Search Results (8,733)

Toll-like receptors (TLRs) are essential components of the innate immune system that enable host cells to sense microbial and endogenous danger signals and to initiate inflammatory and antimicrobial responses. Activation of TLRs triggers complex intracellular signaling networks that culminate in the induction of pro-inflammatory cytokines, type I interferons, and co-stimulatory molecules. In addition to the well-characterized nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) pathways, mitogen-activated protein kinases (MAPKs) play a critical modulatory role in TLR signaling. MAPK/ERK kinase (MEK) inhibitors were originally developed for the treatment of cancer and are widely used in clinical oncology. Accumulating evidence indicates that pharmacological inhibition of MEK/extracellular signal regulated kinase (ERK) signaling profoundly affects immune cell function and TLR-driven responses. Depending on timing, dose, and disease context, MEK inhibition can attenuate excessive inflammation but may also interfere with protective host defense mechanisms. This duality highlights the context-dependent role of MEK/ERK signaling in infection and inflammation. In this review, I summarize current knowledge on the integration of MEK/ERK signaling into TLR-mediated innate immune responses and discuss the immunological consequences of MEK inhibition in infectious and inflammatory settings. By synthesizing mechanistic and translational studies, I aim to provide a framework for understanding MEK inhibitors as immune modulators rather than as broadly acting anti-inflammatory agents. Full article

Copper azides are promising energetic materials for miniaturized pyrotechnic devices and micro explosive trains owing to their short detonation growth distance and high initiation energy. However, controllable preparation of copper nanoparticle precursors and their in situ conversion to copper azides under mild conditions remains challenging. In this study, copper nanoparticles were synthesized via a coordination-assisted aqueous reduction method at room temperature under air atmosphere using nitrilotriacetic acid disodium salt (NTA·H·2Na) as the complexing agent. The resulting nanoparticles were pressed into polyester rings to construct confined precursor structures, and copper azide micro-charges were prepared through in situ gas–solid reaction with HN₃ gas generated from NaN₃ and concentrated phosphoric acid at 60 °C. SEM characterization revealed that the morphological evolution of copper azides followed a three-stage pattern: “product island nucleation, branch/block coalescence growth, and continuous product layer formation and structural reconstruction”. Detonation velocity tests using the electrical probe method showed an average value of (5.10 ± 0.07) × 10³ m/s. Flyer impact initiation tests demonstrated that, with a charge thickness of 1.00 mm, both a 30 μm polyimide flyer and a 40 μm titanium flyer could successfully initiate a HNS–IV explosive. The preparation methodology and performance characterization established in this work provide an experimental basis for the application of copper azides in micro-initiation systems. Full article

This research reports on the challenges of curriculum change in Early Childhood Education and Care (ECEC) in Ireland, and how changes have highlighted the opportunities for innovative pedagogical practices in the university programmes for ECEC educators. We employed a self-study of practice (S-SP) methodology to better understand the outdoor learning (OL) practice of one university lecturer teaching an undergraduate ECEC degree. The 2024 revisions to the Irish national early childhood curriculum framework (Aistear) created both challenges and opportunities. The framework identifies the merits of learning outdoors for creating greater recognition of the outdoors as an important site for learning with children aged zero to six years. The focus of the study was the lecturer’s pedagogical approach to meeting that challenge and creating opportunities to build students’ competence to deliver the Aistear’s curricular aims through OL. In this qualitative S-SP study, the researchers used reflective journals, critical friendship dialogues, and group interviews with students to interrogate the lecturer’s pedagogical strategies and their impact. Using reflexive thematic analysis, five themes developed, concerning pedagogical strategies, student learning dispositions, new knowledge for practice, student gains and experiences, and key aspects of the lecturer’s practice. Findings show that purposeful experiential teaching methods fostered student agency and confidence to facilitate OL with young children. Although based upon one cohort, this research illustrates how self-study can act as an effective method to illuminate the complexities of teaching using outdoor pedagogies in HE, and can contribute to the preparation of agentic and innovative ECEC educators. Full article

