Search Results (109)

This work investigates the impact of an internal electric field on the annihilation characteristics of positrons implanted in a $180\left(10\right)\mathrm{nm}$ SiO₂ layer of a Metal-Oxide-Silicon (MOS) capacitor, using Positron Annihilation Lifetime Spectroscopy (PALS). By varying the gate voltage, electric fields up to $1.72\mathrm{MV}/\mathrm{cm}$ were applied. The measurements reveal a field-dependent suppression of positronium (Ps) formation by up to $64\%$, leading to an enhancement of free positron annihilation. The increase in free positrons suggests that vacancy clusters are the dominant defect type in the oxide layer. Additionally, drift towards the SiO₂/Si interface reveals not only larger void-like defects but also a distinct population of smaller traps that are less prominent when drifting to the Al/SiO₂ interface. In total, by combining positron drift with PALS, more detailed insights into the nature and spatial distribution of defects within the SiO₂ network and in particular near the SiO₂/Si interface are obtained. Full article

This study presents a methodological framework for optimizing “blank” solid lipid nanoparticles (SLNs), focusing on the use of a design of experiments (DOE) approach. Rather than emphasizing the applications of SLNs, the objective is to identify and optimize critical formulation and process parameters—specifically those influencing particle size (PS), polydispersity index (PDI), and zeta potential (ZP)—during early development stages. A non-classical mixed design was applied using AZURAD^® software (version 4.4.1), incorporating a mixture variable for lipid composition (comprising carnauba wax, glyceryl behenate, glyceryl distearate), and two quantitative factors: the percentage of polysorbate 80 (P80) in the P80/sorbitan oleate surfactant system and ultrasound (US) treatment time. The DOE analysis identified P80 concentration as a key parameter, with optimal formulations observed when P80 ranged between 35% and 45%. A fixed P80 ratio of 41% and a US time of 7.5 min enabled precise adjustment of lipid composition. Following a desirability function analysis, an optimized formulation was obtained with a PS of 176.3 ± 2.78 nm, a PDI of 0.268 ± 0.022, and a ZP of −35.5 ± 0.36 mV. These findings validate the relevance of our DOE-based strategy, offering a scalable, cost-effective platform that reduces material use, time, and analytical effort in SLN development. Full article

Background: Skin cancer has become a global health issue because of increasing exposure to environmental contaminants and UV radiation. Terbinafine hydrochloride (TRB), a broad-spectrum antifungal medication, has demonstrated notable anti-tumor properties in previous studies; however, its repurposing for skin cancer therapy remains underexplored. Objective: This study reports for the first time, the development of a new delivery system: a nanoemulsion (NE)–foam hybrid system, i.e., “nanoemulfoam” (NEF), designed to enhance the topical TRB delivery to the skin. The study applied this new hybrid system on TRB for managing skin cancer. Method: The TRB-loaded NEF was produced by loading TRB into a liquid NE. then this was incorporated into a liquid foam base and actuated into foam using a non-propellant mechanism. The NE was developed utilizing peppermint oil as the oil phase and Tween-20/ethanol as the surfactant/co-surfactant combination (Smix). The formulation underwent optimization using the D-optimal design that enabled the simultaneous evaluation of the impact of oil concentration and Tween 20 concentration in the Smix on the particle size (PS), zeta potential (ZP), and dissolution efficiency percent (DE%). Results: The optimal NE formula displayed a small PS of 186.60 ± 2.84 nm, ZP of −13.90 ± 0.99 mV, and DE% of 68.50 ± 1.78% (mean ± SD, n = 3). After incorporation into the foam system, the produced TRB-loaded NEF demonstrated a 7.43-fold increase in the drug transdermal flux in comparison with plain drug foam (p < 0.05). The TRB-loaded NEF showed no signs of inflammation or irritation when applied to abdominal rabbit skin, indicating its safety. The optimum formula exhibited a statistically significant 10-fold increase in cytotoxicity against A-431 skin cancer cells compared to TRB alone, along with a 1.54-fold increase in apoptosis (p < 0.05). Molecular docking studies targeting CDK2, a key regulator of cell proliferation and a known TRB target, revealed that TRB displayed highly favorable binding scores compared to the reference drug. Conclusions: The TRB-loaded NEF represents a promising nanotechnology-based approach for the topical treatment of skin cancer, supporting further investigation toward clinical translation. Full article

