Search Results (38,835)

The global prevalence of autoimmune diseases ranges from 3% to 8%, with women at a significantly higher risk than men. The core mechanisms underlying these diseases include impaired T-cell and B-cell immune tolerance, abnormal cytokine production, and aberrant activation of related signaling pathways. Conventional treatments primarily focus on suppressing immune responses, but their efficacy remains limited and they are often associated with substantial side effects. Nanomedicine leverages nanoscale materials to enable precise diagnosis and targeted therapy. Nanocarriers can penetrate biological barriers, enhance cellular uptake, and prolong circulation time in vivo, demonstrating considerable potential for drug delivery. Common nanoscale drug delivery platforms include nanoparticles, polymeric micelles, liposomes, dendrimers, mesoporous materials, hydrogels, and exosomes. Each carrier type possesses distinct characteristics in terms of drug-loading capacity, stability, responsiveness, and biocompatibility, thereby enabling targeted delivery and controlled release. This review summarizes recent advances in nano-delivery technologies for three representative chronic autoimmune diseases: diabetes mellitus (DM), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Nano-delivery systems can improve therapeutic outcomes by optimizing drug delivery, targeting complications, and modulating the pathological microenvironment. They enhance drug bioavailability, reduce off-target and systemic adverse effects, and provide novel strategies for the precise and efficient treatment of chronic autoimmune diseases. Full article

Background/Objectives: Although influenza A viruses with partially truncated NS1 proteins are substantially attenuated and immunogenic due to enhanced innate immune activation; residual NS1-mediated antagonism of antiviral innate responses may support viral replication in the lower respiratory tract and constrain optimal immune responses. Strategies to further improve their immunogenicity and protective efficacy by incorporating immunomodulatory cytokines, such as IL-2, have been successfully explored. Methods: Here, we extended this approach to chemokine expression by engineering an NS1-truncated PR8-based virus (PR8/NS124) to express the immunomodulatory chemokine CXCL10 from the NS segment and compared it with the parental vector. Results: The recombinant NS124_SS_CXCL10 virus replicated to high titers in embryonated chicken eggs and MDCK cells. In vivo, however, CXCL10 expression reduced viral replication in mouse lungs by ~10⁴-fold, resulting in a near-non-replicating phenotype. In contrast to the parental virus, the vector did not induce weight loss and exhibited a strongly attenuated phenotype. This effect was associated with altered innate immune signaling, including increased IRF7 expression and early induction of IFN-α responses in the lungs, together with modulation of TLR-dependent sensing pathways in the upper respiratory tract. Despite severely impaired replication, intranasal immunization induced antigen-specific T-cell responses comparable to those elicited by the parental vector. Following intraperitoneal immunization, when replication of both vectors was minimal, the CXCL10-expressing vector induced significantly higher frequencies of antigen-specific CD8⁺ and CD4⁺ effector-memory T cells. This was accompanied by enhanced antigen-specific T-cell recall responses in the lungs following intranasal challenge. Importantly, the CXCL10-expressing vector demonstrated protective efficacy comparable to that of the parental NS124 vector against heterologous H3N2 challenge while exhibiting an improved safety profile. Conclusions: These findings support the incorporation of CXCL10 as a strategy to improve the safety and T-cell immunogenicity of NS1-truncated influenza vectors. Full article

Cancer progression is closely associated with dysregulation of apoptosis, enabling malignant cells to evade programmed cell death and develop resistance to therapy. Among the key regulators of this process, the tumor suppressor protein p53 and the Bcl-2 family of proteins play central and interconnected roles in controlling cell survival and mitochondrial integrity. In recent years, naturally occurring flavonoids have attracted considerable attention as potential modulators of these pathways due to their diverse biological activities and relatively low toxicity. This review provides a focused and integrative overview of how different subclasses of flavonoids modulate the p53–Bcl-2 signaling axis to regulate apoptosis in cancer cells. Particular emphasis is placed on the mechanistic interplay between p53 stabilization, transcriptional regulation of apoptotic targets, mitochondrial outer membrane permeabilization, and caspase activation. In contrast to previous general reviews on flavonoids and cancer, this work provides an integrated overview of evidence across multiple flavonoid subclasses and experimental cancer models, highlighting both shared and pathway-specific apoptotic responses. Experimental findings from in vitro and in vivo studies are discussed, including the effects of quercetin, kaempferol, myricetin, epigallocatechin gallate, and related compounds on cell-cycle arrest, oxidative stress, mitochondrial dysfunction, and intrinsic apoptotic signaling. Furthermore, the review examines the relationship between flavonoid chemical structure and biological activity, with particular attention to bioavailability, metabolic transformation, and strategies aimed at improving therapeutic efficacy, including structural modification and nanocarrier-based delivery systems. Despite promising preclinical findings, significant translational challenges remain, including poor pharmacokinetic properties, variability among experimental models, and limited clinical validation. Overall, flavonoids represent a promising class of bioactive compounds capable of targeting apoptosis through modulation of the p53–Bcl-2 network, and a deeper mechanistic understanding of their activity may support the development of novel targeted and combination anticancer therapies. Full article

