Search Results (4,146)

Lipid nanoparticle (LNP)-based delivery systems are promising tools for advancing RNA-based therapies. However, there are underlying challenges for the oral delivery of LNPs. In this study, we optimized an LNP formulation, which we encapsulated in a pH-sensitive Eudragit^® S 100 (Eu) coating. LNPs were prepared using the DLin-MC3-DMA ionizable lipid, cholesterol, DMG-PEG, and DSPC at a molar ratio of 50:38.5:10:1.5. LNPs were coated with 1% Eu solution via nanoprecipitation using 0.25% acetic acid to get Eu-coated LNPs (Eu-LNPs). Particle characteristics of LNPs were determined by using dynamic light scattering (DLS). Ribogreen and agarose gel retardation assays were used to evaluate nucleic acid entrapment and stability. LNPs and Eu-LNPs were ~120 nm and 4.5 μm in size, respectively. Eu-LNPs decrease to an average size of ~191 ± 22.9 nm at a pH of 8. Phosphate buffer (PB)-treated and untreated Eu-LNPs and uncoated LNPs were transfected in HEK-293 cells. PB-treated Eu-LNPs showed significant transfection capability compared to their non-PB-treated counterparts. Eu-LNPs protected their nucleic acid payloads in the presence of a simulated gastric fluid (SGF) with pepsin and maintained transfection capacity following SGF or simulated intestinal fluid. Hence, Eu coating is a potentially promising approach for the oral administration of LNPs. Full article

Appropriate carriers or templates are crucial for maintaining the stability, biological activity, and bioavailability of selenium nanoparticles (SeNPs). Selecting suitable templates remains challenging for fully utilizing SeNPs functionalities and developing applicable products. Exosome-like nanoparticles (ELNs) have gained importance in drug delivery systems, yet research on selenium products prepared using exosomes remains limited. To address this gap, we utilized Cyperus bean ELNs to deliver SeNPs, investigated three preparation methods for SeNPs-ELNs, identified the optimal approach, and performed characterization studies. Notably, all three methods successfully loaded SeNPs. Ultrasonic cell fragmentation is the optimal approach, achieving significant increases in selenium loading (5.59 ± 0.167 ng/μg), enlargement of particle size (431.17 ± 10.78 nm), and reduced absolute zeta potential (−4.1 ± 0.43 mV). Moreover, both exosome formulations demonstrated enhanced stability against aggregation during storage at 4 °C, while their stability varied with pH conditions. In vitro digestibility tests showed greater stability of SeNP-ELNs in digestive fluids compared to ELNs alone. Additionally, neither ELNs nor SeNP-ELNs exhibited cytotoxicity toward LO₂ cells, and the relative erythrocyte hemolysis remained below 5% at protein concentrations of 2.5, 7.5, 15, 30, and 60 μg/mL. Overall, ultrasonic cell fragmentation effectively loaded plant-derived exosomes with nano-selenium at high capacity, presenting new opportunities for their use as functional components in food and pharmaceutical applications. Full article

SnRK kinases, central regulators of plant stress response, remain uncharacterized in Taxus—an ancient gymnosperm valued for paclitaxel production. This study aimed to identify the Taxus SnRK family and elucidate its functional roles. Specifically, we identified SnRK genes through genomic analysis and assessed tissue-specific expression via transcriptomics, while regulatory networks were deciphered using WGCNA. To overcome experimental constraints, a PEG-mediated protoplast transient expression system was developed using calli, followed by dual-luciferase assays. Consequently, 19 SnRK genes (2 SnRK1, 4 SnRK2, 13 SnRK3) were identified, with tissue-specific expression revealing TaSnRK1.2 upregulation under methyl jasmonate (MeJA) and in stress-resilient tissues (bark/root). Subsequently, WGCNA uncovered a bark/root-specific module containing TaSnRK1.2 with predicted TF interactions (TaGRAS/TaERF). Critically, homologous dual-luciferase assays demonstrated TaSnRK1.2 activates TaGRAS and TaERF promoters (4.34-fold and 3.11-fold induction, respectively). This study establishes the Taxus SnRK family and identifies TaSnRK1.2 as a hub integrating stress signals (e.g., MeJA) to modulate downstream TF networks, while the novel protoplast system enables future functional studies in this medicinal plant. Full article

