Search Results (20,169)

Insulin resistance (IR) is a central driver of cardiometabolic disease and an increasingly recognized modifier of inflammatory and vascular pathology. Beyond impaired glucose homeostasis, IR emerges from chronic, metabolically induced inflammation (“meta-inflammation”) and convergent cellular stress programs that propagate across tissues and organ systems, ultimately shaping endothelial dysfunction, atherogenesis, and cardiometabolic complications. Here, we synthesize multilevel links between insulin receptor signaling, intracellular stress modules (oxidative, endoplasmic reticulum, inflammatory, and fibrotic pathways), tissue-level dysfunction, and systemic inflammatory amplification. This work is a conceptual narrative review informed by targeted database searches and citation tracking, with explicit separation of mechanistic/experimental evidence from human observational and interventional data; causal inferences are framed primarily on mechanistic and interventional findings, whereas associative statements are reserved for observational evidence. We propose an integrative framework in which stress-response pathways are context-dependent and become maladaptive when chronically activated under nutrient excess and persistent inflammatory cues, generating self-reinforcing loops between IR and inflammation that accelerate vascular injury. This framework highlights points of convergence that can guide mechanistic prioritization and translational hypothesis testing. Full article

Immersive technologies such as Desktop Virtual Reality (DVR), Immersive Rooms (IR), and fully immersive Virtual Reality (VR) are transforming K-12 education by enabling experiential, multisensory, and participatory learning. Yet their pedagogical impact depends not only on hardware fidelity but on the interplay between technological affordances, instructional design, and learner characteristics. Guided by the Cognitive Affective Model of Immersive Learning (CAMIL), this mixed-methods study examined how these factors jointly shape affordances, challenges, students perceived learning, and self-assessment in authentic classroom contexts. Data were collected from 31 teachers and 252 students across 21 schools using teacher interviews, classroom observations, and student questionnaires. Findings revealed that agency and presence emerged as central affordances but also as potential challenges, depending on lesson design and cognitive load. DVR consistently supported higher perceived learning and stronger links between engagement and self-assessment, while IR showed the weakest outcomes and VR displayed trade-offs between immersion and control. The study proposes a revised CAMIL framework that integrates social co-presence, learner characteristics, and perceived learning as essential components for understanding immersive learning in schools. These results highlight that effective immersion arises from pedagogical orchestration, not technological intensity alone. Full article

B7-H3 (CD276), a member of the B7 family of proteins, is known to play a key role in the progression of a number of cancers. This protein is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. Various investigations, including a number of clinical trials, have reported high levels of expression of this protein in cancerous tissues compared to their healthy counterparts. This difference in expression attracted various research efforts to establish whether such a difference can be linked to the therapeutic potential of this molecule. It is worth noting that B7-H3 is not the only immune checkpoint expressed at different levels in cancerous and healthy cells. Therapeutic strategies, based on different levels of expression, have been tested with other checkpoints. To inhibit the expression of some checkpoints, immune checkpoint inhibitors (ICIs) were developed. The introduction of these inhibitors for the treatment of some forms of advanced-stage tumors has been justly described as an important milestone in the landscape of immune therapy. Years after the launch of these inhibitors, numerous clinical trials revealed that these inhibitors benefit a narrow subset of patients suffering from advanced-stage tumors, while the majority of patients treated with these inhibitors either did not respond positively or simply did not respond at all (refractory patients). Other clinical trials showed that this form of treatment can provoke serious immune-related adverse events (irAEs). It is fair to state that changes in the expression level of a given protein in diseased tissue is an important parameter to take into account in the assessment of such a protein as a therapeutic target. However, the last ten years have demonstrated that taking the level of expression of a given checkpoint within a cancerous tissue is not sufficient to consider such expression a reliable predictive biomarker for the investigated disease. On the other hand, to establish a solid base for a given therapeutic strategy, these varying levels of expression have to be combined with a deep understanding of the biology of the molecule under investigation, as well as the identification and thorough analysis of the relevant signaling pathways, particularly those communicating with both the investigated molecule and the immune system. Recently, a number of pharmaceutical and biotechnology firms have suggested that B7-H3 is a highly promising therapeutic target for the development of immune therapeutics. In this review, we ask why hopes of better therapeutic performance are attached to this immune checkpoint. A partial answer to this question is provided through the careful consideration of the available data generated by various clinical trials. The contribution of mass spectrometry-based proteomics to this area of research is highlighted. Full article

