cell periphery., (© American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Interleukin-2 (IL-2) is a classical pro-inflammatory cytokine known to display neuroprotective roles in the central nervous system including the retina. In the present study, we investigate the molecular targets involved in the neurotrophic effect of IL-2 on retinal ganglion cells (RGC) after optic nerve axotomy. Analysis of retrograde labeling of RGC showed that common cell survival mediators, as Trk receptors, Src, PI3K, PKC, and intracellular calcium do not mediate the neurotrophic effect of IL-2 on RGC. No involvement of MAPK p38 was also observed. However, other MAPKs as MEK and JNK appear to be mediating this IL-2 effect. Our data also indicate that JAK2/3 are important intracellular proteins for the IL-2 effect. Interestingly, we demonstrate that the IL-2 effect depends on dopamine D1 receptors (D1R), the cAMP/PKA pathway, interleukin-10 (IL-10), and NF-κB, suggesting that RGC survival induced by IL-2 encompasses a molecular network of major complexity. In addition, treatment of retinal cells with recombinant IL-10 or 6-Cl-pb (D1R full agonist) was able to increase RGC survival similar to IL-2. Taken together, our results suggest that after optic nerve axotomy, the increase in RGC survival triggered by IL-2 is mediated by IL-10 and D1R along with the intracellular pathways of MAPKs, JAK/STAT, and cAMP/PKA.

Aims: We examined the effects of treatment with 1-nitro-2-phenylethane (NP), a novel soluble guanylate cyclase stimulator, on monocrotaline (MCT)-induced PAH in rats., Main Methods: At day 0, male adult rats were injected with a single subcutaneous (s.c.) dose of monocrotaline (60 mg/kg). Control (CNT) rats received an equal volume of monocrotaline's vehicle only (s.c.). Four weeks later, MCT-treated rats were treated orally for 14 days with NP (50 mg/kg/day) (MCT-NP group) or its vehicle (Tween 2%) (MCT-V group). At the end of the treatment period and before invasive hemodynamic study, rats of all experimental groups were examined by echocardiography., Key Findings: With respect to CNT rats, MCT-V rats showed significant; (1) increases in pulmonary artery (PA) diameter, RV free wall thickness and end-diastolic RV area, and increase of Fulton index; (2) decreases in maximum pulmonary flow velocity, PA acceleration time (PAAT), PAAT/time of ejection ratio, and velocity-time integral; (3) increases in estimated mean pulmonary arterial pressure; (4) reduction of maximal relaxation to acetylcholine in aortic rings, and (5) increases in wall thickness of pulmonary arterioles. All these measured parameters were significantly reduced or even abolished by oral treatment with NP., Significance: NP reversed endothelial dysfunction and pulmonary vascular remodeling, which in turn reduced ventricular hypertrophy. NP reduced pulmonary artery stiffness, normalized the pulmonary artery diameter and alleviated RV enlargement. Thus, NP may represent a new therapeutic or a complementary approach to treatment of PAH., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cosmogenic 7 Be was used to evaluate soil loss in a mountainous micro-watershed near Belo Horizonte, Southwest Brazil. Two nearby sites were selected, a reference site in a flat area and an eroded site in a hill slope. At the reference site, soil samples were collected monthly throughout the year in order to evaluate seasonal variations of 7 Be inventory in soil and its relation with the precipitation regime. Additionally, rainwater was collected and the expected 7 Be soil content was predicted. At the reference site, the 7 Be inventory shows seasonal variations, in accordance with the rainy season, and its distribution in the soil profile shows an exponential decrease in depth ( h 0  = 6.9 ± 0.6 kg m -2 ; r 2  = 0.97). At the eroded site, two soil sampling campaigns were performed in order to measure soil erosion in the watershed. The estimated net erosion was 42.2 ± 3.7 t ha -1 , indicating the loss of upper 5mm of soil per year. This corresponds to soil losses in the area in the range from moderate to severe erosion.

Amblyomma sculptum is a common human-biting tick in Brazil, where it plays an important role as a vector of Rickettsia rickettsii, the agent of the Brazilian spotted fever. Herein, we studied the seasonal dynamics of A. sculptum in an urban area of the Cerrado biome in midwestern Brazil, where human rickettsiosis is endemic. Ticks were collected in two sites located within the campus of Federal University of Goiás. The collections were done by dragging, flagging and visual search. In total, 117,685 ticks were collected, including 100,627 Amblyomma spp. larvae, 10,055 nymphs and 6977 adults of A. sculptum, and one nymph and 25 adults of Amblyomma dubitatum. The highest peak of larvae occurred in June 2018 and in July 2019, whereas nymphs peaked in July 2018 and September 2019. Adults reached their highest numbers in March 2018 and November 2019. These data suggest that A. sculptum develops one generation per year in this urban area of the Cerrado biome in midwestern Brazil. Interestingly, the peak of nymphs occurred during the same period of all confirmed cases of rickettsiosis in Goiás, suggesting a possible relationship between the seasonal dynamics of this tick stage and rickettsiosis transmission in this state.

This study evaluated the performance of 6 commercially available hard hat designs-differentiated by shell design, number of suspension points, and suspension tightening system-in regard to their ability to attenuate accelerations during vertical impacts to the head. Tests were conducted with impactor materials of steel, wood, and lead shot (resembling commonly seen materials in a construction site), weighing 1.8 and 3.6 kg and dropped from 1.83 m onto a Hybrid III head/neck assembly. All hard hats appreciably reduced head acceleration to the unprotected condition. However, neither the addition of extra suspension points nor variations in suspension tightening mechanism appreciably influenced performance. Therefore, these results indicate that additional features available in current hard hat designs do not improve protective capacity as related to head acceleration metrics.

