Search Results (25,190)

In response to the complexity and uncertainty in assessing the safety and economic impacts of the Changed Product Rule (CPR) in civil aviation products’ airworthiness certification, this paper constructs a comprehensive evaluation model based on a cost–benefit analysis framework. In previous research, studies on aircraft modification costs have consistently been conducted from the perspective of design organizations, focusing on modeling and optimizing the one-time engineering costs of the modifications themselves or remaining confined to the level of safety performance without addressing the calculation of economic value. The model proposed in this paper considers the entire aircraft service lifecycle and uniformly quantifies potential impacts into monetary terms for comparison. The model encompasses safety improvements, cost estimation, and discounted cash flow analysis, aiming to provide decision-makers with quantitative tools for determining the applicability of the “impracticality exception” standard. This ensures that modifications to aviation products balance safety with economic viability. Through case studies involving fuel tank access panel design changes and Auxiliary Power Unit (APU) inlet duct fire protection requirements, the effectiveness and practicality of the model are validated, offering an empirical foundation for future policy formulation and industry regulation. Nevertheless, the parameters in the model depend on historical data, and appropriate parameters must be carefully selected. Although the model has taken into account the entire lifecycle of the aircraft, it is still based on static assumptions and fails to consider the impact of the rapid development of the aviation industry over time. Ongoing model refinement, international data collection, and integration of non-economic factors remain key directions for future research. Full article

Capacitive sensors are widely adopted in compact robotic systems due to their simple structure, ease of fabrication, and scalability for miniaturized designs. However, sensor miniaturization inevitably leads to reduced sensitivity and increased sensitivity imbalance, particularly in torque measurements, due to limited electrode area and spatial constraints. To address these limitations, this paper presents a compact six-axis force/torque (F/T) sensor based on a redundant capacitive sensing architecture. The proposed sensing architecture employs a symmetric arrangement of multiple capacitive electrodes, providing redundant capacitance measurements that enhance sensitivity while reducing coupling errors under multi-axis loading conditions. By exploiting redundant capacitive responses rather than relying on complex mechanical separation, the proposed design effectively improves measurement robustness. Based on this architecture, a compact six-axis F/T sensor with a diameter of 20 mm and a height of 12 mm is developed. Experimental validation demonstrates that the proposed sensor achieves linearity (>98.2%) with reduced cross-axis interference, confirming improved sensitivity and reliable multi-axis F/T measurement. This work provides a practical and scalable solution for integrating high-performance six-axis F/T sensing into space-constrained robotic systems. Full article

Ensuring production safety and enabling rapid emergency response in complex industrial environments remains a critical challenge. Traditional inspection robots are often limited by perception delays when confronted with sudden dynamic threats. This paper presents a vision-driven dynamic digital twin system designed to enhance real-time monitoring and emergency management capabilities. The framework constructs high-fidelity 3D models using SolidWorks 2024, Scaniverse 5.0.0, and 3ds Max 2024, and integrates them into a unified digital twin environment via the Unity 3D engine. Its core contribution is a vision-driven dynamic mapping mechanism: robots operating on the Robot Operating System (ROS) and equipped with ZED stereo cameras and embedded YOLOv5m models perform real-time detection, such as personnel and fire sources. Recognized targets trigger the dynamic instantiation of corresponding virtual models from a pre-built library, enabling automated, real-time reconstruction within the digital twin. An integrated service platform further supports early warning, status monitoring, and maintenance functions. Experimental validation confirms that the system satisfies key performance metrics, including data collection completeness exceeding 99.99%, incident detection accuracy of 80%, and state synchronization latency below 90 milliseconds. The system improves the dynamic updating efficiency of digital twins and demonstrates strong potential for proactive safety assurance and efficient emergency response in dynamic industrial settings. Full article

Adipocyte browning refers to the inducible transdifferentiation or de novo recruitment of thermogenically active beige adipocytes within white adipose tissue depots. Beige adipocytes, characterized by multilocular lipid droplets and high mitochondrial density, express uncoupling protein 1 and possess a metabolic phenotype similar to that of classical brown adipocytes. This plasticity of adipose tissue is regulated by a complex network of transcriptional coactivators (e.g., PRDM16, PGC-1α), epigenetic modulators, non-coding RNAs, and hormonal signals. Environmental cues, such as chronic cold exposure, exercise, and caloric restriction, further potentiate browning via sympathetic nervous system activation and endocrine crosstalk. At the systemic level, adipocyte browning enhances energy expenditure, improves insulin sensitivity, and mitigates lipid accumulation, making it a promising target for the treatment of obesity, type 2 diabetes mellitus, and other metabolic syndromes. Several browning agents (natural products and repositioned drugs) and novel chemicals that induce browning have been reported. However, the translational application of these agents in humans faces challenges related to interspecies differences, depot-specific responses, and long-term safety. This review critically examines molecular regulators, existing browning agents, and the discovery of novel browning agents, with the aim of harnessing them for metabolic disease intervention. Full article

