Search Results (1,781)

Exposure of healthy tissue to ionizing radiation (IR) occurs due to nuclear accidents and terrorism, as well as radiotherapy. The vascular endothelium is a key target of IR, and microvascular endothelial cells (ECs) are particularly vulnerable to radiation. IR induces EC activation leading to endothelial cell injury. Human ghrelin is a stomach-derived peptide with pleiotropic effects, including protection against inflammation. We hypothesize that human ghrelin improves survival in total body irradiation (TBI) and that ghrelin’s protective effect could be mediated by attenuating endothelial cell injury. To test this, mice were exposed to TBI and after 24 h were treated subcutaneously with human ghrelin once daily for 4 days and monitored for 30 days. The survival rate of the human ghrelin-treated group was significantly higher than that of the vehicle group. Subsequently, human ghrelin treatment showed an effective dose modification factor of 1.0681. On day 4 after TBI, human ghrelin significantly attenuated EC permeability in the lungs and improved tight junction protein ZO-1 expression. Human ghrelin also improved ZO-1 and Claudin5 expression in primary mouse lung vascular endothelial cells. Taken together, these results indicate that human ghrelin improves survival after TBI, and its survival benefit is in part due to the attenuation of EC permeability and microvascular barrier dysfunction. Full article

Background and Objectives: Pro-inflammatory diet and high-fat diet (HFD) often coexist in real-world, but their combined impact on the gut–liver axis and potential nutritional countermeasures remain insufficiently studied. This study aimed to evaluate a pro-inflammatory–high-fat composite dietary pattern on the intestine and liver in the population, and to further evaluate the protective potential of astaxanthin (ATX) in complementary experimental systems. Methods: Data from the NHANES 2005–2010 were used to construct four composite exposure groups based on the dietary inflammation index (DII) and energy from fat. Survey-weighted regression analyses were performed to examine associations with systemic inflammation and liver injury. Interaction and C-reactive protein (CRP)-mediated effect analyses were conducted. Fifty SD rats were randomly divided into control group, model group induced by HFD combined with inflammatory factors, and low-, medium-, and high-dose Haematococcus pluvialis (HP) intervention groups. Serum lipids, liver enzymes, liver and colon pathology, and inflammatory and oxidative markers were measured in rats. In an in vitro organ-on-chip barrier model, the effect of ATX was observed when colonic barrier damage was induced using palmitic acid and lipopolysaccharides. Results: The high DII combined with HFD showed the largest increases in CRP, liver enzymes, and fatty liver index. A synergistic interaction was observed between DII and HFD, with CRP mediating approximately 20% of the effect. In rat model, HP-derived ATX improved the lipid profile, attenuated hepatic steatosis and oxidative damage, and reduced colonic pro-inflammatory cytokines, while restoration of tight junction proteins was limited. In colon organoid model, ATX showed limited efficacy in improving inflammation and barrier function. Conclusions: The pro-inflammatory–high-fat dietary pattern synergistically exacerbates gut–liver dysfunction. HP-derived ATX alleviates metabolic and inflammation-induced enterohepatic comorbidity, but its effect on repairing barrier structure is limited. Full article

Modeling immune cell recruitment within a wound-relevant microenvironment remains challenging. Here, we developed a novel skin-derived extracellular matrix (ECM) hydrogel model to study monocyte (THP-1) entry and phenotypic changes within a dermal fibroblast-populated (NHDF) matrix. The main novelty of this study is that it compares the effects of fibroblast-derived soluble signals and active monocyte infiltration in a 3D biomimetic model. Signaling by fibroblast-secreted soluble factors enhanced a pro-angiogenic secretome (e.g., >3-fold upregulation of VEGFA at day 1) and promoted endothelial tube formation (increasing network junctions to 1.16 ± 0.16 vs. 0.93 ± 0.23 in monoculture). In contrast, this paracrine signaling did not induce the matrix-driven pro-fibrotic response in hydrogels. Crucially, physical immune infiltration restricted monocyte penetration (mean depth of 8.92 ± 2.27 μm vs. 121.1 ± 15.9 μm in monoculture at day 5), reduced hydrogel-induced myofibroblast activation (decreasing α-SMA+ cells from 79.1% to 54.3% upon initial contact), and was associated with slower collagen loss during the early phase. (retaining a high-density collagen ratio of 3.46 ± 0.33 vs. 2.02 ± 0.29 in monoculture at day 1). These observations were accompanied by a shift toward a matrix-stabilizing profile, including increased TIMP expression and reduced pro-fibrotic markers. (ACTA2 and COL1A1). By including active immune infiltration (which was absent in previous tSVF models), we capture the transition from inflammation to the proliferation stage. Although the later stages of extensive ECM remodeling appear suppressed here, they may occur as repair progresses. Overall, our findings highlight that the immune cell is a key regulatory component for coordinating matrix preservation and vascular support. Importantly, this model replicates the early phases of wound healing, a stage where the monocyte–fibroblast secretome supports endothelial network formation. We established this innovative 3D ECM hydrogel system as a practical and physiologically relevant platform to investigate immune–matrix–stromal crosstalk. Full article

