Search Results (379)

The global emergence of the avian influenza virus (AIV) H5N1 clade 2.3.4.4B since 2016 has caused substantial losses in wild bird and poultry populations, along with heightened risks of transmission to humans and other mammals. Vaccination of poultry has been a key strategy to curb the virus’s spread and mitigate its socioeconomic impact. This report describes an outbreak of high pathogenicity avian influenza virus (HPAIV) H5N1 clade 2.3.4.4B in a flock of 15,000 brown layer chickens (170 days old), all of which had received a four-dose vaccination regimen with H5N1/H5N8 commercial vaccines at 17, 50, 100, and 125 days of age. Despite this vaccination history, H5N1 infection was confirmed approximately seven weeks post-vaccination. H5N1 infection was confirmed by RT-qPCR, virus isolation, and full genome sequencing covering all eight gene segments, followed by phylogenetic and molecular analyses. Clinical signs included reduced feed intake, decreased egg production, and a cumulative mortality rate of 35% over 52 days. Hemagglutination inhibition (HI) testing with various H5 antigens revealed inconsistent antibody titers (geometric mean: 4.0 to 9.1 log2). Genetic analysis of the full-length HA and NA gene sequences further revealed strong similarity to contemporaneous H5N1 clade 2.3.4.4B strains circulating in Egypt, with multiple mutations in the HA head domain, particularly near immunogenic epitopes and receptor binding sites. These findings highlight the limitations of current vaccination strategies under conditions of antigenic mismatch and complex immunization schedules, emphasizing the need for improved vaccine matching and continuous molecular surveillance. To improve outbreak management in poultry, enhanced vaccination protocols, stringent biosecurity measures, and rigorous monitoring practices are critical. Full article

Background/Objectives: Alzheimer’s disease (AD) is the most common cause of dementia worldwide; however, there is incomplete understanding of AD pathogenesis, and there are few disease-modifying treatments for AD. Research has begun to demonstrate that necroptosis, which is a regulated type of cell death mediated by receptor-interacting protein kinase 1 (RIPK1), plays a significant role in neurodegeneration and neuropathology associated with AD. The purpose of this review is to summarize current research regarding the role of RIPK1 in AD and possible therapeutic uses of RIPK1 inhibitors. Methods: This study is a narrative review of the literature summarizing experimental and clinical studies on RIPK1 signaling, necroptosis, neuroinflammation, and blood–brain barrier (BBB) dysfunction in AD. Results: The cumulative evidence demonstrates that RIPK1 activation associates with common AD pathways and particularly increases the severity of amyloid-β (Aβ) and tau pathology; promotes microglial activation; decreases the integrity of the BBB; and increases neuroinflammatory signaling in AD. Preclinical studies have shown that inhibiting RIPK1 genetically or pharmacologically in preclinical models decreased the extent of neurodegeneration and the rate of cognitive decline. Conclusions: RIPK1 is a key molecular link between necroptosis and neuroinflammation in AD. While the preclinical data are encouraging, further clinical research will be necessary to investigate RIPK1 changes in the brain, which may help better understand AD and establish the safety and effectiveness of potential therapeutic RIPK1 inhibitors in AD. Full article

Soil acidity is a major constraint in many agricultural regions, where increased aluminum (Al³⁺) solubility at low pH severely affects plant health by inhibiting root elongation, disrupting nutrient uptake, and inducing oxidative stress. Recent studies have highlighted melatonin, a widely occurring indoleamine with strong antioxidant and stress-modulating properties, which alleviates Al-induced damage in crops. This review synthesizes current physiological, biochemical, and agronomic evidence demonstrating that exogenous melatonin enhances plant tolerance to aluminum toxicity. Across multiple model and crop species, melatonin application has been shown to improve root elongation by 20–45%, reduce lipid peroxidation by 30–60%, and enhance key antioxidant enzymes such as SOD, POD, and CAT by 25–70% under Al stress. Case studies in soybean, wheat, maize, and rice further indicate that melatonin protects root meristems from oxidative damage, stabilizes photosynthetic machinery, and improves nutrient acquisition. In acidic soils (pH 4.5), melatonin-treated soybean exhibited 28% greater biomass and 15–22% higher N and P uptake, while wheat plants demonstrated 10–18% higher grain filling under field-simulated Al stress. Emerging long-term studies show that melatonin also benefits soil health. Multi season experiments reveal that melatonin enhances root exudates that support beneficial rhizosphere microbes, increases soil enzymatic activities (urease, phosphatase) by 20–35%, and lowers exchangeable Al by 12–18%. These improvements contribute to cumulative yield gains of 10–18% over successive cropping cycles. Additionally, genetic approaches aimed at increasing endogenous melatonin levels in plants have demonstrated 12–30% yield improvement in acid soil conditions. This review highlights the need for multi-year, multi-location studies to further clarify how melatonin can support sustainable agricultural practices, enhance soil fertility, and mitigate aluminum toxicity in acid-affected regions. Full article

