Search Results (270)

Background/Objectives: The accumulation of Nε-carboxymethyllysine (CML), a major advanced glycation end product (AGE), has been implicated in neuronal dysfunction by promoting oxidative stress, endoplasmic reticulum (ER) stress, and dysregulation of amyloid-β (Aβ) metabolism. This study evaluated the neuroprotective properties of coixol, a naturally occurring polyphenolic compound derived from the outer layers of Coix lacryma-jobi L. var. ma-yuen, in a CML-induced injury model using IMR-32 human neuronal-like cells. Methods: Cells were pretreated with coixol (1 μmol/L), N-acetyl-L-cysteine (NALC, 1 mmol/L), or 4-phenylbutyric acid (4-PBA, 200 μmol/L) for 1 h prior to CML (100 μmol/L) exposure for 24 h. Cell viability was determined by colorimetric analysis of 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide, while intracellular reactive oxygen species (ROS) generation was quantified using a fluorescence-based oxidative stress probe. Activities of key antioxidant enzymes and caspase-3 were determined using commercial assay kits. The expression of Aβ isoforms, amyloidogenic enzymes, ER stress markers, and apoptosis-related signaling proteins was quantified through validated immunoassays. Results: Coixol pretreatment significantly enhanced cell viability by attenuating ROS accumulation and restoring antioxidant enzyme activities. Concurrently, coixol suppressed ER stress signaling via downregulation of the protein kinase R-like ER kinase/C/EBP homologous protein axis and modulated apoptosis by increasing B-cell lymphoma (Bcl)-2, reducing Bcl-2-associated X protein expression, and inhibiting caspase-3 activation and DNA fragmentation. Furthermore, coixol regulated Aβ metabolism by inhibiting the expression of β-site amyloid precursor protein-cleaving enzyme 1 and presenilin 1, while restoring insulin-degrading enzyme and neprilysin levels, leading to reduced accumulation of Aβ40 and Aβ42. Conclusions: Compared to NALC and 4-PBA, coixol demonstrated comparable or superior modulation across multiple pathological pathways. These findings highlight coixol’s potential as a neuroprotective candidate in AGE-associated neurodegenerative conditions. Full article

Aquatic animal welfare has been gaining increasing attention globally in the last few years. The Aquatic Animal Welfare Research and Practice Seminar was held in Hangzhou, China, from 28th to 29th March 2025. The Seminar gathered leading scientists and industry stakeholders from across the world who presented their recent research in aquatic animal welfare. This report presented the seminar’s key outcomes and discussions, highlighting current advances, challenges and future directions in aquatic animal welfare research and implementation. Full article

Objective: The objective of this study was to compare the performance and robustness of a deep learning reconstruction method against established alternatives for soft tissue CT image reconstruction. Materials and Methods: Images were generated from portal venous phase chest–abdomen–pelvis CT scans (n = 99) acquired on a dual-layer spectral detector CT using filtered back projection, iterative model reconstruction (IMR), and deep learning reconstruction (DLR) with three parameter settings, namely ‘standard’, ‘sharper’, and ‘smoother’. Experienced raters performed a quantitative assessment by considering attenuation stability and image noise levels in ten representative structures across all reconstruction methods, as well as a qualitative assessment using a four-point Likert scale (1 = poor, 2 = fair, 3 = good, 4 = excellent) for their overall perception of ‘smoother’ DLR and IMR images. One scan was excluded due to cachexia, which limited the quantitative measurements. Results: The inter-rater reliability for quantitative measurements ranged from moderate to excellent (r = 0.63–0.96). Attenuation values did not differ significantly between reconstruction methods except for DLR against IMR in the psoas muscle (mean + 3.0 HU, p < 0.001). Image noise levels differed significantly between reconstruction methods for all structures (all p < 0.001) and were lower than FBP with any DLR parameter setting. Image noise levels with ‘smoother’ DLR were predominantly lower than or equal to IMR, while they were higher with ‘standard’ DLR and ‘sharper’ DLR. The ‘smoother’ DLR images received a higher mean rating for overall image quality than the IMR images (3.7 vs. 2.3, p < 0.001). Conclusions: ‘Smoother’ DLR images were perceived by experienced readers as having improved quality compared to FBP and IMR while also exhibiting objectively lower or equivalent noise levels. Full article

