Search Results (28,249)

Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease of preterm infants, increasingly viewed as a cytokine-driven disorder of the immature intestine. We aimed to characterize local peritoneal concentrations of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in a standardized neonatal rat NEC model and relate them to histopathological injury. Seventy-four SPRD/Mol/Lodz rat pups were allocated to a control group (CTRL; n = 12) or subjected to a hypoxia-hypothermia-formula-feeding NEC protocol (NEC; n = 62). After 72 h, small-intestinal samples were scored using a four-tier NEC scale (0–3), and peritoneal fluid cytokine levels were measured by ELISA. All CTRL animals exhibited normal histology (grade 0), whereas NEC pups showed a wide spectrum of lesions, with 66.6% classified as grade 2–3 and a significantly higher mean NEC score in NEC than CTRL (p < 0.001). Peritoneal IL-1β and TNF-α concentrations were markedly elevated in NEC versus CTRL animals (both p < 0.001), while IL-6 levels showed no statistically significant between-group difference. These findings indicate that experimental NEC in this model is accompanied by a pronounced local pro-inflammatory response dominated by IL-1β and TNF-α, whereas IL-6 may follow distinct temporal or compartment-specific kinetics. Peritoneal cytokine profiling may help refine mechanistic understanding and guide future biomarker and immunomodulatory strategies in NEC. Full article

Despite antiretroviral therapy, HIV proteins, such as Tat, persist in tissues, driving chronic inflammation. Cervical inflammation in females not only accelerates HIV progression but also increases the risk of other STIs; hence, understanding the underlying factors/regulators is vital. However, Tat-induced cervical inflammation and its regulation are hitherto poorly understood, which we investigated using TZM-bl cells. Tat stimulation in these cervical epithelial cells significantly increased the expression of various inflammatory mediators, including cytokines (IL-1β, TNF-α, IL-6, IL-17a, GM-CSF), chemokines (MIP-1α, MIP-1β), adhesion molecules (ICAM-1, P-Selectin, E-Selectin), and ROS. Further upregulation of inflammatory mediators (NF-κB, IRAK-4) along with TLR7 was observed in Tat-stimulated cells. Interestingly, Tat stimulation decreased miR-204-5p expression in these cells, suggesting a role in regulating Tat-mediated inflammatory processes. Using a gain-of-function approach, we further observed that the overexpression of miR-204-5p reduced the expression of IL-1β, TNF-α, IL-6, MIP-1α, MIP-1β, ICAM-1, P-Selectin, and ROS in the Tat-stimulated TZM-bl cells, along with NF-κB, IRAK-1, and IRAK-4. Using Western blotting and luciferase assays, miR-204-5p was further shown to directly target NF-κB. Here, we report that HIV-1 Tat stimulation in cervical epithelial cells downregulates hsa-miR-204-5p, thereby activating the pro-inflammatory TLR7/NF-κB axis, highlighting its relevance to understanding mechanisms underlying cervical inflammation. Full article

Cervical cancer remains a significant global health burden, with chemoradioresistance representing a major obstacle to successful treatment. To elucidate the mechanisms underlying this resistance, we established a unique pair of isogenic primary cervical cancer cell lines, AdMer35 and AdMer43, obtained from a patient with squamous cell carcinoma of the cervix before and after radiation therapy. The aim of our study was to characterize the transcriptomic and cellular heterogeneity of these cells. We conducted an in-depth comparative analysis using single-cell RNA sequencing. Analysis of this paired, patient-derived isogenic model suggests that chemoradioresistance can arise through coordinated multilevel cellular adaptations. Resistant AdMer43 cells demonstrated transcriptional reprogramming, with the upregulation of embryonic stemness factors (HOX, POU5F1, SOX2), a shift in extracellular matrix from fibrillar to non-fibrillar collagens, and activation of inflammatory pathways. We identified and characterized critical cell-state dynamics: resistant cells exhibited a remodeled ecosystem with a metabolically reprogrammed senescent-like cell population showing an enhanced pro-tumorigenic communication via EREG, SEMA3C, BMP, and WNT pathways. Furthermore, we identified a progenitor-like cell population with a minimal CNV burden, potentially serving as a reservoir for tumor persistence. These findings offer novel insights for developing targeted strategies to eliminate resistant cell pools and improve cervical cancer outcomes. Full article

