Search Results (192)

Background: Cerebral aneurysm (CA) is a focal or diffuse pathological dilation of the cerebral arterial wall that arises due to various etiological factors. It represents a serious vascular condition, particularly affecting the elderly, and carries a high risk of rupture and neurological morbidity. Clonidine (CL), an α2-adrenergic receptor agonist, has been reported to suppress aneurysm progression; however, its underlying molecular mechanisms, especially in relation to cerebral endothelial dysfunction, remain unclear. This study aimed to investigate the potential of CL to mitigate CA development by modulating apoptosis, inflammation, and oxidative stress in an Angiotensin II (Ang II)-induced endothelial injury model. Methods: Human brain microvascular endothelial cells (HBMECs) were used to establish an in vitro model of endothelial dysfunction by treating cells with 1 µM Ang II for 48 h. CL was administered 2 h prior to Ang II exposure at concentrations of 0.1, 1, and 10 µM. Cell viability was assessed using the MTT assay. Oxidative stress markers, including reactive oxygen species (ROS) and Nitric Oxide (NO), were measured using 2′,7′–dichlorofluorescin diacetate (DCFDA). Gene expression levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP-2 and MMP-9), high mobility group box 1 (HMGB1), and nuclear factor kappa B (NF-κB) were quantified using RT-qPCR. Levels of proinflammatory cytokines; tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and interferon-gamma (IFN-γ); were measured using commercial ELISA kits. Results: Ang II significantly increased ROS production and reduced NO levels, accompanied by heightened proinflammatory cytokine release and endothelial dysfunction. MTT assay revealed a marked decrease in cell viability following Ang II treatment (34.18%), whereas CL preserved cell viability in a concentration-dependent manner: 44.24% at 0.1 µM, 66.56% at 1 µM, and 81.74% at 10 µM. CL treatment also significantly attenuated ROS generation and inflammatory cytokine levels (p < 0.05). Furthermore, the expression of VEGF, HMGB1, NF-κB, MMP-2, and MMP-9 was significantly downregulated in response to CL. Conclusions: CL exerts a protective effect on endothelial cells by reducing oxidative stress and suppressing proinflammatory signaling pathways in Ang II-induced injury. These results support the potential of CL to mitigate endothelial injury in vitro, though further in vivo studies are required to confirm its translational relevance. Full article

Precision agriculture increasingly relies on real-time data from soil sensors to optimize irrigation and nutrient application. Soil moisture and electrical conductivity (EC) are key indicators in irrigation and fertigation systems, directly affecting water-use efficiency and nutrient delivery to crops. This study evaluates the performance of an IoT-based soil-monitoring system for real-time tracking of EC and soil moisture under varied fertigation conditions in both laboratory and field scenarios. The EC sensor showed strong agreement with laboratory YSI measurements (R² = 0.999), confirming its accuracy. Column experiments were conducted in three soil types (sand, sandy loam, and loamy sand) to assess the EC and soil moisture response to fertigation. Sand showed rapid infiltration and low retention, with EC peaking at 420 µS/cm and moisture 0.33 cm³/cm³, indicating high leaching risk. Sandy loam retained the most moisture (0.35 cm³/cm³) and showed the highest EC (550 µS/cm), while loamy sand exhibited intermediate behavior. Fertilizer-specific responses showed higher EC in Calcium Ammonium Nitrate (CAN)-treated soils, while Monoammonium Phosphate (MAP) showed lower, more stable EC due to limited phosphorus mobility. Field validation confirmed that the IoT system effectively captured irrigation and fertigation events through synchronized EC and moisture peaks. These findings highlight the efficacy of IoT-based sensor networks for continuous, high-resolution soil monitoring and their potential to support precision fertigation strategies, enhancing nutrient-use efficiency while minimizing environmental losses. Full article