Urbanization in mountainous regions alters hydrologic systems, yet the spatial patterning of residential (RA) and non-residential (NRA) areas in response to hydrologic constraints remains poorly quantified. In this study, we analyzed how such constraints shaped the distinct locational logic of RA and NRA expansion in the mountainous Kunming Core Region (KCR), Southwest China, from 1975 to 2020. Using the Global Human Settlement Layer (GHS-BUILT-S) built-up fraction data and its functionally classified RA and NRA layers at 100 m resolution, we quantified multi-decadal urban land changes via regression and centroid migration analyses. Six hydrologic factors, namely altitude, slope, surface roughness, distance to river (DTR), depth to water table (DTWT) and vegetation root depth (VRD), were derived from global terrain, groundwater, and rooting depth datasets, and harmonized to a common grid. Results show a two-phase urbanization pattern: moderate, compact growth before 1995 followed by rapid, near-exponential expansion, dominated by RA. RA consistently clustered in hydrologically favorable zones (low–moderate roughness, mid-altitudes, lower slopes, proximal rivers, shallow–moderate DTWT, moderate VRD), whereas NRA expanded into more hydrologically variable terrain (higher roughness, intermediate DTR, deeper DTWT, higher altitudes, deeper VRD). Contribution-weighting analysis revealed a temporal shift in dominant drivers: for RA, from river proximity and slope in 1975 to terrain roughness in 2020; for NRA, from vegetation root depth and moderate topography to root depth plus altitude. Geographic centroids of both RA and NRA migrated northeastward, indicating coordinated yet functionally distinct peri-urban and corridor-oriented growth. These findings provide a hierarchical, factor-based framework for integrating hydrologic constraints into risk-informed land-use planning in topographically complex basins. Full article

Intelligent Tutoring Systems are increasingly used in higher education to support personalized learning and academic monitoring in large-scale digital environments. However, existing systems are predominantly based on static architecture and rigid rule-based mechanisms, which limit scalability and hinder effective adaptation to heterogeneous learners, evolving learning behaviors, and real-world educational contexts. This paper presents a self-adaptive multi-agent architecture based on Reinforcement Learning for autonomous decision-making in intelligent systems deployed in real environments. The proposal integrates an RL Meta-Agent that dynamically optimizes the selection of specialized agents through an intelligent switching mechanism, considering the user’s state, behavior, and interaction patterns. The architecture was implemented in Moodle using flows orchestrated in n8n, LLMs, databases, APIs developed in Django, and real academic data. For the empirical evaluation, a real and a simulated case study were designed. A questionnaire was administered to university students, considering dimensions of usability, satisfaction and usefulness, and accessibility and interaction, to understand the perception of the system and improvements. The quantitative data were analyzed using descriptive statistics and nonparametric tests (Mann–Whitney U and Kruskal–Wallis), while the qualitative data were examined using thematic categorization. A simulated case study was conducted to analyze the behavior of the system. The results show that the RL Meta-Agent significantly improves system efficiency, response relevance, and adaptive agent selection, demonstrating that self-adaptive RL-based MAS architectures are a viable solution for intelligent systems applied in real-world contexts, providing empirical evidence of their performance and adaptability in complex scenarios such as higher education. Full article

There is a growing pressure for further breast cancer treatment development to improve patient quality of life and clinical effectiveness while reducing drug resistance and side effects. Clinical research, however, remains both expensive and time-consuming, highlighting the importance of advancing preclinical studies. The ability of a model to accurately replicate the biological environment is essential for generating reliable data. Although research on two-dimensional in vitro cell culture systems has been conducted for over a century, their limited complexity hinders further development of cancer treatments. Consequently, the response to tested medications is artificial, since some drugs appear to be effective only in the two-dimensional model and not in clinical settings. A multicellular spheroid (MCS) is a three-dimensional assembly of cancer cells, used in oncology to study cancer biology and drug sensitivity. MCSs serve as valuable in vitro models in preclinical drug development. They can also be used in a clinical setting as a personalized tool for drug susceptibility screening. The objective of this review is to highlight new possibilities for improved anticancer drug screening and the development of personalized treatment regimens with multicellular spheroids. Full article

