Search Results (40,638)

The effective suppression of inflammation using disease-modifying therapies is essential in the treatment of multiple sclerosis (MS). Anti-CD20 monoclonal antibodies are commonly used long-term as maintenance therapies, largely due to the lack of reliable biomarkers to guide dosing and evaluate treatment response. However, prolonged use increases the risk of infections and other immune-mediated side effects. The unique ability of brain-derived blood extracellular vesicles (EVs) to cross the blood–brain barrier and reflect the central nervous system (CNS) immune status has sparked interest in their potential as biomarkers. This study aimed to assess whether blood-derived L1CAM⁺ EVs could serve as biomarkers of treatment response to rituximab (RTX) in patients with relapsing-remitting MS (RRMS). Serum samples (n = 25) from the baseline (month 0) and after 6 months were analyzed from the RTX arm of the ongoing randomized clinical trial OVERLORD-MS (comparing anti-CD20 therapies in RRMS patients) and were compared with serum samples from healthy controls (n = 15). Baseline cerebrospinal fluid (CSF) samples from the same study cohort were also included. EVs from both serum and CSF samples were characterized, considering morphology, size, and concentration, using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The immunophenotyping of EV surface receptors was performed using flow cytometry with the MACSPlex exosome kit, while label-free quantitative proteomics of EV protein cargo was conducted using a proximity extension assay (PEA). TEM confirmed the presence of EVs with the expected round morphology with a diameter of 50–150 nm. NTA showed significantly higher concentrations of L1CAM⁺ EVs (p < 0.0001) in serum total EVs and EBNA1⁺ EVs (p < 0.01) in serum L1CAM⁺ EVs at baseline (untreated) compared to in healthy controls. After six months of RTX therapy, there was a significant reduction in L1CAM⁺ EV concentration (p < 0.0001) and the downregulation of TNFRSF13B (p = 0.0004; FC = −0.49) in serum total EVs. Additionally, non-significant changes were observed in CD79B and CCL2 levels in serum L1CAM⁺ EVs at baseline compared to in controls and after six months of RTX therapy. In conclusion, L1CAM⁺ EVs in serum showed distinct immunological profiles before and after rituximab treatment, underscoring their potential as dynamic biomarkers for individualized anti-CD20 therapy in MS. Full article

Fumonisin B1, deoxynivalenol (DON), and zearalenone (ZEA) are toxic secondary metabolites produced by Fusarium molds. These mycotoxins are common food and feed pollutants and represent a risk to human and animal health. Although the mycotoxins produced by this genus can cross the blood–brain barrier in many species, their effect on neuronal function remains unclear. We investigated the cell viability effects of these toxins on specified neural cell types, including mouse primary neuronal, astroglial, and mixed-cell cultures 24 or 48 h after mycotoxin administration. DON decreased cell viability in a dose-dependent manner, independent of the culture type. Fumonisin B1 was toxic in pure neuronal cultures only at high doses, but toxicity was attenuated in mixed and pure astroglial cultures. ZEA had significant effects on all culture types in 10 nM by increasing cell viability and network activity, as revealed by multi-electrode array measurements. Since ZEA is a mycoestrogen, we analyzed the effects of ZEA on the expression of estrogen receptor isotypes ERα and ERβ and the mitochondrial voltage-dependent anion channel via qRT-PCR. In neuronal and mixed cultures, ZEA administration decreased ERα expression, while in astroglial cultures, it induced the opposite effect. Thus, our results emphasize that Fusarium mycotoxins act in a cell-specific manner. Full article

