Search Results (13,552)

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

Based on the principle of symmetry, we propose a variable step-size FxLMS algorithm with double nonlinear functions cooperative coupling (DNVSS-FxLMS), aiming to optimize the contradiction between convergence rate and steady-state error in the active pressure pulsation control system of hydraulic systems. The algorithm innovatively couples two types of nonlinear mechanisms (rational-fractional and exponential-function-based), constructing a refined error-step mapping relationship to achieve a balance between rapid convergence and low steady-state error. Simulation experiments were conducted considering the complex time-varying operating environment of a simulation-based hydraulic system. The results demonstrate that, when the system undergoes unstable random changes, the DNVSS-FxLMS algorithm converges at least twice as fast as traditional and existing variable step size algorithms, while reducing steady-state error by 2–5 dB. The proposed DNVSS-FxLMS algorithm exhibits significant advantages in convergence rate, steady-state error reduction, and tracking capability, providing a highly efficient and robust solution for real-time active control of hydraulic system pressure pulsation under complex operating conditions. Full article

Due to the limitations of high speed and short time in plasma-spraying experiments, this study established a simulation model of Y₂O₃ multi-particle deposition to discuss the influence of laser loading on coating-deposition behavior and performance. According to the simulation results, the temperature of coating particles under laser loading displays a gradient distribution, with the surface having the highest temperature. The particles deposit on the substrate to form uniform pits of a certain depth. Plastic deformation causes maximum stress to occur at the edges of the pits and maximum strain to occur on the sidewall of the pits. The deposition region had both compressive and tensile stresses, and laser loading greatly reduced the tensile stresses’ magnitude while having less of an impact on the particle strains. Laser assistance promotes further melting of particles, reduces coating thickness, lowers coating porosity to 3.94%, increases hardness to 488 MPa, reduces maximum pore size from 68 µm to 32 µm, and causes particle sputtering to gradually evolve from being disc-shaped to being finger-shaped, creating cavities at the coating edges. The comparison between the surface morphology and the cross-section pores of the experimentally prepared coating verified the rationality and viability of the simulation work. Full article

Flexible energy sources such as electric vehicles and the battery energy storage systems of intelligent distribution systems can provide system-wide auxiliary services such as frequency regulation for power systems. This paper proposes an optimal method for operating the local energy community that is based on two-stage scheduling. Firstly, the basic concepts of the local energy community and flexible service are introduced in detail. Taking LEC as the reserve unit of artificial frequency recovery, an energy information interaction model among LEC, balance service providers, and the power grid is established. Then, a two-stage scheduling framework is proposed to ensure the rationality and economy of community energy scheduling. In the first stage, day-ahead scheduling uses the energy community management center to predict the up/down flexibility capacity that LEC can provide by adjusting the BESS control parameters. In the second stage, real-time scheduling aims at maximizing community profits and scheduling LEC based on the allocation and activation of standby flexibility determined in real time. Finally, the correctness of the two-stage scheduling framework is verified through a case study. The results show that the control parameters used in the day-ahead stage can significantly affect the real-time profitability of LEC, and that LEC benefits more in the case of low BESS utilization than in the case of high BESS utilization and non-participation in frequency recovery reserve. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new technology such as single-nuclei sequencing (snRNAseq) and spatial transcriptomics, led to a better understanding of the glioma cells’ plasticity and their ability to transition between diverse cellular states. GBM cells can mimic neurodevelopmental programs to resemble oligodendrocyte or neural progenitor behavior and hitchhike the local neuronal network to support their growth. The tumor microenvironment, especially under hypoxic conditions, drives the tumor cell clonal selection, which then reshapes the immune cells’ functions. These adaptations contribute to immune evasion by progressively disabling T cell and myeloid cell functions, ultimately establishing a highly immunosuppressive tumor milieu. This complex and metabolically constrained environment poses a major barrier to effective antitumor immunity and limits the success of conventional therapies. Understanding the dynamic interactions between glioma cells and their microenvironment is essential for the development of more effective immunotherapies and rational combination strategies aimed at overcoming resistance and improving patient outcomes. Full article