Alterations in tight junction (TJ) organization and dysregulation of cancer stem cell (CSC)-associated markers are increasingly recognized as molecular features linked to colorectal cancer (CRC) progression, heterogeneity and clinical outcome. Bioactive dietary compounds such as spermidine (SPD) and eugenol (EUG) have been proposed as modulators of cancer-related molecular pathways; however, their combined effects on CRC spheroid models relevant to molecular characterization remain insufficiently defined. In the present study, the molecular impact of SPD and EUG, administered individually or in combination, was evaluated in primary and metastatic CRC spheroids. First-generation spheroids derived from Caco-2 and SW620 cells were exposed to SPD, EUG, or SPD+EUG at the time of seeding, and spheroid growth and self-renewal capacity were monitored across successive generations. The expression of TJ- and CSC-associated markers was assessed at both the transcript and protein levels using reverse transcription–quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunohistochemistry. The combined SPD+EUG treatment was associated with a marked reduction in spheroid area and self-renewal capacity in both CRC models. Baseline molecular profiling revealed higher TJ marker expression in Caco-2 spheroids and enrichment of CSC-associated markers in SW620 spheroids. Treatment-induced modulation of CSC- and TJ-related transcripts was observed; however, transcript-level changes were not consistently mirrored at the protein level, indicating the involvement of post-transcriptional regulatory mechanisms. In particular, Occludin (OCLN), Zonula occludens-1 (ZO-1), CD133, ALDH1A1, SOX2 and VE-cadherin exhibited divergent RNA and protein expression patterns depending on cell type and treatment condition. Collectively, these findings underscore the relevance of three-dimensional CRC spheroid models for molecular profiling studies and highlight the importance of integrating transcript- and protein-level analyses when evaluating bioactive compounds with potential diagnostic and translational relevance in colorectal cancer. Full article

With the rapid development of electrified railways in high-altitude regions, section insulators in catenary systems frequently experience gap breakdown and surface flashover under low atmospheric pressure conditions, posing serious threats to safe train operation. This paper investigates the discharge mechanisms of section insulators in high-altitude environments and conducts research on discharge characteristics under extremely non-uniform electric fields, along with structural optimization. First, the physical mechanisms of gap discharge and surface flashover in section insulators are analyzed. A three-dimensional electric field simulation model of the section insulator is established, and numerical analysis is performed to reveal the electric field distribution characteristics. The results indicate that the electric field is predominantly concentrated at the junction between metal electrodes and insulators, as well as at the tip of the arcing horn. The local maximum field strength reaches 3.84 × 10⁵ V/m, exceeding the corona inception field strength of air, which readily induces discharge. Subsequently, power frequency and lightning impulse discharge tests are conducted in both plain region and regions at an altitude of 4300 m. The results show that under high-altitude conditions, the power frequency breakdown voltage decreases by 28%, and the 50% lightning impulse breakdown voltage decreases by 42%. The discharge voltages under standard atmospheric conditions are obtained through correction. Finally, optimization schemes involving arcing horn structural modification and surface coating application are proposed. Adjusting the arcing horn angle to 55° and adding a grading ring structure with a radius of 70 mm reduces the local maximum field strength by 26%. After applying an RTV insulating coating, the field strength at the junction decreases by 35.9%, effectively enhancing the insulation performance of section insulators in high-altitude regions. Full article

