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Unveiling the therapeutic potential of phenolic compounds from Boletus edulis in osteoarthritis treatment
Dual effects of indoxyl sulfate on modulation of human hepatic CYP3A activity, with individual differences
This study aimed to identify gut microbiota-derived metabolites governing the activity of hepatic CYP3A in blood level. Indole propionic acid (IPA) and lithocholic acid, ligands of the pregnane X receptor, a transcriptional regulator of CYP3A, and various gut microbiota-derived metabolites in blood level were analyzed. Results revealed that IPA and lithocholic acid did not affect CYP3A activity, while indoxyl sulfate (IS), a uremic toxin, affected CYP3A across different cell lines. The effects of IS on primary hepatocytes from three donors were analyzed, and a concentration-dependent impact was observed, as the CYP3A activity decreased in one donor and increased in another. These findings offer initial insights into blood-level gut microbiota-derived metabolites influencing hepatic CYP3A. Furthermore, the study demonstrates that the response to IS, beyond its concentration, can cause variations in hepatic CYP3A activity among individuals. This study advocates accounting for the dual effects of IS and the benefits of personalized medicine.
Energy efficiency enhancement in two European data centers through CFD modeling
Abstract The new reporting scheme adopted by the European Union focuses on the efficiency assessment of data centers based on key performance indicators (KPIs). This has the potential to lead to further measures for improving energy efficiency of data centers. Consequently, a systematic approach is crucial for assessing and improving data center performance. This study investigates efficiency assessment of two European pilot data centers, located in Denmark and Poland, according to the KPIs calculated through Computational Fluid Dynamics (CFD) simulations of airflow and thermal structures. Two separate experimental approaches were adopted at the pilot sites. One measured airflow and temperatures using external sensors at server inlets and outlets, while the other measured inlet temperatures from embedded server sensors. The good agreement observed between simulated and experimental data confirmed the accuracy of the computational model. The validated CFD model was applied to investigate efficiency improvement opportunities by retrofitting the thermal environment such as rack positioning, containment implementation, and guided airflow control. A series of numerical simulations are performed using the validated numerical model and KPIs are calculated for each design. Numerical simulations demonstrate that the efficiency of an existing data center can be enhanced by up to 75% using the presented approach, although the improvement varied significantly with the specific KPIs. The computational approach proposed here can be readily generalized to guide the efficiency assessment and improvement of existing data centers.
Green tea consumption rapidly enhances cognitive performance and flow state during mental tasks in healthy young adults
This study examined green tea’s effects on task performance, mental fatigue, workload, and flow experience. Twenty-two healthy young male participants (mean ± SD age = 21.86 ± 1.96 years, range = 18–26 years) completed two 5-min mental tasks (arithmetic and sequential digit search) under three beverage consumption conditions: no beverage (NONE), WATER, and TEA (green tea). In the WATER and TEA conditions, participants consumed 70 mL of beverage three times during the session (total: 210 mL). Subjective Fatigue Feelings was assessed before and after each condition, and subjective evaluations including NASA Task Load Index, Flow Experience Checklist, and Duration Judgment Ratio, were conducted after each task. Results showed no significant differences in task performance across conditions (p > 0.05, η² = 0.11 and η² = 0.02 for MATH and SDS tasks, respectively), likely due to ceiling effects (accuracy > 95%). In the TEA condition, arousal levels were maintained and no increase in mental fatigue was observed, unlike the other conditions. The flow state score in the TEA condition was significantly higher than that in other conditions (NONE vs TEA: p = 0.0009), and participants perceived shorter task duration (NONE vs TEA: p = 0.0016, WATER vs TEA: p = 0.0061). These effects were observed even with small amounts of beverage and short consumption periods, suggesting that habitual intake of low-dose green tea may enhance task engagement and flow experience in everyday tasks.
