Search Results (4,735)

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in the world. The disease progresses from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The modern concept of “multiple parallel hits” interprets disease progression as the result of the synergistic action of lipotoxicity, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, proinflammatory signals, and gut–liver axis dysfunction. Against the background of the limited translation of preclinical data from animal models due to interspecies differences, the importance of human-oriented in vitro platforms compatible with controlled design and high-throughput screening is increasing. The current review analyzes MASLD models based on the HepG2 cell line, systematizing steatosis induction protocols, evaluating the metabolic characteristics and limitations of this cell, and comparing 2D monocultures, 3D systems, and co-cultures. HepG2 has been shown to demonstrate a predictable steatogenic response to free fatty acids (FFAs) and is convenient for reproducing early stages of pathogenesis and primary pharmacological selection of compounds. At the same time, key limitations of the model are highlighted, namely tumor origin, glycolytic shift (Warburg effect), reduced β-oxidation, impaired very-low-density lipoprotein (VLDL) assembly and secretion, and sharply reduced cytochrome P450 (CYP450) activity, as well as limited reproducibility of fructose-induced de novo lipogenesis (DNL). Comparative analysis demonstrates an increase in physiological relevance with the transition from 2D to 3D and multicomponent co-cultures, accompanied by increased complexity and cost, but allowing for the modeling of inflammation and fibrogenesis. The review justifies approaches to selecting the appropriate platform based on the specific research task. Full article

Acute lung injury (ALI) is a severe inflammatory condition associated with high morbidity and mortality, and there are currently no specific pharmacological treatments available. In this context, plants and natural products have emerged as promising therapeutic alternatives. SteLL (Schinus terebinthifolia Raddi leaf lectin) has demonstrated several biological activities, including anti-inflammatory and immunomodulatory effects. This study evaluated the anti-inflammatory effects of SteLL in a murine model of lipopolysaccharide (LPS)-induced ALI. Female BALB/c mice received intraperitoneal (i.p.) administration of SteLL (1, 5, or 10 mg/kg), dexamethasone (2 mg/kg), or vehicle (PBS). Sixty minutes later, ALI was induced by intranasal instillation of 25 µL of LPS (1 μg/μL). After 24 h, the animals were euthanized. Bronchoalveolar lavage fluid (BALF) was obtained to evaluate inflammatory parameters and lungs were collected for histopathological analysis. The tested doses of SteLL resulted in a 45–66% lower leukocyte infiltration. The group treated with 5 mg/kg exhibited a lower proportion of neutrophils and a higher proportion of mononucleated cells. Pre-treatment with SteLL also minimized plasma leakage and myeloperoxidase (MPO) activity. Furthermore, SteLL attenuated the release of pro-inflammatory cytokines at all tested doses as well as prevented nitric oxide (NO) production at the highest dose (10 mg/kg). Histopathological analysis showed that SteLL (5 and 10 mg/kg) attenuated LPS-induced lung injury. Overall, SteLL demonstrated significant anti-inflammatory effects, showing its potential as a plant-derived compound for modulating pulmonary inflammation. Full article

The practical application of inorganic ferroelectric fillers in flexible piezoelectric composites is critically constrained by low polarization efficiency and severe interfacial incompatibility with polymer matrices. Herein, we report a multi-level in situ surface modification strategy that simultaneously addresses both limitations. High-purity one-dimensional tetragonal barium titanate nanofibers (BTO NFs) are first synthesized via sol–gel electrospinning combined with a two-step gradient annealing process, which precisely controls phase evolution and preserves structural continuity. To overcome the detrimental acid-induced degradation of BTO NFs during functionalization, a polydopamine (PDA) buffer layer is first conformally coated, followed by the liquid-phase deposition of a conductive polypyrrole (PPy) shell, forming a robust core–shell PPy@PBT NFs architecture. Incorporating only 4 wt% of these multifunctional fillers into a poly(vinylidene fluoride) (PVDF) matrix yields a dramatic enhancement in electromechanical performance. The resulting flexible piezoelectric energy harvesters achieve a piezoelectric coefficient (d₃₃) of 28.7 pC/N, an output voltage of 13 V, and an output current of 0.7 μA, representing substantial improvements over unmodified filler systems. This synergistic enhancement originates from the PDA-mediated interfacial stress transfer and the PPy-induced Maxwell–Wagner polarization intensification, establishing a robust and generalizable paradigm for high-performance flexible piezoelectric composites in self-powered wearable electronics. Full article

