Search Results (130)

Drug- and alcohol-induced liver injury involves impaired bile acids or bilirubin secretion, but it is not known how senescence influences the secretion of hepatocytes exposed to drugs and alcohol. In this study, the toxic effects of ritonavir, lopinavir, and alcohol on hepatocyte transporters and the secretion of bile acids and bilirubin were investigated in hydrogen peroxide-induced senescent HepG2 and doxorubicin-induced senescent primary human hepatocytes. In HepG2, intracellular conjugated bilirubin increased upon senescence and extracellular conjugated bilirubin in culture medium was decreased by ritonavir and lopinavir treatment. In the primary hepatocytes, intracellular bile acids or medium bilirubin were not significantly changed upon senescence. However, intracellular bile acids were increased, and medium conjugated bilirubin were decreased in senescent primary hepatocytes treated with alcohol and the two drugs. Transcriptional expressions of adenosine triphosphate (ATP)-binding cassette (ABC) transporters (ABCB4, ABCC6, ABCB11, and ABCD3) were decreased whereas UDP-glucuronosyltransferase (UGT1A1) was increased by ritonavir and lopinavir in senescent HepG2. In senescent primary hepatocytes, expressions of ABCB11, ABCC1, ABCC2, ABCC3, ABCC4, and ABCC6 were apparently reduced whereas UGT1A1 and the cytochrome P450 enzyme CYP7A1 were markedly increased by alcohol combined with ritonavir and lopinavir. Selective ABCC6 knockdown in the primary hepatocytes altered expressions of two senescence markers, Lamin A/C and cyclin-dependent kinase inhibitor CKI (p21), increased expressions of CYP7A1 and hydroxy methyl glutaryl-CoA reductase (HMGCR), and increased intracellular bile acids. Further, anti-cholestasis agents, ursodeoxycholic acid and glycyrrhizin, significantly ameliorated the impaired secretions of bile acids and bilirubin as well as reducing intracellular lipid accumulation and cell death caused by ritonavir, lopinavir, and alcohol in the primary hepatocytes with ABCC6 knockdown. These results indicate that senescence moderately impairs the ABC transporters of hepatocytes and secretion of bile acids or bilirubin, which become worse in the presence of the drugs and alcohol but could be improved by anti-cholestasis agents. Full article

This study experimentally evaluates the mechanical and microstructural performance of single- and double-layer intraply hybrid composite (IRC) laminates produced using the hand lay-up method, focusing on Glass–Aramid (GA), Aramid–Carbon (AC), and Carbon–Glass (CG) configurations. Tensile, flexural, compressive, and density tests were conducted in accordance with relevant ASTM standards to assess the influence of hybrid type and layer number under field-representative manufacturing conditions. Microstructural investigations were performed using optical microscopy and scanning electron microscopy (SEM) to identify fabrication-induced imperfections and their relationship to mechanical behavior. The results demonstrate that increasing the laminate configuration from single to double layer significantly enhances mechanical performance across all hybrid types. Double-layer AC laminates exhibited the highest tensile strength (330.4 MPa) and Young’s modulus (11.93 GPa), corresponding to improvements of approximately 85% and 59%, respectively, compared to single-layer counterparts. In flexural loading, the highest strength was observed in double-layer CG laminates (97.14 MPa), while compressive strength was maximized in double-layer AC laminates (34.01 MPa), indicating improved stability and resistance to compression-driven failure. Statistical analysis confirmed that layer number is the dominant parameter governing mechanical response, exceeding the influence of hybrid configuration alone. Microstructural observations revealed fiber misorientation, incomplete resin impregnation, and localized voids inherent to manual fabrication. However, these imperfections were consistently distributed across all specimens and did not obscure comparative mechanical trends. Coefficients of variation generally remained below 10%, indicating acceptable repeatability despite non-ideal manufacturing conditions. Full article

Driven by regulatory and environmental demands, composite structures must combine high structural performance, recyclability, and resource efficiency. Here, an investigation on the structural adhesive bonding of glass-fibre-reinforced thermoplastic Elium© composite laminates is undertaken. Substrates are manufactured using vacuum infusion. Evaluation is performed on the following three commercial two-component adhesives cured at RT: an epoxy (EP), a polyurethane (PU), and an acrylate system (AC). Based on Dynamic Mechanical Analysis, the glass transition temperatures of the EP, PU, and AC adhesives are 56.5, 102.9, and 111.9 °C, respectively. The AC adhesive exhibits the highest shear strength and displacement at failure, reflecting a superior load-bearing capacity. Fractographic analysis further supports these findings: AC joints show a mixed substrate/cohesive failure mode, while EP samples fail exclusively by adhesion failure and PU samples predominantly by a mixture of special cohesion, adhesion and substrate failure. Regarding processing, the EP samples show the highest pot life, followed by PU and then AC. Nonetheless, the pot life of the AC adhesive does not limit its range of application.. The results highlight the advantages of adhesive bonding of Elium© in enabling lightweight and more circular composites. RT-cured adhesives eliminate the need for drilling and energy-intensive thermal curing, allowing design flexibility and reductions in CO₂ footprint within composite production. Full article