Plastic pollution has recently become a serious environmental problem, since the continuous increase in plastic production and use has generated enormous amounts of plastic waste that decomposes to form micro- and nanoparticles (MPs/NPs). Recent evidence suggests that nanoplastics may be potent toxins because they are able to freely cross biological barriers, posing health risks, particularly to developing organisms. Therefore, the aim of the current study was to investigate the toxic potential of polystyrene nanoparticles (PS-NPs) on the jejunum of immature rats. Two-week-old animals were orally exposed to environmentally relevant dose of small PS-NPs (1 mg/kg b.w.; 25 nm) for 3 weeks. We detected a significant accumulation of PS-NPs in the epithelium and subepithelial layer of the intestine, which resulted in significant changes in the expression of genes related to gut barrier integrity, nutrient absorption, and endocrine function. Moreover, increased expression of proinflammatory cytokines was observed together with decreased antioxidant capacity and increased markers of oxidative damage to proteins. Additionally, in the jejunal extracts of exposed rats, we also noted changes in the metabolite profile, mainly amino acids involved in molecular pathways related to cellular energy, inflammation, the intestinal barrier, and protein synthesis, which were consistent with the observed molecular markers of inflammation and oxidative stress. Taken together, the results of the metabolomic, molecular, and biochemical analyses indicate that prolonged exposure to PS-NPs may disrupt the proper function of the intestine of developing organisms. Full article

Background/Objectives: Paclitaxel (PTX) is widely used in the treatment of a variety of solid tumours due to its broad-spectrum anti-tumour activity, but its use in brain gliomas is limited by insufficient blood–brain tumour barrier (BBTB) penetration and systemic toxicity. The aim of this study was to develop a Solutol HS-15-based micellar nanoparticle (PSM) to enhance the brain glioma targeting of PTX and reduce toxicity. Methods: PSMs were prepared by solvent injection and characterised for particle size, encapsulation rate, haemolysis rate and in vitro release properties. A C6 in situ glioma mouse model was used to assess the brain targeting and anti-tumour effects of the PSM by in vivo imaging, tissue homogenate fluorescence analysis and bioluminescence monitoring. Meanwhile, its safety was evaluated by weight monitoring, serum biochemical indexes and histopathological analysis. Results: The particle size of PSMs was 13.45 ± 0.70 nm, with an encapsulation rate of 96.39%, and it demonstrated excellent cellular uptake. In tumour-bearing mice, PSMs significantly enhanced brain tumour targeting with a brain drug concentration 5.94 times higher than that of free PTX. Compared with Taxol, PSMs significantly inhibited tumour growth (terminal luminescence intensity <1 × 10⁶ p/s/cm²/Sr) and did not cause significant liver or kidney toxicity or body weight loss. Conclusions: PSMs achieve an efficient accumulation of brain gliomas through passive targeting and EPR effects while significantly reducing the systemic toxicity of PTX. Its simple preparation process and excellent therapeutic efficacy support its use as a potential clinically translational candidate for glioma treatment. Full article

Biogenic silver nanoparticles (AgNPs) were synthesized via a green chemistry strategy using wheat extract and subsequently functionalized with a carboxymethyl chitosan–cinnamaldehyde (CMC=CIN) conjugate through covalent imine bonding. The resulting nanohybrid (AgNP–CMC=CIN) was extensively characterized to confirm successful biofunctionalization: UV–Vis spectroscopy revealed characteristic cinnamaldehyde absorption peaks; ATR-FTIR spectra confirmed polymer–terpene bonding; and TEM analysis evidenced uniform nanoparticle morphology. Dynamic light scattering (DLS) measurements indicated an increase in hydrodynamic size upon coating (from 59.46 ± 12.63 nm to 110.17 ± 4.74 nm), while maintaining low polydispersity (PDI: 0.29 to 0.27) and stable surface charge (zeta potential ~ −30 mV), suggesting colloidal stability and homogeneous polymer encapsulation. Antifungal activity was evaluated against Fusarium oxysporum, Penicillium citrinum, Aspergillus niger, and Aspergillus brasiliensis. The minimum inhibitory concentration (MIC) against F. oxysporum was significantly reduced to 83 μg/mL with AgNP–CMC=CIN, compared to 708 μg/mL for uncoated AgNPs, and was comparable to the reference fungicide tebuconazole (52 μg/mL). Seed priming with AgNP–CMC=CIN led to improved germination (85%) and markedly reduced fungal colonization, while maintaining a favorable phytotoxicity profile. These findings highlight the potential of polysaccharide-terpene-functionalized biogenic AgNPs as a sustainable alternative to conventional fungicides, supporting their application in precision agriculture and integrated crop protection strategies. Full article

