Search Results (2,839)

Microglia-mediated chronic neuroinflammation is a common pathological feature of Parkinson’s disease (PD). Strong evidence suggests that activated microglia can lesion neurons by releasing exosomes. However, the mechanisms of exosome release from activated microglia remain unclear. We recently revealed a key role of complement receptor 3 (CR3) in regulating microglial activation in the process of progressive neurodegeneration. This study aimed to investigate whether CR3 can regulate exosome release from activated microglia, as well as the underlying mechanisms. We found that LPS, an inducer of microglial M1 activation, induced exosome release from activated microglia. Inhibition of exosome synthesis suppressed LPS-induced microglial activation, gene expression of proinflammatory factors, and related neurotoxicity. Silencing or knocking out CR3 attenuated LPS-induced exosome release in microglia. NADPH oxidase (NOX2) was further identified as a downstream signal of CR3, mediating microglial exosome release and related neurotoxicity. CR3 silencing blocked LPS-induced NOX2 activation and superoxide production through inhibition of p47^phox phosphorylation and membrane translocation. Moreover, NOX2 activation elicited by PMA or supplementation of H₂O₂ recovered exosome release from CR3-silenced microglia. Subsequently, we demonstrated that the CR3-NOX2 axis regulates syntenin-1 to control microglial exosome release. Finally, we observed that the expression of CR3 was increased in the brain of LPS-treated mice, and genetic ablation of CR3 significantly reduced LPS-induced NOX2 activation, microglial M1 polarization, and exosome production in mice. Overall, our findings revealed a critical role of the CR3-NOX2 axis in controlling microglial exosome release and related neurotoxicity through syntenin-1, providing a novel target for the development of a therapeutic strategy for neuroinflammation-mediated neurodegeneration. Full article

The growing demand for sustainable plant-based dairy alternatives has spurred interest in valorizing agro-industrial byproducts like hazelnut cake, a protein-rich byproduct of oil extraction. This study developed formulations for vegan ice cream using unfermented (HIC) and Aspergillus oryzae-fermented hazelnut cake (FHIC), comparing their physicochemical, functional, and sensory properties to conventional dairy ice cream (DIC). Solid-state fermentation (72 h, 30 °C) enhanced the cake’s bioactive properties, and ice creams were characterized for composition, texture, rheology, melting behavior, antioxidant activity, and enzyme inhibition pre- and post-in vitro digestion. The results indicate that FHIC had higher protein content (64.64% vs. 58.02% in HIC) and unique volatiles (e.g., benzaldehyde and 3-methyl-1-butanol). While DIC exhibited superior overrun (15.39% vs. 4.01–7.00% in vegan samples) and slower melting, FHIC demonstrated significantly higher post-digestion antioxidant activity (4.73 μmol TE/g DPPH vs. 1.44 in DIC) and angiotensin-converting enzyme (ACE) inhibition (4.85–7.42%). Sensory evaluation ranked DIC highest for overall acceptability, with FHIC perceived as polarizing due to pronounced flavors. Despite textural challenges, HIC and FHIC offered nutritional advantages, including 18–30% lower calories and enhanced bioactive compounds. This study highlights fermentation as a viable strategy to upcycle hazelnut byproducts into functional vegan ice creams, although the optimization of texture and flavor is needed for broader consumer acceptance. Full article

The administration of isolated mitochondria is a promising strategy for protecting cells from oxidative damage. This study aimed to identify mitochondrial characteristics that contribute to stronger protective effects. We compared two types of mitochondria isolated from C6 cells with similar ATP-producing capacity but differing in outer membrane integrity. To evaluate their stability in extracellular conditions, we examined their behavior in serum. Both types underwent mitochondrial permeability transition to a similar extent; however, under intracellular-like conditions after serum incubation, mitochondria with intact membranes retained more polarized mitochondria. Notably, mitochondria with intact outer membranes were internalized more efficiently than those with damaged membranes. In H9c2 cells, both types of mitochondria similarly increased intracellular ATP levels 1 h after administration under all tested conditions. When co-administered with H₂O₂, both suppressed oxidative damage to a comparable degree, as indicated by similar H₂O₂-scavenging activity in solution, comparable intracellular ROS levels, and equivalent preservation of electron transport chain activity. However, at higher H₂O₂ concentrations, cells treated with mitochondria possessing intact outer membranes exhibited greater survival 24 h after co-administration. Furthermore, when mitochondria were added after H₂O₂-induced damage and their removal, intact mitochondria conferred superior cell survival compared to damaged ones. These findings suggest that while both mitochondrial types exert comparable antioxidant effects, outer membrane integrity prior to administration plays a critical role in enhancing cell survival under conditions of oxidative stress. Full article

