Search Results (4,016)

Avian influenza A viruses (IAVs) pose a persistent threat to the poultry industry, causing substantial economic losses. Although traditional vaccines have helped reduce the disease burden, they typically rely on multivalent antigens, emphasize humoral immunity, and require intensive production. This study aimed to establish a genetically matched host–cell system to evaluate antigen-specific immune responses and identify conserved CD8+ T cell epitopes in avian influenza viruses. To this end, we developed an MHC class I genotype (B21)-matched host (Lohmann VALO SPF chicken) and cell vector (DF-1 cell line) model. DF-1 cells were engineered to express the hemagglutinin (HA) gene of clade 2.3.4.4b H5N1 either transiently or stably, and to stably express the matrix 1 (M1) and nucleoprotein (NP) genes of A/chicken/South Korea/SL20/2020 (H9N2, Y280-lineage). Following prime-boost immunization with HA-expressing DF-1 cells, only live cells induced strong hemagglutination inhibition (HI) and virus-neutralizing (VN) antibody titers in haplotype-matched chickens. Importantly, immunization with DF-1 cells transiently expressing NP induced stronger IFN-γ production than those expressing M1, demonstrating the platform’s potential for differentiating antigen-specific cellular responses. CD8+ T cell epitope mapping by mass spectrometry identified one distinct MHC class I-bound peptide from each of the HA-, M1-, and NP-expressing DF-1 cell lines. Notably, the identified HA epitope was conserved in 97.6% of H5-subtype IAVs, and the NP epitope in 98.5% of pan-subtype IAVs. These findings highlight the platform’s utility for antigen dissection and rational vaccine design. While limited by MHC compatibility, this approach enables identification of naturally presented epitopes and provides insight into conserved, functionally constrained viral targets. Full article

Carbon deposits on the crown of engine pistons can markedly reduce combustion efficiency and shorten service life. Conventional cleaning techniques often fail to simultaneously ensure a high carbon removal efficiency and maintain optimal surface integrity. To enable efficient and precise carbon removal, this study proposes the application of hybrid laser cleaning—combining continuous-wave (CW) and pulsed lasers—to piston carbon deposit removal, and employs response surface methodology (RSM) for multi-objective process optimization. Using the N52B30 engine piston as the experimental substrate, this study systematically investigates the combined effects of key process parameters—including CW laser power, pulsed laser power, cleaning speed, and pulse repetition frequency—on surface roughness (Sa) and carbon residue rate (RC). Plackett–Burman design was employed to identify significant factors, the method of the steepest ascent was utilized to approximate the optimal region, and a quadratic regression model was constructed using Box–Behnken response surface methodology. The results reveal that the Y-direction cleaning speed and pulsed laser power exert the most pronounced influence on surface roughness (F-values of 112.58 and 34.85, respectively), whereas CW laser power has the strongest effect on the carbon residue rate (F-value of 57.74). The optimized process parameters are as follows: CW laser power set at 625.8 W, pulsed laser power at 250.08 W, Y-direction cleaning speed of 15.00 mm/s, and pulse repetition frequency of 31.54 kHz. Under these conditions, the surface roughness (Sa) is reduced to 0.947 μm, and the carbon residue rate (RC) is lowered to 3.67%, thereby satisfying the service performance requirements for engine pistons. This study offers technical insights into the precise control of the hybrid laser cleaning process and its practical application in engine maintenance and the remanufacturing of end-of-life components. Full article

This study focuses on the exchange of mono- and divalent metal cations in FAU-type zeolite and their behavior in gas-phase CO₂ adsorption measurements and liquid-phase methylene blue (MB) adsorption in the absence of oxidizing agents under dark conditions. Firstly, zeolites exchanged with different cations were characterized by several techniques, such as XRD, SEM, XRF, XPS, and N₂ adsorption–desorption, to reveal the impact of the cations on the zeolite texture and structure. The adsorption studies revealed a positive effect of cation exchange on the adsorption capacity of the zeolite, particularly for silver-loaded FAU zeolite. In liquid-phase experiments, Ag-Y zeolite also demonstrated the highest MB removal, with a value of 79 mg/g. Kinetic studies highlighted that Ag-Y could reach the MB adsorption equilibrium within 1 h, with its highest rate of adsorption occurring during the first 5 min. In gas-phase adsorption studies, the highest CO₂ adsorption capacity was also achieved over Ag-Y, yielding 10.4 µmol/m² of CO₂ captured. Full article