This paper proposes a Hybrid-Field DD (HFDD) coupler designed for wireless power transfer (WPT) in mobile robots within smart manufacturing environments, utilizing a dual-coupling mechanism of magnetic and electric fields. The proposed coupler integrates Double-D coils for vertical magnetic field concentration with a split metal plate structure for enhanced electric field coupling in a compact, low-profile design. To evaluate the electromagnetic performance and the impact of inevitable eddy current interference, two distinct configurations—Front Plate Arrangement (FPA) and Back Plate Arrangement (BPA)—are analyzed through both theoretical modeling and 3D full-wave simulations (HFSSs). The comparative results demonstrate that the FPA model reduces the peak induced current intensity by 56.23 A/m compared to the BPA and achieves a peak leakage magnetic field intensity of 1.12 A/m, which is 28% lower than the 1.56 A/m observed in the BPA, offering a superior solution for suppressing leakage magnetic field and contributing to robust coupling stability. The high consistency between the proposed analytical methodology and numerical simulations underscores the theoretical robustness of the HFDD structure, establishing a clear design framework for efficient power transfer in robotic applications. Full article

Polymer films and coatings play an increasingly critical role in extending material functionality across industrial, biomedical, and environmental applications. Recent advances in surface engineering have enabled precise control of interfacial properties, leading to enhanced durability, cleanliness, and protection. This review summarizes state-of-the-art strategies for modifying polymer surfaces, with an emphasis on plasma-based surface modification and plasma-induced polymerization as versatile, solvent-free methods for tailoring wettability, chemical functionality, and adhesion. Furthermore, it examines emerging classes of self-cleaning and self-sterilizing coatings that leverage photocatalytic, hydrophobic, or antimicrobial mechanisms to mitigate contamination, biofouling, and pathogen transmission. Additionally, developments in high-performance barrier films designed to protect food products and electronic devices through improved resistance to gases, moisture, and chemical agents are highlighted. By integrating insights from materials chemistry, surface physics, and nanostructured coating design, this review provides a comprehensive overview of current achievements and future directions in functional polymer films and coatings aimed at anti-pollution, antibacterial, and anti-corrosion performance. Full article

We conducted a paired gravity and seismic survey at Kentland Crater with the goal of investigating its subsurface density structure. Our results show that the complex crater hosts a ~4.5 mGal Bouguer gravity high corresponding to the central uplift. The southeastern portion of the crater structure exhibits a low-gravity annulus at 3.5–4.5 km radius, with an adjacent high that we define as the rim at ~5.0 km radius, implying a 10 km apparent diameter. Passive seismic data is used to characterize the low-density glacial till layer, which blankets the bedrock throughout the study area. The central gravity anomaly persists after removing the gravitational influence of the till layer. Kentland’s large, positive central gravity anomaly is likely due to the removal of the low-density material beneath the original crater floor by extensive erosion via glacial scouring. We therefore suggest that the impact-induced porosity at Kentland Crater was likely confined to the original near-surface (<900 m), which aligns with recent numerical modeling. Due to the wide range of diameter estimates, we conclude that the current geometry of Kentland Crater remains ill-defined. Compiled datasets are provided here for use in future investigations. Full article

Flexible resistive bend sensors are essential for monitoring human movement in smart rehabilitation and soft robotics. However, widespread adoption is currently hindered by a trade-off between the high cost of metal-film technologies and the performance degradation (significant hysteresis and non-linearity) of low-cost carbon/polymer composites. This study presents a geometrically customizable bending sensor fabricated from conductive thermoplastic polyurethane (TPU) using Fused Deposition Modeling (FDM) technology as an accessible alternative to commercial sensors. By parametrically optimizing physical dimensions—including trace width, layer thickness, and pattern geometry—the sensors were tailored to achieve target resistance values within a target window of 20–50 kΩ (achieved: ~44 kΩ nominal) for specific finger-joint applications. Electromechanical characterization revealed a negative gauge factor (GF), where resistance decreases upon bending or elongation due to conductive pathway formation and densification within the polymer matrix. This behavior cannot affect sensor operation, and required bend-resistance responses were acquired using geometrical optimization. To compensate for inherent viscoelastic-induced hysteresis and non-linear behavior, a third-degree polynomial modeling approach was implemented. This modeling approach yielded a coefficient of determination (R²) of approximately 0.90. Compared to standard commercial sensors, the proposed FDM-printed design successfully overcomes geometric limitations while offering a cost-effective, high-performance solution for tailor-made wearable technologies and smart rehabilitation gloves. Full article

