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Potentiated zinc and monovalent copper oxide as dietary supplements for weanling piglets: effects on systemic and mucosal immunity, gut permeability, and fecal microbiota composition
No full textThis study examines the potential of modulating gut health parameters in piglets by varying zinc/copper ratios administered through specialty oxide sources. A total of 84 piglets were selected after weaning and divided into four experimental treatment groups; the trial lasted 28 days. During the initial phase (1–14 d), the positive control (PC) received 2500 ppm of zinc, provided as conventional zinc oxide. In parallel, three additional treatment groups were formed, in which copper (Cu) and zinc (Zn) were supplemented using potentiated zinc oxide (Pot-ZnO) and monovalent copper oxide (Cu2O), at both European and Non-European recommended inclusion levels: EU (120 ppm of Zn; 140 ppm of Cu), Non-EU+ (300 ppm of Zn; 200 ppm of Cu), and Non-EU− (300 ppm of Zn; 140 ppm of Cu). Lower Zn/Cu ratios characterized the second phase (15–28 d). Growth performance and fecal score were monitored throughout the trial. Blood samples were collected on days 1 and 14 from one subject per replicate to assess serum proinflammatory cytokines, immunoglobulins, and biomarkers of intestinal permeability. On day 28, one subject per replicate was slaughtered to obtain jejunal mucosa for the determination of jejunal secretory immunoglobulin A (sIgA) and alkaline phosphatase. Fecal samples collected on days 14 and 28 were used to analyze Zn and Cu content and to evaluate microbiota composition. A better fecal score was detected on day 4 in PC group compared to EU (p < 0.01). Serum immunoglobulin A increased in Non-EU− vs. PC group (p < 0.05) at day 14. Serum diamine oxidase decreased in the PC and Non-EU+ groups vs. Non-EU− group (p < 0.05) at day 14. sIgA increased in PC vs. Non-EU− group (p < 0.01) at day 28. Zn was higher in PC fecal samples (p < 0.01), whereas fecal Cu increased in EU and Non-EU+ treatments at day 14 (p < 0.05). Analysis of fecal microbiota performed at day 14 showed decreased. Observed, Shannon, and Simpson metrics in the Non-EU− group compared to the EU group (p < 0.05). Beta diversity highlighted a significant separation among groups at day 14 (p < 0.01). Differential abundance analysis revealed notable changes in genera composition among PC and EU groups at day 14 (p < 0.05). In conclusion, balanced Pot-ZnO and Cu2O administered at inclusion levels compliant with European levels of inclusion (EU) represent a valid strategy to enhance gut health of piglets during the first two weeks after weaning
Jurassic uranium-bearing phosphorites of the Ionian Zone, Albania
No full textThis study presents a comprehensive petrographic, mineralogical, and geochemical investigation of Lower Jurassic uranium-bearing phosphorite deposits from the Bogaz and Fushëbardha localities within the Ionian Zone, Southern Albania. The phosphorites occur within carbonate successions and were analysed using thin section petrography, X-ray Diffraction (XRD), Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM-EDS), Electron Micro-Probe Analyses (EMPA) and Geiger-Müller radiation measurements. At Bogaz, phosphorites occur as interparticle cement within breccias composed of angular carbonate clasts. Brecciated carbonate facies consist of packstone with peloids, Pliensbachian (Lower Jurassic) benthic foraminifera (Siphovalvulina) and green dasycladacean algae (Palaeodasycladus mediterraneus), and wackestone with fenestrae indicative of shallow-marine, peritidal depositional environments. XRD and EMPA analyses confirm fluorapatite, francolite (carbonate fluorapatite), and calcite as dominant phases, with uranium incorporated within the apatite lattice. Carbonate fluorapatite crystals form rosette structures, tens of microns in diameter. These features suggest a tectonically influenced formation of hydraulic breccias and diagenetic fluid circulation driving a secondary diagenetic infiltration-type phosphogenesis. At Fushëbardha, the phosphorites form mainly nodular or lenticular structures within a carbonate matrix, with interbedded packstone and grainstone containing Bositra-type thin-shelled, pelagic bivalves. The stratiform phosphorites at Fushëbardha are interpreted as primary deposits linked to the Early Jurassic Toarcian Oceanic Anoxic Event (OAE), reflecting phosphogenesis in low-energy, oxygen-depleted marine environments associated with microbial organic remains as observed at SEM. Fluorapatite occurs as microcrystalline prisms with hexagonal base and radial rosettes; uranium is spatially restricted to phosphate nodules. The dual occurrence of diagenetic (Bogaz) and sedimentary stratiform (Fushëbardha) phosphorites reflects two distinct phosphogenic pathways in the Ionian Zone. These findings emphasize the role of global climate and ocean anoxia, tectonic regime, diagenesis, microbial mediation and redox-sensitive geochemical environments in the genesis of Mediterranean phosphorites. Albanian phosphate mining sites should be further evaluated for radioactivity hazard as part of any mining feasibility study in the future
