Balanced Profile Research Articles

EPCO-04. H3F3A K27M MUTATION DRIVES A REPRESSIVE TRANSCRIPTOME VIA REDUCED SERINE 31 PHOSPHORYLATION BY MODULATING CHROMATIN ACCESSIBILITY, INDEPENDENT OF H3K27ME3 IN DIFFUSE MIDLINE GLIOMA

Abstract Heterozygous H3.3 K27M mutations are central to the pathogenesis of diffuse midline gliomas (DMG), causing a global reduction in H3K27 trimethylation (H3K27me3) and subsequent epigenetic dysregulation. H3.3 contains a unique Serine 31 (S31) phosphorylation site crucial for mitotic checkpoint regulation. In DMG cells, reduced mitotic S31 phosphorylation correlates with chromosomal instability and aneuploidy. Using a mouse model, we demonstrate that both H3.3K27M and H3.3S31A mutations promote high-grade glioma development, whereas wild-type H3.3 does not. Importantly, S31A, which maintains normal K27me, suggests that S31 phosphorylation loss alone is oncogenic. The H3.3K27M mutation disrupts epigenetic regulation by inhibiting the Polycomb Repressive Complex 2 (PRC2), leading to decreased H3K27me3 and unintended gene induction. Concurrently, K27M exerts a compensatory repressive effect on the transcriptome, mediated by reduced S31 phosphorylation, independent of PRC2 activity. Using CRISPR-engineered isogenic DMG cells and analyzing the transcriptome and chromatin accessibility with RNA-seq and ATAC-seq, we found that the K27M mutation produces a balanced gene expression profile, while PRC2 loss primarily leads to gene induction. Notably, cells with S31A mutations also maintain this balanced profile, linking the PRC2-independent effect of K27M to reduced S31 phosphorylation. Conversely, cells with wild-type K27 but S31A mutation show a repressive genomic state, evidenced by an up/down gene ratio of 0.75, owing to functional PRC2. We further show that the genes uniquely dysregulated by K27M or S31A, independent of PRC2, overlap significantly, with dysregulated genes displaying altered chromatin accessibility. This suggests that the effect of K27M and S31A mutations on gene regulation is primarily due to changes in chromatin state. This complex interplay points to targeting K27M-associated pathways, particularly S31 phosphorylation, as a promising therapeutic avenue in DMG, a malignancy with fewer effective treatments and dismal prognosis.

Surface Metabolite Amino Acids and Collagen Profiling in Refrigerated Tilapia Fish (Oreochromis niloticus): Implications for Identification and Quality Assessment

Nile tilapia (Oreochromis niloticus) by-products, including the scales, skin, and mucus, are rich sources of protein with a balanced amino acid profile and high collagen content. Cold storage at 4 ℃ is commonly used to maintain the freshness of tilapia fish in retail settings. This study aims to investigate the changes in surface metabolites and collagen content in tilapia fish during cold storage at 4 ℃. Fresh tilapia fish was stored at 4 ℃ for 7 days to monitor physicochemical and metabolite changes. Fish collagen content was extracted using acetic acid and pepsin, pH values were measured using a calibrated pH meter, protein content was determined via the Bradford method, and creatine and phenylalanine levels were assessed using High-Performance Liquid Chromatography (HPLC). Analysis was conducted on days 0, 3, and 7 of cold storage. Significant reductions (p<0.05) in collagen content from fish scales were observed on the 3rd day of storage, declining from 72.60 ± 12.40% to 30.17 ± 17.62%. pH levels of fish scales and mucus showed a slight alkaline shift, while the skin turned acidic due to bacterial and enzymatic activities. Protein content in the scales, skin, and mucus showed a substantial loss exceeding 50% after 7 days of cold storage. Changes in creatine and phenylalanine concentrations in the mucus further indicated a decline in tilapia fish freshness due to biochemical reactions post-mortem, compromising overall quality. In conclusion, the duration of cold storage significantly affects the composition of tilapia fish scales, skin, and mucus, with a 7-day storage period identified as a suitable freshness indicator in compliance with FDA guidelines permitting fresh fish to be stored at 4 °C for up to two days.