Investigation on overburden failure and subsurface subsidence characteristics in fully mechanized top-coal caving of “Three-Soft” Thick coal seams
Coarse-grained molecular dynamics investigation on the interaction between κ- and β-casein aggregates and curcumin
Effect of interacting minds on response criterion in two person perceptual decision making
A behaviour change intervention promoting physical activity following dysvascular amputation: Protocol for a pilot study
Background Diabetes-related lower limb amputation (LLA) is a leading cause of disability globally, impacting individuals’ physical and mental health, and ultimately their quality of life. Physical activity can reduce risk of chronic disease and mortality while improving quality of life. However, people with LLA often have reduced balance and walking ability resulting in sedentary behaviour. We co-created a physical activity intervention, IMproving Physical Activity through Coaching and Technology following Lower Limb Loss (IMPACT-L3), to support physical activity behaviour change in people with dysvasular LLA. To date, no studies have assessed a peer-led physical activity behaviour change intervention for people with LLA. Prior to launching a large trial, a pilot study is required to assess feasibility and optimize design of a future trial. Methods This pilot study is a parallel group randomized controlled trial (RCT) with an embedded qualitative component. The intervention group will have access to once-weekly virtual peer coaching sessions with a peer trained in brief action planning; web-based physical activity modules; and a wearable activity monitor for 8 weeks. The control group will continue usual care and be offered the intervention at the end of the follow-up period. Data on feasibility will be collected including assessment of process, resource, management and treatment indicators. The proposed primary outcomes will be measured at baseline, post-intervention and one month later: total physical activity counts per day measured by the ActiGraphTM activity monitor and self-efficacy measured by the Self-efficacy for Exercise scale. Secondary measures include patient reported outcome measures of physical activity, mobility, depression, social participation, balance confidence and quality of life. Semi-structured interviews will explore feasibility and acceptability of the intervention to participants and peers. Discussion This study will inform the design of a definitive RCT to determine the effectiveness of a peer-led physical activity intervention for people with dysvascular LLA.
Comprehensive multi-omics and machine learning framework for glioma subtyping and precision therapeutics
Monitoring cognitive resilience in military personnel in extreme operational environments: The role of smart technologies and nutritional strategies—A scoping review protocol
Introduction Maintaining cognitive performance in extreme operational environments is essential for military personnel efficiency. Exposure to multiple stressors, including sleep deprivation, intense physical exertion, and limited access to food resources, can affect cognitive function and decision-making ability. Although studies on military nutrition and smart technologies exist, an integrated synthesis that analyzes their interactions is currently lacking. Materials and methods This scoping review follows the JBI methodology, with a structured study selection and data synthesis process. The analysis includes international databases and grey literature, with results presented both narratively and in tabular form, Objectives This scoping review aims to map and analyze the literature on smart technologies used for monitoring the cognitive resilience of military personnel deployed in extreme operational environments, as well as the role of nutritional strategies in supporting cognitive resilience, following the PCC criteria. Inclusion criteria Studies published after 2000 that investigated nutritional strategies and the use of smart technologies to monitor or support the cognitive resilience of military personnel will be included. Research focusing solely on physical performance or pharmacological interventions unrelated to operational nutrition was excluded, Registration This scoping review protocol was registered in the OSF (Open Science Framework): [https://doi.org/10.17605/OSF.IO/EC7MG].