The fight against illicit firearms in the European Union legal framework: among armed conflicts and rearmament
No full textQuesto saggio esamina il quadro giuridico dell’UE per la prevenzione e la repressione
della fabbricazione e del traffico illeciti di armi da fuoco, considerati una delle principali
minacce criminali per gli Stati membri dell’UE. L’instabilità del contesto politico
internazionale nelle regioni limitrofe e lo scoppio di conflitti armati alle porte
dell’Unione giustificano il rafforzamento delle norme interne dell’Unione europea volte
a prevenire il traffico illecito di armi da fuoco. Tra le altre cose, questa minaccia
potrebbe aumentare in futuro come effetto collaterale dell’attuale piano europeo di
riarmo. Lo studio mira a valutare l'adeguatezza delle norme dell'UE finora stabilite per
contrastare il traffico illecito di armi da fuoco, concentrandosi in particolare sull’atto legislativo più recente adottato dall'Unione (Regolamento UE 2025/41). Esso esamina
inoltre l’interazione tra tale regime e il quadro giuridico dell'Unione per la lotta alla
proliferazione delle armi da fuoco militari che si collocano nella categoria delle armi di
piccolo calibro e leggere (SALW). La ricerca si basa sul presupposto che solo un quadro
legislativo unificato in grado di regolamentare in modo coerente i trasferimenti di armi
da fuoco militari e civili sia all'interno che all'esterno dell’UE possa affrontare
efficacemente le sfide più importanti legate alla proliferazione delle armi da fuoco
illegali. Il saggio conclude che il quadro legislativo dell’UE contiene tutti i requisiti
necessari per raggiungere efficacemente obiettivi strategici quali l’armonizzazione della
legislazione degli Stati membri dell’UE nel contrasto della proliferazione delle armi da
fuoco illecite.This essay examines the EU legal framework for preventing and suppressing the illicit
manufacture and trafficking of firearms, which are considered one of the main criminal
threats to EU member states. The instability of the international political context in
neighbouring regions, coupled with the outbreak of armed conflicts on the Union's
doorstep, justifies the need to strengthen the European Union’s internal rules to prevent
the illicit trafficking of firearms. This threat could potentially escalate in the future as a
consequence of the ongoing European rearmament initiative. This study aims to evaluate
the effectiveness of the EU’s current legislation in addressing the illicit trafficking of
civilian firearms, with a particular focus on the most recent legislative act adopted by the
Union (Regulation EU 2025/41). The interplay between this regime and the EU’s legal
framework for combating the proliferation of military firearms in the category of small
arms and light weapons (SALW) is also considered. The research is based on the premise
that only a unified legislative framework capable of coherently regulating both intra- and
extra-EU civilian and military firearms transfers can effectively address the most
significant challenges associated with the proliferation of illicit firearms. The essay
concludes that the EU legislative framework provides all the requirements necessary to
effectively achieve strategic objectives, such as harmonising EU Member State legislation
to tackle illicit firearms trafficking
Prevalence, type, and clinical implications of CFTR variants in bronchiectasis
No full textPrevalence, type, and clinical implications of CFTR variants in
bronchiectasis
Andrea Gramegnaa,b, Lucia Allavenaa,b, Gianfranco Alicandroa,c, Elisa Canellaa,b, Mattia Nigrod,e,
Chiara Premudaa,b, Margherita Orib, Martina Santambrogiob, Luigi Porcarof, Daniele Pratig,
Luca Valentia,g, Stefano Alibertid,e and Francesco Blasia,b
aDepartment of Pathophysiology and Transplantation, University of Milan, Milan, Italy; bRespiratory Unit and Cystic Fibrosis Center,
Internal Medicine Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; cMother and Child
Department, Cystic Fibrosis, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; dDepartment of Biomedical
Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; eRespiratory Unit, IRCCS Humanitas Research Hospital, Milan, Italy;
fMedical Genetics Laboratory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; gDepartment of
Transfusion Medicine and Biological Resource Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
ABSTRACT
Background and objective: Bronchiectasis is a chronic lung condition characterised by
persistent respiratory symptoms and permanent bronchial dilation. CFTR variants are
commonly reported in patients with bronchiectasis with unclear clinical implications.
