7-day Period Research Articles

Bacillus subtilis supplementation enhances the growth performance, immune indicators, and stability of the intestinal flora of Cherax quadricarinatus

The addition of Bacillus subtilis to the diet can enhance the natural defenses of aquatic creatures and improve their ability to combat diseases. We conducted a study to assess the effects of different concentrations (1.5×106 CFU/g, 1.5×107 CFU/g, and 1.5×108 CFU/g) of B. subtilis on the growth, development, immune response, and gut microbiota of Cherax quadricarinatus over a 45-day period. The highest final weight and growth rate were observed in the group that received 1.5×106 CFU/g of B. subtilis. Furthermore, enzyme activities—including α-amylase, trypsin, alanine aminotransferase, aspartate aminotransferase, and superoxide dismutase (SOD)—were higher in the groups supplemented with B. subtilis compared to those in the control group. Analysis of the gut microbiome through metagenomic sequencing showed consistent levels of α-Proteobacteria but varying levels of Bacteroidetes, Firmicutes, and Actinobacteria. Aeromonas was inhibited during the early stages of culture, leading to enhanced resistance to infection in crayfish that received B. subtilis supplementation. Subsequent infection tests with Aeromonas versonii revealed significantly higher enzyme activities (alkaline phosphatase, acid phosphatase, and SOD) in the experimental groups. The expression of antilipopolysaccharide factor (ALF) and SOD was also notably higher in the experimental groups. Overall, supplementing with B. subtilis showed beneficial effects on the immune response and gut microbiota composition in red claw crayfish.

Bioconversion of sulfamethazine-contaminated chicken manure by black soldier fly larvae: Effects on antibiotic resistance genes and microbial communities.

Sulfamethazine (SM2), a widely detected antibiotic in livestock manure, poses environmental and health risks due to its persistence and the proliferation of antibiotic resistance genes (ARGs). In this study, we investigated the degradation of SM2 and the elimination of sulfonamide ARGs (sul1 and sul2) in chicken manure contaminated with varying concentration of SM2 by black soldier fly larvae (BSFL). Quantitative PCR and 16S rRNA gene sequencing were employed to monitor changes in sulfa ARGs and microbial community composition within both the larvae gut and chicken manure. During the 12-day test period, BSFL exhibited strong tolerance to SM2, significantly reducing SM2 concentrations by 80.54%-92.22% across different treatment groups. Concurrently, the abundance of sul1 and sul2 decreased by 79.27% and 79.92% in chicken manure, respectively. Additionally, microbial genera such as Firmicutes (47.18-65%) and Bacillus (9.32-10.25%), which were enriched in both the BSFL gut and chicken manure, were identified as potential contributors to SM2 degradation. These findings provide a promising biotechnological strategy for mitigating antibiotic contamination in livestock manure.

Combined ecotoxicity of polystyrene microplastics and Di-(2-ethylhexyl) phthalate increase exposure risks to Mytilus coruscus based on the bioaccumulation, oxidative stress, metabolic profiles, and nutritional interferences.

Di-(2-ethylhexyl) phthalate (DEHP) and microplastics (MPs) are emerging contaminants frequently detected in the marine environment. However, the influence of MPs on DEHP bioaccumulation and their combined effects on eco-environmental risks remain underexplored. Mytilus coruscus (M. coruscus) were exposed to DEHP (200.0µg/L), polystyrene (PS) (0.050, 0.50, and 5.0mg/L), and their combination at environmentally relevant concentrations for 15-day, followed by a 7-day depuration period. The amount of DEHP accumulation followed the order of digestive gland >gills >muscles >gonad, with PS dose-dependently amplifying DEHP bioaccumulation in digestive gland. The changes in antioxidant enzyme activity indicated disruptions in oxidative defense. Furthermore, metabolomic analysis revealed that PS and DEHP considerably altered the lipid, energy, and citric acid cycles in digestive gland and gonad. Post-depuration analysis showed combined exposure resulted in persistent effects. Compared with single exposures, combined exposure had a greater adverse effect on the metabolism of essential amino acids, fatty acids, and volatile compounds, potentially influencing edibility and nutritional value of M. coruscus. This study underscores cumulative eco-environmental toxicity of PS and DEHP toward M. coruscus and highlights the potential increased risks of co-pollution.

