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IntroductionStroke, the second leading cause of death and disability in Europe, is primarily caused by interrupted blood supply, leading to ischemia–reperfusion (IR) injury and subsequent neuronal death. Current treatment options are limited, highlighting the need for novel therapies. Neural stem cells (NSCs) have shown promise in treating various neurological disorders, including stroke. However, the underlying mechanisms of NSC-mediated recovery remain unclear.MethodsEighty C57Bl/6–Tyrc-Brd mice underwent ischemic stroke induction and were divided into four groups: sham, stroke-affected, stroke-affected with basal cell medium injection, and stroke-affected with NSCs transplantation. NSCs, isolated from mouse embryos, were stereotaxically transplanted into the stroke-affected brains. Magnetic resonance imaging (MRI) and neurological scoring were used to assess recovery. Immunohistochemical analysis and gene expression assays were performed to evaluate pyroptosis and necroptosis markers.ResultsNSC transplantation significantly improved neurological recovery compared to control groups. In addition, although not statistically significant, NSCs reduced stroke volume. Immunohistochemical analysis revealed upregulation of Gasdermin D (GSDMD) expression post-stroke, predominantly in microglia and astrocytes. However, NSC transplantation led to a reduction in GSDMD signal intensity in astrocytes, suggesting an effect of NSCs on GSDMD activity. Furthermore, NSCs downregulated Mixed Lineage Kinase Domain-Like Protein (Mlkl) expression, indicating a reduction in necroptosis. Immunohistochemistry demonstrated decreased phosphorylated MLKL (pMLKL) signal intensity in neurons while stayed the same in astrocytes following NSC transplantation, along with increased distribution in microglia.DiscussionNSC transplantation holds therapeutic potential in stroke recovery by targeting pyroptosis and necroptosis pathways. These findings shed light on the mechanisms underlying NSC-mediated neuroprotection and support their further exploration as a promising therapy for stroke patients.

The atomic force microscope (AFM) enables the measurement of sample surfaces at the nanoscale. Reference standards with calibration gratings are used for the adjustment and verification of AFM measurement devices. Thus far, there are no guidelines or guides available in the field of atomic force microscopy that analyze the influence of input parameters on the quality of measurement results, nor has the measurement uncertainty of the results been estimated. Given the complex functional relationship between input and output variables, which cannot always be explicitly expressed, one of the primary challenges is how to evaluate the measurement uncertainty of the results. The measurement uncertainty of the calibration grating step height on the AFM reference standard was evaluated using the Monte Carlo simulation method. The measurements within this study were conducted using a commercial, industrial atomic force microscope.

Citrullinemia type I is a rare autosomal-recessive disorder caused by deficiency of argininosuccinate synthetase (ASS1). The clinical presentation includes the acute neonatal form, characterized by ammonia and citrulline accumulation in blood, which may lead to encephalopathy, coma, and death, and the milder late-onset form. Current treatments are unsatisfactory, and the only curative treatment is liver transplantation. We permanently modified the hepatocyte genome in lethal citrullinemia mice (Ass1fold/fold) by inserting the ASS1 cDNA into the albumin locus through the delivery of two AAV8 vectors carrying the donor DNA and the CRISPR-Cas9 platform. The neonatal treatment completely rescued mortality ensuring survival up to 5 months of age, with plasma citrulline levels significantly decreased, while plasma ammonia levels remained unchanged. In contrast, neonatal treatment with a liver-directed non-integrative AAV8-AAT-hASS1 vector failed to improve disease parameters. To model late-onset citrullinemia, we dosed postnatal day (P) 30 juvenile animals using the integrative approach, resulting in lifespan improvement and a minor reduction in disease markers. Conversely, treatment with the non-integrative vector completely rescued mortality, reducing plasma ammonia and citrulline to wild-type values. In summary, the integrative approach in neonates is effective, although further improvements are required to fully correct the phenotype. Non-integrative gene therapy application to juvenile mice ensures a stable and very efficient therapeutic effect.

