Search Results (4,045)

Neural progenitor cell (NPC) fate decisions are governed by transcriptional and signaling programmes, yet the epigenetic mechanisms stabilising early neuronal versus glial lineage trajectories remain unresolved. Here, DNA methylation landscapes in two widely used human NPC models—ReNcell VM (RVM) and ReNcell CX (RCX)—were examined under several different culture conditions to define regulatory pathways shaping lineage specification. Exploratory analyses revealed that the ReNcell lines exhibited methylation similar to primary glial populations rather than neuronal subtypes, with RCX cells positioned further along a maturation trajectory and RVM cells retaining a multipotent state. RCX cultures displayed hypomethylation of neuronal markers (DCX, ENO2, MAP2), whereas RVM cultures showed consistent GFAP hypomethylation, indicative of glial or early progenitor identity. Signaling pathways regulating lineage commitment were highlighted, including TGFβ, Wnt, and Notch signaling. Within the Notch pathway, RCX cells exhibited higher gene expression of NOTCH2 and JAG ligands, consistent with active lateral induction and a developmentally advanced state. In contrast, RVM cells exhibited higher DLL1 and NOTCH1 expression, supporting lateral inhibition and cellular heterogeneity. Knockdown of syndecan-4 (SDC4) revealed opposing effects on Notch activity. Together, these findings established DNA methylation as a determinant of lineage-specific signaling in human NPCs. Full article

Background: Community-acquired pneumonia (CAP) in children may be complicated by necrotizing pneumonia (NP), complicated parapneumonic effusion (CPPE), and lung abscess. These complications prolong hospitalization and require medical and surgical intervention. Objectives. To describe clinical course, diagnostic workup, and management of cCAP (complicated CAP) in children admitted to the Women’s and Children’s Health Department, Padua University Hospital, between January 2022 and September 2024. To identify factors associated with disease severity and evaluate outcomes. Methods: All children hospitalized for cCAP during the study period were included. Data collected comprised clinical features, laboratory and imaging findings, medical and surgical management, and outcomes. Results: Forty patients (mean age 4.4 y; 13.15% of pneumonia admission) were included: 67.5% had NP with CPPE, 22.5% isolated effusion, 10% NP without effusion. All patients were febrile at onset, 62.2% had cough, 32.5% abdominal pain, 30% rhinitis. NP was confirmed by contrast-enhanced chest CT. Thirty patients (75%) had positive microbiological testing, mainly Streptococcus pneumoniae and Streptococcus pyogenes. 77.5% required oxygen therapy (five invasive ventilation and one with ECMO). Median fever duration 18 days (IQR 15–27) with elevated CRP (median peak 300 mg/L). Pleural drainage was performed in 66.7%, fibrinolytics in 17.5%, thoracoscopic decortication in 12.5%, and lobectomy in one patient. Radiological resolution occurred at a median of 31 days post-discharge, with normal pulmonary function at a median of 15 months. Conclusions: Despite pediatric cCAP severity, short- and long-term outcomes are favorable. Early recognition and integrated management are crucial, and further prospective studies are warranted to optimize care and identify severity predictors. Full article