Enhancer–promoter interactions (EPIs) play a key role in epigenetic regulation of gene expression, dominating cellular identity and functional diversity. Dissecting these interactions is crucial for understanding transcriptional regulatory networks and their significance in cell differentiation, development, and disease. Here, we propose a novel deep learning framework, EPIFBMC (Enhancer-Promoter Interaction prediction with FBMC network) that leverages DNA sequence and genomic features for accurate EPI prediction. The FBMC network consists of three key modules: the Four-Encoding module first encodes the DNA sequence in multiple dimensions to extract key sequence information; then the BESL (Balanced Ensemble Subset Learning) adopts an integrated subset learning strategy to optimize the feature-learning process of positive and negative samples; finally, the MCANet module completes the training of EPI prediction based on a Multi-channel Network. We evaluated EPIFBMC on three cell line datasets (HeLa, IMR90, and NHEK), and validated its generalizability across three independent datasets (K562, GM12878, HUVEC) through cross-cell-line experiments, comparing favorably with state-of-the-art methods. Notably, EPIFBMC balances genomic feature richness and computational complexity, significantly accelerating training speed. Ablation studies identified two key DNA sequence features—positional conservation and positional specificity score—which showed critical predictive value across a benchmark dataset of six diverse cell lines. The computational testing show that EPIFBMC shows excellent performance in the EPI prediction task, providing a powerful tool for decoding gene regulatory networks. It is believed that it will have important application prospects in developmental biology, disease mechanism research, and therapeutic target discovery. Full article

Background: The increasing popularity of fruit juices as part of perceived healthy dietary choices has raised concerns regarding their erosive effects on dental enamel. While prior in vitro studies have largely relied on commercial fruit drinks and non-human enamel samples, this study adopts a more ecologically valid approach by using fresh local fruit juices and extracted human teeth to evaluate enamel erosion. Objectives: This study aimed to assess the consumption patterns, oral hygiene behaviours, and awareness of the erosive potential of fruit juices among Malaysian adults and to evaluate the erosive effects of freshly squeezed local fruit juices on human dental enamel under simulated oral conditions. Methods: A questionnaire-based cross-sectional survey (n = 189) was conducted among dental clinic attendees to assess fruit juice intake habits, oral health practices, and awareness levels. In parallel, an in vitro study was performed using 40 extracted premolar teeth immersed in lime juice, pineapple juice, citric acid (positive control), or distilled water (negative control) over a 10-day period. Enamel volume loss, surface roughness, and microhardness were analysed pre- and post-immersion. Results: Fruit juice consumption was highly prevalent, with lime (57.7%) being the most commonly consumed, followed by watermelon (53.0%), star fruit (15.9%), and pineapple (15.4%). The majority of respondents preferred sweetened juices (75.7%) and demonstrated only moderate oral hygiene, with just 53.4% reporting brushing their teeth twice daily. Awareness of the dental effects of acidic beverages was limited. In vitro results confirmed that both lime and pineapple juices significantly reduced enamel microhardness and increased surface roughness (p < 0.0001), with lime juice causing the greatest enamel volume loss due to its higher acidity. Conclusions: These findings highlight the need for public health strategies that raise awareness on the implications of dietary acids and promote protective oral health behaviours. Dental practitioners should incorporate dietary counselling in routine care, particularly for populations at higher risk. Full article

