Search Results (496)

Background: Gastric cancer (GC) is characterized by aggressive invasion and early peritoneal dissemination, which are strongly driven by chronic inflammation and epithelial–mesenchymal transition (EMT). c-Jun N-terminal kinase (JNK), a stress-responsive serine/threonine kinase within the mitogen-activated protein kinase (MAPK) family, integrates inflammatory cues to promote EMT and metastasis. Huangjin Shuangshen granules (HJSS) is a multi-component traditional Chinese medicine (TCM) formula derived from Simiao Yong’an Decoction and clinically used as an adjuvant therapy for GC. However, whether HJSS restrains inflammation-driven metastasis through modulation of JNK-associated EMT signaling remains unclear. Methods: The anti-metastatic efficacy of HJSS was evaluated using integrated in vivo and in vitro models, combined with transcriptomics, network pharmacology and molecular validation. Results: HJSS markedly attenuated LPS-induced metastatic behavior and inflammatory activation. Multilevel analyses converged on MAPK8/JNK as a central regulatory node. HJSS reversed EMT progression and inhibited nuclear phosphorylation of JNK without affecting its upstream kinases. Thermal-shift assays and molecular docking supported potential target engagement of HJSS-derived constituents, including possible interactions with JNK-related signaling targets. Pharmacologic reactivation of JNK partially abrogated the inhibitory effects of HJSS, confirming JNK-dependent action. Conclusions: HJSS suppresses inflammation-driven GC metastasis primarily by attenuating JNK-associated EMT, potentially through modulation of JNK activation by its bioactive constituents. These findings provide mechanistic insight into HJSS as a low-toxicity anti-metastatic strategy and support further exploration of its active constituents. Full article

The central role of YB-1 in messenger ribonucleoprotein particle (mRNP) metabolism and stress-granule biology highlights the importance of defining the determinants of its self-assembly. YB-1 fibrillogenesis has been attributed primarily to the cold shock domain (CSD). Here, we show that the YB-1 fragment spanning residues 1–129 (AP–CSD) form amyloid fibrils under near-physiological ionic strength (0.12–0.15 M KCl). Fibrillization proceeds without a pronounced exponential growth phase and increases approximately linearly over 45–50 h. Far-UV circular dichroism (CD) and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) indicate no substantial change in overall secondary-structure content during aggregation. In parallel, ¹H nuclear magnetic resonance (NMR) spectroscopy reveals the depletion of soluble species, and oriented fiber X-ray diffraction displays the hallmark cross-β reflections at approximately 4.7 Å and 10 Å. The prolonged formation time implies an activation barrier that is unlikely to require global refolding. Instead, it may reflect early association events such as dimerization or other local rearrangements required for primary nucleation, followed by consolidation into stable intermolecular contacts. Aggregation that preserves a largely native-like fold while establishing cross-β order may reduce recognition by cellular quality-control systems that preferentially target globally unfolded or strongly destabilized states. This provides a plausible framework for how YB-1 derived assemblies could persist under stress and during age-associated proteostasis decline. Full article

Low temperature during grain filling is a major constraint affecting rice quality in cold regions. This study investigated how low temperature influences rice quality and starch characteristics at different periods of the grain-filling stage using two Japonica rice cultivars, Kenjing 7 (KJ7, moderate stress tolerance) and Kenjing 8 (KJ8, strong stress tolerance). Low-temperature treatments (17/13 °C, day/night) were applied during the early (5–11 days after anthesis), middle (12–18 days), and late (19–25 days) grain-filling stages and milling, appearance, nutritional, eating and cooking qualities as well as starch physicochemical properties were evaluated. Responses differed markedly between cultivars and treatment periods. Under low-temperature conditions, brown rice and milled rice rates of KJ8 increased during the early and middle grain-filling stages, whereas those of KJ7 declined during the late stage. Low-temperature stress increased protein, total starch, and amylose contents, while reducing gel consistency and the taste value of KJ7. Grain chalkiness increased significantly during the late stage, whereas during the early and middle stages, grain chalkiness, peak viscosity, and breakdown decreased and setback increased. Low temperature increased starch granule size and the proportions of short and intermediate chains of amylopectin, reduced medium-long and long chain and relative crystallinity, without altering starch crystalline type, and produced uneven starch particle surfaces with small pores. These effects were most pronounced during the late grain-filling stage. Overall, low temperature altered starch content and structure, thereby modifying pasting properties and ultimately leading to differences in rice quality. Full article

