Effects of Exercise Intensity and Duration on Acute-Phase Proteins in Thoroughbred Racehorses

Physical exercise represents a physiological stressor capable of activating the acute-phase response (APR) in horses. However, the relative contribution of exercise intensity versus duration to acute-phase protein (APP) dynamics remains incompletely defined. This study compared the effects of short, high-intensity gallop exercise (2400 m flat race; n = 12) and prolonged, low-intensity endurance exercise (40 km; n = 13) on serum amyloid A (SAA), haptoglobin (Hp), and ceruloplasmin (Cp) in Thoroughbred racehorses. Blood samples were collected before exercise and at defined post-exercise time points. Between-group comparisons were performed at shared time points (72 h and 96 h post-exercise) using mixed-effects modeling and effect size analysis. The significant Group × Time inter-action for SAA indicates that exercise duration plays a key role in determining the mag-nitude and persistence of the late-phase systemic inflammatory response. Serum amyloid A emerged as the most sensitive biomarker of cumulative physiological stress following prolonged exercise. These findings support the use of SAA monitoring during recovery to assist training management in equine athletes. Because early post-exercise sampling was not performed in the gallop group, conclusions primarily reflect differences in late-phase (72–96 h) APP kinetics

Phenolic compounds and multifunctional properties of thinned apples: revalorizing fruit by-products for industrial applications

Thinned apples are a common by-product of apple orchards, produced in abundant quantities through thinning or natural drop, leading to the loss of substantial amounts of phenolic compounds with potential bioactive properties. Ten thinned apple samples, representing both commercial and autochthonous cultivars, were ultrasonicated using ethanol as green solvent, with the main goal of reusing their phenolic content for industrial and nutritional applications. For this reason, the phenolic content was characterized with high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The antioxidant, antidiabetic, and cardiovascular activities were evaluated and correlated with the targeted phenolic compounds. Under noncytotoxic conditions in Caco-2, HepG2 and HFF-1 cells, Amarilla de Octubre and Pomera de Pomes Agrias showed the strongest antioxidant-antiglycation activity as well as ACE inhibition, while Reineta and Verde Doncella excelled in HMGR and ACE inhibition. Pomera de Pomes Agrias, Vadiello-02, Reineta and Verde Doncella led digestive enzymes under Caco-2 safety

Evaluation of Hsp70 and Apoptotic Markers in Canine Cutaneous Lupus Erythematosus

Heat shock proteins 70 (HSP 70) are molecular chaperonins ubiquitously expressed in both prokaryotes and eukaryotes and are involved in the modulation and exacerbation of the immune response. The present study aimed to assess the immunohistochemical expression of HSP70 and apoptosis markers, such as TUNEL and Caspase-3, in 17 cases of cutaneous lupus erythematosus (CLE) in dogs to determine whether HSP70 expression correlates with cell apoptosis and to highlight possible involvement of HSP70 in the pathogenesis of CLE. The results revealed positive HSP70 expression in epidermal and inflammatory cells across all cases, with a significant correlation between HSP70 expression score and TUNEL-positive cells but not with Caspase-3-positive cells. This correlation could indicate a possible role for HSP70 in cell death via a caspase-independent apoptotic mechanism or other programmed cell death mechanisms, such as pyroptosis or necroptosis. The precise mechanisms by which HSP70 acts in this specific pathological context remain incompletely understood, but the results of this study provide important information for future investigations into autoimmune skin disease in dogs

A Hybrid LLM–Knowledge Graph Architecture for Information Retrieval in Smart Buildings

