Search Results (134)

Nuclear lamins are the core molecular bridge linking the extracellular mechanical microenvironment to intranuclear gene regulation, and play a central regulatory role in cellular mechanosensation and mechanotransduction. Here, we systematically integrate the latest global research progress on nuclear lamins, delineating the cascade regulatory mechanism by which lamins mediate the transmission of mechanical signals across the nuclear envelope and the subsequent regulation of chromatin remodeling and epigenetic modification, with a focus on the molecular characteristics and functional specificity of distinct nuclear lamin subtypes and their interaction modes with the Linker of Nucleoskeleton and Cytoskeleton complex (LINC complex) and chromatin. Existing studies have established that nuclear lamins are mainly divided into three categories: A-type lamins (Lamin A/C), B-type lamins (Lamin B1, B2), and germ cell-specific subtypes. Among these, A-type lamins directly determine the mechanical stiffness of the nucleus and serve as the core mediators of intranuclear mechanical signal transduction. Each subtype of B-type nuclear lamins has a well-defined, non-redundant functional division: Lamin B1 and Lamin B2 indirectly maintain nuclear structural stability and regulate epigenetic status by anchoring facultative heterochromatin and constitutive heterochromatin, respectively. Notably, Lamin A/C distributed in the nucleoplasm also bears significant mechanical tension, which challenges the long-standing view that the mechanical functions of nuclear lamins are restricted to the nuclear envelope region. After mechanical force is transmitted across the nuclear envelope to nuclear lamins via the LINC complex, it can regulate the spatial conformation of chromatin and epigenetic modifications, thereby determining core cellular life activities including proliferation, differentiation, and migration. Dysregulation of this pathway is closely associated with a wide spectrum of human diseases, including cardiovascular diseases, progeria, muscular dystrophy, and neurodevelopmental disorders. Taken together, this review systematically delineates the hierarchical regulatory network of the “LINC complex–nuclear lamina–chromatin” axis, advances our understanding of the fundamental principles of cellular mechanobiology, and provides a theoretical framework for deciphering the pathological mechanisms and developing targeted therapeutic drugs for related diseases. Full article

Lamin A/C is emerging as a promising candidate regulator at the intersection of nuclear mechanics, chromatin organization, and gene regulation, linking structure and regulation, mechanics and epigenetics, constraint and plasticity. Lamin A/C was previously considered a static structural scaffold; however, it is now recognized as a dynamic component of nuclear organization that links physical cues to epigenetic and transcriptional states. Lamin A/C regulates three-dimensional genome structure, constrains chromatin mobility, and influences cell transitions between plastic and committed states through its interactions with heterochromatin at the nuclear periphery and active chromatin domains in the nuclear interior. In cancer, these functions appear to be dependent on the context. Lamin A/C has been implicated in crucial biological processes, including invasion, survival under mechanical stress, lineage plasticity, and therapeutic response. Its prognostic value varies across tumor types. This heterogeneity indicates that lamin A/C does not function as a traditional oncogene or oncosuppressor; instead, it operates as a nuclear rheostat, influencing the behavior and development of tumor cells. This review examines the potential clinical benefits of lamin A/C while considering its implications for normal tissue functions. It aims to improve understanding of cellular adaptability and vulnerability in cancer through the exploration of lamin A/C biology. Full article

Background/Objectives: Recurrences and metastases occur frequently in chordoma and are the main factors influencing overall survival. However, prognostic biomarkers for recurrence remain limited. This study examines whether quantitative nuclear morphometry can capture recurrence evolution and whether it aligns with immunophenotype and genomic profiling. Methods: A total of 26 specimens from 12 adults (8 patients with non-recurrent tumors and 4 patients with multiple long-term recurrences and metastases over 7 to 16 years) were analyzed using whole-exome sequencing, immunohistochemistry, and nuclear morphometry. Results: Imaging studies and routine histology showed no consistent differences between groups. Morphometry revealed substantial intertumoral variability among non-recurrent tumors and significant longitudinal nuclear remodeling throughout recurrences, dominated by increased nuclear size and asymmetry, as well as altered shape. Primary tumors from patients who later recurred had smaller, more asymmetric, and denser nuclei than non-recurrent tumors. Recurrent samples showed higher proliferation and decreased lamin A/C expression, with focal disruption and detachment from the nuclear envelope in pleomorphic nuclei. The tumor mutational burden was low overall, varied between patients and timepoints, and tended to be higher in recurrent cases. Conclusions: Quantitative nuclear morphometry, integrated with immunophenotyping and genomic profiling, captures recurrence-associated phenotypic remodeling in chordoma and may provide a quantitative framework for future digital pathology or AI approaches, pending validation in larger cohorts. Full article

Myocarditis is a complex inflammatory myocardial disease. Although traditionally regarded as exclusively immune-mediated, recent evidence highlights the significant role of underlying genetics on susceptibility, phenotypic variability, and long-term prognosis. This narrative review examines the evolving genetic architecture of myocarditis and its relationship to inherited cardiomyopathies, integrating mechanistic insights from molecular, imaging, and clinical studies. Variants in desmosomal genes such as desmoplakin (DSP) and plakophilin-2 (PKP2) are increasingly linked to recurrent myocarditis that may evolve into arrhythmogenic cardiomyopathy, supporting the concept of a genetically predisposed myocardium in which inflammatory stressors can act as triggers. Truncating variants in titin (TTN) and Filamin C (FLNC) are associated with fulminant or dilated phenotypes. Conversely, mutations in Lamin A/C (LMNA), Desmin (DES), and BCL2-Associated Athanogene 3 (BAG3) contribute to inflammatory myocardial remodeling and other forms of inherited cardiomyopathies. These findings collectively have the potential to redefine myocarditis as an inflammatory disorder influenced by genetic factors. Furthermore, advancements in genetic testing and multi-omics approaches show promise in enhancing diagnostic accuracy and informing management strategies. Full article

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