This study aims to investigate the prevalence of CFTR variants in people with bronch-
iectasis and their association with clinical characteristics.
Methods: Patients were recruited from two centres in Milan, Italy and screened for CFTR
variants. The prevalence of CFTR variants in people with bronchiectasis was compared to
that of a control group of healthy blood donors. Sweat chloride levels, pulmonary
function tests, airway microbiology, disease severity and respiratory symptoms were
compared between CFTR variant carriers and non-carriers.
Results: The study included 454 adults with bronchiectasis and 250 individuals in the
control group. Among those with bronchiectasis, 178 individuals (39.2%) carried at least
one CFTR variant, with 41 (9.0%) identified as having a CF-causing variant. This preva-
lence was higher than that observed in the control group (n = 10, 4%). The odds ratio of
carrying a CF-causing variant among bronchiectasis patients was 2.83 (95% CI: 1.39–5.79,
p = 0.004). No significant association was found between CFTR carrier status and clinical
outcomes.
Conclusions: CFTR variants are frequently observed in patients with bronchiectasis,
although they are not associated with increased disease severity
Nutritional outcomes in people with cystic fibrosis receiving elexacaftor/tezacaftor/ivacaftor: A 24-month real-world study
No full textBackground
The highly effective CFTR modulator elexacaftor/tezacaftor/ivacaftor therapy has revolutionized the care of cystic fibrosis (CF) leading to significant improvement in patient outcomes. However, data on long-term evolution of nutritional outcomes are limited.
Methods
We conducted a prospective study to evaluate changes in nutritional outcomes in people with CF (pwCF), including weight, body mass index (BMI), fat absorption and fat-soluble vitamin levels. Study outcomes were measured before treatment initiation and after 12 and 24 months. Mean changes and 95% confidence intervals (CI) were obtained using generalized estimating equations.
Results
A total of 84 patients with a median age of 19 years (range:12-32) were enrolled. At the 24-month follow-up visit, weight increased by 4.7 kg (95% CI: 3.5, 6.0) and BMI increased by 0.40 standard deviation scores (95% CI: 0.27, 0.53). The prevalence of overweight and obesity increased from 4.8% to 10.7%. After 24 months of ETI therapy, levels of vitamin A and E, as well as international normalized ratio (used as a marker of vitamin K status) were lower than baseline values, while vitamin D did not significantly change.
Conclusions
ETI has primarily led to significant improvements in the nutritional status of pwCF, resulting in increased BMI. However, a shift from the traditional hypercaloric and high fat diet to a balanced, healthy diet is essential to avoid excessive weight gain. Additionally, our findings underscore the need for ongoing monitoring of fat-soluble vitamin levels and adherence to supplementation
EFFECTS OF DAPAGLIFLOZIN ON EXERCISE CAPACITY, RESPIRATORY FUNCTION, BIOMARKERS, SLEEP APNEA, AND LEFT VENTRICULAR REMODELING IN PATIENTS WITH HEART FAILURE: A PROSPECTIVE, SINGLE CENTER, NON RANDOMIZED STUDY
No full textBackground: Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has become a cornerstone in the management of heart failure with reduced ejection fraction (HFrEF). Its clinical efficacy is well-established, primarily attributed to its effects on diuresis and hemodynamic unloading. However, despite its widespread use and therapeutic success, the precise mechanisms through which dapagliflozin exerts its beneficial effects remain incompletely understood. Current research is focused on elucidating the broader physiological pathways involved. Given the complexity of its actions, a more comprehensive understanding of its multifaceted effects will require detailed, multidomain assessments, spanning metabolic, cardiovascular, and renal functions.