As a branch of nondestructive testing (NDT), Pulsed Eddy Current Testing (PECT) is characterized by its wide frequency spectrum and high penetration depth. After years of development, it has been widely applied to defect detection and material characterization of key components in industries such as petrochemicals, new energy, and aerospace. With the large-scale application of new energy sources like liquefied natural gas (LNG), methanol, and liquid hydrogen, the demand for NDT of non-ferromagnetic materials (e.g., austenitic stainless steel) has surged. However, challenges such as electromagnetic leakage caused by low magnetic permeability and the lift-off effect induced by protective layers impose stricter requirements on inspection technologies, driving the evolution of PECT towards adaptability in complex scenarios. This paper systematically reviews the latest advances in PECT technology, covering detection sensors, modeling methods, detection signal processing, and engineering applications. With a particular emphasis on research outcomes from the past decade, this paper also proposes potential directions for future development, aiming to provide a reference for innovative research and the industrial promotion of PECT technology. Full article

Glioblastoma (GBM) remains among the most treatment-refractory human malignancies. It is characterized by profound radioresistance and a highly immunosuppressive tumor microenvironment, limiting the durable efficacy of radiotherapy. Beyond direct cytotoxicity, ionizing radiation can induce immunogenic cell death and the release of damage-associated molecular patterns (DAMPs), including surface-exposed calreticulin, HMGB1, extracellular ATP/adenosine, and tumor-derived DNA. These signals engage pattern-recognition receptors and cGAS–STING–type I interferon pathways, transiently promoting antigen presentation and immune activation. In GBM, however, DAMP signaling frequently evolves toward chronic inflammation and immune suppression, characterized by myeloid cell recruitment, adenosine accumulation, and immune checkpoint upregulation, thereby contributing to tumor regrowth and radioresistance. This dual immune-regulatory role of DAMPs highlights the importance of temporal and contextual interpretation of radiation-induced immune responses. In this review, we summarize current mechanistic and translational evidence on DAMP-mediated immunomodulation in GBM radiotherapy; discuss modality-dependent considerations across photon, proton, and high-LET irradiation; and evaluate the emerging potential of DAMPs as dynamic biomarkers of treatment response. We further outline how integration of DAMP profiling with liquid biopsy, imaging, and nanotheranostic platforms may support biologically informed and adaptive radiotherapy strategies for glioblastoma. Full article

The dynamic field of radiopharmaceuticals is currently experiencing an explosion of growth due in part to excitement over the emerging field of theranostics (therapy and diagnostics). Radiopharmaceuticals use physiological targeting methods to deliver radionuclides with medically relevant decay properties to disease biomarkers for diagnosis and treatment, offering opportunities for early disease imaging and radiation therapy treatment in disease pathologies that are inoperable or refractory to other forms of radiotherapy. Sustaining this rapidly growing field depends heavily on the continued design and production of novel, effective radiopharmaceuticals. Effective therapeutic radiopharmaceuticals cause complex and varied cellular responses, and to choose radionuclides that maximize therapeutic response, researchers must understand radiation biology. Cellular radiation response depends heavily on factors including linear energy transfer (LET), dose, dose rate, targeted location, direct or indirect energy deposition mechanisms, the broader cellular matrix, cellular stress signaling pathways, and endogenous radiation protection mechanisms. Because of the extensive application of low-LET external beam radiation on clinical cancer treatments, biological responses to low-LET form the basis of radiation biology and are generally considered transferable to high-LET radiopharmaceuticals. However, increased focus on high-LET, radiopharmaceutical therapy-specific radiation biology is motivated by differences between low- and high-LET radiation, external beam versus radiopharmaceutical therapy-induced biological response, and the observed varied clinical responses to radiopharmaceutical therapies. This review article summarizes historical understanding of low- and high-LET radiation responses within cells, with emphasis on radiopharmaceutical-specific responses when available, and discusses current gaps in understanding in the radiation biology of radiotheranostic pharmaceuticals. Full article