In this study, we propose a bidirectional chemical sensor platform based on a reconfigurable ion-sensitive field-effect transistor (R-ISFET) architecture. The device incorporates Ni-silicide Schottky barrier source/drain (S/D) contacts, enabling ambipolar conduction and bidirectional turn-on behavior for both p-type and n-type configurations. Channel polarity is dynamically controlled via the program gate (PG), while the control gate (CG) suppresses leakage current, enhancing operational stability and energy efficiency. A dual-control-gate (DCG) structure enhances capacitive coupling, enabling sensitivity beyond the Nernst limit without external amplification. The extended-gate (EG) architecture physically separates the transistor and sensing regions, improving durability and long-term reliability. Electrical characteristics were evaluated through transfer and output curves, and carrier transport mechanisms were analyzed using band diagrams. Sensor performance—including sensitivity, hysteresis, and drift—was assessed under various pH conditions and external noise up to 5 V_pp (i.e., peak-to-peak voltage). The n-type configuration exhibited high mobility and fast response, while the p-type configuration demonstrated excellent noise immunity and low drift. Both modes showed consistent sensitivity trends, confirming the feasibility of complementary sensing. These results indicate that the proposed R-ISFET sensor enables selective mode switching for high sensitivity and robust operation, offering strong potential for next-generation biosensing and chemical detection. Full article

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

Titanium is widely recognized as an interesting material for electrodes due to its excellent corrosion resistance, mechanical strength, and biocompatibility. However, further functionalization is often necessary to impart advanced interfacial properties, such as selective ion transport or stimuli responsiveness. In this context, the integration of smart polymers, such as poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA)—noted for its dual pH- and thermo-responsive behavior—has emerged as a promising approach to tailor surface properties for next-generation devices. This work compares two covalent immobilization strategies for PDMAEMA on titanium: the “graft-to” method, involving the attachment of pre-synthesized polymer chains, and the “graft-from” method, based on surface-initiated polymerization. The resulting materials were characterized with size exclusion chromatography (SEC) for molecular weight, Fourier-transform infrared spectroscopy (FTIR) for chemical structure, scanning electron microscopy (SEM) for surface morphology, and contact angle measurements for wettability. Electrochemical impedance spectroscopy and polarization studies were used to assess electrochemical performance. Both strategies yielded uniform and stable coatings, with the mode of grafting influencing both surface morphology and functional stability. These findings provide valuable insights into the development of adaptive, stimuli-responsive titanium-based interfaces in advanced electrochemical systems. Full article

The electrooxidation (EO) of three important environmental contaminants, anticorrosive 1H-benzotriazole (BTA), plasticizer dibutyl phthalate (DBP), and non-ionic surfactant Triton X-100 (tert-octylphenoxy[poly(ethoxy)] ethanol, t-OPPE), was studied as a possible means to improve their elimination from wastewaters, which are an important emission source. EO was performed in a batch reactor with a boron-doped diamond (BDD) anode and a stainless steel cathode. Different supporting electrolytes were tested: NaCl, H₂SO₄, and Na₂SO₄. Results were analysed from the point of their efficacy in terms of degradation rate, kinetics, energy consumption, and transformation products. The highest degradation rate, shortest half-life, and lowest energy consumption was observed in the electrolyte H₂SO₄, followed by Na₂SO₄ with only slightly less favourable characteristics. In both cases, degradation was probably due to the formation of persulphate or sulphate radicals. Transformation products (TPs) were studied mainly in the sulphate media and several oxidation products were identified with all three contaminants, while some evidence of progressive degradation, e.g., ring-opening products, was observed only with t-OPPE. The possible reasons for the lack of further degradation in BTA and DBP are too short of an EO treatment time and perhaps a lack of detection due to unsuitable analytical methods for more polar TPs. Results demonstrate that BDD-based EO is a robust method for the efficient removal of structurally diverse organic contaminants, making it a promising candidate for advanced water treatment technologies. Full article