Dynamic instability of water-saturated granular coal in tectonic stress zones is a critical safety issue in coal mining. This study adopts raw coal granules from the Daping Coal Mine to investigate the dynamic response and instability mechanisms under coupled confining pressure, median particle size (d₅₀), and water saturation via dynamic impact tests, 2D equivalent modeling, and theoretical analysis. The results indicate that confining pressure and median particle size jointly regulate the dynamic mechanical properties of coal, with liquid bridge volume serving as a key mediating variable. The study reveals a dual-path coupling instability mechanism of “liquid bridge softening and confining pressure strengthening”: a critical confining pressure of 12 MPa divides the dominant force from liquid bridge to friction. Small-particle units show a stronger strengthening effect, and large-particle units have a slightly higher critical confining pressure. Field observation validates the theoretical patterns, identifying areas near faults as high-risk zones for dynamic instability. Accordingly, a three-tier prevention and control strategy of “tectonic stress unloading, flexible support, grouting modification” is proposed. The research findings enhance the theory of water-saturated granular coal instability and provide theoretical and engineering foundations for disaster prevention and control in tectonic stress zones of coal mines. Full article

Glycation of superoxide dismutase 1 (SOD1) has been shown to modulate the cytosolic levels of phosphorylated TAR DNA-binding protein 43 (TDP-43), a hallmark of amyotrophic lateral sclerosis (ALS) pathology. In this study, we investigated the interaction between TDP-43 and SOD1 and assessed how methylglyoxal (MGO)-induced glycation and the ALS-associated G93A SOD1 mutation affect this interplay in H4 cells. MGO exposure reduced SOD1 activity and TDP-43 phosphorylation in cells expressing WT SOD1, but not in those expressing G93A SOD1. Both WT and mutant SOD1 interacted with TDP-43 in the nucleus and cytosol; however, cytosolic interactions were more prevalent in G93A-expressing cells. Although MGO did not significantly alter the overall interaction between TDP-43 and WT SOD1, it induced cytosolic inclusion formation at 0.4 mM, a concentration associated with reduced cell viability. These inclusions did not colocalize with stress granules, indicating alternative aggregation pathways. Treatment with cyclosporin A, which inhibits the phosphatase calcineurin, decreased both TDP-43–WT SOD1 inclusions and cytosolic interactions between TDP-43 and G93A SOD1. Together, these findings suggest that SOD1 damage, induced by glycation or ALS-linked mutation, may affect TDP-43 phosphorylation status and promote its cytosolic mislocalization and aggregation, providing new insights into ALS-associated proteinopathy. Full article

Conventional cement-based foamed lightweight soil (FLS) faces cost and environmental challenges. This study develops a sustainable polyvinyl alcohol (PVA) fiber-reinforced solid waste-based FLS (PVA-SWFLS) by entirely replacing cement with a ternary system of red mud, granulated blast furnace slag, and fly ash. PVA fibers were incorporated to mitigate inherent brittleness and cracking. The effects of fiber content (0–0.9 vol%), length (3–15 mm), water–binder ratio (0.35–0.55), and wet density (550–950 kg/m³) on the fluidity and compressive strength were evaluated, along with analyses of microstructure and pore characteristics using scanning electron microscopy and mercury intrusion porosimetry. Findings reveal that fiber addition reduces flowability (up to 34.9%) but significantly bolsters compressive strength, depending on fiber content and length. For 0.3% and 0.5% contents, optimal fiber lengths of 12 mm and 9 mm were observed, respectively; the 28-day compressive strength reached a maximum of 2.97 MPa at the 0.3% content with 12 mm fibers. Beyond these optimal points, and particularly for higher contents (0.7–0.9%), strength decreased monotonically with increasing fiber length due to fiber agglomeration and reduced compactness. Furthermore, strength correlated positively with wet density and negatively with the water–binder ratio, while fluidity increased with both. The hierarchy of influence was identified as: fiber content > fiber length, and wet density > water–binder ratio, while all four parameters significantly governed fluidity. The stress–strain behavior under different parameter combinations was analyzed, and a parametric constitutive model was established to support practical applications. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with drug resistance representing the primary barrier to effective treatment. Current research has largely focused on individual signaling pathways or isolated organelle functions, yet a comprehensive understanding of how these subcellular structures coordinate to drive resistance remains lacking. This review synthesizes current knowledge through the perspective of subcellular structural homeostasis, the dynamic balance maintained by intracellular organelles. We examine how key subcellular structures, the cell membrane, mitochondria, endoplasmic reticulum, ribosomes, lysosomes, exosomes, and stress granules, undergo functional remodeling to promote drug resistance. It is crucial that these organelles do not work independently but form an integrated and dynamic communication network. Mitochondria serve as the intracellular signaling hub, integrating calcium signals, metabolic progress, and stress responses, while exosomes function as intercellular messengers that spread the anti-drug-resistant phenotype between cells. This framework reveals why targeting individual structures often fails and highlights the therapeutic potential of disrupting inter-organelle communication. We discuss emerging clinical strategies targeting subcellular structures and identify critical knowledge gaps, including the need for non-invasive biomarkers and combination approaches that target multiple network nodes. By shifting the focus from isolated organelles to their coordinated interplay, this review offers a new paradigm for overcoming drug resistance in PDAC. Full article