To identify novel field control strategies against Pyrrhalta aenescens (Coleoptera: Chrysomelidae) and provide scientific support for its biocontrol in urban tree management, this study investigated the virulence of Beauveria bassiana against this pest under laboratory conditions, as well as its physiological and biochemical effects. Bioassays using the dipping method showed that B. bassiana was pathogenic to all developmental stages of P. aenescens, with the highest virulence observed against early-instar larvae (1st and 2nd instars). For these stages, corrected mortality and mycosis rate were positively correlated with conidial concentration, and the median lethal time (LT₅₀) was the shortest. In contrast, pupae and eggs exhibited the strongest resistance to fungal infection. In leaf-disk choice tests, larvae significantly preferred untreated leaves or those treated with low concentrations of B. bassiana, displaying a concentration-dependent repellent response to the fungus. Physiological measurements revealed that larval body length and weight gain were significantly inhibited following fungal exposure. Further analysis indicated that B. bassiana infection markedly reduced total hemocyte counts and triggered intense melanization and nodulation responses, particularly in younger larvae. Overall, these results suggest that B. bassiana has strong potential for the biological control of P. aenescens. Control measures targeting early-instar larvae are recommended for cost-effective management, providing a scientific basis for developing eco-friendly control technologies based on this entomopathogenic fungus. Full article

Rheumatoid arthritis (RA) remains a recalcitrant clinical challenge, as modern therapies are often hampered by adverse effects, suboptimal responses, and failure to achieve radical cure. Traditional Chinese Medicine (TCM) and Tujia ethnomedicine, with centuries of accumulated experience in managing RA (classified as “Bi Syndrome” in TCM), offer distinct theoretical frameworks and abundant therapeutic resources. TCM emphasizes syndrome differentiation-based holistic regulation, while Tujia ethnomedicine relies on indigenous medicinal plants and empirically derived therapies shaped by its unique geographical context. This review aims to accelerate the integration of traditional wisdom with contemporary pharmacology for the development of novel RA therapies. A comprehensive literature search was performed across PubMed, Web of Science, CNKI, and ethnomedical monographs to synthesize data on their theoretical underpinnings, therapeutic strategies, mechanisms of action, and clinical efficacy. TCM and Tujia ethnomedicine possess significant anti-RA effects, characterized by multi-component, multi-target synergistic mechanisms that complement modern medicine. However, they face common challenges including unclear material bases of active components, insufficient standardized clinical evidence, and inadequate quality control protocols. This review provides a critical foundation for integrating TCM/Tujia ethnomedicine with modern pharmacology, highlighting the urgent need for further research to clarify active constituents, establish standardized protocols, and validate clinical efficacy—ultimately facilitating the development of safer, more effective RA therapies. Full article

Parallel multi-blade centrifugal fans present a challenge in simultaneously reducing aerodynamic noise and maintaining efficiency. This study presents a multi-objective optimization using a radial basis function (RBF)-assisted Bayesian optimization framework, with three volute parameters (tongue radius, tongue clearance, and axial gap) as design variables. Computational fluid dynamics (CFD) combined with the Ffowcs Williams–Hawkings (FW-H) acoustic analogy was employed to evaluate noise and total pressure efficiency. To reduce computational cost, an RBF surrogate model was constructed from 30 Latin hypercube samples, achieving leave-one-out cross-validation (LOOCV) R² values of 0.978 and 0.995 for noise and efficiency, respectively. A Bayesian search using the log expected hypervolume improvement (logEHVI) acquisition function was performed on the RBF response surfaces, converging to a hypervolume of approximately 0.72, consistent with an NSGA-II benchmark. Based on household fan requirements, a 70/30 noise-efficiency weighting was adopted, yielding RBF-predicted values of 59.04 dB and 0.545 for the selected low-noise-preference candidate. An independent CFD recalculation yielded 59.19 dB and 0.554. The SPL at the characteristic frequency of 2550 Hz was reduced by 9.9 dB. Flow field analysis revealed that the optimized tongue clearance weakened the impingement on the volute tongue and suppressed unsteady vortex shedding. This framework provides an efficient strategy for multi-objective aerodynamic and acoustic optimization of parallel centrifugal fan systems. Full article