Obstructive sleep apnea (OSA) is a prevalent disorder linked to metabolic complications such as diabetes and cardiovascular disease. By fragmenting normal sleep architecture, OSA perturbs the growth hormone/insulin-like growth factor (GH/IGF) axis and alters circulating levels of IGF-binding proteins (IGFBPs). A prior clinical observation of elevated IGFBP4 in OSA patients motivated the present investigation in a controlled animal model. Building on the previously reported protocol, OSA was induced in male C57BL/6 mice (9–12 weeks old) through intralingual injection of polytetrafluoroethylene (PTFE), producing tongue hypertrophy, intermittent airway obstruction, and hypoxemia. After 8–10 weeks, the study assessed (1) hypoxia biomarkers—including HIF-1α and VEGF expression—and (2) neurobehavioral outcomes in anxiety and cognition using the open-field and novel object recognition tests. PTFE-treated mice exhibited a significant increase in circulating IGFBP4 versus both baseline and control groups. Hepatic Igfbp4 mRNA was also upregulated. Behaviorally, PTFE mice displayed heightened anxiety-like behavior and impaired novel object recognition, paralleling cognitive deficits reported in human OSA. These findings validate the PTFE-induced model as a tool for studying OSA-related hypoxia and neurocognitive dysfunction, and they underscore IGFBP4 as a promising biomarker and potential mediator of OSA’s systemic effects. Full article

With the increasing detection of artemisinin resistance to front-line antimalarials in Africa and notwithstanding the planned roll-out of RTS’S and R21 in Africa, the search for new vaccines with high efficacy remains an imperative. Towards this endeavour, we performed in silico screening to identify Plasmodium falciparum gametocyte stage genes that could be targets of protection or diagnosis. Through the analysis we identified a gene, Pf3D7_1105800, coding for a Plasmodium falciparum subtilisin-like domain-containing protein (PfSDP) and thus dubbed the gene Pfsdp. Genetic diversity assessment revealed the Pfsdp gene to be relatively conserved across continents with signs of directional selection. Using RT qPCR and Western blots, we observed that Pfsdp is expressed in all developmental stages of the parasite both at the transcript and protein level. Immunofluorescence assays found PfSDP protein co-localizing with PfMSP-1 and partially with Pfs48/45 at the asexual and sexual stages, respectively. Further, we demonstrated that anti-PfSDP peptide-specific antibodies inhibited erythrocyte invasion by 20–60% in a dose-dependent manner, suggesting that PfSDP protein might play a role in merozoite invasion. We also discovered that PfSDP protein is immunogenic in children from different endemic areas with antibody levels increasing from acute infection to day 7 post-treatment, followed by a gradual decay. The limited effect of antibodies on erythrocyte invasion could imply that it might be more involved in other processes in the development of the parasite. Full article

Background: COVID-19 is associated with coagulopathy and increased mortality. The ABO blood group system has been implicated in modulating susceptibility to SARS-CoV-2 infection and disease severity, but its relationship with viral RNAemia, spike gene mutations, and thrombosis remains underexplored. Methods: We analyzed 446 hospitalized COVID-19 patients between 2021 and 2022. SARS-CoV-2 RNAemia was assessed via RT-qPCR on whole blood, and spike gene mutations were identified through whole-genome sequencing in RNAemia-positive samples. ABO blood groups were determined by agglutination testing, and thrombotic events were evaluated using coagulation markers. Statistical analyses included chi-square tests and Kruskal–Wallis tests, with significance set at p < 0.05. Results: RNAemia was detected in 26.9% of patients, with no significant association with ABO blood group (p = 0.175). Omicron was the predominant variant, especially in blood group A (62.5%). The N501Y mutation was the most prevalent in group O (53.2%), and K417N was most prevalent in group B (36.9%), though neither reached statistical significance. Thrombotic events were significantly more common in blood group A (OR = 2.08, 95% CI = 1.3–3.4, p = 0.002), particularly among RNAemia-positive patients. Conclusions: ABO blood group phenotypes, particularly group A, may influence thrombotic risk in the context of SARS-CoV-2 RNAemia. While no direct association was found between blood group and RNAemia or spike mutations, the observed trends suggest potential host–pathogen interactions. Integrating ABO typing and RNAemia screening may enhance risk stratification and guide targeted thromboprophylaxis in COVID-19 patients. Full article