Inspection, maintenance, and repair (IMR) operations on underwater infrastructure remain costly and time-intensive because fully teleoperated remote operated vehicle s(ROVs) lack the range and dexterity necessary for precise cooperative underwater manipulation, and the alternative of using professional divers is ruled out due to the risk involved. This work presents and experimentally validates an autonomous, dual-I-AUV (Intervention–Autonomous Underwater Vehicle) system capable of assembling rigid pipeline segments through coordinated actions in a confined underwater workspace. The first I-AUV is a Girona 500 (4-DoF vehicle motion, pitch and roll stable) fitted with multiple payload cameras and a 6-DoF Reach Bravo 7 arm, giving the vehicle 10 total DoF. The second I-AUV is a BlueROV2 Heavy equipped with a Reach Alpha 5 arm, likewise yielding 10 DoF. The workflow comprises (i) detection and grasping of a coupler pipe section, (ii) synchronized teleoperation to an assembly start pose, and (iii) assembly using a kinematic controller that exploits the Girona 500’s full 10 DoF, while the BlueROV2 holds position and orientation to stabilize the workspace. Validation took place in a 12 m × 8 m × 5 m water tank. Results show that the paired I-AUVs can autonomously perform precision pipeline assembly in real water conditions, representing a significant step toward fully automated subsea construction and maintenance. Full article

Carbon nanotubes (CNTs) have attracted intense research interest owing to their unique one-dimensional structure and exceptional properties. However, when individual CNTs are assembled to macrostructures such as films and fibers, their electrical performance often deteriorates significantly. This review offers a comprehensive look at the recent progress in the electrical properties and measurement techniques of CNTs, ranging from individual nanotubes to their assemblies. Firstly, we explore the methods for measuring the electrical properties of individual CNTs, including scanning tunnelling microscopy, electron microscope-based nanoprobes, and measurements using nanodevices. Secondly, we examine how structural characteristics of CNTs (e.g., chirality, diameter, and defects) influence their electrical behaviors. A critical comparison between individual CNTs and their assemblies reveals the difficulties in transferring the electrical properties from nanoscale to bulk materials. Finally, we put forward strategies to boost the electrical conductivity of CNT assemblies and also sketch out future research and development directions. Full article

Coronary microvascular obstruction and dysfunction (CMVO) frequently arise following primary percutaneous coronary intervention (PCI), particularly in individuals with myocardial infarction. Despite the restoration of epicardial blood flow, microvascular perfusion might still be compromised, resulting in negative clinical outcomes. CMVO is a complex condition resulting from a combination of ischemia, distal thrombotic embolization, reperfusion injury, and individual susceptibilities such as inflammation and endothelial dysfunction. The pathophysiological features of this condition include microvascular spasm, endothelial swelling, capillary plugging by leukocytes and platelets, and oxidative stress. Traditional angiographic assessments, such as Thrombolysis in Myocardial Infarction (TIMI) flow grade and myocardial blush grade, have limited sensitivity. Cardiac magnetic resonance imaging (CMR) stands as the gold standard for identifying CMVO, while the index of microvascular resistance (IMR) is a promising invasive option. Treatment approaches involve powerful antiplatelet drugs, anticoagulants, and supersaturated oxygen, yet no treatment has been definitively shown to reverse established CMVO. CMVO remains a significant therapeutic challenge in coronary artery disease management. Enhancing the comprehension of its core mechanisms is vital for the development of more effective and personalized treatment strategies. Full article

