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Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin
Metformin (MET) is a commonly used drug for the treatment of type 2 diabetes in the department of endocrinology. In recent years, due to the few clinically effective treatment options including glioma, some scholars have proposed the possibility of metformin in the treatment of glioma, and studies have shown that metformin has a certain inhibitory effect on this tumor. This review explores the multiple mechanisms through which metformin exerts its antitumor effects, focusing on signaling pathways such as AMPK/mTOR, ferroptosis, autophagy, apoptosis and chloride ion channels (CLIC1). Metformin’s inhibition of glioma proliferation involves complex cellular processes, including mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and modulation of immune responses. Additionally, metformin affects glioma stem cells by inhibiting key pathways, including STAT3, mTOR, and AKT, and altering the tumor microenvironment. While preclinical studies suggest that metformin enhances radiosensitivity and reduces tumor recurrence, its clinical application remains in early stages, with further studies needed to optimize dosing regimens and understand its full therapeutic potential. This review provides a comprehensive analysis of metformin’s molecular mechanisms in glioma treatment and highlights its potential as a novel therapeutic strategy, especially for treatment-resistant gliomas
“Don’t Even Smoke But I’ll Buy That” Twitch as a New Venue for E-Cigarette Promotion
ObjectivesThis study examines the covert promotion of e-cigarettes, specifically Juul, on the video live-streaming platform Twitch, focusing on the content and platform-specific dynamics that may influence its effectiveness.MethodsThis qualitative case study of a non-gaming Twitch stream included data from influencer conversations, viewer comments and visual elements. Thematic analysis, coding, and categorisation were conducted using ATLAS.ti.ResultsThe livestream, which attracted over ten thousand viewers, featured three friends vaping and discussing their personal experiences with Juul. Themes included curiosity, device sharing, and smoking cessation benefits. The stream fostered a casual, engaging atmosphere, with viewers interacting extensively with the influencers and also other viewers. Despite suspicions of industry sponsorship, viewers reacted positively and even joked about the sponsorship. Several viewers, including those who claimed not to smoke, expressed interest in Juul.ConclusionThe study highlights concerns about the promotion of harmful commodities on Twitch, where strong community engagement, monetary incentives, and a lack of specific content policies create a conducive environment for such practices. This underscores the need for greater scrutiny and regulation of e-cigarette promotions on the platform
HCG 57: Evidence for Shock-heated Intergalactic Gas from X-Rays and Optical Emission Line Spectroscopy
We present Chandra and XMM-Newton X-ray observations of the compact group HCG 57, and optical integral field spectroscopy of the interacting galaxy pair HCG 57A/D. These two spiral galaxies recently suffered an off-axis collision with HCG 57D passing through the disk of A. We find evidence of a gas bridge linking the galaxies, containing ∼10 ^8 M _⊙ of hot, ∼1 keV thermal plasma and warm ionized gas radiating in H α , H β , [O iii ] and [N ii ] lines. The optical emission lines in the central regions of HCG 57D show excitation properties consistent with H ii -regions, while the outer rim of HCG 57D parts of the bridge and the outer regions of HCG 57A show evidence of shocked gas consistent with shock velocities of 200–300 km s ^−1 . In contrast, the X-ray emitting gas requires a collision velocity of 650–750 km s ^−1 to explain the observed temperatures. These different shock velocities can be reconciled by considering the contributions of rotation to collision velocity in different parts of the disks, and the clumpy nature of the preshock medium in the galaxies, which likely lead to different shock velocities in different components of the turbulent postshocked gas. We examine the diffuse X-ray emission in the group members and their associated point sources, identifying X-ray active galactic nuclei in HCG 57A, B, and D. We also confirm the previously reported ∼1 keV intra-group medium and find it to be relaxed with a low central entropy (18.0 ± 1.7 keV cm ^2 within 20 kpc) but a long cooling time (5.9 ± 0.8 Gyr)
Magnetic polymeric ionic liquid for both catalysis application and magnetic solid phase extraction approach