Unmanned Aerial Vehicle (UAV) platforms enable flexible and cost-effective vehicle detection for intelligent transportation systems, yet small-scale vehicles in complex aerial scenes pose substantial challenges from extreme scale variations, environmental interference, and single-sensor limitations. We present AMSRDet (Adaptive Multi-Scale Remote Sensing Detector), an adaptive multi-scale detection network fusing infrared (IR) and visible (RGB) modalities for robust UAV-based vehicle detection. Our framework comprises four novel components: (1) a MobileMamba-based dual-stream encoder extracting complementary features via Selective State-Space 2D (SS2D) blocks with linear complexity $O\left(HWC\right)$, achieving 2.1× efficiency improvement over standard Transformers; (2) a Cross-Modal Global Fusion (CMGF) module capturing global dependencies through spatial-channel attention while suppressing modality-specific noise via adaptive gating; (3) a Scale-Coordinate Attention Fusion (SCAF) module integrating multi-scale features via coordinate attention and learned scale-aware weighting, improving small object detection by 2.5 percentage points; and (4) a Separable Dynamic Decoder generating scale-adaptive predictions through content-aware dynamic convolution, reducing computational cost by 48.9% compared to standard DETR decoders. On the DroneVehicle dataset, AMSRDet achieves 45.8% mAP@0.5:0.95 (81.2% mAP@0.5) at 68.3 Frames Per Second (FPS) with 28.6 million (M) parameters and 47.2 Giga Floating Point Operations (GFLOPs), outperforming twenty state-of-the-art detectors including YOLOv12 (+0.7% mAP), DEIM (+0.8% mAP), and Mamba-YOLO (+1.5% mAP). Cross-dataset evaluation on Camera-vehicle yields 52.3% mAP without fine-tuning, demonstrating strong generalization across viewpoints and scenarios. Full article

In response to ionizing radiation (IR), both adult and cancer stem cells enter reversible cell cycle arrest at the G1/S transition to evade apoptosis and subsequently re-enter the cell cycle to regenerate damaged tissue. Entry into and exit from this arrest, known as “quiescence,” is governed by the inhibition of mTORC1. The pharmacological suppression of mTORC1 with rapamycin prevents quiescent stem cells from re-entering the cell cycle and impairs tissue regeneration. Rapamycin holds great therapeutic promise in preventing tumor regrowth from dormant cancer stem cells. Yet the extent to which genetic background impacts the known variation in the pharmacological response of rapamycin remains unknown. Here, we show that natural genetic variation across the Drosophila Genetics Reference Panel (DGRP) drives substantial differences in the rapamycin-mediated suppression of post-IR quiescence and regeneration. To define the basis of this differential sensitivity, we examined mitochondrial turnover and DNA damage repair—processes controlling IR-induced dormancy. Our analyses reveal that variation in rapamycin sensitivity is more strongly associated with differences in mitochondrial dynamics than with DNA damage response following radiation. Together, these findings demonstrate that genetic background is a critical determinant of rapamycin efficacy and identify mitochondrial regulation as a key mechanism underlying differential therapeutic response. Full article