Forest structure parameters are critical for understanding and managing forest ecosystems, yet sparse forests have received limited attention in previous studies. To address this research gap, this study systematically evaluates and compares the sensitivity of active Synthetic Aperture Radar (SAR) and passive optical remote sensing to key forest structure parameters in sparse forests, including Diameter at Breast Height (DBH), Tree Height (H), Crown Width (CW), and Leaf Area Index (LAI). Using the novel computer-graphics-based radiosity model applicable to porous individual thin objects, named Radiosity Applicable to Porous Individual Objects (RAPID), we simulated 38 distinct sparse forest scenarios to generate both SAR backscatter coefficients and optical reflectance across various wavelengths, polarization modes, and incidence/observation angles. Sensitivity was assessed using the coefficient of variation (CV). The results reveal that C-band SAR in HH polarization mode demonstrates the highest sensitivity to DBH (CV = −6.73%), H (CV = −52.68%), and LAI (CV = −63.39%), while optical data in the red band show the strongest response to CW (CV = 18.83%) variations. The study further identifies optimal acquisition configurations, with SAR data achieving maximum sensitivity at smaller incidence angles and optical reflectance performing best at forward observation angles. This study addresses a critical gap by presenting the first systematic comparison of the sensitivity of multi-band SAR and VIS/NIR data to key forest structural parameters across sparsity gradients, thereby clarifying their applicability for monitoring young and middle-aged sparse forests with high carbon sequestration potential. Full article

The planktonic pteropod Limacina helicina is increasingly studied as a bioindicator of climate-driven changes in polar marine ecosystems. Although broadly distributed across the Arctic Basin and the North Pacific, its population structure and dispersal pathways remain poorly understood, especially in the Siberian Arctic. We analyzed mitochondrial COI sequences from populations sampled in the Barents, Kara, Laptev, East Siberian, and White Seas, as well as adjacent Pacific regions. Three major haplogroups (H1, H2, H3) were identified with distinct spatial patterns. H1 is widespread, occurring across the Pacific and most Arctic seas except the White Sea. H2 is confined to the western Arctic shelves (Barents–Kara–Laptev), and H3 is unique to the White Sea. We found a pronounced genetic discontinuity corresponding to hydrographic barriers, particularly the strong freshwater inflow from the Lena River, which restricts eastward dispersal of H2 from the Laptev to the East Siberian Sea. These patterns suggest postglacial expansions from geographically separated populations that survived the Last Glacial Maximum in isolated marine regions. The White Sea population is highly isolated and genetically distinct. Our results highlight how both glacial history and modern oceanography shape Arctic plankton diversity and define biogeographic boundaries in a rapidly changing climate. Full article

In order to explore the essence of the anticoccidiosis of anticoccidial drugs under bioelectric currents, the intermolecular double-proton transfer and conformational transformation of 4-pyridone-3-carboxylic acid were investigated by quantum chemistry calculations (at the M06-2X/6-311++G**, M06-2X/aug-cc-pVTZ and CCSD(T)/aug-cc-pVTZ levels) and finite temperature string (FTS) under external electric fields. The solvent effect of H₂O on the double-proton transfer was evaluated by the integral equation formalism polarized continuum model. The results indicate that the influences of the external electric fields along the direction of the dipole moment on double-proton transfer are significant. The corresponding products are controlled by the direction of the external electric field. Due to the first-order Stark effect, some good linear relationships form between the changes of the structures, atoms in molecules (AIMs) results, surface electrostatic potentials, barriers of the transition state, and the external electric field strengths. From the gas to solvent phase, the barrier heights increased. The spatial order parameters (ϕ, ψ) of the conformational transformation could be quickly converged through the umbrella sampling and parameter averaging, and thus the free-energy landscape for the conformational transformation was obtained. Under the external electric field, there is competition between the double-proton transfer and conformational transformation. The external electric field greatly affects the cooperativity transfer, while it has little effect on the conformational transformation. This study is helpful in the selection and updating of anticoccidial drugs. Full article

In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca²⁺ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca²⁺ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article

This study presents data from Reverse Osmosis (RO) and Nanofiltration (NF) spiral-wound polyamide modules tested in a semi-pilot plant with multicomponent mixtures of Volatile Fatty Acids (VFAs) comprising acetic, propionic, butyric, valeric, and hexanoic acids. A robust method combining film theory and dissociation equilibria was developed to estimate interfacial concentrations, enabling accurate analysis of concentration polarization, real rejection, and effective transmembrane driving force. Concentration polarization strongly affects NF membranes, resulting in real rejections up to 20% higher than apparent values, while its effect is negligible for RO membranes. NF rejections show marked sensitivity to pH and VFA feed concentration: at 20 g/L and highest flux, acetic acid real rejection increases from 80% to 91% as pH rises from 6 to 9. At pH 7, rejections decline with feed concentration, with acetic acid dropping from 55% at 20 g/L to 32% at 63 g/L, at the same flux. These changes correlate with the molecular weight of the acids. Conversely, RO rejections are marginally affected by pH and not influenced by concentration due to dominant steric exclusion. Membrane permeabilities remain unaffected by VFAs and align with pure water values. The data analysis framework is effective and applicable across a wide range of conditions and membranes. Full article