With continued scaling of CMOS technology, the critical charge required for state retention in SRAM cells has decreased, leading to increased vulnerability to radiation-induced soft errors such as single-event upsets (SEUs) and single-event multi-node upsets (SEMNUs) in space environments. To address these reliability challenges, this paper proposes a 16-transistor radiation-hardened SRAM cell, EWS-16T, designed to improve resilience against soft errors. The performance of the proposed EWS-16T cell was evaluated through the 90 nm CMOS process and compared with previously reported radiation-hardened cells, including QCCS, SCCS, SAW16T, HP16T, RHSCC16T, and S8P8N. The results show that EWS-16T achieves the shortest write access time (22.11 ps) and the highest word line write trip voltage (WWTV) (279 mV) among all comparison cells. In addition, it demonstrates excellent performance in terms of critical charge tolerance (>300 fC) and low hold power consumption (53 nW). Furthermore, a comprehensive performance evaluation using the electrical quality metric (EQM) confirms that the EWS-16T cell achieves an outstanding balance among write efficiency, power consumption, and soft error resilience. These results indicate that EWS-16T is a highly promising SRAM design capable of ensuring reliable operation even in radiation-intensive space environments. Full article

A conventional microchannel plate framing camera is typically utilized for inertial confinement fusion diagnosis. However, as a vacuum electronic device, it has inherent limitations, such as a complex structure and the inability to achieve single-line-of-sight imaging. To address these challenges, a CMOS image sensor that can be seamlessly integrated with an electronic pulse broadening system can provide a viable alternative to the microchannel plate detector. This paper introduces the design of an 8 × 8 pixel-array ultrashort shutter-time single-framing CMOS image sensor, which leverages silicon epitaxial processing and a 0.18 μm standard CMOS process. The focus of this study is on the photodiode and the readout pixel-array circuit. The photodiode, designed using the silicon epitaxial process, achieves a quantum efficiency exceeding 30% in the visible light band at a bias voltage of 1.8 V, with a temporal resolution greater than 200 ps for visible light. The readout pixel-array circuit, which is based on the 0.18 μm standard CMOS process, incorporates 5T structure pixel units, voltage-controlled delayers, clock trees, and row-column decoding and scanning circuits. Simulations of the pixel circuit demonstrate an optimal temporal resolution of 60 ps. Under the shutter condition with the best temporal resolution, the maximum output swing of the pixel circuit is 448 mV, and the output noise is 77.47 μV, resulting in a dynamic range of 75.2 dB for the pixel circuit; the small-signal responsivity is 1.93 × 10⁻⁷ V/e⁻, and the full-well capacity is 2.3 Me⁻. The maximum power consumption of the 8 × 8 pixel-array and its control circuits is 0.35 mW. Considering both the photodiode and the pixel circuit, the proposed CMOS image sensor achieves a temporal resolution better than 209 ps. Full article