Aniline (ANI) was electropolymerized on ITO substrates with different surface resistivities. The process was performed by cyclic voltammetry from an aqueous, homogeneous solution containing sulfuric acid and the aniline monomer using various numbers of cycles and scan rates. The resulting polymer films (PANI) were characterized by ATR-IR spectroscopy, spectroscopic ellipsometry and atomic force microscopy. The influence of ITO surface resistivity on the electropolymerization process, the quality of the obtained PANI layers, and their optical properties was evaluated. Homogeneous PANI films were produced on ITO substrates with surface resistivities of 15–25 Ω/sq, encompassing both emeraldine salt and emeraldine base forms. Although the film’s growth was rapid, it also led to adhesion issues. In contrast, for ITO substrates with surface resistivities of 70–100 Ω/sq and 80–100 Ω/sq, the resulting films showed improved adhesion but were less homogeneous. Nevertheless, the conductive emeraldine salt form of polyaniline was successfully obtained. The conductive form of polyaniline was obtained without any additional modifications to the electropolymerization procedure. Notably, the literature provides no systematic analysis of electropolymerization on ITO substrates with different surface resistivities, which opens up new research opportunities and provides a basis for the rational design and optimization of PANI-based electro-optical coatings for advanced sensing applications. Full article

The triad association among type 2 diabetes mellitus (T2DM), metabolic associated fatty liver disease (MAFLD), and incretin secretion dysfunction, including GLP-1 (glucagon-like peptide-1) secretion dysfunction, maintains a critical cardiovascular risk and liver-related mortality. The aim of this study is to establish interactions between the GLP-1 plasma levels and metabolic syndrome clusters and adipokines profile (leptin, adiponectin, resistin) and proinflammatory cytokines (TNFα, IL-6, IL1β, IL-17) in diabetic subjects with or without MAFLD. The data revealed that insulin resistance (HOMA-IR) is present in all groups. MAFLD is more common in men than in women. The average FLI score in group IV was ≥70, confirming the diagnosis of MAFLD. The disorder of GLP-1 secretion is more pronounced in women than in men. HOMA-IR is negatively associated with plasma GLP-1 depletion in the MAFLD, T2DM, and MAFLD + T2DM groups. Adiponectin levels are decreased in all groups, as for GLP-1. In contrast, leptin, resistin, TNFα, IL-6, IL-1β, and IL-17 levels show an inverse correlation with GLP-1. GLP-1 accurately reflects metabolic and inflammatory status in subjects with MAFLD, T2DM, and diabetes—steatosis. The applied multivariate linear regression model confirms a highly significant association between MAFLD and GLP-1. It appears that plasma GLP-1 can be considered as biomarker in MAFLD and T2DM related to sex-gender disparities. Longitudinal studies are required to confirm these data. Full article

Insulin is an anabolic hormone involved in the regulation of several processes, such as the storage of glucose into glycogen, decrease of glucose output, stimulation of glucose transport into cells, etc. The hormone binds to its receptor, thereby activating an intracellular signaling cascade. Once activated, the insulin receptor (INSR) phosphorylates multiple intracellular substrates, which initiate the downstream signaling pathway. The nature of insulin signaling pathways may vary depending on the organ or tissue. In the central nervous system (CNS), INSRs are expressed in all cell types. This observation may suggest that insulin signaling is involved in important and diverse processes. It regulates glucose metabolism, supports cognitive functions, enhances the outgrowth of neurons, as well as plays a role in the modulation of release and uptake of catecholamine, among other roles. Importantly, insulin can freely cross the blood–brain barrier (BBB) from the circulation and is also synthesized locally within the brain. Insulin resistance (IR) impairs insulin signaling, which may accelerate brain aging, affect plasticity, and potentially contribute to neurodegeneration. Dysregulation of insulin signaling has been implicated in several diseases, including diabetes mellitus, metabolic syndrome, certain cancers, and neurodegenerative diseases, such as Alzheimer’s disease. There are two principal insulin signaling pathways: the PI3K/AKT pathway, primarily associated with metabolic effects, and the MAPK pathway, which is involved in cell growth, survival, and gene expression. Our review describes the role of insulin in the human brain, as well as the disturbances in insulin signaling resulting from brain insulin resistance, with a particular focus on its association with Alzheimer’s disease. Full article

