Search Results (55,815)

Adenosine plays a crucial role in various pathophysiological conditions, including neuroinflammation and neurodegeneration. Neuroinflammation can be either beneficial or detrimental to the central nervous system, depending on the intensity and duration of the inflammatory response. Across a wide range of brain disorders, neuroinflammation contributes to both the onset and progression of disease. Notably, neuroinflammation is not limited to conditions primarily classified as neuroinflammatory but is also a key factor in other neurological disorders, including life-threatening neurodegenerative diseases. All four adenosine receptor subtypes (A₁, A_2A, A_2B, and A₃) are implicated, to varying degrees, in these conditions. This review aims to summarize the roles of individual adenosine receptor subtypes in neuroinflammation and neurodegenerative diseases, emphasizing their therapeutic potential. While some therapeutic applications are well-established with clinically approved drugs, others warrant further investigation due to their promising potential. Full article

This study presents a comprehensive Quantitative Microbial Risk Assessment (QMRA) for Escherichia coli in northeastern Greece’s riverine and deltaic aquatic systems, evaluating potential human health risks from recreational water exposure. The analysis integrates seasonal microbiological monitoring data—E. coli, total coliforms, enterococci, Salmonella spp., Clostridium perfringens (spores and vegetative forms), and physicochemical parameters (e.g., pH, temperature, BOD₅)—across multiple sites. A beta-Poisson dose–response model within a Monte Carlo simulation framework (10,000 iterations) was applied to five exposure scenarios, simulating varying ingestion volumes for different population groups. Median annual infection risks ranged from negligible to high, with several locations (e.g., Mandra River, Konsynthos South, and Delta Evros) surpassing the World Health Organization (WHO)’s benchmark of 10⁻⁴ infections per person per year. A Gradient Boosting Regressor (GBR) model was developed to enhance predictive capacity, demonstrating superior accuracy metrics. Permutation Importance analysis identified enterococci, total coliforms, BOD₅, temperature, pH, and seasons as critical predictors of E. coli concentrations. Additionally, sensitivity analysis highlighted the dominant role of ingestion volume and E. coli levels across all scenarios and sites. These findings support the integration of ML-based tools and probabilistic modelling in water quality risk governance, enabling proactive public health strategies in vulnerable or high-use recreational zones. Full article

Existing multivariate signal decomposition methods insufficiently account for the mechanical characteristics of gear systems, limiting their capability in fault feature extraction. To address this limitation, we propose a novel method, Multivariate Blaschke-based Mode Decomposition (MBMD). In MBMD, multivariate vibration signals are modeled as multi-dimensional responses of the gear system. Using Stochastic Adaptive Fourier Decomposition (SAFD), these signals are represented as a unified combination of Blaschke products, enabling adaptive multi-channel information fusion. To achieve modal alignment, we introduce the concept of Blaschke multi-spectra, reformulating the decomposition problem as a spectrum segmentation task, which is solved via a joint spectral segmentation algorithm. Furthermore, a voting-based filter bank, designed according to gear fault mechanisms, is employed to suppress noise and enhance fault feature extraction. Experimental validation on gear fault signals demonstrates the effectiveness of MBMD, showing that it can efficiently integrate multivariate information and achieve more accurate fault diagnosis than existing methods, providing a new perspective for mechanical fault diagnosis. Full article

This study aimed to develop an environmentally friendly and relatively efficient method for extracting natural antioxidants from avocado by-products while investigating the antioxidant mechanisms of their core bioactive components on multiple dimensions. In vitro antioxidant assays (ABTS, FRAP, SAFR, SFR, ORAC, DPPH) demonstrated that flavonoid procyanidin was the primary antioxidant component in avocado seeds, exhibiting the strongest activity (DPPH EC₅₀ = 3.6 µg/mL). The Hill model indicated a positive synergistic effect (n = 3.1). Chemical and molecular mechanism analyses revealed that avocado seeds exert antioxidant activity predominantly through hydrogen atom transfer (HAT) and electron transfer (ET) pathways. The model predictions suggested procyanidins may stably bind to protein targets in the Keap1-Nrf2 pathway and NOX2 via hydrogen bonding, hydrophobic interactions, and π-cation interactions. Furthermore, response surface methodology (RSM) was employed to optimize the extraction process of avocado seed antioxidants in an ethanol-water system. This study underscores the considerable health benefits and antioxidant capacity of avocado by-products, supporting their promising application in functional foods formulations. Full article