Transcutaneous electrical stimulation in chronic post-stroke oropharyngeal dysphagia: pooled biomechanical and kinematic analysis from a one-year randomized controlled clinical trial
In silico identification of promising PD-L1 inhibitors from selected indian medicinal plants for treatment of triple negative breast cancer
Triple-negative breast cancer (TNBC) is the most aggressive among the breast cancer subtypes and poses unique therapeutic challenges due to its distinct characteristics like lack of specific therapeutic targets. TNBC demonstrates poor survival rate enhanced immunogenic characteristics and a more favorable tumor microenvironment than other breast cancer variants. Also, TNBC patients show elevated levels of programmed death ligand-1 (PD-L1) expression in contrast to non-TNBC patients. Binding of PD-L1 with PD-1 produces an inhibitory signal, resulting in suppression of T-cell. Therapeutic approaches utilizing immunotherapies against PD-L1 exhibit promising outcomes in the treatment of TNBC. Limitations like suboptimal efficacy, inadequate oral bioavailability, and associated immune-related adverse effects of antibody-mediated anti PD-1/PD-L1 therapies have necessitated the exploration of alternative therapeutic approaches. Thus, small molecules become an alternate option for PD-1/PD-L1 inhibition. In the present study, we have used virtual screening to identify potential phytochemicals from selected Indian medicinal plants as PD-L1 inhibitors. A total of 953 phytochemicals derived from eleven selected medicinal plants were initially screened through molecular docking using the PyRx tool. Among the 953 identified phytochemicals, the top 20 compounds exhibiting the highest binding affinities in docking study were selected for further analysis. Following comprehensive ADMET analyses, 2 compounds were ultimately identified as suitable candidates for a molecular dynamics (MD) simulation study. The study identified 4-hydroxychalcone and flavylium from Glycyrrhiza glabra and Catharanthus roseus, respectively as potential PD-L1 inhibitors with enhanced stability relative to the reference molecule. Both compounds also showed enhanced gastrointestinal absorption with no predicted cytotoxic and immunotoxic effects. Consequently, these compounds present promising candidates for novel PD-L1 inhibitor development in TNBC therapy. Further experimental investigations are necessary to facilitate their clinical translation.
Evaluation of complex multi-physics phenomena at gas diffusion electrodes during high-pressure water electrolysis with AEMs
Abstract The alkaline water electrolysis is a well-established process for producing green hydrogen from renewable energy sources. With up-to-dateAEM electrolyzers, electrochemical gas compression can be realized with water electrolysis and ion pumping membranes, to avoid costly mechanical compression. In this experimental study, we researched an electrolyzer cell with a strong metal structure, for internal pressure difference of up to 100 bar. Micro-porous gas diffusion electrodes containing non-precious nickel catalysts as well as different separators, alkaline membranes and AEMs have been investigated in the range of 300 to 800 mA cm − 2 . For one preferred AEM, characteristics are shown for hydrogen pressures between 20 and 80 bars, while the anode remains at ambient 1 bar. Impedance spectroscopy diagrams are used to display the individual cell components: the ohmic resistance of the AEM and the complex impedances of both electrodes. Therewith, we could visualize the complex multi-physics phenomena and show that the oxygen electrode works as a Wartburg-element, especially due to higher diffusion rates and therewith entropy production during bubble formation.
Genome diversity and signatures of natural selection in mainland Southeast Asia
EBV-miR-BART5-5p regulates RORA to promote proliferation and migration of gastric cancer cells
Background Epstein-Barr virus-associated gastric cancer (EBVaGC) represents a distinct molecular subtype of gastric cancer. EBV encodes various viral RNAs, including BamHI-A rightward transcripts (BARTs), which are implicated in the carcinogenic processes of EBVaGC. This study aims to explore the function and underlying mechanisms of EBV-miR-BART5-5p in gastric cancer, providing a basis for the identification of more effective biomarkers for EBVaGC. Methods Gene expression data were first downloaded from the GSE51575 dataset to identify differentially expressed genes and construct a WGCNA network, which led to the identification of RORA as a key gene associated with EBV-miR-BART5-5p. We then analyzed the TCGA dataset to investigate the differential expression and prognostic significance of RORA in gastric cancer. Further analysis explored RORA’s enriched pathways and its relationship with immune response, tumor mutation burden, and drug sensitivity. Single-cell gene expression characteristics of RORA were assessed using the GSE134520 dataset. RT-qPCR was employed to determine RORA expression levels in both EBV-positive and -negative gastric cancer cell lines. Western blotting and dual-luciferase reporter assays confirmed the targeting of RORA’s 3’ UTR by EBV-miR-BART5-5p. Finally, a series of functional experiments demonstrated that EBV-miR-BART5-5p promotes proliferation and migration of both EBV-positive and -negative gastric cancer cells. Results In this study, differential expression and WGCNA analyses identified 910 co-expressed genes. We then investigated miR-BART5-5p in EBV-positive gastric cancer and identified RORA as a potential target gene. Our analysis revealed that RORA expression is lower in tumor samples compared to normal samples, and single-cell analysis showed significant upregulation of RORA in CD8 + T cells. Experimental data further demonstrated that RORA is expressed at lower levels in EBV-positive gastric cancer cell lines and that EBV-miR-BART5-5p targets the 3’ UTR of RORA. This suggests that EBV-miR-BART5-5p may promote gastric cancer cell proliferation and migration by regulating RORA. Conclusion Our study reveals the molecular characteristics of EBV-associated gastric cancer, establishes a prognostic model for RORA in gastric cancer, and demonstrates that EBV-miR-BART5-5p may target and inhibit RORA to promote gastric cancer cell proliferation and migration. These findings highlight EBV-miR-BART5-5p could serve as a diagnostic biomarker and a potential therapeutic target for gastric cancer.