Due to the indiscriminate use of antimicrobial drugs in the treatment of infectious diseases, human pathogenic bacteria have developed resistance to many commercially available antibiotics. Medicinal plants such as Convolvulus arvensis represent a renewable resource for the development of alternative therapeutic agents. This study aimed to evaluate the antibacterial activity of silver nanoparticles (AgNPs) biosynthesized from C. arvensis against two clinical antibiotic-resistant bacterial isolates. The pathogenic isolates were identified as Staphylococcus aureus MRSA and Escherichia coli ESBL using 16S rRNA gene sequencing. Silver nanoparticles were synthesized via a green synthesis approach, and their physicochemical properties were characterized using UV–Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, zeta potential, and dynamic light scattering (DLS). The synthesized C. arvensis–AgNPs exhibited a surface plasmon resonance peak at 475 nm and predominantly spherical morphology with particle sizes ranging from 102.34 to 210.82 nm. FTIR analysis indicated the presence of O–H, C–O, C–N, C–H, and amide functional groups. The nanoparticles showed a zeta potential of −18.9 mV and an average hydrodynamic diameter of 63 nm. The antibacterial activity of the biosynthesized AgNPs was evaluated against methicillin-resistant S. aureus (MRSA and ATCC 29213) and E. coli (ESBL and ATCC 25922) using agar diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays. Inhibition zones ranged from 10 to 13 mm, with MIC and MBC values of 12.5–25 µg/mL and 25–50 µg/mL, respectively. In addition, the nanoparticles exhibited antioxidant activity (DPPH assay, IC₅₀ = 0.71 mg/mL) and anti-inflammatory effects as determined by protein denaturation inhibition. No cytotoxic effects were observed in the MCF-7 cell line at the MIC level. These findings suggest that C. arvensis–AgNPs have potential as natural antimicrobial, antioxidant, and anti-inflammatory agents. Full article

Background/Objectives: Maternal immune activation (MIA) increases the risk of Autism Spectrum Disorders (ASD). Experimental models demonstrate that maternal exposure to bacterial endotoxin or the viral mimic polyinosinic:polycytidylic acid [poly (I:C)] reliably recapitulates ASD-like behavioral abnormalities in offspring, yet the underlying neurobiological mechanisms linking MIA to altered neurodevelopment remain incompletely understood. Increasing evidence highlights the placenta as a critical mediator in shaping fetal brain development through immunological and hormonal regulation. Likewise, disruption of placental regulatory functions upon MIA may therefore represent a mechanistic pathway. Here, we investigated how alterations in placental cytokine profiles, innate immune cell composition, and endocrine outputs relate to neuroinflammation and neurogenesis in the offspring. Methods: Pregnant mice at gestational day 12.5 received a single intraperitoneal injection of poly (I:C). Placental macrophages, neutrophils, inflammatory cytokines, and nerve growth factor (NGF) expression were examined 72 h later. Neurodevelopmental outcomes, including microglial activity and neurogenic markers, were evaluated in mouse offspring at postnatal day (P) 1 and 6. Results: MIA induced a significant accumulation of monocytes and neutrophils in the placenta, which was associated with elevated levels of a broad spectrum of inflammatory mediators, including Th17-biased proinflammatory cytokines, chemokines, and adhesion proteins, in the placenta and amniotic fluid. In contrast, the placenta-derived NGF levels were significantly reduced. MIA induced strong and sustained microglial activation in the fetal and neonatal brain. This inflammatory milieu was accompanied by disrupted cortical neurogenesis, characterized by a marked increase in Ki67+ neuronal progenitor cells (NPCs) in the subventricular zone (SVZ), overproduction of early-born Tbr1+ neurons at P1, later-born Satb2+ neurons at P6. Conclusions: Collectively, these findings suggest that heightened Th17 inflammatory signaling, coupled with impaired placental endocrine function, contributes to dysregulated cortical neurogenesis in the offspring. Full article

Greenly synthesised Ni-doped Ag nanoparticles utilising Caralluma umbellata root extracts, and an investigation into their optical properties, biological properties, and characterisation, is the focus of the study. Characterisation was performed using FTIR analysis, UV-Vis, X-ray diffraction, and field emission scanning electron microscopy. The synthesis of Ni-doped Ag nanoparticles was confirmed through UV-Vis spectroscopy, revealing a peak at 396 nm and a band gap energy of 3.24 eV. XRD analysis revealed a face-centred cubic structure with a crystallite size of 55.22 nm (as-prepared) and 18.56 nm (annealed at 200 °C). Reduction and capping were demonstrated by FTIR, as evidenced by the presence of phytochemicals. The Ag NPs demonstrated potent antibacterial activity against both Gram-positive and Gram-negative bacteria, with a minimal inhibitory concentration of 1.25 μg/mL observed against Streptococcus mutans. Their vigorous anti-oxidant activity, as well as in vitro anti-diabetic potential through alpha-amylase and alpha-glucosidase inhibition, also proves suitable for biomedical applications. Full article