Angiotensin II (AngII), the primary effector of the renin-angiotensin system, is essential for maintaining blood pressure and fluid-electrolyte homeostasis. However, elevated AngII levels are a feature of disease conditions such as heart failure and chronic kidney disease, where it is associated with pathological tissue remodeling and fibrosis. AngII-mediated fibrosis has been documented in multiple organs and is characterized by fibroblast expansion, myofibroblast differentiation, and excessive extracellular matrix deposition. Periostin has recently emerged as a marker of fibroblast activation. Notably, periostin expression is highly upregulated during fibrotic remodeling in the kidney and lung, which is strongly linked with impaired organ function. While AngII-induced activation of periostin-lineage (Postn^Lin) cells is well established in the heart, the temporal dynamics of Postn^Lin activation in response to AngII infusion in the lung and kidney remain unexplored. Here, we used a Postn-MerCreMer lineage-tracing approach, combined with continuous AngII infusion over an experimental period of one week and two weeks to assess Postn^Lin responses in lung and kidney. Our findings reveal a progressive activation of Postn^Lin cells in both organs, characterized by myofibroblast phenotype, together with increased collagen deposition and macrophage infiltration. These results highlight the potential of Postn^Lin fibroblasts as a key effector of AngII-mediated tissue remodeling and fibrosis in the lung and kidney. Full article

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that affects women more frequently than men. This sex gap has widened over the past century, and appears to be shaped by lifestyle factors more than biological factors. This narrative review examines the evidence for sex-specific differences in lifestyle risk factors and their impact on both MS susceptibility and disease progression, with implications for diagnosis, monitoring, and treatment. Smoking, obesity, vitamin D deficiency, ultraviolet radiation exposure, and Epstein–Barr virus infection all interact with sex-related biological pathways to influence MS risk. Women appear to be more vulnerable to the pathogenic effects of smoking and obesity, both independently and in synergy with genetic risk alleles, while vitamin D and UV exposure confer stronger protective effects in females than in males. EBV infection also exhibits sex-dependent immune responses, shaped by hormonal regulation and host–virus genetic interactions. Sex-related lifestyle factors also modulate MS progression. Women experience more inflammatory activity and relapses, whereas men more often develop a progressive phenotype with greater neurodegeneration. Hormonal changes during female reproductive phases, such as pregnancy, breastfeeding, menopause, and hormone-based therapies, critically influence disease activity and progression in MS. Obesity, smoking, vitamin D status, diet, and gut microbiota further interact with sex hormones and genetic background, contributing to variable disease trajectories, also modulated by social determinants such as education level. These findings underscore the need to integrate into clinical practice the evaluation of lifestyle factors in a sex-specific way for diagnosis, monitoring, and treatment of MS. Full article