Rotating parts can be found in almost all operational equipment in the industry and are of great importance for proper operation. However, reliability theory explains that every industrial system can change its state when failure happens. Predictive maintenance as one of the latest maintenance strategy emerged from the Maintenance 4.0 concept. Nowadays, this concept can include Industrial Internet of Things (IIoT) devices to connect industrial assets thus enable data collection and analysis that can help make better decisions about maintenance activity. Robust data acquisition system is a prerequisite for any modern predictive maintenance task as it provides necessary data for further analysis and health assessment of the industry asset. Fault diagnosis is an important task in the maintenance of industrial rotating subsystems, considering that early state change diagnosis and fault identification can prevent system failure. Vibration analysis in theory and practice is considered a correct technique for early detection of state changes and failure diagnostics of rotating subsystems. The identified technical state should be considered in a context of the ability and different inability states. Therefore, early different inability states identification is the next step in the rotary machinery diagnostics procedure. Most of the existing techniques for fault diagnosis of rotating subsystems that use vibrations involve the step of extracting features from the raw signal. Considering that the features that describe the behavior of the rotary subsystem can differ significantly depending on the type of equipment, such an approach usually requires an expert in the field of signal processing and rotary subsystems who can define the necessary features. Recently, the emergence of machine deep learning and its application in maintenance promises to provide highly efficient fault diagnostics while simultaneously reducing the need for expert knowledge and human labour. This paper presents authors aim to use self-developed IIoT system built as an IIoT accelerometer as the edge device, web API and database with convolutional neural network as deep learning-based data-driven fault diagnosis to detect and identify different inability states of rotating subsystems. Large dataset for two different rotational speed is collected using IIOT system and multiple convolutional neural network models are trained and tested to examine possibility of using IIOT for inability state prediction.

This paper presents a method for the estimation of key parameters of limit cycle oscillations (amplitude and frequency) during a relay experiment used for automatic tuning of proportional-integral (PI) and proportional-integral-derivative (PID) feedback controllers. The limit cycle parameter estimator is based on the first-order extended Kalman filter (EKF) for resonance frequency estimation, to which a second-order generalized integrator (SOGI) is cascaded for the purpose of limit cycle amplitude estimation. Based on thus-obtained parameters of the limit cycle oscillations, the ultimate gain and the ultimate period of the limit cycle oscillations are estimated. These are subsequently used for the tuning of PI and PID controller according to Takahashi modifications of Ziegler-Nichols tuning rules. The proposed PI and PID controller auto-tuning method is verified by means of simulations and experimentally on the heat and air-flow experimental setup for the case of air temperature feedback control. The results have shown that the proposed auto-tuning system based on relay control experiment for the heat and air-flow process PI/PID temperature control can capture the ultimate gain and period parameters fairly quickly in simulations and in experiments. Subsequent controller tuning according to Takahashi modifications of Ziegler-Nichols rules using thus-obtained ultimate point parameters can provide favourable closed-loop load disturbance rejection, particularly in the case of PID controller.

Abstract Barium hexaferrite nanoplatelets (BHF NPLs) are permanent nanomagnets with the magnetic easy axis aligned perpendicular to their basal plane. By combining this specific property with optimised surface chemistry, novel functional materials were developed, e.g., ferromagnetic ferrofluids and porous nanomagnets. We compared the interaction of chemically different phosphonic acids, hydrophobic and hydrophilic with 1–4 phosphonic groups, with BHF NPLs. A decrease in the saturation magnetisation after functionalising the BHF NPLs was correlated with the mass fraction of the nonmagnetic coating, whereas the saturation magnetisation of the NPLs coated with a tetraphosphonic acid at 80 °C was significantly lower than expected. We showed that such a substantial decrease in the saturation magnetisation originates from the disintegration of BHF NPLs, which was observed with atomic-resolution scanning transmission electron microscopy and confirmed by a computational study based on state-of-the-art first-principles calculations. Fe K-edge XANES (X-ray absorption near-edge structure) and EXAFS (Extended X-ray absorption fine structure) combined with Fourier-transformed infrared (FTIR) spectroscopy confirmed the formation of an Fe–phosphonate complex on the partly decomposed NPLs. Comparing our results with other functionalised magnetic nanoparticles confirmed that saturation magnetisation can be exploited to identify the disintegration of magnetic nanoparticles when insoluble disintegration products are formed.