Objectives: Most antiviral vaccines are created by inactivating the virus using chemical methods. The inactivation and production of viral vaccine preparations after the irradiation of viruses with accelerated electrons has a number of significant advantages. Determining the integrity of the genome of the resulting viral particles is necessary to assess the quality and degree of inactivation after irradiation. Methods: This work was performed on the Sabin 2 model polio virus. To determine the most sensitive and most radiation-resistant part, the polio virus genome was divided into 20 segments. After irradiation at temperatures of 25 °C, 2–8 °C, −20 °C, or −70 °C, the amplification intensity of these segments was measured in real time. Results: The best correlation between the amplification cycle and the irradiation dose at all temperatures was observed for segment 3D, left. Consequently, this section of the poliovirus genome is the least resistant to the action of accelerated electrons and is the most representative for determining genome integrity. The worst dependence was observed for the VP1 right section, which, therefore, cannot be used to determine genome integrity during inactivation. The electrochemical approach was also employed for a comparative assessment of viral RNA integrity before and after irradiation. An increase in the irradiation dose was accompanied by an increase in signals indicating the electrooxidation of RNA heterocyclic bases. The increase in peak current intensity of viral RNA electrochemical signals confirmed the breaking of viral RNA strands during irradiation. The shorter the RNA fragments, the greater the peak current intensities. In turn, this made the heterocyclic bases more accessible to electrooxidation on the electrode. Conclusions: These results are necessary for characterizing the integrity of the viral genome for the purpose of creating of antiviral vaccines. Full article

This study investigates the effects of low nitrogen (N) and phosphorus (P) stress on the growth and yield of nine barley (Hordeum vulgare L.) genotypes (1267-2, 1749-1, 1149-3, 2017Y-2, 2017Y-16, 2017Y-17, 2017Y-18, 2017Y-19, and XBZ17-1-61), all of which are spring two-rowed hulled barley types from the Economic Crops and Beer Material Institute, Gansu Academy of Agricultural Sciences. Data were collected over two consecutive growing seasons (2021–2022) at Huangyang Town (altitude 1766 m, irrigated desert soil with 1.71% organic matter, 1.00 g·kg⁻¹ total N, 0.87 g·kg⁻¹ total P in 0–20 cm plough layer) to elucidate the correlation between stress tolerance traits and yield performance. Field experiments were conducted under two treatment conditions: no fertilization (NP0) and normal fertilization (180 kg·hm⁻² N and P, NP180). Growth indicators (plant height, spike length, spikelets per unit area, etc.) and quality indicators (proportion of plump/shrunken grains, 1000-grain weight, protein, starch content) were measured, and data were analyzed using correlation analysis, principal component analysis, and structural equation modeling. The results revealed that low N and P stress significantly impacted quality indicators, such as the proportion of plump and shrunken grains, while having a minimal effect on growth indicators like plant height and spike length. Notably, the number of spikelets per unit area emerged as a critical factor positively influencing yield. Among the tested genotypes, 1749-1, 1267-2, 1149-3, 2017Y-16, 2017Y-18, 2017Y-19, and XBZ17-1-61 exhibited superior yield performance under low N and P stress conditions, indicating their potential for breeding programs focused on stress resilience. Included among these, the 1749-1 line showed the best overall performance and consistent results across both years. Full article