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The kidney is among the organs most susceptible to sepsis-induced injury, and acute kidney injury frequently develops in this context, thereby markedly increasing mortality in affected patients. With continued advances in research, a more comprehensive understanding has been achieved regarding the clinical risk factors, pathophysiological mechanisms, therapeutic responses, and renal recovery processes associated with sepsis-associated acute kidney injury (SA-AKI). These advances have strengthened the capacity for prevention, early detection, and effective management of SA-AKI. Despite this progress, substantial gaps remain in the overall understanding of SA-AKI pathogenesis, including the complex interplay among pathophysiological mechanisms and the extensive cross-regulation of multiple signaling pathways. Consequently, SA-AKI remains a major clinical challenge and imposes a substantial global healthcare burden. There is therefore an urgent need for further research to elucidate the underlying mechanisms of SA-AKI and to identify more effective therapeutic strategies. Unlike previous reviews that primarily focused on individual mechanisms or isolated therapeutic targets, the present review synthesizes the most recent evidence on SA-AKI. Particular emphasis is placed on its pathogenic processes, associated molecular mechanisms and signaling pathways, and emerging therapeutic targets. Special attention is given to the hierarchical relationships among distinct mechanisms during disease progression and their implications for clinical translation. This review aims to inform clinical practice and to identify future research directions, thereby providing valuable insights for both researchers and clinicians in this field. Full article

Rabies is an acute and fatal zoonotic disease caused by the rabies virus, responsible for approximately 59,000 deaths worldwide each year. Once clinical symptoms manifest, the case fatality rate approaches 100%. Vaccination remains the only effective strategy for prevention and control. Currently, human rabies vaccines approved by regulatory authorities such as the U.S. Food and Drug Administration (FDA), and the China National Medical Products Administration (NMPA) are all inactivated, adjuvant-free formulations. These vaccines are associated with several limitations, including weak immunogenicity, delayed induction of neutralizing antibodies, complex immunization schedules, and poor patient compliance. Adjuvants, as nonspecific immunoenhancers, can potentiate the immune response even at low antigen doses and reduce the number of required doses, offering a promising approach to overcome the aforementioned challenges. This article reviews recent advances in adjuvants suitable for rabies vaccines and discusses the key challenges currently faced in the development of adjuvanted rabies vaccines. Full article

Soil salinization and alkalinization critically constrain alfalfa (Medicago sativa L.) productivity, yet the regulatory mechanisms underlying its responses to salt–alkali stress are not fully understood. In this study, the alfalfa variety “Zhongmu No. 1” was used as experimental material. The seeds were subjected to salt stress (75 mM NaCl), alkali stress (15 mM NaHCO₃), and combined salt–alkali stress (50 mM NaCl + 5 mM NaHCO₃) in dishes, with ddH₂O serving as the control (CK). After 7 days of germination, the seedlings were transferred to a hydroponic system containing Hoagland nutrient solution supplemented with the corresponding treatments. Following 32 days of stress exposure, leaf and root tissue samples were collected for morphological and physiological measurements, as well as mRNA and miRNA sequencing analyses. Physiological assays revealed significant growth inhibition and increased electrolyte leakage under stress conditions. Transcriptome profiling identified over 5000 common differentially expressed genes (DEGs) in both leaves and roots under stress conditions, mainly enriched in pathways related to “iron ion binding”, “flavonoid biosynthesis”, “MAPK signaling”, and “alpha-Linolenic acid metabolism”. MiRNA sequencing detected 453 miRNAs, including 188 novel candidates, with several differentially expressed miRNAs (DEMs) exhibiting tissue- and stress-specific patterns. Integrated analysis revealed 147, 81, and 140 negatively correlated miRNA–mRNA pairs across three treatment groups, highlighting key regulatory modules in hormone signaling and metabolic pathways. Notably, in the ethylene and abscisic acid signaling pathways, ERF (XLOC_006645) and PP2C (MsG0180000476.01) were found to be regulated by miR5255 and miR172c, respectively, suggesting a post-transcriptional layer of hormonal control. DEM target genes enrichment pathway analyses also identified stress-specific regulation of “Fatty acid degradation”, “Galactose metabolism”, and “Fructose and mannose metabolism”. qRT-PCR validation confirmed the expression trends of selected DEGs and DEMs. Collectively, these findings reveal the complexity of miRNA–mRNA regulatory networks in alfalfa’s response to salt–alkali stress and provide candidate regulators for breeding stress-resilient cultivars. Full article

