Search Results (7,350)

Glaesserella parasuis cytolethal distending toxin (GpCDT) can induce cell cycle arrest and apoptosis. Our laboratory’s previous work demonstrated that GTPase 4b (Rab4b) is a key host protein implicated in GpCDT-induced cytotoxicity. This study investigated the probable involvement of Rab4b in the process. Our study used CRISPR/Cas9 technology to create a Rab4b-knockout cell line. The results showed greater resistance to GpCDT-induced cell cytotoxicity. In contrast, forced Rab4b overexpression increased GpCDT-induced cytotoxicity. Further immunoprecipitation study reveals that GpCDT may bind with Rab4b. In PK-15 cells, GpCDT is transported to the early endosomes and late endosomes, while after knocking out Rab4b, GpCDT cannot be transported to the early endosome via vesicles. Rab4b appears essential for GpCDT-induced cytotoxicity in PK-15 cells. Full article

Compound 1 was previously identified by our team as a glycogen phosphorylase (GP) inhibitor with glucose-lowering activity and demonstrated to have protective effects against myocardial and cerebral ischemia. However, its impact on muscle function has not been clarified. This study is the first to evaluate the long-term effects of GP inhibitors on muscle function and metabolism. After a 28-day administration of Compound 1, we performed assays to assess muscle function and biochemical parameters in rats. We observed reductions in peak holding force, duration, tetanic contraction force, single-contraction force, and electromyographic signals under 20 s and 10 min contraction stimuli. The metabolic analysis showed no significant effects on muscle glycogen, ATP, lactic acid, and uric acid levels at low doses. In contrast, medium to high doses resulted in increased glycogen, decreased ATP, and reduced lactic acid (only at high doses), without affecting uric acid. These findings suggest that Compound 1 may adversely affect muscle function in rats, potentially due to the glycogen inhibition effects of GP inhibitors. This study provides crucial safety data and insights into the long-term effects of GP inhibitors on rat muscles, which will guide future developments and applications. Full article

Vitis vinifera L., commonly known as grapes, is one of the most widely cultivated crops worldwide, with over 80% used for wine production. However, the winemaking process generates substantial residues, including grape pomace (GP), wine lees, and wastewater, which can pose significant environmental and economic challenges. Among these, GP stands out not only as a waste product but also as a rich source of polyphenols—bioactive compounds with recognized antioxidant and anti-inflammatory properties. Recent advancements have expanded the application of GP-derived extracts, particularly in the health and food industries, due to their potent bioactive properties. This review provides a comprehensive overview of the valorization of GP, focusing on its phenolic composition and therapeutic potential. It evokes innovative, environmentally friendly extraction techniques and integrated methods for the chemical analysis of these valuable compounds. Additionally, the health benefits of GP polyphenols are explored, with recent experimental findings examining their metabolism and highlighting the key role of gut microbiota in these processes. These insights contribute to a deeper understanding of the biological activity of GP extracts and underscore their growing significance as a high-added-value product. By illustrating how winemaking by-products can be transformed into natural therapeutic agents, this review emphasizes the importance of sustainable development and eco-friendly waste management practices, significantly contributing to the advancement of a circular economy. Full article

The gabapentenoids such as gabapentin (GP) and pregabalin are approved for the treatment of chronic pain, but their utility is limited by persistent side effects. These adverse effects result from GPs affecting many types of neurons and muscle cells, not just the pain-sensing neurons that are the intended targets. We have recently discovered a type of peripheral neuron, rat sympathetic neurons from the superior cervical ganglion (SCG), that is uniquely insensitive to GP effects. Currents were measured using whole-cell patch-clamp electrophysiology from cells in primary culture from either the SCG or the Nodose Ganglion (NDG) as a positive control for the effects of GP. We find that the calcium current density was dramatically reduced by GP pretreatment in NDG neurons, but that neurons from the SCG were resistant. Further, when GP was cytoplasmically injected into these neurons, the resistance of SCG neurons to GP treatment persisted. These data demonstrate that rat sympathetic neurons appear to be uniquely resistant to GP treatment. These results may help us to better understand the mechanism of action of, and resistance to, GP in altering calcium channel current density, which may help to develop future treatments with fewer side effects. Full article