Background/Objectives: Body Protection Compound-157 (BPC 157) is a stable gastric pentadecapeptide with cytoprotective, pro-angiogenic, and nitric oxide (NO)-modulating properties that has gained increasing attention for its therapeutic potential. Although vasodilatory effects have been demonstrated in animal models, functional evidence in human arterial tissue remains limited. This study investigated the effects of BPC 157 on vascular tone in human internal mammary artery (IMA) rings and evaluated the contribution of endothelial NO signaling. Methods: Residual IMA segments obtained from elective coronary artery bypass graft surgeries (n = 12) were dissected into endothelium-intact and endothelium-denuded rings. Following equilibration, the rings were challenged by phenylephrine (PheE; 3 × 10⁻⁶ M) to induce contraction. Cumulative concentration–response curves of BPC 157 (0.01–1 mg/mL) for five consecutive doses were constructed. The involvement of NO was assessed by BPC 157 dose–response curves in the nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 10⁻⁶ M) pre-incubated rings. Maximum force of contraction, area under the curve, maximum response (Emax), and negative logarithm of the half-maximal effective concentration (pEC50) values were analyzed. Results: BPC 157 produced a concentration-dependent reduction in PheE-induced contraction in both groups, with significantly greater relaxation in endothelium-intact rings (p < 0.05). L-NAME increased contractile responsiveness in intact rings and attenuated BPC 157-induced relaxation. Under NOS inhibition, differences between groups progressively diminished and concentration–response curves converged at higher concentrations. Emax analysis demonstrated that endothelial integrity markedly enhanced maximal vasorelaxation, whereas this advantage was largely abolished after NOS inhibition. Conclusions: BPC 157 induces concentration-dependent vasorelaxation in human arterial tissue, predominantly mediated via an endothelium-dependent NO pathway. Endothelial integrity primarily enhances maximal efficacy, while residual effects indicate additional mechanisms. These findings provide early mechanistic evidence for the vascular activity of BPC 157, although further molecular and in vivo studies are required to clarify its clinical relevance. Full article

Background: Ponatinib (PON), an effective tyrosine kinase inhibitor for leukemias harboring the T315I mutation, is limited by severe cardiotoxicity, including myocardial infarction and heart failure. Here, we investigated the therapeutic potential of Bone Morphogenetic Protein-7 (BMP-7), an anti-inflammatory growth factor, in a murine model of PON-induced cardiotoxicity. Methods: C57BL/6J mice were distributed into experimental groups receiving PON (25 mg/kg cumulative dose) either alone or with BMP-7 (600 μg/kg cumulative dose), along with a corresponding control group. Cardiac analyses included molecular and histological assessments. Results: PON administration induced a marked increase in monocyte infiltration and M1 macrophage polarization. These inflammatory events led to the upregulation of the pyroptotic cascade, leading to activation of the TGF-β1/SMAD2/3 signaling axis. In contrast, BMP-7 significantly attenuated these pathological responses by suppressing inflammation-induced pyroptosis and the TGF-β1/SMAD2/3 signaling axis. Conclusions: These findings identify inflammation-induced pyroptosis as a central driver of the pathological changes in PON-induced cardiotoxicity. Notably, our work highlights BMP-7’s capacity to inhibit these disease-related alterations. Collectively, these results expand on the current knowledge of the mechanistic framework of PON-induced cardiotoxicity, while also emphasizing BMP-7 as a promising therapeutic candidate with potential translational relevance. Full article