Abandoned slopes often encounter problems such as compacted soil and lack of nutrients. Biochar, as a promising soil amendment agent, can effectively enhance soil fertility. Moreover, evaluating the nutrient and microbial characteristics during the improvement process is of great significance for revealing its mechanism of action in improving abandoned land. This study analyzed the characteristics of soil nutrients, microbial community structure, and co-occurrence network after reclamation under different application rates (0%, 1%, 2.5%, 4%, 5.5%, hereinafter referred to as CK, T1, T2, T3, T4) of corn straw biochar. The results showed that biochar significantly increased soil organic carbon (by 60.74–164.82%), total nitrogen (11.31–27.73%), and total phosphorus (13.32–56.03%) content, and the effect was best at a rate of 4% (T3). With the increase in biochar application rate, soil bulk density generally showed a downward trend, and pH generally showed an upward trend. Significant levels (p < 0.05) were reached from T2 to T4. There was a strong linear correlation between biochar application rate and soil organic matter, total nitrogen, and pH in the fitted model, with R² values reaching 0.753, 0.601, and 0.706, respectively. Microbial community analysis showed that biochar application changed the bacterial community structure. With the increase in soil depth, the Shannon index and Chao index of each treatment generally increased, indicating that soil depth is one of the key factors regulating the community structure. Biochar application promoted the proliferation of beneficial bacterial groups such as Pseudomonadota and Acidobacteriota, by increasing the number of co-occurrence network nodes and edges enhancing the complexity and stability of the microbial network. Full article

The Q-Learning Relational Game (QLRG) framework provides a theoretically rigorous method for identifying minimal winning coalitions in online social networks (OSNs) under the restrictive assumption of global agent symmetry or uniform matroid structure. Real-world OSNs, however, exhibit significant asymmetry. This paper introduces the Cluster-Based Q-Learning Relational Game (C-QLRG), a practical extension that relaxes the global symmetry requirement by leveraging community structure. We partition the agent set into communities with bounded internal variation and represent the state solely by community membership counts of the seed set. Because the closure operator already captures all eventual influence spread, the problem reduces to a sequential seed selection task where the agent decides, at each step, from which community to add the next seed. We prove that the optimal Q-function of a suitably regularized reach-efficiency objective is Lipschitz continuous and derive a performance bound for the learned policy. The full algorithm is presented, and its complexity is analyzed. Empirical evaluations on a synthetic asymmetric network and Zachary’s Karate Club demonstrate that C-QLRG is highly sensitive to reward parameters, where default settings lead to premature stopping, but parameter tuning combined with a corrected minimality verification recovers high-efficiency coalitions by removing non-contributing agents. With tuned parameters, C-QLRG produces a near-winning coalition of size 11 and 99% reach on the synthetic network, surpassing the greedy baseline’s efficiency (size 12) despite a one-node coverage gap, while identifying the optimal winning coalition of size 1 on the Karate Club dataset, matching all baselines. The framework thus offers a principled trade-off between model fidelity and scalability, with the reward design choice being critical for practical deployment. Full article

The aim of this systematic review was to assess the influence of different final irrigation protocols and activation methods on the dentinal tubular penetration of calcium silicate-based sealers (CSSs). The review followed the PRISMA 2020 guidelines, and the protocol was registered in the Open Science Framework (OSF; DOI: 10.17605/OSF.IO/5HTVN). A PICOS-based research question was formulated, and a comprehensive literature search was conducted in MEDLINE, Scopus, Embase, Web of Science, and SciELO up to October 2025. After study selection, a qualitative synthesis of methodologies and outcomes was performed, and methodological quality was assessed using the QUIN tool. Twenty-one in vitro studies were included, all of which used single-rooted teeth or single roots. The available evidence suggests that final irrigation protocols may influence CSS penetration, although the magnitude and consistency of this effect varied substantially across studies. Sodium hypochlorite (NaOCl) and 17% EDTA were the most frequently investigated irrigants and were generally associated with improved penetration, but no irrigation protocol or activation technique can currently be considered superior. Current research trends include the evaluation of chelating agents, continuous chelation protocols, and irrigant activation systems such as passive ultrasonic irrigation, sonic activation, laser activation, and XP-Endo Finisher. Future studies should standardize irrigation protocols, activation methods, sealer types, obturation techniques, microscopy-based assessment procedures, and penetration outcome measures, while also including larger samples and more anatomically complex root canal systems. Full article

