Search Results (21,164)

The transition to electric mobility has intensified efforts to develop battery technologies that are not only high-performing but also environmentally sustainable. A critical element in battery system design is the structural housing, which must provide effective impact protection to ensure passenger safety and prevent catastrophic failures. This study examines the impact response of an innovative sheet molding compound (SMC) composite battery housing, manufactured from an Elium resin modified with Martinal ATH matrix, reinforced with glass fibers, that combines fire resistance and recyclability, unlike conventional thermoset and metallic housings. The material was characterized through standardized mechanical tests, and its impact performance was evaluated via drop-weight experiments on plates and a full-scale housing. The impact tests were conducted at varying energy levels to induce barely visible impact damage (BVID) and visible impact damage (VID). A finite element model was developed in LS-DYNA using the experimentally derived material properties and was validated against the impact tests. Parametric simulations of ground and pole collisions revealed the critical velocity thresholds at which housing deformation begins to affect the first battery cells, while lower-energy impacts were absorbed without compromising the pack. The study provides one of the first combined experimental and numerical assessments of Elium SMC in battery enclosures, emphasizing its potential as a sustainable alternative for next-generation battery systems for transport applications. Full article

Introduction: Gastrointestinal stromal tumors (GISTs) are primarily driven by mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) or PDGFRA (platelet-derived growth factor receptor alpha), but resistance to tyrosine kinase inhibitors (TKIs) such as imatinib remains a major clinical challenge. Alterations in fibroblast growth factor receptor 2 (FGFR2), although rare, are emerging as important contributors to tumor progression and drug resistance. This review evaluates the molecular mechanisms, expression profiles, detection methods, and therapeutic implications of FGFR2 in GIST. Methods: We searched PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for studies published between January 2010 and June 2025, using combinations of keywords related to FGFR2, gastrointestinal stromal tumor, resistance mechanisms, gene fusion, amplification, polymorphisms, and targeted therapy. Eligible studies were critically assessed to distinguish GIST-specific data from evidence extrapolated from other cancers. Results:FGFR2 is expressed in multiple normal tissues and at variable levels in mesenchymal-derived tumors, including GIST. Its alterations occur in approximately 1–2% of GIST cases, most commonly as gene fusions (e.g., FGFR2::TACC2, <1%) or amplifications (1–2%); point mutations and clinically significant polymorphisms are extremely rare. These alterations activate the MAPK/ERK and PI3K/AKT pathways, contribute to bypass signaling, and enhance DNA damage repair, thereby promoting TKI resistance. Beyond mutations, mechanisms such as amplification, ligand overexpression, and microenvironmental interactions also play roles. FGFR2 alterations appear mutually exclusive with KIT/PDGFRA mutations but occasional co-occurrence has been reported. Current clinical evidence is largely limited to small cohorts, basket trials, or case reports. Conclusions:FGFR2 is an emerging oncogenic driver and biomarker of resistance in a rare subset of GISTs. Although direct evidence remains limited, particularly regarding DNA repair and polymorphisms, FGFR2-targeted therapies (e.g., erdafitinib, pemigatinib) show potential, especially in combination with TKIs or DNA-damaging agents. Future research should prioritize GIST-specific clinical trials, the development of FGFR2-driven models, and standardized molecular diagnostics to validate FGFR2 as a therapeutic target. Full article

In conventional mechanized garlic seeding process, seed remains a persistent challenge that is difficult to avoid. This study proposes a solution by designing and testing a garlic seeding device based on a rigid–flexible coupling mechanism, aimed at minimizing seed damage during sowing. The seeding pocket was constructed from a flexible metal sheet, which served as its structural foundation. A slider moving along a fixed track enabled the retraction and release of the pocket, thereby facilitating seed collection and discharge. The effects of pocket radius, rotational speed of seed discharge disc, and thickness of metal sheet on the stress of garlic seeds were investigated through the finite element method. Subsequently, an experimental bench was set up to analyze the effects of influence of these parameters on seed damage rate, single-seed rate, and leakage rate. Results demonstrated that under optimal parameters—a pocket radius of 12 mm, a seed discharge disc rotational speed of 0.21 rad/s, and a metal sheet thickness of 0.15 mm—the mechanism achieved a single-seed rate of 78.4%, a leakage rate of 11.4%, and a maximum stress on garlic seeds of only 0.535 MPa. Notably, this stress level was well below the damage threshold of garlic seeds, resulting in zero damage that outperformed conventional rigid seeding devices. These findings demonstrate the mechanism’s strong potential to preserve seed integrity, although the overall seeding performance remains modest and warrants further optimization in future designs. Full article