The environmental threat posed by small, single-use sachets sourced from 48% annual waste from excessive packaging has been assessed by investigating the development of nano-incorporated bioplastic films from the high-yield plant, maguey (Agave cantala). Maguey cellulose was acetylated (using 10 and 15 mL of acetic anhydride for 16, 24, and 32 h), successfully yielding a high of 81.34% maguey cellulose acetate (MCA). MCA was confirmed to contain acetate groups (C=O, C-H, C-O) via FT-IR and exhibited a hydrophobicity of a 121.897° contact angle. Bioplastic films were fabricated using MCA solution combined with 15% (w/w) commercial cellulose acetate (CCA)/MCA and reinforced with nanoclay (NC) at 0.5%, 1%, and 3% (w/w) concentrations. Nanomaterial incorporation generally improved properties; however, mechanical strength declined with increasing NC concentration, recording tensile strengths of 2.01 MPa, 0.89 MPa, and 0.78 MPa for the 0.5%, 1%, and 3% NC films, respectively. Conversely, the 3% NC film showed the best barrier property, with a water vapor transmission rate (WVTR) of 31.14 g/m² h. Surface morphology confirmed NC integration (nanomaterial sizes 29.74 nm to 107.3 nm), and the 0.5% NC film displayed the smooth structure ideal for sustainable packaging. The slight increase in contact angle observed between the 0% NC (60.768°) and 0.5 NC (62.904°) films suggested limitations in NC dispersion. Overall, the findings demonstrate the potential of using regenerated maguey cellulose acetate to create nano-bioplastic films with tailored mechanical and barrier properties for sustainable packaging, though optimization of NC loading and dispersion is necessary to maximize strength. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and is characterized by excessive lipid accumulation in hepatocytes. Endoplasmic reticulum (ER) stress and inflammation play important roles in hepatic lipid accumulation. Although CILP2 has been implicated in lipid metabolism, its role in MASLD remains unclear. Hepatic steatosis was induced in mice by a high-fat diet in this study. CILP2 was overexpressed in mouse livers and in vitro hepatocytes using the Ad-CILP2 adenovirus. CILP2 KO mice were also used in the experiments. Liver tissues and hepatocytes were collected for further analysis. CILP2 expression was upregulated in steatotic liver tissue and hepatocytes. CILP2 overexpression upregulated genes related to fatty acid synthesis (Srebp-1c, Fasn, Acc, Scd1, and Cd36), promoted lipid accumulation, and elevated the expression of proinflammatory cytokines (Il6, Tnf, and Il1b). Conversely, CILP2 knockout reduced high-fat diet-induced hepatic steatosis and improved glucose metabolism. Mechanistically, CILP2 activated the IRE1α/XBP1 branch of the ER stress pathway, thereby promoting lipid synthesis and inflammation, effects that were partially alleviated by 4-PBA and STF-083010 treatments. Our findings indicate that CILP2 contributes to hepatic lipid accumulation and inflammation via the IRE1α/XBP1 pathway and may represent a potential therapeutic target for MASLD intervention. Full article

Electrocatalytic hydrogenation (ECH) represents an environmentally friendly pathway for converting 5-hydroxymethylfurfural (HMF) into the high-value chemical 2,5-bis(hydroxymethyl)furan (BHMF). However, its selectivity and Faradaic efficiency are often constrained by competitive hydrogen evolution at the cathode and insufficient supply of active hydrogen at the surface. To address this challenge, this study developed an Ir-decorated copper oxide nanowire catalyst (denoted as CuIr) featuring a hydrogen-rich adsorption (H_ads) surface. The incorporation of Ir significantly enhances the catalyst’s water dissociation capacity, creating abundant H_ads sources that selectively accelerate HMF hydrogenation while suppressing side reactions. Under a mild applied potential of −0.45 V vs. RHE and a current density of approximately −20 mA cm⁻², the optimal CuIr₄₀ catalyst achieved near-complete conversion of HMF (99%), a BHMF yield of 99%, and a high Faradaic efficiency of 97% within 120 min of electrolysis. Mechanistic studies reveal that this catalytic leap stems from the synergistic functional interaction between Cu and Ir sites in substrate activation and hydrogen supply. This work presents a novel strategy for designing efficient electrocatalysts for biomass hydrogenation by regulating surface H_ads concentration. Full article