Integrating artificial intelligence (AI) and cause-related marketing has reshaped corporate social responsibility practices while triggering a conflict between technological instrumental rationality and moral value transmission. Building on the Persuasion Knowledge Model (PKM) and AI aversion literature, this research employs two experiments to reveal that AI disclosure exerts a unique inhibitory effect on consumers’ purchase intentions in cause-related marketing contexts compared to non-cause-related marketing scenarios. Further analysis uncovers a chain mediation pathway through consumer skepticism and advertisement attitudes, explaining the psychological mechanism underlying AI disclosure’s impact on purchase intentions. The study also identifies the moderating role of AI aversion within this chain model. The findings provide a new theoretical perspective for integrating AI disclosure, consumer psychological responses, and marketing effectiveness while exposing the “value-instrumentality” conflict inherent in AI applications for cause-related marketing. This research advances the evolution of the PKM in the digital era and offers practical insights for cause-related marketing enterprises to balance AI technology application with optimized disclosure strategies. Full article

Background/Objectives: The clinical potential of antimicrobial peptides (AMPs) against dual threats like antimicrobial resistance (AMR) and cancer is often limited by their high host cell toxicity. Here, we focused on brevinin-2OS (B2OS), a novel peptide from the skin of Odorrana schmackeri with potent haemolytic activity. The objective was to study the structure–activity relationship and optimise the safety via targeted modifications. Methods: A dual-modification strategy involving C-terminal truncation and subsequent N-terminal D-amino acid substitution was employed. The bioactivities and safety profiles of the resulting analogues were evaluated using antimicrobial, haemolysis, and cytotoxicity assays. Result: Removal of the rana box in B2OS(1-22)-NH₂ substantially reduced haemolysis while maintaining bioactivities. Remarkably, the D-leucine substitution in [D-Leu²]B2OS(1-22)-NH₂ displayed a superior HC₅₀ value of 118.1 µM, representing a more than ten-fold improvement compared to its parent peptide (HC₅₀ of 10.44 µM). This optimised analogue also demonstrated faster bactericidal kinetics and enhanced membrane permeabilisation, leading to a greater than 22-fold improvement in its therapeutic index against Gram-positive bacteria. Conclusions: The C-terminal rana box is a primary determinant of toxicity rather than a requirement for activity in the B2OS scaffold. The engineered peptide [D-Leu²]B2OS(1-22)-NH₂ emerges as a promising lead compound, and this dual-modification strategy provides a powerful design principle for developing safer, more effective peptide-based therapeutics. Full article

Gradual climate warming is favoring viticulture in Poland. At the same time, there is a lack of information about the suitability of grape varieties grown in Poland for processing. The primary aim of the study was to determine the effect of pre-treatment on the pressing yield of grape juice and its qualitative assessment. The study applied pre-treatment of raw material, involving either enzymatic liquefaction of the pulp in the first case or freezing and thawing of the pulp prior to pressing in the second case. There was considerable variation among the grape varieties studied in terms of the characteristics under analysis. The varietal characteristics had a significant effect on the pressing yield and the quality of the juice obtained. Pre-treatment had different effects on the pressing yield of the individual grape varieties and the quality of the obtained juices. The research carried out may improve the efficiency and quality of agricultural production with the rational use of locally grown grape hybrids. Full article

This study conducts an in-depth analysis of the dynamic characteristics of a single reheat steam turbine generator unit and its speed control system under variable operating conditions. A comprehensive simulation model was constructed to comprehensively evaluate the impact of the heat extraction system on the dynamic behavior of the unit, which integrates the speed control system, actuator, single reheat steam turbine body, and once-through boiler dynamic coupling. This model focuses on revealing the mechanism of the heat extraction regulation process on the core operating parameters of the unit and the system frequency regulation capability. Based on the actual parameters of a 300 MW heat unit in a power plant in Guangxi, the dynamic response of the established model under typical dynamic conditions such as extraction flow regulation, primary frequency regulation response, and load step disturbance was simulated and experimentally verified. The results show that the model can accurately characterize the dynamic characteristics of the heat unit under variable operating conditions, and the simulation results are in good agreement with the actual engineering, with errors within an acceptable range, effectively verifying the dynamic performance of the heat system module and the rationality of its control parameter design. This study provides a reliable theoretical basis and model support for the accurate simulation of the dynamic behavior of heat units in the power system and the design of optimization control strategies for system frequency regulation. Full article