Soil extracellular enzyme activity reflects microbial resource acquisition and metabolic efficiency. However, applying enzyme stoichiometry to explore microbial metabolic limitations and carbon use efficiency (CUE) in rhizosphere and bulk soils under saline conditions remains limited. In this study, rhizosphere and bulk soils of Tamarix austromongolica were sampled along a salinity gradient in the Yellow River Delta to assess microbial metabolic limitation and CUE. Results showed that increasing salinity intensified microbial metabolic limitations and markedly reduced CUE, identifying salinity as the dominant factor constraining microbial efficiency. Rhizosphere soils consistently exhibited phosphorus limitation, whereas bulk soils shifted from balanced N–P limitation to pronounced N limitation with increasing salinity. Despite stronger microbial C limitation, CUE remained significantly higher in the rhizosphere than in the bulk soils, suggesting that continuous carbon inputs and enhanced enzyme activity partially mitigated salinity-induced stress. These findings highlight the complex interplay between salinity stress and rhizosphere effects in regulating microbial nutrient acquisition and carbon metabolism. Overall, this study demonstrates the utility of enzyme stoichiometry for evaluating microbial functional adaptation in saline habitats and provides insights that may contribute to the theoretical basis for vegetation restoration in saline-alkali ecosystems. Full article

Folate receptor alpha is expressed at low levels in normal tissues, but is elevated in aggressive breast cancer types and can be utilized for targeted nanoparticle delivery. Hence, we prepared a hybrid nanocarrier based on in-house synthesized mesoporous silica nanoparticles (MSNs) which were further lipid-coated and reinforced with folic acid (FA). Thorough physicochemical evaluation was performed including dynamic light scattering (DLS), powder x-ray diffraction (PXRD), thermogravimetric analysis (TGA), and nitrogen physisorption. In vitro dissolution of the model drug doxorubicin was carried out in release media with pH 7.4 and pH 5.5. The cytotoxic potential and cellular uptake were investigated in MCF-7 breast cancer cells via the MTT assay, doxorubicin fluorescence measurement, and microscopy. The potential amelioration of doxorubicin’s cardiotoxicity was evaluated in vitro on the H9c2 cell line. The results showed MSNs with significant pore volume (1.38 cm³/g) and relatively small sizes (98.05 ± 1.34 nm). The lipid coat and FA attachment improved the physicochemical stability and sustained release pattern over 24 h. MSNs were non-toxic, while when doxorubicin-loaded, they caused moderate cytotoxicity. The highest cytotoxic activity was observed with folate-functionalized, doxorubicin-loaded nanoparticles (NPs). Even though non-loaded folate-functionalized NPs exhibited significant cytotoxicity, their physical mixture with doxorubicin was inferior in MCF-7 cytotoxicity as opposed to the corresponding loaded nanocarrier. Fluorescence-based quantification showed a higher intracellular accumulation of doxorubicin when delivered via NPs. These results demonstrate the potential to use folate-functionalized NPs as carriers for doxorubicin delivery in breast cancer cells. Its cardiotoxicity was significantly reduced in the case of loading onto the folic acid-functionalized lipid-coated MSNs. All these findings provide a promising proof-of-concept, although further experimental validation, particularly regarding targeting selectivity and safety, is required. Full article