Pharmacokinetics and ADME Profiling of Tanimilast Following an Intravenous 14C-Microtracer co-administered with an Inhaled Dose in Healthy Male Individuals.

Tanimilast is an inhaled phosphodiesterase-4 inhibitor currently in phase 3 clinical development for treating chronic obstructive pulmonary disease (COPD) and asthma. This trial aimed to characterize the pharmacokinetics, mass balance, and metabolite profiling of tanimilast. Eight healthy male volunteers received a single dose of non-radiolabeled tanimilast via powder inhaler (NEXThaler® (3200μg)), followed by a concomitant intravenous (IV) infusion of a microtracer ([14C]-tanimilast: 18.5μg and 500nCi). Plasma, whole blood, urine, and feces samples were collected up to 240 hours post-dose to quantify non-radiolabeled tanimilast, [14C]-tanimilast, and total-[14C]. The inhaled absolute bioavailability of tanimilast was found to be approximately 50%. Following IV administration of [14C]-tanimilast, plasma clearance was 22 L/h, the steady-state volume of distribution was 201 L, and the half-life was shorter compared to inhaled administration (14 vs. 39 hours, respectively), suggesting that plasma elimination is limited by the absorption rate from the lungs. 79% (71% in feces; 8% in urine) of the IV dose was recovered in excreta as total-[14C]. [14C]-tanimilast was the major radioactive compound in plasma, while no recovery was observed in urine and only 0.3% was recovered in feces, indicating predominant elimination through metabolic route. Importantly, as far as no metabolites accounting for more than 10% of the circulating drug-related exposure in plasma or the administered dose in excreta were detected, no further qualification is required according to regulatory guidelines. This study design successfully characterized the absorption, distribution, and elimination of tanimilast, providing key pharmacokinetic parameters to support its clinical development and regulatory application. Significance Statement This trial investigates PK and ADME profile of tanimilast, an inhaled PDE4 inhibitor for COPD and asthma. Eight male volunteers received a dose of non-radiolabeled tanimilast via NEXThaler® and a microtracer IV dose. Results show pivotal PK results for the characterization of tanimilast, excretion route and quantification of significant metabolites, facilitating streamlined clinical development and regulatory approval.

Interactions between the human milk oligosaccharide 2′-fucosyllactose and Bifidobacterium longum subspecies infantis in influencing systemic immune development and function in piglets

IntroductionThe oligosaccharide 2′-fucosyllactose (2′-FL) is a predominant component of human milk, serving as a prebiotic for gut microbiota and influencing immune development in infants. Bifidobacterium longum subspecies infantis (B. infantis) is a commensal bacterium found in breastfed infants. Both 2′-FL and a specific strain of B. infantis, Bi-26™, are commercially available. This study investigates the potential synbiotic relationship between 2′-FL and Bi-26™ on immune development.MethodsTwo-day-old piglets (n = 53) were randomized in a 2 × 2 design, receiving either a commercial milk replacer ad libitum without (CON) or with 1.0 g/L 2′-FL (FL). Piglets in each diet were further randomized to receive either glycerol stock alone or Bi-26™ (109 CFU) (BI and FLBI) orally once daily. On postnatal day (PND) 34/35, animals were euthanized, and blood was collected for serum cytokine analysis. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated for ex vivo stimulation and flow cytometry analysis. Serum and ex vivo cytokines were analyzed using a multivariate model. All other outcomes were analyzed using a two-way ANOVA, considering prebiotic and probiotic fixed effects. The significance level was set at a p value <0.05, with trends reported for 0.05 < p < 0.1.ResultsImmune cell populations in PBMCs were unaffected by the experimental treatment. However, serum interleukin (IL)-1RA, IL-1β, IL-12, and IL-18 were all higher (p < 0.05) in the FL group than in the CON group. In isolated PBMCs, lipopolysaccharide (LPS) stimulation resulted in higher IL-1RA and a trend for higher IFN-γ secretion in the FL group vs. the CON group.Conclusion2′-FL stimulates a balanced cytokine profile in healthy piglets without changing immune cell populations. When immune cells are stimulated ex vivo with LPS, 2′-FL primes T-cells for a proinflammatory response, which is moderated by co-administration of Bi-26™.

