Search Results (31,509)

This study aimed to systematically elucidate the antihyperlipidemic mechanism of paeoniflorin, and we adopted an integrated multi-omics strategy to screen the key molecular targets and regulatory pathways involved in its action, followed by experimental validation to verify the potential regulatory effects of paeoniflorin on the screened targets and metabolic processes. Rats with high-fat diet-induced hyperlipidemia received paeoniflorin treatment. Liver histopathology was evaluated using hematoxylin–eosin and Oil Red O staining. Serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bile acids, activated partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen were measured using a biochemical analyzer. Integrated multi-omics analyses were performed to investigate paeoniflorin’s lipid-lowering mechanism. Critical pathways and targets identified were validated using Western blotting. Paeoniflorin alleviated pathological liver damage in hyperlipidemic rats and improved blood lipid levels, coagulation function, and liver function markers. Multi-omics analyses verified that paeoniflorin downregulated the expression of TREM-1, TLR4, NF-κB, TNF-α, and IL-1β, thereby alleviating hepatic inflammation. Paeoniflorin also upregulated the expression of low-density lipoprotein receptors (LDLR), liver X receptor alpha (LXRα), and ATP-binding cassette subfamily G member 1 (ABCG1), while downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, contributing to balanced cholesterol metabolism. Paeoniflorin normalized glycerophospholipid and branched-chain amino acid metabolism, which correlated with reduced inflammation and improved cholesterol metabolism. Paeoniflorin ameliorates hyperlipidemia through multitarget mechanisms, potentially by suppressing the TREM-1-TLR4-NF-κB signaling pathway to reduce inflammation and by regulating cholesterol metabolism via the PCSK9-LDLR and LXRα-ABCG1 pathways. Full article

Salinity stress impairs maize growth by inducing osmotic stress, pigment degradation, and ionic imbalance, particularly during early seedling development. This study investigated the morpho-physiological and ionic responses of different maize genotypes exposed to increasing salinity levels (control, 3, 6, and 9 dS/m) at the seedling stage. Salinity caused a reduction in biomass accumulation (shoot fresh weight and shoot dry weight), plant height, and K⁺/Na⁺ ratio, with pronounced effects under severe stress. Significant genotypic variability was detected for photosynthetic pigments (chlorophyll a, chlorophyll b, total chlorophyll and carotenoids) growth traits, and ionic regulation, indicating diverse physiological adaptation strategies. Stress tolerance indices and multivariate analysis revealed that chlorophyll stability, carotenoid accumulation, and maintenance of ionic homeostasis (K⁺/Na⁺ ratio) were the dominant physiological determinants of salinity tolerance. Additionally, principal component analysis showed a shift from biomass-driven variation under non-stress conditions to pigment- and ion-driven variation under higher salinity. Based on the results, genotypes BML 6 and HKI 163 maintained higher pigment content and improved K⁺/Na⁺ balance, enabling better growth under saline conditions. These findings highlight key physiological traits underlying salinity tolerance and provide insight into early-stage adaptive mechanisms in maize. Full article

Background/Objectives: Chronic traumatic spinal cord injury (SCI) causes persistent neurological deficits for which no clinically effective regenerative therapy is currently available. Mesenchymal stromal/stem cells (MSCs), particularly Wharton’s jelly-derived MSCs (WJ-MSCs), demonstrate immunomodulatory and neurotrophic potential. This phase I/II study evaluated the safety and efficacy of intrathecal allogeneic WJ-MSC administration in individuals with chronic incomplete cervical SCI. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial (NCT05054803, EudraCT 2021-000346-18), 18 participants with chronic (1–5 years post-injury) incomplete cervical SCI (AIS B–D) received two intrathecal injections of WJ-MSCs (0.7–1.3 × 10⁶ viable cells/kg) or a placebo at baseline and 3 months. Seventeen participants completed the 12-month follow-up. Primary outcomes assessed safety, and secondary endpoints included International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor and sensory scores, spasticity, neuropathic pain, functional independence, neurophysiological measures, and quality of life. Results: Intrathecal WJ-MSC administration was safe and well tolerated. Eighty adverse events occurred (placebo: 26; WJ-MSC: 54), predominantly mild or moderate; four severe events were unrelated to treatment. Both groups demonstrated significant within-group improvements in total motor scores at 12 months, with no between-group difference. No treatment effects were observed for sensory scores, electrophysiological measures, functional independence, spasticity, pain, or patient-reported outcomes. Conclusions: In this first randomised, placebo-controlled trial evaluating intrathecal WJ-MSCs in chronic incomplete cervical SCI, WJ-MSC administration demonstrated a favourable safety profile; however, no significant between-group differences were detected relative to the placebo. Given the limited sample size and early-phase design, the efficacy findings should be interpreted cautiously. Future research should explore enhanced cell products, intensified dosing schedules, optimised delivery strategies, early intervention, and multimodal therapeutic combinations. Full article

