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Perfluorooctane sulfonate (PFOS), a persistent environmental pollutant, is associated with cognitive dysfunction through mechanisms involving neuroinflammation, oxidative stress, and metabolic disruption. Icaritin, a bioactive flavonoid with antioxidant and anti-inflammatory properties, exhibits therapeutic potential, though its efficacy against PFOS-induced cognitive impairment remains unexplored. Herein, a mouse model of PFOS-induced cognitive dysfunction was established and treated with oral ICT. Integrated 16S rRNA sequencing and untargeted metabolomics revealed that ICT restored gut microbial homeostasis by enriching beneficial genera (e.g. Akkermansia, Lactobacillus) and reducing ammonia-producing bacteria (e.g. Proteus, Helicobacter, Escherichia), thereby improving gut barrier integrity. Metabolomic profiling identified significant perturbations in ammonia-related pathways, particularly arginine and proline metabolism, underscoring ammonia dysmetabolism as a pivotal mediator of PFOS neurotoxicity. These modifications attenuated systemic and cerebral ammonia accumulation, mitigated neuroinflammation and oxidative stress, and ultimately improved cognitive function. Our findings elucidate ammonia dysmetabolism as a central mechanism in PFOS-induced cognitive decline and highlight the microbiota-gut-brain axis as a promising therapeutic target. This study provides a mechanistic foundation for targeting microbial and metabolic pathways in environmental neurotoxicity.

Metabolic and immune development in neonates are shaped by the succession of the gut microbiome. Maternal obesity can perturb this process by altering interactions of human milk bioactive elements, including oligosaccharides (HMOs), microbial populations, and metabolites. We conducted a longitudinal study of Mexican mother-infant dyads to examine maternal BMI-associated variations in HMOs and infant fecal microbiota. Breastmilk samples from 97 mothers were collected at 48 h, one month, and three months postpartum. We used targeted and untargeted metabolomics to profile breastmilk samples, while shotgun metagenomics was used to analyze infant fecal microbiome composition in a subset of samples. Mothers with obesity showed decreased concentration of key HMOs shortly after birth, correlating with an altered succession of their infant's gut microbiota. This included reduced early colonizers (Enterobacteriaceae) and increased abundance of intermediate and late colonizers (Bifidobacterium and members of the Lachnospiraceae family), over subsequent months. These taxa negatively correlated with HMOs such as 6'SL, LNnT, and LNT. Additionally, functional profiling revealed alterations in metabolic pathways related to polyamine biosynthesis, suggesting changes in microbial metabolism linked to maternal BMI. Despite the cohort's size, our study offers unique insights into the relationship between maternal obesity, HMO composition, and early infant microbial colonization in Latin-American mothers. This exploratory research serves as proof of concept, underscoring the need for larger-scale studies to validate these findings and better understand their implications for infant health. More importantly, our results highlight the interplay between maternal BMI and human milk bioactives, underscoring the importance of correlating microbial succession with maternal metabolic health to better understand early immune development in neonates.

Glioblastoma (GBM) is the most common primary central nervous system tumor with a dismal prognosis and limited treatment options. Recent success utilizing immunotherapies for treating other solid tumors have been largely unsuccessful in GBM. One of the primary mechanisms of GBM immunotherapeutic resistance is because of excessive infiltration of myeloid cells that create an immunosuppressive tumor microenvironment (TME). Among these infiltrating myeloid cells, tumor-associated macrophages (TAMs), comprise a substantial portion of the TME and are associated with poor prognosis in GBM patients. Researchers have only recently begun to dissect the dynamics and complexity of TAMs. However, reliable and reproducible translational methods for generating GBM TAMs in vitro are lacking. Here, we have investigated an in vitro, reproducible murine-based model for bone marrow-derived, glioma-educated macrophages (gTAMs) and performed rigorous analysis to expand our understanding of gTAMs to provide a validated tool for investigating therapeutic response.

Globally, childhood immunization remains a major public health concern, with 19.4 million children not fully vaccinated in 2018, the majority from low- and middle-income countries. Ethiopia, in particular, reports alarmingly low immunization coverage, with nearly one million children unvaccinated and vaccine-preventable diseases accounting for approximately 16% of childhood mortality. This study aimed to examine the spatiotemporal distribution and associated factors of immunization among children aged 12-23 months in Ethiopia. Data were obtained from four rounds of the Ethiopia Demographic and Health Survey (EDHS) conducted between 2000 and 2016, comprising a sample of 6767 children. Spatial analysis was performed using ArcGIS, and statistical analysis was carried out using SAS software. The spatial partial proportional odds model was used due to the violation of the proportional odds assumption. Full immunization coverage showed a gradual increase from 14.6% in 2000 to 39.4% in 2016. Spatial clustering of immunization coverage was observed in all survey years, indicating nonrandom distribution across regions. Children born to mothers with primary education were significantly more likely to be fully vaccinated than those whose mothers had no education. The model identified several significant predictors of immunization status, including region, residence, maternal education, religion, household wealth, maternal employment, place of delivery, antenatal care, and health worker visits. A significant negative spatial auto-covariance suggested that areas with low coverage were often surrounded by higher-coverage zones. Targeted interventions, particularly in identified hotspot areas, and increased public health education are recommended, along with further research using recent data.