Adequate coordination between healthcare levels has been proven to improve clinical indicators, care costs, and user satisfaction. This is more relevant to complex or vulnerable patients, who often require increased care. This study aims to evaluate the differences between hospital discharge follow-up indicators, including number of general practitioners’ (GPs) and community nurses’ (CNs) consultations, presentiality of consultations, type of first post-discharge consultation, and time between hospital discharge and first consultation. Vulnerable and non-vulnerable patients were compared. A longitudinal retrospective study was carried out in the north of Tenerife on the post-discharge care of patients discharged from the Canary Islands University Hospital (Spanish acronym HUC) between 1 January 2018 and 31 December 2022. The results obtained show deficiencies in the care provided to patients by primary care (PC) after being discharged from the hospital, including delayed first visits, low presentiality of those visits that were less frequent even with increased patient complexity, scarce first home visits to functionally impaired patients and delays in such visits, and a lack of priority visits to patients with increased follow-up needs. Addressing these deficiencies could help those most in need of care to receive PC, thus reducing inequalities and granting equal access to healthcare services in Spain. Full article

This study explored the polymorphism of the leucine aminopeptidase (LAP3) gene and its relationship with milk quality characteristics in Gannan yak. A cohort of 162 Gannan yak was genotyped utilizing the Illumina Yak cGPS 7K BeadChip, and the identified single nucleotide polymorphisms (SNPs) were evaluated for their association with milk protein, casein, lactose, and fat concentrations. The results showed that four SNPs (g.4,494G > A, g.5,919A > G, g.8,033G > C, and g.15,615A > G) in the LAP3 gene exhibited polymorphism with information content values of 0.267, 0.267, 0.293, and 0.114, respectively. All four SNPs were in Hardy–Weinberg equilibrium (p > 0.05). The g.4,494G > A and g.5,919A > G SNPs were significantly associated with protein content (p < 0.05), with homozygous genotypes showing significantly higher protein content than heterozygous genotypes (p < 0.05). The g.8,033G > C SNP was significantly associated with casein content, protein content, non-fat solids, and acidity (p < 0.05), with the CC genotype having significantly higher casein, protein, and non-fat solids content than the GG and GC genotypes (p < 0.05). The g.15,615A > G SNP was significantly associated with average fat globule diameter (p < 0.05). In general, the mutations within the LAP3 gene demonstrated a positive impact on milk quality traits in Gannan yak, with mutated genotypes correlating with enhanced milk quality. These results indicate that the LAP3 gene could be a significant or candidate gene affecting milk quality traits in Gannan yak and offer potential genetic markers for molecular breeding programs in this species. Full article

To address the class imbalance issue in network intrusion detection, which degrades performance of intrusion detection models, this paper proposes a novel generative model called VAE-WACGAN to generate minority class samples and balance the dataset. This model extends the Variational Autoencoder Generative Adversarial Network (VAEGAN) by integrating key features from the Auxiliary Classifier Generative Adversarial Network (ACGAN) and the Wasserstein Generative Adversarial Network with Gradient Penalty (WGAN-GP). These enhancements significantly improve both the quality of generated samples and the stability of the training process. By utilizing the VAE-WACGAN model to oversample anomalous data, more realistic synthetic anomalies that closely mirror the actual network traffic distribution can be generated. This approach effectively balances the network traffic dataset and enhances the overall performance of the intrusion detection model. Experimental validation was conducted using two widely utilized intrusion detection datasets, UNSW-NB15 and CIC-IDS2017. The results demonstrate that the VAE-WACGAN method effectively enhances the performance metrics of the intrusion detection model. Furthermore, the VAE-WACGAN-based intrusion detection approach surpasses several other advanced methods, underscoring its effectiveness in tackling network security challenges. Full article

With growing concerns over climate change, accurately predicting temperature trends is crucial for informed decision-making and policy development. In this study, we perform a comprehensive comparative analysis of four advanced time series forecasting models—Autoregressive Integrated Moving Average (ARIMA), Exponential Smoothing (ETS), Multilayer Perceptron (MLP), and Gaussian Processes (GP)—to assess changes in minimum and maximum temperatures across four key regions in the United States. Our analysis includes hyperparameter optimization for each model to ensure peak performance. The results indicate that the MLP model outperforms the other models in terms of accuracy for temperature forecasting. Utilizing this best-performing model, we conduct temperature projections to evaluate the hypothesis that the rates of change in temperatures are greater than zero. Our findings confirm a positive rate of change in both maximum and minimum temperatures, suggesting a consistent upward trend over time. This research underscores the critical importance of refining time series forecasting models to address the challenges posed by climate change and supporting the development of effective strategies to mitigate the impacts of rising temperatures. The insights gained from this work emphasize the need for continuous advancement in predictive modeling techniques to better understand and respond to the dynamics of climate change. Full article