Context: Glutamine supplementation has been applied clinical practice to treat inflammatory bowel disease (IBD). However, scientific evidence about this is still controversial., Objective: In this review, we systematically evaluated the effects of glutamine supplementation on IBD, based on evidence from randomized clinical trials., Data Source: This review was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We used the PubMed and SciVerse Scopus databases. The Cochrane collaboration tool was used to assess the risk of bias in clinical trials., Data Extraction: The review was carried out by two independent researchers according to the established inclusion criteria. The PICO (patient, intervention, comparison, and outcomes) strategy was used, with the descriptors: "glutamine," "supplementation," "inflammatory bowel diseases," "Crohn's disease," and "ulcerative colitis"., Data Synthesis: Seven research articles were selected for this systematic review. In these studies, glutamine was administered to the participants through oral (21-30g or 0.5g per kg of participant's body weight), enteral (7.87g-8.3 g/100g of the enteral formula), and/or parenteral (0.3  g/kg of the participant's body weight) routes. No changes in anthropometry or biochemical parameters were observed. However, in one study reduced intestinal permeability and morphometry were reported. In two other studies, a slight effect of glutamine on inflammation and oxidative stress was observed. Additionally, two other studies reported an effect of glutamine supplementation on disease activity., Conclusions: The findings obtained through this systematic review indicate that glutamine supplementation has no effect on disease course, anthropometric measurements, intestinal permeability and morphology, disease activity, intestinal symptoms, biochemical parameters, oxidative stress and inflammation markers in patients with IBD, regardless of the route of administration, either treated at a hospital or as outpatients., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to evaluate the effects of glutamine supplementation or exercise on gastric emptying and intestinal inflammation in rats with ulcerative colitis (UC). Strength exercise consisted of jump training 4 × 10 repetitions/5 days a week/8 weeks with progressive overload. Endurance exercise consisted of swimming without overload for a period of 1 h a day/5 days a week/8 weeks. Another group (sedentary) of animals was supplemented with L-glutamine (1 g/kg of body weight) orally for 8 weeks before induction of UC. Colitis was induced by intra-colonic administration of 1 mL of 4% acetic acid. We assessed gastric emptying, macroscopic and microscopic scoring, oxidative stress markers, and IL-1β, IL-6, and (TNF-α) levels. The UC significantly increased (p < 0.05) the gastric emptying compared with the saline control group. We observed a significantly decrease (p < 0.05) in body weight gain in UC rats compared with the control groups. Both exercise interventions and L-glutamine supplementation significantly prevented (p < 0.05) weight loss compared with the UC group. Strength and endurance exercises significantly prevented (p < 0.05) the increase of microscopic scores and oxidative stress (p < 0.05). L-glutamine supplementation in UC rats prevented hemorrhagic damage and improved oxidative stress markers (p < 0.05). Strength and endurance exercises and glutamine decreased the concentrations of inflammatory cytokines IL-1β, IL-6, and TNF-α compared with the UC group (p < 0.05). Strength and endurance exercises and L-glutamine supplementation prevented intestinal inflammation and improved cytokines and oxidative stress levels without altering gastric dysmotility in rats with UC.

Since the Coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was announced, we had an unprecedented change in the way we organize ourselves socially and in our daily routine. Children and adolescents were also greatly impacted by the abrupt withdrawal from school, social life and outdoor activities. Some of them also experienced domestic violence growing. The stress they are subjected to directly impacts their mental health on account of increased anxiety, changes in their diets and in school dynamics, fear or even failing to scale the problem. Our aim is to bring up a discussion under different aspects and to alert public health and government agents about the need for surveillance and care of these individuals. We hope that the damage to their mental health as a result of the side effect of this pandemic can be mitigated by adequate and timely intervention., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cisplatin treatment induces an autonomic dysfunction and gastrointestinal and cardiovascular disorders. Physical exercise as well as pyridostigmine treatment induces improves in the autonomic nervous system. In the current study, we investigated the effect of physical exercise and pyridostigmine treatment on gastrointestinal and cardiovascular changes in cisplatin-treated rats. Rats were divided into groups: Saline (S), Cisplatin (Cis), Exercise (Ex), Cisplatin+Exercise (Cis+Ex), Pyridostigmine (Pyr), and Cisplatin+Pyridostigmine (Cis+Pyr). We induced gastrointestinal dysmotility by administering 3 mg kg -1 of cisplatin once week for 5 weeks. The Ex was swimming (1 h per day/5 days per week for 5 weeks with 5% b.w.). GE was evaluated through the colorimetric method of fractional red phenol recovery 10 min after feeding. Pyr groups received 1.5 mg kg -1 , p.o. or concomitant Cis treatment. Moreover, gastric contraction in vitro and hemodynamic parameters such as MAP, HR, and evoked baroreflex sensitivity were assessed, as well as sympathetic and parasympathetic tone and intrinsic heart rate (IHR). Cis decrease GE vs. saline (p<0.05). Cis+Ex or Cis+Pyr prevented (p<0.05) decrease in GE vs. Cis rats. Cis decreased (p<0.05) gastric responsiveness in vitro vs. saline. Cis+Ex or Cis+Pyr prevented this phenomenon. Cis treatment increase MAP and decrease in HR (p<0.05) vs saline. Cis+Ex or Cis+Pyr attenuated (p<0.05) both alterations. Cis increased sympathetic tone and decreased vagal tone and IHR (p<0.05) vs. the saline. Cis+Ex or Cis+Pyr prevented those effects vs. the Cis group. In conclusion, physical exercise and pyridostigmine treatment improves autonomic dysfunction and prevented GE delay and changes in hemodynamic parameters, baroreflex sensitivity, and cardiac autonomic control in cisplatin-treated rats., (Copyright © 2020 Elsevier Inc. All rights reserved.)