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Cyclodextrin-Based Formulations as a Promising Strategy to Overcome the Blood–Brain Barrier: Historical Overview and Prospects in Glioblastoma Treatment
No full textGlioblastoma (GB) is one of the most aggressive and treatment-resistant cancers affecting the central nervous system (CNS), predominantly in adults. Despite significant advancements in this field, GB treatment still relies primarily on conventional approaches, including surgical resection, radiotherapy, and chemotherapy, which, due to its complex pathological characteristics, resistance mechanisms, and restrictive nature of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), remain of limited efficacy. In this context, the development of innovative therapeutic strategies able to overcome these barriers, induce cancer cell death, and improve patient prognosis is crucial. Recently, nanoparticle platforms and focused ultrasounds seem to be promising approaches for cancer treatment. Nanoparticles enable targeting and controlled release, whilst focused ultrasounds enhance tissue permeation, increasing drug accumulation in a specific organ. However, nanoparticles can suffer from synthesis complexity, long-term biocompatibility and accumulation in the body with consequent toxicity, whereas focused ultrasounds require specialized equipment and can potentially cause thermal damage, hemorrhage, or cavitation injury. Cyclodextrins (CYDs) possess good properties and represent a versatile and safer alternative able to improve drug stability, solubility, and bioavailability, and depending on the type, dose, and administration route, can reduce local and systemic toxicity. Thus, CYDs emerge as promising novel excipients in GB treatment. Despite these advantages, CYD complexes suffer from receptor specificity, reducing their potential in precision medicine. By combining CYD complexes with polymeric or lipidic platforms, the advantages of CYD safety and drug solubilization together with their specific targeting can be obtained, thus enhancing selectivity and maximizing efficacy while minimizing recurrence and systemic toxicity. This review provides a comprehensive overview of GB pathology, conventional treatments, and emerging CYD-based strategies aimed at enhancing drug delivery and therapeutic efficacy
Coding and non-coding transcripts modulated by transparent and blue PET micro-nanoplastics in Arabidopsis thaliana
No full textTrophic Ecology of Slender Snipe Eel Nemichthys scolopaceus Richardson, 1848 (Anguilliformes: Nemichthyidae) in the Central Mediterranean Sea
No full textThe slender snipe eel Nemichthys scolopaceus Richardson, 1848 is cosmopolitan in tropical and temperate seas, inhabiting the mesopelagic and bathypelagic zone between 200 and 1000 m depth. It is known to be an active predator in the DSL (Deep Scattering Layer) and the NBA (Near Bottom Aggregation), feeding mostly on decapod and euphausiid crustaceans, and playing a central role in carbon fluxes through meso- and bathypelagic ecosystems. Despite its potential importance in the deep trophic web ecosystem, the trophic ecology of Nemichthys scolopaceus is not well known. The aim of this study was to start to fill this knowledge gap. A total of 35 specimens of N. scolopaceus caught through bottom trawling in the Mediterranean Sea were analyzed in the laboratory for stomach content composition. As expected, mainly decapod crustaceans were found, in particular Plesionika martia, Pasiphaea multidentata, Funchalia woodwardi, and Robustosergia robusta species. The degree of digestion of prey in the stomachs was high in all cases. Our findings seem to confirm the specialist diet of Nemichthys scolopaceus based on shrimp-like crustaceans
Bontadini e l'attualismo
No full textLa costruzione della metafisica è consentita o
impedita dal proseguimento delle rivendicazioni
attualistiche circa il primato del pensiero? Ma
cosa va salvato delle tesi gentiliane affinché la
metafisica possa crescere come un sapere incontrovertibile?