Due to the increasing presence of industrial hemp (Cannabis sativa L.) and its multiple possibilities of use, the influence of different light and several biopreparations based on beneficial fungi and bacteria on hemp’s morphological and physiological properties were examined. Different biopreparations and their combinations were inoculated on hemp seed and/or substrate and grown under blue and white light. A completely randomized block design was conducted in four replications within 30 days. For biopreparation treatment, vesicular arbuscular mycorrhiza (VAM) in combination with Azotobacter chroococum and Trichoderma spp. were inoculated only on seed or both on seed and in the substrate. Generally, the highest morphological parameters (stem, root and plant length) were recorded on plants in white light and on treatment with applied Trichoderma spp., both on seed and substrate. Blue light negatively affected biopreparation treatments, resulting in lower values of all morphological parameters compared to control. Leaves pigments were higher under blue light, as compared to the white light. At the same time, 1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), flavonoids, total flavanol content and phenolic acids were not influenced by light type. Biopreparation treatments did not significantly influence the leaves’ pigments content (Chl a, Chl b and Car), nor the phenolic and flavanol content.

Summary: Obesity-related complications such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are well-established risk factors for the development of hepatocellular carcinoma (HCC). This review provides insights into the molecular mechanisms that underlie the role of steatosis, hyperinsulinemia and hepatic inflammation in HCC development and progression. We focus on recent findings linking intracellular pathways and transcription factors that can trigger the reprogramming of hepatic cells. In addition, we highlight the role of enzymes in dysregulated metabolic activity and consequent dysfunctional signalling. Finally, we discuss the potential uses and challenges of novel therapeutic strategies to prevent and treat NAFLD/T2D-associated HCC.

This paper investigates the energy efficiency of a Direct Driven Hydraulic (DDH) system and a proportional electrohydraulic system. A detailed analysis of their energy efficiency is carried out based on experimental results obtained in laboratory conditions using a fully loaded cylinder and sine wave reference trajectory. To ensure fairness in the testing process, the same cylinder with the same initial conditions is used for both systems. The cylinder velocity is estimated online using a novel algebraic differentiator approach based on measured cylinder position. The power of each component is calculated from the obtained measurements, and the energy efficiency of the system is given, along with the losses for each component. Based on the obtained results, it is concluded that the efficiency of the DDH system with a fully loaded cylinder is 28%, while that of the proportional electrohydraulic system is 4%. The significantly higher energy efficiency of the DDH system is attributed to its use of a power-on-demand approach, in contrast to the proportional electrohydraulic system.