Granule-bound starch synthase (GBSS) is primarily recognized for its role in amylose production and starch granule formation in plant plastids. While its biochemical function in storage organs has been well documented, its broader contribution to plant growth and stress adaptation remains less defined. To explore these aspects, the maize gene ZmGBSS1 was ectopically expressed in Arabidopsis thaliana and its physiological effects were examined. Subcellular localization assays confirmed that ZmGBSS1 is specifically localized to chloroplasts. Phenotypic analysis of transgenic lines revealed that overexpression of ZmGBSS1 significantly altered early seedling development, promoted root elongation, and accelerated flowering, with flowering occurring approximately four days earlier than in wild-type plants. Changes in development were accompanied by increased starch accumulation, elevated amylose levels, and a higher abundance of enlarged starch granules within chloroplasts. Under drought and PEG-induced osmotic stress, transgenic plants maintained improved growth performance and recovery capacity, together with greater proline accumulation and chlorophyll retention. These physiological advantages coincided with more rapid starch utilization and clear rises in transcripts for proline synthesis enzymes (AtP5CS1, AtP5CS2) and starch-degrading proteins (AtBAM1, AtBAM3, AtDPE1). Collectively, these findings suggest that ZmGBSS1 not only regulates starch biosynthesis but also plays a crucial role in coordinating plant development and drought stress responses, highlighting its potential for improving stress tolerance through metabolic regulation. Full article

Building 3D printing technology exhibits remarkable construction advantages, with solid waste-based 3D printing slurry emerging as a research hotspot in the field. Phosphogypsum is compatible with diverse solid wastes for the fabrication of geopolymer, whereas its feasibility as a 3D printing material merits further investigation. In this study, calcium carbide slag (CS), ground granulated blast-furnace slag (GGBS), recycled concrete powder (RCP), and phosphogypsum (PG) underwent co-activation. The mix proportion received optimization via response surface methodology (RSM), and printability assessment proceeded based on the optimized proportion. Key conclusions include the following: PG exerts a role in optimizing the internal structure within the geopolymer matrix. The 28-day compressive strength of the composite geopolymer exceeds 25 MPa. Application as a 3D printing material facilitates enhancement of slurry stability in the later stage. Excessive PG addition elevates the shear stress and viscosity of the 3D printing paste, shortens the paste open time, and impedes paste extrusion and molding. Based on a comprehensive analysis of printability and the performance of printed specimens, the optimal mix proportion of the phosphogypsum-based geopolymer 3D printing paste was determined as follows: CS: 22.5%; GGBS: 45%; RCP: 22.5%; PG: 10%; W/b: 0.4. Full article

Plasma-facing materials (PFMs) for future fusion reactors require advanced mechanical and thermal properties to withstand the extreme challenges of high heat flux, plasma exposure, and neutron irradiation. Tungsten is one of the most suitable materials for use as a PFM in the divertor region. However, considering the high thermal loading/thermal stress combining plasma exposure and neutron irradiation/embrittlement, one of the major concerns for tungsten in PFMs is its intrinsic brittleness. To avoid cracking and components failure, tungsten toughening has been widely investigated, including the development of tungsten fiber-reinforced tungsten composites (W_f/W) using an extrinsic toughening mechanism, which could provide damage resilience against neutron embrittlement. Recently, a type of aligned long-fiber W_f/W (L-W_f/W) based on a powder metallurgical fabrication process was developed, demonstrating advanced fracture toughness while retaining other application-relevant properties. For L-W_f/W, the relatively easy production process suggests the feasibility and basis of industrialization. This work reports on the initial progress in industrializing L-W_f/W, with a focus on adapting the lab sintering process to a sintering process with industrial partner (Dr. Fritsch Sondermaschinen GmbH) and optimizing the process parameters. To improve the sinterability of tungsten and achieve higher density, various tungsten powders were explored, including commercial W powders, bimodal mixtures of different particle sizes, and granulated W powders. At the dedicated yttria interface, the thickness of yttria coating on the fibers was also optimized to ensure effective separation between the fibers and the matrix. Series of samples were produced with different dimensions up to 100 mm × 100 mm × 4 mm. After optimization, samples with 93% density and desired pseudo-ductility were prepared. Similarly to production in the lab, a major challenge in this work involved balancing the densification of the tungsten matrix with controlling fiber recrystallization and mitigating damage to the yttria interface. Full article