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus, Romboutsia, and Enterobacter. Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC. Full article

Treatment for acute liver failure (ALF) is constrained by shortages of liver transplant donors and immune rejection. Porcine bone marrow mesenchymal stem cells (pBMSCs) demonstrate clinical potential in xenotransplantation due to their abundant availability, low immunogenicity, and strong proliferative activity. This study is the first to investigate the reparative effects and mechanisms of pBMSCs derived from Luopan Mountain pigs in a D-galactosamine (D-GalN)-induced ALF rat model. The results demonstrated that tail-vein transplantation of pBMSCs significantly improved survival rates in ALF rats; reduced serum ALT, AST, and TBIL levels; enhanced hepatic glycogen metabolism; and mitigated histopathological liver damage. Additionally, pBMSC transplantation upregulated serum HGF, IGF-1, and VEGF levels while inhibiting hepatocyte apoptosis. Mechanistic studies indicate that pBMSCs promote liver function recovery and regeneration by activating the PI3K/Akt/mTOR signaling pathway and suppressing its key negative regulator, PTEN, by regulating the expression of key genes involved in inflammation, fibrosis, proliferation, and apoptosis. This study provides crucial experimental evidence for the use of pBMSCs in treating acute liver failure (ALF) and lays the groundwork for its clinical translation in the field of xenotransplantation. Full article

Extracellular vesicles (EVs) secreted by glioblastoma multiforme and other types of cancer cells are key factors contributing to the aggressiveness of the disease and its resistance to therapy. Chloroquine (CHQ), a lysosomal inhibitor, has shown potential as an enhancer of temozolomide (TMZ) cytotoxicity against glioblastoma cells. Since both CHQ and TMZ are known to modulate EV secretion, we sought to investigate their potential interplay in this process. Simultaneous treatment of TMZ-sensitive (U87-MG) and TMZ-resistant (U138-MG) glioblastoma cells with TMZ and CHQ led to a synergistic upregulation of EV secretion. Although CHQ did not enhance the TMZ cytotoxicity in U87-MG cells, it synergized with the latter to upregulate the release of extracellular nucleic acids implicating activation of unconventional secretory pathways. Synergistic upregulation of the autophagy markers LC3B-II and p62 by CHQ and TMZ in both cells and EVs indicates that secretory autophagy is likely involved in the observed unconventional secretion. Moreover, a significant enrichment of caveolin-1 in small EVs highlights their potential role in modulating tumor aggressiveness. The synergy in EV upregulation was not confined to the specific biological activity of TMZ and CHQ; similar effects were observed upon co-treatments with CHQ and etoposide (a topoisomerase inhibitor) and TMZ and Bafilomycin A1 (another lysosomal inhibitor). Heightened EV release was also observed in THP-1 monocytes and macrophages treated with Bafilomycin and TMZ, highlighting a broader, cell-type-independent mechanism. These findings indicate that combined DNA damage and lysosomal inhibition synergistically stimulate secretory autophagy and EV release, potentially impacting the tumor microenvironment and driving disease progression. Full article

Diabetic retinopathy (DR) is a leading cause of vision loss globally and represents one of the most common microvascular complications of diabetes. In addition to metabolic disturbances associated with hyperglycemia, oxidative stress has emerged as a critical contributor to the onset and progression of DR. Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms, leads to cellular injury, inflammation, and increased vascular permeability. In the diabetic retina, excessive ROS production promotes endothelial cell apoptosis, breakdown of the blood-retinal barrier (BRB), and induction of angiogenic factors such as vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of the pathophysiology of DR, focusing on the molecular mechanisms of oxidative stress. Relevant studies were identified through a structured search of PubMed, Web of Science, and Scopus (2000–2025) using terms such as ‘diabetic retinopathy’, ‘oxidative stress’, and ‘antioxidants’. We explore current knowledge on oxidative stress-related biomarkers and therapeutic strategies targeting oxidative damage, including antioxidant compounds and mitochondrial protective agents. Recent findings from both experimental and clinical studies are summarized, highlighting the translational potential of oxidative stress modulation in DR management. Finally, future research directions are discussed, including biomarker standardization, personalized medicine approaches, and long-term clinical validation of antioxidant-based therapies. A deeper understanding of oxidative stress may offer valuable insights into novel diagnostic and therapeutic strategies for DR. Full article