Plant-derived extracellular vesicles release combined with systemic DOX exhibits synergistic effects in 3D bioprinted triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, lacking targeted therapeutic options. Hydrogels, particularly gelatin methacrylate (GelMA), have emerged as promising materials for localized drug delivery due to their biocompatibility and tunable properties. This study investigates a dual-delivery system for enhancing the treatment efficacy of triple-negative breast cancer (TNBC) using a combination of extracellular vesicles (EVs) derived from Citrus limon L. and the chemotherapeutic drug doxorubicin (DOX). We fabricated 3D bioprinted GelMA scaffolds to achieve localized and controlled release of EVs and evaluated their synergistic effects with systemic DOX delivery on both primary and metastatic 3D TNBC models.The GelMA scaffolds, especially those with 95 % methacrylation, exhibited higher stiffness, which enhanced their sustained release. Following 48-h incubation, the combination of EVs and DOX significantly increased cytotoxicity in the primary 3D TNBC model, reducing cell viability to approximately 30 % compared to controls. This was notably more effective than treatments with DOX or EVs alone. During the extended 7-day incubation period, the combination treatment continued to show superior efficacy, with persistently high levels of ROS generation and further reduction in cell viability. In a metastatic 3D TNBC model, a significant sensitivity to the combined treatment was observed, which notably inhibited aggregate formation and migration. Importantly, EVs-embedded scaffolds promoted the proliferation of human fibroblasts, highlighting their non-toxic nature, while concurrently inhibiting TNBC cell growth. This approach provides a promising strategy to improve the treatment outcomes of TNBC by exploiting the synergistic effects of local EVs release and systemic chemotherapy.

Optimizing λ-cyhalothrin for the effective control of Alphitobius diaperinus: Temperature and food effect revealed

The lesser mealworm, Alphitobius diaperinus, presents substantial challenges as a secondary pest in global stored-product management, especially within the poultry industry. This study examines the effectiveness of λ-cyhalothrin, a synthetic pyrethroid, against A. diaperinus larvae and adults under various abiotic and biotic conditions. Bioassays were conducted at both half-label and label doses across different post-exposure temperatures ranging from 20 to 35 °C. The results demonstrate that λ-cyhalothrin exhibits temperature-dependent efficacy within a 7-day exposure period, with higher temperatures resulting in increased mortality rates for both tested life stages. For larvae, mortalities ranged 81.1 (20 °C)–94.4% (35 °C) (half-label dose in the absence of food), 90.0 (20 °C)–100.0% (35 °C) (label dose in the absence of food), 72.2 (20 °C)–85.6% (35 °C) (half-label in the presence of food), 88.9 (20 °C)–100.0% (35 °C) (label dose in the presence of food) 7 days post-exposure. For adults, mortalities ranged 35.6 (20 °C)–74.4% (35 °C) (half-label dose in the absence of food), 43.3 (20 °C)–97.8% (35 °C) (label dose in the absence of food), 24.4 (20 °C)–65.6% (35 °C) (half-label in the presence of food), 38.9 (20 °C)–94.4% (35 °C) (label dose in the presence of food) after 7 days of exposure. Additionally, the significance of food substrate presence in absorbing and providing a barrier against insecticidal toxicity is highlighted, as it negatively impacted mortality rates. Overall, these findings elucidate the complex interactions among temperature, dosage, and environmental factors that optimize λ-cyhalothrin administration efficiently managing A. diaperinus.