Terraced vineyards are cultural landscapes with a special value. The increase in costs and the lack of professional workers make viticulture on terraces difficult to be maintained. Thus, in the face of climate change and production challenges, we aimed to study the impact of slope-wise cultivation on wine quality. The quality of Merlot wines from terraced and slightly lower non-terraced vineyards within a small area characterised by similar mesoclimatic features was compared in the seasons 2019 and 2020. The non-terraced and terraced vineyards differed in both soil profile and morphology. The number of buds, number of clusters, and leaf area were standardised, and the stem water potential (SWP) was measured during wine-growing seasons. Upon reaching maturity, grapes were hand-picked on the same day in all vineyards and microvinified. The wines were analysed chemically and sensorially. In both years, the SWP showed higher water stress in the vines from terraces. The yield, berry weight, and leaf area were lower on terraced than on non-terraced vineyards in both years, and the skin- and seed-to-flesh ratios were higher. The darker seed colour pointed to the advanced ripening on terraces, where the wines had a higher alcohol concentration and a higher total dry extract. The wines from terraces had higher concentrations of total polyphenols, anthocyanins, and proanthocyanidins (PAs) than the wines from non-terraced vineyards in both years, and the PAs in the wines from terraces in 2019 had fewer prodelphinidins and were more galloylated. Higher concentrations of higher alcohols and lower concentrations of esters and methoxypyrazines were found in the wines from terraces. The sensory analysis revealed a preference for wines from terraces with better colour intensity, fruitiness, astringency, midpalate, and overall quality. Under experimental conditions (the same harvest date, standardised viticultural variables), the wines from terraces had both better phenolic potential and better sensory quality than the wines from non-terraced vineyards.

The aim of this study was to further describe the oral microbiota of healthy dogs by DNA shotgun sequencing and compare those to dogs with oral tumors. Oral swabs (representative of all niches of the oral cavity) were collected from healthy dogs (n = 24) and from dogs with different oral tumors (n = 7). DNA was extracted from the swabs and shotgun metagenomic sequencing was performed. Only minor differences in microbiota composition were observed between the two groups. At the phylum level, the Bacteroidota, Proteobacteria, Actinobacteriota, Desulfobacterota and Firmicutes were most abundant in both groups. Observed Operational Taxonomic Units—OTUs (species richness) was significantly higher in the healthy patients, but there was no significant difference in the Shannon diversity index between the groups. No significant difference was found in beta diversity between the groups. The core oral microbiota consisted of 67 bacterial species that were identified in all 24 healthy dogs. Our study provides further insight into the composition of the oral microbiota of healthy dogs and in dogs with oral tumors.

NaYF4 nanoparticles codoped with Yb3+ and Tm3+ exhibit upconversion fluorescence in near-infrared and visible spectral range. Consequently, such upconverting nanoparticles (UCNPs) can be used as contrast agents in medical diagnostics and bioassays. However, they are not chemically stable in aqueous dispersions, especially in phosphate solutions. Protective amphiphilic-polymer coatings based on poly(maleic anhydride-alt-octadec-1-ene) (PMAO) and bis(hexamethylene)triamine (BHMT) were optimised to improve the chemical stability of UCNPs under simulated physiological conditions. Morphologies of the bare and coated UCNPs was inspected with transmission electron microscopy. All samples showed intense UC fluorescence at ~800 nm, typical for Tm3+. The colloidal stability of aqueous dispersions of bare and coated UCNPs was assessed by dynamic light scattering and measurements of zeta potential. The dissolution of UCNP in phosphate-buffered saline at 37 °C, was assessed potentiometrically by measuring the concentration of the dissolved fluoride. Protection against the dissolution of UCNPs was achieved by PMAO and PMAO crosslinked with BHMT.

Modern maintenance strategies, such as predictive and prescriptive maintenance, which derived from the concept of Industry and Maintenance 4.0, involve the application of the Industrial Internet of Things (IIoT) to connect maintenance objects enabling data collection and analysis that can help make better decisions on maintenance activities. Data collection is the initial step and the foundation of any modern Predictive or Prescriptive maintenance strategy because it collects data that can then be analysed to provide useful information about the state of maintenance objects. Condition monitoring of rotary equipment is one of the most popular maintenance methods because it can distinguish machine state between multiple fault types. The topic of this paper is the presentation of an automated system for data collection, processing and interpretation of rotary equipment state that is based on IIoT framework consisting of an IIoT accelerometer, edge and fog devices, web API and database. Additionally, ISO 10816-1 guidance has been followed to develop module for evaluation of vibration severity. The collected data is also visualized in a dashboard in a near-real time and shown to maintenance engineering, which is crucial for pattern monitoring. The developed system was launched in laboratory conditions using rotating equipment failure simulator to test the logic of data collection and processing. A proposed system has shown that it is capable of automated periodic data collection and processing from remote places which is achieved using Node RED programming environment and MQTT communication protocol that enables reliable, lightweight, and secure data transmission.