Background/Objective: Osimertinib (OSI) is a third-generation tyrosine kinase inhibitor approved for non-small cell lung cancer (NSCLC) therapy. OSI is administered orally; this route limits the amount of OSI reaching the tumor in the lungs and is associated with serious systemic toxicity. This study aimed to develop a dry powder inhalable formulation to provide tumor-targeted delivery and minimize systemic toxicity. To the best of our knowledge, this is the first study to prepare and evaluate a dry powder inhalation formulation of OSI. Methods: Chitosan-coated PLGA nanoparticles (PLGA-C NPs) encapsulating OSI were prepared using a single emulsion-solvent evaporation technique. PLGA-C NPs were assembled into respirable nanocomposite microparticles (NCMPs) via spray drying with L-leucine as a carrier. PLGA-C NPs were characterized for particle size, zeta-potential, encapsulation efficiency, and in vitro efficacy in A-549 cell line. NCMPs were evaluated for solid-state properties, aerosolization performance, stability and in vitro release. Results: PLGA-C NPs exhibited a particle size of 145.18 ± 3.0 nm, high encapsulation efficiency and a positive zeta potential. In vitro studies demonstrated a 3.6-fold reduction in IC50 compared to free OSI, superior antimigratory effects and enhanced cell cycle arrest. Solid-state characterization of NCMPs demonstrated drug encapsulation in the polymer without chemical interaction. NCMPs exhibited excellent aerosolization (mass median aerodynamic diameter of 1.09 ± 0.23 μm, fine particle fraction of 73.48 ± 8.6%) and sustained drug release (61.76 ± 3.9% at 24 h). Stability studies confirmed the physicochemical stability integrity. Conclusions: These findings suggest that this novel dry powder inhalable OSI formulation may improve therapeutic outcomes while reducing systemic toxicity. Full article

The rapid proliferation of misinformation on social media underscores the urgent need for scalable digital-literacy instruction. This study presents the design and evaluation of a Generative AI-enhanced serious game system that integrates Large Language Models (LLMs) to drive adaptive non-player characters (NPCs). Unlike traditional scripted interactions, the system employs role-based prompt engineering to align real-time AI dialogue with the Currency, Relevance, Authority, Accuracy, and Purpose (CRAAP) framework, enabling dynamic scaffolding and authentic misinformation scenarios. A mixed-method experiment with 60 undergraduate students compared this AI-driven approach to traditional instruction using a 40-item digital-literacy pre/post test, the Intrinsic Motivation Inventory (IMI), and open-ended reflections. Results indicated that while both groups improved significantly, the game-based group achieved larger gains in credibility-evaluation performance and reported higher perceived competence, interest, and effort. Qualitative analysis highlighted the HCI trade-off between the high pedagogical value of adaptive AI guidance and technical constraints such as system latency. The findings demonstrate that Generative AI can be effectively operationalized as a dynamic interface layer in serious games to strengthen critical reasoning. This study provides practical guidelines for architecting AI-NPC interactions and advances the theoretical understanding of AI-supported educational informatics. Full article

Spinal cord injury (SCI) remains one of the most formidable challenges in regenerative medicine, often resulting in permanent loss of motor, sensory, and autonomic function. Cell-based therapies offer a promising path toward repair by providing donor neurons and glia capable of integrating into host circuits, modulating the injury environment, and restoring function. Early studies employing fetal neural tissue and neural progenitor cells (NPCs) have demonstrated proof-of-principle for survival, differentiation, and synaptic integration. More recently, pluripotent stem cell (PSC)-derived donor populations and engineered constructs have expanded the therapeutic repertoire, enabling precise specification of interneuron subtypes, astrocytes, and oligodendrocytes tailored to the injured spinal cord. Advances in genetic engineering, including CRISPR-based editing, trophic factor overexpression, and immune-evasive modifications, are giving rise to next-generation donor cells with enhanced survival and controllable integration. At the same time, biomaterials, pharmacological agents, activity-based therapies, and neuromodulation strategies are being combined with transplantation to overcome barriers and promote long-term recovery. In this review, we summarize progress in designing and engineering donor cells and tissues for SCI repair, highlight how combination strategies are reshaping the therapeutic landscape, and outline opportunities for next-generation approaches. Together, these advances point toward a future in which tailored, multimodal cell-based therapies achieve consistent and durable restoration of spinal cord function. Full article

