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The ability of children to ask curiosity-driven questions is an important skill that helps improve their learning. For this reason, previous research has explored designing specific exercises to train this skill. Several of these studies relied on providing semantic and linguistic cues to train them to ask more of such questions (also called "divergent questions"). But despite showing pedagogical efficiency, this method is still limited as it relies on generating the said cues by hand, which can be a very long and costly process. In this context, we propose to leverage advances in the natural language processing field (NLP) and investigate the efficiency of using a large language model (LLM) for automating the production of key parts of pedagogical content within a curious question-asking (QA) training. We study generating the said content using the "prompt-based" method that consists of explaining the task to the LLM in natural text. We evaluate the output using human experts annotations and comparisons with hand-generated content. Results suggested indeed the relevance and usefulness of this content. We then conduct a field study in primary school (75 children aged 9-10), where we evaluate children's QA performance when having this training. We compare 3 types of content: (1) hand-generated content that proposes "closed" cues leading to predefined questions; (2) GPT-3-generated content that proposes the same type of cues; (3) GPT-3-generated content that proposes "open" cues leading to several possible questions. Children were assigned to either one of these groups. Based on human annotations of the questions generated, we see a similar QA performance between the two "closed" trainings (showing the scalability of the approach using GPT-3), and a better one for participants with the "open" training. These results suggest the efficiency of using LLMs to support children in generating more curious questions, using a natural language prompting approach that affords usability by teachers and other users not specialists of AI techniques. Furthermore, results also show that open-ended content may be more suitable for training curious question-asking skills.

Abstract An essential role of glial cells is to comply with the large and fluctuating energy needs of neurons. Metabolic adaptation is integral to the acute stress response, suggesting that glial cells could be major, yet overlooked, targets of stress hormones. Here we show that Dh44 neuropeptide, Drosophila homologue of mammalian corticotropin-releasing hormone (CRH), acts as an experience-dependent metabolic switch for glycolytic output in glia. Dh44 released by dopamine neurons limits glial fatty acid synthesis and build-up of lipid stores. Although basally active, this hormonal axis is acutely stimulated following learning of a danger-predictive cue. This results in transient suppression of glial anabolic use of pyruvate, sparing it for memory-relevant energy supply to neurons. Diverting pyruvate destination may dampen the need to upregulate glial glycolysis in response to increased neuronal demand. Although beneficial for the energy efficiency of memory formation, this mechanism reveals an ongoing competition between neuronal fuelling and glial anabolism.

Abstract Extracellular vesicles (EVs) have shown great promise as drug delivery system (DDS). However, their complex and costly production limit their development for clinical use. Interestingly, the plant kingdom can also produce EV-like nanovesicles that can easily be isolated and purified from a large quantity of raw material at a high yield. In this study, olive-derived nanovesicles (ODNVs) were isolated from raw fruits using serial centrifugations and their physical and biological features characterized to demonstrate their promising potential to be used as a DDS. Nanotracking particle analysis indicated an average size of 109.5 ± 3.0 nm and yield of 1012 ODNVs/mL for the purest fraction. Microscopy imaging, membrane fluidity assay and lipidomics analysis showed the presence of a rich lipid bilayer that significantly varied between different sources of ODNVs but showed a distinct signature compared to human EVs. Moreover, ODNVs were enriched in PEN1 and TET8 compared to raw fruits, suggesting an extracellular origin. Interestingly, ODNVs size and yield stayed unchanged after exposure to high temperature (70 °C for 1 h), wide pH range (5–10), and 50–100 nm extrusion, demonstrating high resistance to physical and chemical stresses. This high resistance allowed ODNVs to stay stable in water at 4 °C for a month, or with the addition of 25 mM trehalose for long-term freezing storage. Finally, ODNVs were internalized by both 2D and 3D cell culture without triggering significant cytotoxicity and immunogenicity. Importantly, the anticancer drug doxorubicin (dox) could be loaded by passive incubation within ODNVs and dox-loaded ODNVs decreased cell viability by 90% compared to only 70% for free dox at the same concentration, indicating a higher efficiency of drug delivery by ODNVs. In addition, this high cytotoxicity effect of dox-loaded ODNVs was shown to be stable after a 2-week storage at 4 °C. Together, these findings suggested that ODNVs represent a promising candidate as drug nanocarrier for various DDS clinical applications, as demonstrated by their biocompatibility, high resistance to stress, good stability in harsh environment, and improvement of anticancer drug efficacy.