Protective role of 2-aminothiazole derivative against ethanol-induced teratogenic effects in-vivo zebrafish

Teratology investigates the origins of congenital disabilities, often linked to environmental factors such as ethanol (EtOH) exposure. Ethanol at 150 μM has been associated with teratogenic effects, oxidative stress, immunological responses, and endocrine disruptions. Fetal alcohol spectrum disorder (FASD) arises from maternal alcohol consumption during pregnancy, leading to developmental delays and cognitive impairment. Due to their diverse therapeutic applications, amino thiazole derivatives are crucial in drug development. This study aimed to determine whether the 2-amino thiazole derivative, notably the 1-(4-chlorophenyl)-N-(6-nitrobenzo[d]thiazol-2-yl)ethan-1-imine (N4) compound, reduces teratogenic effects induced by embryonic EtOH exposure in a zebrafish model. Teratogenic effects, mortality, locomotion behaviour, oxidative stress, gene expression, and tissue damage were evaluated in larvae over a 7-day experimental period using three treatment concentrations (50, 100, and 150 μM). Results showed that EtOH induced morphological defects in the head, eyes, and body length of exposed larvae, along with behavioural abnormalities and oxidative damage. N4 effectively mitigated these toxic effects in a concentration-dependent manner reducing oxidative damage, preventing teratogenic effects, and averting tissue damage induced by EtOH exposure. This study highlights the potential of N4 to enhance antioxidant and anti-inflammatory effects against ethanol-induced oxidative stress, offering promising therapeutic strategies for FASD treatment.

Effects of aging methods combined with enzyme treatments on the quality parameters of beef striploins

The objective of this study was to evaluate the combined effects of different enzyme (papain, bromelain and fungal protease) treatments and aging methods (dry and wet aging) on physico-chemical and microbiological parameters, lipid oxidation, sarcomere length, colour, shear force and sensory attributes of beef striploins during 28-day aging period. For this purpose, Longissimus lumborum muscles (n=24, 12 carcasses) at 24h postmortem were subjected to dry (2±1°C, 75% relative humidity and 2 m/s air-flow) and wet (vacuum-packaged, 2±1°C) aging methods after enzyme treatments. The microbial growth (P < 0.05) and lipid oxidation (P < 0.001) in wet-aged beef were lower than dry-aged beef, and a decrease in those treated with fungal protease was observed (P < 0.05), while an increase in sarcomere length and water holding capacity, and a decrease in cooking losses were provided with dry aging (P < 0.001). Dry aging combined with papain enzyme enhanced and accelerated meat tenderization in a reduced aging time (P < 0.001), whereas an improvement in flavour and aroma was achieved with bromelain and fungal protease treatments. Surface colour of dry and wet-aged beef showed significant differences during aging period (P < 0.05), while lower b*, h* values and metmyoglobin content were recorded in enzyme-treated striploins. Consequently, combined usage of aging methods with enzyme treatments can be prefered as an effective application to improve the tenderness and palatability of beef with accelerated aging period, and provides an opportunity for meat industry to supply value adding beef in a shorter time.

The Study of Nitrogen and Phosphorus Removal Efficiency in Urbanized River Systems Using Artificial Wetland Systems with Different Substrates

This study evaluated the effectiveness of five commercial substrates (zeolite, volcanic rock, gravel, magic rack, and ceramic pellets) in removing nitrogen (N) and phosphorus (P) from urban river systems using constructed wetlands. By employing X-ray CT and NGS technologies, we analyzed the physical structure of the substrates and the microbial communities they harbor. The results indicated that volcanic rock and ceramic pellets, due to their high porosity and specific surface area, performed exceptionally well in nitrogen and phosphorus removal. Specifically, the microbial systems with these two substrates achieved ammonia nitrogen removal rates of 89.86% and 88.45%, total nitrogen removal rates of 78.78% and 74.97%, and total phosphorus removal rates of 92.67% and 80.82%, respectively, within a 7-day period. Furthermore, the microbial communities on volcanic rock and ceramic pellets were more diverse, which correlated with their high pollutant removal efficiency. The study further elucidated the synergistic role of substrate characteristics and microbial community structure and function in nitrogen and phosphorus removal, enhancing the understanding of the purification mechanisms in constructed wetlands. These findings provide a scientific basis for the ecological restoration of urban rivers and are significant for improving the quality of urban water environments.

