Search Results (22)

Procoagulant platelets are a specialized subset of activated platelets that externalize phosphatidylserine (PS) on their surface, facilitating the assembly of tenase and prothrombinase complexes and enhancing thrombin generation and clot formation. Although procoagulant platelet formation shares certain features with nucleated cell death pathways, such as mitochondrial dysfunction, calcium (Ca²⁺) overload, membrane blebbing, and microvesiculation, it differs in key molecular mechanisms, notably lacking nuclei and caspase-dependent deoxyribonucleic acid (DNA) fragmentation. Interestingly, molecular components of nucleated cell death pathways in platelets can promote thrombus formation without impacting platelet lifespan. Under pathological conditions, excessive platelet activation may result in platelet lysis, resembling the complete activation of nucleated cell death pathways and contribute to thrombocytopenia. This review compares procoagulant platelet formation with various nucleated cell death pathways, including necrosis, necroptosis, pyroptosis, and ferroptosis, and explores their role in pathological thrombosis and blood clotting. A deeper understanding of mechanisms may help in developing targeted therapies to prevent aberrant blood clotting, platelet death and thrombocytopenia. Full article

Quercetin (Que) is widely recognized for its antioxidant and neuroprotective properties; however, its clinical potential remains limited due to poor solubility and low oral bioavailability. Nasal powders have emerged as a promising strategy to overcome these limitations, taking advantage of nose-to-brain delivery, offering a direct, non-invasive route to the central nervous system while bypassing first-pass metabolism. This study aims to extend previous work by systematically investigating the impact of different preparation methods (spray drying vs. lyophilization) and the incorporation of hydroxypropyl methylcellulose (HPMC) and mannitol/lecithin microparticles (MLMPs) on the physicochemical characteristics, structural properties, and in vitro diffusion behavior of HPβCD-based nasal powder formulations of Que. Thermal behavior and stability were analyzed using TGA, while morphology and particle distribution were assessed via Scanning Electron Microscopy. In vitro diffusion studies using Franz cells and regenerated cellulose membranes were conducted under simulated nasal conditions. Among all tested formulations, the spray-dried HPβCD/Que powder (F4) showed the highest permeation (0.11 ± 0.01 mg/cm² at 120 min). The inclusion of HPMC improved thermal stability but reduced Que diffusion, likely due to increased viscosity and matrix formation. Blending with MLMPs enhanced powder flow and dose placement, although it modestly reduced diffusion efficiency. Overall, this study highlights the potential of HPβCD-based spray-dried powders for nasal Que delivery and demonstrates how HPMC and MLMPs can be strategically employed to tailor performance characteristics. Full article

Micro smart factories (MSFs) represent a new way for small and medium-sized enterprises (SMEs) to build smart factories. Intelligence and manufacturing are two important dimensions of intelligent manufacturing. However, there is still a gap in the research on the coordinated development of intelligence and manufacturing in MSF. Based on survey data from 93 SMEs in Liaoning Province, a dynamic coupling model of the intelligence dimensions (ID) and manufacturing dimensions (MD) of MSF was constructed. Stock increment was used to simulate the development level of the fusion and dynamically evaluate the degree of coupling coordination. The results show that both ID and MD have different advantages in terms of stock and incremental resources, and that the development of intelligence and manufacturing is imbalanced. In addition, in the transformation process of SMEs, the impact of stock factors is significant and the driving force of incremental factors in intelligent manufacturing is insufficient. Finally, SMEs lack comprehensive planning for the development of intelligent manufacturing processes. Full article

Background: In this prospective study, the prognostic role of ADAMTS13 activity and von Willebrand (VWF) antigen (VWF: Ag) levels in ischemic stroke outcomes was investigated. Methods: Patients diagnosed with acute ischemic stroke were prospectively enrolled in this study, while samples for ADAMTS13 activity and VWF: Ag level measurements were collected upon their admission to our unit. The National Institutes of Health Stroke Scale (NIHSS) score was estimated upon admission and at discharge. The modified Rankin scale for neurologic disability (Rankin) score was estimated based on the patient’s history before the stroke onset, during admission (RankinAdm), and at discharge (RankinDis). Results: In the study, 29 patients with a median age of 82.5 (51, 92) were included. In univariate analysis, ADAMTS13 activity during admission was associated with platelet values at the same time point (r = 0.12, p = 0.01) and VWF: Ag levels were associated with age (r = 0.439, p = 0.04), previous ischemic stroke (r = 0.9176, p = 0.031), and glucose levels (r = 0.64, p = 0.049). Associations between ADAMTS13/VWF: Ag Ratio with RankinDis (r = 0.3253, p = 0.03), and the change between RankinDis and RankinAdm (r = 0.1589, p = 0.014) were identified. Additionally, VWF: Ag levels during admission were correlated with RankinDis (r = 0.0072, p = 0.049). Conclusions: These markers might be useful as biomarkers for the prediction of poor outcomes after stroke. Full article