With the growing severity of environmental pollution, people are paying increasing attention to their health. However, naturally occurring wood with health benefits and applications in human healthcare is still scarce. Natural wood exhibits a limited negative oxygen ion release capacity, and this release has a short duration, failing to meet practical application requirements. This study innovatively developed a humidity-responsive, healthy wood material with a high negative oxygen ion release capacity based on fast-growing poplar. Through vacuum cyclic impregnation technology, hexagonal stone powder was infused into the pores of poplar wood, endowing it with the ability to continuously release negative oxygen ions. The healthy wood demonstrated a static average negative oxygen ion release rate of 537 ions/cm³ (peaking at 617 ions/cm³) and a dynamic average release rate of 3,170 ions/cm³ (peaking at 10,590 ions/cm³). The results showed that the particle size of hexagonal stone powder in suspension was influenced by the dispersants and dispersion processes. The composite dispersion process demonstrated optimal performance when using 0.5 wt% silane coupling agent γ-(methacryloxy)propyltrimethoxysilane (KH570), achieving the smallest particle size of 8.93 μm. The healthy wood demonstrated excellent impregnation performance, with a weight gain exceeding 14.61% and a liquid absorption rate surpassing 165.18%. The optimal impregnation cycle for vacuum circulation technology was determined to be six cycles, regardless of the type of dispersant. Compared with poplar wood, the hygroscopic swelling rate of healthy wood was lower, especially in PEG-treated samples, where the tangential, radial, longitudinal, and volumetric swelling rates decreased by 70.93%, 71.67%, 69.41%, and 71.35%, respectively. Combining hexagonal stone powder with fast-growing poplar wood can effectively enhance the release of negative oxygen ions. The static average release of negative oxygen ions from healthy wood is 1.44 times that of untreated hexagonal stone powder, and the dynamic release reaches 2 to 3 times the concentration of negative oxygen ions specified by national fresh air standards. The water-responsive mechanism revealed that negative oxygen ion release surged when ambient humidity exceeded 70%. This work proposes a sustainable and effective method to prepare healthy wood with permanent negative oxygen ion release capability. It demonstrates great potential for improving indoor air quality and enhancing human health. Full article

Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) (PNIPAm), hydrophilic poly(ethylene glycol) (PEG) grafts, and a polycationic poly(L-lysine) (PLL) block of varying lengths ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z, z = 10–65)—were investigated. Plasmid DNA complexation with the copolymers was achieved through temperature-modulated methods. The resulting polyplexes were characterized by evaluating complex strength, particle size, zeta potential, plasmid DNA loading capacity, resistance to anionic stress, stability in serum, and lysosomal membrane destabilization assay. The copolymers’ potential for plasmid DNA delivery was assessed through cytotoxicity and transfection studies in cancer cell lines. Results. Across all complexation methods, the copolymers effectively condensed plasmid DNA into stable polyplexes. Particle sizes (60–90 nm) ranged with no apparent correlation to copolymer type, complexation method, or N/P ratio, whereas zeta potentials (+10–+20 mV) and resistance to polyanionic stress were dependent on the PLL length and N/P ratio. Cytotoxicity analysis revealed a direct correlation between PLL chain length and cell viability, with all copolymers demonstrating minimal cytotoxicity at concentrations required for efficient transfection. PNL-20 ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)₂₀) exhibited the highest transfection efficiency among the tested formulations while maintaining low cytotoxicity. Conclusions. The study highlights the promising potential of (PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z copolymers for effective plasmid DNA delivery to cancer cells. It reveals the importance of attaining the right balance between polyplex tightness and plasmid release to achieve improved biocompatibility and transfection efficiency. Full article

Functional recovery after traumatic brain injury (TBI) is hindered by progressive neurodegeneration resulting from neuroinflammation and other secondary injury processes. Dexamethasone (DX), a synthetic glucocorticoid, has been shown to reduce inflammation, but its systemic administration can cause a myriad of other medical issues. We aim to provide a local, sustained treatment of DX for TBI. Previously, we demonstrated that PEG-bis-AA/HA-DXM hydrogels composed of polyethyleneglycol-bis-(acryloyloxy acetate) (PEG-bis-AA) and dexamethasone-conjugated hyaluronic acid (HA-DXM) reduced secondary injury and improved motor functional recovery at 7 days post-injury (DPI) in a rat moderate controlled cortical impact (CCI) TBI model. In this study, we evaluated the effect of PEG-bis-AA/HA-DXM hydrogel on cognitive function and secondary injury at 14 DPI. Immediately after injury, hydrogel disks were placed on the surface of the injured cortex. Cognitive function was evaluated using the Morris Water Maze test, and secondary injury was evaluated by histological analysis. The hydrogel treatment group demonstrated significantly shorter latency to target, decreased distance to find the hidden target, increased number of target crossings, increased number of entries to the platform zone, and decreased latency to first entry of target zone compared to untreated TBI rats for probe test. We also observed reduced lesion volume, inflammatory response, and apoptosis in the hydrogel treatment group compared to the untreated TBI group. Full article

