Search Results (323)

Dental enamel exhibits a unique combination of high hardness and high toughness. This outstanding mechanical property is closely tied to its multi-scale hierarchical structure. In this study, rat tooth enamel was selected as the research object, the different structural layers and mechanical properties of tooth enamel were investigated and characterized experimentally. The multi-scale mechanical models with different structural layers were developed and analyzed using numerical simulations. The research results indicate that, regarding the load-bearing mechanism, the outer layer of tooth enamel consists of hydroxyapatite crystal bundles arranged in parallel and inclined orientations, and this structural feature enables it to exhibit excellent elastic modulus and resistance to deformation, while the inner layer with cross-arranged crystal bundles shows different mechanical response characteristics. In terms of crack propagation behavior, the outer layer is more prone to crack initiation due to the consistency of crystal orientation, and the cracks tend to extend in a straight line, while the unique cross arrangement of crystals in the inner layer can effectively inhibit crack propagation by inducing crack deflection and branching mechanisms, thus demonstrating more excellent fracture toughness. This “outer hard and inner flexible” gradient structure design elucidates the synergistic mechanism between crystal orientation and crack propagation behavior in tooth enamel, offering significant design insights for biomimetic composite materials. Full article

This work reports the performance evaluation of a newly developed small-animal positron emission tomography (PET) system based on lutetium-yttrium oxyorthosilicate (LYSO) crystals and multi-pixel photon counter (MPPC). Performance was evaluated, including spatial resolution, system sensitivity, energy resolution, scatter fraction (SF), noise–equivalent count rate (NECR), micro-Derenzo phantom imaging, and in vivo imaging of mice and rats. The system achieved a tangential spatial resolution of 0.9 mm in the axial direction at a quarter axial offset using the three-dimensional ordered-subsets expectation maximization (3D OSEM) reconstruction algorithm. The peak sensitivity was 8.74% within a 200–750 keV energy window, with an average energy resolution of 12.5%. Scatter fractions were 12.9% and 30.0% for mouse- and rat-like phantoms, respectively. The NECR reached 878.7 kcps at 57.6 MBq for the mouse phantom and 421.4 kcps at 63.2 MBq for the rat phantom. High-resolution phantom and in vivo images confirmed the system’s capability for quantitative, high-sensitivity small-animal imaging, demonstrating its potential for preclinical molecular imaging studies. Full article

Background: Acute lung injury (ALI) is a life-threatening respiratory condition and one of the leading causes of mortality worldwide, accounting for approximately 20% of global annual deaths. Despite its high prevalence and severity, effective therapeutic options remain limited. Eupatorium lindleyanum DC., a traditional medicinal herb, has demonstrated therapeutic potential against pulmonary diseases, particularly ALI, in both clinical and experimental settings. However, the protective effects and underlying mechanisms of its characteristic sesquiterpene lactone components against ALI remain unclear. Objective: This study aimed to evaluate the protective effects of sesquiterpene lactones from Eupatorium lindleyanum DC. (SLEL) against lipopolysaccharide (LPS)-induced ALI both in vivo and in vitro. Furthermore, it sought to elucidate the underlying mechanisms by integrating network pharmacology, multi-omics approaches (transcriptomics, metabolomics, and 16S rRNA sequencing), and various molecular biology techniques. Results: SLEL significantly attenuated inflammatory injury in alveolar epithelial cells and alleviated pulmonary edema, hemorrhage, and inflammatory infiltration in rats, accompanied by reduced TNF-α, IL-6, and IL-1β levels and improved lung injury indices. Mechanistically, SLEL exerted dual suppression of the PI3K-Akt and MAPK-NF-κB pathways. Network pharmacology, molecular docking, and UPLC-MS analyses identified Eupalinolide A and Eupalinolide K as potential bioactive constituents, which were further validated to inhibit phosphorylation of key signaling proteins, thereby partially accounting for SLEL’s pharmacological effects. Multi-omics integration further revealed that SLEL restored bile acid metabolism, reshaped gut microbial diversity, and reconstructed the microbiota–metabolite–inflammatory cytokine network, thereby maintaining gut–lung axis homeostasis and enhancing anti-inflammatory effects. Conclusions: SLEL alleviates ALI through multi-component synergistic actions that suppress pro-inflammatory signaling and modulate the gut–lung axis. These findings highlight the potential of SLEL as a promising therapeutic candidate for the treatment of ALI. Full article