Methods: A single prospective cohort of stable HFrEF patients was studied in two parallel, complementary investigations. The first focused on exercise capacity, cardiac remodelling, fluid status, and conventional biomarkers. The second investigated alveolar-capillary membrane function through surfactant protein-B (proSP-B), gas exchange, and sleep-disordered breathing. Evaluations were performed at baseline, 2–4 weeks, and after 6 months of treatment with dapagliflozin 10 mg/day.
Results: Among 75 patients enrolled, 67 completed full follow-up. Dapagliflozin improved left ventricular ejection fraction (LVEF), reduced cardiac volumes and pulmonary artery pressures, and enhanced ventilatory efficiency (VE/VCO2 slope). Haemoglobin increased significantly, while peakVO2, natriuretic peptides, and spirometry remained unchanged. DLCO and its subcomponents (Dm and Vcap) were stable, yet a significant reduction in circulating proSP-B was observed, suggesting improved alveolar-capillary membrane integrity. Central sleep apnoea frequency decreased in affected patients, with no impact on obstructive events or total apnoea burden.
Conclusions: In this multidimensional evaluation of a single HFrEF cohort, dapagliflozin showed concordant benefits on cardiac remodelling, ventilatory efficiency, haemoglobin, and alveolar-capillary membrane health, despite unchanged peakVO2 and pulmonary function. These findings reinforce dapagliflozin’s complex therapeutic profile, involving both hemodynamic and non-hemodynamic mechanisms
Non-functional certification of edge-computing satellite systems
No full textSatellite telecommunication networks are playing an increasingly pivotal role in modern communication infrastructures, owing to their expansive coverage, high reliability, and growing capabilities in computing, storage, and bandwidth. In response to evolving market demands, mobile network operators are progressively integrating satellite systems with edge-cloud computing platforms to deliver advanced networking functionalities within a unified architecture. This integration places strong demands on the non-functional assessment (e.g., reliability, availability, and resource efficiency) of satellite-based edge nodes, introducing unprecedented challenges due to their unique operational constraints. In this paper, we propose a lightweight certification framework tailored for satellite computing systems, designed to assess and validate the non-functional posture of satellite edge networks. Our approach explicitly addresses the distinctive characteristics of satellite environments, including intermittent connectivity and constrained resource availability. We validate the proposed scheme through a realistic testbed implementation, modeling a 5G-enabled satellite edge node based on the Tiansuan satellite constellation, an experimental platform jointly developed by Beijing University of Posts and Telecommunications, Spacety, and Peking University
Oral health benefits of Heyndrickxia coagulans: a systematic review and meta-analysis of current evidence
No full textIntroduction: The oral microbiota plays a fundamental role in maintaining both oral and systemic health, while dysbiosis contributes to diseases such as dental caries and periodontitis. Probiotics have gained attention as adjunctive strategies to restore microbial homeostasis. Heyndrickxia coagulans (formerly Bacillus coagulans) is a spore-forming, lactic acid-producing bacterium with documented antimicrobial, antioxidant, and immunomodulatory properties. Its resilience to environmental stressors and industrial processing makes it a promising probiotic candidate. This systematic review and meta-analysis aimed to evaluate the effects of H. coagulans on oral health outcomes. Methods: A comprehensive search was performed across multiple databases up to September 2025 to identify randomized controlled trials (RCTs) and non-randomized studies assessing H. coagulans as a probiotic intervention for oral health. Data extraction followed PRISMA guidelines, and the risk of bias was evaluated using the RoB 2.0 and ROBINS-I tools. Meta-analysis was conducted using Stata SE® 18.5, with changes in salivary Streptococcus mutans levels as the primary outcome measure. Results: Eight studies (seven RCTs and one NRSI) met the inclusion criteria. Most were conducted in India, Iran, and North Macedonia, with sample sizes ranging from 30 to 183 participants aged 5-73 years. Administration of H. coagulans, via chewable tablets, mouthwash, or food matrices, resulted in a significant reduction of salivary S. mutans counts in both children and adults compared with placebo or other probiotics. Meta-analysis of four studies demonstrated a pooled