Colorectal cancer is one of the leading causes of cancer-associated mortality, and multifactorial resistance remains one of the main challenges in its treatment. Essential oils and their main compounds show interesting anticancer properties, but their mechanism of action is yet to be defined. This study aims to assess the cytotoxic effects of eugenol (EU) and cinnamaldehyde (CN) on colorectal cancer (CRC) cells, highlighting possible mechanisms of action. These compounds were tested on normal immortalized colonocytes (NCM-460) and two CRC cell lines: Caco-2, a human colon epithelial adenocarcinoma cell line, and SW-620, colon cancer cells derived from a lymph node metastatic site. The efficacy of EU and CN was evaluated through CellTiter-Glo^® and clonogenic assays and by determining proinflammatory cytokine secretion. Transcriptome analysis was used to identify possible pathways affected by EU and CN treatments. The results confirmed that EU and CN were selectively cytotoxic and pro-apoptotic against CRC cells, with different putative mechanisms. While EU drove cytotoxicity through robust transcriptional remodeling, CN yielded a stronger anti-inflammatory action. We confirmed that EU and CN are promising natural candidates in CRC prevention and treatment, even in association with chemotherapeutic drugs. Full article

Volatile organic compounds (VOCs) emissions from petroleum product storage pose not only a significant environmental concern but also a potential threat to occupational health. This study investigates geospatial analysis of VOCs on an industrial platform in Romania, utilizing a combination of portable field detectors and geostatistical modeling techniques. For more than 10 months, we conducted measurements at 41 georeferenced sampling points across three operational zones, using FID/PID instruments calibrated and validated in accordance with national standards. To evaluate dispersion conditions, meteorological data were simultaneously collected. VOC concentrations were measured under varying meteorological scenarios and analyzed using the Empirical Bayesian Kriging (EBK) method in ArcGIS Pro 3.1.0. Maximum concentrations reached up to 229.46 mg/m³ in central tank areas, with some point samples exceeding this level. Peripheral zones generally showed values below 65 mg/m³, although concentrations above 100 mg/m³ were still observed at 10% of the monitoring sites. The results indicate apparent spatial clustering of elevated VOC levels, particularly under low wind speed and high humidity. Our study highlights the relevance of continuous monitoring and site-specific mitigation strategies in high-risk industrial settings in Romania. Full article

Cell senescence is increasingly recognized as a key driver of atherosclerosis progression. Senescent smooth muscle cells (SMCs) lose their proliferative capacity and adopt a pro-inflammatory profile, contributing to impaired vessel repair and weakening of the fibrous cap. Moreover, senescence promotes SMC dedifferentiation and phenotypic modulation into unfavorable phenotypes associated with plaque destabilization. In this review, we will discuss how cell senescence is induced in atherosclerotic plaques, how this influences SMC plasticity, and how this impacts plaque stability. We will also evaluate the potential of current and experimental anti-atherosclerotic drugs to target SMC senescence and/or SMC phenotypic modulation. Full article

Background: Aging exerts a progressive and multifaceted impact on the microcirculatory system, undermining the structural and molecular integrity that sustains endothelial stability across both peripheral and cerebral vascular territories. A sustained shift toward oxidative imbalance, chronic low-grade inflammation, and progressive endothelial exhaustion converges to destabilize microvascular networks, linking peripheral artery disease (PAD) with heightened susceptibility to cerebral microvascular dysfunction and neurovascular decline. As redox homeostasis deteriorates, endothelial cells progressively lose barrier-selective properties, intercellular communication with pericytes weakens, and pro-thrombotic tendencies subtly emerge, creating a permissive environment for early neurovascular injury and impaired cerebrovascular resilience. Methods: This narrative review integrates mechanistic evidence derived from experimental, clinical, and translational studies examining the interplay between oxidative stress, inflammatory signaling cascades, endothelial senescence, and blood–brain barrier (BBB) disruption across peripheral and cerebral microvascular systems. A comparative framework was applied to PAD and cerebral microcirculatory pathology to identify convergent molecular drivers and systemic mechanisms underlying endothelial deterioration. Results: Accumulating evidence demonstrates that oxidative stress disrupts endothelial mitochondrial function, compromises tight junction architecture, and accelerates angiogenic failure. Concurrent inflammatory activation amplifies these alterations through cytokine-mediated endothelial activation, enhanced leukocyte adhesion, and promotion of a pro-thrombotic microenvironment. Progressive endothelial senescence consolidates these insults into a persistent state of microvascular dysfunction characterized by diminished nitric oxide bioavailability, capillary rarefaction, and compromised barrier integrity. Notably, these pathological features are shared between PAD and the aging cerebral circulation, reinforcing the concept of a unified systemic microvascular aging phenotype. Conclusions: Microvascular failure in the aging brain should be understood as an extension of systemic endothelial deterioration driven by oxidative stress, chronic inflammation, and senescence-associated vascular exhaustion. Recognizing the shared molecular architecture linking peripheral and cerebral microcirculatory dysfunction offers a strategic framework for developing targeted therapeutic interventions aimed at restoring endothelial resilience, stabilizing BBB integrity, and preserving neurovascular homeostasis in aging populations. Full article