Background: Previous research has demonstrated that 20 kHz probe or 37 kHz bath sonication of poloxamers comprising polypropylene glycol (PPG) and polyethylene glycol (PEG) blocks can generate degradation byproducts that are toxic to mammalian cells and organisms. Herein, an investigation of a PEGylated phospholipid micelle was undertaken to identify low-molecular-weight sonolytic degradation byproducts that could be cytotoxic. The concern here lies with the fact that sonication is a frequently employed step in drug delivery manufacturing processes, during which PEGylated phospholipids can be subjected to shear forces and other extreme oxidative and thermal conditions. Methods: Control and 20 kHz-sonicated micelles of DSPE-mPEG2000 were analyzed using dynamic light scattering (DLS) and zeta potential analyses to study colloidal properties, matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) mass spectroscopy (MS) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy to study the structural integrity of DSPE-mPEG2000, and ¹H-NMR spectroscopy and high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection to quantitate the formation of low-molecular-weight degradation byproducts. Results: MALDI-TOF-MS analyses of 20 kHz-sonicated DSPE-mPEG2000 revealed the loss of ethylene glycol moieties in accordance with depolymerization of the PEG chain; ¹H-NMR spectroscopy showed the presence of formate, a known oxidative/thermal degradation product of PEG; and HPLC-UV showed that the generation of formate was dependent on 20 kHz probe sonication time between 5 and 60 min. Conclusions: It was found that 20 kHz sonication can degrade the PEG chain of DSPE-mPEG2000, altering the micelle’s PEG corona and generating formate, a known ocular toxicant. Full article

Accurate diagnosis of gastrointestinal (GI) diseases typically requires invasive procedures or imaging studies that pose the risk of various post-procedural complications or involve radiation exposure. Bowel sounds (BSs), though typically described during a GI-focused physical exam, are highly inaccurate and variable, with low clinical value in diagnosis. Interpretation of the acoustic characteristics of BSs, i.e., using a phonoenterogram (PEG), may aid in diagnosing various GI conditions non-invasively. Use of artificial intelligence (AI) and improvements in computational analysis can enhance the use of PEGs in different GI diseases and lead to a non-invasive, cost-effective diagnostic modality that has not been explored before. The purpose of this work was to develop an automated AI model, You Only Listen Once (YOLO), to detect prominent bowel sounds that can enable real-time analysis for future GI disease detection and diagnosis. A total of 110 2-minute PEGs sampled at 44.1 kHz were recorded using the Eko DUO^® stethoscope from eight healthy volunteers at two locations, namely, left upper quadrant (LUQ) and right lower quadrant (RLQ) after IRB approval. The datasets were annotated by trained physicians, categorizing BSs as prominent or obscure using version 1.7 of Label Studio Software^®. Each BS recording was split up into 375 ms segments with 200 ms overlap for real-time BS detection. Each segment was binned based on whether it contained a prominent BS, resulting in a dataset of 36,149 non-prominent segments and 6435 prominent segments. Our dataset was divided into training, validation, and test sets (60/20/20% split). A 1D-CNN augmented transformer was trained to classify these segments via the input of Mel-frequency cepstral coefficients. The developed AI model achieved area under the receiver operating curve (ROC) of 0.92, accuracy of 86.6%, precision of 86.85%, and recall of 86.08%. This shows that the 1D-CNN augmented transformer with Mel-frequency cepstral coefficients achieved creditable performance metrics, signifying the YOLO model’s capability to classify prominent bowel sounds that can be further analyzed for various GI diseases. This proof-of-concept study in healthy volunteers demonstrates that automated BS detection can pave the way for developing more intuitive and efficient AI-PEG devices that can be trained and utilized to diagnose various GI conditions. To ensure the robustness and generalizability of these findings, further investigations encompassing a broader cohort, inclusive of both healthy and disease states are needed. Full article