Efficient thermal management is critical to the performance and acceptance of battery electric vehicles (BEVs). In the event of coolant leakage, contact between conventional water–glycol coolants and polarized battery components may induce hydrogen evolution via electrolysis, posing a serious safety hazard. This study investigates the impact of copper corrosion inhibitors and coolant electrical conductivity on hydrogen gas formation through linear sweep voltammetry (LSV) using copper electrodes. Results indicate that commonly used corrosion inhibitors—Tolyltriazole (TTZ), Benzotriazole (BTZ), and Sodium Mercaptobenzothiazole (MBT-Na)—do not significantly reduce hydrogen evolution, even in synergistic combinations. On the other hand, lowering the coolant electrical conductivity markedly decreased hydrogen evolution, with a linear reduction in cathodic current observed in low-conductivity coolants due to the reduced ionic mobility of the electrolyte. Low-conductivity BEV coolant (86 µS/cm) presented a cathodic current density 96% lower than a high-conductivity ICE coolant (2577 µS/cm) at the same overpotential. These findings suggest that optimizing coolant conductivity is a more effective mitigation strategy than relying on corrosion inhibitor formulations. Full article

Objectives: A simple method for quantifying fluconazole in small blood volumes has been developed using volumetric absorptive microsampling (VAMS^®) technology and isocratic high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Methods: For sample collection, Mitra^® devices are used to keep the sample volume at 10 µL. For the quantitative determination of fluconazole, the Mitra^® samples are extracted using acetonitrile as the extraction agent, containing 2-(4-chlorophenyl)-1,3-bis(1,2,4-triazol-1-yl)propan-2-ol as the internal standard. A Synergi 4 μm Polar-RP 80 Å (150 × 2 mm) column forms the stationary phase, and a mixture of acetonitrile and phosphate buffer is the mobile phase. The UV detection is set at a wavelength of 210 nm. The therapeutic concentration range of 5 to 160 mg/L is covered, and the linear equation with 1/x² weighting is used to determine unknown samples. This method has been validated according to the current EMA and FDA guidelines for bioanalytical methods. Results: The validation data obtained after analysing whole blood samples (EDTA) showed within- and between-run accuracy between 94.4% and 115% and precision between 0.4% and 9.4%, respectively. A lower limit of quantification (LLOQ) of 5 mg/L was sufficient for therapeutic drug monitoring in paediatric patients receiving fluconazole as antifungal prophylaxis after haematopoietic cell transplantation. Conclusions: So far, 211 samples from 49 patients were successfully analysed, and concentrations between 5.84 mg/L and 107 mg/L were determined for whole blood Mitra^® samples. To our knowledge, this is the first application of VAMS^® technology using simple and cheap HPLC-UV quantification. Full article

Heavy metal contamination of soil and water is a growing environmental concern, especially mercury, lead, and cadmium. Therefore, fast and reliable methodologies to assess contamination in the field are in demand. However, many methodologies require laborious, expensive, and cumbersome equipment that is not convenient for rapid field analysis. Mobile phone technology coupled with bioluminescent assays provides accessible hands-on alternatives that has already been shown to be feasible. Previously, we demonstrated that firefly luciferases can be harnessed as luminescence color-tuning sensors for toxic metals. An assay based on such a principle was already successfully applied for teaching biochemistry laboratory lessons, which demonstrates the effect of cadmium on enzyme function based on bioluminescence color change. For analytical detection of cadmium in water, here, we developed a novel bioluminescence assay using the cadmium-sensitive Amydetes vivianii firefly luciferase coupled with a cell phone provided with a program to quantify cadmium concentration based on luminescence color discrimination. The application has proven to be efficient with high precision between 0.10 and 2 mM of cadmium, being appliable to diluted water samples (0.1–2 µM) upon concentration and relying on reference cadmium standards values. The light emitted by the reference standards and samples in a dark box is captured by the smartphone’s camera, which, using computer vision, automatically quantifies cadmium according to the RGB color. CadmiLume is a simple and easy luminescent enzymatic biosensor for cadmium contamination in water samples, which instantaneously can provide results with the convenience of a smartphone in the palm of one’s hands. Full article