Mechanical signals play key roles in the regulation of epidermal homeostasis and regeneration after injury. Integrins are key components of focal adhesions, and these complexes are major contributors to mechanotransduction. In keratinocytes, integrin-linked kinase (ILK) modulates essential processes for epidermal homeostasis and wound repair. However, its functions in the transduction of mechanical stimuli have remained virtually unexplored. In this study, we characterized epidermal tissues and primary keratinocytes from mice with epidermis-restricted inactivation of the Ilk gene (ILK-KO). ILK-deficient epidermis exhibits abnormalities in key components of mechanotransduction cascades, including disruptions in hemidesmosomal Collagen XVII immunoreactivity at the dermal–epidermal junction, and marked reduction in the nuclear localization of the mechanosensitive transcriptional regulator YAP. In wild-type (ILK+), but not in ILK-KO-cultured keratinocytes, exposure to cyclic bidirectional strain induced marked F-actin cytoskeletal rearrangements, characterized by the assembly of thick cortical actin bundles and stress fibers, as well as YAP nuclear translocation and transcriptional activity. Exposure to mechanical strain was additionally accompanied by differential changes in miRNA expression between ILK+ and ILK-KO cells. These findings reveal multiple and previously unappreciated key regulatory roles for ILK in epidermal keratinocyte responses to mechanical signals. Full article

Retained placenta (RP) is a significant postpartum complication in dairy cows. Although abnormal estradiol (E₂) levels are implicated, the underlying cellular mechanisms remain poorly defined. Through RNA-seq analysis of postpartum blood from cows with or without RP, we identified Serum and Glucocorticoid-regulated Kinase 1 (SGK1) as a differentially expressed gene candidate. Analysis of fetal cotyledonary tissues revealed that SGK1 expression was significantly elevated in these tissues, concomitant with markers of suppressed apoptosis, increased levels of tight junction proteins, and an inhibited epithelial–mesenchymal transition (EMT) phenotype. To explore a potential mechanistic link between E₂ and these cellular alterations, we investigated the E₂-SGK1 axis in bovine endometrial epithelial cells in vitro. E₂ treatment upregulated SGK1 expression, reduced apoptosis, increased tight junction protein levels, and suppressed EMT. Conversely, SGK1 knockdown induced apoptosis, disrupted tight junctions, and impaired EMT. Notably, E₂ could not rescue the apoptosis and EMT alterations in SGK1-knockdown cells, indicating that SGK1 is a critical mediator of these E₂ effects in this cellular model. Based on these initial correlative findings in tissues, combined with the subsequent mechanistic experiments in cells, we propose a novel model whereby dysregulation of the E₂- SGK1 axis could contribute to RP pathogenesis by stabilizing the placental interface. Our findings provide the first experimental evidence linking SGK1 to RP and establish a foundation for future in vivo validation. Full article

Droplet microfluidics enables precise manipulation of picoliter-to-nanoliter-scale droplets and supports key operations such as merging, splitting, sorting, and trapping, facilitating controlled handling of minute fluid volumes. These capabilities have significantly advanced high-throughput drug discovery, single-cell analysis, molecular diagnostics, and synthetic biology. Among these operations, droplet splitting is particularly important for multi-step biochemical assays and parallel processing. Splitting strategies can be broadly categorized as passive, relying on channel geometry or microstructures, or active, employing external stimuli such as thermal, magnetic, acoustic, or electric fields. Electric-field-based methods are especially attractive due to their rapid response and tunability; however, many reported systems require relatively high operating voltages. Here, we present a low-voltage microfluidic platform that integrates tilted interdigitated electrodes (IDEs) with an asymmetric Y-junction to enable electrically tunable droplet splitting and sorting within a single device architecture. Two independently addressable tilted IDE arrays generate localized electric-field gradients that induce dielectrophoretic droplet deflection at moderate voltages. By adjusting the applied voltage amplitude and selectively activating the electrode arrays, droplets can be dynamically routed into designated outlets or deterministically split in real time, providing adaptable electrohydrodynamic control with minimal structural complexity. Full article

(−)-Epigallocatechin 3-gallate (EGCG) is a potent natural antioxidant, but its strong bitterness and poor palatability limit its application in animal production. This study aimed to evaluate the protective effects and underlying mechanisms of chemically synthesized EGCG derivatives against oxidative stress using a diquat-induced mouse model. A total of 36 male ICR mice were randomly assigned into six groups (n = 6): Control (T0), Diquat (T1), EGCG + Diquat (T2), Epigallocatechin octanoate (EGCO) + Diquat (T3), Epigallocatechin p-chloromethylbenzoate (EGCP) + Diquat (T4), and Epigallocatechin ibuprofen ester (EGCI) + Diquat (T5). Oxidative stress was induced by intraperitoneal injection of diquat at day 27 of the experiment, while EGCG or its derivatives were administered via dietary supplementation. At day 28, the mice were weighed, killed, and the tissues were sampled. Diquat challenge significantly impaired growth, increased serum injury markers (ALT, AST, DAO, and D-LA) (p < 0.05), suppressed hepatic and jejunal antioxidant enzymes (GPx, SOD, and TAOC) while elevating MDA (p < 0.05), damaged jejunal morphology (villus atrophy) (p < 0.05), and downregulated tight junction proteins (ZO-1 and Occludin) (p < 0.05). Chemically synthesized EGCG derivatives, especially EGCI, effectively alleviated diquat-induced growth impairment and hepatic and intestinal oxidative damage by improving intestinal barrier function and enhancing systemic antioxidant capacity, possibly in part through activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Compared with EGCG, EGCI exhibited reduced bitterness and improved palatability, which favored normal feed intake. These findings provide strong theoretical support for the future application of EGCG derivatives, especially EGCI, as functional antioxidant additives in broiler production. Full article

