Search Results (15,115)

2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid (EC), acting as a full agonist at both CB1 and CB2 cannabinoid receptors. It is synthesized on demand in postsynaptic membranes through the sequential action of phosphoinositide-specific phospholipase Cβ1 (PLCβ1) and diacylglycerol lipase α (DAGLα), contributing to retrograde signaling upon interaction with presynaptic CB1. However, 2-AG production might also involve various combinations of PLC and DAGL isoforms, as well as additional intracellular pathways implying other enzymes and substrates. Three other alternative pathways of 2-AG synthesis rest on the extracellular cleavage of 2-arachidonoyl-lysophospholipids by three different hydrolases: glycerophosphodiesterase 3 (GDE3), lipid phosphate phosphatases (LPPs), and two members of ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPP6–7). We propose the names of AlterAG-1, -2, and -3 for three pathways sharing an ectocellular localization, allowing them to convert extracellular lysophospholipid mediators into 2-AG, thus inducing typical signaling switches between various G-protein-coupled receptors (GPCRs). This implies the critical importance of the regioisomerism of both lysophospholipid (LPLs) and 2-AG, which is the object of deep analysis within this review. The precise functional roles of AlterAGs are still poorly understood and will require gene invalidation approaches, knowing that both 2-AG and its related lysophospholipids are involved in numerous aspects of physiology and pathology, including cancer, inflammation, immune defenses, obesity, bone development, neurodegeneration, or psychiatric disorders. Full article

Brønsted acid-catalysed/mediated reactions of the 2-alkynylanilines are reported. While metal-catalysed reactions of these valuable building blocks have led to the establishment of robust protocols for the selective, diverse-oriented syntheses of significant heterocyclic derivatives, we here demonstrate the practical advantages of an alternative methodology under metal-free conditions. Our investigation into the key factors influencing the product selectivity in Brønsted acid-catalysed/mediated reactions of 2-alkynylanilines reveals that different reaction pathways can be directed towards the formation of diverse valuable products by simply choosing appropriate reaction conditions. The origins of chemo- and regioselectivity switching have been explored through Density Functional Theory (DFT) calculations. Full article

In the fixed time-step electromagnetic transient (EMT)-type program, an interpolation process is applied to deal with switching events. The interpolation method frequently reduces the algorithm’s accuracy when dealing with power electronics. In this study, we use the Butcher tableau to analyze the defects of linear interpolation. Then, based on the theories of Runge–Kutta integration, we propose two three-stage diagonally implicit Runge–Kutta (3S-DIRK) algorithms combined with the trapezoidal rule (TR) and backward Euler (BE), respectively, with TR-3S-DIRK and BE2-3S-DIRK for the interpolation and synchronization processes. The proposed numerical integral interpolation scheme has second-order accuracy and does not produce spurious oscillations due to the size change in the time step. The proposed method is compared with the critical damping adjustment method (CDA) and the trapezoidal method, showing that it does not produce spurious numerical oscillations or first-order errors. Full article

Road markings are important elements of road infrastructure, influencing traffic safety. Since they are deteriorating systems, their upkeep through renewals is important. To assure the quality of the renewal jobs, the systematic testing of retroreflectivity, which is the key performance parameter of road markings, was imposed in Croatia. Results from two decades of annual measurements of renewal jobs are provided. For the first decade, the measurements were taken statically, at spot locations, and later dynamically, across the entire road segments. When the evaluation started, only 1 out of 18 tested job sites was exceeding the minimum requirements; only after 8 years of measurements, 100% of the jobs exceeded the minimum demands. A subsequent switch to dynamic testing revealed that, on average, only 71% of the renewed road markings were in satisfactory condition and approximately 1.22% of the analysed line lengths had grossly substandard retroreflectivity. These results demonstrated that the field verification of jobs quality is necessary and simultaneously showed that static localised testing was not adequate. The outcome underlines the need for the strict supervision of road maintenance contracts to maximise the benefits for the society: through the better visibility of road markings, road safety should also improve, and the entire system will become more sustainable. Full article