Deep unconventional oil and gas reservoirs are critical to hydrocarbon exploration and development in China. However, their complex geological and petrophysical features, including high temperature, high pressure, high salinity, multiple pressure systems, and intricate pore–fracture structures, make them highly susceptible to formation damage during drilling, completion, stimulation, and production. Effective reservoir protection is therefore essential for minimizing damage and improving development efficiency. This paper systematically reviews recent advances in reservoir protection for deep unconventional reservoirs, with a focus on evaluation methods and protective materials. Laboratory evaluation methods, including permeability recovery, nuclear magnetic resonance, pressure decay, and spontaneous imbibition, together with field-based approaches such as well testing and production decline analysis, are summarized and assessed for their applicability to complex damage characterization. Major damage mechanisms, including liquid-phase trapping, solid invasion, sensitivity damage, stress sensitivity, and wettability alteration, are analyzed with emphasis on working fluid–reservoir interactions under multi-field coupling conditions. Recent progress in protective materials is also reviewed, covering polymer-based materials such as gel sealing agents, delayed-swelling hydrogels, water-/oil-soluble temporary plugging agents, and film-forming polymers, as well as ultrafine CaCO₃ and fiber-based materials. In addition, related protection technologies, including temporary plugging, film-forming fluid-loss control, underbalanced drilling, and low-damage completion fluids, are discussed. Existing models developed for conventional sandstone reservoirs are insufficient for deep unconventional systems. Future research should prioritize integrated evaluation and protection methods tailored to deep tight, shale, and fractured–vuggy carbonate reservoirs. This review provides a basis for understanding complex damage mechanisms, developing functional protective materials, and advancing integrated reservoir protection technologies for the efficient development of deep unconventional resources. Full article

Soybean root rot, a destructive soilborne disease complex caused by a consortium of pathogenic fungi, poses a persistent threat to global soybean productivity. During 2022–2023, a total of 990 fungal isolates were recovered from symptomatic soybean roots across Heilongjiang Province, Northeast China. Of these, 279 isolates were identified as Fusarium equiseti through integrated morphological characterization and multilocus phylogenetic analysis. Notably, F. equiseti exhibited markedly elevated isolation frequencies (5.6–58.9%) across surveyed regions, confirming its status as the emerging dominant causal agent of root rot in this agroecological zone. Pathogenicity evaluations revealed that 76.67% of isolates displayed moderate virulence, with one strain classified as highly virulent (3.33%). In vitro fungicide sensitivity assays indicated that F. equiseti was most susceptible to prochloraz (mean EC₅₀ = 0.0010 µg·mL⁻¹) and fludioxonil (mean EC₅₀ = 0.0042 µg·mL⁻¹). When deployed as seed treatments, these two fungicides achieved 53.61% and 47.32% control efficacy against root rot, respectively, while significantly enhancing soybean seedling emergence, root length, and fresh weight. Collectively, these findings provide a scientific foundation for the precise, sustainable management of F. equiseti-mediated root rot in cold-region soybean production systems. Full article

Coordinating robot swarms requires jointly solving the interdependent Multi-Robot Task Allocation (MRTA) and Multi-Agent Path Finding (MAPF) problems under strict time and communication constraints, yet most existing methods rely on centralized planning or expose agents’ exact positions. In this study, a fully decentralized algorithm is proposed in which each agent estimates the positions and intended plans of others from broadcast bid values rather than shared coordinates, anticipating conflicts at intersections before moving and dynamically altering its movement or task assignment when it predicts it cannot reach its task in time. The method combines the Priority Inheritance with Backtracking (PIBT) algorithm for collision-free navigation with a novel Interval Type-3 Fuzzy Logic (IT3FL) mechanism for conflict resolution and congestion-aware rerouting. The approach was evaluated across seven benchmark environments against the centralized methods Enhanced Conflict-Based Search (ECBS) and ECBS with Task Allocation (ECBS-TA) and the Consensus-Based Auction Algorithm (CBAA). It reduced path cost by up to 7.10% relative to ECBS in open environments, while centralized methods remained superior in complex corridor-based maps. In the most demanding constrained scenario, it reduced solution cost by up to 47.03% and improved task completion by 35% over CBAA, demonstrating a robust, scalable decentralized alternative. Full article

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high costs, patient compliance issues, and increasing interest in safer, multi-targeted therapeutic strategies. In this context, plant-derived bioactive compounds have gained attention as complementary or alternative approaches to metabolic disease management. Gymnema sylvestre (Retz.) R.Br. ex Sm (GS), traditionally known as “gurmar” (“sugar destroyer”), is one of the most extensively studied medicinal plants with significant antidiabetic potential. This review evaluates the antidiabetic effects of G. sylvestre, focusing on its phytochemical composition, molecular mechanisms, and impact on diabetes-related complications. Major bioactive constituents, including triterpenoid saponins (gymnemic acids), gurmarin-like peptides, flavonoids, and sterols, regulate glucose homeostasis, inhibit intestinal glucose absorption, preserve pancreatic β-cell function, stimulate insulin secretion, modulate lipid metabolism, and suppress inflammatory signaling pathways. Experimental and clinical evidence indicates that G. sylvestre modulates oxidative stress and inflammation associated with complications such as nephropathy, neuropathy, retinopathy, vascular dysfunction, and dyslipidemia. This review adopts a mechanism-oriented framework integrating phytochemical structure–molecular target–metabolic outcome relationships and discusses emerging strategies, including nanotechnology-based delivery systems, molecular docking, and multi-component phytotherapy. Overall, G. sylvestre represents a promising multi-target phytotherapeutic agent, highlighting directions for future mechanistic and clinical research. Full article