Mechanobiology plays a pivotal role in skeletal development and bone remodeling. Mechanical signals such as matrix stiffness, fluid shear stress, and hydrostatic pressure activate the Runt-related transcription factor 2 (RUNX2) bone-specific transcription factor through pathways including the mitogen-activated protein kinase (MAPK) signaling cascade and yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) effectors. RUNX2 itself affects chromatin remodeling and nuclear architecture via Lamin A/C and Nesprin 1, thereby directing osteogenic differentiation. Thus, RUNX2 acts both as a mechanosensor and mechanoregulator, whereas RUNX2’s mechanosensitivity has been leveraged as a target to achieve bone regeneration. Notably, post-translational modifications and epigenetic alterations can orchestrate this regulation, integrating metabolic and circadian signals. However, due to RUNX2’s nuclear localization, its targeting remains a challenging issue. To this end, indirect targeting, through mammalian/mechanistic target of rapamycin complex 1 (mTORC1) or microRNAs (miRNAs), offers new strategies to employ biomechanics in an attempt to intervene with bone diseases driven by mechanical cues or degeneration, and ultimately repair and regenerate the damaged tissues. Herein we critically elaborate upon molecular aspects of RUNX2 regulation towards exploitation at the clinical level. Full article

This research examines the influence of various concentrations (0%, 1%, 1.4% and 1.8% by weight) of activated carbon nanoparticles (AC NPs) on the performance of Elium biocomposites reinforced with hemp fibers. Unidirectional [0°/0°] laminates with 20% fiber volume fraction were fabricated via hand layup using two layers of 150 GSM hemp fabric and compression molded to achieve 0.9 mm cured thickness. Quasi-static tensile testing (ASTM D3039, 2 mm/min, 100 mm gauge length) revealed a pronounced non-monotonic relationship between AC NPs loading and mechanical properties, with optimal performance at 1.0 wt.% fillers and catastrophic degradation at 1.8 wt.%. AC NPs filled composites, which were then characterized by their electrical and thermal behavior. Electrically, it also achieved minimum resistivity (1.62 Ω·m) and maximum conductivity (0.62 S·m⁻¹), in contrast to the elevated resistance (42.5 kΩ) found in samples with a higher filler content. Thermal analysis showed a slight effect on the degradation of the onset temperature (300 °C) and a higher charring after addition of AC NP. Finite element analysis (FEA) provided a corroboration for these experimental findings, with simulations verification. Microscopy revealed cohesive fractures in the 1.0 wt.% composite whereas voids and brittle failure were evident in samples with higher loading. Hence, the concentration of 1.0 wt.% AC NP offers the best trade off of mechanical, electrical, and thermal properties. Full article

Transformer modeling is a crucial method for analyzing transient phenomena such as inrush currents. The primary characteristic of a transformer transient model is its ability to reflect how the transformer’s structure and material properties influence the magnetic and electric fields. In high-voltage direct current (HVDC), the single-phase converter adopts a double-core-limb and double-side-limb configuration, whose core structure, magnetic flux distribution, and ferromagnetic materials differ from conventional power transformers. This paper conducts research on low-frequency transient modeling of single-phase four-limb converter transformers. This study first determines the magnetic field distribution of the single-phase converter transformer with the inclusion of leakage flux. Subsequently, a corresponding model is derived from the principle of duality. Due to the laminated structure, the iron core exhibits different excitation characteristics from those of a single silicon steel sheet. For the excitation branch, AC-DC hybrid excitation is used to measure incremental excitation inductance and the nonlinear excitation curve is calculated based on this inductance. Furthermore, the allocation method of this curve in the core limb, side limb, and yoke is proposed to establish the converter transformer model. The results of no-load and inrush current tests based on the scaled model validate the effectiveness of this model, which can accurately calculate the inrush current under different remanence and closing conditions. Full article