Members of Sideritis sect. Empedoclia (Lamiaceae), known as ‘mountain tea’, are widely used medicinal plants. Their taxonomic classification is complex due to frequent hybridization and subtle morphological distinctions. This study examines 12 populations of eight native Sideritis taxa from Greece: S. clandestina subsp. clandestina, S. clandestina subsp. peloponnesiaca, S. euboea, S. raeseri subsp. raeseri, S. raeseri subsp. attica, S. scardica, S. sipylea, and S. syriaca subsp. syriaca. The objectives were to (1) monitor non-polar secondary metabolites (mainly terpenoids) using gas chromatography; (2) shed light on their phylogenetic relationships; (3) evaluate the correlation between genetic and chemical data. Diterpenes, particularly sideridiol, siderol, 7-epicandicandiol, and ent-3α,18-dihydroxy-kaur-16-ene, were the most abundant chemical compounds. Categorical Principal Component Analysis revealed that S. raeseri subsp. attica is chemically distinct, while the rest are grouped into two clusters: one comprising S. clandestina and S. sipylea, and the other including all the rest. Genetic analysis based on chloroplast DNA (matK, psbA-trnH, trnL-F), showed that S. sipylea and S. syriaca subsp. syriaca were the most phylogenetically distant groups. Our study enhances the understanding of Sideritis chemovariability and phylogeny, supporting also taxonomic, authentication, and breeding efforts. Full article

This study evaluated birch and oak ash extracts as alternative extractants for isolating humic substances (HSs) from peat and lignite. The effects of ultrasound intensity, extraction time, and temperature were optimized using a Box–Behnken design and validated statistically. The highest HSs yields were obtained from peat with oak ash extract (pH 13.18), compared to birch ash extract (pH 12.09). Optimal process parameters varied by variant, falling within 309–391 mW∙cm⁻², 116–142 min, and 67–79 °C. HSs extracted under optimal conditions were fractionated into humic acids (HAs) and fulvic acids (FAs), and then analyzed by elemental analysis, Fourier Transform Infrared Spectroscopy (FTIR), and Cross-Polarization Magic Angle Spinning Carbon-13 Nuclear Magnetic Resonance Spectroscopy (CP/MAS ¹³C NMR). The main differences in HSs quality were influenced by raw material and fraction type. However, the use of birch ash extract consistently resulted in a higher proportion of carboxylic structures across all fractions. Overall, wood ash extract, especially from oak, offers a sustainable and effective alternative to conventional extractants, particularly for HSs isolation from lignite. Notably, HSs yield from lignite with oak ash extract (29.13%) was only slightly lower than that achieved with 0.5 M NaOH (31.02%), highlighting its practical potential in environmentally friendly extraction technologies. Full article

PVDF/TiO₂ composite membranes show some potential to be used for water treatment as they combine the advantages of polymers and ceramics. However, conventional PVDF-based composite membranes are always fabricated by using conventional toxic solvents. Herein, PolarClean was used as a green solvent to fabricate PVDF/TiO₂ composite membranes via the phase inversion method. In this process, Pluronic F127 was used as a dispersion agent to distribute TiO₂ particles in the PVDF matrix and to serve as a pore former on the membrane surface. TiO₂ particles were well distributed on the membrane surface and bulk. TiO₂ particles in the PVDF matrix enhanced the mechanical strength and hydrophilic characteristics of the resulting composite membrane, facilitating water transport through the composite membranes and enhancing their water permeability. Membrane microstructures and mechanical strength of the composite membranes were finely tuned by varying the PVDF concentration, TiO₂ concentration, and coagulation bath temperature. It was demonstrated that the resulting green PVDF/TiO₂ composite membrane showed a high water permeance compared with those using conventional toxic solvents in terms of its small pore size. In addition, the particle rejection of green PVDF/TiO₂ membrane showed a 99.9% rejection rate in all the filtration process, while those using NMP showed 91.1% after 30 min of filtration. The water flux was similar at 121 and 130 Lm⁻²h⁻¹ for green and conventional solvents, respectively. This work provides important information for the future application of sustainable membranes. Full article