Nitrates can cause severe ecological imbalances in aquatic ecosystems, with considerable consequences for human health. Therefore, monitoring this inorganic form of nitrogen is essential for any water quality management structure. This research was conducted to develop a novel Nitrate Portable Measurement System (NPMS) to monitor nitrate concentrations in water samples. NPMS is a reagent-free ultraviolet system developed using low-cost electronic components. Its operation principle is based on the Beer–Lambert law for measuring nitrate concentrations in water samples through light absorption in the spectral range of 295–315 nm. The system is equipped with a ready-to-use ultraviolet sensor, light emission diode (LED), op-amp, microcontroller, liquid crystal display, quartz cuvette, temperature sensor, and battery. All the components are assembled in a 3D-printed enclosure box, which allows a very compact self-contained equipment with high portability, enabling field and near-real-time measurements. The proposed methodology and the developed instrument were used to analyze multiple nitrate standard solutions. The performance was evaluated in comparison to the Nicolet Evolution 300, a classical UV–Vis spectrophotometer. The results demonstrate a strong correlation between the retrieved measurements by both instruments within the investigated spectral band and for concentrations above 5 mg NO₃⁻/L. Full article

It is generally accepted that local muscular fatigue can negatively affect position sense. Interestingly, it has been proposed that in women, position sense and neuromuscular coordination may be affected by fluctuations of estrogen and progesterone levels. The aim of this study was to examine the possible effect of localized muscle fatigue on knee joint position sense at two phases of the menses: follicular and luteal. Twenty physically active females aged 19–30 years, with normal menses, volunteered for this study. An isokinetic dynamometer was used to evaluate proprioception and perform the fatigue protocol of the knee extensors and flexors. Knee proprioception at rest and after fatigue at three knee target angles (30°, 45°, 60°) was measured. A three-way ANOVA analysis with repeated measures was performed. The results showed that the main effect of fatigue was significant, but no main effect of the menstrual cycle phase was found. Additionally, a main effect was found for the target angle (more flexed target knee joint angles were associated with larger angular error deviations). In conclusion, localized muscle fatigue can significantly reduce the accuracy of active knee joint repositioning in both the luteal and the follicular menstrual phases in young, physically active healthy women. Full article

Ropinirole is a non-ergolinic dopamine agonist used to manage Parkinson’s disease and it is characterized by poor oral bioavailability. This study aimed to design and develop advanced drug delivery systems composed of poloxamer 407, a non-ionic surfactant (Tween 80), and cyclodextrins (methyl-β-CD or hydroxy-propyl-β-CD) for possible brain targeting of ropinirole after nasal administration for the treatment of Parkinson’s disease. The hybrid systems were formed by the thin-film hydration method, followed by an extensive physicochemical and morphological characterization. The in vitro cytotoxicity of the systems on HEK293 cell lines was also tested. In vitro release and ex vivo mucosal permeation of ropinirole were assessed using Franz cells at 34 °C and with phosphate buffer solution at pH 5.6 in the donor compartment, simulating the conditions of the nasal cavity. The results indicated that the diffusion-controlled drug release exhibited a progressive increase throughout the experiment, while a proof-of-concept experiment on ex vivo permeation through rabbit nasal mucosa revealed a better performance of the prepared hybrid systems in comparison to ropinirole solution. The encouraging results in drug release and mucosal permeation indicate that these hybrid systems can serve as attractive platforms for effective and targeted nose-to-brain delivery of ropinirole with a possible application in Parkinson’s disease. Further ex vivo and in vivo studies to support the results of the present work are ongoing. Full article