Nickel (Ni) is a heavy metal element and environmental pollutant that significantly threatens human health. Selenoprotein M (SelM) is a selenium-containing protein with antioxidant properties. However, the role of SelM deficiency in Ni -induced colonic tissue damage in mice remains unclear. To address this, in vivo and in vitro models were established, including SelM knockout (SelM^(−/−)) and/or nickel chloride (NiCl₂)-treated mice. In vitro, an MCEC model was used to establish Ni exposure and SelM knockdown conditions. The results showed that NiCl₂ induced significant inflammatory cell infiltration and lesions in the microstructure of the mouse colon. Additionally, Ni exposure was found to enhance the production of reactive oxygen species (ROS) in mice’s colonic tissue, activating oxidative stress, which in turn led to the formation of autophagosomes and the onset of inflammation. Significantly, SelM knockout exacerbated these outcomes. The oxidative stress inhibitor NAC and the autophagy inhibitor 3-MA were introduced to elucidate the underlying mechanisms further. The results showed that autophagy was reduced following NAC treatment, and inflammation was alleviated after 3-MA administration. Taken together, these findings suggest that SelM alleviated Ni -induced colonic inflammation in mice through suppression of oxidative stress-mediated excessive autophagy. Full article

Cellular senescence, a state of stable cell cycle arrest accompanied by a complex senescence-associated secretory phenotype (SASP), is a fundamental biological process implicated as a key driver of lung aging and lung age-related diseases (LARDs). This review provides a comprehensive overview of the rapidly evolving field of senotyping based on cellular heterogeneity in lung development and aging in health and disease. It also delves into the molecular mechanisms driving senescence and SASP production, highlighting pathways such as p53/p21, p16^INK4a/RB, mTOR, and p38 MAPK as therapeutic targets. The involvement of various novel SASP proteins, such as GDP15, cytokines/chemokines, growth factors, and DNA damage response proteins. We further highlight the effectiveness of senotherapeutics in mitigating the detrimental effects of senescent cell (SnC) accumulation within the lungs. It also outlines two main therapeutic approaches: senolytics, which selectively trigger apoptosis in SnCs, and senomorphics (also known as senostatics), which mitigate the detrimental effects of the SASP without necessarily removing the senescent cells. Various classes of senolytic and senomorphic drugs are currently in clinical trials including natural products (e.g., quercetin, fisetin, resveratrol) and repurposed drugs (e.g., dasatinib, navitoclax, metformin, rapamycin) that has demonstrated therapeutic promise in improving tissue function, alleviating LARDs, and extending health span. We discuss the future of these strategies in lung research and further elaborate upon the usability of novel approaches including HSP90 inhibitors, senolytic CAR-T cells, Antibody drug conjugate and galactose-modified prodrugs in influencing the field of personalized medicine in future. Overall, this comprehensive review highlights the progress made so far and the challenges faced in the field of cellular senescence including SnC heterogeneity, states of senescence, senotyping, immunosenescence, drug delivery, target specificity, long-term safety, and the need for robust cell-based biomarkers. Future perspectives, such as advanced delivery systems, and combination therapies, are considered critical for translating the potential of senotherapeutics into effective clinical applications for age-related pulmonary diseases/conditions. Full article