Due to its nutritional value, wheatgrass (Triticum aestivum L.) is considered to be a functional food, becoming increasingly popular as a supplement to the people’s quotidian diet. The study aimed to determine the influence of the number of cuttings and cultivars on the total antioxidant activity (DPPH), the content of chloroplast pigments, vitamin C, phenols, and flavonoids in the wheatgrass juice. Two genotypes of wheatgrass, T. aestivum ssp. aestivum (variety Katarina) and T. aestivum ssp. sphaerococcum, respectively, were cut twice during the experiment. In both cuttings, the genotype significantly differed in the flavonoid level and antioxidant activity, while the number of cuttings influenced the content of phenols, vitamin C, and antioxidant activity in the wheatgrass juice. T. sphaerococcum had a higher concentration of flavonoids and a significantly lower antioxidant activity when compared to the Katarina wheat variety. On an average, the first cut implicated an increased content of phenols and vitamin C concerning both genotypes, followed by a higher antioxidant value. In the Katarina variety, a significantly higher phenol content and antioxidant activity was detected in the first cut. In the T. Sphaerococcum, a decrease in the total content of the examined antioxidants was apparent in the second cut.

Introduction: Stroke, the second leading cause of death and disability in Europe, is primarily caused by interrupted blood supply, leading to ischemia--reperfusion (IR) injury and subsequent neuronal death. Current treatment options are limited, highlighting the need for novel therapies. Neural stem cells (NSCs) have shown promise in treating various neurological disorders, including stroke. However, the underlying mechanisms of NSC-mediated recovery remain unclear. Methods: Eighty C57Bl/6--Tyrc-Brd mice underwent ischemic stroke induction and were divided into four groups: sham, stroke-affected, stroke-affected with basal cell medium injection, and stroke-affected with NSCs transplantation. NSCs, isolated from mouse embryos, were stereotaxically transplanted into the stroke-affected brains. Magnetic resonance imaging (MRI) and neurological scoring were used to assess recovery. Immunohistochemical analysis and gene expression assays were performed to evaluate pyroptosis and necroptosis markers. Results: NSC transplantation significantly improved neurological recovery compared to control groups. In addition, although not statistically significant, NSCs reduced stroke volume. Immunohistochemical analysis revealed upregulation of Gasdermin D (GSDMD) expression post-stroke, predominantly in microglia and astrocytes. However, NSC transplantation led to a reduction in GSDMD signal intensity in astrocytes, suggesting an effect of NSCs on GSDMD activity. Furthermore, NSCs downregulated Mixed Lineage Kinase Domain-Like Protein (Mlkl) expression, indicating a reduction in necroptosis. Immunohistochemistry demonstrated decreased phosphorylated MLKL (pMLKL) signal intensity in neurons while stayed the same in astrocytes following NSC transplantation, along with increased distribution in microglia. Discussion: NSC transplantation holds therapeutic potential in stroke recovery by targeting pyroptosis and necroptosis pathways. These findings shed light on the mechanisms underlying NSC-mediated neuroprotection and support their further exploration as a promising therapy for stroke patients. [ABSTRACT FROM AUTHOR]