Background: Anthralin is known for its efficacy in treating psoriasis and acne, possessing poor solubility. Addressing these limitations, the present study endeavors to develop a microemulgel formulation of anthralin aimed at enhancing solubility. Method: The solubility study was performed in various solvents. An o/w (oil-in-water) emulsion was formed using the water titration method, which was optimized by statistical experimental design half-run CCD. The final optimized batch was evaluated for physicochemical and in vitro properties Result: The final optimized batch showed a particle size (PS) of 417 nm, −25.2 mV zeta potential (ZP) and pH 5.8, which remained stable upon centrifugation, heating–cooling and freeze–thawing cycle. Furthermore, microemulsion with Carbopol 943 5% w/v was selected as the gel base for the formation of microemulgel characterized by PS, ZP, pH, and viscosity of 230 nm, −50.6 mV, 6.9 and 14,200 cps, respectively, that ensured it a high enough stability. In silico molecular docking between ligand and protein provides the binding energies validating the interaction. Hence, the in silico study was performed for psoriasis and P. acne proteins. An in vitro antibacterial activity study on Propionibacterium revealed a significant efficiency of the formulation and MTT assay using L929 cell line in the presence of the drug-loaded microemulgel indicated an inhibition of growth proving that formulation has anti-psoriatic activity. Conclusions: Combination therapy with Clindamycin might improve efficacy while reducing antibiotic resistance risks. Full article

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy associated with a poor prognosis. Activating mutations in the FLT3 gene occur in approximately 30% of AML cases, with internal tandem duplications in the juxtamembrane domain (FLT3-ITD; 75%) and mutations in the tyrosine kinase domain (FLT3-TKD; 25%). FLT3-ITD mutations are linked to poor prognosis and offer significant clinical predictive value, whereas the implications of FLT3-TKD mutations are less understood. The Hedgehog–Gli pathway is an established therapeutic target in AML, and emerging evidence suggests crosstalk between FLT3-ITD signaling and Gli expression regulation via non-canonical mechanisms. Post-translational modifications involving myristic and palmitic acids regulate various cellular processes, but their role in AML remains poorly defined. In this study, we investigated the role of fatty acid synthase (FASN), which synthesizes myristic and palmitic acids and catalyzes palmitoyl-acyltransferation, in regulating FLT3-ITD-Gli signaling. FASN knockdown using shRNA and the FASN inhibitor TVB-3166 was performed in FLT3-ITD-mutated AML cell lines (MOLM13, MV411) and Baf3-FLT3-ITD cells. The impact of FASN inhibition was assessed through Western blot and kinome profiling, while biological implications were evaluated by measuring cell viability and proliferation. FASN inhibition resulted in reduced levels of phospho-Akt (pAkt) and phospho-S6 kinase (pS6) and decreased expression of Hedgehog–Gli1, confirming non-canonical regulation of Gli by FLT3-ITD signaling. Combining TVB-3166 with the Gli inhibitor GANT61 significantly reduced the survival of MOLM13 and MV411 cells. Full article

Microalgae–fungal pellets (MFPs) effectively degrade pollutants in high-density aquaculture wastewater; however, their structural instability limits their long-term applicability. This study evaluated the effects of three crosslinking agents, sodium alginate (SA), chitosan (CTS), and polyvinyl alcohol (PVA), on enhancing the stability of MFPs. The results demonstrated that the initial 20 g/L SA-crosslinked MFP sample (SMFP₀) exhibited significantly improved structural stability, maintaining superior mechanical hardness (57.05 g) after 9 days. Further analysis revealed that SMFP₀ exhibited a more negative absolute Zeta potential (−13.05 mV), increased fluorescence intensity (0.020) in its tightly bound extracellular polymeric substances (TB-EPSs), and significantly higher protein (PN, 64.22 mg/L) and polysaccharide (PS, 56.99 mg/L) concentrations compared with the control (p < 0.05). These findings suggest that SMFP₀ possesses physicochemical properties that are conducive to microalgae–fungal aggregation. A scanning electron microscopy (SEM) analysis confirmed that the SA gel network enhanced the system’s stability by strengthening the microalgae–fungal interfacial adhesion and maintaining a porous, light-permeable structure. In practical wastewater treatment, SMFP₀ achieved superior removal rates for COD (84.19%), ammonia nitrogen (95.29%), total nitrogen (89.50%), and total phosphorus (93.46%) compared with non-crosslinked MFPs (p < 0.05). After 9 days of continuous operation (SMFP₉), the pollutant removal efficiencies remained comparable to those observed in the initial stage of the non-crosslinked system, indicating improved structural durability for extended practical application. Full article