The Smart Building paradigm promises a future where buildings are intelligent, adaptive, and sustainable, offering real-time information retrieval that supports decision-making to enhance energy efficiency, occupant comfort, and security. However, achieving this paradigm is highly complex, one major reason being the seamless integration of (a) physical and functional representations of buildings (i.e., Building Information Modeling) and (b) real-time IoT (i.e., Internet of Things) data. To address this challenge, we propose a hybrid LLM–Knowledge Graph approach in which, on the one hand, a knowledge graph retains the buildings’ knowledge structures and a time-series database stores IoT data. On the other hand, a Large Language Model (LLM) serves as a mediator between a facility manager and the knowledge graph and IoT data, facilitating data-driven decision-making processes. Adopting the Design Science Research (DSR) methodology, we executed two distinct iterations within the implementation phase to investigate contrasting knowledge representation paradigms: Resource Description Framework (RDF) and Labeled Property Graph (LPG). Each iteration was evaluated to assess the effectiveness of the corresponding systems. Finally, we compared the RDF- and LPG-based implementations of the proposed architecture and drew insights

Gestione adattiva del rapporto giuridico e affidabilità delle informazioni

Nella società moderna emerge la esigenza di adattabilità dei provvedimenti amministrativi, che si presenta oggi in modo più evidente in ragione del progresso tecnologico: si evoca spesso il concetto di “società del rischio” , di una società cioè in cui l’evoluzione della tecnica e della scienza è talmente rapida da richiede un particolare sforzo per l’adeguamento del diritto da parte dei legislatori. La menzionata esigenza di adattabilità interessa un po' tutti gli ordinamenti giuridici, come ad esempio accade negli Stati Uniti rispetto alle prerogative delle agenzie statunitensi ; anche se tali agenzie presentano caratteri peculiari rispetto alla nostra autorità amministrativa (tutto sommato anche rispetto alle autorità amministrative indipendenti italiane). Il contributo analizza il concetto di “gestione adattiva”, che non sembra coincidere né con il momento dell'esercizio del potere al cui esito è adottato l’atto, né con quello dell’eventuale intervento in autotutela: la gestione adattiva evoca più il concetto di ‘gestione del rapporto giuridico’ frutto dell’esercizio del potere

The plastisphere and river systems as reservoirs for antibiotic resistant bacteria

Antimicrobial resistance (AMR) is a critical global health threat. This phenomenon involves the diffusion of bacteria and genes among humans, animals and the environment. In particular, the presence of third generation cephalosporin (3GC)-resistant Enterobacteriaceae in natural environments is of high concern as they are classified as critical-priority pathogens of public health importance. In this work we studied the relation among plastic pollution in freshwater ecosystems, the spread of multidrug-resistant (MDR) bacteria and diffusion of antibiotic resistance genes (ARGs). Caged plastic fragments were deliberately introduced in a river of central Italy. Plastic samples were collected and analyzed in parallel with river water samples. Out of 267 cefotaxime (CTX) resistant isolates obtained, 65 CTX-resistant Enterobacteriaceae were selected for further analysis. Most of the isolates (75% of plastic-derived and 84% of water-derived isolates) were MDR with seven being carbapenem-resistant enterobacteria (CRE). Five of them synthesize KPC (Klebsiella pneumoniae carbapenemases) enzymes, and two strains were positive for metallo-β-lactamases (NDM). Among the KPC producers, three isolates were identified as K. pneumoniae sequence type ST1519. Their isolation in a natural ecosystem is alarming because they can potentially re-enter human populations through environmental pathways. Shotgun metagenomic analysis provided a comprehensive snapshot of the microbial communities associated to the plastisphere, revealing dominance of families such as Comamonadaceae, Sphaerotilaceae, and Flavobacteriaceae, which play key roles in environmental biofilm formation and stability. The resistome analysis highlighted the presence of ARGs conferring resistance to clinically important antibiotics, such as beta-lactams, vancomycin, and tetracyclines, alongside mobile genetic elements (MGEs) such as integrons, which facilitate the horizontal transfer of resistance genes. This study provides crucial experimental evidence that riverine plastic debris acts as a genetic reservoir and could act as an efficient vehicle for the accumulation and transfer of clinically relevant resistance determinants

The global extent of the grassland biome and implications for the terrestrial carbon sink