Abstract In this project, a new heterogeneous polymeric ionic liquid catalyst based on vinylimidazole, stabilized on magnetic nanoparticles )Fe3O4@Al2O3@[PBVIm]HSO4) was prepared. Then the desired catalyst was identified by TGA, FT-IR, VSM, and TEM techniques. The efficiency of this catalyst was measured in the synthesis of chromene, xanthene, and dihydropyrimidinone. Moreover, the capability of the prepared sorbent for the extraction and determination of BPA (bisphenol A) was studied. Under the optimum conditions, the linearity range of the technique was between 0.5 and 100 µg L−1 with the coefficient of determination (r2) of 0.9948. Relative standard deviations for intra- and inter-day precision for the BPA (bisphenol A) at 20 µg L−1 were in the range of 3.1–3.9% and 3.7–4.2%, respectively. The limit of detection and limit of quantification were 0.07 and 0.48 µg L−1 respectively. Excellent efficiency, compatibility with environmental conditions, and easy recycling of the catalyst are among the most important features of the synthetic catalyst
Global, regional, and national burden of children and adolescents with acute lymphoblastic leukemia from 1990 to 2021: a systematic analysis for the global burden of disease study 2021
BackgroundAcute lymphoblastic leukemia (ALL) is a common cancer in children and adolescents, severely affecting their survival and health. With the discovery of new drugs and improved treatment options, the survival rate of ALL in children and adolescents has improved significantly.MethodsWe used the GBD (global burden of disease) database to collect patients aged 0–19 years (0–5 years, 5–9 years, 10–14 years, 15–19 years) diagnosed with ALL between 1990 and 2021. Disease status and change were analyzed by learning about the prevalence, death, incidence, DALYs (disability-adjusted life years), percentage change, and the estimated annual percentage change (EAPC).ResultsIn 2021, there were 53,485 new cases of childhood and adolescent ALL, 23,991 deaths, and an estimated 1960,922 DALYs. Incidence, deaths and DALYs have declined globally, with only a rise in low-SDI regions. In 2021, middle-SDI regions have the highest cases of prevalence, incidence, deaths, and DALYs, accounting for approximately one-third of the global total. High-SDI regions have the lowest deaths and DALYs. East Asia has the highest prevalence and incidence. Australasia has the lowest death and DALYs. From 1990 to 2021, children and adolescent ALL deaths and DALYs show a declining trend in about 72.5% of countries, with only Sub-Saharan Africa showing an increase. The prevalence of ALL in children and adolescents is higher in males, with the highest cases in patients under 5 years of age.ConclusionOur study highlights the trend of decreasing deaths and DALYs of ALL in children and adolescents. However, there is a need to improve healthcare prevention and timely standardized treatment in developing countries and less developed regions
Numerical investigation of infrared imaging of multi-UAV formation under cloud and rain weather conditions
Infrared imaging is essential for detecting multiple unmanned aerial vehicle (UAV) targets detection to capture flight altitude and behavior. This study focused on a typical stealth UAV formation with a flying-wing configuration. Considering the attenuation effects of clouds and rain on the infrared spectrum, a ground-based infrared imaging algorithm was developed. Infrared radiation imaging was conducted using the apparent ray tracing method and mesh clipping technology. The infrared radiation intensity distribution of the UAV formation target within the 8.0–12.0 μm band was calculated, and infrared thermal images incorporating the occlusion effect were obtained. The results showed that the radiance of the multi-UAV formation was approximately 8.0 × 10−5 W/Sr, which was 103–104 orders of magnitude lower than that under standard atmospheric conditions under cloudy weather conditions. The infrared radiance was approximately 1.7 × 10−5 W/Sr, which was 104–105 lower than that under standard atmospheric conditions under rainy weather conditions
Pharmacovigilance imbalance analysis of VEGFR-TKI-related taste and smell disorders
Abstract Taste and smell disorders (TSDs) can induce diminished interest in food, inadequate nutrient intake, and emotional irregularities, particularly among cancer patients. Previous research found that the main culprits of TSD development in cancer patients are cytotoxic drugs such as taxol, fluorouracil, cyclophosphamide, and anthracycline-based drugs. The advent of targeted drugs such as vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) has significantly extended the survival time of cancer patients, and thus widely used in clinical practice. However, the association between the use of VEGFR-TKIs and the development of TSDs havs not been studied.The adverse event(AE) reports related to VEGFR-TKIs were downloaded from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis was conducted to assess the correlation between VEGFR-TKIs and TSDs. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) were used to analyze the AEs of TSDs. The study found a statistically significant correlation between the occurrence of TSDs and the use of VEGF-TKIs (cabozantinib, axitinib, pazopanib, sunitinib, nintedanib, and lenvatinib).However, the instructions for Nintedanib, Sorafenib and Lenvatinib were not mentioned. Capbottinib demonstrated the highest number of reports(1790 cases), also with the strongest association (ROR 95%CI-low = 16.51; PRR = 16.18; IC025 = 3.96) when analyzing the narrow SMQ of TSDs. Dysgeusia, taste disorder, and ageusia were the most commonly reported preferred terms (PTs) in VEGFR-TKI-related TSDs, accounting for more than 90% of the reported cases. Cabozantinib showed the highest number of reports and strongest correlation with ageusia, taste disorder, parosmia, and anosmia. The study found significant association between the reports of TSDs and the use of VEGFR-TKIs, indicating the monitoring of TSD development and appropriate management in clinical is necessary