The neuromuscular junction (NMJ) is responsible for transmitting neural signals that trigger muscle contraction. Muscle injuries cause damage to cellular structures and trigger local inflammatory processes. In this context, eccentric contraction was used as an experimental model because it involves excessive stretching, generating mechanical stress. Twenty-five adult male Wistar rats were distributed into groups: Control (C) (n = 5) and Injury (I) (n = 20). The protocol was performed on a treadmill and consisted of 18 sets/5 min/16 m/min speed, with intervals, and with a negative incline (−16º). The analyses consisted of histochemical techniques, such as myofibrillar ATPase and immunofluorescence (calcium channels, synaptophysin and α-bungarotoxin). Group I-0H showed alterations in the presynaptic region and an increase in Type I fibers. I-24H presented disorganization in the postsynaptic region. In I-4D, we observed the reorganization of neuromuscular activity, while I-7D presented greater density and cross-sectional area (CSA) of Type II fibers. It is concluded that the protocol promotes changes in NMJ structure and fiber distribution, mainly in I-24H. In I-4d, a reorganization of neuromuscular activity is observed, and in I-7D, a structural indicator consistent with recovery demonstrates the skeletal muscle’s ability to adapt to injury. Full article

We analyze the spectral stability of travelling waves in a $\delta$-regularized dissipative sine-Gordon equation modelling refined long Josephson junction dynamics. Linearization about a wave yields a singularly perturbed fourth-order spectral problem with intrinsic slow–fast spatial structure. Using an Evans-function formulation on a domain of consistent spatial splitting, we establish a local factorization separating slow and fast modes and prove that the $\delta$-induced fast subsystem remains uniformly hyperbolic and does not generate an additional point spectrum near $\lambda =0$. Hence, the local point spectrum coincides with that of the classical dissipative sine-Gordon equation. Numerical computations of the essential spectrum and Evans winding numbers confirm the analysis and show that the higher-order terms enhance high-frequency damping without altering low-frequency spectral stability. Full article

Environmental toxins can impair gut microbiota and increase intestinal permeability, contributing to various health problems. While many such toxins are known to disrupt tight junctions and compromise barrier function, research specifically examining carbon tetrachloride (CCl₄) as a trigger of intestinal epithelial barrier dysfunction remains limited. In this study, 54 young Western albino male rats, weighing 180–200 g, were randomly assigned to nine experimental groups, each comprising six rats. Group 1 received 1 mL of oral saline and served as a control. Groups 2 and 3 received 0.2 g/kg body weight probiotic and prebiotic, respectively, for four weeks. CCl₄ (1 mL/kg, i.p.) was administered either at the beginning of day 1 (damage induction; Group 4) or at the end of day 28 (protection assessment; Group 7). Intervention groups received probiotics and prebiotics for 4 weeks after (therapeutic) CCl₄ exposure on day 1 in Groups 5 and 6, respectively. Groups 8 and 9 received probiotics and prebiotics for 4 weeks before CCl₄ exposure on day 28, respectively. Quantification of gut bacterial populations, serum levels of Occludin and Zonulin, as biomarkers of intestinal permeability, and histopathological analysis of intestinal tissue were conducted. CCl₄ induces significant intestinal epithelial barrier dysfunction with marked histopathological alterations. Probiotic treatment was more effective than prebiotics at normalizing serum Zonulin and Occludin levels in CCl₄-induced intestinal damage. Probiotics restore microbial balance by suppressing the overgrowth of pathogenic organisms, while prebiotics confer partial protection. CCl₄-induced gut barrier disruption is restored through probiotic supplements by restoring gut microbial balance and normalizing tight junction-associated biomarkers. Full article