DNA shotgun sequencing is an untargeted approach for identifying changes in relative abundances, while qPCR allows reproducible quantification of specific bacteria. The canine dysbiosis index (DI) assesses the canine fecal microbiota by using a mathematical algorithm based on qPCR results. We evaluated the correlation between qPCR and shotgun sequencing using fecal samples from 296 dogs with different clinical phenotypes. While significant correlations were found between qPCR and sequencing, certain taxa were only detectable by qPCR and not by sequencing. Based on sequencing, less than 2% of bacterial species (17/1190) were consistently present in all healthy dogs (n = 76). Dogs with an abnormal DI had lower alpha-diversity compared to dogs with normal DI. Increases in the DI correctly predicted the gradual shifts in microbiota observed by sequencing: minor changes (R = 0.19, DI < 0 with any targeted taxa outside the reference interval, RI), mild-moderate changes (R = 0.24, 0 < DI < 2), and significant dysbiosis (R = 0.54, 0.73, and 0.91 for DI > 2, DI > 5, and DI > 8, respectively), compared to dogs with a normal DI (DI < 0, all targets within the RI), as higher R-values indicated larger dissimilarities. In conclusion, the qPCR-based DI is an effective indicator of overall microbiota shifts observed by shotgun sequencing in dogs.

The reliable operation of a process plant is critical to the safety, performance, and profitability of a business. Failure Mode and Effects Analysis (FMEA) is a process of reviewing systems, subsystems, and equipment that identify potential failure modes, their root causes, and consequences. FMEA is also a risk assessment tool that has been used successfully in a wide range of process industries as an integral part of reliability-centered maintenance, safety management, and continuous improvement. The method has indeed been criticized, especially in the area of system assessment, but engineers still predominantly use traditional, unmodified FMEA best practices. In this study, a new conceptual model is proposed to improve the traditional technique and make FMEA a more autonomous, data-driven, and accurate method. The conceptual model of improved FMEA uses ANFIS and FIS models in one automated process that aims to solve the defect handling process from failure detection to quantification of risk level and prioritization of dedicated mitigation action.

Conformity assessment refers to activities undertaken to check whether some product, service or process meets certain criteria and specifications given by internationally accepted standards. The decision on whether a property of interest is aligned with the set standards is made based on measurement. However, uncertainty associated with the measurement results may lead to incorrect decisions. Measurement results may be falsely rejected as non-conforming, although they meet specifications. This is referred to as the producer’s risk. If the measurement result that does not meet the required specifications is accepted as conforming, this is referred to as the consumer’s risk. This paper covers calculations of global consumer's and producer's risk using the Bayesian approach and deals with the application of metrics related to confusion matrices in conformity assessments. These techniques have been used to assess the conformity of the bearing ring diameter with the given specifications. Based on the behavior of these metrics, the optimal length of the guard band was determined with the aim of minimizing the global consumer’s and producer’s risk.

This study aimed to improve the understanding of 2-aminoacetophenone (2-AAP) formation in white wines, a compound responsible for atypical ageing (ATA) associated with a rapid loss of white wine fruity aroma and to the development of unpleasant odors. Two surveys performed in 139 white wines from Central Europe investigated the varietal effect on wine tendency to form 2-AAP during ageing. The role of some antioxidants and important transition metal ions present in wine (Fe, Cu and Mn) in the formation of 2-AAP was also investigated. The surveys highlighted that Muscat and Riesling wines showed significantly higher concentrations of 2-AAP than Chardonnay and some other regional varieties found in Central Europe such as Grüner Veltliner, Welschriesling and Zelen. The origin of such varietal effects could not be related to the level of any 2-AAP precursor. On the other hand, some of the important wine matrix effects were highlighted. A certain variability in capacity of different antioxidants to limit 2-AAP formation was observed. Supplementations of commercial tannins in wines tended to be more efficient than glutathione in preserving wines from the formation of 2-AAP. Transition metal ions significantly impacted 2-AAP synthesis through complex interactions. Generally, Fe and Mn tended to promote formation of 2-AAP, while the presence of Cu limited it. The higher concentration of transition metal ions significantly improved the efficiency of antioxidants to reduce 2-AAP formation. Further studies investigating the origin of varietal effects and the complex matrix effects involving metal ions and antioxidants in 2-AAP production are warranted.