The development of functional polymer films on porous paper substrates is inherently constrained by substrate-induced defects that hinder film continuity and barrier performance. In this study, process-controlled amylose–Poly(Vinyl alcohol) (PVA) coatings incorporating ZnO nanoparticles (ZnO NPs) were fabricated via aqueous deposition to investigate the process-structure-property relationship governing oxygen barrier behavior on paper. The moisture resistance of the coating was also evaluated. Single-layer coatings exhibited severe barrier failure due to insufficient film formation and pervasive pinhole defects. In contrast, systematic multi-layer deposition enabled the formation of continuous polymer films. A pronounced non-linear reduction in oxygen transmission rate was observed once the dry coating thickness exceeded approximately 5 µm. Under these conditions, the oxygen transmission rate decreased to approximately 15 cc/m²·day·atm at 20 °C and 65% relative humidity. This transition was correlated with the elimination of substrate-induced defects, as confirmed by morphological analysis. In addition to enhanced barrier performance, ZnO NP-loaded coatings demonstrated strong and broad-spectrum antimicrobial activity against both Escherichia coli and Staphylococcus aureus, indicating their multifunctional potential for active packaging applications. Supporting evaluations further indicated adequate mechanical flexibility and high repulpability, highlighting the suitability of the coating for sustainable paper-based packaging. Overall, this work identifies a quantitative critical film thickness that serves as process-specific design guideline for engineering high-performance functional polymer coatings on porous paper substrates. Full article

Thorium carbide (${\mathrm{ThC}}_{2\pm x}$) nano-structured thin disc-like pellets were produced from thoria nanoparticles (${\mathrm{ThO}}_2$-NP) and multi-walled carbon nanotubes (MWCNT). These composites are to be studied as a target material candidate for radioactive ion beam (RIB) production via nuclear reactions upon impact with high-energy proton beams on a stack of solid pellets. The ${\mathrm{ThO}}_2$-NP precursor was produced via precipitation of thorium oxalate from a thorium nitrate solution with oxalic acid and subsequent hydrothermal oxidation of the oxalate, creating the thoria nanoparticles. The ${\mathrm{ThO}}_2$-NP were then mixed with MWCNT in isopropyl alcohol and sonicated by two different methods to create a nanoparticle dispersion. This dispersion was then heated under medium vacuum to evaporate the solvent; the resulting powder was pressed into pellets and taken to an inert-atmosphere oven, where it was heated to 1650 °C and carbothermally reduced to ${\mathrm{ThC}}_{2\pm x}$. The resulting pellets were characterized via XRD, SEM-EDS, and Raman spectroscopy. The resulting thorium pellets exhibited, at most, trace levels of the oxide precursor. Furthermore, the nanotube structures were still present in the final product and are expected to contribute positively towards faster radioisotope release times by lowering isotope diffusion times, which is required for the efficient extraction of the shortest-lived (<1 s half-life) radioisotopes. Full article

Since the molecular mechanisms underlying sex determination in Procambarus clarkii are still unclear, it is important to investigate the genetic basis of sex determination in crustaceans. Currently, the molecular mechanisms of sex determination and the gender-specific markers in this species remain poorly understood. In this study, a total of 14,046,984 SNPs and 2,160,652 InDels were identified through genome-wide resequencing of 89 individuals (45 females and 44 males). Further analysis confirmed that the candidate chromosome was Chr38, the sex determination system was identified as XY, and the sex determination region was located at Chr38: 6,000,000–21,100,000 bp. A pair of sex-specific molecular markers has been identified based on a 21 bp female-specific insertion within the candidate sex-determining region. Additionally, SOAT, NPC1, PTGS2, FANCD1, and VAlRS were identified as candidate sex-determining genes through the screening of candidate genes and RT-qPCR validation analysis. These findings provide a robust foundation for investigating sex-determining mechanisms in crustaceans. Through the integration of genome-wide association studies (GWAS), selection signals, and transcriptome analysis, we identified, for the first time, genes associated with sex determination, growth, and immunity. These genes represent promising candidates for further functional studies and genetic improvement in Procambarus clarkii. Full article