Microalgae-Assisted Treatment of Wastewater Originating from Varied Sources, Particularly in the Context of Heavy Metals and Antibiotic-Resistant Bacteria

The increasing prevalence of heavy metals and antibiotic-resistant bacteria in wastewater (WW) raises serious environmental and public health concerns. This study investigates the efficiency of the microalgal strain Chlorella vulgaris EV-465 in treating wastewater and evaluates the antibiotic resistance profile of bacterial strains obtained from WW samples. Chlorella vulgaris EV-465 was used to treat four types of wastewater—domestic, municipal, hospital, and industrial wastewater—through 21 days of incubation. The findings demonstrated pH stabilization and significant decreases in nutrients (total nitrogen—TN, total phosphorus—TP), biological oxygen demand (BOD), chemical oxygen demand (COD), heavy metal (HM) concentrations, and bacterial count. Copper (Cu) showed the highest reduction, decreasing by 80% in industrial wastewater within 14 days, while lead (Pb) proved more resistant to removal, with only a 50% decrease by day 21. Additionally, the algae decreased bacterial counts, lowering colony-forming units (Log CFU/mL) from 9.04 to 4.65 in municipal wastewater over the 21-day period. Antibiotic susceptibility tests for isolated bacterial strains revealed high levels of resistance, with seven out of nine bacterial strains exhibiting multidrug resistance. Notably, Enterococcus faecium (PBI08), Acinetobacter baumannii (YBH19), and Pseudomonas aeruginosa (NBH16) displayed resistance to all nine antibiotics tested. Among the tested antibiotics, Ciprofloxacin showed the highest efficacy, with 66% susceptibility of tested bacterial strains. Cluster and phylogenetic analyses showed that the majority of the isolated bacterial strains belonged to the genera Pseudomonas and Escherichia, highlighting their genetic diversity and varied resistance mechanisms.

Efficient Solar-Powered Bioremediation of Hexavalent Chromium in Contaminated Waters by Chlorella sp. MQ-1

Microalgae are known for their efficient removal of hexavalent chromium (Cr(VI)) through biosorption and bioaccumulation, yet the subsequent release of Cr(VI) upon cell death remains a challenge. The reduction of Cr(VI) to the less toxic trivalent chromium [Cr(III)] is another critical remediation strategy that mitigates the risk of Cr(VI) re-release, but research on microalgal reduction of Cr(VI) is scarce. In this study, a microalgal strain designated as MQ-1 was isolated from chromium-contaminated mine effluent, demonstrating the capability to tolerate and remove Cr(VI). Phylogenetic analysis revealed that MQ-1 is closely related to the genus Chlorella; hence, it is classified as Chlorella sp. MQ-1. This strain exhibited robust growth at Cr(VI) concentrations below 2 mg/L, achieving a removal rate higher than 82% for initial Cr(VI) concentrations between 0.5 and 1 mg/L after a 5-day incubation period. Mechanistic studies revealed that MQ-1 promoted the removal of Cr(VI) mainly through intracellular bioreduction and bioaccumulation processes, in which more than 60% of Cr(VI) was reduced to the less toxic Cr(III) and stocked in the cells. A two-stage cultivation strategy, involving initial biomass accumulation followed by Cr(VI) treatment, significantly enhanced the removal efficiency, which was further accelerated under illuminated conditions. Notably, MQ-1 cultures with initial OD680 values of 4 and 6 accomplished 84.28% and 91.31% Cr(VI) removal from 2 mg/L solutions, respectively, within 30 hours under light exposure. These findings highlight the potential of MQ-1 to utilize renewable solar energy to reduce Cr(VI) and to mitigate the risk of its re-release into the environment. This characteristic positions MQ-1 as a potentially sustainable and cost-effective solution for Cr(VI) remediation and suggests its significant potential for large-scale implementation in bioremediation strategies aimed at Cr(VI)-contaminated waters.