The food packaging industry requires sustainable solutions to reduce plastic waste and replace synthetic additives. This study addresses the need for scalable methods to transform conventional polyethylene terephthalate (PET) packaging into active food preservation systems using natural biocides. Commercial PET packaging was surface-activated using industrial-scale corona treatment, followed by coating with natural biocides—carvacrol (CV) and trans-cinnamaldehyde (tCN). The resulting active packaging materials (PET-CV and PET-tCN) were characterized using XRD, FTIR, SEM, AFM, and desorption kinetics. Packaging properties including mechanical strength, oxygen barrier, antioxidant (DPPH), and antibacterial activity (against S. aureus and E. coli) were evaluated. Real-food preservation tests were conducted using fresh minced pork (4 °C, 6 days) and table olives (23 °C, 21 days), monitoring microbiological (TVC), colorimetric (CIE L*a*b*), and pH changes. Corona treatment successfully anchored both biocides through physical adsorption, with tCN exhibiting stronger surface interaction (desorption energy: 128.0 kJ/mol). Both coatings significantly improved oxygen barrier properties (61% reduction for PET-CV, 80% for PET-tCN). PET-tCN demonstrated superior antibacterial activity (inhibition zones: 15.0 mm against E. coli). In pork preservation, PET-tCN achieved a 2-log reduction in TVC, maintained meat redness (a*: 12.80 vs. 5.10 for control), and stabilized pH. For olives, PET-tCN reduced TVC by 2.35 log cycles and preserved green color. This corona-assisted coating approach, demonstrated here at laboratory scale, successfully transforms inert PET into multi-functional active packaging with potent antimicrobial, antioxidant, and barrier properties, significantly extending food shelf-life and offering a sustainable solution for reducing food waste. Full article

With rising global energy demand and the gradual depletion of petroleum-based resources, interest in alternative fuels for internal combustion diesel engines (ICDEs) has increased. In ICDEs, firing-related and mechanical excitations may result in adverse vibration and noise responses. This study examines whether incorporating sour cherry pit pyrolysis oil (SCPO) with n-butanol and 2-ethylhexyl nitrate (2-EHN) may reduce vibration and noise under constant-load, steady-state operating conditions compared with neat diesel (D100). For the experimental tests, five fuel types were prepared: one neat diesel fuel and four blended fuels with a constant diesel fraction of 40% and a fixed 2-ethylhexyl nitrate (2-EHN) content of 5%, while the SCPO and n-butanol fractions were varied (D40/SCPO0/B55/2-EHN5, D40/SCPO5/B50/2-EHN5, D40/SCPO10/B45/2-EHN5, and D40/SCPO15/B40/2-EHN5). Experiments were performed using a single-cylinder ICDE at a fixed load of 10 Nm under steady-state conditions at engine speeds of 1500, 1800, 2400, 3000, and 3600 rpm. For each operating condition, vibration and noise data were recorded over a 10.4 s window. Experimental findings indicate that D40/SCPO10/B45/2-EHN5 yielded the lowest mean overall RMS vibration, with a 37.5% reduction relative to neat diesel (D100), and the lowest equivalent sound level (LAeq) among the tested fuels. Under the investigated steady-state constant-load conditions, the D40/SCPO10/B45/2-EHN5 fuel blend demonstrates the potential to achieve lower measured vibration and noise levels than neat diesel. Full article