Efficient and financially sustainable social protection systems are essential under conditions of economic instability and increasing social demand. However, traditional administrative models are often characterized by high operational costs, procedural complexity, and delayed benefit delivery. This study examines the role of digitalization, process automation, and AI-driven administrative solutions in reducing administrative expenses while enhancing the sustainability and resilience of social protection systems. An integrated Automation Index is developed using standardized proxy indicators that reflect reductions in operational and transaction costs associated with digital and automated technologies. To assess future trajectories of administrative expenses, scenario-based modelling is applied under three digital transformation paths—baseline, moderate, and intensive. Administrative efficiency is estimated using a translog Stochastic Frontier Analysis (SFA) framework. The results indicate that digitalization and automation significantly reduce administrative costs only when supported by favorable institutional conditions, including decentralized governance, effective inter-agency coordination, and clearly regulated administrative procedures. Under the intensive digital transformation scenario, administrative expenses decline substantially relative to the baseline, while system responsiveness and beneficiary coverage improve. In contrast, weak institutional environments limit the efficiency gains of technological solutions. The study concludes that AI agents and automated systems should be viewed not as substitutes for human decision-making but as tools for optimizing administrative architectures. This transition from resource-intensive to technology-intensive models is particularly important for developing countries seeking sustainable social protection under constrained fiscal conditions. Full article

Globally, Trichogramma Westwood (Hymenoptera: Trichogrammatidae) is known as the most effective biological control agent due to its ability to parasitize insect pest eggs. However, identifying an appropriate host is vital for Trichogramma to prosper. Therefore, this study delves into the complex role of semiochemicals in shaping the host-seeking behavior of Trichogramma parasitoids, with a particular focus on their responses to both plant-derived and host-derived cues. The mechanism of semiochemical reception in Trichogramma wasps relies on a highly specialized, sensitive olfactory and gustatory system to locate host eggs and mates. Semiochemicals, which mediate ecological interactions, have been identified as pivotal in influencing the parasitic efficiency of Trichogramma species. Trichogramma’s host-seeking behavior is influenced not solely by ovipositional cues but also by the intrinsic physical attributes of Lepidopteran hosts, such as the scales on the wings and abdomen, which emit semiochemicals capable of eliciting positive chemotactic responses, thereby guiding parasitoids toward optimal sites for oviposition. Furthermore, the interplay between insect-derived and plant-derived chemical cues exhibits a synergistic effect, collectively enhancing the chemotactic attraction of Trichogramma, thereby fine-tuning its host-seeking behavior with greater precision and specificity. This study further underscores Trichogramma’s innate behavioral ability to discriminate between host eggs of varying developmental stages, facilitating the precise identification and selection of the most suitable host for parasitization. Age and experience both make Trichogramma more selective of hosts, but younger parasitoids may take a broader approach to host selection due to their greater life expectancy. Furthermore, the removal of these cues affects their host localization and learning abilities. Associative learning enables Trichogramma to exhibit flexible behaviors, providing them with a selective advantage; allows them to explore various hosts; and reduces environmental uncertainty. Plant structure, host density, and host age are the key factors that significantly influence the foraging and parasitism of Trichogramma. The searching speed of this parasitoid is significantly influenced by temperature. Heat stress increases VOC emissions in plants such as potato via stomatal opening, reducing herbivore attraction and enhancing parasitoid recruitment. Furthermore, air pollution, including CO₂, O₃, and NOx, impairs parasitoid efficiency by disrupting volatile-mediated host location and reducing biological control performance. Trichogramma wasps are generally effective biological control agents, but their success depends on the species used, target pest, crop, release density, and field conditions. Overall, species such as T. ostriniae, T. japonicum, and T. leucaniae show the strongest performance in several crops by increasing parasitism, reducing pest damage, and improving yield. This study highlights the successful integration of semiochemical cues in pest management programs and the effective utilization of Trichogramma in conjunction with entomopathogenic bacteria to control Lepidopteran pests. This approach contributes to the development of more effective pest management strategies, thereby promoting agricultural sustainability. Full article