Despite treatment and other interventions, an effective prophylactic HIV vaccine is still an essential goal in the control of HIV. Inducing robust and long-lasting antibody responses is one of the main targets of an HIV vaccine. The delivery of HIV envelope glycoproteins (Env) using nanoparticle (NP) platforms has been shown to elicit better immunogenicity than soluble HIV Env. In this paper, we describe the development of a nanoparticle-based vaccine decorated with HIV Env using the SpyCatcher/SpyTag system. The Env utilised in this study, CAP255, was derived from a transmitted founder virus isolated from a patient who developed broadly neutralising antibodies. Negative stain and cryo-electron microscopy analyses confirmed the assembly and stability of the mi3 into uniform icosahedral NPs surrounded by regularly spaced CAP255 gp140 Env trimers. A three-dimensional reconstruction of CAP255 gp140 SpyTag–SpyCatcher mi3 clearly showed Env trimers projecting from the centre of each of the pentagonal dodecahedral faces of the NP. To our knowledge, this is the first study to report the formation of SpyCatcher pentamers on the dodecahedral faces of mi3 NPs. To investigate the immunogenicity, rabbits were primed with two doses of DNA vaccines expressing the CAP255 gp150 and a mosaic subtype C Gag and boosted with three doses of the NP-developed autologous Tier 2 CAP255 neutralising antibodies (Nabs) and low levels of heterologous CAP256SU NAbs. Full article

Foam concrete has been used in various real-life applications for decades. Simple manufacturing methods, lightweight, high flowability, easy transportability, and low cost make it a useful construction material. This study aims to develop foam concrete mixtures for various civil and geotechnical engineering applications, such as in-fill, wall backfill and soil replacement work. A blended binder mix containing cement, fly ash and silica fume was produced for this study. Its compressive strength performance was compared against conventional general purpose (GP) cement-based foam concrete. Polypropylene (PP) fibre was used for both mixtures and the effect of various percentages of foam content on the compressive strength was thoroughly investigated. Additionally, two types of foaming agents were used to examine their impact on density, strength and setting time. One foaming agent was conventional, whereas the second foaming agent type can be used to manufacture permeable foam concrete. Results indicate that an increase in foam content significantly decreases the strength; however, this reduction is higher in GP mixes than in blended mixes. Nevertheless, the GP mixes attained two times higher compressive strength than the blended mix’s compressive strengths at any foam content. It was also found that the foaming agent associated with creating permeable foam concrete lost its strength (reduced by more than half), even though the density is comparable. The compressive stress–deformation behaviour showed that densification occurs in foam concrete due to its low density, and fibres contributed significantly to crack bridging. These two effects resulted in a long plateau in the compressive stress–strain behaviour of the fibre-reinforced foam concrete. Full article

(1) Background: The increasing use of e-cigarettes/vaping in children and adolescents has been recognised as a global health concern. We aim to explore the Knowledge, Attitude, and Practice of General Practitioners (GPs) in Sydney regarding the use of e-cigarettes in children and adolescents and identify the barriers to addressing this issue. (2) Methods: This pilot study was a cross-sectional study conducted using an electronic questionnaire with a Likert scale and free-text responses. (3) Results: Fifty-three GPs participated in the study (male = 24 and female = 29) with a mean age of 50 ± 5.5 years. There was strong agreement (mean 4.5) about respiratory adverse effects and addictive potential. However, there was less awareness of cardiac side effects and the occurrence of burns. There is a lack of conversation about e-cigarettes in GP practice and a deficit of confidence in GPs regarding managing e-cigarette use in children and adolescents. (4) Conclusions: Our pilot study has shown that GPs are somewhat knowledgeable about the potential adverse effects of the use of e-cigarettes in children and adolescents, though there is a lack of knowledge of the complete spectrum of adverse effects and more importantly, there is a paucity of a structured approach to discuss the use of e-cigarettes with children and adolescents, and there is a low level of confidence in addressing these issues. There is a need for educational interventions for GPs to increase awareness of the potential adverse effects of using e-cigarettes and build confidence in providing management to children and adolescents regarding the use of e-cigarettes. Full article