Background: Accurate identification of patients at high risk of perioperative blood transfusion is essential for optimizing patient blood management (PBM) strategies in oncological surgery. However, the performance of standard PBM eligibility criteria in real-world oncological settings remains incompletely characterized. Material and Methods: We conducted a retrospective, single-center analysis of 4228 consecutive patients undergoing elective oncological surgery of any complexity or liver transplantation over a 9-month period to assess transfusion need and estimate access to preoperative patient blood management (PBM) strategies to improve anemia management. Transfusion events were assessed within 24 h after surgery (PS24) and during the perioperative period (PO; 48 h before to 72 h after surgery). Two PBM eligibility strategies were applied to the same patient cohort and compared: (A) an observational approach, based on predefined PBM indicators (transfusion rate and transfusion index by surgical complexity), and (B) a multivariable modeling approach based on pre- and intraoperative anesthesiology assessment to estimate individual transfusion risk. Predictive performance of both strategies was evaluated using accuracy, Cramér’s V, area under the receiver-operating characteristic curve (AUC-ROC), and Brier score. Results: Overall, 7.7% of patients received transfusion within PS24 and 9.2% during PO. According to the observational approach, 23.8% of patients were classified as PBM-eligible, accounting for 89.2% of PS24 transfusions and 87.1% of PO transfusions. In the multivariable modeling approach, independent predictors of transfusion included surgical type (e.g., sarcoma surgery: OR 22.8 for PS24; OR 6.3 for PO; vs. senology surgery OR 1 for PS24; OR 1 for PO, respectively), anemia severity (moderate anemia: OR 64.3 and OR 107.9, respectively and mild anemia OR 3.38 and OR 3.65, respectively), high surgical complexity, operative time >3 h (>3 h: OR 8.83 and OR 8.65, respectively vs. <3 h OR 1 and OR 1, respectively), and ICU admission risk. The observational approach demonstrated stronger alignment with actual transfusion events (Cramér’s V = 0.44–0.47) and higher overall accuracy (90.8–92.3%); in contrast, a multivariable modeling approach showed superior discrimination (AUC = 0.94–0.95) and lower Brier scores, indicating better individual risk prediction. Conclusions: In a large real-world cohort of oncological surgical patients, standard PBM eligibility criteria effectively identified the majority of patients requiring perioperative transfusion. While multivariable modeling provided greater predictive precision, the observational PBM approach demonstrated strong clinical alignment and practical applicability. Integrating both strategies may support more effective transfusion risk stratification and PBM planning in oncological surgery. Full article

Systemic risk in banking systems arises from losses transmitted through networks of contractual exposures. Yet, most widely used measures rely on market-implied volatility and equity prices rather than structural balance sheet fragilities. This paper develops a flow network framework that models systemic risk as a capacity-constrained loss-diffusion process governed by flow conservation, contractual seniority, and interbank topology. Using regulatory balance sheet data for four major U.S. banks across six quarters of the 2007–2008 financial crisis, we simulate millions of unit-consistent cascade scenarios to characterize the distribution of bank failures and aggregate losses. Despite severe macro-financial stress, the system remains in a subcritical contagion regime, exhibiting frequent single-bank failures, virtually no multi-bank cascades, and quasi-stationary aggregate losses concentrated around USD 420–430B.We extend the model to a stochastic setting in which the initial shock magnitude is randomized while propagation mechanics remain deterministic. The resulting loss distribution remains tightly concentrated and scales approximately linearly with shock size, suggesting that uncertainty in shock realizations does not induce nonlinear cascade amplification. Applying an efficient network benchmark, we estimate that 10–23% of expected systemic loss is attributable to suboptimal network architecture, implying potential gains from structural policy intervention. A comparison with SRISK reveals early divergence and convergence only at peak stress, highlighting the complementary roles of structural and market-based systemic risk measures. Finally, a graph neural network trained on synthetic flow network data fails to reproduce threshold-driven cascade dynamics, underscoring the importance of considering network structures vis-à-vis data-driven approaches. Full article

Soybean mosaic virus (SMV) is a major constraint on global soybean (Glycine max (L.) Merr.) production, causing substantial economic losses worldwide. Despite these losses, the potential of resistance genes as a solution remains largely unexplored. In this study, the COPPER CHAPERONE FOR SUPEROXIDE DISMUTASE (GmCCS) was initially employed as a bait to screen the soybean cDNA library, leading to the identification of a protein homologous to Arabidopsis thaliana COP9 signalosome complex subunit 5B (AtCSN5B), designated as GmCSN5B. Quantitative real-time PCR (qRT-PCR) analysis revealed differential expression of GmCSN5B in the SMV-resistant (Qihuang No.1, QH) and susceptible (Nannong 1138-2, NN) variety following SMV-SC3 strain inoculation. Knockdown of GmCSN5B via Bean pod mottle virus (BPMV)-induced gene silencing (VIGS) significantly enhanced SMV resistance compared to control plants. This work further demonstrated that GmCSN5B can interact with the downstream GmVTC1 protein, which was potentially associated with ascorbic acid (AsA; Vitamin C) synthesis. Moreover, GmVTC1 also responded to SMV infection, and its knockdown led to a reduction in endogenous AsA levels within the host, thereby compromising the plant’s resistance to SMV. Together, these findings suggest that the GmCCS-GmCSN5B-GmVTC1 pathway in soybean modulates host resistance to SMV through the regulation of AsA synthesis. Full article

