Search Results (29,323)

Pancreatic tumors frequently exhibit calcification, suggesting potential osteogenic-related phenotypic plasticity. This study aimed to systematically evaluate whether pancreatic ductal adenocarcinoma (PDAC) cells acquire osteogenic-like features under induction conditions and to assess the associated phenotypic and molecular changes. PDAC cell lines and non-malignant pancreatic epithelial cells were subjected to osteogenic induction. Mineralization, alkaline phosphatase (ALP) activity, osteogenic marker expression, and malignant phenotypes were evaluated. RNA sequencing was performed at defined time points to characterize transcriptional changes. Pharmacological inhibition of MEK and siRNA-mediated knockdown of RUNX2 were applied to examine the involvement of MAPK–ERK signaling and downstream transcriptional regulation. Osteogenic induction led to calcium deposition and increased ALP activity in a subset of PDAC cell lines, accompanied by upregulation of osteogenic-associated markers, including RUNX2 and SPP1. Induced cells exhibited reduced migration, clonogenicity, invasion, and proliferation. Transcriptomic analysis revealed activation of osteogenesis-related and calcium-transport pathways, along with downregulation of cell cycle programs. MAPK–ERK signaling was activated during induction, and MEK inhibition attenuated RUNX2 and ALP expression as well as mineralization-associated changes. Furthermore, RUNX2 knockdown reduced ALP expression and mineralization levels, indicating its contribution to the osteogenic-like phenotype. PDAC cells can acquire osteogenic-like features under defined induction conditions, accompanied by coordinated transcriptional reprogramming and reduced malignant phenotypes. The observed mineralization-associated phenotypes may reflect a combination of active processes and passive calcium deposition. In addition, the MAPK–ERK–RUNX2 axis appears to be involved in this process, although it may reflect a broader adaptive or stress-associated reprogramming rather than lineage commitment. These findings provide insight into the potential relationship between tumor calcification and phenotypic plasticity in PDAC. Full article

Reinforced concrete (RC) columns in cold regions are often exposed to combined seismic actions and cryogenic environments, which can significantly alter their structural response. This study examines the seismic performance of RC columns over a temperature range of 20 °C to −90 °C using numerical simulations, with axial load ratios of 0.0–0.6 and stirrup ratios of 1.0–3.0% considered. The results reveal that failure modes remain generally consistent across temperatures, while damage becomes more pronounced at lower temperatures. A decrease in temperature leads to higher peak load and initial stiffness, accompanied by a reduction in ductility. Taking the specimens with ρ_sv = 1.0% as an example, as the temperature decreases from 20 °C to −30 °C, −60 °C, and −90 °C, the peak load increases by 10.9%, 17.1%, and 32.7%, respectively. As the temperature decreased from 20 °C to −90 °C, the ductility coefficient decreased by 33.3%, and the total dissipated energy increased by 6.4%. Increasing the stirrup ratio enhances deformation capacity and partially mitigates ductility loss. Furthermore, the influence of axial load ratio on hysteretic response follows a similar pattern to that at ambient temperature, but with greater sensitivity under cryogenic conditions. Based on the numerical findings, predictive expressions are proposed to estimate the plastic hinge length and flexural strength considering temperature effects. Full article

316LN stainless steel is widely used in critical nuclear fusion structural components due to its excellent mechanical properties and machinability. However, its high thermal expansion coefficient and low thermal conductivity promote welding distortion, while work hardening causes residual stress accumulation. Thermo-elastic–plastic finite element modeling (FEM) is the primary numerical method for predicting these effects. Yet, despite hardware advances, full-scale simulations—especially for thick plates with multi-pass welds—remain computationally expensive, hindering the balance between efficiency and accuracy. To address the inherent trade-off between welding efficiency and dimensional accuracy in multi-pass, multi-layer welding of thick-section components, this study employs MSC. Marc to develop a finite element model of a 15 mm thick butt-welded joint fabricated from 316LN stainless steel. Three distinct heat source models—instantaneous, enhanced moving, and moving element-set—are systematically implemented to simulate transient temperature fields, residual stress distributions, and welding deformation. All numerical predictions are rigorously validated against experimental measurements to comprehensively assess both accuracy and computational efficiency. Results indicate that: (i) the predicted molten pool geometries and characteristic thermal cycle profiles from all three models exhibit strong agreement with experimental observations; (ii) longitudinal residual stress distributions predicted by all models align closely with measured values; (iii) transverse residual stresses predicted by the moving element-set and enhanced moving heat sources agree well with experiments, whereas those from the instantaneous heat source show marked deviation; (iv) angular distortion predictions from the moving element-set heat source achieve over 90% conformity with experimental data, while the instantaneous heat source substantially underestimates angular distortion, and the enhanced moving heat source yields approximately 65% agreement; and (v) in terms of computational efficiency, the instantaneous heat source requires only ~40% of the computation time needed by the moving heat source. Full article