Background/Objectives: Holy basil (Ocimum tenuiflorum L.) essential oil exhibits antioxidant, antimicrobial, and anesthetic activities, mainly due to eugenol, methyl eugenol, and β-caryophyllene. However, its clinical application is limited by poor water solubility, instability, and low bioavailability. This study developed and compared two delivery systems, self-nanoemulsifying drug delivery systems (SNEDDS) and microemulsions (ME), to enhance their stability and fish anesthetic efficacy. Methods: The optimized SNEDDS (25% basil oil, 8.33% coconut oil, 54.76% Tween 80, 11.91% PEG 400) and ME (12% basil oil, 32% Tween 80, 4% sorbitol, 12% ethanol, 40% water) were characterized for droplet size, PDI, zeta potential, pH, and viscosity. Stability was evaluated by monitoring droplet size and PDI over time and by determining the retention of eugenol, methyl eugenol, and β-caryophyllene after storage at 45 °C. Fish anesthetic efficacy was tested in koi carp (Cyprinus carpio var. koi). Results: SNEDDS maintained a small droplet size (~22.78 ± 1.99 nm) and low PDI (0.188 ± 0.088 at day 60), while ME showed significant size enlargement (up to 177.10 ± 47.50 nm) and high PDI (>0.5). After 90 days at 45 °C, SNEDDS retained 94.45% eugenol, 94.08% methyl eugenol, and 88.55% β-caryophyllene, while ME preserved 104.76%, 103.53%, and 94.47%, respectively. In vivo testing showed that SNEDDS achieved faster anesthesia (114.70 ± 24.80 s at 120 ppm) and shorter recovery (379.60 ± 15.61 s) than ME (134.90 ± 4.70 s; 473.80 ± 16.94 s). Ethanol failed to induce anesthesia at 40 ppm and performed poorly compared to SNEDDS and ME at other concentrations (p < 0.0001). Conclusions: SNEDDS demonstrated superior physical stability and fish anesthetic performance compared to ME. These findings support SNEDDS as a promising formulation for delivering holy basil essential oil in biomedical and aquaculture applications. Full article

The scalability and processability of high-performance membranes remain significant challenges in membrane technology. This work focuses on optimizing the pilot-scale production of patterned polysulfone (PSf) ultrafiltration membranes using the spray-modified non-solvent-induced phase separation (s-NIPS) method on a roll-to-roll pilot line. s-NIPS has already been studied extensively at lab-scale to prepare patterned membranes for various applications including membrane bioreactors (MBR), reverse osmosis (RO) and forward osmosis (FO). Although studied at the lab scale, membranes prepared at a larger scale can significantly differ in performance; therefore, phase inversion parameters, including polymer concentration, molecular weight, and additive type (i.e., polyethylene glycol (PEG) or polyvinylpyrolidine (PVP)) and concentration, were systematically varied when casting on a roll-to-roll, 12″ wide pilot line to identify optimal conditions for achieving defect-free, high-performance, patterned PSf membranes. The membranes were characterized for their pure water permeance, BSA rejection, casting solution viscosities, and resulting morphology. s-NIPS patterned membranes exhibit 150–350% increase in water flux as compared to their reference flat membrane, thanks to very high pattern heights up to 825 µm and formation of finger-like macrovoids. This work bridges the gap between lab-scale and pilot-scale membrane preparation, while proposing an upscaled membrane with great potential for use in water treatment. Full article

Introduction: Myotonia is a rare neuromuscular condition characterized by impaired muscle relaxation. In this study, we provide normative values for clinical tests related to myotonia in the Hungarian population and compare them to patients with myotonic dystrophy type 1 (DM1). Methods: Relaxation tests (10 eye openings, tongue extension, and palm openings), handgrip strength, and the nine-hole peg test were conducted on 139 healthy individuals and 31 patients with DM1. Results: We observed non-significant declines in handgrip strength and relaxation tests with age (p < 0.05). Significant differences were found between controls (n:139) and patients with DM1 (n = 31) in all tests (p < 0.05). Sex differences were noted in the healthy population: men (n:68/139) had stronger handgrip (mean of men 42.45 ± 1.15 vs. women 24.3 ± 0.9) and slower relaxation tests (mean of eye openings in men 3.6 ± 0.2 vs. in women 4.2 ± 0.2, tongue extensions in men 3.7 ± 0.2 vs. in women 4.2 ± 0.2, palm openings in men 4 ± 0.2 vs. in women 4.9 ± 0.2 However, these differences were not present among patients with DM1. Discussion: Normal values for relaxation tests across different age groups were established. These results might be useful for further clinical investigations. Our study supports the usage of averages of healthy population instead of age groups of relaxation tests and their clinical relevance in the evaluation of patients with myotonia. Full article