Improved Antioxidant, Antihypertensive, and Antidiabetic Activities and Tailored Emulsion Stability and Foaming Properties of Mixture of Corn Gluten and Soy Protein Hydrolysates Via Enzymatic Processing and Fractionation

ABSTRACTBioactive peptides and protein hydrolysates have gained considerable attention in the food industry and functional food markets due to their diverse health effects, including antioxidant, antihypertensive, and antidiabetic properties. This study aimed to produce combined soy and corn protein hydrolysates using Alcalase (Al), modification of Al‐hydrolysates through sequential hydrolysis using Flavourzyme (Al‐FL), cross‐linking of Al‐hydrolysates using microbial transglutaminase (MTGase) (Al‐TG), and fractionation of Al‐hydrolysates by ultrafiltration (UF) with molecular weight (MW) cut‐off of 100 (Al‐F4), 30 (Al‐F3), 10 (Al‐F2), and 2 kDa (Al‐F1). Notably, the < 2 kDa fraction (Al‐F1) showcased exceptional biological activities, including antioxidant (81.54% DPPH, 98.02% ABTS), antihypertensive (95.45%), and antidiabetic effects (44.72% α‐glucosidase, 77.52% α‐amylase), linked to its high hydrophobic amino acid content and low molecular weights (111 and 263 Da). Conversely, the higher molecular weight fraction (Al‐TG) excelled in emulsion and foam stability, attributed to its balanced amino acid profile and larger peptides (1385–7057 Da). Our findings reveal that specific protein hydrolysate fractions, particularly Al‐F1 and Al‐TG, are promising for applications in food and pharmaceutical formulations due to their enhanced biological and functional properties.

Development of Nutrient-Rich Complementary Food from Sweet Potatoes, Carrots and Crayfish for Combating Infant Malnutrition in Low-income Communities

This study aimed to enhance traditional cereal-based complementary foods in Nigeria by developing and evaluating a nutrient-dense blend of sweet potato, carrot, and crayfish. The objective was to address protein-energy malnutrition in low-resource settings by improving the nutritional profile of local complementary foods. Samples were analyzed in triplicate for proximate composition and selected micronutrients using AOAC standard techniques. Sensory evaluation was conducted using a 5-point hedonic scale with a panel of ten nursing mothers from the Department of Human Nutrition and Dietetics, Lead City University. Results showed that the blend contained 14.74±0.32% crude protein, 72.19±0.51% carbohydrates, and 0.97±0.02% fat. Micronutrient analysis revealed high levels of vitamin C (19.06±0.70 mg/100ml) and phosphorus (497.33±3.37 mg/100ml). Sensory evaluation indicated that the product was well-accepted, with mean scores of 4.2±0.6 for taste (slightly sweet), 4.0±0.7 for color (light brown), and 3.8±0.8 for flavor (mildly fishy). This novel blend significantly improves upon traditional cereal-based complementary foods by providing a more balanced nutrient profile that meets WHO/FAO recommendations. It offers a practical, locally-sourced solution to enhance infant nutrition in low-resource settings, potentially reducing the prevalence of protein-energy malnutrition. Further studies on its long-term effects on child growth and development are recommended.

Chemical Composition and Crystallization Behavior of Oil and Fat Blends for Spreadable Fat Applications.