The construction of large-scale infrastructure, such as power facilities, requires extensive use of reinforced concrete. The durability degradation of reinforced concrete structures in chloride environments involves multi-physics coupling effects, chloride ion diffusion, rebar corrosion, and concrete damage. Existing models neglect the coupling mechanisms among these processes and the influence of mesoscale structural characteristics. Therefore, this study proposes a diffusive–mechanical coupled phase field by integrating the phase field, chloride ion diffusion, and mechanical equivalence for rebar corrosion, establishing a multi-physics coupling analysis framework at the mesoscale. The model incorporates heterogeneous meso-structure of concrete and constructs a dynamic coupling function between the phase field damage variable and chloride diffusion coefficient, enabling full-process simulation of corrosion-induced cracking under chloride erosion. Numerical results demonstrate that mesoscale heterogeneity significantly affects crack propagation paths, with increased aggregate content delaying the initiation of rebar corrosion. Moreover, the case with corner-positioned rebar exhibits earlier cracking compared to the case with centrally located rebar. Furthermore, larger clear spacing delays delamination failure. Comparisons with the damage mechanics model and experimental data confirm that the proposed model more accurately captures tortuous crack propagation behavior, especially suitable for evaluating the durability of reinforced concrete components in facilities such as transmission tower foundations, substation structures, and marine power facilities. This research provides a highly accurate numerical tool for predicting the service life of reinforced concrete power infrastructure in chloride environments. Full article

High-pressure, high-volume fracturing in unconventional reservoirs often induces perforation erosion damage, endangering operational safety. This paper employs fluid–solid coupling theory to analyze the flow characteristics of fracturing fluid inside the casing during fracturing. Combined with strength theory, the stress distribution and variation law are investigated, revealing the mechanical mechanism of casing perforation erosion damage. The results indicate that the structural discontinuity at the entrance of the perforation tunnel causes an increase in fracturing-fluid velocity, and this is where the most severe erosion happens. The stress around the perforation is symmetrically distributed along the perforation axis. The casing inner wall experiences a combined tensile–compressive stress state, while non-perforated regions are under pure tensile stress, with the maximum amplitudes occurring in the 90° and 270° directions. Although the tensile and compressive stress do not exceed the material’s allowable stress, the shear stress exceeds the allowable shear stress, indicating that shear stress failure is likely to initiate at the perforation, inducing erosion. Moreover, under the impact of fracturing fluid, the contact forces at the first and second interfaces of the casing are unevenly distributed, reducing cement bonding capability and compromising casing integrity. The findings provide a theoretical basis for optimizing casing selection. Full article

The durability of asphalt concrete is highly dependent on the geometry and mineralogy of coarse aggregates, yet their combined influence on mechanical and moisture resistance properties is still not fully understood. This study evaluates the effects of coarse aggregate geometry, specifically flat and elongated particle ratios and angularity, as well as mineral composition (quartz versus calcite), on asphalt mixture durability. The durability of mixtures was evaluated through Marshall properties as well as moisture susceptibility indicators, including the tensile strength ratio (TSR) and index of retained strength (IRS). Statistical analyses (ANOVA and t-tests) were also conducted to confirm the significance of the observed effects. Results showed that mixtures containing higher proportions of flat and elongated particles exhibited greater void content, reduced stability, and weaker moisture resistance, with the 1:5 flat-to-elongated ratio showing the most adverse impact (TSR 73.9%, IRS 69.2%). Conversely, increasing coarse aggregate angularity (CAA) enhanced mixture performance, with TSR values rising from 63.5% at 0% angularity to 81.2% at 100% angularity, accompanied by corresponding improvements in IRS. Mineral composition analysis further demonstrated that calcite-based aggregates achieved stronger bonding with asphalt binder and superior resistance to stripping compared to quartz-based ones. These findings confirm that aggregate geometry and mineralogy exert a decisive influence on asphalt mixture durability. They also highlight the need to revise current specifications that permit the use of uncrushed coarse aggregate in asphalt base courses, particularly when such layers may serve as surface courses in suburban or low-volume roads, where long-term resistance to moisture damage is critical. Full article