The heart–brain axis is a bidirectional communication network composed of neural, humoral, and immune pathways that sustain cardiovascular and brain homeostasis. There is mounting evidence that viral myocarditis—a prototype of inflammatory heart disease—acts beyond the myocardium, triggering systemic immune cascades that lead to central nervous system (CNS) involvement. This involvement creates an inflammatory continuum in which cardiac damage and neuroinflammation reinforce each other via common cytokine and molecular mediators. Central mediators in this axis are the proinflammatory cytokines IL-1β, IL-6, tumor necrosis factor (TNF)-α, IL-17, IL-23, and IL-33. These cytokines are released by infected cardiomyocytes and immune cells during myocarditis, inducing endothelial cell (EC) activation, and causing blood–brain barrier (BBB) disruption. Simultaneously, TLR/NF-κB signaling and the stability of endothelial junctions are modulated by regulatory microRNAs such as miR-155 and miR-146a/b, which respectively enhance or attenuate inflammatory signals. Disruption of the BBB allows cytokines and immune cells to enter the brain parenchyma, where they activate microglia and astrocytes through NF-κB-dependent pathways. The resultant neuroinflammation disrupts autonomic equilibrium and leads to sympathetic overdrive, arrhythmogenesis, and overall worsening of cardiac injury, thus forming a self-perpetuating inflammatory cycle between the heart and the brain. Selective modulation of cytokines (anti-IL-1β, IL-6 receptor antagonists, and TNF-α modulators), blockade of the NLRP3 inflammasome, and miRNA therapy (anti-miR-155 and miR-146a mimics) are potential approaches for interrupting the heart–brain inflammatory circuit. In addition, neurotrophic therapies preserving BBB integrity may reduce secondary neuronal damage. Therefore, a future precision cardio-neuroprotective paradigm will rely on the integration of anti-inflammatory, molecular, and neurovascular strategies aimed at limiting systemic cytokine propagation and restoring bidirectional homeostasis through the heart–brain axis. Full article

Reliable detection of microplastics by surface-enhanced Raman scattering (SERS) is often hindered by poor particle–substrate contact and limited access to plasmonic hotspots on conventional planar substrates optimized for molecular adsorption. Here, we report a rapid microwave-assisted carbothermal shock strategy to fabricate silver nanoparticle-decorated electrospun carbon fibers (AgNPs@ECF) as a three-dimensional plasmonic platform tailored for solid microplastic sensing. Localized microwave-induced heating in a mixed ethanol–hexane system enables Ag nanoparticle nucleation and anchoring on conductive carbon fibers within 45 s, yielding a mechanically compliant, junction-rich architecture without chemical reductants or vacuum processing. The AgNPs@ECF composite was evaluated using morphologically weathered polystyrene (PS) and polyethylene terephthalate (PET) microplastics, along with size-controlled PS bead standards ranging from ~50 nm to 45 μm. Across these models, SERS response is governed primarily by particle–substrate contact geometry and near-field accessibility rather than polymer type. The strongest enhancement occurs in the sub-micrometer regime, where particles can engage multiple AgNP-decorated fiber junctions, while ultrasmall and large, smooth particles show reduced enhancement due to limited contact or rapid field decay. Spatially resolved Raman mapping and finite-difference time-domain simulations support a contact-dominated enhancement mechanism, revealing localized field confinement at particle–fiber interfaces. These results establish the design principles for three-dimensional SERS substrates targeting heterogeneous solid particulates, demonstrating that contact-accessible plasmonic architectures are critical for reliable microplastic detection under realistic solid-particle measurement conditions. Full article

Insulated-gate bipolar transistor (IGBT) power modules suffer efficiency degradation at elevated operating junction temperatures. The thermal sensitivity of the collector–emitter saturation voltage (V_CEsat) induces thermal stress imbalance, constraining system efficiency and reliability. A multi-resistor cascade network model for carrier-storage trench-gate IGBTs (CS-IGBTs) is established. The simulation results agree with the measurements within 10% error. The model decomposes the temperature coefficient contributions of individual structural regions. Analysis reveals that the drift region resistance dominates the V_CEsat temperature coefficient. Based on this finding, a co-doping strategy is proposed through simultaneously increasing the doping concentration in the carrier-storage layer and P⁺ collector. This approach reduces the temperature sensitivity of carrier mobility in the drift region, thereby optimizing V_CEsat’s temperature sensitivity. For the fabricated 1200 V/40 A CS-IGBT, the V_CEsat temperature coefficient decreases from 2.38 mV/K to 1.76 mV/K over 300 K to 450 K, which represents a 25.4% reduction. The total switching loss at 450 K decreases from 9.32 mJ to 8.70 mJ, achieving a 6.7% improvement. This device-level optimization suppresses V_CEsat’s temperature sensitivity and switching losses, enhancing efficiency in high-temperature power module applications. Full article