Objectives: This study characterised and evaluated the stability, solubility, and in vitro drug release of OA- and AA-loaded SLNs. Methods: The OA- and AA-SLNs were formulated using the emulsion solvent evaporation method and characterised based on particle size (PS), polydispersity index (PDI), zeta potential (ZP), and transmission electron microscopy (TEM). Solubility studies were conducted in PBS (pH 1.2 and 6.8) and dH₂O using HPLC, while in vitro drug release was assessed in simulated intestinal fluid (SIF) (pH 6.8). Results: The optimised OA-SLNs (1:1 drug-to-lipid ratio) showed PS, PDI, ZP, and EE% values of 312.9 ± 3.617 nm, 0.157 ± 0.014, −17.0 ± 0.513 mV, and 86.54 ± 1.818%, respectively. The optimised AA-SLNs (1:2 drug-to-lipid: ratio) had a PS of 115.5 ± 0.458 nm, PDI of 0.255 ± 0.007, ZP of −11.9 ± 0.321 mV, and EE% of 76.22 ± 0.436%. The SLNs remained stable for 60 days at 4 °C and room temperature (p < 0.05). The solubility study revealed that free OA and AA showed no measurable values in the three solvents. However, OA-SLNs showed the highest solubility in H₂O (16-fold) followed by PBS at pH 6.8 (10-fold) and pH 1.2 (10-fold). AA-SLNs significantly improved the solubility in PBS at pH 6.8 (88-fold), compared to dH₂O (6-fold) and PBS at pH 1.2 (26-fold). In vitro drug release studies showed that OA release from the SLNs was significantly increased within 300 min (p < 0.05) compared to the free drug. Similarly, AA release from the SLNs was significantly increased within 300 min (p < 0.05) compared to free AA. Conclusions: These results demonstrate that SLNs enhance OA and AA solubility and drug release, suggesting a promising strategy for improving oral bioavailability and therapeutic efficacy. Full article

Background/Objectives: Diabetic mouth ulcers are a pathological condition of the oral mucosa leading to increases in susceptibility to infection and prolonged wound healing time. Still, there is a lack of natural formulations for treating this condition. Our principal objective was to formulate solid lipid nanoparticles (SLNs) that contained Althaea officinalis (marshmallow) (M.) extract with clove oil (CO.), subsequently integrated into a collagen sponge for enhancing stability, solubility, sustained release, antimicrobial efficacy, and healing power when targeting diabetic oral ulcers. Methods: A factorial design of 34 trials was established to evaluate the influence of lipid concentration (A), SAA concentration (B), lipid type (C), and SAA type (D). The optimized M-CO-SLNs was selected using Design Expert^®, the based Poly dispersibility index (Y2), zeta potential (MV) (Y3), and encapsulation efficiency (%) (Y4). The optimized SLNs were integrated into a collagen sponge matrix and tested for their antibacterial and antifungal efficacy against Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, respectively. Moreover, they were tested for their wound healing power in a diabetic mouth ulcer model. Results: The optimized formula (Run 16: 5% lipid concentration, 4% SAA concentration, capric acid) demonstrated P.S (110 ± 0.76 nm), ZP (−24 ± 0.32 mV), PDI (0.18 ± 0.05), and EE% (90 ± 0.65%.). The optimized M-CO-SLNs formula was incorporated into a cross-linked collagen sponge and showed superior antimicrobial efficacy, an increased swelling ratio, and was effective in an in vivo oral ulcer study, as evidenced by ELISA biomarkers, gene expression analysis, and histological analysis. Conclusions: M-CO-SLNs embedded in collagen sponges is a promising therapeutic formula for clinical application against diabetic mouth ulcers. Full article