The treatment of chronic lymphocytic leukemia (CLL) has significantly shifted from chemoimmunotherapy to targeted therapies like Bruton’s tyrosine kinase and BCL2 inhibitors. Despite these advancements, CLL remains an incurable disease characterized by immune dysregulation, therapeutic resistance, and cumulative toxicities. To overcome these challenges, novel immunotherapeutic strategies are emerging as fundamentally different approaches that target immune–tumor interactions. These innovations include novel monoclonal antibodies, bispecific antibodies that redirect T cell cytotoxicity, chimeric antigen receptor (CAR) T-cell therapies, and natural killer (NK) cell-based platforms. By actively engaging cellular cytotoxicity, these approaches show promise in high-risk and treatment-resistant scenarios where standard pathway inhibition is inadequate. Establishing optimal use, toxicity management, and combination strategies for these cell-engaging immunotherapies is now a critical priority in contemporary CLL research. Full article

To achieve the large-scale, high-value utilization of vanadium–titanium slag (VTS) in the metallurgical industry, this study replaces blast furnace slag (BFS) with VTS to construct a quaternary all-solid-waste cementitious system composed of VTS, BFS, steel slag (SS), and desulfurization gypsum (DG). It systematically investigates the effects of VTS content (0–60%) on the mechanical properties, leaching toxicity, and hydration heat behavior of the system. XRD, TG–DSC, and SEM–EDS techniques are employed to explore the influence of VTS on hydration behavior and microstructural evolution. The results show that when VTS replaces 30% of the BFS (A3, VTS:BFS:SS:DG = 3:3:3:1), the 28-day compressive strength reaches 31.33 MPa. The leaching concentrations of heavy metals in all specimens are far below the standards for drinking water quality. Hydration heat analysis reveals that the incorporation of VTS advances the acceleration period of hydration. The A3 specimen maintains a relatively high heat release rate in the middle and later stages (after 72 h), and its cumulative heat release is significantly higher than that of the system without VTS, revealing the “slow hydration” mechanism of VTS at later stages. The [SiO₄]–[AlO₄] bonds in VTS undergo a depolymerization–repolymerization process. In addition, an appropriate amount of VTS promotes the deposition of hydration products such as ettringite (AFt), C–S–H, and C–A–S–H gels through micro-filling effects and heterogeneous nucleation, thereby improving the microstructure of the system. However, excessive VTS (≥45%) significantly inhibits the hydration reaction and reduces gel formation due to the decrease in highly reactive BFS components and the increased TiO₂ content. This study provides new insights into the resource utilization of VTS in multi-solid-waste cementitious materials. In addition, VTS-based cementitious materials are suitable for practical scenarios with low early strength requirements, such as goaf backfilling. Therefore, future studies should further investigate the long-term sulfate resistance and carbonation resistance of these materials under real application conditions. Full article

This study focuses on the production and characterization of polyvinyl alcohol (PVA)-chitosan (CS)-based nanoparticles loaded with vitamin E (VitE) and ephedrine (Ep) via electrospraying for intranasal drug delivery in narcolepsy treatment. The nanoparticles were successfully synthesized using optimized parameters (15.5 kV voltage, 0.3 mL/h flow rate, 25 G needle size, and 14 cm distance). Scanning electron microscopy (SEM) analysis confirmed the formation of spherical particles with an average size of 350–500 nm, while energy-dispersive X-ray spectroscopy (EDS) mapping revealed a homogeneous elemental distribution with oxygen (51.74%), silicon (24.48%), carbon (6.47%), zinc (6.08%), and aluminum (3.82%). Fourier-transform infrared (FTIR) spectra demonstrated the successful encapsulation of VitE and Ep through characteristic peaks at 3285 cm⁻¹ (OH stretching), 1731 cm⁻¹ (C=O stretching), and 1086 cm⁻¹ (C-O-C stretching). In vitro drug release analysis indicated a controlled and sustained release profile, with cumulative VitE and Ep release reaching 78.6% and 84.3%, respectively, over 48 h in phosphate-buffered saline (PBS, pH 7.4). Antioxidant activity assessment using the DPPH assay confirmed an R² value of 18.84 µg/mL, demonstrating significant free radical scavenging potential. The antibacterial activity, tested via the disk diffusion method, exhibited inhibition zones of 18.31 ± 5.8 mm (E. coli) and 21.51 ± 1.57 mm (S. aureus), confirming strong antimicrobial properties. These findings suggest that the developed electrosprayed PVA/CS nanoparticles loaded with VitE and Ep offer a promising intranasal delivery system with enhanced bioavailability, controlled release, antioxidant capacity, and antibacterial properties, making them a viable candidate for narcolepsy treatment. Full article