The shift toward digital and smart manufacturing requires an accurate prediction of cutting behavior, such as cutting forces. Controlling cutting forces in machining is important for maintaining product quality, particularly in steels such as X5CrNi18-10. This steel has high toughness, which resists cutting, thereby increasing overall cutting forces. Proper selection of machining parameters and conditions can help reduce cutting forces during machining. Several studies have been dedicated to understanding the influence of cutting parameters on cutting forces. However, limited attention is given to the influence of the cutting conditions on cutting forces. The primary objective of this study is to understand the behavior of cutting forces in chromium-nickel alloy steel by varying machining parameters, specifically cutting conditions (dry and wet), using a full factorial (3¹ × 2²) design of experiments (DoE). The secondary objective is to develop a multilinear regression model to predict cutting forces. The root mean square (RMS) values of the cutting force components were calculated from the acquired data and analyzed using OriginPro 2025b. In addition, this study analyzes the effects of cutting parameters and cutting forces on root mean square (RMS) surface roughness (R_q) to understand their impact on quality using the AltiSurf 520 profilometer. The results suggest a significant effect of the selected machining parameters and conditions on cutting force reduction and on improved surface quality when cutting forces are low. This research provides a valuable insight into optimizing the machining process for hard steels. Full article

A promising direction for the creation of new biologically active derivatives of the alkaloid lupinine is the synthesis of “hybrid molecules” that combine a fragment of the alkaloid and the pharmacophore of 1,2,3-triazole in their structure. From a biological perspective, this work presents the first X-ray diffraction study of a single crystal of (1S,9aR)-1-({4-[4-(Benzyloxy)-3-methoxyphenyl]-1H-1,2,3-triazol-1-yl}methyl)octahydro-2H-quinolizine, a new, recently synthesized 1,2,3-triazole derivative of lupinine. A comparison of theoretically predicted and experimentally observed structural parameters was carried out. The FTIR spectroscopy study and vibrational properties calculations allowed us to interpret the FTIR absorption spectrum and localize specific vibrational modes in quinolizidine, 1,2,3-triazole, and benzene rings. Such information can be fruitful for further characterization of the synthesis process and products. The molecular docking of the compound was performed. It was shown that the studied molecules are capable of interacting with the Mpro binding site via non-covalent and hydrophobic interactions with subsites S3 (Met165, Glu166, Leu167, Pro168) and S5 (Gln189, Thr190, Gln192), which ensure the stabilization of the Mpro substrate. Blocking of the active site of the enzyme in the region of the oxyanion hole does not occur, but stable stacking interactions with the π-system of one of the catalytic amino acids, His41, are observed. Full article

Industrial surface defect detection is essential for ensuring product quality, but real-world production lines often provide only a limited number of defective samples, making supervised training difficult. Multimodal anomaly detection with aligned RGB and depth data is a promising solution, yet existing fusion schemes tend to overlook modality-specific characteristics and cross-modal inconsistencies, so that defects visible in only one modality may be suppressed or diluted. In this work, we propose DCRDF-Net, a dual-channel reverse-distillation fusion network for unsupervised RGB–depth industrial anomaly detection. The framework learns modality-specific normal manifolds from nominal RGB and depth data and detects defects as deviations from these learned manifolds. It consists of three collaborative components: a Perlin-guided pseudo-anomaly generator that injects appearance–geometry-consistent perturbations into both modalities to enrich training signals; a dual-channel reverse-distillation architecture with guided feature refinement that denoises teacher features and constrains RGB and depth students towards clean, defect-free representations; and a cross-modal squeeze–excitation gated fusion module that adaptively combines RGB and depth anomaly evidence based on their reliability and agreement.Extensive experiments on the MVTec 3D-AD dataset show that DCRDF-Net achieves 97.1% image-level I-AUROC and 98.8% pixel-level PRO, surpassing current state-of-the-art multimodal methods on this benchmark. Full article