Polyethylene oxide (PEO) is the most well-studied polymer used in solid polymer electrolytes (SPEs) for lithium ion batteries (Li-ion batteries). However, ionic conductivity is greatly reduced in the low temperature range due to the crystallization of PEO. Therefore, methods to suppress the crystallization of PEO at room temperature by cross-linking or introducing a branched structure are currently being investigated. In this study, we synthesized new comb-type ion-conducting polyethers with two different side chains such as polydimethylsiloxane (PDMS) and polyethylene glycol monomethyl ether (mPEG) segments as flexible and ion-conducting segments, respectively. The introduction of the PDMS segment was found to prevent a decrease in ionic conductivity in the low-temperature region, but led to an ionic conductivity decrease in the high temperature region. On the other hand, the introduction of mPEG segments improved ionic conductivity in the high-temperature region. The introduction of mPEG segments with longer chains resulted in a significant decrease in ionic conductivity in the low-temperature region. Full article

Glutathione peroxidase (GPX) is crucial in mediating plant responses to abiotic stresses. In this study, bioinformatics methods were used to identify the GPX gene family in quinoa. A total of 15 CqGPX genes were identified at the quinoa genome level and conducted preliminary analysis on their protein characteristics, chromosome distribution, gene structure, conserved domain structure, cis-acting elements, and expression patterns. Phylogenetic analysis showed that the GPX genes of quinoa, Arabidopsis, soybean, rice, and maize were divided into three groups. Most of the CqGPXs had the three characteristic conserved motifs and other conserved sequences and amino acid residues. Six types of cis-acting elements were identified in the CqGPX gene promoter, with stress and hormone response-related cis-acting elements constituting the two main categories. Additionally, the expression patterns of CqGPX genes across various tissues and their responses to treatments with NaCl, PEG, CdCl₂, and H₂O₂ were also investigated. The qRT-PCR results showed significant differences in the expression levels of the CqGPX genes under stress treatment at different time points. Consistently, the activity of glutathione peroxidase enzymes increased under stresses. Heterologous expression of CqGPX4 and CqGPX15 conferred stress tolerance to E. coli. This study will provide a reference for exploring the function of CqGPX genes. Full article

The use of orthodontic microimplants in daily practice is now an indispensable part of orthodontic treatment. Unfortunately, the use of skeletal anchorage is associated with a relatively high risk of loss of microimplant stability because of inflammation developing in the surrounding soft tissues. The aim of this systematic review is to identify possible methods of orthodontic microimplant surface modifications providing antibacterial properties. The PubMed, Web of Science, Embase, and Cochrane Reviews databases were searched, and a literature review was conducted. The search was performed between 1 December 2024 and 31 December 2024. The authors used the PICO format to facilitate the search of abstracts and ensure that the relevant components of the question are well defined. The systematic review was written based on the principles detailed in PRISMA. The quality of the papers was assessed based on a tool developed by the authors. Three papers were rated Low Risk of Bias (RoB), four were rated Moderate RoB, and three were rated High RoB. All of the studies presented a method to increase the antibacterial properties of microimplants. More research with a unified methodology is necessary to confirm the effectiveness of the analyzed methods. ZnO, antibiotics, chlorhexidine, silver compounds, selenium, HA, and PEG polymerization plasma represent an interesting perspective for improving the antibacterial properties of orthodontic microimplants. Full article

The production of water-in-water emulsion droplets, the coalescence of which is prevented by adding oil-in-water micrometric droplets, is reported. Hexadecane (O) and cetyl trimethyl ammonium bromide (CTAB) were added to a W/W emulsion made of dextran (Dex)-enriched droplets in a Polyethyleglycol (PEG)-enriched continuous phase, and the mixture was further sonicated. Using Nile red to label the oil droplets enabled the observation of their presence at the surface of Dex droplets (5 µm), allowing for stabilizing them, preventing coalescence of the W/W emulsion, and mimicking W/O/W double emulsions. The addition of sulfate derivative of Dextran (DexSulf) allowed for stable droplets of a slightly larger diameter. By contrast, the addition of carboxymethyl Dextran (CMDex) destabilized the initial aqueous double-like emulsion, yielding sequestration of the oil droplets within the Dex-rich phase. Interestingly, addition of DexSulf to that unstable emulsion re-yielded stable droplets. Similar findings (destabilization) were obtained when adding sodium dodecyl sulfate (SDS) to the initial double-like emulsion, which reformed stable droplets when adding positively charged Dextran (DEAEDex) derivatives. The use of fluorescently (FITC) labeled derivatives of Dextran (Dex, CMDex, DEAEDex, and DexSulf) allowed us to follow their position within, out of, or at the interface of droplets in the above-mentioned mixtures. These findings are expected to be of interest in the field of materials chemistry. Full article