Dentinal tubule occlusion effects of dipotassium oxalate and diode laser combination: a single-blind in vitro study.

Dentin hypersensitivity (DH) affects many patients. Various therapeutic options have been devised to alleviate this condition by achieving dentinal tubules (DT) occlusion. This research aimed to investigate the effects of dipotassium oxalate-containing mouthwash, diode laser and their combination on DT occlusion. Forty dentin samples were obtained from 20 human single-rooted third molars, 40 dentin specimens were obtained, and exposed DT were created in vitro. They were assigned into four groups: Group 1 (n = 10), the control group where no treatment was applied; Group 2 (n = 10), a mouthwash with a 1.4% dipotassium oxalate was applied twice for 60s during a 5-day period in a shaker at 100rpm; Group 3 (n = 10), a combination of the same mouthwash and an 810nm diode laser at an output power of 0.25W in continuous mode was applied for 60s without contact at a distance of 3-4mm; and Group 4 (n = 10), only a diode laser with the same protocol was applied. Occlusion of the DT was observed by scanning electron microscopy. The analysis revealed occlusion of the DT in all treatment groups; however, the effects were more pronounced in the combined treatment group (Group 3). Compared with the test groups, the control group had significantly more open DT in 100 µm2 (p < 0.01). The difference between the Group 2 and Group 4 was not significant (p > 0.05). DT occlusion was achieved via the use of a mouthwash containing 1.4% dipotassium oxalate and an 810nm diode laser. However, the combination resulted in the greatest results and therefore may be utilized in individuals with DH.

Silymarin attenuates oxidative stress and pathological changes induced by salinomycin in adult male rabbits

AbstractFeed additives are used in animal husbandry to prevent diseases and enhance growth rates. Salinomycin sodium (SAL) is an approved feed additive for rabbit fattening diets, typically administered at a dosage of 20–25 mg/kg feed with a 5-day withdrawal period. However, the misuse or abuse of SAL can result in toxicity in rabbits. This study aimed to evaluate the adverse effects of SAL administration in different organs for the first time and the protective role of silymarin in rabbits. Seven groups of rabbits were randomly allocated. The control group received no additives. The second and third groups received rations with 20 mg SAL/kg and 40 mg SAL/kg, respectively. The fourth and fifth groups received the same SAL doses with silymarin at 6.5 mg/kg body weight (bw) and 13 mg/kg bw, respectively. The sixth and seventh groups were administered silymarin alone at 6.5 mg/kg bw and 13 mg/kg bw, respectively. Rabbits were euthanized and slaughtered on day 29 following the Halal method. SAL at 20 mg/kg ration caused mild to moderate pathological changes compared to the control group, while 40 mg SAL/kg ration induced severe pathological changes. However, silymarin supplementation, alone or with SAL, improved organs histology. Both silymarin doses (6.5 mg/kg bw and 13 mg/kg bw) mitigated SAL's harmful effects. In conclusion, this study highlights the potential detrimental effects of SAL toxicity on different organs in rabbits. The supplementation of silymarin reduced and prevented these hazardous effects. These findings emphasize the promising role of silymarin as a protective agent against SAL-induced toxicity in rabbits.

Investigation of mutagenicity of styrene in tumor target and non-target tissues of transgenic Big Blue® mice.