To meet the expectations of European consumers, who prioritize agro-environmental factors and local resources, the substitution of fats (palm, coconut, shea) and achieving a balanced fatty acid profile in spreadable fats are gaining more attention. The crystallization at 4 °C of a lipid blend composed of rapeseed oil, anhydrous dairy fats, and emulsifiers was studied using a multi-scale approach (DSC and X-ray diffraction techniques) to understand the emergence of polymorphic structures. Although the addition of PUFA from rapeseed oil reduces the atherogenicity and thrombogenicity indices in the blend, controlling the cooling kinetics influences the shapes (needles and spherulites) and sizes of the crystalline structures (small crystals form at a cooling rate of 1 °C min-1, while larger crystals form at higher rates of 5 and 10 °C min-1). The crystallization behavior revealed differences in polymorphic forms at 4 °C in the blend, with a transition to different forms occurring more rapidly compared to dairy fat (stop-and-return method). The study shows crystalline coexistence (α, β', and β) in a 2L lamellar structure, with the β' form being predominant. This structure is ideal for formulating a spreadable product, offering good spreadability (SFC < 32% at 10 °C), mouthfeel, and nutritional benefits compared to butter.

Protein fractionation by microfiltration of goat milk: Influence on proteolysis, metabolites and sensory characteristics of cheeses produced throughout lactation

This study addresses seasonal variations in goat milk by examining the effects of microfiltration (MF) and micro- and diafiltration (MDF) in standardising goat milk composition for cheese production. The research focuses on MF and MDF treatments at two lactation stages, analysing their impact on the quality of a hard goat milk cheese. Key parameters such as total solids, pH, organic acids, free amino acids, protein profiles, and sensory properties during cheese ripening were evaluated. Sensory attributes were assessed using Quantitative Descriptive Analysis (QDA), revealing different profiles between treatments. The MF cheeses showed a balanced profile, while MDF cheeses varied more in sourness, acidity, and texture, also influenced by lactation stage.

Nutritional Approach of Carob Pulp Powder “Ceratonia siliqua L.’’ from Algeria: Potential as Cocoa Substitute in Chocolate Formulations

Background: This study explores the viability of carob pulp flour (CPF) as an alternative to cocoa formulation, focusing on its nutritional attributes and sensory acceptability. Methods: Physicochemical analysis was conducted to assess the composition of CPF, including its fiber, sugar, mineral, protein and fat content using GC-MS. X-ray fluorescence (XRF) was employed to determine essential mineral concentrations. Three chocolate formulations (F0, F1 and F2) were developed and evaluated. Result: CPF was found to be rich in fibers (7%) and sugars (79.64%), with notable levels of potassium (61.76%) and calcium (28.18%). However, it contained relatively low levels of protein (1.51%) and fat (0.6%). The predominant fatty acids in CPF were palmitic acid (16.70%) and oleic acid (18.37%). Among the chocolate formulations tested, F2 (73.3g CPF and 10g sugar) emerged as the most preferred by participants across different demographics and age groups. This suggests that CPF-based chocolate, with a balanced flavor profile and moderate sweetness, provides a highly appealing sensory experience.

Impact of Multicomponent Training Frequency on Health and Fitness Parameters in Postmenopausal Women: A Comparative Study.

Menopause induces physiological changes in women, including increased risks of obesity, cardiovascular diseases, and muscle loss, which can be mitigated by physical exercise. This study aimed to evaluate the effects of a 12-week multicomponent exercise programme, performed 2 or 3 days per week, on health and fitness parameters in postmenopausal women. Eighty-three postmenopausal women (aged 50-65 years) were randomly assigned to three groups: control group (CG, n = 27), 2 days/week exercise group (EG2, n = 28), and 3 days/week exercise group (EG3, n = 28). The intervention included strength, balance, aerobic, and flexibility exercises. Anthropometric measurements (body weight, BMI, waist-to-hip ratio, lean body mass, body fat percentage), lipid profile, and isometric strength were assessed pre- and post-intervention. Data were analysed using a repeated-measures ANOVA, with p < 0.05 considered significant. Significant reductions in body weight, BMI, and waist-to-hip ratio were observed in EG2 and EG3 compared to CG. Lean body mass increased significantly in both EG2 (p < 0.001, ES = 1.37) and EG3 (p < 0.001, ES = 1.50). EG3 showed a greater reduction in body fat percentage than EG2 (p = 0.049). Strength and balance improved significantly in both experimental groups compared to CG, with no significant differences between EG2 and EG3. EG3 also showed superior improvements in lipid profile compared to EG2 and CG. A multicomponent exercise programme, particularly with higher frequency (3 days per week), improves body composition, strength, balance, and lipid profile in postmenopausal women.