It was reported that polyphenols extracted from Korean Artemisia annua L. (pKAL) have higher anticancer effects in oxaliplatin-resistant (OxPt-R) HCT116 cells than in HCT116 cells. In this study, it was tested whether and how As₄O₆ enhances anticancer effects of pKAL in HCT116 and HCT116-OxPt-R colorectal cancer cells. The CCK-8 assay, phase-contrast microscopy, and colony formation assay revealed that As₄O₆ enhanced anticancer effects of pKAL, with induction of nuclear deformity and intracytoplasmic vesicle formation in both cells. Western blot analysis revealed that co-treatment with As₄O₆ and pKAL significantly decreased the expression of NF-kB, EGFR, cyclin D1, CD44, and β-catenin, and upregulated the expression of p62 and LC3B in both cells. It also induced the activation of caspase-8 and γ-H2AX and the cleavage of β-catenin, PARP1, lamin A/C, and p62. These phenomena were inhibited by wortmannin, and further suppressed by co-treatment of wortmannin with an ROS inhibitor, N-acetyl cysteine. This study suggests that As₄O₆ enhanced the anticancer effects of pKAL by inducing autophagic cell death accompanied by apoptosis in both parental HCT116 and HCT116-OxPt-R cells. It also suggests that ROS generation and the downregulation of AKT, NF-κB p65, cyclin D1, EGFR, and β-catenin may play an important role in the As₄O₆-enhanced anticancer effect of pKAL. Full article

Background: Laminopathies are a heterogenous group of heritable diseases caused by variants in the Lamin A/C gene (LMNA). They manifest as cardiac and muscular myopathies, lipodystrophies, neuropathies, and progeria. Cardiac manifestations include dilated cardiomyopathy and arrhythmias. Case presentation: A Finnish woman in her 40s who was found to carry two heterozygous likely pathogenic (LP) variants in LMNA, c.1003C>T p.Arg335Trp and c.1303C>T p.Arg435Cys. She was diagnosed with dilated cardiomyopathy and received cardiac resynchronization therapy with a defibrillator. Conclusions: Double heterozygous LMNA variants are exceedingly rare. Even though the patient presented with two LP variants, the age of onset was typical, and the phenotype was not markedly more severe than in those with only one LP variant. Full article

A giant magnetoelectric coefficient has been discovered in laminated magnetoelectric composites incorporating piezoelectric and magnetostrictive layers, which reveals a high sensitivity in AC magnetic field detection under a DC bias field. However, the DC-biased magnetoelectric composites are not capable of detecting DC magnetic fields due to the interference with the DC signal to be measured. Here, we demonstrate a portable magnetoelectric gaussmeter based on torque effect that can detect both DC and AC magnetic fields. The proposed gaussmeter is equipped with a magnetoelectric sensor, a charge amplification module, a signal processing circuit, a power module, a data processing program, a display module, etc. The proposed gaussmeter indicates such performance indexes as an intensity range of 0~10 Oe, frequency range of DC~500 Hz, AC detection limit of 0.01 Oe, DC detection limit of 0.08 Oe, and frequency resolution of 1 Hz. Being powered by a power adapter (or a battery) of 5V 2A, the whole device system is pocket-size, low-cost, and highly portable, demonstrating its potential for magnetic field detection as a distributed sensor. Full article

Background and Objectives: The pathophysiology of arrhythmogenic cardiomyopathy (ACM), previously known as arrhythmogenic right ventricular cardiomyopathy (ARVC), and its specific biological features remain poorly understood. High-throughput plasma proteomic profiling, a powerful tool for gaining insights into disease pathophysiology at the systems biology level, has not been used to study ACM. This study aimed at characterizing plasmatic protein changes in patients with ACM, which were compared with those of healthy controls, and at exploring the potential role of the identified proteins as biomarkers for diagnosis and monitoring. Materials and Methods: Blood samples were collected from six ACM patients, four patients with other cardiomyopathies, and two healthy controls. Plasma was processed to remove high-abundance proteins and analyzed by two-dimensional gel electrophoresis. Differential protein expressions were assessed using PDQuest software, Bio-Rad US version 8.0.1. Results: The analysis revealed several proteins with altered expressions between ACM patients and controls, including plakophilin-2, junctional plakoglobin, desmoplakin, desmin, transmembrane protein 43, and lamin A/C. Conclusions: The plasma proteomic profiling of ACM suggests that ACM is a distinct disease entity characterized by a unique dysregulation of desmosomal proteins. The identification of plasma biomarkers associated with ACM underscores their potential to improve diagnostic accuracy and facilitate early intervention strategies. Further exploration of mutations in desmosomal proteins and their phosphorylation states may provide deeper insights into the pathophysiology of ACM. Full article