Styrene has been shown to induce lung tumors in mice, but not in rats. The current study investigated the potential role of genotoxicity as an initial key event in the mode of action for styrene-induced lung tumors in mice. Transgenic male B6C3F1 Big Blue® mice were treated by oral gavage for 28 consecutive days with 0 (corn oil), 75, 150, or 300 mg/kg/day of styrene. The 300 mg/kg/day represented the tumorigenic dose in the oral gavage carcinogenicity study conducted in B6C3F1 mice. Following a 28-day expression period, mutant frequencies were assessed at the cII locus of the transgene in the tumor target (lung) and non-target tissues (liver, glandular stomach, and duodenum). Mice treated with N-ethyl-N-nitrosourea (40 mg/kg/day) by oral gavage on Days 1, 2, and 3 of the study and sacrificed on Day 56 served as the positive control group. Genomic DNA was extracted from the selected tissues, processed for the recovery of the transgene into infectious phage, plated onto Escherichia coli strain G1250, and incubated at 37°C for titer determination or at 24°C for the selection of mutant plaques. There were no treatment-related increases in mutant frequency in any of the tissues. The positive control group had a significant increase in the frequency of cII mutants assuring the adequacy of the experimental conditions to detect induced mutations. To conclude, mutagenicity is not considered a plausible initial key event in the mode of action for styrene-induced mouse lung tumors as these data support that styrene is not an in vivo mutagen.

Four-Week GLP Immunotoxicity Assessment of Lactoferrin Alpha Produced by Komagataella phaffii in Sprague-Dawley Rats.

Oral toxicity and toxicokinetic properties of human lactoferrin (LF) alpha produced in Komagataella phaffii (effera™) were investigated in adult Sprague-Dawley rats over a 28-day period under good laboratory practice conditions. Main study dosing used groups of 10 rats/sex/dose, and a secondary study evaluating toxicokinetic parameters used 6 rats/sex/dose. The vehicle control group received sodium citrate buffer, test groups received daily doses of 200, 600, and 2000mg of effera™ per kg body weight, and the comparative control group received 2000mg bovine LF (bLF)/kg body weight per day. T-cell-dependent antibody response against keyhole limpet hemocyanin and immunophenotyping of the spleen were performed as measures of immunotoxicity. Clinical observations, body weight, hematology, coagulation, clinical chemistry, urinalysis, immunotoxicity, gross necropsy, and histopathology were assessed. Toxicokinetic parameters were analyzed as an indication of LF bioavailability, and anti-LF antibody assays were conducted to detect antibodies produced against LF to measure immunogenicity. No treatment related toxicologically significant changes were observed. Based on the absence of toxicologically relevant changes, effera™ is well tolerated in rats at doses up to 2000mg rhLF/kg/day, an amount ∼400 times that of the estimated daily intake at the 90th percentile proposed for human adult use.

Tolerance of fry of three tilapia varieties exposed to low temperatures

As tilapia aquaculture expands globally, cold sensitivity remains a critical issue, leading to significant losses due to poor growth, disease susceptibility, and high mortality. This study evaluated the cold tolerance in fry of three tilapia varieties, incorporating a comprehensive analysis of 3240 specimens. The fry, segregated by variety into different tanks, were observed during summer to assess their performance. The study focused on two commercially prominent varieties, known for their rapid weight gain, and a third variety developed by the Federal University of Lavras, specifically bred for resilience to local climatic conditions. Following a 15-day acclimation period in experimental tanks, the fry were monitored for feeding to apparent satiety. Daily assessments included counting mortalities and measuring water temperature and dissolved oxygen levels. Survival data were analyzed using multivariate Cox regression, with survival curves derived via the Kaplan-Meier method. Lifespan predictions from these curves were compared using the log-rank test. Results indicated that older fry were more resilient to cold stress. Notably, the MGTUP variety, bred for local environmental adaptability, demonstrated superior cold tolerance. This variety also exhibited the lowest mortality rates across all age groups. These findings suggest that utilizing locally adapted tilapia varieties can significantly mitigate losses in aquaculture, especially in cold-prone regions.