Early-age cracking is a common issue in the prefabrication of large-scale box girders, and the application of pre-tensioning techniques to introduce pre-compressive stress is an effective measure to mitigate such cracking. To determine an optimal pre-tensioning scheme for the 60 m large-scale box girder used in the Ningbo–Xiangshan intercity railway, friction coefficient tests and field stress monitoring were conducted. A numerical model simulating the pre-tensioning process of the box girder, accounting for the constraint of the steel formwork, was developed using Abaqus 2021. Based on the validated finite element model, a parametric study was performed to investigate the effects of friction coefficient, internal formwork roof, and prestressing tendon arrangement on the pre-compressive stress. The results indicate that the bond force between cast-in-place concrete and steel formwork is approximately 2.1 times the sliding friction force. As the friction coefficient increases, the pre-compressive stress in the box girder exhibits a notable decreasing trend. For the critical midspan section S40, the inclusion of frictional effects results in a more uniform distribution of pre-compressive stress. Compared to the case without the internal formwork roof, its inclusion leads to a 9.2% to 10.4% reduction in pre-compressive stress at section S40. To mitigate prestress losses transmitted from the ends to the midspan section, it is recommended that the internal formwork be completely removed prior to prestressing tensioning. The pre-compressive stress in the box girder varies considerably with different prestressing combinations. The comparative analysis of different prestressing combinations reveals substantial variations in pre-compressive stress distribution. After evaluating multiple schemes, the optimal pre-tensioning sequence for the 60-m railway box girder is determined as follows: sequentially tensioning tendon groups F1-2, F1-4, F1-5, F1-6, and B2-3, with an anchorage stress controlled at 558 MPa. This scheme ensures that all critical sections of the box girder remain in a pre-compressive state. In particular, the pre-compressive stress at the key midspan section S40 ranges from 1.12 to 1.26 MPa, achieving the desired effect and effectively suppressing early-age cracking in the large-scale box girder concrete. Full article

Background: MSCs possess strong immunoregulatory properties and play a central role in maintaining immune homeostasis by limiting inflammatory responses. Their function is highly plastic and influenced by environmental cues, including viral signals. How SARS-CoV-2-derived antigens affect MSC immunoregulation remains incompletely understood. This study aimed to investigate the impact of SARS-CoV-2 peptides on MSC-mediated immune modulation of T-cells. Methods: MSCs were stimulated directly with SARS-CoV-2 spike protein S peptides or cocultured with SARS-CoV-2 peptide-activated T-cells. TLR4 surface expression and receptor downstream signaling were assessed to evaluate pathway activation. MSC immunoregulatory function was analyzed by measuring suppression of TNF-α and IFN-γ expression and induction of CD4⁺FOXP3⁺ regulatory T-cells. TLR4 inhibition and lipopolysaccharide (LPS) stimulation were used to examine pathway specificity and interaction. Results: SARS-CoV-2 peptides activated TLR4-associated signaling in MSCs, increasing TLR4 expression and NF-κB phosphorylation. Peptide-treated MSCs showed impaired suppression of pro-inflammatory cytokines and reduced induction of regulatory T-cells. TLR4 inhibition prevented these effects. LPS induced similar effects, while combining LPS and peptide stimulation partially restored physiological T-cell cytokine suppression. Conclusions: SARS-CoV-2 peptides modulate MSC immunoregulatory function on T-cells via TLR4-dependent mechanisms. Full article

This work develops a zero-trust, physics-constrained mathematical framework for detecting stealthy drift perturbations in power system dynamical models. Such perturbations constitute adversarial, statistical deviations that preserve first-order operating trends, making them difficult to identify using classical residual-based estimators or unconstrained data-driven models. We introduce ZETWIN, a spatio-temporal learning architecture formulated as a constrained optimization problem in which the nodal admittance matrix $Y_{bus}$ acts as a graph-structured linear operator embedded directly into the loss functional. This construction enforces Kirchhoff-consistent latent representations and yields a mathematically grounded zero-trust decision rule that flags any trajectory violating physical feasibility, independent of prior attack signatures. The proposed framework is evaluated using a PyPSA-based AC–DC meshed network, demonstrating an AUROC = 0.994, and F1 = 0.969. The formulation highlights how physics-informed constraints, graph operators, and spatio-temporal approximation theory can be combined to construct mathematically interpretable zero-trust detectors for complex dynamical systems. Full article