This study examines arsenic contamination in the Caplina Basin, Tacna, Peru, focusing on arsenic speciation and associated risks in surface waters. Arsenic concentrations were quantified using inductively coupled plasma mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Total arsenic levels ranged from 0.0304 mg/L to 0.0730 mg/L across all monitoring points, exceeding the World Health Organization (WHO) limit of 10 µg/L (0.01 mg/L) for drinking water. Arsenite (As(III)), the most toxic and mobile species, reached levels up to 0.0154 mg/L, posing a significant concern at Point 7, characterized by acidic pH (3.82) and high conductivity (1456 µS/cm). Arsenate (As(V)), less toxic but predominant under alkaline conditions, peaked at 0.0260 mg/L at Point 6 (pH 8.42). Organic species such as dimethylarsenic acid (DMA) and monomethylarsenic acid (MMA) were also detected, indicating active methylation processes and anthropogenic influences. The risk assessment revealed carcinogenic risk values ranging from 2.56 × 10⁻⁵ to 6.28 × 10⁻⁵, below the USEPA threshold (1 × 10⁻⁴), but significant for prolonged exposure. Non-carcinogenic hazard quotient (HQ) values ranged from 0.09 to 0.21. These findings highlight severe public health implications and emphasize the urgent need for comprehensive strategies, including continuous monitoring, targeted treatment technologies, and community education, in order to guarantee water quality in vulnerable areas. Full article

The incorporation of biopolymers and natural colorants in smart packaging has garnered significant attention in the food packaging industry. This study investigates the design and characterization of novel fibrous films incorporating betalain extract (BE) from Stenocereus thurberi in poly (lactic acid) (PLA). An electrospinning technique was developed with varying PLA concentrations (2%–12% w/v) and BE concentrations (8%–12% w/v) to create a colorimetric freshness indicator. BE was characterized by quantifying its phytochemical content and assessing its antioxidant capacity. Morphological and structural analyses included scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), polydispersity index (PI), mechanical properties, and functional characteristics such as ammonia sensitivity and total antioxidant activity. The results indicated that the incorporation of BE significantly influenced the average diameter of the nanofibers, ranging from 313 ± 74 nm to 657 ± 99 nm. SEM micrographs showed that PLA12-BE12 films exhibited smooth surfaces without bead formation. The FTIR analysis confirmed effective BE incorporation, revealing intermolecular interactions between the betalain molecules and the PLA matrix, which contributed to enhanced structural and functional stability. The mechanical properties analysis revealed that moderate BE additions (8%–10% w/v) enhanced the Young’s modulus and tensile strength, while higher BE concentrations (12% w/v) disrupted the polymer network, reducing these properties. Additionally, the strain at break decreased significantly with BE incorporation, reflecting limited molecular chain mobility. Increasing BE concentration notably improved antioxidant activity, with the BE concentration of 12% (w/v), the ABTS•+, DPPH•, and FRAP radical scavenging activities at the highest values of 84.28 ± 1.59%, 29.95 ± 0.34%, and 710.57 ± 28.90 µM ET/g, respectively. Ammonia sensitivity tests demonstrated a significant halochromic transition from reddish-pink to yellow, indicating high sensitivity to low ammonia concentrations. The possible mechanism is alkaline pH induces aldimine bond hydrolysis and generates betalamic acid (yellow) and cyclo-DOPA-5-O-ß-glucoside (colorless) The fibrous films also exhibited reversible color changes and maintained good color stability over 30 days, emphasizing their potential for use in smart packaging applications for real-time freshness monitoring and food quality assessment. Full article