Orthopedic implants have a critical role in modern medical practice, being useful in bone regeneration, joint arthroplasty, and healing fractures. The success of osseointegration depends on implant properties (composition, stability, geometry, biocompatibility) and host factors (local reactivity, comorbidities). Preclinical evaluation in animal models is essential before clinical application. In orthopedic implantology, the selection and real utility of a range of animals are important, with an emphasis placed on bone–implant interface, biomechanical function, and long-term integration. Smaller animals such as rabbits and rats have widespread use in early biocompatibility and osseointegration testing, but larger animals such as pigs, sheep, and canines have a larger physiological bone similarity and can, therefore, be utilized for bearing loads in testing. Considering the utility and disadvantages of certain species—including suitability for new biomaterials, coatings, and biomechanical function—this article discusses testing methodologies such as push-out/pull-out tests, histomorphometry, and micro-CT and their utility in testing the integration of implants and regeneration of bone. Conclusions confirm a multi-species model in use in preclinical testing for the development of implants and improvements in clinical success. Unlike previous reviews, this article emphasizes translational strategies, integrates ethical perspectives in model selection, and discusses the synergistic use of imaging modalities with biomechanical tests for comprehensive assessment. 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

Clinical studies have linked glyphosate exposure to substantial morbidity, with acute kidney injury occurring in some cases. Although the toxic effects of glyphosate-based herbicides (GBHs) have been reported in several studies, their molecular impact on renal function remains poorly understood. Given the kidney’s critical role in excretion, it is particularly susceptible to damage from xenobiotic exposure. In this study, we aim to identify N-glycomics and proteomics change in the kidney following chronic GBH exposure, to better understand the mechanisms behind glyphosate-induced kidney damage. Kidney tissues from female and male rats were analyzed using liquid chromatography–tandem mass spectrometry. The results revealed notable changes in the N-glycan composition, particularly in the fucosylated and sialofucosylated N-glycan types. The proteomic analysis revealed the activation of immune signaling and inflammatory pathways, including neutrophil degranulation, integrin signaling, and MHC class I antigen presentation. Transcription regulators, such as IL-6, STAT3, and NFE2L2, were upregulated, indicating a coordinated inflammatory and oxidative stress response. Sex-specific differences were apparent, with female rats exhibiting more pronounced alterations in both the N-glycan and protein expression profiles, suggesting a higher susceptibility to GBH-induced nephrotoxicity. These findings provide new evidence that chronic GBH exposure may trigger immune activation, inflammation, and potentially carcinogenic processes in the kidney. Full article

In clinical medicine, rats are commonly used as experimental subjects. However, their estrous cycle significantly impacts their biological responses, leading to differences in experimental results. Therefore, accurately determining the estrous cycle is crucial for minimizing interference. Manually identifying the estrous cycle in rats presents several challenges, including high costs, long training periods, and subjectivity. To address these issues, this paper proposes a classification network, Spatial Long-distance EfficientNet (SLENet). This network is designed based on EfficientNet, specifically modifying the Mobile Inverted Bottleneck Convolution (MBConv) module by introducing a novel Spatial Efficient Channel Attention (SECA) mechanism to replace the original Squeeze Excitation (SE) module. Additionally, a non-local attention mechanism is incorporated after the last convolutional layer to enhance the network’s ability to capture long-range dependencies. On 2655 microscopy images of rat vaginal epithelial cells (with 531 test), SLENet achieves 96.31% accuracy, surpassing EfficientNet (94.20%). This finding provides practical value for optimizing experimental design in rat-based studies such as reproductive and pharmacological research, but this study is limited to microscopy image data, without considering other factors; thus, future work could incorporate temporal pattern and multi-modal inputs to further enhance robustness. Full article