Among the various available synthesis approaches, hydrolytic precipitation offers a simple, cost-effective, and scalable route for producing phase-pure NiO with a controlled morphology and crystallite size. However, the influence of calcination temperature on its crystalline phase, particle size, and antimicrobial activity remains an active field of research. This study aims to investigate the structural, morphological, and antibacterial properties of NiO nanoparticles synthesized via hydrolytic methods and thermally treated at different temperatures. XRD data indicate the presence of the hexagonal crystallographic phase of NiO (space group 166: R-3m), a structural variant less commonly reported in the literature, stabilized under mild hydrolytic synthesis conditions. The average crystallite size increases significantly from 4.97 nm at 300 °C to values of ~17.8 nm at 500–700 °C, confirming the development of the crystal lattice. The ATR-FTIR analysis confirms the presence of the characteristic Ni–O band for all samples, positioned between 367 and 383 cm⁻¹, with a reference value of 355 cm⁻¹ for commercial NiO. The displacements and variations in intensity reflect a thermal evolution of the crystalline structure, but also an important influence of the size of the crystallites and the agglomeration state. The results reveal a systematic evolution in particle morphology from porous, flake-like nanostructures at 300 °C to dense, well-faceted polyhedral crystals at 900 °C. With an increasing temperature, particle size increases. EDS spectra confirm the high purity of the NiO phase across all samples. Additionally, the NiO nanoparticles exhibit calcination-temperature-dependent antibacterial activity, with the complete inhibition of Escherichia coli and Enterococcus faecalis observed after 24 h for the sample calcined at 300 °C and over 90% CFU reduction within 4 h. A significant reduction in E. faecalis viability across all samples indicates time- and strain-specific bactericidal effects. Due to its remarkable multifunctionality, NiO has emerged as a strategic nanomaterial in fields ranging from energy storage and catalysis to antimicrobial technologies, where precise control over its structural phase and particle size is essential for optimizing performance. Full article

A comparison of two synthesis methods for depositing Au nanoparticles onto TiO₂ was performed: (1) impregnation with HAuCl₄ followed by thermal treatment in argon, and (2) magnetron sputtering from a Au disc. The obtained materials were used for acetaldehyde decomposition in a high temperature reaction chamber and ch aracterised by UV-Vis/DR, XPS, XRD, SEM, and photoluminescence measurements. The process was carried out using an air/acetaldehyde gas flow under UV or UV-Vis LED irradiation. The mechanism of acetaldehyde decomposition and conversion was elaborated by in situ FTIR measurements of the photocatalyst surface during the reaction. Simultaneously, concentration of acetaldehyde in the outlet gas was monitored using gas chromatography. All the Au/TiO₂ samples showed absorption in the visible region, with a maximum around 550 nm. The plasmonic effect of Au nanoparticles was observed under UV-Vis light irradiation, especially at elevated temperatures such as 100 °C, for Au/TiO₂ prepared by the magnetron sputtering method. This resulted in a significant increase in the conversion of acetaldehyde at the beginning, followed by gradual decrease over time. The collected FTIR spectra indicated that, under UV-Vis light, acetaldehyde was strongly adsorbed onto Au/TiO₂ surface and formed crotonaldehyde or aldol. Under UV, acetaldehyde was mainly adsorbed in the form of acetate species. The plasmonic effect of Au nanoparticles increased the adsorption of acetaldehyde molecules onto TiO₂ surface, while reducing their decomposition rate. The increased temperature of the process enhanced the decomposition of the acetaldehyde. Full article

Nanoimprint lithography (NIL) has emerged as a promising sub-10 nm patterning at low cost; yet, robust process control remains difficult because of time-consuming physics-based simulators and labeled SEM data scarcity. We propose a data-efficient, two-stage deep-learning framework here that directly reconstructs post-imprint SEM images from binary design layouts and delivers calibrated pixel-by-pixel uncertainty simultaneously. First, a shallow U-Net is trained on conformalized quantile regression (CQR) to output 90% prediction intervals with statistically guaranteed coverage. Moreover, per-level errors on a small calibration dataset are designed to drive an outlier-weighted and encoder-frozen transfer fine-tuning phase that refines only the decoder, with its capacity explicitly focused on regions of spatial uncertainty. On independent test layouts, our proposed fine-tuned model significantly reduces the mean absolute error (MAE) from 0.0365 to 0.0255 and raises the coverage from 0.904 to 0.926, while cutting the labeled data and GPU time by 80% and 72%, respectively. The resultant uncertainty maps highlight spatial regions associated with error hotspots and support defect-aware optical proximity correction (OPC) with fewer guard-band iterations. Extending the current perspective beyond OPC, the innovatively model-agnostic and modular design of the pipeline here allows flexible integration into other critical stages of the semiconductor manufacturing workflow, such as imprinting, etching, and inspection. In these stages, such predictions are critical for achieving higher precision, efficiency, and overall process robustness in semiconductor manufacturing, which is the ultimate motivation of this study. Full article