effect size of -0.99 (95%CI = -1.60/0.39; p < 0.01), although substantial heterogeneity was observed (I2 = 98.2%). Additional studies reported improvements in Gingival Index, bleeding on probing, and clinical attachment levels among participants with gingivitis or periodontitis. No significant adverse events were reported. Conclusion: H. coagulans appears to exert beneficial effects on oral health by reducing cariogenic bacterial load and improving periodontal parameters, supporting its potential use as an adjunct in caries prevention and gingival health maintenance. H. coagulans may favorably modulate the oral microbiota and contribute to overall oral health. However, further high-quality, large-scale clinical trials are needed to confirm these findings and define their therapeutic role in preventive oral care
Intra-farm dynamic of environmental conditions in commercial rabbitries with respiratory disorders using an innovative IoT device
No full textThe microclimate inside rabbitries is a well-established predisposing factor for respiratory diseases, influencing animal growth and health. This study investigated the fluctuations of key environmental parameters in fattening rabbitries with and without respiratory disorders. To this purpose, six multifunctional IoT (Internet of Things) devices were placed at animal level in different locations within each barn. These devices can measure continuously various parameters, including temperature, relative humidity, light intensity, sound pressure, gas concentrations (ammonia, sulphuric acid, carbon dioxide) and particulate levels. Measurements were collected for 7 to 10 days in each farm, with external conditions simultaneously recorded from local meteorological stations. Considering the optimal welfare values, the continuous monitoring system provided valuable information regarding significant deviations of some parameters, irrespective of the external conditions.
The results highlighted that temperatures were consistently above 20 °C for 51%, 89%, and 100% of the time in three out of four problematic farms, whereas relative humidity was below the suggested value of 60% in all of them for 30% to 89% of the time. Moreover, multi-site measurements within the same building revealed a heterogeneous distribution of the parameters investigated. Differences in ammonia concentrations up to 11 ppm have been found in the same barn, indicating a low uniformity of air quality. Dustiness, sound pressure, and sulphuric acid concentrations never reached levels of concern.
The findings demonstrate the utility of this real-time evaluation method as a valuable tool for farmers' decision-making, specifically in efforts to mitigate the adverse impact of environmental conditions on animal health
SYNTHESIS, CHARACTERIZATION AND EVALUATION OF BIOACTIVE MOLECULES LINKED TO PHOTOREMOVABLE PROTECTING GROUPS FOR SPATIO-TEMPORAL CONTROL OF THEIR ACTIVITY THROUGH PHOTOACTIVATION
No full textBiological processes are highly complex phenomena governed by a series of precise spatio-temporal events. Among the most innovative approaches developed over the last decade to investigate such processes, photopharmacology has emerged as a powerful tool, as it exploits light to control biological functions. In particular, optopharmacology enables the regulation of pathophysiological processes through the use of molecules that become bioactive upon light stimulation. Initially applied mainly to biological investigations, optopharmacology is now increasingly recognized for its great potential in the clinical and medical fields.
Among the various photosensitive systems, molecular switches, molecular motors, photodynamic therapy (PDT), and photoremovable protecting groups (PPGs) play important roles in pharmaceutical research. The focus of this doctoral research lies on PPGs: these are chromophores covalently linked to approved drugs or bioactive molecules at functional groups essential for their activity. The resulting species, generally referred to as photo-prodrugs or caged compounds, are able to release the native drug upon light irradiation at a specific wavelength, which cleaves the bond between the PPG and the bioactive molecule. In the literature, several classes of PPGs have been described, including o-nitrobenzyl, coumarin, and BODIPY derivatives, all of which can cage and release a variety of functional groups. However, when focusing on alcohols, phenols, and primary or secondary amines, these are typically linked through carbonate or carbamate linkers, which are intrinsically unstable under physiological conditions due to the presence of esterases. Moreover, the photorelease of tertiary amines has been only rarely reported for such PPGs.