Atmospheric corrosion of carbon and low-alloy steels causes direct economic losses that are estimated at around 3.4% of the global GDP, and its accurate multi-year prediction is essential for protective coating selection, service-life estimation, and infrastructure maintenance scheduling. In this study, machine learning (ML) algorithms, including gradient boosting regressor (GBR), eXtreme gradient boosting (XGBoost), random forest (RF), support vector regression (SVR), and ridge regression, were trained on a 600-sample physics-grounded dataset to predict the cumulative atmospheric corrosion loss (µm) of low-alloy steels over 1–10 years of exposure. The dataset was constructed using the exact ISO 9223:2012 dose–response function (DRF) for a first-year corrosion rate and the ISO 9224:2012 power-law multi-year kinetic model (C(t) = C₁·t0.5), spanning ISO 9223 corrosivity categories C2–CX across 11 environmental and material input features. All models were evaluated on the original (untransformed) corrosion scale under an 80/20 train/test split and five-fold cross-validation. Gradient boosting achieved the best overall performance with test set R² = 0.968, CV-R² = 0.969, RMSE = 10.58 µm, MAE = 5.99 µm, and MAPE = 12.6%. XGBoost was a close second (R² = 0.958, CV-R² = 0.960). RF achieved an R² of 0.944. SHAP (SHapley Additive exPlanations) analysis identified SO₂ deposition rate, exposure time, relative humidity, Cl⁻ deposition rate, and temperature as the five most influential predictors. The dominance of the SO₂ deposition rate (mean |SHAP| = 26.37 µm) and the high second-place ranking of exposure time (13.67 µm) are fully consistent with the ISO 9223:2012 dose–response function and ISO 9224:2012 power-law kinetics, respectively, while among the material features, Cu and Cr contents showed the strongest negative SHAP contributions, confirming their corrosion-inhibiting roles in weathering steels. These results establish a physics-consistent, interpretable ML benchmark exceeding R² = 0.90 for multi-year cumulative corrosion loss prediction and provide a quantitative tool for alloy screening, coating selection in aggressive atmospheric environments, and service-life planning. Full article

Traditional pedestrian inertial navigation (PDR) algorithms usually assume that the carrying mode of a smartphone is fixed and remains horizontal, while ignoring the significant impact of dynamic changes in the carrying mode on heading estimation, which is the core element of PDR algorithms. In practical application scenarios, pedestrians often change their way of carrying smart terminals (e.g., calling) according to their needs, corresponding to the difference in the heading estimation method; especially when the mode is switched, it will cause a sudden change in heading, which will lead to a significant increase in the localization error if it cannot be corrected in time. Existing smart terminal carrying mode recognition methods that rely on traditional machine learning or set thresholds have poor robustness; lack of universality, especially weak diagnostic ability for mutation; and can not effectively reduce the heading error. Based on these practical problems, this paper innovatively proposes a PDR framework that tries to overcome these limitations. Based on this research purpose, firstly, this paper classifies four types of common carrying modes based on practical applications and designs a CNN-LSTM hybrid model, which can classify the four common carrying modes in near real-time, with a recognition accuracy as high as 99.68%. Secondly, based on the mode recognition results, a multi-layer heading correction strategy is introduced: (1) introducing a quaternion-based universal filter (VQF) algorithm to realize the accurate estimation of initial heading; (2) designing an algorithm to accurately detect the mode switching point and developing an adaptive offset correction algorithm to realize the dynamic compensation of heading in the process of mode switching to reduce the impact of sudden changes; and (3) considering the motion characteristics of pedestrians walking in a straight line segment where lateral displacement tends to be close to zero. This study designs a heading optimization method with lateral displacement constraints to further inhibit the drifting of the heading caused by the slight swaying of the smart terminal. In this study, two validation experiments are carried out in two different environment—an indoor corridor and a tree shelter—and the results show that based on the proposed multi-layer heading optimization strategy, the average heading error of the system is lower than 1.5°, the cumulative positioning error is lower than 1% of the walking distance, and the root mean square error of the checkpoints is lower than 2 m, which significantly reduces the positioning error and shows the effectiveness of the framework in complex environments. Full article