Background/Objectives: Alzheimer’s disease (AD) involves amyloid and tau pathology with neuroimmune dysregulation, and Yixin Yangshen Granules (YXYS) shows neuroprotective promise, though mechanisms remain unclear. This study aimed to elucidate the multi-target mechanisms of YXYS in AD. Methods: The study began by analyzing a public human AD hippocampal snRNA-seq dataset to identify cell-type-specific pathological pathways and profiled YXYS constituents by UPLC-QTOF-MS. In vitro, YXYS cytoprotection against mitochondrial dysfunction and oxidative stress was tested in Aβ_25–35-challenged HT22 cells; in vivo efficacy was assessed in Aβ_1–42-induced mice via behavioral and histopathological analyses. Integrated transcriptomic and proteomic profiling of brain tissue, with ELISA, qRT-PCR, and Western blot validation, confirmed pathway targets. Using the intersection of transcriptomic and proteomic targets as biological input, the DTIAM deep learning framework was employed to prioritize active YXYS constituents. Finally, molecular docking and 100-ns dynamics simulations demonstrated direct binding of Ganosporelactone A to HIF−1α. Results: AD snRNA-seq analysis highlighted HIF−1 and AGE-RAGE signaling as prominent pathways in the AD hippocampus, particularly enriched in brain microvascular endothelial cells, implicating neurovascular hypoxic and inflammatory stress. In Aβ-induced mice, YXYS improved cognition, reduced Aβ pathology, suppressed neuroinflammation, and promoted neuronal survival, consistent with in vitro evidence of restored mitochondrial function. Multi-omics confirmed convergence on HIF−1 and AGE-RAGE pathways, with YXYS rebalancing the neuroimmune microenvironment by reducing pro-inflammatory M0 macrophages. Screening against these consensus signaling hubs, deep learning analysis prioritized Ganosporelactone A as the top-ranked modulator, and molecular further demonstrated the stable binding of Ganosporelactone A to HIF−1α, linking YXYS to mitigation of hypoxic stress. Conclusions: Guided by multi-omics and deep learning, our findings suggest that YXYS may alleviate AD-related phenotypes through multi-target modulation of the HIF−1 and AGE-RAGE pathways, with associated improvements in neuro-immune homeostasis and reductions in oxidative stress, neuroinflammation, and hypoxia. Full article

Background/Objectives: Cancer cells are subjected to various stress conditions and have stress adaptability strategies to survive. Various types of stresses lead to the aggregation of cytoplasmic RNA granules known as stress granules (SGs), seen in normal and tumor cells, and aid in cell survival by avoiding cell apoptosis. G3BP stress granule assembly factor 2 (G3BP2) encodes a multifunctional protein with known roles as a critical component of SGs and is also associated with chemoresistance in cancer, but its known roles in non-small cell cancer (NSCLC) are limited. Methods: We evaluated the expression of G3BP2 via qPCR and immunohistochemistry on a retrospective cohort of NSCLC isolated at surgery in St James’s Hospital, Dublin, Ireland. Expression levels were correlated with clinicopathological parameters. Survival analyses, including Kaplan–Meier analyses, were used to determine the prognostic value. Additional correlations with other available NSCLC datasets were explored. Results: In contrast to other studies, we did not observe upregulated expression of G3BP2. Furthermore, Kaplan–Meier analyses did not identify any prognostic value associated with G3BP2 expression in patient tissues in contrast to other published data. Bioinformatic analyses on these other datasets found strong correlations between G3BP2 and core stress granule genes in NSCLC. Additional analyses also identified correlations between G3BP2 expression and immune cell infiltration, immune cell exhaustion, and DNA Damage Response pathways. An examination of the available datasets did not find any overall prognostic value for altered DNA methylation and survival. However, two individual CpG residues were identified for which higher methylation was associated with worse overall survival. Finally, the effects of a G3BP2 inhibitor on cellular proliferation were assessed. Conclusions: In our analysis, G3BP2 was not associated with survival benefit. However, clear associations were observed between altered expression of this gene and a number of important pathways linked to cancer pathogenesis, and further studies are warranted to assess this gene (and/or) stress granules in cancer. Full article