Cardiovascular diseases remain the leading cause of mortality worldwide, highlighting the urgent need for more effective therapeutic strategies. Despite substantial advances in conventional biomaterials, their limited ability to support functional integration and dynamically interact with the biological microenvironment continues to hinder therapeutic outcomes. Native cardiovascular tissues rely on tightly regulated bioelectrical signaling to coordinate cellular communication, tissue homeostasis, and functional repair. Consequently, recreating these bioelectrical cues has emerged as a key design principle in cardiovascular tissue engineering. Electroactive biomaterials have gained increasing attention as a promising platform to address this challenge by enabling electrical modulation of cellular behavior and tissue function. In this review, we summarize the intrinsic bioelectrical properties of cardiovascular tissues and discuss the roles of electrical stimulation in regulating disease-relevant cellular responses. We further highlight recent advances in the development of conductive, piezoelectric, and other electroactive biomaterials for cardiovascular tissue engineering applications. Finally, we critically discuss the major challenges and future opportunities in the field, including tissue-specific responses, stimulation parameter optimization, long-term safety, and clinical translation. Collectively, electroactive biomaterials represent a promising and rapidly evolving frontier for the development of dynamic, responsive, and next-generation therapies for cardiovascular diseases. Full article

Aquatic environments that support tourism, including coasts, lakes, reservoirs, and estuaries, are experiencing accelerating eutrophication worldwide. This trend increases the frequency and intensity of algal blooms. These blooms undermine ecosystem services and weaken the socio-economic performance of destination areas. Despite these challenges, existing research remains fragmented. Aquatic sciences mainly examine nutrient enrichment and bloom dynamics. In contrast, tourism studies often treat blooms as episodic disturbances and rarely integrate exposure pathways, risk communication, or feedback to destination governance. This review synthesizes evidence across freshwater and marine systems to develop a coupled tourism–water ecosystem perspective. We link eutrophication drivers and bloom typologies to three dimensions. These are the degradation of tourism-supporting ecosystem services, compound health stressors, and communication filters. The first includes losses of water clarity and aesthetic value. The second involves multi-route exposure through contact, inhalation, and seafood ingestion. The third shapes perceived safety, trust, and behavioral adaptation. We further connect perceived health risks to observable tourist behaviors, including cancellation, destination substitution, and activity avoidance. These micro-level responses can aggregate into market-level demand contractions and consumption reallocation. They can also trigger regional economic cascades, including public management costs, employment impacts, and long-term reputational damage. Crucially, tourism is not merely a victim of blooms. It can also act as a reinforcing anthropogenic driver through wastewater burdens, infrastructure expansion, and pulse pressures. These pressures lower ecological resilience, especially under warming and hydrological stabilization. Finally, we identify governance leverage points. These include early-warning systems, threshold-based graded interventions, transparent risk communication, and integrated social–ecological modeling. These strategies can reduce uncertainty-driven losses and support adaptive destination management. Overall, this review reframes algal blooms as systemic social–ecological risks. It provides a structured basis for future empirical attribution and policy design in tourism-dependent waters under climate stress. Full article

Persistent teacher shortages in rural schools continue to challenge the provision of equitable, high-quality education. While research has documented the difficulties of recruiting and retaining teachers in these contexts, less attention has been given to how the conditions of teaching are shaped through leadership in contexts of workforce instability. This study examines how principals in rural schools in Victoria, Australia, respond to ongoing shortages through place-responsive leadership strategies. Drawing on qualitative interview data from principals across diverse rural school settings, the study identifies three interrelated practices: cultivating place-based recruitment pathways, fostering retention through care, professional development and wellbeing, and sustaining the workforce through community embedded practices. These practices shape the conditions under which teachers work by strengthening relationships, supporting wellbeing, and fostering belonging. The study conceptualises workforce sustainability as a professional condition actively constructed through leadership in context. Full article