Exoskeletons transfer loads to the human body via physical human–exoskeleton interfaces (pHEI). However, the human–exoskeleton interaction remains poorly understood, and the mechanical properties of the pHEI are not well characterized. Therefore, we present a novel methodology to precisely characterize pHEI interaction stiffnesses under various loading conditions. Forces and torques were applied in three orthogonal axes to the upper arm pHEI of 21 subjects using an electromechanical apparatus. Interaction loads and displacements were measured, and stiffness data were derived as well as mathematically described using linear and non-linear regression models, yielding all the diagonal elements of the stiffness tensor. We find that the non-linear nature of pHEI stiffness is best described using exponential functions, though we also provide linear approximations for simplified modeling. We identify statistically significant differences between loading conditions and report median translational stiffnesses between 2.1 N/mm along and 4.5 N/mm perpendicular to the arm axis, as well as rotational stiffnesses of 0.2 N·m/° perpendicular to the arm, while rotations around the longitudinal axis are almost an order of magnitude smaller (0.03 N·m/°). The resulting stiffness models are suitable for use in digital human–exoskeleton models, potentially leading to more accurate estimations of biomechanical efficacy and discomfort of exoskeletons. Full article

An external power build-up cavity of a line-narrowed 407-nm laser diode for Raman gas analysis was demonstrated to possess good gas detection capabilities. By employing an ordinary laser diode without anti-reflection coating or and a bandpass interference filter in an external cavity resonance, the laser linewidth was narrowed by resonant optical feedback, and tens of watts of external cavity power were built up. The coupling mechanism between the semiconductor laser and the external cavity are discussed, as well as the noise background in the experimental results. The Raman spectrum of ambient air was analyzed, achieving a methane detection limit of 1 ppm. Full article

As lithium-ion batteries (LIBs) gain widespread use, detecting electrolyte–vapor emissions during early thermal runaway (TR) remains critical to ensuring battery safety; yet, it remains understudied. Gas sensors integrating oxide nanostructures offer a promising solution as they possess high sensitivity and fast response, enabling rapid detection of various gas-phase indicators of battery failure. Utilizing this approach, 3D ordered tin oxide (SnO₂) nanostructures were synthesized using polystyrene sphere (PS) templates of varied diameters (200–1500 nm) and precursor concentrations (0.2–0.6 mol/L) to detect key electrolyte–vapors, especially ethyl methyl carbonate (EMC), released in the early stages of TR. The 3D ordered SnO₂ nanostructures with ring- and nanonet-like morphologies, formed after PS template removal, were characterized, and the effects of template size and precursor concentration on their structure and sensing performance were investigated. Among various nanostructures of SnO₂, nanonets achieved by a 1000 nm PS template and 0.4 mol/L precursor showed higher mesoporosity (~28 nm) and optimal EMC detection. At 210 °C, it detected 10 ppm EMC with a response of ~7.95 and response/recovery times of 14/17 s, achieving a 500 ppb detection limit alongside excellent reproducibility/stability. This study demonstrates that precise structural control of SnO₂ nanostructures using templates enables sensitive EMC detection, providing an effective sensor-based strategy to enhance LIB safety. Full article