The plasma membrane (PM) of eukaryotic cells plays a key role in the response to stress, acting as the first line of defense against environmental changes and protecting cells against intracellular perturbations. In this work, we explore how membrane-bound chaperones and membrane lipid domains work together to shape plasma membrane properties—a partnership we refer to as the “epichaperome–plasma membrane lipid axis.” This axis influences membrane fluidity, curvature, and domain organization, which in turn shapes the spatial and temporal modulation of signaling platforms and pathways essential for maintaining cellular integrity and homeostasis. Changes in PM fluidity can modulate the activity of ion channels, such as transient receptor potential (TRP) channels. These changes also affect processes such as endocytosis and mechanical signal transduction. The PM proteome undergoes rapid changes in response to membrane perturbations. Among these changes, the expression of heat shock proteins (HSPs) and their accumulation at the PM are essential mediators in regulating the physical state and functional properties of the membrane. Because of the pivotal role in stress adaptation, HSPs influence a wide range of cellular processes, which we grouped into three main categories: (i) mechanistic insights, differentiating in vitro (liposome, reconstituted membrane systems) and in vivo evidence for HSP-PM recruitment; (ii) functional outputs, spanning how ion channels are affected, changes in membrane fluidity, transcytosis, and the process of endocytosis and exosome release; and (iii) pathological effects, focusing on how rewired lipid–chaperone crosstalk in cancer drives resistance to drugs through altered membrane composition and signaling. Finally, we highlight Membrane Lipid Therapy (MLT) strategies, such as nanocarriers targeting specific PM compartments or small molecules that inhibit HSP recruitment, as promising approaches to modulate the functional stability of epichaperome assembly and membrane functionality, with profound implications for tumorigenesis. Full article

Background: Appendiceal adenocarcinoma is a rare malignancy, and data guiding its systemic treatment in metastatic settings are limited. This study aimed to determine the clinical outcomes, treatment efficacy, biomarkers, and prognostic factors in patients with metastatic or unresectable appendiceal adenocarcinoma receiving palliative chemotherapy. Methods: We retrospectively reviewed patients with metastatic appendiceal adenocarcinoma who received first-line palliative systemic chemotherapy at the Peter MacCallum Cancer Centre between January 2015 and December 2024. Results: Of the 40 patients included, fluoropyrimidine-based doublet regimens were most commonly used (82.5%) in first-line setting, achieving an objective response rate of 39.4%. Median overall survival (OS) was 21.6 months, and median first-line progression-free survival (PFS) was 8.9 months. 22 patients (55.0%) received second-line treatment. Median OS and PFS were 21.6 and 8.9 months, respectively, among patients treated with oxaliplatin-based doublet regimens, and 66.4 and 10.8 months, respectively, among those treated with irinotecan-based doublet regimens. Molecular biomarker testing was performed in 35 patients (87.5%). KRAS and NRAS mutations were identified in 68.6% and 2.9% of tested patients, respectively. Factors associated with poorer OS included male sex, elevated carcinoembryonic antigen levels, and overweight status. Bevacizumab use was not clearly associated with survival. Conclusions: Palliative systemic chemotherapy, particularly fluoropyrimidine-based doublet regimens, appears to be a reasonable and effective treatment option for patients with advanced appendiceal adenocarcinoma. Although this study was underpowered for formal comparison, the numerically longer OS and PFS of irinotecan-based regimens are hypothesis-generating and support further prospective evaluation. Molecular profiling emphasizes the need for personalized targeted therapeutic strategies. The identified prognostic factors may help guide risk stratification and patient counseling for treatment planning. Full article

This study examines the effects of the extreme drought and heatwaves that occurred in Romania during the summer of 2024 on the microbiological and mycotoxicological quality of wheat (Triticum aestivum) stored until April 2025, as well as on the quality of wholemeal flour and bread derived from it. Comparative analyses were conducted against the contamination in wheat harvested in 2024. The hot and dry conditions significantly influenced the microbial and mycotoxicological contamination of both freshly harvested and stored wheat, as well as the derived flour and bread, due to their notably reduced moisture content and water activity. Although levels of total fungi, Fusarium-damaged kernels, and mycotoxins deoxynivalenol, aflatoxin B1, and ochratoxin A remained well below regulatory thresholds, higher contamination was observed in Transylvania and Moldavia Moldavia—particularly in the Curvature Carpathians, likely due to their cooler and wetter microclimates. The observed quality changes were strongly associated with alterations in physico-chemical, rheological, and colorimetric parameters, posing potential economic challenges for the milling and baking industries. The study recommends implementing integrated regional strategies to enhance wheat resilience, optimize production systems, and improve contamination control in response to increasing climate stress across Southeastern Europe. Full article