Background/Objectives: Postoperative cognitive dysfunction (POCD) represents a significant and potentially preventable complication in elderly patients undergoing colorectal cancer surgery, with reported incidence ranging from 2.8% to 62.2% depending on perioperative management strategies and assessment methods. This narrative review synthesizes current evidence on the epidemiology, pathophysiology, risk factors, and prevention strategies for POCD in this vulnerable population. Methods: A comprehensive narrative review was conducted to examine the current literature on POCD in elderly colorectal cancer patients. Evidence was synthesized from published studies addressing epidemiology, assessment tools, risk factors, pathophysiological mechanisms, and prevention strategies, with a particular focus on Enhanced Recovery After Surgery (ERAS) protocols and multicomponent interventions. Results: Advanced age, pre-existing cognitive impairment, frailty, and surgical complexity emerge as key risk factors for POCD. ERAS protocols demonstrate substantial protective effects, reducing POCD incidence from 35% under conventional care to as low as 2.8% in optimized pathways. The pathophysiology involves multifactorial mechanisms, including neuroinflammation, blood–brain barrier disruption, neurotransmitter dysregulation, and oxidative stress, with surgical trauma triggering systemic inflammatory cascades that activate microglial responses within the central nervous system. Evidence-based prevention strategies include preoperative cognitive and frailty screening, minimally invasive surgical techniques, multimodal opioid-sparing analgesia, regional anesthesia, depth-of-anesthesia monitoring, and structured postoperative care bundles adapted from the Hospital Elder Life Program. Conclusions: The integration of comprehensive perioperative cognitive care protocols represents a critical priority as surgical volumes in elderly populations continue to expand globally. Emerging directions include biomarker development for early detection and risk stratification, precision medicine approaches targeting individual vulnerability profiles, and novel therapeutic interventions addressing neuroinflammatory pathways. Standardized assessment tools, multidisciplinary collaboration, and implementation of evidence-based preventive interventions offer substantial promise for preserving cognitive function and improving long-term quality of life in elderly colorectal cancer patients. Full article

The experiences and repercussions of the cross-border migration process on family life have not yet been synthesized. This study aimed to synthesize the best available qualitative findings on this theme. A systematic review of qualitative evidence with meta-synthesis was conducted. Articles were identified according to predefined extraction criteria in the first half of 2025, across seven databases: Web of Science, MEDLINE/PubMed, PsycINFO, LILACS, CINAHL, SCOPUS, and Social Science Citation Index. Two researchers independently screened and appraised the reports, assessing methodological quality and systematically recording and analyzing relevant information. A protocol was registered in PROSPERO (ID: CRD42024505655). Fifty studies were included, and three main themes emerged: (a) living in multiple possible contexts, where space and relationships influence family functionality, including reduced family time due to long working hours, substance use, fear of losing cultural roots, new financial responsibilities, and the desire to return to the country of origin; (b) challenges and repercussions on family life after migration, such as increased family conflicts, mental health problems, separation, and loss of ties; (c) strategies for maintaining family functioning, including role adjustment, strengthening of family ties, and support through cultural and religious practices. Families undergoing migration face multiple challenges in their new environments, revealing the complexity of adapting to diverse cultural and social contexts. These findings highlight the need to address the emotional and social demands of migrant families to improve well-being and integration. Understanding these dynamics allows healthcare professionals to design culturally sensitive interventions that promote reception and inclusion. Full article