Bioefficacy of Methanolic Leaf Extracts from Coleus amboinicus and Mentha spicata against Aedes aegypti Mosquitoes

Mosquito-borne diseases (MBDs) pose significant public health challenges globally, with India and Sub-Saharan Africa accounting for the majority of cases. Aedes aegypti, a primary vector of dengue fever, thrives in an environment with inadequate water supply and poor waste management. The increasing resistance of mosquito population to chemical insecticides necessitates the exploration of alternative control strategies, such as botanical extracts. This study evaluates the adulticidal efficacy of methanolic leaf extracts of Coleus amboinicus and Mentha spicata against the adults of Ae. aegypti. Fresh leaves of both plants were collected, dried, and extracted with methanol. Phytochemical screening revealed a moderate presence of alkaloids, flavonoids, saponins, terpenoids, and glycosides in C. amboinicus, while phenols are highly prevalent, indicating significant biological activity. In contrast, M. spicata displayed a high concentration of alkaloids, flavonoids, and terpenoids, though saponins, phenols, and glycosides were less abundant. Adulticidal bioassays demonstrated that C. amboinicus achieved higher mortality rates across all concentrations compared to M. spicata. The LC50 value for C. amboinicus was 202.00 ppm, while M. spicata exhibited an LC50 of 230.00 ppm. Similarly, the LC90 values were 428.51 ppm and 457.40 ppm for C. amboinicus and M. spicata, respectively. These findings suggest that C. amboinicus has a more balanced and diverse phytochemical profile, which likely contributes to its superior adulticidal activity against Ae. aegypti. This study highlights the potential of C. amboinicus as a natural alternative for mosquito control, warranting further exploration and development for effective vector management.

Unraveling the genetic basis of oil quality in olives: a comparative transcriptome analysis.

The balanced fatty acid profile of olive oil not only enhances its stability but also contributes to its positive effects on health, making it a valuable dietary choice. Olive oil's high content of unsaturated fatty acids and low content of saturated fatty acids contribute to its beneficial effects on cardiovascular diseases and cancer. The quantities of these fatty acids in olive oil may fluctuate due to various factors, with genotype being a crucial determinant of the oil's quality. This study investigated the genetic basis of oil quality by comparing the transcriptome of two Iranian cultivars with contrasting oil profiles: Mari, known for its high oleic acid content, and Shengeh, characterized by high linoleic acid at Jaén index four. Gas chromatography confirmed a significant difference in fatty acid composition between the two cultivars. Mari exhibited significantly higher oleic acid content (78.48%) compared to Shengeh (48.05%), while linoleic acid content was significantly lower in Mari (4.76%) than in Shengeh (26.69%). Using RNA sequencing at Jaén index four, we analyzed genes involved in fatty acid biosynthesis. Differential expression analysis identified 2775 genes showing statistically significant differences between the cultivars. Investigating these genes across nine fundamental pathways involved in oil quality led to the identification of 25 effective genes. Further analysis revealed 78 transcription factors and 95 transcription binding sites involved in oil quality, with BPC6 and RGA emerging as unique factors. This research provides a comprehensive understanding of the genetic and molecular mechanisms underlying oil quality in olive cultivars. The findings have practical implications for olive breeders and producers, potentially streamlining cultivar selection processes and contributing to the production of high-quality olive oil.