The exponential growth of data-driven applications has intensified performance demands on database systems, where cache management represents a critical bottleneck. Traditional cache replacement policies such as Least Recently Used (LRU) and Least Frequently Used (LFU) rely on simple heuristics that fail to capture complex temporal and frequency patterns in modern workloads. This research presents a modular machine learning-enhanced cache management framework that leverages pattern recognition to optimize database performance through intelligent replacement decisions. Our approach integrates multiple machine learning models—Random Forest classifiers, Long Short-Term Memory (LSTM) networks, Support Vector Machines (SVM), and Gradient Boosting methods—within a modular architecture enabling seamless integration with existing database systems. The framework incorporates sophisticated feature engineering pipelines extracting temporal, frequency, and contextual characteristics from query access patterns. Comprehensive experimental evaluation across synthetic workloads, real-world production datasets, and standard benchmarks (TPC-C, TPC-H, YCSB, and LinkBench) demonstrates consistent performance improvements. Machine learning-enhanced approaches achieve $8.4\%$ to $19.2\%$ improvement in cache hit rates, $15.3\%$ to $28.7\%$ reduction in query latency, and $18.9\%$ to $31.4\%$ increase in system throughput compared to traditional policies and advanced adaptive methods including ARC, LIRS, Clock-Pro, TinyLFU, and LECAR. Random Forest emerges as the most practical solution, providing $18.7\%$ performance improvement with only $3.1\%$ computational overhead. Case study analysis across e-commerce, financial services, and content management applications demonstrates measurable business impact, including $8.3\%$ conversion rate improvements and USD 127,000 annual revenue increases. Statistical validation ($p<0.001$, Cohen’s $d>0.8$) confirms both statistical and practical significance. Full article

Polysaccharide-based wound dressings face challenges in mechanical properties and effective wound repair for infected wound surfaces. This study presents a novel polyvinyl alcohol (PVA)/Salecan (Sal) composite hydrogel dressing with high toughness, biocompatibility, and wound healing capabilities, developed using an interpenetrating polymer network strategy. The primary network was formed through electrostatic interactions between polydopamine (PDA) and biocompatible polysaccharide Salecan, followed by incorporation of AgNO₃, which was in situ reduced to silver nanoparticles within the hydrogel. PVA was introduced as a secondary matrix, further reinforcing the hydrogel network through cyclic freeze–thawing. The resulting hydrogel exhibited a tensile strength of 0.31 MPa, an elongation at break of 158.9%, and a toughness of 31.16 J·m⁻², demonstrating enhanced mechanical performance compared to both Salecan/PDA and previously reported Salecan/Fe³⁺ hydrogel. Co-culture experiments showed the hydrogel’s strong antibacterial effects, inhibiting 80.1% of Escherichia coli (E. coli) and 99.5% of Staphylococcus aureus (S. aureus). Fibroblast culture tests confirmed its excellent cytocompatibility. In vivo studies on infected wounds showed nearly complete healing in the S. aureus + hydrogel group within 12 days. Quantitative immunohistochemical analysis of CD31 revealed that hydrogel treatment significantly upregulated CD31 expression, indicating enhanced neovascularization. Complementary Western blot analysis further demonstrated that hydrogel-treated groups exhibited a marked downregulation of pro-inflammatory factors alongside CD31 upregulation. In summary, the PVA/Sal-based hydrogel represents a valuable strategy for reducing inflammation and promoting regeneration in the management of infected wounds. Full article

Background/Objectives: The cardiac hypoxia- and inflammation-associated processes in patients with chronic coronary artery disease remain unknown. The coronary sinus (CS) can be used to explore changes in cardiac microenvironment. This study sought to evaluate acute changes in the CS concentration of hypoxia and inflammation-associated biomarkers after the percutaneous revascularization of chronic total occlusions (CTO-PCI). Additionally, we explored changes in systemic inflammation and the potential of CS biomarkers to predict left ventricular ejection fraction (LVEF) improvement on follow-up. Methods: Thirty-three patients undergoing CTO-PCI were included. Samples from CS were collected before and after the revascularization. Twenty-six protein biomarkers associated with hypoxia and inflammation were measured using proximity extension assay technology. Systemic inflammation markers and LVEF on cardiac magnetic resonance imaging were assessed at baseline and 6-month follow-up. Results: CTO-PCI yielded a significant decrease in the concentration of CS pro-angiogenic biomarkers (angiopoietin-1, vascular endothelial growth factors). In addition, there was a significant increase in the anti-inflammatory biomarker interleukin-10 and a decrease in several pro-inflammatory biomarkers like interleukin-1β. The acute response in cardiac microenvironment was followed by a mid-term reduction in systemic inflammatory markers, particularly high-sensitivity C-reactive protein. Notably, interleukin-10 showed good performance to identify patients achieving LVEF improvement on follow-up in our cohort. Conclusions: Our results suggest that CTO-PCI might attenuate cardiac hypoxic and inflammatory stress. These exploratory findings warrant confirmation in larger, controlled studies. Full article