E cosa va respinto
Genetic Insight into Expression-Defined Melanoma Subtypes and Network Mechanisms: An in Silico Study
No full textBackground: Melanoma is a highly heterogeneous neoplasia in which transcriptional profile encodes much of the biological diversity that determines tumor progression and therapeutic response. To refine its molecular stratification and profiles characterization, we conducted an in silico transcriptomic analysis. Methods: Public microarray datasets from the GEO and ArrayExpress were examined, and the E-MTAB-6697 expression dataset was selected. We used a K-Means clustering algorithm to stratify 194 tumor samples into expression-driven subgroups and analyzed each one to define their transcriptional and biological profiles. Differential expression analysis between identified clusters and controls was performed. Additionally, we applied Weighted-Gene correlation analysis to identify coordinated expression hubs in the tumor dataset and tested the resulting modules for correlation with the identified clusters. Results: Unsupervised clustering of melanoma transcriptomic profiles identified three distinct molecular subtypes characterized by divergent biological programs. While all clusters shared the dysregulation of pathways involved in epidermal differentiation, immune response, and lipid metabolism, they diverged in proliferation, phenotypic plasticity, metabolic adaptation, and apoptotic regulation. Cluster A was characterized by enrichment in DNA replication, repair, and mitochondrial metabolism modules, suggesting a proliferative yet genomically stable state. Cluster B showed enrichment in immune and cytokine signaling pathways alongside reduced proliferative activity, consistent with a quiescent or transitional phenotype. Cluster C displayed coordinated enrichment in cell-cycle, DNA-maintenance, and neuroectodermal reprogramming pathways, indicating a highly plastic and proliferative subtype. Despite these molecular distinctions, all clusters retained an "immunologically hot" profile (IPS 7-8), indicating potential responsiveness to immunotherapy. Conclusions: These findings provide an overview of the functional characteristics of melanoma heterogeneity and identify biological processes that could be targeted by drugs for the development of tailored therapies for each subtype. Nevertheless, future studies in independent clinically annotated cohorts would be required
Measurement of ω meson production in pp collisions at = 13 TeV
No full textThe pT-differential cross section of ω meson production in pp collisions at s = 13 TeV at midrapidity (|y| < 0.5) was measured with the ALICE detector at the LHC, covering an unprecedented transverse-momentum range of 1.6 < pT< 50 GeV/c. The meson is reconstructed via the ω → π+π−π0 decay channel. The results are compared with various theoretical calculations: PYTHIA8.2 with the Monash 2013 tune overestimates the data by up to 50%, whereas good agreement is observed with Next-to-Leading Order (NLO) calculations incorporating ω fragmentation using a broken SU(3) model. The ω/π0 ratio is presented and compared with theoretical calculations and the available measurements at lower collision energies. The presented data triples the pT ranges of previously available measurements. A constant ratio of Cω/π0 = 0.578 ± 0.006 (stat.) ± 0.013 (syst.) is found above a transverse momentum of 4 GeV/c, which is in agreement with previous findings at lower collision energies within the systematic and statistical uncertainties
Dynamiques scolaires et implantation italienne au Cap Bon: Une lecture géohistorique d'un espace colonial
No full textCet article s'intéresse, selon une démarche d'analyse géohistorique, à la population
scolaire italienne au Cap Bon, en Tunisie, durant la période du Protectorat français
(1881–1956) et la décennie suivante. Celui‐ci vise à contribuer à une meilleure
compréhension des interactions complexes entre colonisation, éducation et immigration
dans un contexte colonial. À travers l'analyse des archives scolaires privées et
des registres matricules, le texte met en lumière l'importance significative et la
répartition spatiale des élèves italiens de même que leur intégration dans les établissements
éducatifs locaux. L'article analyse aussi l'impact des contextes socioéconomiques
et politiques mondiaux, tels que les guerres mondiales et la crise
économique, sur cette population. À cet égard, l'éducation, vue comme enjeu culturel
et identitaire, a été influencée par les tensions entre les langues italienne et
française, reflétant les défis paradoxaux de l'intégration sociale et de la préservation
culturelle. Au final, l'immigration italienne, majoritairement sicilienne, a façonné le
paysage socioéconomique et linguistique du Cap Bon, contribuant au développement
agricole et viticole tout en enrichissant la mosaïque multiculturelle locale
La tassazione degli eventi sportivi
No full textIl lavoro esamina la tematica dell'evento sportivo inteso come erogazione di una attività complessiva, qualificabile all'interno della categoria "spettacolo" da parte di un “organizzatore”. Se ne prendono, pertanto, in considerazione esclusivamente i corrispettivi percepiti da chi organizza la manifestazione o l’evento. Il tema si intreccia con l'imposizione Iva in quanto tali attività sono assoggettate alla predetta imposta sebbene tenendo conto di alcune peculiarità che sono approfondite nell'ambito della trattazione
Artificial Intelligence and Discrimination: A Vignette Experiment of Labour Market Discrimination in Large Language Models
No full textLarge Language Models are increasingly used across various sectors,
including recruitment, where they assist in evaluating candidate profiles and opti-
mizing hiring processes. While Large Language Models offer significant advan-
tages in terms of cost and time efficiency, concerns regarding algorithmic bias have
emerged, particularly in relation to gender and ethnic discrimination. This study
employs a Factorial Survey Experiment to assess biases in six widely used Large
Language Models—Le Chat, ChatGPT, Gemini, DeepSeek, Grok, and MetaAI. By
systematically varying candidate attributes such as sex, ethnicity, education, and
age, we examine whether hiring recommendations are influenced by taste-based or
statistical discrimination. Our findings indicate that among the six models tested,
we find none to exhibit gender bias, while ChatGPT, Grok and DeepSeek show
signs of ethnic discrimination, though at varying degrees. These results underscore
the need for greater transparency and stronger anti-bias measures in Large Lan-
guage Models development and training. We advocate for enhanced oversight in
AI-driven salary discrimination tools to mitigate discrimination risks and ensure
fair and equitable recruitment practices. Our study highlights the broader impli-
cations of biased Artificial Intelligence models, emphasizing the potential risks of
productivity loss and workforce homogeneity if biases remain unaddresse