In this study, the Wasserstein Generative Adversarial Network with Gradient Penalty (WGAN-GP) was used to improve the diagnosis of Alzheimer’s disease using medical imaging and the Alzheimer’s disease image dataset across four diagnostic classes. The WGAN-GP was employed for data augmentation. The original dataset, the augmented dataset and the combined data were mapped using Uniform Manifold Approximation and Projection (UMAP) in both a 2D and 3D space. The same combined interaction network analysis was then performed on the test data. The results showed that, for the test accuracy, the score was 30.46% for the original dataset (unbalanced), whereas for the WGAN-GP augmented dataset (balanced), it improved to 56.84%, indicating that the WGAN-GP augmentation can effectively address the unbalanced problem. Full article

The accuracy and reliability of soil moisture retrieval based on Global Positioning System (GPS) single-star Signal-to-Noise Ratio (SNR) data is low due to the influence of spatial and temporal differences of different satellites. Therefore, this paper proposes a Random Forest (RF)-based multi-satellite data fusion Global Navigation Satellite System Interferometric Reflectometry (GNSS-IR) soil moisture retrieval method, which utilizes the RF Model’s Mean Decrease Impurity (MDI) algorithm to adaptively assign arc weights to fuse all available satellite data to obtain accurate retrieval results. Subsequently, the effectiveness of the proposed method was validated using GPS data from the Plate Boundary Observatory (PBO) network sites P041 and P037, as well as data collected in Lamasquere, France. A Support Vector Machine model (SVM), Radial Basis Function (RBF) neural network model, and Convolutional Neural Network model (CNN) are introduced for the comparison of accuracy. The results indicated that the proposed method had the best retrieval performance, with Root Mean Square Error (RMSE) values of 0.032, 0.028, and 0.003 cm³/cm³, Mean Absolute Error (MAE) values of 0.025, 0.022, and 0.002 cm³/cm³, and correlation coefficients (R) of 0.94, 0.95, and 0.98, respectively, at the three sites. Therefore, the proposed soil moisture retrieval model demonstrates strong robustness and generalization capabilities, providing a reference for achieving high-precision, real-time monitoring of soil moisture. Full article

Precision agriculture (PA) technologies combined with remote sensors, GPS, and GIS are transforming the agricultural industry while promoting sustainable farming practices with the ability to optimize resource utilization and minimize environmental impact. However, their implementation faces challenges such as high computational costs, complexity, low image resolution, and limited GPS accuracy. These issues hinder timely delivery of prescription maps and impede farmers’ ability to make effective, on-the-spot decisions regarding farm management, especially in stress-sensitive crops. Therefore, this study proposes field programmable gate array (FPGA)-based hardware solutions and real-time kinematic GPS (RTK-GPS) to develop a real-time crop-monitoring system that can address the limitations of current PA technologies. Our proposed system uses high-accuracy RTK and real-time FPGA-based image-processing (RFIP) devices for data collection, geotagging real-time field data via Python and a camera. The acquired images are processed to extract metadata then visualized as a heat map on Google Maps, indicating green area intensity based on romaine lettuce leafage. The RFIP system showed a strong correlation (R² = 0.9566) with a reference system and performed well in field tests, providing a Lin’s concordance correlation coefficient (CCC) of 0.8292. This study demonstrates the potential of the developed system to address current PA limitations by providing real-time, accurate data for immediate decision making. In the future, this proposed system will be integrated with autonomous farm equipment to further enhance sustainable farming practices, including real-time crop health monitoring, yield assessment, and crop disease detection. Full article

Improving seed germination and seedling development can potentially increase crop yield and improve quality in direct-seeded rice. This study aimed to detect loci or genes associated with rice seed germination. We reported the phenotypic analysis of seed germination in 103 rice accessions across two years, and a genome-wide association study (GWAS) was conducted to identify loci underlying the genetic regulation of seed germination. A total of seven genetic loci were found to be associated with seed germination, including five loci that overlapped with the previously reported loci/genes, and two novel loci. Of these, two loci (qGP2 and qGP4.1) were stable across different environments. GP4 (Germination percentage 4), encoding a 9-cis-epoxycarotenoid dioxygenase, was identified as the candidate gene of the major locus qGP4.1. A sequence analysis of GP4 revealed that four functional polymorphic sites in the coding region were significantly associated with germination percentage. The disruption of GP4 by gene editing resulted in faster seed germination and seedling establishment. Taken together, we have identified GP4 as a novel gene involved in rice seed germination, and we provide a potential target gene for improving rice seed vigor via gene editing or molecular breeding. Full article