Pharmacokinetics and Bioequivalence of Two Formulations of Montelukast Sodium Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

Montelukast sodium is a leukotriene type 1 receptor antagonist that can be used for the prophylaxis and treatment of asthma. However, the pharmacokinetics of montelukast sodium tablets (10mg) remain unclear in healthy Chinese subjects. Here, a single-dose randomized, open-label, 2-sequence, and 2-period crossover (7-day washout period between treatments) study was performed to compare the pharmacokinetics and bioequivalence between the test products and the reference at a single dose of 10mg among healthy Chinese subjects under fasting and fed conditions. Blood samples were collected at specified time points to analyze the plasma concentrations of montelukast by a validated liquid chromatography-tandem mass spectrometry method. The results showed that the 90% confidence interval values of the geometric mean ratio of test/reference for the maximum plasma drug concentration, area under the concentration-time curve from time 0 to the end, and area under the concentration-time curve from time 0 to infinity were within the range of 80%-125%. Moreover, both the test and reference formulations were safe and well tolerated, with no occurrence of severe adverse events. These results demonstrate that both the test montelukast sodium tablets and the reference showed similar bioequivalence, safety, and tolerability among healthy Chinese subjects under fasting and fed conditions.

Investigating the Antibacterial, Antioxidant, and Cholesterol-lowering Properties of Yogurt Fortified with Postbiotic of Lactobacillus acidophilus and Lactiplantibacillus plantarum in the Wistar Rat Model.

Postbiotics have gained attention in the food industry due to their functional properties and ease of use compared to their live parent cells. Postbiotics are the metabolic byproducts of probiotic microorganisms, offering advantages such as antimicrobial and anti-diabetic effects. The study aimed to explore the potential antibacterial, antioxidant, and cholesterol-lowering effects of postbiotics from Lactobacillus acidophilus (LA) and Lactiplantibacillus plantarum (LbP) through in vitro and in vivo studies. Freeze-dried postbiotics from L. acidophilus BLAC 258 and L. plantarum were used in yogurt to inhibit foodborne pathogens over a 21-day storage period at 4 °C. The cholesterol-lowering effects of the postbiotic yogurt were assessed in Wistar rats fed with Normal Basal Diet (NBD) and High Cholesterol Diet (HCD). All experiments were performed in triplicate, and the collected data were analyzed with a one-way ANOVA using SPSS v.20 (2021) software. The Tukey Honestly Significant Difference (HSD) test was used for means differences at the 95% confidence interval. The results showed that postbiotic-fortified yogurt exhibited significant antioxidant and antibacterial effects. The antioxidant capacity of the yogurt increasingly peaked at 48.81% on day 14. Also, Listeria monocytogenes counts in the postbiotic yogurt decreased by approximately 2 Log10 on day 3. High-cholesterol-fed rats receiving postbiotic yogurt experienced significant reductions in total cholesterol, triglycerides, and LDL levels. Overall results indicate that postbiotics functional yogurt might be a safe and effective strategy for managing cholesterol levels and inhibiting foodborne pathogens.

Characteristics of Dissolved Organic Matter and Their Role in Membrane Fouling during Simultaneous Sludge Thickening and Reduction Using Flat-Sheet Membranes.

Four parallel simultaneous sludge thickening and reduction reactors using flat-sheet membranes were employed for the aerobic digestion of sludge to explore the characteristics of dissolved organic matter and its membrane fouling effect. During the initial 8 days of using flat-sheet membranes for simultaneous sludge thickening and reduction (MSTR), a notable increase was observed in the concentrations of humic acids and compounds that resemble soluble microbial by-products in the effluent. Subsequently, a fluctuating trend in humic acid levels ensued, accompanied by a gradual decline in soluble microbial by-product-like substances. Post the initial 8-day period, the capillary suction time (CST) rose from approximately 400 seconds to over 800 seconds, the viscosity increased from 20 mPa s to 38 mPa s, and the membrane resistance increased from roughly 6.0+11 m-1 to approximately 9.0e+11 m-1. This phenomenon can be attributed to the clogging of pores by foulants whose size is similar to that of the membrane pores leading to the accumulation and deposition of macromolecules and larger particulates forming gel layers and cake layers. The interplay among diverse microorganisms engenders functional modules, collectively influencing the distribution and characteristics of dissolved organic matter within the MSTR. These microorganisms exert their metabolic effects individually and interact reciprocally, creating synergistic and inhibitory mechanisms. Notably, the synergistic interactions among microorganisms predominated, culminating in an enhanced effluent quality within the system.