Land cover data are commonly used to model the terrestrial carbon (C) sink, yet these data have wide margins of error that significantly alter estimates of global C storage. Here we demonstrate this data vulnerability in grasslands, which are critical to C cycling but whose estimated distribution has varied by >50 million km(2) (3.5-42% of the Earth's terrestrial surface). Comparing multiple high-resolution land cover products with expertly annotated grassland data from six continents, we show sources of mapping error and discuss C implications based on 2023 United Nations (UN) FAO estimates. Past misidentification arose from inconsistent definitions on grassland identity and classification flaws especially relating to woody plant cover. Correcting these errors adjusted grassland coverage to 22.8% of the terrestrial land base (30.1 million km(2)), elevating UN projections of soil C stocks to 155.02 Pg (0-30 cm depth). These findings underscore the challenges of biome mapping for ecosystem accounting and policy, when lacking field-validated remotely sensed data

ENVI-met Simulation Dataset — Via Milano, Pescara: Urban Microclimate Assessment, Current Scenario and 2050 Climate Projection

This dataset contains the full ENVI-met simulation outputs and model configuration files for the microclimatic assessment of Via Milano, Pescara (Italy), conducted in support of an urban regeneration project targeting the thermal comfort of a school-adjacent public space. The study adopts a 2×2 scenario matrix (Ante Operam / Post Operam × Current Climate / 2050 Projection), generating four independent simulation runs. The Post Operam scenario models the introduction of a stratified green infrastructure (street trees, aromatic shrub layer, permeable paving as de-paving strategy) along the Via Milano corridor. The 2050 climate scenario applies a thermal offset derived from regional climate projections to the baseline forcing. The simulation design day (21 July 2019) was selected via the Common Representative Day (CRD) algorithm as described in Cocci Grifoni et al. (2025), in adherence to the Life_AGREENET project methodology. Model generation was performed using the ENVI-met Automation Protocol (Marchesani, 2024; https://doi.org/10.5281/zenodo.14548213), a scripted workflow for reproducible ENVI-met model assembly. Simulated parameters include: Potential Air Temperature (Ta), Mean Radiant Temperature (MRT), Wind Speed, Relative Humidity, and the derived Universal Thermal Climate Index (UTCI

The Green Treasure from Appennine Flora for Colon and Liver Health: Characterization and Evaluation of the Protective Effects from Aerial Parts of Helichrysum italicum

Helichrysum italicum Mill. (Asteraceae), a perennial evergreen species native to the Mediterranean basin, has been traditionally employed to treat various inflammatory and infectious diseases, as well as respiratory, digestive, gallbladder, and bladder disorders. The plant is valued for its essential oil. It contains phenols and flavonoids, which play a fundamental role in the protective effects associated with the traditional use of extracts of its aerial parts. The goal of the study was to investigate the phytochemical and biological properties of polar extracts, specifically water and hydroalcoholic (50% ethanol) extracts, obtained from the aerial parts of H. italicum. The extracts were evaluated for phenolic composition and concurrently assessed for antioxidant and enzyme-inhibitory activities. Additionally, the biocompatibility of the extracts was investigated using eco-toxicological models, including Artemia salina lethality and Daphnia magna cardiotoxicity assays, as well as allelopathic studies. CCD841CoN colon epithelial cell viability was also assessed in the presence of the extracts. The extracts’ protective effects were examined in an ex vivo inflammatory model using isolated mouse colon and liver tissues exposed to Escherichia coli lipopolysaccharide (LPS). Their influence on cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) gene expression was investigated, as well. Docking studies were also performed to uncover on the potential mechanisms underpinning the biological effects observed in the study. The phytochemical analysis showed that hydroxycinnamic acids and quercetin derivatives were the primary components in both extracts. In particular, the hydroalcoholic extract showed higher phenol levels and more potent scavenging/reducing and enzyme inhibitory activities against tyrosinase, cholinesterases, glucosidase, and amylase. Using the aforementioned eco-toxicological and in vitro cell models, the extracts’ biocompatibility was determined to be in the range of 200–1000 μg/mL. Within this concentration interval, the extracts effectively mitigated LPS-induced stimulation of COX-2 and IL-6 gene expression. Docking studies suggest that hydroxycinnamic acids (notably chlorogenic acid) and flavonoids (including quercetin, rutin, hyperoside, and isoquercitrin) play a pivotal role in the extracts’ anti-inflammatory activity. In conclusion, this study provides scientific evidence supporting the ethnopharmacological use of H. italicum in managing oxidative stress and inflammatory disorders, especially in the digestive system. Phenolics in the extracts likely enhance their therapeutic potential. These findings warrant further research, including in vivo studies, to assess the extracts’ efficacy and safety profile comprehensively