Background/Objectives: Hypertensive disorders of pregnancy (HDP) remain a significant cause of maternal and perinatal morbidity worldwide. In some healthcare settings, access to angiogenic testing is limited, underscoring the need for affordable biomarkers to guide risk assessment. NT-proBNP, a marker of myocardial wall stress and cardio-renal dysfunction, may offer complementary prognostic value to the angiogenic sFlt-1/PlGF ratio. Methods: In this prospective multicenter observational study, we enrolled 180 pregnant women and categorized them into preeclampsia (PE, n = 95), non-PE HDP (gestational or chronic hypertension, n = 25), and healthy controls (n = 60). NT-proBNP and sFlt-1/PlGF levels were measured at enrollment, after 20 weeks of gestation, predominantly during the second and third trimesters. Associations with proteinuria, uric acid, creatinine, and maternal–fetal complications were examined using multivariable logistic regression adjusted for maternal age, BMI, and gestational age. Discrimination was assessed using receiver operating characteristic (ROC) curve analysis, and the incremental value of NT-proBNP beyond the sFlt-1/PlGF ratio was evaluated using ΔAUC and net reclassification improvement (NRI). Results: Median NT-proBNP levels were significantly higher in PE compared with non-PE HDP and controls (p < 0.01). NT-proBNP ≥200 pg/mL independently predicted maternal–fetal complications (adjusted OR 3.12, 95% CI 1.41–6.90, p = 0.005) and correlated with proteinuria (r = 0.47), creatinine (r = 0.43), and uric acid (r = 0.40) (all p < 0.001). sFlt-1/PlGF alone yielded an AUC of 0.84 (95% CI 0.77–0.89), while NT-proBNP alone demonstrated an AUC of 0.78 (0.71–0.84). Combining both biomarkers improved discrimination (AUC 0.88, 95% CI 0.82–0.92), with a ΔAUC of 0.04 (p = 0.02) and a continuous NRI of 0.21 (p = 0.03). The 200 pg/mL threshold for NT-proBNP achieved 80% sensitivity and 71% specificity (p < 0.001). Conclusions: NT-proBNP provides independent and complementary prognostic value to the sFlt-1/PlGF ratio in predicting maternal–fetal complications in HDP. A practical threshold of 200 pg/mL aids risk assessment, and integrating NT-proBNP into angiogenic models improves prediction. Further multicenter studies are needed to validate multimarker strategies and their cost-effectiveness. Full article

Background/Objectives: Frailty, a syndrome characterized by diminished physiological reserves and increased vulnerability to stressors, is a strong predictor of adverse outcomes in heart failure. The MECKI (Metabolic Exercise Cardiac Kidney Index) score, derived from cardiopulmonary exercise testing and renal function parameters, has demonstrated prognostic value in HF patients. This study aimed to evaluate the prognostic value of physical frailty on mortality in patients with advanced heart failure and to compare it directly with the MECKI score. Methods: A total of 104 patients with advanced HF receiving optimized guideline-directed medical therapy were prospectively enrolled. At baseline, all patients underwent clinical, echocardiographic, and laboratory assessment and CPET for MECKI score calculation. Physical frailty was assessed using a modified Fried phenotype tailored for HF. The composite endpoint comprised all-cause mortality, urgent heart transplantation, or LVAD implantation. Results: Over a mean follow-up of 30.0 ± 15.3 months, there were 25 deaths, 5 urgent heart transplants, and 1 LVAD implantation. Patients who experienced the composite outcome had significantly worse NYHA class, higher NT-proBNP, lower VO₂max, higher VE/VCO₂ slope, higher frailty, and higher MECKI score (all p < 0.001). Frailty was significantly correlated with all MECKI score components, as demonstrated by Spearman’s rank correlation analysis. Both frailty (HR = 1.89; 95% CI 1.22–2.93; p = 0.005) and MECKI score (HR = 1.04; 95% CI 1.00–1.08; p = 0.037) independently predicted outcomes. ROC analysis showed high and comparable discriminative performance (AUC = 0.86 for frailty; AUC = 0.88 for MECKI). Conclusions: Physical frailty and MECKI scores independently predict mortality and adverse events in advanced HF. Physical frailty, despite its simplicity and low cost, provides prognostic insight comparable to the MECKI score and may represent a practical alternative when CPET is unavailable. Full article