The buildup of non-biodegradable plastic waste and poor management of agro-industrial by-products have caused a major environmental crisis. The present research addresses the development of novel materials supporting the circular bioeconomy. This study aimed to develop and characterize bio-composite films derived from native Oxalis tuberosa starch and keratin microparticles (KMPs) extracted from cattle horn waste. The experimental methodology employed a 2³ factorial design and involved the characterization of the films included the evaluation of physical and optical properties and the identification of functional groups via spectroscopy, mechanical tests, and thermogravimetric analysis (TGA). The results revealed significant interactions (p ≤ 0.05). Higher processing temperatures were the main reason for the drop in water activity (a_w) and moisture content (MC) levels. Concurrently, the incorporation of KMPs reduced water solubility, increased opacity, and enhanced thermal stability. FTIR analysis confirmed the existence of intermolecular interactions between the hydroxyl and amide functional groups. In conclusion, bio-composites composed based on Oxalis tuberosa starch and keratin microparticles represent a sustainable alternative to mitigate the use of conventional plastics in the industry. Full article

Tree root-system architecture is vital for forest resilience under rising climate stress, yet techniques like excavation are destructive, slow, and unsuitable for large surveys. We evaluated how Scots pine (Pinus sylvestris) root architecture varies across contrasting environments using non-invasive, high-resolution multichannel ground-penetrating radar (GPR). Plots in the Olkusz Forest District (southern Poland) spanned gradients of soil fertility and stand age. A multichannel radar array produced 3D subsurface volumes, from which two traits were derived: the 2D planar root extent and the 3D rooting-envelope volume. Generalized additive models linked these metrics to site, stand, and tree characteristics. Multichannel GPR revealed clear site-driven differences in root structure and delivered markedly better data quality than single-channel systems. Selective excavation of visible roots confirmed close agreement between radar estimates and true root positions. Root architecture shifted along the fertility gradient and depended strongly on tree size, stand density, and age: rooting volume increased with site productivity and diameter at breast height but declined with stand age and relative spacing. Overall, Scots pine shows strong adaptive plasticity, and multichannel GPR provides a powerful way to integrate below-ground traits into monitoring, modeling, and climate-smart forest management. Full article

This study investigates hydrogen embrittlement in welded joints of X52 (L360) pipeline steel obtained from an operating natural gas transmission network after 31 years of service, with particular emphasis on production (longitudinal) and girth (circumferential) welds. The aim is to elucidate the influence of microstructural heterogeneity across the pipe wall and within different welded joint types on hydrogen transport, trapping behavior, and fracture mechanisms. The investigation combines X-ray diffraction, electrochemical hydrogen permeation testing, fractographic analysis, and transmission electron microscopy. X-ray diffraction results show that the base metal and girth weld consist predominantly of body-centered cubic ferrite, whereas the production weld additionally contains retained austenite associated with an elevated manganese content. These phase-related differences are consistent with transmission electron microscopy observations of martensite–austenite constituents within the weld microstructure. Electrochemical hydrogen permeation measurements reveal pronounced microstructure-dependent hydrogen transport behavior. The production weld exhibits a significantly lower apparent diffusion coefficient and a markedly higher hydrogen trap density, approximately five times greater than those of the base metal and girth weld, providing a mechanistic explanation for the observed differences in hydrogen uptake behavior. Fractographic analysis demonstrates a transition from ductile microvoid coalescence in the uncharged condition to predominantly brittle fracture following hydrogen charging. This transition is accompanied by a substantial increase in the fraction of brittle fracture zones, reaching approximately 53% in hydrogen-charged specimens. A pronounced gradient in hydrogen embrittlement susceptibility is observed across the pipe wall thickness, with outer-wall specimens consistently exhibiting greater susceptibility than inner-wall specimens. This behavior reflects the combined influence of long-term soil corrosion and hydrogen-assisted degradation. Transmission electron microscopy reveals that plastic deformation governs dislocation generation, while hydrogen significantly modifies dislocation behavior by promoting dislocation pile-ups near martensite–austenite constituents and non-metallic inclusions. These observations indicate strong interactions between hydrogen, dislocations, and microstructural heterogeneities. A clear size-dependent role of non-metallic inclusions is identified. Sub-micron inclusions act primarily as irreversible hydrogen trapping sites that contribute to hydrogen redistribution within the microstructure, whereas larger inclusions serve as preferential crack initiation sites under hydrogen charging conditions. Overall, the results demonstrate that hydrogen embrittlement behavior is governed by the combined effects of microstructural state, welded joint type, and long-term service-induced degradation, resulting in distinct hydrogen transport characteristics and fracture responses across the pipe wall. Full article