Enhanced streamflow forecasting using hybrid modelling integrating glacio-hydrological outputs, deep learning and wavelet transformation
Abstract Understanding snow and ice melt dynamics is vital for flood risk assessment and effective water resource management in populated river basins sourced in inaccessible high-mountains. This study provides an AI-enabled hybrid approach integrating glacio-hydrological model outputs (GSM-SOCONT), with different machine learning and deep learning techniques framed as alternative ‘computational scenarios, leveraging both physical processes and data-driven insights for enhanced predictive capabilities. The standalone deep learning model (CNN-LSTM), relying solely on meteorological data, outperformed its counterpart machine learning and glacio-hydrological model equivalents. Hybrid models (CNN-LSTM1 to CNN-LSTM15) were trained using meteorological data augmented with glacio-hydrological model outputs representing ice and snow-melt contributions to streamflow. The hybrid model (CNN-LSTM14), using only glacier-derived features, performed best with high NSE (0.86), KGE (0.80), and R (0.93) values during calibration, and the highest NSE (0.83), KGE (0.88), R (0.91), and lowest RMSE (892) and MAE (544) during validation. Finally, a multi-scale analysis using different feature permutations was explored using wavelet transformation theory, integrating these into the final hybrid model (CNN-LSTM19), which significantly enhances predictive accuracy, particularly for high-flow events, as evidenced by improved NSE (from 0.83 to 0.97) and reduced RMSE (from 892 to 442) during validation. The comparative analysis illustrates how AI-enhanced hydrological models improve the accuracy of runoff forecasting and provide more reliable and actionable insights for managing water resources and mitigating flood risks - despite the paucity of direct measurements
Characterization and genome analysis of a novel phage BP15 infecting Vibrio parahaemolyticus
Abstract Vibrio parahaemolyticus is pathogenic to both humans and marine animals. Antimicrobial-resistant (AMR) bacteria have been reported to cause mortalities in shrimp, with phage therapy presenting an alternative and eco-friendly biocontrol strategy for controlling bacterial diseases. Therefore, this study aimed to isolate and characterize phages for their applicability in lysing Vibrio parahaemolyticus. A novel phage vB_VpaS_BP15 (BP15) belonged to the subfamily Queuovirinae with an icosahedral head measuring 69.11 ± 5.38 nm in length and 65.40 ± 6.89 nm in width, and a non-contractile sheathed tail measuring 139.81 ± 14.79 nm. The one-step growth curve indicated a latent period of 30 min and a burst size of 120 PFUs per cell. Phage BP15 exhibited tolerance to a range of temperatures and pH values. Infection dynamic curves demonstrated that BP15 was highly effective against BCRC12959 at MOIs ranging from 0.01 to 10; even at a low multiplicity of infection (MOI) of 0.001, BP15 still caused growth retention. Phage BP15 possessed a circular double-stranded DNA of 59,584 bp with a G + C content of 46.7% and lacked tRNA genes, virulence genes, and lysogeny genes. These findings highlight the promising potential of phage BP15 as a biocontrol agent against Vibrio parahaemolyticus in Taiwan
Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome
Abstract Mutations of the MECP2 gene lead to Rett syndrome (RTT), a rare developmental disease causing severe intellectual and physical disability. How the loss or defective function of MeCP2 mediates RTT is still poorly understood. MeCP2 is a global gene expression regulator, acting at transcriptional and post-transcriptional levels. Little attention has been given so far to the contribution of alternative splicing (AS) dysregulation to RTT pathophysiology. To perform a comparative analysis of publicly available RNA sequencing (RNA-seq) studies and generate novel data resources for AS, we explored 100 human datasets and 130 mouse datasets from Mecp2-mutant models, processing data for gene expression and alternative splicing. Our comparative analysis across studies indicates common species-specific differentially expressed genes (DEGs) and differentially alternatively spliced (DAS) genes. Human and mouse dysregulated genes are involved in two main functional categories: cell-extracellular matrix adhesion regulation and synaptic functions, the first category more significantly enriched in human datasets. Our extensive bioinformatics study indicates, for the first time, a significant dysregulation of AS in human RTT datasets, suggesting the crucial contribution of altered RNA processing to the pathophysiology of RTT