A self-learning method with domain knowledge integration for intelligent welding sequence planning
LSTM-based prediction method for shape error of steel truss during incremental launching construction
Accurate shape control during steel truss incremental launching remains a persistent challenge in bridge engineering, primarily due to dynamic geometric variations induced by continuous spatial translation. Conventional measurement-based approaches often lead to inaccurate error determination and insufficient control criteria due to continuous geometric variations during structural movement. This study presents a novel Long Short-Term Memory (LSTM)-based methodology for real-time prediction and adaptive control of shape errors in launching processes. First, an error matrix is established based on the actual pushing measurement plan, and numerous error splines are generated using virtual assembly technology. These splines are output as an error matrix and encoded into a machine-readable format, leading to the establishment of a sliding window method for recursive prediction and updates of the predictions (measured values). Then, the LSTM model is trained using this sliding window approach, achieving a root mean square error(RMSE) of 0.03 on the test set. Field experiments demonstrate that the predicted values from the LSTM model closely align with the measured values, maintaining short-term shape error prediction accuracy within 3 mm. However, prediction accuracy diminishes for longer time steps as the step length increases. Following model updates with measured data, the accumulated prediction error rapidly decreases. The proposed prediction method for shape errors during pushing exhibits high accuracy and versatility in similar projects, significantly reducing time spent on manual error handling and minimizing computational inaccuracies.
Research on the network structure evolution characteristics of outdoor sports tourism flow in the Yangtze River Economic belt based on online travel notes
MiR-122 promotes metastasis of hepatoma cells by modulating RBM47-integrin alpha V-TGF-beta signaling
MiR-122 is a liver-abundant miRNA, which is thought to harbor antitumorigenic activity. Elevated transforming growth factor-β (TGF-β) in hepatocellular carcinoma (HCC) microenvironment is a potent inducer for tumor metastasis. However, the involvement of miR-122 in regulation of TGF-β signaling and its implication in TGF-β-related HCC metastasis remains obscure. In this study, we demonstrated that miR-122 significantly enhanced the activities of the TGF-β pathway reporter, the levels of phosphorylation of Smad2 and Smad3, and the expression of mesenchymal markers (N-cadherin and vimentin) in HCC cells. Notably, miR-122 significantly promoted the migration and invasion in vitro and pulmonary metastasis of HCC cells in vivo. Mechanism investigations revealed that miR-122 directly suppressed the expression of RBM47, which was a novel RNA binding protein. RBM47 decreased the level of αv integrin (ITGAV) by promoting the degradation of mRNA via interacting with the AU-rich elements in its 3’UTR. Subsequently, the elevated ITGAV induced by miR-122 promoted activation of the latent TGF-β, thereby boosted the TGF-β signaling and then promoted cell motility. Taken together, miR-122 could promote metastasis of hepatoma cells by regulating RBM47-ITGAV-TGF-β signaling. These findings provide new insight into the regulatory network of miR-122, the complexity and robustness of TGF-β pathway and the mechanisms of HCC metastasis.