Glycine betaine transport systems are widely exploited by bacteria to survive osmotic stress and represent potential entry routes for antimicrobial delivery. Here, we investigate the bactericidal glycine betaine analog Tox-GB and its uptake, intracellular fate, and antimicrobial activity in Escherichia coli K-12 under osmotic stress. We show that the xenobiotic enters cells via a hierarchical uptake route involving the osmotically regulated compatible solute transporters ProU and ProP, ABC- and MFS-type transporters, respectively. ProU functions as the primary high-affinity transporter at low concentrations, whereas ProP provides a secondary uptake route at somewhat higher substrate levels. Loss of either transporter confers partial resistance, while simultaneous inactivation of both systems causes full resistance, underscoring their functional redundancy and the robustness of Tox-GB import. Intracellularly, Tox-GB undergoes oxygen-dependent degradation, yielding 4-nitrobenzaldehyde and dimethylglycine. While 4-nitrobenzaldehyde contributes to toxicity under aerobic conditions, Tox-GB remains bactericidal under anaerobic conditions, indicating additional oxygen-independent mechanisms involving either the parent compound or unidentified metabolites. These findings suggest a complex intracellular fate and multifactorial mode of action. Despite initial promise as a Trojan horse antimicrobial strategy, the use of Tox-GB for practical applications faces key limitations. Resistance readily emerges via transporter inactivation, and intrinsic resistance occurs in species lacking appropriate compatible solute uptake systems. Structural constraints in glycine betaine transporters further restrict design flexibility. Osmotic regulation limits activity to specific niches, and potential host toxicity stemming from reactive metabolites raises safety concerns. Collectively, these findings highlight the mechanistic complexity and translational challenges faced by glycine betaine–derived xenobiotics as antimicrobial agents. Full article

Interzeolite transformation (IZT) has emerged as a versatile strategy for accessing zeolite frameworks through controlled framework reorganization under comparatively simplified synthesis conditions. Unlike traditional synthesis approaches that frequently require organic structure-directing agents (OSDAs), highly alkaline media, and prolonged thermal treatment, IZT converts pre-existing zeolite into a new topology, enabling direct reuse of crystalline matter while reducing synthesis complexity. This review examines how structural drivers, including framework density, structural memory, and building-unit compatibility, govern transformation pathways and phase selectivity across five principal transformation approaches: (i) solution-mediated, (ii) assembly–disassembly–organization–reassembly (ADOR), (iii) mechanically assisted, (iv) steam-assisted, and (v) fully solid-state systems. These approaches promote distinct transformation pathways that govern framework reconstruction, structural inheritance, and phase selectivity. Recent advances in solvent-free, mechanochemical, steam-assisted, and microwave-assisted synthesis demonstrate the potential of IZT to reduce solvent consumption, template usage, and crystallization times. Despite these advances, major challenges remain in predicting transformation outcomes, controlling transient intermediates, and establishing scalable and quantitatively validated sustainability metrics. Collectively, these developments position IZT as a promising platform for the rational and sustainable design of next-generation zeolitic materials. Full article

With the increasing complexity of unmanned aerial vehicle (UAV) missions in complex obstacle environments, cooperative hunting of maneuvering ground targets by UAV swarms has become an important problem for multi-agent autonomous decision-making. This paper focuses on a simulated three-UAV hunting scenario in a two-dimensional obstructed environment, where UAVs must search for, approach, encircle, and continuously track a target while avoiding static obstacles under local observation. To address the problem of multi-UAV cooperative hunting of dynamic targets in complex obstacle environments, this paper proposes a curriculum learning (CL)-based Multi-Agent Proximal Policy Optimization algorithm, termed CL-MAPPO. Specifically, a three-stage progressive training curriculum is designed to overcome the challenges of low exploration efficiency, slow environmental adaptation, and difficult convergence of cooperative hunting policies faced by multi-agent deep reinforcement learning in hunting tasks, thereby gradually enhancing the cooperative hunting capability of UAVs in complex environments. Curriculum I employs fixed obstacles and a stationary target position to train the UAVs’ basic obstacle avoidance and target search abilities. Curriculum II introduces randomly generated obstacles and target positions to improve the UAVs’ adaptability to varying environments. Curriculum III further incorporates a dynamic target, prompting the UAVs to learn effective hunting strategies against maneuvering targets. The simulation experiment includes ablation experiments against MAPPO without curriculum learning and comparative simulations against MADDPG and MADQN, using reward convergence curves and trajectory visualizations to evaluate the training results. The results show that, under the same training episodes in the ablation experiment, CL-MAPPO reaches a higher and more stable reward level than vanilla MAPPO, indicating improved learning efficiency without increasing model complexity. In the comparative experiment, the CL-MAPPO algorithm achieved a higher success rate in cooperative hunting. These simulation experiments verify the effectiveness and superiority of the CL-MAPPO algorithm in multi-agent cooperative hunting tasks. Full article