Background: The aim was to elaborate a predictive model to find responders for the corticosteroid switch (from prednisolone to dexamethasone) at the first prostate-specific antigen (PSA) progression (≥25% increase) during abiraterone acetate (AA) treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: If PSA has decreased (≥25%) after switch, patients were considered responders. Logistic regression of 19 dichotomized parameters from routine laboratory and patients’ history was used to find the best model in a cohort of 67 patients. The model was validated in another cohort of 42 patients. Results: The model provided 92.5% and 90.5% accuracy in the testing and the validation cohorts, respectively. Overall the accuracy was 91.7%. The AUC of ROC curve was 0.92 (95% CI 0.85–0.96). After a median follow-up of 27.9 (26.3–84) months, the median AA+dexamethasone treatment duration (TD) in non-responders and responders was 4.7 (3.1–6.5) and 11.1 (8.5–12.9) months and the median overall survival (OS) was 23.2 (15.6–25.8) and 33.5 (26.1–38) months, respectively. Multivariate Cox regression revealed that responsiveness was an independent marker of TD and OS. Conclusions: A high accuracy model was developed for mCRPC patients in predicting cases which might benefit from the switch. For non-responders, induction of the next systemic treatment is indicated. Full article

Non-conjugated polymer-derived functional nanocomposites are one of the important ways to develop multifunctional hybrids. By increasing the degree of crosslinking, their photophysical properties can be improved. PbS is a class of narrow bandgap infrared active materials. To avoid aggregation and passivation of the surface defects of PbS nanomaterials, a large number of organic and inorganic ligands are usually used. In this study, PbS/C composite nanosheets were synthesized with Pb²⁺ ion-crosslinked sodium alginate gel by one-pot carbonization. The resulting nanosheets were coated on untreated A4 printing paper, and the electrodes were the graphite electrodes with 5B pencil drawings. The photocurrent signals of the products were measured using typical 650, 808, 980, and 1064 nm light sources. The results showed that the photocurrent switching signals were effectively extracted in the visible and near-infrared regions, which was attributed to the mutual passivation of defects during the in situ preparation of PbS and carbon nanomaterials. At the same time, the resulting nanocomposite exhibited electrical switching responses to the applied strain to a certain extent. The photophysical and defect passivation mechanisms were discussed based on the aggregation state of the carbon hybrid and the interfacial electron interaction. This material would have potential applications in broadband flexible photodetectors, tentacle sensors, or light harvesting interdisciplinary areas. This study provided a facile approach to prepare a low-cost hybrid with external stimulus response and multifunctionality. These results show that the interfacial charge transfer is the direct experimental evidence of interfacial interaction, and the regulation of interfacial interaction can improve the physical and chemical properties of nanocomposites, which can meet the interdisciplinary application. The interdisciplinary and application of more non-conjugated polymer systems in some frontier areas will be expanded upon. Full article

Water scarcity is a growing problem in many regions. Therefore, intelligent management of the available water is needed. Aside from using water mains directly in households and farms, hydrophores are often used for local water system creation. Water tanks are filled with water when available in the water mains, and then the water is extracted with a hydrophore. Wells are also used as alternative water sources. Filling the tank manually requires human presence and can lead to water overflow. It is also better if the hydrophore is protected by switching it on or off depending on the water level measured, current, and pressure in its balloon. This paper presents a water management system designed to address these issues. The system utilizes various sensors to monitor water levels, pressure, and current. Microcontrollers analyze sensor data and control hydrophores and valves based on user-defined parameters. The system offers remote monitoring capabilities and can be configured for different water source scenarios (tanks vs. wells). The system was successfully implemented in real-world settings, including a factory. The benefits of the water management system include hydrophore protection, autonomous water management, and valuable data on well recovery rates and hydrophore operation cycles. Full article