Hypersaline environments are unique ecosystems harboring specialized microbial communities with significant biotechnological potential. This study provides a comprehensive characterization of the taxonomic diversity and functional potential of two Tunisian salterns, Abbassia (Kerkennah) and Thyna (Sfax), using an integrated approach that combines 16S/18S rRNA gene amplicons (Illumina and full-length Nanopore) with shotgun metagenomics. Taxonomic profiling revealed a high species richness (S ≈ 1250 taxa); however, the Abbassia site was characterized by extreme taxonomic polarization, with over 95% of the community dominated by specialized halophilic Bacillota (Salinicoccus and Jeotgalicoccus). In contrast, Thyna exhibited a more even distribution dominated by Pseudomonadota and methanogenic Archaea. Beyond taxonomy, functional annotation via the HUMAnN 3.0 pipeline identified site-specific metabolic specializations. Abbassia was enriched in biosynthetic pathways and robust stress-response mechanisms, including ectoine biosynthesis and ppGpp-mediated stringent response, reflecting adaptation to stable hypersaline conditions. Conversely, Thyna’s microbiome prioritized energy extraction and nutrient recycling, with a high abundance of fermentation and glyoxylate cycle pathways. These findings demonstrate that environmental filtering shapes not only the microbial structure but also the metabolic landscape, highlighting the ecological plasticity of microbial life in extreme Tunisian salterns. Full article

N-methyl-D-aspartate receptors (NMDARs) play a context-dependent role in ischemic stroke (IS), contributing to acute excitotoxic injury while also supporting subsequent neuroplasticity. This functional divergence has constrained the therapeutic efficacy of non-selective NMDAR antagonists. During the acute phase, neuronal injury is associated with the redistribution of NMDARs toward extrasynaptic sites and the activation of aberrant non-ionotropic signaling pathways. As the disease progresses, NMDAR-dependent signaling becomes increasingly involved in activity-dependent plasticity, including motor engram consolidation, dendritic remodeling, and large-scale network reorganization. Post-stroke cognitive impairment and depression are increasingly recognized as potential consequences of sustained NMDAR dysregulation, involving interactions with immune signaling and metabolic processes. These observations support a shift toward activity-dependent modulation of NMDAR function, in which neurotoxic signaling is selectively dissociated from physiological receptor activity. Emerging strategies aimed at subunit-specific modulation and disruption of pathological receptor complexes provide a basis for more targeted intervention. Preservation of physiological excitation–inhibition balance may therefore represent a key requirement for optimizing functional recovery after stroke. Full article

Modern wound care is challenged by the emergence of antibiotic-resistant bacterial strains, causing the need for advanced dressing materials that provide infection control while promoting healing. Although polyacrylamide (PAAm) hydrogels are widely investigated due to their biocompatibility, their lack of intrinsic antibacterial activity and poor mechanical properties restrict their clinical use. To overcome these limitations, this study proposes a natural–synthetic hydrogel that combines PAAm with TEMPO-oxidized cellulose nanofiber (TOCNF) functionalized silver nanoparticles (AgNPs). The synthesis is performed through the polymerization of the synthetic monomer in the presence of the TOCNF–AgNPs, the nanofibrillar cellulose simultaneously serving as a reducing and stabilizing agent for AgNPs, and as a plasticizer for the PAAm network. Morpho-structural analysis of the hybrid precursor (TOCNF–AgNPs) revealed two populations of AgNPs, offering a cumulative effect between rapid bacterial penetration and a prolonged ionic reservoir, while maintaining the stability of the system. The subsequent incorporation of the hybrid into PAAm matrix resulted in tunable swelling kinetics and mechanical properties. Wettability and surface stiffness improve with the increase in hybrid content. The antibacterial effect was confirmed by a colony-counting assay for formulations with higher AgNPs content, exhibiting inhibitory metabolic activity against several pathogenic strains. These results suggest that PAAm/TOCNF–AgNPs (PTA) nanocomposites represent a promising mechanically adaptive candidate for wound-care applications. Full article