The design and validation of a reverberation chamber (RC) specifically constructed for conducting large-scale experimental animal carcinogenicity studies using RF electromagnetic fields (EMF) relevant to contemporary 4G and 5G mobile communication (900 MHz, 2.12 GHz, and 3.65 GHz) is proposed. The RC’s electric field (E-field) uniformity is evaluated under four practical loading conditions: empty, apparatus only, and two apparatus variations with 80 experimental animals (Sprague–Dawley rats) with approximate weights 400 g and 520 g, respectively. Measurement results show E-field uniformity better than 1.36 dB under all test conditions, with frequency-dependent variation becoming negligible once the RC is loaded with cage racks and 80 rats. Additionally, a predictive method is introduced to estimate composite E-field intensities under simultaneous multi-frequency exposures, potentially reducing experimental measurements. These findings confirm that the designed RC is capable of accurately evaluating RF EMF exposure in biological studies. Full article

Acute mesenteric ischemia (AMI) is a life-threatening condition characterised by oxidative stress, inflammation, apoptosis, and necrosis of intestinal epithelial cells. Different drugs with vasoactive, antioxidant, and anti-inflammatory properties have been used to treat AMI. Levosimendan is a drug with proven anti-ischemic effects used in the management of acute congestive heart failure. This study evaluated the protective effects of levosimendan pretreatment on intestinal, as well as lung, heart, and kidney tissue in a rat model of mesenteric artery ischemia/reperfusion (I/R) injury. Male Wistar rats (N = 24) were divided into four groups: control, I/R, levosimendan (LS) 1 mg/kg i.p, and LS + I/R (1 mg/kg i.p. 30 min before injury). I/R by itself caused elevation of oxidative markers (thyobarbituric acid reactive species (TBARS), hydrogen peroxide (H₂O₂), super oxide anjon radical (O₂⁻), and nitrogen dioxide (NO₂⁻)), induced inflammation (macrophage infiltration and Interleukin-6 (IL-6) production), and apoptosis (nuclear factor kappa light-chain enhancer of activated B cells (NF-κB), cleaved caspase-3 (CC3), and terminal deoxy-nucleotidyl transferase (TdT)-mediated dUTP nick end labelling (TUNEL)). Levosimendan pretreatment significantly reduced oxidative stress markers and enhanced antioxidant defences (catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)). Histological analysis revealed reduced mucosal damage and preserved goblet cells in intestinal tissue. Similar protective effects of levosimendan were observed in other organs such as lung, heart, and kidney. Immunohistochemistry showed reduced epithelial apoptosis and upregulation of antioxidant and anti-inflammatory proteins. These findings highlight levosimendan’s ability to protect mesenteric I/R tissue injury and multi-organ damage by suppressing oxidative stress, inflammation, and apoptosis, emphasising its therapeutic potential in clinical settings. Full article

This study examines the toxicological effects of carbon nanotubes (CNTs) of different diameters—single-walled CNTs (SWCNT, 2 nm) and multi-walled CNTs (MWCNT, 74 nm)—on two macrophage cell lines, rat alveolar NR8383 cells and human differentiated THP-1. Using standardized exposure conditions and employing an integrated omics approach (transcriptomic and proteomic analyses), both CNT types were found to induce cellular stress responses and inflammation, especially in NR8383 cells, with notable involvement of the Sirtuin signaling pathway. After 24 h, MWCNTs uniquely disrupted lipid metabolism in NR8383 cells, resulting in foam cell formation and syncytia. While SWCNTs were less disruptive to metabolic pathways, they significantly altered gene regulation, particularly RNA splicing mechanisms. The dispersion medium—fetal bovine serum (FBS) versus human surfactant—also modulated the observed toxicological responses, highlighting the critical role of the protein corona in influencing CNT-cell interactions. These findings demonstrate that CNT diameter significantly affects cytotoxicity and cellular response pathways in a cell-type-specific manner. Full article