With the increasing integration of distributed energy sources, fault restoration in power distribution systems faces challenges in terms of real-time performance and adaptability. To effectively manage the uncertainty and volatility of distributed generation, this paper proposes a rapid self-healing strategy based on a dynamic operational grid. By enabling real-time topological reconfiguration and utilizing adaptive resource allocation, the proposed method accommodates the inherent fluctuations of distributed energy sources. First, a dynamic grid weighted graph theory model is constructed, and an emergency control strategy combining particle preprocessing and stepwise optimization is designed to achieve rapid fault response. Then, a “primary-secondary” two-tier restoration mechanism is established: the primary layer integrates the Floyd algorithm with optimized adaptive dynamic programming to achieve millisecond-level restoration of critical loads; the secondary layer employs an improved particle swarm algorithm incorporating Lévy flight perturbations and adaptive weighting to maximize the restoration of general loads. Simulations on a 56-node system demonstrate that this method achieves 100% restoration of critical loads under various fault scenarios. Even under extreme conditions, it can restore 90.88% of secondary loads and 44.63% of tertiary loads, forming a self-healing system characterized by “second-level detection and minute-level restoration,” thereby significantly enhancing system resilience. Full article

Rising heatwaves threaten urban sustainability, necessitating a shift toward heat resilience. This study examines 38 cities across China’s three major coastal urban agglomerations (2016–2024) to quantify dynamic resilience responses. Utilizing a dual-threshold identification method and the Baidu Search Index to construct a Standardized Stress Index (SSI), the research evaluates urban heat vulnerability (UHV) through an exposure–sensitivity–adaptive capacity framework while applying NMF and machine learning models (XGBoost/SHAP) to analyze spatiotemporal heterogeneity. The results show that heatwave pressures peaked in 2022–2023, with Jing–Jin–Ji’s UHV evolving from localized clusters toward regional homogenization. Regional UHV profiles reveal that Jing–Jin–Ji is constrained by population pressures, the Yangtze River Delta (YRD) by resource allocation, and the Pearl River Delta by industrial attributes; notably, the YRD’s systematic coordination effectively offsets structural vulnerability. Furthermore, the optimized XGBoost model achieves strong predictive performance (R² = 0.673), revealing that core factors like summer heat exposure intensity (SHE, 25.65% importance) trigger sharp non-linear surges in social stress upon crossing critical inflection thresholds (e.g., SHE at −0.10). The conclusion will lead to the formulation of differentiated, forward-looking climate adaptation strategies to enhance urban resilience across major regions. Full article

Background: Radioiodine (Na[¹³¹I]I) therapy is the cornerstone of systemic treatment for differentiated thyroid cancer (DTC), exploiting sodium–iodide symporter (NIS) expression for durable control. Up to 30–40% of advanced cases develop radioiodine-refractory disease (RAI-R DTC), marked by impaired iodine uptake, aggressive behavior, and poor response to Na[¹³¹I]I. Locoregional treatments, multikinase inhibitors (MKIs), and selective targeted agents improve progression-free survival but are not curative and carry cumulative toxicity, motivating precision-based alternatives. The primary objective of this review is to clarify the evolving theranostic paradigm in RAI-R DTC; the secondary objectives are to appraise redifferentiation and iodine-based theranostics for restoring or exploiting iodine avidity and to evaluate non-iodine theranostic strategies for cases where iodine biology is absent, impaired, or unreliable. Methods: This narrative review synthesizes contemporary evidence on theranostic strategies in RAI-R DTC, drawn from available studies, clinical trials, and current guidelines, with an emphasis on redifferentiation and non-iodine approaches; a systematic search protocol was not applied. Results: Theranostics couples target-specific molecular imaging with matched radionuclide therapy and response-adapted sequencing. Its most transformative application is redifferentiation, in which pharmacologic modulation of oncogenic signaling can restore iodine avidity and enable renewed, dosimetry-guided Na[¹³¹I]I treatment. Beyond iodine, somatostatin receptor (SSTR) imaging and peptide receptor radionuclide therapy (PRRT) have re-emerged in very selected cases, whereas alpha emitters remain investigational. Refractoriness is increasingly viewed as a reversible continuum rather than a fixed state. Conclusions: Theranostics can individualize RAI-R DTC treatment, restoring or exploiting iodine biology where possible and shifting to non-iodine targets where it is unreliable. Patient selection, timing, and integration with systemic therapy are central, and prospective validation is needed. Full article