Catalases play a crucial role in the metabolism of reactive oxygen species (ROS) by converting H₂O₂ into molecular oxygen and water. They also contribute to virulence and fungal responses to various stresses. Previously, the MrCat1-deletion mutant (ΔMrCat1) was generated using the split-marker method in Metarhizium rileyi. In this study, the Cat1 gene was identified, and its function was evaluated. Under normal culture conditions, there were no significant differences in colony growth or dimorphic switching between ΔMrCat1 and the wild-type (WT) strains. However, under oxidative stress, the colony growth was inhibited, and the yeast–hyphal transition was suppressed in the ΔMrCat1 strain. Hyperosmotic stress did not differ significantly between the two strains. In the ΔMrCat1 strain, microsclerotia (MS) formation was delayed, resulting in less uniform MS size and a 76% decrease in MS yield compared to the WT strain. Moreover, the ΔMrCat1 strain exhibited diminished virulence. Gene expression analysis revealed up-regulation of ΔMrCat1, MrCat2, MrCat4, and MrAox in the ΔMrCat1 strain. These findings indicate that the MrCat1 gene in M. rileyi is essential for oxidative stress tolerance, MS formation, and virulence. Full article

Protein tyrosine kinases (PTKs) function as key molecules in the signaling pathways in addition to their impact as a therapeutic target for the treatment of many human diseases, including cancer. PTKs are characterized by their ability to phosphorylate serine, threonine, or tyrosine residues and can thereby rapidly and reversibly alter the function of their protein substrates in the form of significant changes in protein confirmation and affinity for their interaction with protein partners to drive cellular functions under normal and pathological conditions. PTKs are classified into two groups: one of which represents tyrosine kinases, while the other one includes the members of the serine/threonine kinases. The group of tyrosine kinases is subdivided into subgroups: one of them includes the member of receptor tyrosine kinases (RTKs), while the other subgroup includes the member of non-receptor tyrosine kinases (NRTKs). Both these kinase groups function as an "on" or "off" switch in many cellular functions. NRTKs are enzymes which are overexpressed and activated in many cancer types and regulate variable cellular functions in response to extracellular signaling-dependent mechanisms. NRTK-mediated different cellular functions are regulated by kinase-dependent and kinase-independent mechanisms either in the cytoplasm or in the nucleus. Thus, targeting NRTKs is of great interest to improve the treatment strategy of different tumor types. This review deals with the structure and mechanistic role of NRTKs in tumor progression and resistance and their importance as therapeutic targets in tumor therapy. Full article

The high penetration of distributed photovoltaics (PV) in distribution networks (DNs) results in voltage violations, imbalances, and flickers, leading to significant disruptions in DN stability. To address this issue, this paper proposes a multi-timescale voltage regulation approach that involves the coordinated control of a step voltage regulator (SVR), switched capacitor (SC), battery energy storage system (BESS), and electric vehicle (EV) across different timescales. During the day-ahead stage, the proposed method utilizes artificial hummingbird algorithm optimization-based least squares support vector machine (AHA-LSSVM) forecasting to predict the PV output, enabling the formulation of a day-ahead schedule for SVR and SC adjustments to maintain the voltage and voltage unbalance factor (VUF) within the limits. In the intra-day stage, a novel floating voltage threshold band (FVTB) control strategy is introduced to refine the day-ahead schedule, enhancing the voltage quality while reducing the erratic operation of SVR and SC under dead band control. For real-time operation, the African vulture optimization algorithm (AVOA) is employed to optimize the BESS output for precise voltage regulation. Additionally, a novel smoothing fluctuation threshold band (SFTB) control strategy and an initiate charging and discharging strategy (ICD) for the BESS are proposed to effectively smooth voltage fluctuations and expand the BESS capacity. To enhance user-side participation and optimize the BESS capacity curtailment, some BESSs are replaced by EVs for voltage regulation. Finally, a simulation conducted on a modified IEEE 33 system validates the efficacy of the proposed voltage regulation strategy. Full article