Permanent magnet vernier motors (PMVMs) have significant advantages in low-speed direct-drive fields on account of their high torque density, and their performance improvement is still a research hotspot. To enhance the overall electromagnetic performance and provide an alternative solution for low-speed direct-drive applications, this paper proposes a permanent magnet vernier motor with rotor auxiliary teeth (denoted as “RAT-PMVM”). Firstly, the structure and working principle of RAT-PMVM are introduced. Then, the two-dimensional (2D) finite element method (FEM) is used to comparatively study the influence of the number, position, and tooth profile of the rotor auxiliary teeth on the electromagnetic performance of the proposed motor. The results show that the RAT-PMVM with trapezoidal teeth (denoted as “TT-PMVM”) achieved improvement in output torque, efficiency, and power factor: the output torque increased from 11.32 Nm to 14.19 Nm, the efficiency increased from 88.5% to 92.2%, and the power factor increased from 0.60 to 0.71. Finally, in order to further reduce the torque ripple and improve the torque, power factor, and efficiency, multi-objective optimization of the TT-PMVM is carried out. The optimization yields a 27.3% increase in torque, a 31.8% reduction in torque ripple ratio, an efficiency improvement from 92.2% to 93%, and a power factor enhancement from 0.73 to 0.81, demonstrating significant potential for low-speed direct-drive applications like industrial robots and wind power generation. Full article

Inhalation of multi-walled carbon nanotubes (MWCNTs) poses potential health risks due to their structural similarity to asbestos and their ability to induce chronic lung inflammation, fibrosis, and lung cancer in animal models. This study investigated the pulmonary inflammatory and transcriptomic responses of two distinct MWCNTs—NM-401 (long, rigid) and NM-403 (short, thin)—in rats and mice using intratracheal instillation at matched dose levels at two post-exposure time points. Both MWCNTs induced acute neutrophilic inflammation and dose-dependent transcriptomic alterations in both species, with NM-403 eliciting a stronger response. Transcriptomic profiling revealed a substantial overlap in differentially expressed genes across materials and species, particularly at the early time point. Fibrosis-associated genes were upregulated in both species, with more persistent expression observed in rats. Acute phase response genes, including Orosomucoid 1 and Lipocalin 2 were commonly induced, while Serum Amyloid A3 and Orosomucoid 2 were selectively upregulated in mice. Functional enrichment analyses showed conserved activation of immune and inflammatory pathways. Our findings show that even short, non-fiber-like MWCNTs can provoke potent and persistent pulmonary effects, challenging assumptions based solely on MWCNT properties. Despite differences in long-term responses, the overall inflammatory and transcriptional profiles showed strong interspecies concordance, suggesting that both rats and mice are relevant models for assessing MWCNT-induced pulmonary toxicity. Full article

Diabetic neuropathy (DN) is one of the most prevalent complications of diabetes mellitus, affecting a substantial proportion of patients and contributing to progressive sensorimotor dysfunction. Despite its clinical significance, available treatments are often insufficient and associated with undesirable effects. This study aims to evaluate the potential of Morus alba (MA), Angelica archangelica (AA), Valeriana officinalis (VO), and Passiflora incarnata (PI) extracts in ameliorating nociceptive alterations and inflammatory markers in the alloxan-induced diabetic rat model. Male Wistar rats with alloxan-induced DN received oral administration of the plant extracts (200 mg/kg/day) or gabapentin (100 mg/kg/day) for 15 days, the dosage regimen being established based on prior efficacy data in preclinical neuropathy models. Behavioral assessments of thermal and mechanical hypersensitivity were conducted using hot plate, tail withdrawal, von Frey, and Randall–Sellito tests. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were quantified in brain and liver homogenates to evaluate neuro-inflammatory responses. All plant extracts produced significant improvements in nociceptive thresholds compared to diabetic control, with the most marked effects observed for MA extract. Pro-inflammatory cytokine levels were significantly reduced in all treatment groups, with MA and AA extracts inducing the most significant reductions in TNF-α and IL-6 concentrations. Computational target prediction and molecular docking analyses revealed that key phytochemicals from the plant extracts may exert antihyperalgesic effects through multi-target modulation, notably via interactions with AAK1, a kinase involved in neuropathic pain signaling. The investigated plant extracts displayed significant antihyperalgesic and anti-inflammatory activities in a rat model of DN. Among them, MA extract revealed the most consistent therapeutic profile, supporting its potential role as a strategy for managing DN. Full article