In classic all-dielectric one-dimensional photonic crystals, transparent bands exhibit strong angular dispersion. Herein, we realize an angle-dispersion-free near-infrared transparent band in a one-dimensional photonic hypercrystal containing hyperbola-dispersion metamaterials. As the incident angle increases from 0° to 80°, the relative shifts of the wavelengths of four transmittance peaks within the transparent band are smaller than 1.5% and the bandwidth of the transparent band marginally fluctuates from 1098.2 to 1132.5 nm. Particularly, the angle-dispersion-free property of the transparent band is quite robust with respect to the layer thickness disturbance. Our work not only offers a viable method of achieving angle-dispersion-free transparent bands but also facilitates the development of transparency-based optical devices. Full article

With the development of a quantum computer in the near future, classical public-key cryptography will face the challenge of being vulnerable to quantum algorithms, such as Shor’s algorithm. As communication technology advances rapidly, a great deal of personal information is being transmitted over the Internet. Based on our observation that the Kyber algorithm exhibits a significant number of idle cycles during execution when implemented following the conventional software procedure, this paper proposes a high-throughput scheduling for Kyber by parallelizing the SHA-3 function, the sampling algorithm, and the NTT computations to improve hardware utilization and reduce latency. We also introduce the 8-stage pipelined SHA-3 architecture and multi-mode polynomial arithmetic module to increase area efficiency. By also optimizing the hardware architecture of the various computational modules used by Kyber, according to the implementation result, an aggregate throughput of 877.192 kOPS in Kyber KEM can be achieved on TSMC 40 nm. In addition, our design not only achieves the highest throughput among existing studies but also improves the area and power efficiencies. Full article

The salinization of agricultural soils is a serious threat to farming and ecological balance in arid and semi-arid regions. Accurate estimation of soil water-soluble ions (calcium, carbonate, magnesium, and sulfate) is necessary for correct monitoring of soil salinization and sustainable land management. Hyperspectral ground-based data are valuable in soil salinization monitoring, but the acquisition cost is high, and the coverage is small. Therefore, this study proposes a two-stage deep learning framework with multispectral remote-sensing images. First, the wavelet transform is used to enhance the Transformer and extract fine-grained spectral features to reconstruct the ground-based hyperspectral data. A comparison of ground-based hyperspectral data shows that the reconstructed spectra match the measured data in the 450–998 nm range, with R² up to 0.98 and MSE = 0.31. This high similarity compensates for the low spectral resolution and weak feature expression of multispectral remote-sensing data. Subsequently, this enhanced spectral information was integrated and fed into a novel multiscale self-attentive Transformer model (MSATransformer) to invert four water-soluble ions. Compared with BPANN, MLP, and the standard Transformer model, our model remains robust across different spectra, achieving an R² of up to 0.95 and reducing the average relative error by more than 30%. Among them, for the strongly responsive ions magnesium and sulfate, R² reaches 0.92 and 0.95 (with RMSE of 0.13 and 0.29 g/kg, respectively). For the weakly responsive ions calcium and carbonate, R² stays above 0.80 (RMSE is below 0.40 g/kg). The MSATransformer framework provides a low-cost and high-accuracy solution to monitor soil salinization at large scales and supports precision farmland management. Full article

Bacterial meningitis remains a critical public health issue globally due to its high morbidity and mortality. Understanding regional epidemiological trends is essential to inform vaccination strategies and public health interventions. This observational, retrospective study analyzed cerebrospinal fluid (CSF) isolates collected from 731 confirmed cases of bacterial meningitis between 2014 and 2024 in Lombardy, Italy. Pathogen identification and serotyping of Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), and Haemophilus influenzae (HI) were conducted using culture-based and molecular techniques. Trends were assessed across age groups and time using Kruskal–Wallis and chi-square tests. Results: SP was the predominant pathogen (78.4%), followed by NM (13.0%) and HI (8.6%). Significant temporal variation was observed for SP and NM, while HI trends remained stable. The impact of COVID-19-related restrictions was evident in a reduction in cases during 2020–2021. SP serotypes 3 and 8, HI non-typeable strains, and NM serogroup B were most frequent. No major shifts in serotype distribution were observed. Long-term surveillance data from Lombardy underscore the dominance of vaccine-targeted serotypes, ongoing circulation of resilient clones, and post-pandemic epidemiological shifts. These findings support continuous surveillance and inform vaccine strategy adjustments at the regional and national levels. Full article