High-precision magnetometers play a crucial role in ocean exploration, geophysical prospecting, and military and security applications. Installing them on human-occupied vehicle (HOV) platforms can greatly enhance ocean exploration capabilities and efficiency. However, most existing magnetometers suffer from low sensitivity and excessively large size. This study presents a high-sensitivity, miniaturized magnetometer based on cesium optically pumped probes. The designed magnetometer utilizes a three-probe design to eliminate the detection dead zone of the cesium optically pumped probe and enable three-dimensional magnetic detection. The proposed magnetometer uses a flux gate probe to detect the three-axis magnetic field and ensure that the probe does not enter the dead zone. The three probes can automatically switch by measuring the geomagnetic elements and real-time attitude of the HOV platform. This article primarily introduces the cesium three-probe optically pump, flux gate sensor, and automatic switching scheme design of the above-mentioned magnetometer. Moreover, it is proven through testing that the core indicators, such as the accuracy and sensitivity of the cesium three-probe optically pumped and flux gate sensor, reach international standards. Finally, the effectiveness of the automatic switching scheme proposed in this study is demonstrated through drone-mounted experiments. Full article

The primary objective of this paper focuses on developing a control approach to improve the operational performance of a three-level neutral point clamped (3LNPC) shunt active power filter (SAPF) within a grid-tied PV system configuration. Indeed, this developed control approach, based on the used 3LNPC-SAPF topology, aims to ensure the seamless integration of a photovoltaic system into the three-phase four-wire grid while effectively mitigating grid harmonics, grid current unbalance, ensuring grid unit power factor by compensating the load reactive power, and allowing power sharing with the grid in case of an excess of generated power from the PV system, leading to overall high power quality at the grid side. This developed approach is based initially on the application of the four-wire instantaneous p-q theory for the identification of the reference currents that have to be injected by the 3LNPC-SAPF in the grid point of common coupling (PCC). Whereas, the 3LNPC is controlled based on using the finite control set model predictive control (FCS-MPC), which can be accomplished by determining the convenient set of switch states leading to the voltage vector, which is the most suitable to ensure the minimization of the selected cost function. Furthermore, the used topology requires a constant DC-link voltage and balanced split-capacitor voltages at the input side of the 3LNPN. Hence, the cost function is adjusted by the addition of another term with a selected weighting factor related to these voltages to ensure their precise control following the required reference values. However, due to the random changes in solar irradiance and, furthermore, to ensure efficient operation of the proposed topology, the PV system is connected to the 3LNPN-SAPF via a DC/DC boost converter to ensure the stability of the 3LNPN input voltage within the reference value, which is achieved in this paper based on the use of the maximum power point tracking (MPPT) technique. For the validation of the proposed control technique and the functionality of the used topology, a set of simulations has been presented and investigated in this paper following different irradiance profile scenarios such as a constant irradiance profile and a variables irradiance profile where the main aim is to prove the effectiveness and flexibility of the proposed approach under variable irradiance conditions. The obtained results based on the simulations carried out in this study demonstrate that the proposed control approach with the used topology under different loads such as linear, non-linear, and unbalanced can effectively reduce the harmonics, eliminating the unbalance in the currents and compensating for the reactive component contained in the grid side. The obtained results prove also that the proposed control ensures a consistent flow of power based on the sharing principle between the grid and the PV system as well as enabling the efficient satisfaction of the load demand. It can be said that the proposal presented in this paper has been proven to have many dominant features such as the ability to accurately estimate the power sharing between the grid and the PV system for ensuring the harmonics elimination, the reactive power compensation, and the elimination of the neutral current based on the zero-sequence component compensation, even under variable irradiance conditions. This feature makes the used topology and the developed control a valuable tool for power quality improvement and grid stability enhancement with low cost and under clean energy. Full article