The use of opioids for cancer-related pain is essential but poses significant challenges due to the risk of misuse and the development of opioid use disorder (OUD). This review takes a multidisciplinary perspective based on the current scientific literature to analyze the pharmacological mechanisms, classification, and therapeutic roles of opioids in oncology. Key risk factors for opioid misuse—including psychiatric comorbidities, prior substance use, and insufficient clinical monitoring—are discussed in conjunction with validated tools for pain assessment and international guidelines. The review emphasizes the importance of integrating toxicological, pharmacological, physiological, and public health perspectives to promote rational opioid use. Pharmacogenetic variability is explored as a determinant of treatment response and addiction risk, underscoring the value of personalized medicine. Evidence-based strategies such as early screening, psychosocial interventions, and the use of buprenorphine-naloxone are presented as effective measures for managing OUD in cancer patients. Ultimately, this work advocates for safe, patient-centered opioid prescribing practices that ensure effective pain relief without compromising safety or quality of life. Full article

This study evaluated the effects of liquid oregano oil, chitosan nanoparticles with encapsulated liquid oregano oil, and a negative control of empty chitosan nanoparticles on in vitro ruminal fermentation. Three Boer goats were used as ruminal fluid donors, fed with a formulated ration for 21 d for inoculum adaptation. Treatments tested on in vitro assays were diet without oregano oil or nanoparticles (CON); diet with 100 ppm of oregano oil in nanoparticles (100N); diet with 300 ppm of liquid oregano oil (300L); diet with 300 ppm of oregano oil in nanoparticles (300N); and diet with 300 ppm of empty nanoparticles (300CHN). The variables studied were in vitro dry matter digestibility (ivDMD), in vitro neutral detergent fiber digestibility (ivNDFD_om), total gas production (TGP), ammonia nitrogen concentration (NH₃), and pH. The experimental design was a randomized complete block design. Linear and quadratic regressions were used to identify dependence and inflection points. The ivDMD increased at 12, 36, and 48 h, with 300N and with 300L exhibiting increased ivNDFD_om at 36 h. Ruminal pH was highest (p < 0.05) with 300CHN at 36 h. For first-order regression analysis of TGP, coefficients (β) were highest (p < 0.05) for 300N. In conclusion, 300N increased ruminal fermentation in vitro, as reflected by increases in ivDMD, ivNDFD_om, and TGP. Full article

Protein–polyelectrolyte nanostructures assembled via electrostatic interactions offer versatile applications in biomedicine, tissue engineering, and food science. However, several open questions remain regarding their intermolecular interactions and the influence of external conditions—such as temperature and pH—on their assembly, stability, and responsiveness. This study explores the formation and stability of networks between poly(acrylic acid) (PAA) and lysozyme (LYZ) at the nanoscale upon thermal treatment, using a combination of experimental and simulation measures. Experimental techniques of static and dynamic light scattering (SLS and DLS), Fourier transform infrared spectroscopy (FTIR), and circular dichroism (CD) are combined with all-atom molecular dynamics simulations. Model systems consisting of multiple PAA and LYZ molecules explore collective assembly and complexation in aqueous solution. Experimental results indicate that electrostatic complexation occurs between PAA and LYZ at pH values below LYZ’s isoelectric point. This leads to the formation of nanoparticles (NPs) with radii ranging from 100 to 200 nm, most pronounced at a PAA/LYZ mass ratio of 0.1. These complexes disassemble at pH 12, where both LYZ and PAA are negatively charged. However, when complexes are thermally treated (TT), they remain stable, which is consistent with earlier findings. Atomistic simulations demonstrate that thermal treatment induces partially reversible structural changes, revealing key microscopic features involved in the stabilization of the formed network. Although electrostatic interactions dominate under all pH and temperature conditions, thermally induced conformational changes reorganize the binding pattern, resulting in an increased number of contacts between LYZ and PAA upon thermal treatment. The altered hydration associated with conformational rearrangements emerges as a key contributor to the stability of the thermally treated complexes, particularly under conditions of strong electrostatic repulsion at pH 12. Moreover, enhanced polymer chain associations within the network are observed, which play a crucial role in complex stabilization. These insights contribute to the rational design of protein–polyelectrolyte materials, revealing the origins of association under thermally induced structural rearrangements. Full article