Background/Objectives: Ovarian cancer (OC) remains the most lethal gynecologic malignancy, largely due to late-stage diagnosis and high rates of recurrence following platinum-based chemotherapy. Growing evidence implicates cancer stem-like cells (CSCs) in OC relapse, as these cells exhibit enhanced chemoresistance, stemness, epithelial–mesenchymal transition (EMT), and the capacity to remodel the tumor microenvironment. Inhibitors of DNA-binding (ID) 1-4 proteins are transcription factors with known redundancy; however, their collective role in OC chemotherapy response remains poorly defined. Here, we examined how ID family signaling responds to chemotherapy and contributes to CSC-associated features and microenvironment remodeling. Methods: Publicly available patient data, OC cell lines, and a subcutaneous xenograft mouse model were used to correlate changes in ID1-4 expression with CSCs, EMT, and the tumor microenvironment (TME). OC cell lines were used for in vitro assays to evaluate CSC features and IL-6 production in the presence of carboplatin and/or a small molecule inhibitor of ID proteins, AGX51. Results: Analysis of clinical datasets, cell lines, and in vivo models revealed enrichment of ID1-4 following chemotherapy, with additive increases across treatment cycles. In vivo ID2 and ID4 expression was associated with IL-6 secretion and loss of anti-tumoral macrophages. Pan-ID inhibition demonstrated that cumulative ID activity minimally supports CSC maintenance during chemotherapy, while more strongly regulating IL-6 secretion. Conclusions: IL-6 production from cancer cells was at least partially dependent on ID proteins, linking collective ID signaling to microenvironment remodeling and relapse potential in ovarian cancer. Full article

Recent evidence links lens epithelial cell (LEC) dysfunction and cellular senescence—an irreversible cell cycle arrest with a pro-inflammatory secretory phenotype—to age-related cataract (ARC) progression. This systematic review synthesizes current knowledge on LEC senescence, its molecular features, and laboratory methods for senescence assessment in the ARC. Following PRISMA guidelines, a comprehensive search of PubMed, Scopus and Cochrane databases retrieved 3417 records from inception to 9 February 2025, with 14 studies ultimately included (821 patients and multiple in vitro LEC models). The following multiple senescence expression pathways were identified: SA-β-gal activity, p53/p21 and p16INK4A pathway activation, mitochondrial dysfunction, oxidative stress, and secretion of senescence-associated secretory phenotype (SASP) factors. Notably, cortical cataract demonstrated direct association with local senescent cell accumulation, while nuclear cataract reflected cumulative oxidative damage from impaired LEC-mediated antioxidant defense. Senescence markers correlated positively with cataract severity across multiple studies. Several potential therapeutic targets emerged, including metformin (AMPK activation/autophagic restoration), circMRE11A silencing, NLRP3 inflammasome inhibition, and modulation of FYCO1/PAK1 and MMP2 pathways. This review establishes LEC senescence as a central process in ARC pathogenesis and highlights promising senotherapeutic approaches. Future research should prioritize human surgical samples, develop standardized senescence detection panels (SA-β-gal + p21/p16 + SASP factors), and conduct longitudinal studies to establish causal relationships between senescence accumulation and cataract progression. Full article