Chemotherapy-induced cognitive impairment (CICI), often referred to as “chemobrain,” is a common and sometimes persistent consequence of cancer treatment, characterized by deficits in memory, attention, executive function, and processing speed; it disproportionately affects older adults and women, suggesting a role for aging- and sex-related biological factors, including estrogen depletion. This work examines the potential of dietary phenolic compounds as multi-target modulators of mechanisms underlying CICI. A narrative synthesis of preclinical and clinical evidence was conducted, focusing on major phenolic subclasses (flavonoids, phenolic acids, stilbenes, lignans, and secoiridoids) and their effects on pathways implicated in chemotherapy-related neurotoxicity. The reviewed data indicate that phenolic compounds can influence redox balance, neuroinflammatory responses, mitochondrial function, synaptic plasticity, and estrogen-related signaling, with effects that appear to be structure-dependent; however, evidence remains heterogeneous and largely derived from experimental models rather than studies in humans. Overall, the current findings suggest that selected phenolic compounds could mitigate vulnerability to CICI, particularly in higher risk groups such as older individuals and women with low estrogen levels. These compounds represent promising and safe adjunctive strategies, although further well-designed clinical studies are needed to confirm their efficacy and clarify the underlying mechanisms. Full article

Brain-on-a-chip (BOC) refers to a miniaturized in vitro platform that integrates living neuronal networks on a micro-engineered chip, enabling the simulation of brain functions, neural activities and physiological responses. BOC technology is an advanced evolution of microphysiological systems (MPS) and Lab-on-a-Chip platforms, providing novel paradigms for in vitro modeling and exploring early-stage biocomputing by interfacing living neural networks with engineered electronics. Microelectrode arrays (MEAs) serve as the critical physical interface for bidirectional communication in these systems. In this review, we systematically examine the technological landscape and engineering requirements of MEAs tailored for BOC applications, evaluating them across electrical characteristics, structural properties, and biocompatibility. Two primary classes of current MEA technologies, including planar arrays for 2D neural cultures and 3D flexible arrays for brain organoids, are discussed in detail. We highlight the transition from passive planar electrodes to high-density active CMOS and TFT-based arrays, and detail how 3D flexible MEAs utilize endogenous integration and exogenous wrapping strategies to overcome tissue-mechanics mismatches. Furthermore, the integration of MEAs with microfluidics, optoelectronics, and electrochemical sensors to enable multimodal monitoring is explored. With the advantages of the various MEAs, the application of MEAs for BOC, particularly in biological computing and network plasticity research, is discussed. Finally, future technological developments in scalability bottlenecks, chronic stability, and the incorporation of artificial intelligence for MEAs of BOC are prospected. Full article

Breast cancer surgical management encompasses a spectrum of options that extend beyond oncologic control and carry substantially different cumulative surgical burdens. Although breast-conserving therapy (BCT) and mastectomy offer equivalent survival outcomes in many clinical scenarios, the downstream implications of these choices, including the number of operations, complication profiles, recovery timelines, and need for revision, are often underrecognized during initial treatment planning. This review aims to provide non-plastic surgeons with a practical framework for understanding the surgical burden associated with BCT compared with mastectomy and, when mastectomy is selected, the implications of subsequent reconstructive pathways. By discussing breast cancer surgery through the lens of cumulative surgical burden rather than isolated procedural choices, this review seeks to support more informed, multidisciplinary counseling and shared decision-making. A clearer understanding of reconstructive trajectories may help align surgical recommendations with patient values, optimize expectations, and reduce unanticipated downstream interventions across the continuum of breast cancer care. Full article