A notable exception is represented by derivatives of 8-cyano-7-hydroxyquinolin-2-ylmethyl (8CyHQ), which have been specifically developed and optimized for the release of tertiary aliphatic amines and tertiary anilines upon both one-photon excitation (1PE, 365–405 nm) and two-photon excitation (2PE, 740 nm). The interest of this thesis is focused on the photorelease of tertiary amines through 1PE. Consequently, the first objective of this work was the optimization study of the quinoline core to achieve both absorption maxima shifted toward safer irradiation wavelengths (>420 nm) and higher chemical yield of payload release. Starting from 8-bromo-7-hydroxyquinolin-2-ylmethyl (8BHQ), the first quinoline based PPG described, we first demonstrated the ability of it in releasing tertiary amines, exploiting a residual absorption tail at 440 nm. From this starting point, we synthesized novel quinoline-based PPGs bearing various electron-withdrawing substituents at position 8 with the aim of improving 8BHQ properties. Unfortunately, among all the newly synthesized derivatives, only 8BHQ proved to be the most efficient quinoline-based PPG for tertiary amine release at 440 nm, even outperforming the well-established 8CyHQ. However, upon 365 nm light irradiation all new derivatives showcase excellent photoreactivity, in particular the compound containing a CF3 which demonstrated to have a significant superior quantum yield (Qu) value. We subsequently explored substitution at position 3, introducing different substituents of diverse electronic and steric nature while keeping the 8BHQ substitution pattern otherwise constant. Although this study is still ongoing, several derivatives have already shown improved performance compared to the 8BHQ reference, in particular the derivative bearing a cyano group in C3 significantly improved 8BHQ performance dramatically increasing photoreactivity and the yield of released leaving amine upon blue light irradiation.
In parallel with this photochemical optimization, two photopharmacological projects were also pursued.
The first project involved the photocaging of ivabradine in order to achieve selective antagonism of different subtypes of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Ivabradine is a clinically used bradycardic agent indicated for the treatment of stable angina pectoris. Its mechanism of action involves antagonism of the HCN4 channel; however, the drug itself is unable to discriminate between the four HCN subtypes. Through a photocaging strategy, ivabradine was covalently linked to 8BHQ, and its effective photorelease was demonstrated in vitro, ex vivo on neuronal HCN channels, and in vivo on cardiac HCN channels in zebrafish. This study has been completed and published, and it opens the way to new perspectives for the use of caged ivabradine in diseases involving dysregulation of non-cardiac HCN channels, such as HCN2-related neuropathic pain.
The second project focused on the photocaging of the antitubercular drug bedaquiline, a highly potent agent against Mycobacterium tuberculosis due to its ability to deplete ATP resources by inhibiting the enzyme ATP synthase (ATPe). However, its clinical use is limited by severe cardiac and hepatic toxicities. The rationale behind designing 8BHQ-caged bedaquiline was therefore to reduce the systemic side effects of the native drug. Unlike the ivabradine project, however, we observed residual anti-mycobacterial activity of caged bedaquiline in the dark, particularly against M. tuberculosis in macrophages. To address this issue, a series of novel quinoline-based PPGs was synthesized, introducing polyethylene glycol (PEG) chains of variable length at position C4 of the quinoline chromophore. This modification was hypothesized to hinder enzymatic cleavage of the drug–PPG linkage by activated macrophage enzymes. Among the synthesized derivatives, the compound bearing a triethylene glycol chain proved the most promising, as it displayed complete inactivity in the dark. This project is currently nearing completion, with ongoing experiments to evaluate the light-induced uncaging and anti-mycobacterial activity of these derivatives in infected macrophages