Glioblastoma (GBM) is one of the most aggressive human cancers, with therapeutic failure driven by pronounced intratumoral heterogeneity, microenvironmental plasticity, immune suppression, blood–brain barrier (BBB)-related pharmacological constraints, and adaptive resistance mechanisms. A major limitation in GBM research is the lack of a human-relevant experimental system able to reproduce these dynamic features while generating interpretable, multimodal datasets. In this context, we propose a testable organ-on-chip (OoC)-extracellular vesicle (EV)-deep learning (DL) framework in which patient-derived GBM cells, endothelial cells, astrocytes, pericytes, stromal cells, and immune components are organized within perfused microphysiological systems. EVs are selectively and temporally harvested from defined compartments, and imaging, barrier-function, sensor, and EV-cargo data are integrated through modality-specific and multimodal DL architectures. This framework is intended not as an immediately validated clinical tool but as an experimental roadmap for linking EV-mediated communication to measurable phenotypes such as BBB disruption, invasion, immune reprogramming, and drug response. We critically discuss the technical requirements of BBB-on-chip systems, EV source attribution, immune-component integration, DL model selection, data scarcity, overfitting, batch effects, domain shift, regulatory barriers, cost, throughput, and reproducibility. By repositioning OoC-EV-DL integration as a staged translational strategy rather than a clinically established solution, this work aims to define a realistic and biologically grounded route for advancing precision oncology in GBM. Full article

Internal combustion engines are a well-established, efficient and dispatchable solution for distributed power generation and they are widely used in various sectors including grid balancing, data centers and combined heat and power systems. Current research efforts focus on further increasing efficiency, enabling decarbonization through renewable fuels and improving responsiveness to electricity demand in the presence of variable renewable energy sources. In this context, the free-piston linear generator (FPLG) stands out as a highly promising technology, as it directly converts piston motion into electricity, offering high efficiency, reduced mechanical complexity and seamless grid integration. Initially explored for its high-efficiency potential with homogeneous charge compression ignition combustion at extreme compression ratios, opposed-piston FPLGs are now commercially available for distributed power generation, delivering global efficiencies exceeding 45%, near-zero emissions and multi-fuel capability. Building on the detailed studies conducted by Svrcek and co-authors, this work investigates the power-generation potential of low-temperature homogeneous combustion using CFD simulations with detailed chemical kinetics. First, rapid compression machine (RCM) experiments with methane were reproduced in simulations to validate the proposed methodology and to consolidate experimental findings on the maximum achievable efficiency. Subsequently, an extensive RCM simulation campaign supported the identification of optimal operating conditions in terms of air–fuel ratio using methane as fuel. The RCM results enabled the definition of a preliminary methane-fueled opposed-piston FPLG configuration. Full-cycle simulations including gas exchange, mixing and combustion demonstrated an indicated efficiency of 58% at an equivalence ratio $\varphi =0.5$ and a compression ratio of 50. The key novelties of this study are the development of a novel RCM-2 configuration that more closely reproduces the dynamic behavior of an opposed-piston FPLG including air-spring effects and the introduction of a divided intake port strategy to simultaneously reduce fuel slip and mitigate knocking behaviour through charge stratification. The simulation results for the proposed configuration confirm the potential of opposed-piston FPLGs for high-efficiency power generation and highlight key parameters affecting performance and emissions formation. Full article

Collaborative business ecosystems (CBEs) face persistent disruptions, including pandemics, geopolitical instability, climate shocks, cyber threats, resource scarcity, and sustainability transition pressures. Building on prior CBE resilience–antifragility research and a mathematical framework that introduced plasticity as a viable below-baseline response trajectory, this integrative review aims to develop a sustainability-oriented framework explaining how CBEs can align response modes, strategies, capabilities, governance mechanisms, and enabling infrastructures under persistent disruption. The review synthesizes the 2019–2026 literature on sustainable business model innovation (SBMI), circular and regenerative perspectives, digital capability infrastructures, and ecosystem governance. Drawing on 99 sources, it proposes a six-layer Sustainable Resilience–Antifragility Framework for CBEs (SRA-CBE Framework), linking disruption sources, ecosystem vulnerabilities, viable response modes, strategy and capability portfolios, governance mechanisms, and sustainability-oriented outcomes. The synthesis shows that sustainable CBEs require aligned strategy bundles, adaptive and sustainability-oriented capabilities, governance arrangements that prevent collaboration and digitalization from becoming fragility sources, and enablers such as SBMI, circularity, scenario simulation, and governed digital infrastructures. The paper contributes by sharpening the link between disruption response and sustainability-oriented ecosystem design, repositioning viable response modes as design positions, and outlining managerial and research implications for sustainable collaborative ecosystems. Full article