Objective: This study aims to develop an intranasal (IN) delivery system for glioblastoma multiforme (GBM) management using repurposed superparamagnetic iron-oxide (SPION) loaded with atorvastatin (ATO)-nanostructured lipid carrier (NLC). Methods: Emulsification and ultrasonication were used to formulate ATO-NLCs, and the best formula was loaded with SPION to make the final atorvastatin/superparamagnetic iron oxide-loaded nanostructured lipid carrier (ASN) formulation. Entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and drug release after 6 h (Q6h) were evaluated for NLCs. ASN was tested for cytotoxicity on T98G cancer cells, and the cell cycle was examined to determine cell death. Furthermore, the ability of the optimal formulation to suppress the levels of inflammatory biomarkers was investigated in Lipopolysaccharide (LPS)-induced inflammation. The brain-targeting behavior of IN-ASN was visualized in rabbits via confocal laser scanning microscopy (CLSM). Results: The optimum NLC exhibited a spherical shape, EE% of 84.0 ± 0.67%, PS of 282.50 ± 0.51 nm, ZP of −18.40 ± 0.15 mV, and Q6h of 89.23%. The cytotoxicity of ASN against cancer cells was 4.4-fold higher than ATO suspension, with a 1.3-fold increment in cell apoptosis. ASN showed significantly reduced pro-inflammatory biomarkers (IL-β, IL-6, TNF-α, TLR4, NF-қB), whereas CLSM revealed enhanced brain delivery with no observed histopathological nasal irritation. The in silico analysis demonstrated enhanced ATO-ADME (absorption, distribution, metabolism, and excretion) properties, while the network pharmacology study identified 10 target GBM genes, among which MAPK3 was the most prominent with a good binding score as elucidated by the simulated docking study. Conclusions: These findings may present ATO/SPION-NLCs as significant evidence for repurposing atorvastatin in the treatment of glioblastoma multiforme. Full article

Objectives: This study aimed to develop hesperidin solid lipid nanoparticles (HESP-SLNs) to enhance their stability, solubility, and sustained release for wound healing; further enhancement was achieved through prepared nanostructured lipid carriers (HESP-NLCs) using Tea Tree Oil (TTO) to explore their synergistic efficacy. Methods: A factorial design of 2⁴ trials was established to evaluate the influence of lipid type (X1), lipid conc (%) (X2), surfactant type (X3), and sonication amplitude (%) (X4) of prepared HESP-SLNs on the particle size (nm) (Y1), polydispersibility index (Y2), zeta potential (Y3), and encapsulation efficiency (%) (Y4). The optimized HESP-SLNs formula was selected utilizing Design Expert^® software version 13, which was additionally enhanced by preparing TTO-loaded HESP-NLCs. In vitro release, Raman spectroscopy, and transmission electron microscopy were carried out for both lipid nanoparticles. Cytotoxicity, in vivo wound-healing assessments, and skin irritancy tests were performed to evaluate the performance of TTO-incorporated HESP-NLCs compared to HESP-SLNs. Results: The optimized formula demonstrated PS (280 ± 1.35 nm), ZP (−39.4 ± 0.92 mV), PDI (0.239 ± 0.012), and EE% (88.2 ± 2.09%). NLCs enhanced Q6% release, (95.14%) vs. (79.69%), for SLNs and showed superior antimicrobial efficacy. Both lipid nanoparticles exhibited spherical morphology and compatibility between HESP and excipients. NLCs achieved the highest wound closure percentage, supported by histological analysis and inflammatory biomarker outcomes. Cytotoxicity evaluation showed 87% cell viability compared to untreated HSF cells, and the skin irritancy test confirmed the safety of NLCs. Conclusions: TTO-loaded HESP-NLCs are promising candidates exhibiting superior wound-healing capabilities, making them a potential therapeutic option for cutaneous wound management. Full article