This article examines the global efforts to govern and regulate Artificial Intelligence (AI) in response to its rapid development and growing influence across many parts of society. It explores how governance takes place at multiple levels, including international bodies, national governments, industries, companies, and communities. The study draws on a wide range of official documents, policy reports, and international agreements to build a timeline of key regulatory and standardization milestones. It also analyzes the challenges of coordinating across different legal systems, economic priorities, and cultural views. The findings show that while some progress has been made through soft-law frameworks and regional partnerships, deep divisions remain. These include unclear responsibilities, uneven enforcement, and risks of regulatory gaps. The article argues that effective AI governance requires stronger international cooperation, fair and inclusive participation, and awareness of power imbalances that shape policy decisions. Competing global and commercial interests can create obstacles to building systems that prioritize the public good. The conclusion highlights that future governance models must be flexible enough to adapt to fast-changing technologies, yet consistent enough to protect rights and promote trust. Addressing these tensions is critical for building a more just and accountable future of AI. Full article

The static nature of traditional military symbology, such as MIL-STD-2525D, hinders effective real-time threat detection and response in modern cybersecurity operations. This research introduces the Dynamic Adaptive Symbol System (DASS), a novel framework enhancing cyber situational awareness in military and enterprise environments. The DASS addresses static symbology limitations by employing a modular Python 3.10 architecture that uses machine learning-driven threat detection to dynamically adapt symbol visualization based on threat severity and context. Empirical testing assessed the DASS against a MIL-STD-2525D baseline using active cybersecurity professionals. Results show that the DASS significantly improves threat identification rates by 30% and reduces response times by 25%, while achieving 90% accuracy in symbol interpretation. Although the current implementation focuses on virus-based scenarios, the DASS successfully prioritizes critical threats and reduces operator cognitive load. Full article

p-Benzoquinone (PBQ), a highly toxic compound, is the main active component in larval oral secretions of red palm weevil (RPW), Rhynchophorus ferrugineus, playing critical roles in external immunity and pathogen defense. In this study, we demonstrated that pathogens effectively induce RPW larval external immune responses. On this basis, the toxicity of PBQ to third-instar larvae was determined, with poisoning symptoms observed. The differences in gene expression between larvae before and after treatment with PBQ were analyzed by transcriptome sequencing to potentially involve the mechanisms of PBQ toxicity on larvae and the mechanisms of detoxification in the infected larvae. The results indicated that PBQ exposure was associated with altered expression of chitinase (CHI) and phenoloxidase (PO) genes in RPW larvae, which not only affects the digestion and degradation of the old cuticle but also activates phenoloxidase, further oxidizing tyrosine for its conversion into DOPA and dopamine, resulting in the generation of melanin and different degrees of cuticular melanization. The transcriptional changes further suggest that RPW larvae may employ metabolic processes to counteract the external immune-active compound PBQ toxicity by regulating the expression levels of detoxifying enzyme-encoding genes, such as cytochrome P450 (CYP450), glutathione S-transferase (GST), and ATP-binding cassette transporter (ABC). Our research provides potential novel strategies for pest control by targeting insect metabolic detoxification systems. Full article

Peritoneal dialysis (PD) is a widely used renal replacement therapy in which hyperosmolar solutions are instilled into the abdominal cavity to facilitate the removal of excess water, electrolytes, and metabolic waste products. During PD treatment, homeostasis is maintained through adaptive responses of the neuroendocrine system to high glucose exposure, changes in circulating blood volume, and shifts in electrolyte balance. Clinical observations and limited experimental studies suggest that these neurohormonal dynamics may influence both the complications and therapeutic efficacy of PD. However, systematic investigations remain scarce, largely because hormonal and neural responses are highly dynamic, involve complex interactions, and are substantially influenced by individual patient characteristics. In this review, we synthesize current clinical and experimental evidence linking PD-related complications with hidden hormone dynamics, with particular emphasis on hypothalamic hormones such as arginine vasopressin. We also discuss how the biocompatibility of PD solutions—traditionally assessed by their effects on peritoneal mesothelial cells—could be reconsidered when neuroendocrine aspects are taken into account. We propose that integrating both clinical insights and emerging basic research will provide a more comprehensive understanding of neuroendocrine regulation in PD and may contribute to the development of novel therapeutic strategies. Full article