Background: Neuroinflammation and gut–brain axis (GBX) dysregulation are key pathological drivers of stress-related neuropsychiatric disorders. Zhi-Zi-Chi Decoction (ZZCD), a classic Traditional Chinese Medicine (TCM) formula, has been clinically used to alleviate mental disturbances via the TCM principle of “clearing heat and relieving restlessness.” Still, its modern neuroprotective mechanisms, especially its links to gut microbiota and central signaling pathways, remain incompletely elucidated. Purpose: This study aimed to systematically investigate the therapeutic effects of ZZCD on chronic restraint stress (CRS)-induced neurodysfunction in mice and clarify its mechanisms from the perspectives of TCM theory, material basis, gut microbiota–metabolite axis, and central signaling pathways. Method: CRS mice were treated with ZZCD or protocatechuic acid. Behavioral tests evaluated depression- and anxiety-like behaviors. UHPLC-Q-TOF/MS identified ZZCD’s chemical constituents; 16S rRNA sequencing and untargeted metabolomics analyzed gut microbiota and metabolite changes. Western blot, immunofluorescence, and proteomics examined neuroinflammation, microglial polarization, and signaling pathway activity (PI3K/Akt/mTOR, AMPK). Results: ZZCD reversed CRS-induced depression- and anxiety-like behaviors and suppressed neuroinflammation. Mechanistically, UHPLC-Q-TOF/MS identified 424 ZZCD constituents, with prenol lipids, organooxygen compounds, and flavonoids as the most abundant. ZZCD reversed CRS-induced imbalance in gut microbiota, reducing pro-inflammatory Prevotella and enriching beneficial Lactobacillus, and mediated the enrichment of the prebiotic metabolite PCA in colonic and serum samples, which crossed the blood–brain barrier (BBB) to exert neuroprotection. Additionally, ZZCD and PCA normalized the PI3K/Akt/mTOR pathway and activated AMPK, promoting M2 microglial polarization and restoring synaptic plasticity. Conclusions: ZZCD exerts antidepressant effects by a gut-microbiota-dependent modulation of PCA-PI3K/Akt/mTOR and AMPK dual axes that converts microglia from M1 to M2, providing ethnopharmacological evidence and a mechanistic rationale for its clinical application in major depressive disorder. Full article

Marine by-products represent a promising source of bioactive peptides. This study aimed to isolate and characterize a low-molecular-weight peptide fraction with antioxidant activity from Argentine shortfin squid carcass by-products, and to evaluate in vitro its cytocompatibility and protective effects against corticosterone (CORT)-induced oxidative injury in rat adrenal pheochromocytoma (PC12) cells and human astrocyte (hACs) cells. Argentine squid antioxidant peptide (PASN) was obtained by size-exclusion chromatography and fractionation-based screening. PASN exhibited the strongest overall free-radical-scavenging activity and consisted predominantly of components below 1 kDa (211.73–1013.48 Da). Spectroscopic analyses indicated that enzymatic hydrolysis transformed its structure from a rigid triple-helix conformation to a more flexible conformation dominated by β-turns (50.78%) and random coils (17.38%). In addition, thermogravimetric analysis confirmed its excellent thermal stability, with an onset decomposition temperature as high as 244.81 °C, supporting its potential applicability in high-temperature food-processing matrices. In vitro assays demonstrated that PASN exhibited high biocompatibility and promoted proliferation of both PC12 cells and hACs, while significantly improving cell viability under CORT challenge. PASN also reduced lactate dehydrogenase (LDH) leakage (hACs: 38.31%; PC12: 31.17%) in both cell models and restored total superoxide dismutase (T-SOD) activity (hACs: 69.46%, PC12: 66.40%). Immunofluorescence further revealed that PASN rescued the expression of brain-derived neurotrophic factor (BDNF) (hACs: 35.23%, PC12: 12.50%) and glutamate decarboxylase (GAD1/2) (hACs: 102.66%, PC12: 31.31%), key markers associated with synaptic plasticity and GABAergic sleep regulation. Collectively, PASN is a thermally stable squid-derived peptide fraction that exerts antioxidant and cytoprotective effects in neural cell models in vitro and represents a promising sustainable candidate for nutraceutical development. Full article

Plastic pollution has emerged as one of the most pervasive environmental challenges, with microplastics (MPs) widely distributed across marine ecosystems worldwide. This study aimed to assess the uptake of MPs by key fish and invertebrate species from different locations in the coastal zone of the Bulgarian Black Sea. Fish were collected during routine monitoring surveys in September–November 2024, while invertebrates were obtained via scuba diving. The presence of MPs in fish stomachs and invertebrate soft tissues, and their polymer composition, shape and size were analyzed using an Agilent 8700 LDIR Chemical Imaging System. Potential biological effects of ingested MPs were evaluated by an integrated Specific Oxidative Stress (SOS) index. The results revealed MP uptake levels comparable to those reported globally. Small-sized particles (<50 µm) with rounded shapes were most abundant across studied taxa. Polymer composition varied considerably depending on species and sampling region, indicating differences in exposure sources and environmental conditions. Oxidative stress levels in both fish and invertebrates showed substantial interspecific variation, and clear differences between the northern and southern region of the Bulgarian Black Sea. Overall, elevated uptake of MPs appears to contribute to oxidative stress in marine organisms, potentially affecting their health status, resilience, and adaptive capacity, as reflected by increased SOS index values. Full article