Most of the existing Virtual World (VW)-based curriculum-related educational systems use conventional non-player characters (NPCs) to interact with users, represented as avatars, to guide and help them to accomplish learning activities. Also, a few of them use some kind of gamification and keep data for user interactions and activities, and even fewer allow for real-time tutor intervention. In this paper, we present the design, implementation, and evaluation of an educational system based on VW technology, which employs gamification features; two types of NPCs, one conventional and another LLM-based; and a database that stores, apart from educational information, information about the interactions users have with NPCs. Furthermore, we designed and implemented a learning management unit for online-tutor tracing and for supporting the learning progress of users. The evaluation of the system, via experimental use and questionnaires, shows that both types of NPCs were useful for different reasons, although there was a preference for the LLM-based NPC. LLM-based NPCs made dialogues more interesting and were perceived as more friendly and helpful, but conventional ones provided more targeted help. However, both were less interesting than the two gamification features: a scoring system and quizzes. Additionally, the effectiveness of the tutoring system was confirmed in terms of learning outcomes and overall experience, although in a subjective manner. Finally, online-tutor support was recognized as a very positive capability. Full article

Background: Irisin, a muscle-derived hormone, enhances the energy metabolism by activating the brown adipose tissue and acts as a bone-forming agent across the entire life span. No consistent clinical data in humans have been published so far to highlight if blood irisin as glucose/bone biomarker should be refined based on the vitamin D status (deficient or sufficient). Therefore, we aimed to objectively assess the level of irisin in female adults with abnormal and normal vitamin D status, as reflected by the level of 25-hydroxyvitamin (25OHD) in relationship with glucose and bone metabolic parameters. Methods: This pilot, prospective, exploratory study included eighty-nine menopausal women aged over 50. We excluded subjects with malignancies, bone and metabolic disorders, insulin treatment, and active endocrine disorders. Fasting profile included glycaemia, insulin, and glycated haemoglobin A1c (HbA1c). Then, 75 g oral glucose tolerance test (OGTT) included glycaemia and insulin assay after 60 and 120 min. Bone status involved bone turnover markers and central dual-energy X-ray absorptiometry providing bone mineral density (BMD) and trabecular bone score. Results: Eighty-nine subjects were included in the following two groups depending on 25OHD: vitamin D-deficient (VDD) group (N = 48; 25OHD < 30 ng/mL) and vitamin D-sufficient (VDS) group (N = 41; 25OHD ≥ 30 ng/mL). The two groups had similar age and menopausal period (62.29 ± 10.19 vs. 63.56 ± 8.16 years, respectively; 15.82 ± 9.55 vs. 16.11 ± 9.00 years, p > 0.5 for each). A statistically significant higher body mass index (BMI) was found in VDD vs. VDS group (32.25 ± 5.9 vs. 28.93 ± 4.97 kg/m², p = 0.006). Circulating irisin was similar between the groups as follows: median (IQR) of 91.85 (44.76–121.76) vs. 71.17 (38.76–97.43) ng/mL, p = 0.506. Fasting profile and OGTT assays showed no between-group difference. Median HOMA-IR in VDD group pointed out insulin resistance of 2.67 (1.31–3.29). Lowest mean/median T-scores at DXA for both groups were consistent with osteopenia category, but they were confirmed at different central sites as follows: femoral neck in both groups [VDD versus VDS group: −1.1 (−1.20–−0.90) vs. −1.1 (−1.49–−0.91), p = 0.526, respectively], only at lumbar spine for VDS group (T-score of −1.18 ± 1.13). The correlations between irisin and the mentioned parameters displayed a different profile when the analysis was performed in the groups with different 25OHD levels. In VDD group, irisin levels statistically significantly correlated with serum phosphorus (r = −0.32, p = 0.022), osteocalcin (r = −0.293, p = 0.038), P1NP (r = −0.297, p = 0.04), HbA1c (r = 0.342, p = 0.014), and BMI (r = 0.408, p = 0.003). Conclusions: This pilot study brings awareness in the analysis of irisin in relationship with glucose and bone-related biomarkers correlates, showing a distinct type of association depending on 25OHD level, which might represent an important crossroad in the multitude of irisin-activated signal transduction pathways. Full article