Excessive consumption of vegetable oils such as soybean and canolla oils containing ω-6 polyunsaturated fatty acids is considered one of the most important epidemiological factors leading to the progression of lifestyle-related diseases. However, the underlying mechanism of vegetable-oil-induced organ damage is incompletely elucidated. Since proopiomelanocortin (POMC) neurons in the hypothalamus are related to the control of appetite and energy expenditure, their cell degeneration/death is crucial for the occurrence of obesity. In patients with metabolic syndrome, saturated fatty acids, especially palmitate, are used as an energy source. Since abundant reactive oxygen species are produced during β-oxidation of the palmitate in mitochondria, an increased amount of 4-hydroxy-2-nonenal (4-HNE) is endogenously generated from linoleic acids constituting cardiolipin of the inner membranes. Further, due to the daily intake of deep-fried foods and/or high-fat diets cooked using vegetable oils, exogenous 4-HNE being generated via lipid peroxidation during heating is incorporated into the blood. By binding with atheromatous and/or senile plaques, 4-HNE inactivates proteins via forming hybrid covalent chemical addition compounds and causes cellular dysfunction and tissue damage by the specific oxidation carbonylation. 4-HNE overstimulates G-protein-coupled receptors to induce abnormal Ca²⁺ mobilization and µ-calpain activation. This endogenous and exogenous 4-HNE synergically causes POMC neuronal degeneration/death and obesity. Then, the resultant metabolic disorder facilitates degeneration/death of hippocampal neurons, pancreatic β-cells, and hepatocytes. Hsp70.1 is a molecular chaperone which is crucial for both protein quality control and the stabilization of lysosomal limiting membranes. Focusing on the monkey hippocampus after ischemia, previously we formulated the ‘calpain–cathepsin hypothesis’, i.e., that calpain-mediated cleavage of carbonylated Hsp70.1 is a trigger of programmed neuronal death. This review aims to report that in diverse organs, lysosomal cell degeneration/death occurs via the calpain–cathepsin cascade after the consecutive injections of synthetic 4-HNE in monkeys. Presumably, 4-HNE is a root substance of lysosomal cell death for lifestyle-related diseases. Full article

Energy harvesting plays an important role in advancing personalized wearables by enabling continuous monitoring, enhancing wearable functionality and facilitating sustainable solutions. We aimed to develop a flexible piezoelectric energy harvesting system based on inorganic piezoelectric materials that convert mechanical energy into electricity to power a wide range of mobile and portable electronic devices. There is significant interest in flexible piezoelectric energy harvesting systems that use inorganic piezoelectric materials due to their exceptional physical features and prospective applications. Herein, we successfully demonstrated a flexible piezoelectric nanogenerator (PENG) designed by the co-doped rare-earth element ceramics (RE-PMN-PT) embedded in PVDF and PDMS composite film and attained a significant output performance while avoiding electrical poling process. The impact of dielectric characteristics on the electrical output of nanogenerators was investigated, together with the structure of the composites. The Sm/La-PMN-PT particles effectively amplify both the voltage and current output, showcasing their potential to power portable and wearable devices, as demonstrated by their capacity to illuminate LEDs. The maximal output power of 2 mW was correlated with the high voltage (220 V) and current (90 µA) of Sm/La-PMN-PT/PVDF, which demonstrated that the device has the potential for energy harvesting in biomedical applications. Full article

Helminth infections pose a significant global health challenge, as existing drugs often lack efficacy and may be contraindicated in some populations. Progress in the development of new drugs is hindered by the lack of innovative models for use in drug research. Metarhabditis blumi nematodes, which are associated with parasitic otitis in cattle, can severely affect the nervous system, leading to death. The treatment and control of this pathology face similar limitations to those for other parasitic diseases. Our study aimed to standardize M. blumi as a model for evaluating the anthelmintic activity of new drugs. Larvae (L3) and adult worms were treated with the reference drugs albendazole (16 µM) and ivermectin (2.5 µM) diluted in an NGM medium for 24 h, and various parameters were evaluated. Motility and mobility were analyzed using a video tracking and analysis program. Morphological and ultrastructural characterizations were performed after chemical fixation using light and scanning electron microscopy (SEM). The results showed that ivermectin was more effective than albendazole in treating M. blumi adults and L3. The SEM images revealed drug-induced ultrastructural changes. Compared to previous studies using the established Caenorhabditis elegans model, M. blumi demonstrated greater resistance to both albendazole and ivermectin. We conclude that M. blumi is a viable model for drug discovery assays and a valuable new experimental model for various biological studies, highlighting that, unlike C. elegans, M. blumi is associated with parasitism. Full article