The use of segmented stator and rotor designs in AC electric machine construction offers several significant advantages, including a high-copper fill factor, increased torque density, improved field-weakening performance, simplified manufacturing processes, and enhanced mechanical strength. Additionally, segmented designs allow for the incorporation of oriented steel—either partially or fully—which exhibits excellent magnetic properties in the rolling direction, resulting in more efficient machine performance. However, lamination segmentation also introduces challenges. Parasitic air gaps between segments and an increased number of cut edges in the assembled stack can alter the magnetic properties of the machine, potentially leading to degraded performance. Furthermore, the use of oriented steel remains complex, as its highly nonlinear magnetic properties vary depending on the direction of the magnetic flux. This paper reviews the widely adopted stator and rotor segmentation techniques available in the literature, discussing their potential benefits and limitations. It also covers key aspects such as popular manufacturing approaches, the impact of segmentation on machine performance, advanced finite-element analysis (FEA) techniques for numerical modeling, and experimental methods for evaluating the performance of segmented stator and rotor constructions in AC machines. By addressing these areas, this work provides a comprehensive resource for machine designers seeking to develop AC machines with segmented stators and rotors. Full article

A growing body of evidence suggests that actin plays a role in nuclear architecture, genome organisation, and regulation. Our study of human lung adenocarcinoma cells demonstrates that the equilibrium between actin isoforms affects the composition of the nuclear lamina, which in turn influences nuclear stiffness and cellular behaviour. The downregulation of β-actin resulted in an increase in nuclear area, accompanied by a decrease in A-type lamins and an enhancement in lamin B2. In contrast, the suppression of γ-actin led to upregulation of the lamin A/B ratio through an increase in A-type lamins. Histone H3 post-translational modifications display distinct patterns in response to decreased actin isoform expression. The level of dimethylated H3K9me2 declined while acetylated H3K9ac increased in β-actin-depleted A549 cells. In contrast, the inhibition of γ-actin expression resulted in a reduction in H3K9ac. Based on our observations, we propose that β-actin plays a role in chromatin compaction and deactivation, and is involved in the elevation of nuclear stiffness through the control of the lamins ratio. The non-muscle γ-actin is presumably responsible for chromatin decondensation and activation. The identification of novel functions for actin isoforms offers insights into the mechanisms through which they influence cell fate during development and cancer progression. Full article

Laminopathies represent a wide range of genetic disorders caused by mutations in gene-encoding proteins of the nuclear lamina. Altered nuclear mechanics have been associated with laminopathies, given the key role of nuclear lamins as mechanosensitive proteins involved in the mechanotransduction process. To shed light on the nuclear partners cooperating with altered lamins, we focused on Src tyrosine kinase, known to phosphorylate proteins of the nuclear lamina. Here, we demonstrated a tight relationship between lamin A/C and Src in skin fibroblasts from two laminopathic patients, assessed by advanced imaging-based microscopy techniques. With confocal laser scanning and Stimulated Emission Depletion (STED) microscopy, a statistically significant higher co-distribution between the two proteins was observed in patients’ fibroblasts. Furthermore, the time-domain fluorescence lifetime imaging microscopy, combined with Förster resonance energy transfer detection, demonstrated a decreased lifetime value of Src (as donor fluorophore) in the presence of lamin A/C (as acceptor dye) in double-stained fibroblast nuclei in both healthy cells and patients’ cells, thereby indicating a molecular interaction that resulted significantly higher in laminopathic cells. All these results demonstrate a molecular interaction between Src and lamin A/C in healthy fibroblasts and their aberrant interaction in laminopathic nuclei, thus creating the possibilities of new diagnostic and therapeutic approaches for patients. Full article

The reliability of components of industrial electrical assets fed by power electronics might be at risk due to the type and extent of electrothermal stresses. The move of power electronics toward higher levels of voltage, switching frequency, slew rate, and specific power increases the risk of partial discharge inception and thus of accelerated extrinsic aging and premature failure. The reaction to this challenge is to embrace the concept of partial discharge-free (PD-free) design and operation. This paper presents a PD-free approach to the design of laminated busbars, considering both AC and DC insulation subsystems, and focusing on surface insulation. The availability of a recently proposed model to estimate the inception field is a key tool. The model is validated through PD measurements performed on a laminated busbar, using new automatic software that can identify the type of source generating PD. Combined with electric field calculations, the model provides estimates of the PD inception voltage which are almost coincident with the measurement results. Inception voltages in the order of 10 kV and 20 kV have been observed for AC and DC excitation, respectively. In the case of DC supply, tests at different ambient temperatures, 25 °C and 60 °C, indicate that the inception voltage does not change significantly with temperature. Disposability, scalability to any voltage/power, and capability to work, potentially, for any other type of insulation system, are interesting features of the proposed approach, which are discussed in the paper. Full article

The bi- or multinucleated Reed–Sternberg cell (RS) is the diagnostic cornerstone of Epstein–Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: (i) to be of GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL. Full article