Background: Coronary heart disease (CHD) remains the most prevalent pathology within the circulatory system. Among its chronic complications, ischemic mitral valve regurgitation (IMR) is observed in approximately 15% of patients with sustained myocardial ischemia. The presence of this complex valvular defect significantly increases both overall mortality and the incidence of adverse cardiovascular events. Notably, the presence of moderate to severe mitral regurgitation in patients undergoing surgical revascularization has been shown to double the risk of death. Despite the well-established etiology of IMR, data regarding the efficacy of surgical interventions and the determinants of postoperative outcomes remain inconclusive. Methods: The objective of the present study was to evaluate both early and long-term outcomes of surgical treatment of mitral regurgitation in patients undergoing coronary artery bypass grafting (CABG) due to ischemic heart disease. Particular attention was given to the influence of the severity of regurgitation, left ventricular ejection fraction (LVEF), and the dimensions of the left atrium (LA) and left ventricle (LV) on the postoperative prognosis. An additional aim was to identify preoperative risk factors associated with increased postoperative mortality and morbidity. A retrospective analysis was conducted on 421 patients diagnosed with ischemic mitral regurgitation who underwent concomitant mitral valve surgery and CABG. Exclusion criteria included emergent and urgent procedures as well as non-ischemic etiologies of mitral valve dysfunction. Results: The study cohort comprised 34.9% women and 65.1% men, with the mean age of 65.7 years (±7.57). A substantial proportion (76.7%) of patients were aged over 60 years. More than half (51.5%) presented with severe heart failure symptoms, classified as NYHA class III or IV, while over 70% were categorized as CCS class II or III. Among the surgical procedures performed, 344 patients underwent mitral valve repair, and 77 patients required mitral valve replacement. Additionally, 119 individuals underwent concomitant tricuspid valve repair. Short-term survival was significantly affected by the presence of hypertension, prior cerebrovascular events, and chronic kidney disease. In contrast, hypertension and chronic obstructive pulmonary disease were identified as significant predictors of adverse late-term outcomes. Conclusions: Interestingly, neither the preoperative severity of mitral regurgitation nor the echocardiographic measurements of LA and LV dimensions were found to significantly influence surgical outcomes. The perioperative risk, as assessed by the EuroSCORE II (average score: 10.0%), corresponded closely with observed mortality rates following mitral valve repair (9.9%) and replacement (10.4%). Notably, the need for concomitant tricuspid valve surgery was associated with an elevated mortality rate (12.4%). Furthermore, the preoperative echocardiographic evaluation of LA regurgitation severity, as well as LA and LV dimensions, did not exhibit a statistically significant impact on either early or long-term surgical outcomes. However, a reduced LVEF was correlated with increased long-term mortality. The presence of advanced clinical symptoms and the necessity for tricuspid valve repair were independently associated with a poorer late-term prognosis. Importantly, the annual mortality rate observed in the late-term follow-up of patients who underwent surgical treatment of ischemic mitral regurgitation was lower than rates reported in the literature for patients managed conservatively. The EuroSCORE II scale proved to be a reliable and precise tool in predicting surgical risk and outcomes in this patient population. Full article

The risk of non-human primate (NHP) malaria transmission to humans is increasing, with Plasmodium knowlesi and Plasmodium cynomolgi emerging as significant zoonotic threats, particularly in Malaysia. While P. knowlesi is well-documented, P. cynomolgi infections in humans remain underreported, largely due to diagnostic challenges. Routine microscopy and standard molecular diagnostic tools often misdiagnose P. cynomolgi infections as P. vivax due to morphological similarities and genetic homology. We report a new case of a human P. cynomolgi infection misdiagnosed as Plasmodium vivax in a 32-year-old male with no prior malaria history or travel to endemic countries. The initial diagnoses made by the microscopy and qPCR conducted by the Kota Bharu Public Health Laboratory in Kelantan identified the infection as P. vivax. However, cross-examination by the Institute for Medical Research (IMR) revealed the presence of mixed-species infection, prompting further analysis. The real-time PCR and sequencing performed at MAPELAB, Spain, confirmed the co-infection of P. vivax and P. cynomolgi. This case highlights the diagnostic limitations in detecting P. cynomolgi, which shares high genetic similarity with P. vivax, leading to potential cross-reactivity and diagnostic inaccuracies. As P. cynomolgi emerges as the second zoonotic malaria species after P. knowlesi capable of infecting humans in Southeast Asia, improved diagnostic methods are urgently needed. Enhanced molecular diagnostics and comprehensive epidemiological studies are essential to elucidate transmission dynamics, assess public health implications, and inform effective malaria control strategies. Full article

Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are challenging multidrug-resistant pathogens. This study evaluated the in vitro susceptibility of CRE and CRPA blood isolates from Korea to novel β-lactam/β-lactamase inhibitor combinations: ceftolozane/tazobactam (C/T), ceftazidime/avibactam (CZA), imipenem/cilastatin/relebactam (IMR), and meropenem/vaborbactam (MEV). Methods: Blood isolates of CRE (n = 55) and CRPA (n = 65) collected between September 2017 and September 2022 in a Korean tertiary hospital were included. Carbapenemase production was determined using phenotypic and molecular methods. In vitro susceptibility to C/T, CZA, IMR, and MEV was determined primarily by broth microdilution using current CLSI/EUCAST breakpoints. Clinical characteristics and in-hospital mortality were retrospectively reviewed. Results: Among non-carbapenemase-producing (non-CP) CRPA isolates (n = 47), susceptibility rates were 83.0% to C/T and 70.2% to CZA. For KPC-producing CRE isolates (n = 28), susceptibility rates were high to CZA (92.9%), IMR (82.1%), and MEV (96.4%). However, non-CP CRE isolates (n = 22) showed low susceptibility to C/T (18.2%) but high susceptibility to CZA (100%), IMR (81.8%), and MEV (95.5%). CRE infections were associated with higher rates of hematologic malignancy, immunosuppression, and in-hospital mortality (63.6% vs. 18.5% for CRPA, p < 0.001). Conclusions: The susceptibility of CRE and CRPA to novel β-lactam/β-lactamase inhibitors varies significantly by species and carbapenemase production. CZA, IMR, and MEV showed promising activity against KPC-producing CRE. These findings can inform empirical therapy and stewardship efforts in Korea. Full article

Background: Synchronous computation of coronary angiography-derived fractional flow reserve (CAG-FFR) and coronary angiography-derived index of microcirculatory resistance (CAG-IMR) is a novel coronary angiography-based method for on-site assessment of suspected myocardial ischemia in patients with coronary artery disease (CAD). Methods: This trial is a prospective, multicenter, controlled study designed to assess the diagnostic performance of CAG-FFR and CAG-IMR in patients with suspected myocardial ischemia using wire-based FFR and IMR as reference standards. The functional parameters were calculated using a reduced order computational fluid dynamics solver that incorporates thrombolysis in myocardial infarction (TIMI) frame count and aortic pressure recorded by a disposable invasive pressure sensor. Results: CAG-FFR was computed in 325 patients, demonstrating a patient-level diagnostic accuracy of 95.4%, sensitivity of 95.9%, and specificity of 95.1%. The area under the receiver operating characteristic curve (AUC) of CAG-FFR was 0.977. Patient-specific aortic pressure adoption significantly improved the accuracy of CAG-FFR in the “gray zone” compared to fixed-pressure models. In addition, CAG-IMR was successfully computed in 180 patients, showing a patient-level diagnostic accuracy of 95.5%, sensitivity of 96.4%, and specificity of 95.2%. The AUC of CAG-IMR in diagnosing abnormal coronary microcirculatory dysfunction was 0.973. Conclusions: Synchronous computation of CAG-FFR and CAG-IMR demonstrated higher feasibility and excellent diagnostic accuracy compared to wire-based FFR and IMR, highlighting its clinical potential for CAD evaluation. Full article

Objectives: Beta-emitting radionuclide therapy, exemplified by ¹⁷⁷Lu-Oxodotreotide (Lutathera^®), enables targeted treatment of neuroendocrine tumors by delivering β-radiation to tumor cells. However, the dose-dependent molecular mechanisms underlying cellular damage remain insufficiently characterized. This study aimed to investigate the phenotypic changes in IMR-32 human neuroblastoma cells following Lutathera exposure, with a focus on the dose-dependent relationship between radiation and cellular damage. Methods: IMR-32 cells were allocated to control, low- (0.05 MBq/mL), medium- (0.5 MBq/mL), and high-dose (5 MBq/mL) groups and treated with ¹⁷⁷Lu-Oxodotreotide for 24 h. Flow cytometry was employed to assess cell viability, apoptosis, mitochondrial membrane potential, γ-H2AX expression (a marker of DNA damage), and proliferation. Results: Lutathera induced dose-dependent cytotoxic effects. Cell viability declined linearly with increasing dose (control: 100% vs. high-dose: 13.48%; r = −0.955, p < 0.001). Apoptosis was significantly elevated (control: 35.34% vs. high-dose: 88.12%; r = 0.999), accompanied by increased γ-H2AX levels (control: 5.26 × 10⁴ vs. high-dose: 13.13 × 10⁴; r = 0.930), indicating DNA double-strand breaks. Mitochondrial membrane potential decreased (control: 6.06 × 10⁴ vs. high-dose: 46.27 × 10⁴; r = 0.999), and proliferation was suppressed (control: 91.10 × 10⁴ vs. high-dose: 103.84 × 10⁴; r = 0.954), both showing strong dose correlations (p < 0.001). Conclusions: ¹⁷⁷Lu-Oxodotreotide exerts dose-dependent cytotoxicity in IMR-32 cells via DNA damage, mitochondrial dysfunction, and apoptosis induction. These findings underscore the necessity of optimizing dosing regimens to balance therapeutic efficacy and safety in clinical settings, providing a foundation for personalized β-emitter therapies. Full article