Microplastics (MPLs) and nanoplastics (NPLs) are smaller particles derived from larger plastic material, polymerization, or refuse. In context to environmental health, they are separated into the industrially-created “primary” category or the degradation derivative “secondary” category where the particles exhibit different physiochemical characteristics that attenuate their toxicities. However, some particle types are more well documented in terms of their fate in the environment and potential toxicological effects (secondary) versus their industrial fabrication and chemical characterization (primary). Fourier Transform Infrared Spectroscopy (FTIR/µ-FTIR), Raman/µ-Raman, Proton Nuclear Magnetic Resonance (H-NMR), Curie Point-Gas Chromatography-Mass Spectrometry (CP-gc-MS), Induced Coupled Plasma-Mass Spectrometry (ICP-MS), Nanoparticle Tracking Analysis (NTA), Field Flow Fractionation-Multiple Angle Light Scattering (FFF-MALS), Differential Scanning Calorimetry (DSC), Thermogravimetry (TGA), Differential Mobility Particle [Sizing] (DMPS), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Scanning Transmission X-ray Microspectroscopy (STXM) are reviewed as part of a suite of characterization methods for physiochemical ascertainment and distinguishment. In addition, Optical-Photothermal Infrared Microspectroscopy (O-PTIR), Z-Stack Confocal Microscopy, Mueller Matrix Polarimetry, and Digital Holography (DH) are touched upon as a suite of cutting-edge modes of characterization. Organizations, like the water treatment or waste management industry, and those in groups that bring awareness to this issue, which are in direct contact with the hydrosphere, can utilize these techniques in order to sense and remediate this plastic polymer pollution. The primary goal of this review paper is to highlight the extent of plastic pollution in the environment as well as introduce its effect on the biodiversity of the planet while underscoring current characterization techniques in this field of research. The secondary goal involves illustrating current and theoretical avenues in which future research needs to address and optimize MPL/NPL remediation, utilizing nanotechnology, before this sleeping giant of a problem awakens. Full article

A highly accurate, precise, and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for ketotifen (KTF) estimation from Beagle dog plasma was developed and validated, with ketotifen-d3 (KTF-d3) as the internal standard (IS). KTF and IS were detected on an API 4000 mass spectrometer in multiple reaction monitoring (MRM) mode in electrospray ionization (ESI) positive ionization mode. The transitions were monitored at m/z 310.2 → 96.0 for KTF and m/z 313.2 → 99.1 for IS. KTF and IS were extracted from plasma using liquid-liquid extraction with methyl tertiary-butyl ether and then analyzed for 3 min with extracted samples (7 µL) into the LC–MS/MS system. Analytes were separated on a Luna^® Hilic column (50 × 2.0 mm i.d., 3 μm) using the Nexera X2 HPLC. The mobile phase A consisted of 10 mmol/L ammonium formate (pH 3.0), while mobile phase B consisted of 0.05% formic acid in acetonitrile. The ratio of mobile phase was 5:95 (v/v) at a flow rate of 0.2 mL/min. The method has been thoroughly validated in accordance with the bioanalytical method validation guidelines established by the Ministry of Food and Drug Safety in Korea and the U.S. Food and Drug Administration, addressing selectivity, lower limit of quantification, linearity, carryover, precision, accuracy, recovery, matrix effect, and stability. The developed LC–MS/MS method was effectively utilized for the bioequivalence assessment of ketotifen in Beagle dog plasma following the oral administration of ketotifen syrup. Full article