Abstract Pseudomonas aeruginosa (Pa) and Methicillin susceptible Staphylococcus aureus (MSSA) are the predominant bacteria found in the airways of people with cystic fibrosis (pwCF), significantly contributing to lung disease progression. While various factors influencing the initial acquisition (IA) of these pathogens are known, the impact of environmental conditions remains understudied. This epidemiological study assessed the risk of MSSA and Pa initial acquisitions in relation to seasonality and climatic zones among 1,184 French pwCF under 18 years old. The age at IA for Pa (Pa-IA) and MSSA (MSSA-IA) was estimated using the Kaplan–Meier method. Seasonality and climatic zones were analysed as risk factors using time-varying Cox regression models. The median age at MSSA-IA was notably earlier (2.0 years) than that at Pa-IA (5.1 years). MSSA-IA occurred increasingly younger in more recent birth cohorts, while the age at Pa-IA remained stable over time. The risk of Pa-IA was consistently higher in all seasons compared with spring, peaking in autumn (HR = 1.53), irrespective of climatic zones. In Oceanic and Continental climates, the highest risk for MSSA-IA was in winter (HRs = 1.45 and 1.20 respectively). In the Mediterranean climate, the risk of MSSA-IA was lower in winter compared to spring (HRs = 0.68 and 0.61 respectively), and the median age at MSSA-IA later than for Pa-IA. This study demonstrates that seasonality and meteorological factors may influence acquisition of MSSA and Pa in pwCF. These findings suggest that environmental factors play a role in pathogen acquisition dynamics in CF and could inform the development of preventive strategies.

Abstract Since 2011, holopelagic Sargassum have been massively stranding in the coastal environments of the Caribbean Islands inducing damages to coastal ecosystems, public health and the economy. To limit the risks associated with Sargassum stranding, floating barriers with nets can be placed in front of sensitive areas, to divert Sargassum away from the coast. To evaluate the potential transfer of metallic trace element (MTE) from Sargassum to adjacent marine life, seagrasses (Halophila stipulacea, Thalassia testidinum) and urchin (Lytechinus variegatus) were sampled, both close (0 m) and far (200 m) from barriers installed during 4 years in two bays: Baie Cayol (BC) and Cap Est (CE) in Martinique (FWI). A bay without barriers Baie-Tresor (BT) was also sampled in order to compare the effects of Sargassum accumulated in a natural environment versus an environment with floating barriers. The short-term effects of barriers were evaluated by measuring the evolution of MTE after four days, in the algae (Dictyota spp.), located close to Sargassum accumulations. All sampling was realized during two periods of active (July 2021) and reduced (January 2022) Sargassum stranding. The measured concentrations of 19 metal(loid)s trace elements revealed that the proximity of Sargassum to the barriers did not increase MTE concentration. The absence of increase in MTE was observed all sites (BT, BC and CE) and during periods of limited and important Sargassum stranding. Similarly, translocations of Dictyota close to Sargassum accumulations did not reveal any increase in MTE concentrations in the algae after 4 days. The present study suggests that the use of barriers to manage Sargassum stranding would not constitute an important threat of MTE contamination of marine environments.

This research significantly enhances the applicability of thermoplastic olefins (TPOs) in the automotive industry using supercritical [N.sub.2] as a physical foaming agent, effectively addressing the limitations of traditional chemical agents. It merges experimental results with simulations to establish detailed material-process-microstructure-performance (MP2) relationships, targeting 5-20% weight reductions. This innovative approach labeled digital lifecycle (DLC) helps accurately predict tensile, flexural, and impact properties based on the foam microstructure, along with experimentally demonstrating improved paintability. The study combines process simulations with finite element models to develop a comprehensive digital model for accurately predicting mechanical properties. Our findings demonstrate a strong correlation between simulated and experimental data, with about a 5% error across various weight reduction targets, marking significant improvements over existing analytical models. This research highlights the efficacy of physical foaming agents in TPO enhancement and emphasizes the importance of integrating experimental and simulation methods to capture the underlying foaming mechanism to establish material-process-microstructure-performance (MP2) relationships. Highlights * Establishes a material-process-microstructure-performance (MP2) for TPO foams * Sustainably produces TPO foams using supercritical (ScF) N2 with 20% lightweighting * Shows enhanced paintability for TPO foam improved surface aesthetics * Digital lifecycle (DLC) that predicts both foam microstructure and properties * DLC maps process effects & microstructure onto FEA mesh for precise prediction KEYWORDS automotive Lightweighting, digital lifecycle (DLC), integrated computational materials engineering (ICME), microcellular foaming, microstructure-process-property relationships (MP2), thermoplastic foams, thermoplastic olefins, 1 | INTRODUCTION Given that the global transportation industry is the second highest contributor to climate change, there has been a concerted effort to spearhead research in economic light-weighting technologies; [...]