Robust visual perception and geometric alignment are crucial for intelligent automation in various domains, such as industrial processes and infrastructure monitoring. Accurately aligning structured visual elements, such as floor markings or road-marking templates, is essential for tasks like automated guidance, verification, and condition assessment. However, traditional feature-based methods struggle with templates that feature simple geometries and lack rich textures, making reliable feature matching and alignment difficult, even under controlled conditions. To address this, we propose GeoTemplateKPNet, a novel self-supervised deep-learning framework, built upon Convolutional Neural Networks (CNNs), designed to learn robust, geometrically consistent keypoints specifically in synthetic template images. The model is trained exclusively in a synthetic template dataset by enforcing equivariance to geometric transformations and utilizing self-supervised losses, including inside mask loss, peakiness loss, repulsion loss, and keypoint-driven image reprojection loss, thereby eliminating the need for manual keypoint annotations. We evaluate the method in a synthetic template test set, using metrics such as a keypoint-matching comparison, the Inside Mask Rate (IMR), and the Alignment Reconstruction Error (ARE). The results demonstrate that GeoTemplateKPNet successfully learns to predict meaningful keypoints on template structures, enabling accurate alignment between templates and their transformed counterparts. Ablation studies reveal that the number of keypoints (K) impacts the performance, with K = 3 providing the most suitable balance for the overall alignment accuracy, although the performance varies across different template geometries. GeoTemplateKPNet offers a foundational self-supervised solution for the robust geometric analysis of templates, which is crucial for downstream alignment tasks and applications. Full article

The accumulation of senescent cells is a major contributor to aging and various age-related diseases, making developing senolytic compounds that are capable of clearing these cells an important area of research. However, progress has been hampered by the limited number of known senolytics and the incomplete understanding of their mechanisms. This study presents a powerful senolytic predictor built using phenotypic data and machine learning techniques to identify compounds with potential senolytic activity. A comprehensive training dataset consisting of 111 positive and 3951 negative compounds was curated from the literature. The dataset was used to train machine learning models, incorporating traditional molecular fingerprints, molecular descriptors, and MoLFormer molecular embeddings. By applying MoLFormer-based oversampling and testing different algorithms, it was found that the Support Vector Machine (SVM) and Multilayer Perceptron (MLP) models with MoLFormer embeddings exhibited the best performance, achieving Area Under the Curve (AUC) scores of 0.998 and 0.997, and F1 scores of 0.948 and 0.941, respectively. This senolytic predictor was then used to perform virtual screening of compounds from the DrugBank and TCMbank databases. In the DrugBank database, 98 structurally novel candidate compounds with potential senolytic activity were identified. For TCMbank, 714 potential senolytic compounds were predicted and 81 medicinal herbs with possible senolytic properties were identified. Moreover, pathway enrichment analysis revealed key targets and potential mechanisms underlying senolytic activity. In an experimental screening of predicted compounds, panaxatriol was found to exhibit senolytic activity on the etoposide-induced senescence of the IMR-90 cell line. Additionally, voclosporin was found to extend the lifespan of C. elegans more effectively than metformin, demonstrating the value of our model for drug repurposing. This study not only provides an efficient framework for discovering novel senolytic agents, but also highlights the predicted novel senolytic compounds and herbs as valuable starting points for future research into senolytic drug development. Full article