Eye drops derived from human blood components (Eye Drops of Human Origin—EDHO) have proven effective in reducing ocular pain associated with severe keratopathies. Among these, Cord Blood Serum (CBS) is particularly promising for its high content of growth and neurotrophic factors. This study evaluated the ability of CBS to modulate inflammatory and nociceptive activation in the human conjunctival epithelial cell (HCEC) line exposed to hyperosmotic stress. CBS batches were characterized for brain-derived neurotrophic factor (BDNF) content and classified as CBS_high (levels > 18.0 ng/mL) or CBS_low (levels < 10.0 ng/mL). HCECs were exposed to NaCl (450 mOsm/L) with or without 5% CBS. Cell viability was evaluated, and the expression of Major Histocompatibility Complex Class II (HLA-DR) (a marker of immune activation) and Transient Receptor Potential Vanilloid 1 (TRPV1) (a nociceptive ion channel responsive to osmotic stress) was assessed via Real Time PCR (RT-PCR). CBS significantly improved HCEC viability under hyperosmotic stress. Exposure to NaCl alone upregulated HLA-DR and TRPV-1 expression. Both CBS preparations attenuated these responses, producing comparable reductions in HLA-DR mRNA and decreasing TRPV-1 expression. Partial reversal of CBS effects by the pan-neurotrophin receptor inhibitor K252a supported neurotrophin involvement. CBS reduces hyperosmolarity-driven inflammation and nociception via HLA-DR and TRPV1 downregulation, supporting its role as a bioactive tear substitute in neuroinflammatory ocular surface disease. Full article

Background: Virus-like particles (VLPs) represent key tools for the development of vaccines due to their ability to induce a potent immune response to epitopes presented on their surface. However, the decoration of VLPs with a complete heterologous protein on the surface remains a bottleneck for clinical translation due to the complexity of manufacture. We present a novel platform, EPIclip™, for the decoration of VLPs mediated by high-affinity protein binding partners, colicin E7 (ColE7) and immunity protein 7 (Im7), within a single prokaryotic host. We evaluate this approach using a modified hepatitis B core capsid protein and IL-31 as a model epitope. IL-31 is a prominent therapeutic target for the development of pruritic diseases. Methods: We explore the design and development of the platform, including the use of T-cell-stimulating peptides. We demonstrate several small-scale purification methods for the candidate VLP, as well as morphological analysis by transmission electron microscopy (TEM). Further, we vaccinate mice with IL-31-displaying VLPs to evaluate immunogenicity and the ability to prevent IL-31-induced pruritus in vivo. Results: Our results demonstrate that decorated VLPs dosed in mice elicit an IgG response against IL-31 with at least six months of durability. In addition, IL-31-displaying VLPs suppress the development of IL-31-induced pruritus, confirming in vivo target neutralisation. Notably, IL-31-displaying VLPs induce a strong T-cell response against the VLP capsid but not against the cytokine, confirming a B-cell-biased immune response and the absence of detrimental autoreactive T cells. We further demonstrate the translation of this system with an additional virus capsid: tomato aspermy virus (TAV). Conclusions: Taken together, the novel EPIclip™ platform may represent a promising therapeutic approach for pruritic diseases. Additionally, this modular system could be adapted for a wide range of research as well as human and veterinary therapeutic applications. Full article

Triple-negative breast cancer (TNBC) is an aggressive and clinically challenging subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. This molecular phenotype narrows the availability of targeted therapies and contributes to high rates of early relapse, therapeutic resistance, and poor clinical outcomes. Mounting evidence pinpoints the tumor microenvironment (TME) as a central driver of TNBC progression, immune evasion, and resistance to treatment. The TME encompasses a complex and dynamic network of immune and stromal cells, extracellular matrix components, and soluble mediators that collectively shape tumor behavior and influence therapeutic response. Notably, TNBC often displays an immunologically active microenvironment, marked by high levels of tumor-infiltrating lymphocytes and immune checkpoint expression, opening a window for immune-based therapeutic strategies. This narrative review summarizes current knowledge on the cellular, molecular, and structural features of the TNBC tumor microenvironment, with particular focus on immunosuppressive mechanisms mediated by tumor-associated macrophages, myeloid-derived suppressor cells, cancer-associated fibroblasts, and dysfunctional T cells. We describe the clinical development and therapeutic impact of monoclonal antibodies, including immune checkpoint inhibitors and antibody–drug conjugates. Additionally, we discuss strategies aimed at modulating the TME to enhance monoclonal antibody efficacy, including immune cell reprogramming, extracellular matrix remodeling, cytokine/chemokine blockade, and combination treatment strategies. Finally, we highlight the role of biomarker-driven patient stratification and personalized therapeutic strategies, addressing current challenges and future directions in TME-targeted drug development. Together, these insights underscore the potential of integrating immune modulation and monoclonal antibody-based therapies to improve outcomes for TNBC patients. Full article