Image encryption methods aim to transform a secret image into a noise-like, texture-like image. Since this behavior of the encrypted image indicates that it is encrypted, it provokes a large number of attacks. One of the most effective methods to counter this threat is to protect the information by transforming the original image into a new, meaningful image. The bottleneck of this approach is that the new image in which the information is embedded must have a high visual quality that is indistinguishable from the real image. Another critical requirement is obtaining the original image without loss. In this paper, we propose a reversible image camouflage method based on lossless matrix transformation and two-dimensional wavelet transformation. Random matrix perturbation is introduced and applied as an effective method for the lossless transformation of low-frequency or flat regions. The proposed method was applied to different datasets for performance analysis. The PSNR values of the plain/camouflage image pair are above 55 dB, and the SSIM values obtained by our method are very close to 0.9999 on these datasets. The experimental results demonstrate that the method’s performance is independent of the content of the plain/target image and of the fragment size. Furthermore, in cases where the target image is specifically chosen, PSNR values exceed 58 dB. Additionally, the efficacy of the method in generating camouflage images has been demonstrated through histogram analysis and performance analysis in the low- and high-frequency regions. Full article

Background/Objectives: Hand, foot, and mouth disease (HFMD) is a major public health concern primarily caused by human enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), coxsackievirus A6 (CVA6), and certain coxsackievirus B serotypes. Currently available EV-A71 vaccines lack cross-protective efficacy against other serotypes, highlighting the urgent need for multivalent and broadly effective enterovirus vaccines. Methods: Immunoinformatics approaches were used to predict highly immunogenic B-cell and T-cell epitopes, which were assembled to construct a novel multivalent epitope vaccine, rCV-A3V, followed by in silico validation. Recombinant protein expression was confirmed by Western blotting and immunofluorescence assays. The immunogenicity was evaluated in Balb/c mice following intranasal immunization. Results: A preliminary safety evaluation demonstrated that the rCV-A3V vaccine was well tolerated in the mouse model, with no abnormal changes in body weight observed after immunization. In addition, the target protein was successfully expressed. Intranasal immunization induced a strong Th1-biased immune response, robust serum neutralizing and IgG antibody responses, and pronounced mucosal immunity, including elevated sIgA and IgG levels in nasal lavage fluid, sIgA in feces, and substantial sIgA responses in milk. Dominant epitope peptides were also identified. Conclusions: The intranasal live attenuated rCV-A3V vaccine successfully induced humoral, mucosal, and cellular immune responses against EV-A71, CVA16, CVA6, and CVB3, demonstrating broad immunogenicity. These findings provide experimental evidence supporting its potential as a candidate vaccine for HFMD. Full article

This study investigated the effects of four LED light qualities, red+blue+far-red (WRS-LED), blue+red (BR-LED), blue (B-LED), and red (R-LED), and exogenous L-glutamic acid at 10 ppm on the growth and quality of red mustard spinach (Brassica rapa var. perviridis) cultivated in a plant factory using a recirculating deep-flow hydroponic system. Plants were exposed to four LED light quality treatments at 180 ± 10 μmol·m⁻²·s⁻¹ PPFD for 28 days after transplanting. L-glutamic acid at 10 ppm was applied once to the recirculating nutrient solution 15 days after transplanting, resulting in 13 days of exposure prior to final harvest on day 28. All growth and quality parameters were measured at the final harvest after 28 days of cultivation. WRS-LED promoted the greatest biomass production. Additionally, vitamin C content, DPPH radical scavenging activity, and total phenolic content were highest under BR-LED and B-LED conditions. Notably, under B-LED, L-glutamic acid treatment increased total phenolic content to approximately twice that of the control. Leaf redness, expressed as Hunter a* values, was observed exclusively under BR-LED. Principal component analysis revealed that LED light quality was the primary determinant of treatment responses, with growth-related traits associated with WRS-LED and R-LED, and quality-related traits with B-LED and BR-LED. Overall, BR-LED combined with L-glutamic acid represents the most suitable treatment for red mustard spinach cultivation in plant factories, achieving a favorable balance between growth and nutritional quality. Full article

The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health. Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species. Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site, enabling systemic viral spread, alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals. Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation, particularly within the haemagglutinin and polymerase complex. Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccination strategies are advancing beyond traditional adjuvanted inactivated vaccines toward next-generation platforms, including mRNA and virus-like particle vaccines, designed for rapid deployment and broader immune protection. However, ongoing viral evolution, constrained vaccine availability, and gaps in coordinated surveillance underscore the urgent need for an integrated One Health approach to reduce panzootic risk. Full article