Background: The pain experienced by people with fibromyalgia (FM) is thought to be the result of altered nociceptive processing, impaired descending inhibition and reduced tolerance to physical load. However, the relationship between the amount of exercise and pain reduction remains unclear. Methods: This study synthesized randomized controlled trials of exercise interventions for FM to quantify the combined analgesic effects of different types of exercise. A secondary aim was to standardize exposure using metabolic equivalent of task (MET)-based metrics and examine the association between cumulative intervention dose (MET·h) and analgesic response (Hedges’ g) across intervention arms. Following the PRISMA guidelines, a search was conducted in PubMed for randomized controlled trials published up to 31 December 2025. After screening and a full-text assessment, 15 trials were included. The protocols were converted into MET-defined intensity and weekly MET·min exposure, and the cumulative dose was calculated as the total MET·h accrued over the intervention period. Random-effects models were used to estimate the pooled effects within modality subgroups. Results: Across modalities, exercise was associated with reductions in pain, with effects typically falling within the small-to-moderate range. Larger improvements were observed in structured or supervised programs. The dose-response scatter plot showed wide variability across the dose range, with overlapping confidence intervals. An exploratory fourth-degree polynomial fit explained limited variance (R² = 0.1615) and did not indicate a monotonic dose-response pattern. This suggests that cumulative workload alone is a weak proxy for therapeutic response. Conclusions: Based on these findings, a pain-responsive algorithm combining weekly Visual Analogue Scale (VAS), ΔVAS and Talk Test thresholds was implemented as a preliminary online calculator to support the prescription of exercise tailored to symptoms. Full article

In this study, pristine biochar (BC1) and magnesium-modified biochar (BC2) were prepared from corn straw. Different nitrogen deposition intensities (0, 8, 30, and 50 kg N/(ha·yr)) were simulated by adding NH₄NO₃ solution. A laboratory incubation experiment was conducted to investigate the effects of biochar addition and N deposition on CO₂ emissions, CH₄ uptake, and microbial community structure in soils from a temperate mixed conifer–broadleaf forest. The results showed that BC1 significantly increased cumulative CO₂ emissions (p < 0.05), while no significant difference was observed between BC2 and the control. N deposition had no significant effect on CO₂ emissions. Biochar addition significantly promoted cumulative CH₄ uptake (p < 0.05), with BC2 exhibiting a stronger promoting effect than BC1. In contrast, N deposition significantly inhibited CH₄ uptake (p < 0.05) in a dose-dependent manner. Spearman’s correlation analysis revealed that cumulative CO₂ emissions were significantly or highly significantly negatively correlated with the relative abundances of Elusimicrobiota, Actinomycetota, Chloroflexota, Planctomycetota, Acidibacter, Bacillus, Paenibacillus, Acidothermus, and Mycobacterium, and significantly positively correlated with Bacteroidota, Bdellovibrionota, Pseudomonadota, Devosia, and Mesorhizobium. Cumulative CH₄ uptake was highly significantly positively correlated with the relative abundance of Bacteroidota and significantly negatively correlated with Chloroflexota, Candidatus_Eremiobacterota, and Mycobacterium. These findings demonstrate that N deposition has no significant impact on soil CO₂ emissions but significantly inhibits CH₄ uptake, while magnesium-modified corn straw biochar promotes CH₄ uptake without substantially increasing CO₂ emissions, highlighting its promising application potential. Full article

Industrial activities have caused heavy metals, such as cadmium (Cd), chromium (Cr), lead (Pb), and copper (Cu), to seriously threaten groundwater safety through seepage pathways. This study explored the formation of biofilms using microbe-induced calcium carbonate precipitation (MICP) technology to simultaneously reduce seepage in contaminated water and immobilize heavy metals. By optimizing the cementation fluid concentration and the intermittent grouting time, the optimal operating conditions for forming a biofilm were determined to be 1.5 mol/L cementation fluid and an intermittent time of 12 h, under which the stable infiltration rate of the sandy loam soil column can be reduced by more than 80%. We found that this biofilm can effectively inhibit the convective transport of Cd, Cr, Pb, and Cu, with the cumulative convective flux reduction rates reaching 56.25%, 56.25%, 54.54%, and 55.59%, respectively. SEM and XRD analysis indicate that the physical blockage of soil pores by calcium carbonate crystals is the dominant mechanism controlling infiltration flow, while the detection of new mineral phases, such as lead carbonate (PbCO₃), cadmium carbonate (CdCO₃), and basic copper carbonate (Cu₂(OH)₂CO₃) provides direct evidence for the chemical co-precipitation immobilization of heavy metals. This study demonstrates that MICP biofilm is a green and sustainable technology for in situ remediation of heavy metal pollution through physical–chemical synergistic effects, offering a promising alternative with a lower environmental footprint compared to conventional methods. Full article