Very short answer questions (VSAQs) have gained attention for their superior psychometric properties compared to multiple-choice questions (MCQs). While VSAQs require knowledge recall, MCQs primarily involve knowledge recognition. This difference in cognitive processes may lead to varying cognitive workloads, defined as the amount of mental processing in working memory. Previous studies have not demonstrated consistent differences, likely due to reliance on self-reported measures. Eye tracking provides objective, process-level indicators of cognitive workload. This study investigated whether answering VSAQs requires a higher cognitive workload than answering MCQs. In a within-subject randomized crossover experiment, sixth-year medical students answered both VSAQs and MCQs. Cognitive workload was measured using screen-based eye tracking, focusing on the number of fixations and revisitations as objective indicators of mental effort. Data were analyzed using mixed-effects models. Thirty-four medical students participated, yielding 1,326 observations, which is the multiplication of the number of students by the number of questions (39 questions). Mixed-effects models showed a significant effect of question type on both workload indicators: VSAQs elicited more fixations and revisitations than MCQs (β_std = 0.30-0.39, p < .001). This effect remained after controlling for accuracy. Incorrect answers were associated with higher workload (β_std = -0.15--0.16, p < .01). Heatmaps confirmed these findings, showing denser fixations on key diagnostic features for VSAQs and on answer options for MCQs. Answering VSAQs imposed a higher cognitive workload than MCQs. The presence of answer options in MCQs may reduce workload by providing unintentional cues, while VSAQs require active retrieval. Eye tracking proved valuable for distinguishing cognitive workload across assessment formats.

Interleukin (IL)-1β is known to promote lung cancer growth in both humans and mice. However, in the context of the current standard of care, which includes chemotherapy and immune checkpoint inhibitors, IL-1β can overcome resistance.

Mesoporous silica nanoparticles (MSNs) have garnered significant attention across various disciplines, including chemistry, physics, and materials science, owing to their distinctive properties and functionalities. Numerous studies have demonstrated that MSNs possess several advantageous characteristics, such as tunable pore sizes, excellent biocompatibility, and a high specific surface area. These attributes render mesoporous silica nanoparticles promising for diverse applications in medical fields, including in vivo targeting, drug delivery, and disease diagnosis. Nevertheless, recent research has indicated that mesoporous silica may induce cellular and tissue toxicity in humans, necessitating further evaluation of its long-term safety. Additionally, parameters such as the shape, particle size, and surface modification of MSNs require careful control to enhance their biodegradability, regulate the circulation time of nanomaterials within the body, and mitigate the immunogenicity of mesoporous silica, thereby facilitating the clinical translation of mesoporous silica nanoparticles. This article reviews the advancements in research concerning the use of mesoporous silica nanomaterials in targeted therapy, drug delivery, and tissue engineering. This work evaluates the potential applications of mesoporous silica materials in the biomedical sector and delineates future research directions for MSNs by examining and summarizing their biological toxicity and associated risks.

Maternal services and policies are initiated, envisioned and established under a colonial premise. Cheko Gǫįtì (gift of the child) is an effort to analyze and document how maternal care programs and policies affect maternal child services in 4 communities of the Northwest Territories (NT). Two frameworks were adapted, 2-eyed seeing and analyzing public policies. These frameworks guided the research process (community engagement, data collection and analysis and knowledge mobilization). The findings are grouped under the policy dimensions of effectiveness, unintended effects, equity, cost, feasibility and acceptability. What we learned informed our recommendations towards decolonizing the predominant westernized system.

Nuclear trafficking is essential for cellular function and biomedical applications such as nucleus-targeted drug delivery; however, how passive nuclear transport varies across cell types and phenotypic states remains poorly understood. Here, we investigate passive nuclear transport of fluorescent molecular cargoes spanning 500-20,000 Da across multiple cell lines. We observe cell-line-specific nuclear restrictions and find that passive nuclear uptake does not exhibit a monotonic dependence on molecular weight, suggesting non-Fickian transport behavior. Furthermore, transforming a healthy breast cell model into an invasive-like phenotype via TGF-Beta treatment significantly altered passive nuclear transport characteristics, closely resembling those of a well-established invasive breast cancer cell line. These phenotype-dependent changes in nuclear permeability provide new insight into fundamental biophysical alterations associated with cancerous cellular transformation.

Commensal bacteria have been a centerpiece for understanding interkingdom impacts on viral replication. Multiple groups have investigated the roles commensal bacteria played in regulating enteric virus infection and it has been found that the mechanisms through which this regulation occurs varies between the viruses and bacteria explored. For noroviruses, commensal bacteria enhance or suppress viral infection in a region-dependent manner. Recently, it was found that the extracellular vesicles (EVs) produced by commensal bacteria can suppress norovirus infection. In this study, we used murine norovirus (MNV) to probe the immunological mechanisms induced by bacterial EVs. Global analysis of gene expression pointed to induction of cytosolic DNA pathways; thus, we evaluate the DNA content packaged within the bacterial EVs and DNA-sensing pathways that activate type I interferons (IFN), including STING and TLR9. Our results showed that loss of sting or tlr9, significantly decreased IFNβ production and recovered MNV replication in the presence of bEVs. Collectively, these data demonstrated bEVs of certain gram-negative bacteria can initiate antiviral DNA-mediated type I IFN production pathways and that these pathways are involved in the suppression of MNV replication. These findings expose novel mechanisms through which the native microbiota aids the host in controlling an enteric viral infection and offers a fresh perspective on interkingdom host‒microbiota interactions.