REGULATORY SCIENCE STRATEGIES TO ASSURE PATIENT ACCESSTO SAFE FOOD PRODUCTS IN THE HEALTHCARE SETTING

This doctoral thesis investigates the regulatory, clinical and market dimensions of food products used for the dietary management of diseases and for the modulation of physiological functions, with a specific focus on foods for special medical purposes (FSMPs), food supplements and novel foods in the European Union and the United States. The work adopts a regulatory science perspective, analysing how legal classifications, evidence requirements and reimbursement arrangements influence both the safety of these products and patients’ access to them. Methodologically, the thesis combines comparative legal analysis, systematic reviews of the clinical and toxicological literature, and empirical examination of market data and reimbursement policies in key jurisdictions, including an in‐depth exploration of the Italian National Health Service and its National FSMP Registry. The first part of the thesis maps the global regulatory frameworks for medical foods and FSMPs, elucidating the criteria that distinguish them from both conventional foods and medicinal products and documenting the absence of systematic effectiveness assessment requirements comparable to those applied to medicines, despite their essential therapeutic role in conditions such as Glut‐1 Deficiency Syndrome (GLUT‐1 DS). Subsequent chapters examine the real‐world use of FSMPs in clinical practice and analyse reimbursement policies across G7 countries, highlighting cross‐national disparities and showing that Italy is currently the only European country guaranteeing comprehensive public coverage for FSMPs indicated in GLUT‐1 DS, with significant implications for equity of access and continuity of care. The thesis also reviews the evidence on the efficacy and safety of specific FSMPs, such as salt‐substitute products for arterial hypertension and ketogenic‐diet‐related FSMPs and discusses the methodological limitations of the available studies and their consequences for health technology assessment (HTA). The second part of the thesis addresses food supplements and novel foods, starting from an analysis of the global food supplements market and its rapid expansion, particularly in the segment of herbal products. Through a case study on hemp seed oil and an investigation of highly concentrated plant extracts used in supplements, the research shows how gaps in the application of Regulation (EU) 2015/2283 on novel foods and the American framework for new dietary ingredients can result in the marketing of products with potential hepatotoxicity in the absence of adequate pre‐market authorisation and post‐market surveillance. A systematic review of clinical cases of liver injury associated with herbal extracts demonstrates that only a small proportion of publications provide sufficient detail on composition, titration and history of consumption to allow a robust regulatory assessment, thereby underscoring the need for enhanced analytical characterisation and better integration between toxicological evidence and regulatory decision‐making. In its final part, the thesis articulates the original contributions of the research and their implications for policy, clinical practice and future studies. Conceptually, it proposes the tripartite tension between innovation, 3 safety and access as a unifying framework for understanding the regulatory challenges posed by FSMPs, food supplements and novel foods, and argues that these products should be more systematically integrated into HTA processes adapted to nutritional interventions. Empirically, it offers new comparative insights into European– American regulatory convergence and divergence, documents the unique role of the Italian FSMP Registry as a tool for guaranteeing access and enabling nutri‐surveillance, and quantifies key evidence gaps in the toxicological characterisation of high‐concentration plant extracts. The thesis concludes by outlining priority areas for future research and capacity building, including the development of long‐term observational studies on ketogenic diet use in GLUT‐1 DS, the refinement of criteria for determining novel food status in the context of herbal extracts, the extension of reimbursement analyses to additional jurisdictions, and the strengthening of interdisciplinary training in food regulatory science for healthcare professionals