Background: Thymic epithelial tumors (TETs), including thymic carcinomas and thymomas, are rare malignancies originating in the mediastinum. Therapeutic options remain limited for patients experiencing disease progression following platinum-based chemotherapy. High tumor mutational burden (TMB) is uncommon in thymic malignancies but may predict response to immunotherapy. We report a patient with TMB-high TET who participated in the KOSMOS-II study in South Korea and achieved a durable response to atezolizumab without developing immune-related adverse events (irAEs). Case presentation: A 73-year-old woman who had been treated for thymoma 20 years ago presented with a left neck mass. A biopsy of the neck mass confirmed recurrent thymoma, type B3, and her disease progressed despite platinum-based chemotherapy and subsequent pemetrexed treatment. TMB-high thymoma is very rare, but based on the next-generation sequencing (NGS) results, she was diagnosed with TMB-high (20.3 mutations/Mb) thymoma. As TMB-based immunotherapy is not approved in Korea, she was enrolled in the KOSMOS-II study and initiated on atezolizumab following molecular tumor board review. She achieved stable disease after three cycles and has remained progression-free for 14 months, completing 20 cycles without significant irAEs. Notably, her underlying myasthenia gravis did not worsen during treatment. Conclusions: This case demonstrates a favorable outcome with biomarker-directed ICI treatment in recurrent thymoma with limited treatment options, highlighting the importance of appropriate molecular markers to predict drug response. Although TMB-based immunotherapy is FDA-approved in the U.S., it remains unavailable in Korea, underscoring the need to explore flexible access pathways, including the potential use of immunotherapy beyond current indications, to improve treatment options for patients with life-threatening conditions. Full article

Background/Objectives: Insulin-Resistant Normal Weight and Insulin-Sensitive Obesity are atypical cardiometabolic phenotypes whose clinico-biological features, management, and prognosis are a subject of extensive scientific debate. The current study aimed to assess the prevalence of metabolic phenotypes of obesity and to evaluate their association with markers related to diabesity, adipokines profile, and two single nucleotide polymorphisms of CNR1 gene. Methods: We performed a cross-sectional analysis in a random sample of 487 individuals (53.03 ± 13.71 years, 48.3% male) which were classified based on body mass index (</≥25 kg/m²) and insulin resistance (HOMA-IR cut-off value 2.5) as Insulin-Sensitive/Insulin-Resistant Normal Weight (ISNW/IRNW) and Insulin-Sensitive/Insulin-Resistant Obesity (ISO/IRO). Results: The ISO phenotype frequency was 24.2%, with a higher prevalence in the 40–60 years age group (47.0%) and in men (44.9%), while the prevalence of IRNW was 7.0%, predominating in women (61.8%). Participants with IRNW had a more altered glycoregulation profile (fasting and 2 h OGTT blood glucose, prediabetes, and hyperinsulinism), hypercholesterolemia, and adiposity indices (ABSI) than those with ISNW, but comparable to those with IRO. Participants with ISO had a more favorable glycoregulation profile, lipid profile, adipocytokines, and adiposity indices than those with IRO. IRNW had higher odds of being associated with prediabetes (OR 10.75; p < 0.001) than ISNW, while younger age, CUN-BAE, and ABSI were independently associated with both ISO and IRNW phenotypes. Conclusions: The IRNW phenotype should be actively evaluated to intervene on the cardiometabolic risk, while further studies are needed to confirm the sustainability of the favorable cardiometabolic profile of the ISO phenotype. Full article