Morphological changes in erythrocytes during disease, aging, or reactions to external agents are significant as they can influence disease progression. However, the exact mechanisms behind these temporary alterations and their potential to cause dysfunction remain unclear. Using a saponin-induced erythrocyte shape transition (EST) model, we studied the gradual shift of erythrocytes towards echino-stomato-spherocytic forms and its link to hemolysis and thrombosis. We observed that different saponin concentrations elicited varying shape transformations. At low concentrations, erythrocytes transition from discocytic shapes to echinocytic, echino-stomatocytic, and ultimately stomatocytic forms. As the concentration moderately increases, the morphology evolves into stomato-spherocytic forms. At higher saponin concentrations, the erythrocytes completely transform into spherocytic forms. Regardless of the transformation degree, all forms showed increased phosphatidylserine exposure (PS) and microvesicle (MV) production, primarily due to increased scramblase and decreased flippase activity, which were influenced by elevated calcium levels and caspase 3 activity, effectively managing PS distribution and influencing cell membrane expansion and invagination. These alterations increased thrombin production, erythrocyte adhesion, and aggregation, promoting thrombosis in rats. Altogether, our findings indicate that the shift towards echino-stomato-spherocytic forms fosters a hypercoagulable state through PS externalization, heightening thrombotic risk. Full article

Background: Infectious bronchitis virus (IBV) causes a significant illness in birds, making it a leading source of financial loss in the poultry business. The objective of this study was to assess the effectiveness of proliposomes (PLs) containing ivermectin (IVM) against IBV using embryonated chicken eggs (ECEs). Methods: A three-factor, two-level (2³) full factorial design was employed; carrier/lipid phase ratio (A), stearyl glycyrrhetinate amount (B), and phospholipid type (C) were studied as independent variables, while product yield (PY), entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and cumulative percentage of drug released after 6 h (Q6h) were characterized. The selected formulations (PL2 and PL6) were subjected to further characterizations, including IVM toxicity and anti-viral activity. Results: The PY% ranged from 88.6 ± 2.19% to 98.8 ± 0.45%, EE% was from 71.8 ± 2.01% to 96.1 ± 0.51%, PS was from 330.1 ± 55.65 nm to 1801.6 ± 45.61 nm, PDI was from 0.205 ± 0.06 to 0.603 ± 0.03, ZP was from −18.2 ± 0.60 mV to −50.1 ± 1.80 mV, and Q6h was from 80.95 ± 1.36% to 88.79 ± 2.03%. IVM-loaded PLs had lower toxicity in ECEs than pure IVM; the mortality rate was substantially reduced in IBV-infected ECEs injected with PL2 rather than pure IVM. As further evidence of IVM’s anti-viral action against IBV, quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the PL2-treated group exhibited further reduction in IBV’s copies in comparison with the pure IVM-treated group. Conclusions: PLs loaded with IVM are an innovative and potentially effective way to inhibit IBV. Full article

Background. Pulmonary vein isolation (PVI) represents the cornerstone of paroxysmal (PAF) and persistent atrial fibrillation (PsAF) ablation. Impedance values provide insights on tissue conductive properties. Methods. Consecutive patients undergoing PAF and PsAF ablation were prospectively enrolled. All the patients underwent a preprocedural multidetector computed tomography (MDCT) to evaluate left atrial wall thickness (LAWT). Electroanatomic maps were acquired with the ablation catheter, and impedance values (Ω) and voltage amplitude (mV) of bipolar electrograms were collected. Results. A total of 60 patients (40 with PAF and 20 with PsAF) were included in the study. In all PAF cases, no voltage value lower than 0.5 mV was found at LA mapping; the corresponding mean impedance value was 151.5 ± 5.4 Ω. In PsAF cases, voltage values inferior to 0.05 mV have been reported in 19/20 patients. PsAF patients showed a mean impedance value of 129.1 ± 3.8 Ω. The correlation analysis between bipolar voltage and impedance reported an r_s value of 0.4166 (p < 0.001), showing a positive correlation between the two variables. On the contrary, no direct correlation was found between voltage and LAWT and between impedance and LAWT (rsv-t = 0.1838; rsi-t = 0.1133, respectively). Conclusions. This research study suggests a correlation between voltage amplitude and impedance values, so that impedance might be used for arrhythmogenic substrate characterization. Full article