Background/Objectives: Radiotherapy can cause severe and irreversible brain damage, including cognitive impairment, increased dementia risk, debilitating depression, and other neuropsychiatric disorders. Current radioprotective drugs face limitations, such as single-target inefficacy or manufacturing hurdles. Isoliquiritigenin (ISL), a natural flavonoid derived from licorice root, exhibits broad bioactivities. It exhibits anti-inflammatory, anti-cancer, immunoregulatory, hepatoprotective, and cardioprotective activities. This study aimed to elucidate ISL’s neuronal radiation mitigation effects and key targets. Methods: In vitro and in vivo models of radiation-induced neuronal injury were established. ISL’s bioactivities were evaluated through cellular cytotoxicity assays, LDH release, ROS, ATP, glutamate, and GSH levels. In vivo, ISL’s radiation mitigation effect was evaluated with sucrose preference test, IL-β level, histopathological analysis, and Golgi-Cox staining analysis. Proteomics, pathway enrichment, and ensemble models (four machine learning models, weighted gene co-expression network, protein–protein interaction) identified core targets. Molecular docking and dynamic simulations validated ISL’s binding stability with key targets. Results: ISL attenuated radiation-induced cellular cytotoxicity, reduced LDH/ROS, restored ATP, elevated GSH, and mitigated glutamate accumulation. In rats, ISL alleviated anhedonia-like phenotypes and hippocampal synaptic loss. ISL also significantly suppressed radiation-induced neuroinflammation, as evidenced by reduced levels of the pro-inflammatory cytokine IL-1β. Proteomic analysis revealed that ISL’s main protective pathways included the synaptic vesicle cycle, glutamatergic synapse, MAPK signaling pathway, SNARE interactions in vesicular transport, insulin signaling pathway, and insulin secretion. Grm8, Grik3, and Grin3a were identified as key targets using the integrated models. The expression of these targets was upregulated post-radiation and restored by ISL. Molecular docking and dynamic simulations indicated that ISL showed stable binding to these receptors compared to native ligands. Conclusions: ISL demonstrates multi-scale radiation mitigation activities in vitro and in vivo by modulating synaptic and inflammatory pathways, with glutamate receptors as core targets. This work nominates ISL as an important natural product for mitigating radiotherapy-induced neural damage. Full article

Salivary gland dysfunction is a common but underexplored complication of menopause that contributes to oral dryness, dysphagia, and increased risk of infection. Although ferroptosis, a form of regulated necrotic cell death driven by iron-dependent lipid peroxidation, has recently been implicated in postmenopausal tissue degeneration, its regulatory mechanisms in salivary glands remain unclear. In this study, we investigated the roles of mitochondrial dysfunction and mitophagy in driving ferroptosis-induced salivary gland injury in an ovariectomized (OVX) rat model of estrogen deficiency. OVX rats exhibited elevated markers of oxidative stress, lipid accumulation, and iron overload, and suppression of GPX4 activity in the salivary glands, consistent with ferroptotic activation. These changes were accompanied by impaired mitochondrial dynamics (MFN1 and OPA1), decreased expression of mitochondrial antioxidant regulators (PGC-1α, SOD, and catalase), and upregulation of mitophagy-related genes (PINK1, ULK1, Rab9, and LC3B), as well as LAMP, a lysosomal marker involved in autophagosome–lysosome fusion, while ferritinophagy (NCOA4) remained unchanged. Early administration of ferrostatin-1 effectively suppressed these pathological changes, preserving both glandular structure and function, as evidenced by the restored AQP5 and AMY2A expression. Collectively, our findings reveal that ferroptosis in estrogen-deficient salivary glands is regulated by mitochondrial instability and aberrant mitophagy, and ferrostatin-1 mitigates this cascade through multi-level mitochondrial protection. These results highlight ferrostatin-1 as a promising preventive agent against menopause-associated salivary gland dysfunction, with broader implications for organ-specific ferroptosis modulation. Full article