This study analyzes the lacustrine hydrocarbon source rocks of the Lower Cretaceous in the Erdengsumu sag of the Erlian Basin, evaluating their characteristics and identifying areas with oil resource potential, while also investigating the ancient lake environment, material source input, and controlling factors, ultimately developing a sedimentary model for lacustrine hydrocarbon source rocks. The findings suggest the following: (1) The lower Tengger Member (K₁bt₁) and the Aershan Formation (K₁ba) are the primary oil-producing strata, with an effective hydrocarbon source rock exhibiting a lower limit of total organic carbon (TOC) at 0.95%. The Ro value typically remains below 0.8%, indicating that high-maturity oil production has not yet been attained. (2) The oil generation threshold depths for the Dalestai and Sayinhutuge sub-sags are 1500 m and 1214 m, respectively. The thickness of the effective hydrocarbon source rock surpasses 200 m, covering areas of 42.48 km² and 88.71 km², respectively. The cumulative hydrocarbon generation intensity of wells Y1 and Y2 is 486 × 10⁴ t/km² and 26 × 10⁴ t/km², respectively, suggesting that the Dalestai sub-sag possesses considerable petroleum potential. The Aershan Formation in the Chagantala sub-sag has a maximum burial depth of merely 1800 m, insufficient to attain the oil generation threshold depth. (3) The research area’s productive hydrocarbon source rocks consist of organic matter types I and II₁. The Pr/Ph range is extensive (0.33–2.07), signifying a reducing to slightly oxidizing sedimentary environment. This aligns with the attributes of small fault lake basins, characterized by shallow water and robust hydrodynamics. (4) The low ratio of ∑nC₂₁₋/∑nC₂₂₊ (0.36–0.81), high CPI values (>1.49), and high C₂₉ sterane concentration suggest a substantial terrestrial contribution, with negligible input from aquatic algae–bacterial organic matter. Moreover, as sedimentation duration extends, the contribution from higher plants progressively increases. (5) The ratio of the width of the deep depression zone to the width of the depression in the Erdengsumu sag is less than 0.25. The boundary fault scale is small, its activity is low, and there is not much input from the ground. Most of the source rocks are in the reducing sedimentary environment of the near-lying gently sloping zone. Full article

Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover markers (BTM), and bone mineral density (DXA-BMD), respectively, to assess the 10-year fracture probability of major osteoporotic fractures (MOF) and hip fracture (HF) upon using conventional FRAX without/with femoral neck BMD (MOF-FN/HF-FN and MOF+FN/HF+FN) and the novel model (FRAXplus) with adjustments for T2D (MOF+T2D/HF+T2D) and lumbar spine BMD (MOF+LS/HF+LS). Methods: This retrospective, cross-sectional, pilot study, from January 2023 until January 2024, in menopausal women (aged: 50–80 years) with/without T2D (group DM/nonDM). Inclusion criteria (group DM): prior T2D under diet ± oral medication or novel T2D (OGTT diagnostic). Exclusion criteria: previous anti-osteoporotic medication, prediabetes, insulin therapy, non-T2D. Results: The cohort (N = 136; mean age: 61.36 ± 8.2y) included T2D (22.06%). Groups DM vs. non-DM were age- and years since menopause (YSM)-matched; they had a similar osteoporosis rate (16.67% vs. 23.58%) and fracture prevalence (6.66% vs. 9.43%). In T2D, body mass index (BMI) was higher (31.80 ± 5.31 vs. 26.54 ± 4.87 kg/m²; p < 0.001), while osteocalcin and CrossLaps were lower (18.09 ± 8.35 vs. 25.62 ± 12.78 ng/mL, p = 0.002; 0.39 ± 0.18 vs. 0.48 ± 0.22 ng/mL, p = 0.048), as well as 25-hydroxyvitamin D (16.96 ± 6.76 vs. 21.29 ± 9.84, p = 0.013). FN-BMD and TH-BMD were increased in T2D (p = 0.007, p = 0.002). MOF+LS/HF+LS were statistically significant lower than MOF-FN/HF-FN, respectively, MOF+FN/HF+FN (N = 136). In T2D: MOF+T2D was higher (p < 0.05) than MOF-FN, respectively, MOF+FN [median(IQR) of 3.7(2.5, 5.6) vs. 3.4(2.1, 5.8), respectively, 3.1(2.3, 4.39)], but MOF+LS was lower [2.75(1.9, 3.25)]. HF+T2D was higher (p < 0.05) than HF-FN, respectively, HF+FN [0.8(0.2, 2.4) vs. 0.5(0.2, 1.5), respectively, 0.35(0.13, 0.8)] but HF+LS was lower [0.2(0.1, 0.45)]. Conclusion: Type 2 diabetic menopausal women when compared to age- and YSM-match controls had a lower 25OHD and BTM (osteocalcin, CrossLaps), increased TH-BMD and FN-BMD (with loss of significance upon BMI adjustment). When applying novel FRAX model, LS-BMD adjustment showed lower MOF and HF as estimated by the conventional FRAX (in either subgroup or entire cohort) or as found by T2D adjustment using FRAXplus (in diabetic subgroup). To date, all four types of 10-year fracture probabilities displayed a strong correlation, but taking into consideration the presence of T2D, statistically significant higher risks than calculated by the traditional FRAX were found, hence, the current model might underestimate the condition-related fracture risk. Addressing the practical aspects of fracture risk assessment in diabetic menopausal women might improve the bone health and further offers a prompt tailored strategy to reduce the fracture risk, thus, reducing the overall disease burden. Full article