Associations among negative weight-related experiences, weight bias internalization, and body-related self-conscious emotions in adolescents: A daily diary study.

The present study examined the between- and within-person associations among negative weight-related experiences, weight bias internalization, and body shame, embarrassment, and pride in adolescents. Participants were 93 Canadian students (Mage = 15.54, 59.10% girls, 40.86% white) who completed a 5-day daily diary study in 2021. Multilevel models were estimated to examine the between- and within-person associations, as well as the cross-level interactions. Fifty-nine negative weight-related experiences were reported from 22 participants (23.66%) over the 5-day study period. Adolescents with higher average negative weight-related experiences (OR = 19.60, 95% CI = 1.90-202.67) and weight bias internalization (OR = 3.66, CI = 2.07-6.46) had greater odds of reporting shame. Similarly, higher average negative weight-related experiences (OR = 16.29, CI = 3.65-72.75) and weight bias internalization (OR = 2.08, CI = 1.53-2.82) was associated with greater odds of embarrassment. No within-person effects were noted, such that reporting more negative weight-related experiences or weight bias internalization than one's own average was not related to body emotions. This distinction underscores that the persistent, rather than episodic, aspects of negative weight-related experiences and weight bias internalization are most impactful on adolescents' body image. These findings have implications for recruitment and screening for individual-level interventions for internalized weight bias and body image, and highlight the need for system-level policies and changes that prohibit negative weight-related experiences and messages to reduce likelihood of internalizing weight bias among adolescents.

EXTH-41. COMBINATION TREATMENT WITH RAF/MEK AND FAK INHIBITION ENHANCES TUMOR GROWTH INHIBITION IN MENINGIOMA

Abstract BACKGROUND Patients with meningiomas who have progressed after multimodal treatments face a significant shortage of viable therapeutic options. Recent advancements in the molecular understanding of meningiomas have identified the FAK and RAF/MEK signaling pathways as potential promising targets for progressive meningiomas. METHODS In vitro, we tested two human meningioma cell lines, IOMM-Lee (NF2 wild-type and CDKN2A loss) and CH157-MN (NF2 mutant). The cells were plated in Matrigel-coated wells, treated with defactinib (FAK inhibitor), VS-6766 (RAF/MEK inhibitor, avutometinib) and the combination over a 7-day period and assessed for cell viability using the CellTiter-Glo 3D assay. In vivo, we tested the efficacy of the FAK inhibitor VS-4718 (possessing favorable pharmacokinetic properties in mice) and RAF/MEK inhibitor VS-6766, both given daily via oral gavage, in athymic nude mice bearing IOMM-Lee or CH157-MN tumors. RESULTS In the matrigel assay, VS-6766 suppressed IOMM-Lee and CH157-MN cells in a dose dependent manner. The drug combination was mostly additive in IOMM-Lee cells. However, CH157-MN cells showed a strong synergistic response across all drug concentrations tested. In the IOMM-Lee flank tumor model, VS-4718 alone had no effect, while VS-6766 alone or in combination significantly reduced tumor growth and extended median survival from 25 days to 47 days (p &amp;lt; 0.05). In the CH157 flank tumor model, VS-4718 monotherapy did not affect tumor growth or survival, but VS-6766 monotherapy slowed tumor growth and increased median survival from 10 days to 31 days (p &amp;lt; 0.001). Combining both drugs further reduced tumor growth and extended median survival to 42 days (p &amp;lt; 0.001). CONCLUSION Treatment with FAK and RAF/MEK inhibitors showed synergistic or combination effects in the NF2 mutant CH157-MN model in vitro and in vivo. RAF/MEK inhibitor monotherapy was effective for the IOMM-Lee model (NF2 wild-type), without clear benefit of combining with the FAK inhibitor. Investigations in intracranial tumor models are underway.