Exploring the Gut Microbiota Landscape in Cow Milk Protein Allergy: Clinical Insights and Diagnostic Implications in Pediatric Patients

Cow milk protein allergy (CMPA) is a significant health concern characterized by adverse immune reactions to cow milk proteins. Biomarkers for the accurate diagnosis and prognosis of CMPA are lacking. This study analyzed the clinical features of CMPA, and 16S RNA sequencing was used to investigate potential biomarkers through fecal microbiota profiling. Children with CMPA exhibit a range of clinical symptoms, including gastrointestinal (83% of patients), skin (53% of patients), and respiratory manifestations (26% of patients), highlighting the complexity of this condition. Laboratory analysis revealed significant differences in red cell distribution width (RDW) and inflammatory markers between the CMPA and control groups, suggesting immune activation and inflammatory responses in CMPA. Microbial diversity analysis revealed higher specific diversity indices in the CMPA group compared with those in control group, with significant differences at the genus and species levels. Bacteroides were more abundant in the CMPA group, whereas Bifidobacterium, Ruminococcus, Faecalibacterium, and Parabacteroides were less abundant. The control group exhibited a balanced microbial profile, with a predominant presence of Bifidobacterium bifidum and Akkermansia muciniphila. The significant abundance of Bifidobacterium in the control group (23.19% vs 9.89% in CMPA) was associated with improved growth metrics such as height and weight, suggesting its potential as a probiotic to prevent CMPA and enhance gut health. Correlation analysis linked specific microbial taxa such as Coprococcus and Bifidobacterium to clinical parameters such as family allergy history, weight and height, providing insights into CMPA pathogenesis. Significant differences in bacterial abundance suggested diagnostic potential, with a panel of 6 bacteria achieving high predictive accuracy (area under curve (AUC) = 0.8708). This study emphasizes the complex relationship between the gut microbiota and CMPA, offering valuable insights into disease mechanisms and diagnostic strategies.

Disposition of orally administered atuliflapon, a novel 5-lipoxygenase-activating protein inhibitor in healthy participants.

In this study, the mass balance, pharmacokinetics (PK) and metabolism of atuliflapon, a novel 5-lipoxygenase-activating protein inhibitor, were investigated in healthy male subjects. A single oral dose of 200 mg [14C]atuliflapon suspension was administered to six healthy male subjects. Mass balance, PK and metabolite profiles of atuliflapon were analyzed using radioactivity monitoring and liquid chromatography with mass spectrometry analysis. The safety of atuliflapon was assessed during the study. Atuliflapon was rapidly absorbed with a median tmax of 1.5 h, followed by a biphasic decline in plasma exposure rendering a terminal half-life of ~20 h. Unchanged atuliflapon was the predominant radioactive component in plasma, accounting for 40.1% of the total drug-related exposure (DRE), while a direct N-glucuronide was the only metabolite exceeding 10% of DRE, accounting for 20.9%. Renal excretion of intact atuliflapon accounted for <1% of the administered dose. In total 85.2% of administered radioactivity was recovered over 312 h with 79.3% and 5.9% in feces and urine, respectively. Parent atuliflapon contributed to approximately 40% of the recovered dose in excreta, while metabolites resulting from phase 1 oxidative pathways accounted for more than 30% of the excreted dose. Overall, a single oral dose of 200 mg [14C]atuliflapon suspension was well tolerated in healthy male subjects. The human metabolism and disposition data obtained will support future development and submissions of atuliflapon as a potential candidate drug for the treatment of cardiovascular, cardiorenal, and respiratory indications.

Pediatric sedation outside the operating room integrating dexmedetomidine for MRI and CT scan procedures: A systematic review

This systematic review evaluates the efficacy and safety of dexmedetomidine as a sedative for pediatric patients undergoing MRI and CT scans outside the operating room. A comprehensive search of databases, including PubMed, MEDLINE, and Cochrane Library, identified relevant studies. Data on sedation success rates, onset and recovery times, adverse events, dosing, administration, and hemodynamic stability were extracted and analyzed. The results indicate that dexmedetomidine has high sedation success rates and a favorable safety profile, effectively achieving the desired sedation level with minimal adverse events, primarily manageable hemodynamic changes. Onset and recovery times were generally acceptable for clinical practice, and the flexibility in administration routes and dosing highlighted its adaptability to various clinical needs and settings. Overall, dexmedetomidine is a reliable and safe sedative for pediatric patients undergoing MRI and CT scans, offering a balanced profile of efficacy and safety, and its use can be optimized based on clinical context, patient characteristics, and procedural requirements.