Objective: To investigate the neuroprotective effects of a Rho-associated kinase (ROCK) inhibitor on retinal ganglion cells (RGCs) in vitro and in vivo. Methods: For in vivo studies, a unilateral optic nerve crush mouse model was established. Then, 100 mM Y-27632 (a ROCK inhibitor) or saline was applied to the experimental eyes once a day for 14 days. The effects of the ROCK inhibitor were evaluated by counting the surviving RGCs in the enucleated flat retina tissues and measuring the inner retinal thickness using optical coherence tomography (OCT), the amplitude of the electroretinogram (ERG), and the change in intraocular pressure (IOP). For the in vitro study, RGCs were isolated from five-day-old mice using a modified immunopanning method with magnetic beads. The isolated RGCs were incubated for 72 h with various concentrations of Y-27632, after which TUNEL assays were performed to determine the number of surviving RGCs. Results: Y-27632 has neuroprotective effects, as it significantly increased the number of surviving RGCs by approximately 6.3%. OCT and ERG data also revealed that Y-27632 induced neuroprotective effects in vivo; furthermore, Y-27632 reduced IOP by approximately 18.3%. The in vitro study revealed the dose-dependent neuroprotective effects of Y-27632, with the highest dose of Y-27632 (1000 nM) increasing the RGC survival rate after 72 h of incubation compared with that of the control. Conclusions: The ROCK inhibitor Y-27632 may exert some neuroprotective effects on RGCs when it is used as an eye drop through an IOP-independent mechanism. Full article

Various SARS-CoV-2 remdesivir resistance-associated substitutions (RAS) have been reported, but a comprehensive comparison of their resistance levels is lacking. We identified novel RAS and performed head-to-head comparisons with known RAS in Vero E6 cells. A remdesivir escape polyclonal virus exhibited a 3.6-fold increase in remdesivir EC₅₀ and mutations throughout the genome, including substitutions in nsp12 (E796D) and nsp14 (A255S). However, in reverse-genetics infectious assays, viruses harboring both these substitutions exhibited only a slight decrease in remdesivir susceptibility (1.3-fold increase in EC₅₀). The nsp12-E796D substitution did not impair viral fitness (Vero E6 cells or Syrian hamsters) and was reported in a remdesivir-treated COVID-19 patient. In replication assays, a subgenomic replicon containing nsp12-E796D+nsp14-A255S led to a 16.1-fold increase in replication under remdesivir treatment. A comparison with known RAS showed that S759A, located in the active site of nsp12, conferred the highest remdesivir resistance (106.1-fold increase in replication). Nsp12-RAS V166A/L, V792I, E796D or C799F, all adjacent to the active site, caused intermediate resistance (2.0- to 11.5-fold), whereas N198S, D484Y, or E802D, located farther from the active site, showed no resistance (≤2.0-fold). In conclusion, our classification system, correlating replication under remdesivir treatment with RAS location in nsp12, shows that most nsp12-RAS cause moderate resistance. Full article