Background: Antibody-drug conjugates (ADCs) have ushered in a new era of precision oncology by combining the targeting specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic drugs. However, the cellular and molecular mechanisms underlying their dose-limiting ocular toxicity remain unclear. Elahere™, the first FDA-approved ADC targeting folate receptor α (FRα), demonstrates remarkable efficacy in platinum-resistant ovarian cancer but causes keratitis and other ocular toxicities in some patients. Notably, FRα is not expressed in the corneal epithelium—the primary site of damage—highlighting the urgent need to elucidate its underlying mechanisms. The aim of this study was to identify the cell-type-specific molecular mechanisms underlying Elahere-induced ocular toxicity. Methods: Sprague-Dawley rats were treated with intravenous Elahere (20 mg/kg) or vehicle weekly for five weeks. Ocular toxicity was determined by clinical examination and histopathology. Corneal single-cell suspensions were analyzed using the BD Rhapsody single-cell RNA sequencing (scRNA-seq) platform. Bioinformatic analyses to characterize changes in corneal cell populations, gene expression, and signaling pathways included cell clustering, differential gene expression, pseudotime trajectory inference, and cell-cell interaction modeling. Results: scRNA-seq profiling of 47,606 corneal cells revealed significant damage to the ocular surface and corneal epithelia in the Elahere group. Twenty distinct cell types were identified. Elahere depleted myeloid immune cells; in particular, homeostatic gene expression was suppressed in phagocytic macrophages. Progenitor populations (limbal stem cells and basal cells) accumulated (e.g., a ~2.6-fold expansion of limbal stem cells), while terminally differentiated cells decreased in corneal epithelium, indicating differentiation blockade. Endothelial cells exhibited signs of injury and inflammation, including reduced angiogenic subtypes and heightened stress responses. Folate receptor alpha, the target of Elahere, was expressed in endothelial and stromal cells, potentially driving stromal cells toward a pro-fibrotic phenotype. Fc receptor genes were predominantly expressed in myeloid cells, suggesting a potential mechanism underlying their depletion. Conclusions: Elahere induces complex, multi-compartmental ocular toxicity characterized by initial perturbations in vascular endothelial and immune cell populations followed by the arrest of epithelial differentiation and stromal remodeling. These findings reveal a cascade of cellular disruptions and provide mechanistic insights into mitigating Elahere-associated ocular side effects. Full article

The long-distance high-voltage transmission tower-line system, frequently traversing active fault zones, is vulnerable to severe symmetry-breaking damage during earthquakes due to asymmetric permanent ground displacements. However, the seismic performance of such systems, particularly concerning symmetry-breaking effects caused by asymmetric fault displacements, remains inadequately studied. This study investigates the symmetry degradation mechanisms in a 1:40 scaled 500 kV tower-line system subjected to cross-fault ground motions via shaking table tests. The testing protocol incorporates representative fault mechanisms—strike-slip and normal/reverse faults—to systematically evaluate their differential impacts on symmetry response. Measurements of acceleration, strain, and displacement reveal that while acceleration responses are spectrally controlled, structural damage is highly fault-type dependent and markedly asymmetric. The acceleration of towers without permanent displacement was 35–50% lower than that of towers with permanent displacement. Under identical permanent displacement conditions, peak displacements caused by normal/reverse motions exceeded those from strike-slip motions by 50–100%. Accordingly, a fault-type-specific amplification factor of 1.5 is proposed for the design of towers in dip-slip fault zones. These results offer novel experimental insights into symmetry violation under fault ruptures, including fault-specific correction factors and asymmetry-resistant design strategies. However, the conclusions are subject to limitations such as scale effects and the exclusion of vertical ground motion components. Full article

Background and Objectives: Sensorineural hearing loss (SNHL) is influenced by various causes, including thyroid diseases. For example, hypothyroidism and thyroid autoimmunity can damage the inner ear through hormonal, immune, and vascular mechanisms. Vestibular disorders like Ménière’s disease (MD) and benign paroxysmal positional vertigo (BPPV) also show possible associations with thyroid dysfunction. Materials and Methods: A review following PRISMA guidelines searched PubMed, Scopus, and Google Scholar for studies linking thyroid disorders with inner ear dysfunction. Results: Out of 985 screened records, 30 studies met inclusion criteria, involving various thyroid disorders, primarily hypothyroidism and autoimmune thyroiditis. Scientific evidence supports a correlation between hypothyroidism and hearing impairment. However, some studies also suggest a link between hyperthyroidism and inner ear disorders, particularly focusing on the role of autoimmunity in this context. Concerning vestibular dysfunction, the available studies are less abundant and support a significant association between thyroid disease and Meniere’s disease. Conclusions: There is a clear correlation between hypothyroidism and auditory function. A substantial body of literature also supports an association with vestibular disorders, although some discrepancies remain. Further research is needed to elucidate the underlying pathophysiological mechanisms (e.g., autoimmune, vascular, metabolic) involved with this correlation. Full article