Open-heart surgery with cardiopulmonary bypass (CPB) is a high-risk procedure with significant morbidity and mortality. CPB, tissue injury, blood loss, endotoxemia and ischemia–reperfusion injury induce a pronounced systemic inflammatory response, leading to endothelial glycocalyx (EG) damage and vascular endothelial dysfunction. Consequently, immune cells, reactive oxygen species, and enzymes gain free access to vascular endothelial cells, resulting in their dysfunction and enhancing inflammation, vascular permeability, and microvascular impairment. EG degradation is most commonly assessed by measuring the circulating levels of its degradation products. Additionally, CPB triggers an early inflammatory response that is characterized by the secretion of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha, and IL-18, which play roles in initiating the process of EG injury. EG damage is further propagated by the sustained release of cytokines, inhibiting the regeneration of the glycocalyx layer. Heparanase and matrix metalloproteinases are enzymatic pathways involved in cytokine-mediated EG degradation after cardiac surgery, and the balance between the pro- and anti-inflammatory cytokines determines the magnitude and duration of the inflammatory response and EG impairment, which correlates with adverse clinical outcomes, including myocardial dysfunction, acute lung and kidney injury, neurological complications, and prolonged need for intensive care. Thus, identifying patients with an exaggerated cytokine response could potentially provide more personalized therapy based on the circulating biomarkers of EG shedding, and cytokine-directed preservation of EG represents a promising therapeutic strategy in vascular dysfunction prevention during and after open-heart surgery. In this review, we summarize the current knowledge on cytokine-mediated EG impairment following open-heart surgery with CPB. Full article

Neurological complications, particularly seizures, represent a significant and often under-recognized clinical challenge in pediatric hematologic malignancies. Distinguishing CNS leukemia-associated epilepsy from chemotherapy-induced neurotoxicity is critical for optimizing therapy but remains difficult due to overlapping clinical presentations. This review highlights the distinct molecular mechanisms underlying these two entities. CNS leukemia-associated seizures are primarily driven by blood–brain barrier (BBB) disruption following leukemic infiltration, which triggers a neuroinflammatory cascade involving pro-inflammatory cytokines such as IL-6 and TNF-α, and impairs glutamate homeostasis. In contrast, chemotherapy-induced seizures, particularly those associated with high-dose methotrexate, arise from disrupted folate metabolism, intracellular oxidative stress, and subsequent N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. We provide a comparative analysis of these pathways, integrating current evidence on pharmacogenomic susceptibility—including polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and drug transporter genes—as well as epigenetic factors. By synthesizing these molecular insights, we propose a mechanistic framework for precise clinical differentiation, which may inform biomarker-driven diagnostic approaches and targeted neuroprotective strategies in this vulnerable population. Full article

Background/Objectives: Although the etiopathogenesis of autism spectrum disorder (ASD) remains incompletely elucidated, current evidence supports a multifactorial model involving genetic and environmental factors that interact to induce a heterogeneous range of symptoms. In recent years, epigenetic mechanisms, particularly DNA methylation, have been recognized as key contributors to ASD pathophysiology. Alterations in mitochondrial DNA (mtDNA) methylation are also emerging as relevant contributors in several human conditions. The mitochondrial D-loop, a non-coding control region essential for mtDNA replication and transcription, is considered a hotspot for epigenetic regulation and its methylation levels have been found altered in various diseases, such as cancer, metabolic disorders, and neurological illness. However, to date, no studies have investigated mtDNA methylation changes in ASD. Methods: We analyzed the average methylation levels of a fragment containing ten CpG sites within the D-loop region and the mtDNA copy number in peripheral blood samples from 49 children with ASD and 50 neurotypically developing (NT) controls using Methylation-Sensitive High-Resolution Melting and quantitative PCR. Results: No significant differences in D-loop methylation levels were observed between ASD and NT children. Similarly, the mtDNA copy number did not differ between the two groups. No significant correlations were found between D-loop methylation or mtDNA copy number and either ASD severity or age. Conclusions: This is the first study investigating mtDNA methylation in ASD. Our results indicate that methylation of the D-loop region and the mtDNA copy number are not altered in ASD children. Further studies including larger cohorts and extended mtDNA regions are warranted to confirm and expand these findings. Full article