This research investigates the shear performance of sustainable self-compacting reinforced geopolymer concrete (GPC) beams incorporating granite waste powder (GWP) and ground granulated blast-furnace slag (GGBFS) as eco-friendly binding agents through experimental and numerical analyses. Five geopolymer reinforced concrete beam specimens (100 mm × 150 mm × 1500 mm) were tested under two-point loading conditions to evaluate the influence of longitudinal reinforcement ratio (0.85% to 2.0%) and shear span-to-effective depth ratio on the structural shear performance. The experimental investigation revealed that geopolymer reinforced concrete beams exhibit shear behavior characteristics similar to conventional Portland cement concrete beams, with the 2.0% reinforcement ratio achieving 18.3% higher shear strength compared to the 0.85% reinforcement ratio, while shear capacity increased proportionally with increasing shear span-to-depth ratio. Experimental data, including load–displacement response, shear strength measurements, strain distributions, failure modes, and crack patterns, were studied. Finite element nonlinear analysis was conducted by modifying the concrete modulus and stress–strain relationships to reflect the properties of geopolymer concrete using ABAQUS software integrated with the concrete damaged plasticity model. The results demonstrated that for the tested geopolymer reinforced concrete beams, first cracking load, steel yielding load, and ultimate load capacity increased systematically with increasing tension steel reinforcement ratio and proportionally with higher shear span-to-depth ratios. Full article

Low-carbon and highly printable cementitious materials are crucial for the practical application of extrusion-based three-dimensional concrete printing (3DCP). This study develops and optimizes a one-part alkali-activated concrete suitable for 3D printing through an integrated experimental and evaluation approach. An orthogonal experimental design was employed to investigate the effects of precursor ratio (ground granulated blast-furnace slag, GGBFS, to fly ash, FA), water-to-binder ratio, activator dosage, and retarder content on fresh-state properties, rheological behavior, setting characteristics, and mechanical performance. The optimal mixture was determined using the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) multi-criteria decision method. The mixtures exhibited suitable rheology, with a yield stress of 90–141 Pa and a plastic viscosity of 3.5–7.2 Pa·s, a setting time of 40–96 min, and mechanical performance with compressive and flexural strengths of 29–71 MPa and 4.2–6.9 MPa, respectively. The optimal mixture provided a 95-min printing open time and an acceptable pumping pressure of 1.77 MPa, while full-scale tests confirmed stable extrusion and good print quality. Furthermore, within the defined cradle-to-gate, materials-stage boundary and the adopted inventory factors, the optimized alkali-activated mixture exhibited an embodied CO₂ emission of 0.113 kg CO₂/L, which is approximately 61% lower than that of the reference cement-based printable mixture. The proposed approach provides a systematic framework for designing low-carbon, high-performance one-part alkali-activated materials for extrusion-based 3D concrete printing applications. Full article

This study investigates the production of recycled aggregates (RAs) derived from construction spoil (CS) and their influence on the mechanical properties of geopolymer concrete. Two manufacturing routes, disc pelletization and crushing granulation, were employed to produce CS-based RAs. The resulting RAs were characterized in terms of particle size distribution and geopolymer compressive strength development. Geopolymer concretes incorporating disc-pelletized and crushed aggregates achieved 7-day compressive strengths of 31.0–32.5 MPa and 37.9–38.4 MPa, 21-day compressive strengths of 31.6–36.5 MPa and 40.8–41.5 MPa, 28-day compressive strengths of 36.9–37.1 MPa and 42.3–43.5 MPa, respectively. These results confirm the technical feasibility of using CS as a high-value RA resource in structural geopolymer concrete. At the same time, the approach offers environmental and economic benefits by reducing the reliance on conventional natural aggregates and lowering the associated carbon footprint. Compared with disc-pelletized RAs, crushed RAs exhibit superior performance in improving concrete compressive strength, which is attributed to their angular morphology and higher apparent density that enhance the overall structural integrity of the concrete matrix. In contrast, disc-pelletized RAs display higher porosity and smoother surfaces, which tend to induce stress concentration and thus reduce the mechanical performance of geopolymer concrete. Overall, the findings provide practical guidance for the valorization of construction spoil through RAs production. They demonstrate that crushed CS-derived RAs can effectively replace natural aggregates in structural concrete, thereby mitigating the impacts of aggregate mining and contributing to circular economy and low-carbon construction objectives. Full article