A recently proposed method called “controlled swelling of monolithic films” was implemented to prepare ultra-high-molecular-weight polyethylene (UHMWPE) ultrafiltration membranes. For the first time, the effect of UHMWPE molecular weight (MW) on the structure and properties of the membranes prepared via this special case of thermally induced phase separation was studied in detail. The morphology and properties of the membranes were studied using SEM, DSC, liquid–liquid displacement porometry, and standard methods for the evaluation of mechanical properties, permeance, rejection, and abrasion resistance. High-quality membranes with a tensile strength of 5.0–17.8 MPa, a mean pore size of 25–50 nm, permeance of 17–107 L m⁻² h⁻¹ bar⁻¹, rejection of model contaminant (blue dextran) of 72–98%, and great abrasion resistance can be prepared only if the MW of the polymer in the initial monolithic film is sufficiently high. The properties of the membranes can effectively be controlled by changing the MW of the polymer and the mass fraction of the latter in the swollen film. Shrinkage is responsible for the variation in the membrane properties. The membranes prepared from a higher-MW polymer are more prone to shrinking after the removal of the solvent. Shrinkage decreases before rising again and minimizes with an increase in the polymer content in the swollen film. Full article

Human induced pluripotent stem cell-derived cardiomyocytes (iCMs) provide a powerful platform for investigating cardiac biology. However, structural, metabolic, and electrophysiological immaturity of iCMs limits their capacity to model adult cardiomyocytes. Currently, no universally accepted criteria or protocols for effective iCMs maturation exist. This study aimed to identify practical culture conditions that promote iCMs maturation, thereby generating more physiologically relevant in vitro cardiac models. We evaluated the effects of short- and long-term culture in media supplemented with various stimulatory compounds under 2D conditions, focusing on intracellular content and localization of slow skeletal troponin I (ssTnI) and cardiac troponin I (cTnI) isoforms. Our findings demonstrate that the multicomponent metabolic maturation medium (MM-1) effectively enhances the transition toward a more mature iCM phenotype, as evidenced by increased cTnI expression and formation of cross-striated myofibrils. iCMs cultured in MM-1 more closely resemble adult cardiomyocytes and are compatible with high-resolution single-cell techniques such as electron microscopy and patch-clamp electrophysiology. This work provides a practical and scalable approach for advancing the maturation of iPSC-derived cardiac models, with applications in disease modeling and drug screening. Full article

A vast proportion of scientific data remains locked behind dynamic web interfaces, often called the deep web—inaccessible to conventional search engines and standard crawlers. This gap between data availability and machine usability hampers the goals of open science and automation. While registries like FAIRsharing offer structured metadata describing data standards, repositories, and policies aligned with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles, they do not enable seamless, programmatic access to the underlying datasets. We present FAIRFind, a system designed to bridge this accessibility gap. FAIRFind autonomously discovers, interprets, and operationalizes access paths to biological databases on the deep web, regardless of their FAIR compliance. Central to our approach is the Deep Web Communication Protocol (DWCP), a resource description language that represents web forms, HyperText Markup Language (HTML) tables, and file-based data interfaces in a machine-actionable format. Leveraging large language models (LLMs), FAIRFind combines a specialized deep web crawler and web-form comprehension engine to transform passive web metadata into executable workflows. By indexing and embedding these workflows, FAIRFind enables natural language querying over diverse biological data sources and returns structured, source-resolved results. Evaluation across multiple open-source LLMs and database types demonstrates over 90% success in structured data extraction and high semantic retrieval accuracy. FAIRFind advances existing registries by turning linked resources from static references into actionable endpoints, laying a foundation for intelligent, autonomous data discovery across scientific domains. Full article