Background/Objectives: Workplace violence remains an important vocational psycho-social risk for nurses employed in the emergency department (ED). We investigated the characteristics of workplace violence against ED nurses, and associations with self-assessed resilience, socio-demographic and vocational parameters, including turnover intention. Methods: ED nurses employed in all public hospitals in the Republic of Cyprus (RC) participated. After obtaining informed consent, data were collected using census sampling (January–June 2024) via the translated 2016 Italian National Survey on Violence towards Emergency Nurses Questionnaire (QuINVIP16) for investigating workplace violence characteristics, and the Connor-Davidson Resilience Scale (CD-RISC-25) for assessing self-perceived resilience. Results: A total of 132 nurses (53.0% response rate) participated. Verbal violence was reported by 70.5% to 92.4% of participants. Long waiting times, overcrowded EDs, and perception of inadequate attention from healthcare professionals were reported as the primary triggers for violence towards participants by patients/visitors. One-third of participants reported that violence-reporting systems were unclear, while 1 out of 4 reported inadequate safety measures against violence. Participants with higher scores of self-perceived resilience were less likely to report turnover intention due to workplace violence (p < 0.001), while those with lower self-perceived resilience reported a significant decrease in work motivation (p = 0.005). Those who experienced decreased work motivation after exposure to a violent episode were more likely to consider a) leaving the profession [OR (95%CI): 79.1(17.7–353.2); p < 0.01], and b) moving to a different work setting [OR (95%CI): 17.0(3.8–76.2); p < 0.01], and actually applying to be transferred to a different work setting [OR (95%CI): 19.6(4.2–91.5); p < 0.01]. Moreover, those who had not attended communication skills training were 4 times more likely to consider leaving the profession following exposure to violence [OR (95%CI): 4.2(1.1–16.2); p = 0.04]. Conclusions: This study is among the few to link workplace violence with both resilience and actual turnover behaviors among emergency nurses, in general and particularly in the post-pandemic era. By showing how personal resilience in the face of violence is shaped by organizational support, such as reporting systems and training, the present findings move beyond individuals-level explanations, and highlight workplace violence as a systematic administrative challenge. This insight represents an important advance in current knowledge, and calls for multifaceted interventions that strengthen both personal and institutional capacity to address violence. Full article

The Chang 7 member of the Ordos Basin hosts abundant shale oil and gas resources and plays a vital role in the development of unconventional energy. This study investigates differences in damage evolution and underlying mechanisms between representative shale oil and shale gas reservoir cores from the Chang 7 member under fracturing fluid hydration. A combination of high-temperature expansion tests, nuclear magnetic resonance (NMR), and micro-computed tomography (Micro-CT) was used to systematically characterize macroscopic expansion behavior and microscopic pore structure evolution. Results indicate that shale gas cores undergo faster expansion and higher imbibition rates during hydration (reaching stability in 10 h vs. 23 h for shale oil cores), making them more vulnerable to water-lock damage, while shale oil cores exhibit slower hydration but more pronounced pore structure reconstruction. After 72 h of immersion in fracturing fluid, both core types experienced reduced pore volumes and structural reorganization; however, shale oil cores demonstrated greater capacity for pore reconstruction, with a newly formed pore volume fraction of 34.5% compared to 24.6% for shale gas cores. NMR and Micro-CT analyses reveal that hydration is not merely a destructive process but a dynamic “damage–reconstruction” evolution. Furthermore, the addition of clay stabilizers effectively mitigates water sensitivity and preserves pore structure, with 0.7% identified as the optimal concentration. The research results not only reveal the differential response law of fracturing fluid damage in the Chang 7 shale reservoir but also provide a theoretical basis and technical support for optimizing fracturing fluid systems and achieving differential production increases. Full article