Background: Rabies is a highly fatal zoonotic disease that causes approximately 59,000 human deaths worldwide each year. Current inactivated rabies vaccines require multiple doses and are associated with high costs. The full-length rabies virus glycoprotein (RVG), a membrane protein, exhibits substantial instability in its trimeric structure during recombinant expression. This instability makes it difficult to obtain high-purity, correctly folded antigens. Objectives: This study focuses on the preparation of a full-length recombinant RVG subunit vaccine candidate expressed in a glycoengineered Pichia pastoris system with mammalian-like glycosylation. Methods: The full-length RVG gene (including the transmembrane domain and cytoplasmic tail) from the Challenge Virus Standard-11 (CVS-11) strain was codon-optimized and inserted into the pPICZαA vector to construct the recombinant expression plasmid pPICZαA-RVG. The plasmid was transformed into glycoengineered Pichia pastoris X33-7 (low-mannose type) by electroporation for inducible expression. The target protein was purified by nickel affinity chromatography, anion-exchange chromatography, and Superdex-200 size-exclusion chromatography. The structural characteristics of the purified protein were analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The purified antigen was formulated with the adjuvants AS03 or MF59. BALB/c mice (n = 5 per group) were immunized intramuscularly following a four-dose schedule (days 0, 7, 14, and 28). Antigen-specific IgG antibody titers were measured by ELISA, and neutralizing antibody titers were determined using the rapid fluorescent focus inhibition test (RFFIT). Results: Glycoengineered Pichia pastoris yeast strains expressing wild-type RVG (RVG-WT) or a mutant variant (RVG-M6: R84S, R199S, H270P, R279S, K300S, and R463S) were successfully constructed. The purified RVG antigen formed nanoparticles with an average particle size of approximately 75 nm. Immunized mice generated robust RVG-specific IgG responses, with titers reaching approximately 6.31 × 10⁵ for RVG-WT after the fourth immunization, compared to 3.16 × 10³ for RVG-M6 and 5.62 × 10³ for the RVG-WT-PEG control. Two weeks after the fourth immunization, RVG-WT formulated with AS03 or MF59 induced significant neutralizing antibody responses compared with the control group (p < 0.0001 and p < 0.01, respectively). The neutralizing antibody titers reached 1:79.43 in the AS03 group and 1:33.11 in the MF59 group, whereas the WT-PEG + AS03 control group showed a low titer of 1:3.72. In contrast, RVG-M6 formulated with MF59 failed to induce detectable neutralizing antibodies (1:3.02). Furthermore, RVG-WT + AS03 induced significantly higher neutralizing antibody responses than the WT-PEG + AS03 control group (p < 0.0001), and a significant difference was also observed between the RVG-WT + MF59 and RVG-M6 + MF59 groups (p < 0.01). Conclusions: The glycoengineered Pichia pastoris expression system successfully produced uniform full-length rabies virus glycoprotein nanoparticles with high purity. When formulated with the AS03 adjuvant, RVG-WT induced high-titer neutralizing antibodies in mice, suggesting a promising strategy for the development of recombinant subunit vaccines against rabies. However, this study is limited by the absence of challenge studies and validation in target animal species, which will be further investigated in future work. Full article

Titanium alloys are widely used for biomedical implants due to their favorable mechanical properties, corrosion resistance, and biocompatibility. However, the development of multifunctional implant materials requires not only structural stability but also controlled electrochemical responsiveness, an important property for electrochemical sensing. This study developed ultrafine-grained Ti–xMo alloys (x = 28 and 31 wt.%) via mechanical alloying followed by powder metallurgy to investigate the effect of high Mo content on phase stability, corrosion behavior, and electrochemical sensing response. Both alloys exhibited predominantly β-phase microstructures, with β-phase fractions exceeding 93%, confirming effective stabilization at elevated Mo concentrations. Electrochemical tests conducted in 0.01 M PBS and Ringer’s solution revealed that pure Ti exhibited the highest impedance modulus and lowest corrosion current density, indicating superior passive film barrier properties. In contrast, high-Mo alloys showed reduced polarization resistance and increased charge-transfer contribution, associated with modifications in passive film defect chemistry and electronic properties induced by Mo enrichment. Among the investigated compositions, Ti-31 wt.% Mo demonstrated improved electrochemical stability compared to Ti-28 wt.% Mo, exhibiting lower corrosion current density and higher impedance values within the high-Mo regime. Cyclic voltammetry performed in 0.01 M PBS containing 1 mM K₃[Fe(CN)₆] confirmed enhanced heterogeneous electron-transfer capability for Mo-rich alloys relative to pure Ti. Overall, Ti-31 wt.% Mo provides a balanced combination of β-phase stabilization, moderate corrosion resistance, and improved electrochemical responsiveness potentially suitable for sensing interfaces. Full article