Corticosteroid receptor signaling in primary afferent neurons of the dorsal root ganglion (DRG) has emerged as a potential target to modulate nociception via genomic and nongenomic mechanisms shown in animal pain models. However, the expression landscape of glucocorticoid receptors (GRs) relative to mineralocorticoid receptors (MRs) in human DRG, their association with pain-related markers, and their functional relevance remain incompletely defined. We analyzed human and rat DRG by mRNA profiling and immunofluorescence confocal microscopy to assess GR/MR expression and complemented these studies with a clinical evaluation of neuraxial corticosteroid delivery. Here, GR transcripts in human DRG were the most abundant among corticosteroid receptor-related genes examined (including MR) and were observed alongside transcripts of pain-signaling molecules. Human DRG immunofluorescence analysis revealed substantial colocalization of GR with calcitonin gene-related peptide (CGRP), a marker of nociceptive unmyelinated C-fibers and thinly myelinated Aδ-fibers, as well as with gial fibrillary acidic protein (GFAP), a marker of satellite glial cells (SGCs), but minimal expression in myelinated neurofilament 200 (RT-200) immunoreactive (IR) human DRG neurons. In addition, GR immunoreactivity was primarily distributed to medium-diameter neurons (40–65 µm). Functionally, preclinical experiments showed that GR activation and MR blockade attenuate inflammatory pain via rapid, nongenomic neuronal mechanisms that counter an intrinsic mineralocorticoid receptor-mediated pronociceptive drive. Consistently, clinical analgesia over at least 3 months after transforaminal plus caudal epidural delivery of GR agonists in chronic radicular pain supports a functional role for neuronal GR signaling within spinal cord and DRG circuits. Together, these molecular, functional, and clinical findings identify GR as a key modulator of sensory neuron excitability and pain, highlight MR as a pronociceptive counterpart, and suggest that selectively enhancing GR signaling or inhibiting MR signaling may offer a potential strategy for improving corticosteroid-based analgesic therapies. Full article

Background: Current guidelines for NSCLC follow-up lack specific recommendations on surveillance duration. This study aims to analyze survival and surveillance data in resected stage I NSCLC. Methods: We retrospectively reviewed 759 pathological stage I NSCLC (9thTNM ed.) patients with no history of lung cancer (LC) undergoing surgery from January 2003 to December 2018. Overall survival (OS), incidence of relapse (IR), and incidence of new primary LC (NP) were analyzed. Long-term effect of follow-up beyond 5 years was assessed by landmark analysis of OS, IR, and NP at 10 years, restricted to individuals alive without relapse or NP at 5 years (5-year event-free survivors, 5y-EFSs). Results: The rates of 10-year OS, 10-year IR, NP incidence, and 5y-EFSs were, respectively, 75%, 18%, 1.1%/year, and 59.1% (449 patients). Carcinoid IA/IB (0–10%) and adenocarcinoma IA/IB without lung nodules (LNs) (8–12%) had a similarly lower risk of relapse (p = 0.5088) compared to adenocarcinoma with LNs (p = 0.0191). Similarly, carcinoid (0–0.2%/year) and adenocarcinoma without LNs (0-0.3%/year) had the same lower incidence of NP (p = 0.8062) compared to patients with LNs (p < 0.0001). The group of 5y-EFSs had a conditional 10-year OS, IR, and NP incidence of 92%, 5%, and 0.8%/year. In 5y-EFSs, 10-year OS was better in carcinoid (100%) and adenocarcinoma (94%, p = 0.0009) patients; 10-year IR was lower in stage IA (4%) vs. IB (10%, p = 0.0444), and NP was lower in patients with no pre-surgery (0.5 vs. 1.5%/year, p = 0.0147) and no post-surgery LNs (0.6 vs. 1.1%/year, p = 0.0202). Conclusions: Based on our results, we propose a tailored surveillance strategy by de-escalating follow-up for low-risk patients while maintaining intensive monitoring for high-risk individuals. Full article