Farm animals harbour bacterial pathogens, which are often viewed as important indicators of animal health and determinants of food safety. To better understand the prevalence and inform treatment, we audited laboratory data at the Bacteriology Laboratory of the NVRI from 2018–2021. Antibiotics were classified into seven basic classes: quinolones, tetracyclines, beta-lactams, aminoglycosides, macrolides, nitrofuran, and cephalosporins. Trends were analysed using a generalised linear model with a log link function for the Poisson distribution, comparing proportions between years with an offset to account for the variability in the total number of organisms per year. Avian (73.18%) samples were higher than any other sample. The major isolates identified were Escherichia. coli, Salmonella spp., Klebsiella spp., Staphylococcus spp., Proteus spp., and Pseudomonas spp. We found that antimicrobial resistance to baseline antibiotics increased over the years. Of particular concern was the increasing resistance of Klebsiella spp. to cephalosporins, an important second-generation antibiotic. This finding underscores the importance of farm animals as reservoirs of pathogens harbouring antimicrobial resistance. Effective biosecurity, surveillance, and frugal use of antibiotics in farms are needed because the health of humans and animals is intricately connected. Full article

Quercetin (QUE) is a flavonol that has recently received great attention from the research community due to its important pharmacological properties. However, QUE’s low solubility and extended first-pass metabolism limit its oral administration. This review aims to present the potential of various nanoformulations in the development of QUE dosage forms for bioavailability enhancement. Advanced drug delivery nanosystems can be used for more efficient encapsulation, targeting, and controlled release of QUE. An overview of the primary nanosystem categories, formulation processes, and characterization techniques are described. In particular, lipid-based nanocarriers, such as liposomes, nanostructured-lipid carries, and solid-lipid nanoparticles, are widely used to improve QUE’s oral absorption and targeting, increase its antioxidant activity, and ensure sustained release. Moreover, polymer-based nanocarriers exhibit unique properties for the improvement of the Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADME(T)) profile. Namely, micelles and hydrogels composed of natural or synthetic polymers have been applied in QUE formulations. Furthermore, cyclodextrin, niosomes, and nanoemulsions are proposed as formulation alternatives for administration via different routes. This comprehensive review provides insight into the role of advanced drug delivery nanosystems for the formulation and delivery of QUE. Full article

Cancer-associated inflammation has been established as a hallmark feature of almost all solid cancers. Tumor-extrinsic and intrinsic signaling pathways regulate the process of cancer-associated inflammation. Tumor-extrinsic inflammation is triggered by many factors, including infection, obesity, autoimmune disorders, and exposure to toxic and radioactive substances. Intrinsic inflammation can be induced by genomic mutation, genome instability and epigenetic remodeling in cancer cells that promote immunosuppressive traits, inducing the recruitment and activation of inflammatory immune cells. In RCC, many cancer cell-intrinsic alterations are assembled, upregulating inflammatory pathways, which enhance chemokine release and neoantigen expression. Furthermore, immune cells activate the endothelium and induce metabolic shifts, thereby amplifying both the paracrine and autocrine inflammatory loops to promote RCC tumor growth and progression. Together with tumor-extrinsic inflammatory factors, tumor-intrinsic signaling pathways trigger a Janus-faced tumor microenvironment, thereby simultaneously promoting or inhibiting tumor growth. For therapeutic success, it is important to understand the pathomechanisms of cancer-associated inflammation, which promote cancer progression. In this review, we describe the molecular mechanisms of cancer-associated inflammation that influence cancer and immune cell functions, thereby increasing tumor malignancy and anti-cancer resistance. We also discuss the potential of anti-inflammatory treatments, which may provide clinical benefits in RCCs and possible avenues for therapy and future research. Full article

This study is the first to provide information on the parasite fauna of Sardinella maderensis along the coasts of Benin and Ghana, and the first to investigate the potential use of parasites as biological tags in fish population studies in the area. It may thus serve as a starting point for upcoming studies. From February to June 2021, a total of 200 S. maderensis were sampled from the fishing port of Cotonou (Benin) and the Elmina landing site (Ghana). The prevalence and abundance of each parasite were recorded. The following are the outcomes of this study: Parasite species, such as Parahemiurus merus, Mazocraeoides sp. and Hysterothylacium fortalezae, were recorded along the coasts of Benin and Ghana, while Anisakis sp(p). and Tentacularia coryphaenae were only recorded along the coast of Benin. Parahemiurus merus was the most prevalent and abundant among all the parasites recorded. Anisakis sp(p). and T. coryphaenae were selected as having potential in the stock identification of S. maderensis. Both parasites were only recorded along the coast of Benin at a low prevalence. As a result, examinations of more S. maderensis from each location for these parasites may justify their use in stock identification studies. Full article

Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin, regulating important platelet functions such as platelet adhesion and thrombus growth. Although the blockade of GPVI function is widely recognized as a potent anti-thrombotic approach, there are limited studies focused on site-specific targeting of GPVI. Using computational modeling and bioinformatics, we analyzed collagen- and CRP-binding surfaces of GPVI monomers and dimers, and compared the interacting surfaces with other mammalian GPVI isoforms. We could predict a minimal collagen-binding epitope of GPVI dimer and designed an EA-20 antibody that recognizes a linear epitope of this surface. Using platelets and whole blood samples donated from wild-type and humanized GPVI transgenic mice and also humans, our experimental results show that the EA-20 antibody inhibits platelet adhesion and aggregation in response to collagen and CRP, but not to fibrin. The EA-20 antibody also prevents thrombus formation in whole blood, on the collagen-coated surface, in arterial flow conditions. We also show that EA-20 does not influence GPVI clustering or receptor shedding. Therefore, we propose that blockade of this minimal collagen-binding epitope of GPVI with the EA-20 antibody could represent a new anti-thrombotic approach by inhibiting specific interactions between GPVI and the collagen matrix. Full article

In this work, a newly developed self-contained, portable, and compact iron measurement system (IMS) based on spectroscopy absorption for determination of Fe²⁺ in water is presented. One of the main goals of the IMS is to operate the device in the field as opposed to instruments commonly used exclusively in the laboratory. In addition, the system has been tuned to quantify iron concentrations in accordance with the values proposed by the regulations for human consumption. The instrument uses the phenanthroline standard method for iron determination in water samples. This device is equipped with an optical sensing system consisting of a light-emitting diode paired with a photodiode to measure absorption radiation through ferroin complex medium. To assess the sensor response, four series of Fe²⁺ standard samples were prepared with different iron concentrations in various water matrices. Furthermore, a new solid reagent prepared in-house was investigated, which is intended as a “ready-to-use” sample pre-treatment that optimizes work in the field. The IMS showed better analytical performance compared with the state-of-the-art instrument. The sensitivity of the instrument was found to be 2.5 µg Fe²⁺/L for the measurement range established by the regulations. The linear response of the photodiode was determined for concentrations between 25 and 1000 µg Fe²⁺/L, making this device suitable for assessing iron in water bodies. Full article

There is a large volume of literature in international business on multinationality. There is an equally large volume of literature in finance on stock price crash risk. However, very few studies have attempted to provide a link between these two research areas. Using an unbalanced panel data consisting of 473 multinational corporations (MNCs) publicly listed in the Chinese stock markets during 2004 to 2020, this paper is one of the first to empirically investigate whether and to what extent multinationality affects stock price crash risk. The paper finds strong evidence that multinational operation is negatively related to stock price crash risk. In addition, MNCs with better corporate governance quality experience larger decline in stock price crash risk when the degree of multinationality increases. Furthermore, MNCs with higher stock market liquidity experience lower crash risk. An important implication is that companies should strengthen their corporate governance and market liquidity while “going global”. Full article

Qualified Securities for Short-sale Refinancing (QSSR) is a unique trading mechanism that has exogenously increased the supply of loanable securities in Chinese stock markets. Using difference-in-differences (DID) methodology, this paper is the first to investigate whether and to what extent additions to the QSSR eligibility list affect short selling activities and stock price behaviors. The paper finds that stocks added to the QSSR list exhibit better liquidity and less negative skewness in returns than non-QSSR stocks. However, QSSR stocks are more volatile and display a higher frequency of extreme negative returns. In addition, on average, QSSR stocks experience larger negative abnormal returns (ARs) and cumulative abnormal returns (CARs) relative to non-QSSR stocks, and the difference in CARs is positively related to investor heterogeneity. The results indicate that short selling has mixed effects on stock prices. Removing short-sale constraints can improve liquidity and reduce price bubbles, but can also increase return volatility and amplify market crashes. Full article