The Analytical Quality by Design (AQbD) concept was adopted to establish a quantitative analysis of multi-components with a single marker (QAMS) method for industrial lanolin alcohol, targeting cholesterol, lanosterol, and 24,25-dihydrolanosterol. The potential critical method parameters (CMPs) were identified as column temperature, flow rate, and gradient. Definitive screening design and statistical modeling were employed to optimize the gradient conditions of the mobile phase, column temperature, and flow rate. The Method Operable Design Region (MODR) was determined using a risk-based quantification approach. The robustness was assessed using a Plackett–Burman experimental design, followed by methodological validation. Optimal analytical conditions were as follows: acetonitrile (B)—water (A) mobile phase system; flow rate of 1.58 mL/min; detection wavelength of 205 nm; injection volume of 10 µL; and column temperature of 37 °C. A gradient elution program was implemented as follows: 0–19.0 min, 90.5% B; 19.0–25.0 min, 90.5–100% B; and 25.0–55.0 min, 100% B. Cholesterol served as an internal standard for quantifying lanosterol and 24,25-dihydrolanosterol, with relative correction factors of 0.4227 and 0.8228, respectively. This analytical method utilized only the cholesterol reference substance as an internal standard to quantify the content of cholesterol, lanosterol, and 24,25-dihydrolanosterol in industrial lanolin alcohol. It reduced the testing costs and enhanced efficiency, making it potentially suitable for widespread adoption in lanolin alcohol processing industries. Full article

The P2Y₆ receptor (P2Y₆R), a G_q-coupled receptor, is a potential drug discovery target for various inflammatory and degenerative conditions. Antagonists have been shown to attenuate colitis, acute lung injury, etc. In the search for competitive antagonists, we have investigated the SAR of 3-nitro-2-(trifluoromethyl)-2H-chromene derivatives, although high affinity is lacking. We now reveal that long-chain amino-functionalized congeners display greatly enhanced affinity in the antagonism of UDP-induced Ca²⁺ mobilization in human (h) P2Y₆R-transfected 1321N1 astrocytoma cells. A 6-(Boc-amino-n-heptylethynyl) analogue 30 (MRS4940) had an IC₅₀ of 162 nM, which was a 123-fold greater affinity than the corresponding unprotected primary alkylamine, 107-fold greater than the corresponding pivaloyl derivative 30, and 132-fold selective compared to the P2Y₁₄R. However, similar Boc-amino chains attached at the 8-position produced weak µM affinity. Thus, the P2Y₆R affinity depended on the chain length, attachment point, and terminal functionality. Off-target activities, at 45 sites, were tested for acylamino derivatives 20, 24, 26, 30, 31, and 37, which showed multiple interactions, particularly at the biogenic amine receptors. The more potent analogues may be suitable for evaluation in inflammation and cancer models, which will be performed in future studies. Full article

In this study, a liquid chromatographic method was developed for the fast determination of lincomycin, polymyxin and vancomycin in a preservation solution for transplants. A Kinetex EVO C18 (150 × 4.6 mm, 2.6 µm) column was utilized at 45 °C. Gradient elution was applied using a mixture of mobile phases A and B, both including 30 mM phosphate buffer at pH 2.0 and acetonitrile, at a ratio of 95:5 (v/v) for A and 50:50 (v/v) for B. A flow rate of 1.0 mL/min, an injection volume of 20 µL and UV detection at 210 nm were used. A degradation study treating the three antibiotics with 0.5 M hydrochloric acid, 0.5 M sodium hydroxide and 3% H₂O₂ indicated that the developed method was selective toward lincomycin, polymyxin, vancomycin and their degradation products. Other ingredients of the preservation solution, like those from the cell culture medium, did not interfere. The method was validated with good sensitivity, linearity, precision and accuracy. Furthermore, lincomycin, polymyxin and vancomycin were found to be stable in this preservation solution for 4 weeks when stored at −20 °C. Full article