Efflux is one of the key mechanisms used by Gram-negative bacteria to reduce internal antibiotic concentrations. These active transport systems recognize and expel a wide range of toxic molecules, including antibiotics, thereby contributing to reduced antibiotic susceptibility and allowing the bacteria to acquire additional resistance mechanisms. To date, unlike other resistance mechanisms such as enzymatic modification or target mutations/masking, efflux is challenging to detect and counteract in clinical settings, and no standardized methods are currently available to diagnose or inhibit this mechanism effectively. This review first outlines the structural and functional features of major efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. It then explores various strategies used to curb their activity, with a particular focus on efflux pump inhibitors under development, detailing their structural classes, modes of action, and pharmacological potential. We discuss the main obstacles to their development, including the structural complexity and substrate promiscuity of efflux mechanisms, the limitations of current screening methods, pharmacokinetic and tissue distribution issues, and the risk of off-target toxicity. Overcoming these multifactorial barriers is essential to the rational development of less efflux-prone antibiotics or of efflux pump inhibitors. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. Methods: A systematic literature search was carried out for the period between October 2016 to September 2024. Phase II and III randomized trials evaluating ICI monotherapy, ICI–chemotherapy combinations, and dual ICI regimens in patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). Results: PD-1-targeted therapies demonstrated superior OS compared to PD-L1-based regimens, with cemiplimab monotherapyranking highest for OS benefit (posterior probability: 90%), followed by sintilimab plus platinum-based chemotherapy (PBC) and pemetrexed—PBC. PFS atezolizumab plus bevacizumab and PBC, and camrelizumab plus PBC were the most effective regimens. ICI–chemotherapy combinations achieved higher ORRs but were associated with greater toxicity. The most favorable safety profiles were observed with cemiplimab, nivolumab, and avelumab monotherapy, while atezolizumab plus PBC and sugemalimab plus PBC carried the highest toxicity burdens. Conclusions: In PD-L1-unselected advanced NSCLC, PD-1 blockade—particularly cemiplimab monotherapy—and rationally designed ICI–chemotherapy combinations represent the most efficacious treatment strategies. Balancing efficacy with safety remains critical, especially in the absence of predictive biomarkers. These findings support a patient-tailored approach to immunotherapy and highlight the need for further biomarker-driven and real-world investigations to optimize treatment selection. Full article

This study used all-atom molecular dynamics simulations to investigate the structural dynamics of Ves a 1, a phospholipase from Vespa affinis venom, and its interactions within a lipid membrane environment, both alone and in the presence of the inhibitor voxilaprevir. Simulations conducted over 1 $\mathsf{\mu }$s for triplicate runs demonstrated system stability and convergence of structural properties. Our findings reveal that Ves a 1 engages in dynamic interactions with the lipid bilayer, involving key regions such as its lids, catalytic triad, and auxiliary site. The presence of voxilaprevir was observed to subtly alter these membrane interaction patterns and influence the enzyme’s catalytic area, reflecting the inhibitor’s impact within its physiological context. These results emphasize the crucial role of the lipid bilayer in shaping enzyme function and highlight voxilaprevir as a promising candidate for further inhibitor development, offering vital insights for rational drug design targeting membrane-associated proteins. Full article