Background: Multiple vaccinations have potential inimical effects on the immune system aging process. We examined whether response to SARS-CoV-2 vaccination with Tozinameran is associated with immunosenescence and immunoexhaustion in kidney transplant recipients (KTRs). Methods: In this prospective observational study, we observed 39 adult kidney transplant recipients (KTRs) who had no pre-existing anti-SARS-CoV-2 antibodies and were on stable immunosuppression. CD4+ and CD8+ T-cell subpopulations [comprising CD45RA+CCR7+ (naïve), CD45RA−CCR7+ (T-central memory, TCM), CD45RA−CCR7− (T-effector memory, TEM) and CD45RA+CCR7− (T-effector memory re-expressing CD45RA, T_EMRA, senescent), CD28− (senescent) and PD1+ (exhausted)] were evaluated at 2 time points: T1 (48 h prior to the 3rd), and T2 (3 weeks following the 3rd Tozinameran dose administration). At each time point, patients were separated into Humoral and/or Cellular Responders and Non-Responders. Results: From T1 to T2, CD4+TCM and CD8+TEM were increased, while naïve CD4+ and CD8+ proportions were reduced in the whole cohort of patients, more prominently among responders. At T2, responders compared to non-responders had higher CD8+CD28+ [227.15 (166) vs. 131.44 (121) cells/µL, p: 0.036], lower CD4+CD28− T-lymphocyte numbers [59.65 (66) cells/µL vs. 161.19 (92) cells/µL, p: 0.026] and percentages [6.1 (5.5)% vs. 20.7 (25)%, p: 0.04]. Conclusion: In KTRs, response to vaccination is not associated with an expansion of senescent and exhausted T-cell concentrations, but rather with a switch from naïve to differentiated-activated T-cell forms. Full article

Diabetic retinopathy (DR) is one of the most prevalent secondary complications associated with diabetes. Specifically, Type 1 Diabetes Mellitus (T1D) has an immune component that may determine the evolution of DR by compromising the immune response of the retina, which is mediated by microglia. In the early stages of DR, the permeabilization of the blood–retinal barrier allows immune cells from the peripheral system to interact with the retinal immune system. The use of new bioactive molecules, such as 3-(2,4-dihydroxyphenyl)phthalide (M9), with powerful anti-inflammatory activity, might represent an advance in the treatment of diseases like DR by targeting the immune systems responsible for its onset and progression. Our research aimed to investigate the molecular mechanisms involved in the interaction of specific cells of the innate immune system during the progression of DR and the reduction in inflammatory processes contributing to the pathology. In vitro studies were conducted exposing Bv.2 microglial and Raw264.7 macrophage cells to proinflammatory stimuli for 24 h, in the presence or absence of M9. Ex vivo and in vivo approaches were performed in BB rats, an animal model for T1D. Retinal explants from BB rats were cultured with M9. Retinas from BB rats treated for 15 days with M9 via intraperitoneal injection were analyzed to determine survival, cellular signaling, and inflammatory markers using qPCR, Western blot, or immunofluorescence approaches. Retinal structure images were acquired via Spectral-Domain–Optical Coherence Tomography (SD-OCT). Our results show that the treatment with M9 significantly reduces inflammatory processes in in vitro, ex vivo, and in vivo models of DR. M9 works by inhibiting the proinflammatory responses during DR progression mainly affecting immune cell responses. It also induces an anti-inflammatory response, primarily mediated by microglial cells, leading to the synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). Ultimately, in vivo administration of M9 preserves the retinal integrity from the degeneration associated with DR progression. Our findings demonstrate a specific interaction between both retinal and systemic immune cells in the progression of DR, with a differential response to treatment, mainly driven by microglia in the anti-inflammatory action. In vivo treatment with M9 induces a switch in immune cell phenotypes and functions that contributes to delaying the DR progression, positioning microglial cells as a new and specific therapeutic target in DR. Full article

The behavior of pedestrians in a non-constrained environment is difficult to predict. In wearable robotics, this poses a challenge, since devices like lower-limb exoskeletons and active orthoses need to support different walking activities, including level walking and climbing stairs. While a fixed movement trajectory can be easily supported, switches between these activities are difficult to predict. Moreover, the demand for these devices is expected to rise in the years ahead. In this work, we propose a cloud software system for use in wearable robotics, based on geographical mapping techniques and Human Activity Recognition (HAR). The system aims to give context to the surrounding pedestrians by providing hindsight information. The system was partially implemented and tested. The results indicate a viable concept with great extensibility prospects. Full article