Effect of different combinations of feed material of cattle dung with kitchen waste on growth rate of earthworm Eutyphoeus waltoni Michaelsen

In this study the effect of different combinations of animal dung (buffalo, cow, and goat) with kitchen wastes (vegetable wastes and banana peels) on the growth rate of Eutyphoeus waltoni during vermicomposting has been investigated. To identify the most potential feed material combination for enhancement of earthworm growth, the experiment was conducted using different combination of animal dung with kitchen waste as well as dung alone. Significant growth rate of Eutyphoeus waltoni was observed in all the binary combinations of animal dung with vegetable waste and banana peels whereas; the maximum growth rate was observed in the combination of buffalo dung and vegetable waste present in (1:1) ratio. It may be due to the balanced nutrient profile provided by the mixture, which enhances the decomposition process and creates an ideal environment for earthworm growth. The feed material combination of buffalo dung and vegetable waste in (1:1) ratio is suitable for better growth and development of earthworm Eutyphoeus waltoni which not only enhances the growth rate of earthworm but also contribute to efficient waste management by converting organic waste into nutrient-rich vermicompost.

Promoting Sustainable Well-Being: Burnout and Engagement in South African Learners

This study aimed to analyze the latent profiles of burnout and engagement of learners and to investigate differences between these profiles regarding demographic and contextual variables and academic boredom. The findings have practical implications for educators and professionals in the fields of education and psychology. Grade 9 and 10 South African learners (N = 544) studying English and Mathematics as school subjects participated in the study. Five learner burnout and engagement profiles were identified: healthy engaged (10.66%), moderately balanced (27.57%), slightly disengaged (30.7%), moderately burned-out (20.4%), and burned-out (10.66%). Academic boredom in Mathematics and English was linked to burnout-engagement profiles. The healthy engaged and moderately balanced profiles exhibited significantly lower academic boredom levels in both subjects than the other profiles. Positive relationships with teachers and interest in the subject were crucial across all profiles to diminish academic boredom and enhance engagement, especially in English. Various demographic and contextual variables were associated with burnout-engagement profiles. Home study environments, nurturing positive teacher-learner relationships, and fostering intrinsic interest in subjects can enhance engagement and mitigate burnout in secondary school learners. Sustainable interventions could be created by teachers or researchers, implemented by schools, and taken up in important policies within South Africa, showcasing how the SGDs of improved health and well-being and delivering quality education could be achieved.

Investigation of oral toxicity of WS2 nanosheets to mouse intestine: Pathological injury, trace element balance, lipid profile changes, and autophagy.

The success of graphene oxides has gained extensive research interests in developing novel 2D nanomaterials (NMs). WS2 nanosheets (NSs) are novel transition metal-based 2D NMs, but their toxicity is unclear. In this study, we investigated the oral toxicity of WS2 NSs to mouse intestines. Male mice were administrated with vehicles, 1, 10, or 100 mg/kg NSs via intragastric route, once a day, for 5days. The results indicate that the NSs did not induce pathological or ultrastructural changes in intestines. There were minimal changes of trace elements that the exposure did not induce W accumulation, and only Co levels were dose-dependently increased. Lipid droplets were observed in all groups of mice, but lipidomics data indicate that WS2 NSs only significantly decreased four lipid species, all belonging to phosphatidylcholine (PC). The levels of proteins regulating autophagic lipolysis, namely, LC3, lysosomal associated membrane protein 2 (LAMP2) and perilipin 2 (PLIN2), were increased, but it was only statistically significantly different for LC3. The results of this study suggest that repeated intragastric exposure to WS2 NSs only induced minimal influences on pathological injury, trace element balance, autophagy, and lipid profiles in mouse intestines, indicating relatively high biocompatibility of WS2 NSs to mouse intestine via oral route.

Nutritional Composition of Developed Bars and Their Impact on Work Performance of Adolescent Swimmers’ Girls

With the growing interest in sports nutrition and its impact on athletic performance, understanding the specific needs of adolescent athletes, particularly females, is crucial for optimizing their training and performance outcomes. The three variants of the Protein-rich bar (PB1, PB2, PB3) with the CB were developed by using different ingredients. The research employs a mixed-methods approach, combining nutritional analysis of developed bars with performance assessments among adolescent swimmers’ girls. Firstly, organoleptic evaluation (9-point hedonic scale) was performed on the variants of Protein-rich bar with the CB. Then nutritional analysis involves proximate (moisture, ash, protein, crude fat, crude fiber, CHO), mineral (calcium, iron), as well as antioxidant analysis (DPPH, TPC, vitamin C) assessed on selected variants of Protein-rich bar with the CB. Pre- and post-intervention were done on two groups for 3 months and performance assessments included anthropometric measurement, sit and reach test, hand grip strength test, Nelson hand reaction time test, and Tuttle pulse ratio test. Preliminary findings suggested that the developed bars (PB1) provide a more balanced nutritional profile than the CB. Moisture 10.2±0.66%, ash 3.7±0.27%, protein 22.3±0.74 g, crude fat 13.1±0.41 g, crude fiber 11.5±0.02 g, CHO 39.4±0.19 g, iron 4.4±0.15 mg, calcium 82.4±0.21 mg, DPPH 47.6±0.31%, TPC 53.1±0.11 mg GAE, and vitamin C 11.2±0.19 mg in 100 g respectively in PB1 and significantly difference at (p&lt;0.05). Additionally, the consumption of PB1 bar appears to positively impact higher work performance among adolescent swimmers girls. Overall, this study contributes to the growing body of research on sports nutrition tailored to adolescent athletes, particularly focusing on the nutritional needs of swimmers girls.

Absorption, Distribution, Metabolism, and Excretion of Icenticaftor (QBW251) in Healthy Male Volunteers at Steady State and In Vitro Phenotyping of Major Metabolites.

Icenticaftor (QBW251) is a potentiator of the CFTR protein and is currently in clinical development for the treatment of chronic obstructive pulmonary disease and chronic bronchitis. An absorption, distribution, metabolism, and excretion (ADME) study was performed at steady state to determine the pharmacokinetics, mass balance, and metabolite profiles of icenticaftor in humans. In this open-label study, six healthy men were treated with unlabeled oral icenticaftor (400 mg b.i.d.) for 4 days. A single oral dose of [14C]icenticaftor was administered on Day 5, and unlabeled icenticaftor was administered b.i.d. from the evening of Day 5 to Day 12. Unchanged icenticaftor accounted for 18.5% of plasma radioactivity. Moderate to rapid absorption of icenticaftor was observed (median Tmax: 4 hours), with 93.4% of the dose absorbed. It exhibited moderate distribution (Vz/F: 335 L) and was extensively metabolized, principally through N-glucuronidation, O-glucuronidation, and/or O-demethylation. The metabolites M8 and M9, formed by N-glucuronidation and O-glucuronidation of icenticaftor, respectively, represented the main entities detected in plasma (35.3% and 14.5%, respectively) in addition to unchanged icenticaftor (18.5%). The apparent mean T1/2 of icenticaftor was 15.4 hours in blood and 20.6 hours in plasma. Icenticaftor was eliminated from the body mainly through metabolism followed by renal excretion, and excretion of radioactivity was complete after 9 days. In vitro phenotyping of icenticaftor showed that cytochrome P450 and uridine diphosphate glucuronosyltransferase were responsible for 31% and 69% of the total icenticaftor metabolism in human liver microsomes, respectively. This study provided invaluable insights into the disposition of icenticaftor. Significance Statement The ADME of a single radioactive oral dose of icenticaftor was evaluated at steady state to investigate the nonlinear pharmacokinetics observed previously with icenticaftor. [14C]Icenticaftor demonstrated good systemic availability after oral administration and was extensively metabolized and moderately distributed to peripheral tissues. The most abundant metabolites, M8 and M9, were formed by N-glucuronidation and O-glucuronidation of icenticaftor, respectively. Phenotyping demonstrated that [14C]icenticaftor was metabolized predominantly by UGT1A9 with a remarkably low Km value.