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Investigating the impact of vitamin B6 deficiency on tumor development and metabolic homeostasis in Drosophila melanogaster
No full textVitamin B6, in its active form pyridoxal 5’-phosphate (PLP), is an essential cofactor required for over one hundred enzymatic reactions involved in amino acid, carbohydrate, and lipid metabolism, as well as in one-carbon and antioxidant pathways. Despite its fundamental role in cellular homeostasis, the biological consequences of vitamin B6 deficiency remain incompletely understood, particularly in the context of genome instability and cancer susceptibility. The aim of this work was to investigate how PLP deficiency influences both metabolic and genomic integrity in Drosophila melanogaster, and to explore whether these perturbations interact to promote tumorigenic processes. In the first part of the study, the Drosophila Rasv12 tumor model was used to test the hypothesis that vitamin B6 deficiency promotes tumor malignancy. Pharmacological inhibition of PLP synthesis using 4-deoxypyridoxine (4DP) or gingkotoxin (GT) cooperated with oncogenic Ras to convert benign overgrowths into invasive malignant tumors. PLP deficiency increased tumor size and promoted metastatic behavior, as indicated by basement membrane rupture and upregulation of Mmp1. Molecular analyses revealed elevated reactive oxygen species (ROS), reduced activity of the PLP-dependent enzyme serine hydroxymethyltransferase (SHMT), and the formation of chromosome aberrations (CABs), indicating that oxidative stress and impaired dTMP biosynthesis contribute to genomic instability. Supplementation with antioxidants or dTMP partially rescued both chromosomal and tumor phenotypes, suggesting a mechanistic link between redox imbalance, nucleotide metabolism and cancer progression. In the second part, NMR-based metabolomic profiling was applied to characterize the systemic metabolic alterations induced by vitamin B6 deficiency in wild-type larvae. The analysis revealed substantial increases in branched-chain and aromatic amino acids, glycine and glucose-1-phosphate, accompanied by a global reduction in lipids, including phospholipids and triglycerides. These shifts are consistent with decreased activity of PLP-dependent aminotransferases, decarboxylases and enzymes of lipid synthesis, indicating broad metabolic reprogramming under conditions of PLP shortage. The observed alterations parallel metabolic signatures described in diabetes, insulin resistance and cancer, reinforcing the physiological relevance of this model. Taken together, the results of this thesis suggest that vitamin B6 deficiency may generate a cellular environment in which metabolic imbalance and genomic instability intersect to promote oncogenic transformation. Although further studies are required to establish causality and tissue-specific mechanisms, this work highlights Drosophila melanogaster as a powerful model for dissecting how micronutrient deficiency can couple metabolism, redox regulation and genome integrity to influence disease susceptibility and cancer development
Fetal growth velocity as a predictor of small for gestational age at birth and adverse perinatal outcomes: systematic review and meta-analysis
No full textOBJECTIVE: This study aimed to evaluate the role of fetal growth velocity in predicting small-for-gestational-age at birth and adverse perinatal outcomes. DATA SOURCES: A systematic review and meta-analysis was conducted through an electronic search of PubMed, Embase, and CINAHL, including studies published between January 2000 and February 2025. STUDY ELIGIBILITY CRITERIA: Both prospective and retrospective studies of pregnancies undergoing longitudinal growth assessment, from the second to the third trimester or within the third trimester, were included. METHODS: This study was registered with PROSPERO (International Prospective Register of Systematic Reviews) (CRD42025642750). Pooled sensitivity and pooled specificity with 95% confidence interval and pooled risk estimates were synthesized using random- and fixed-effects models, respectively. Risk of bias was assessed using the Newcastle-Ottawa scale and the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies), whereas certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: The electronic search yielded 5.440 citations. Following full-text review of the potentially eligible studies, 21 studies were included. The predictive and risk stratification value of fetal growth velocity for small-for-gestational-age at birth and adverse perinatal outcomes was assessed across cohorts of 185.441 and 164.341 singleton pregnancies, respectively. Slowing fetal growth velocity showed suboptimal predictive performance for small-for-gestational-age at birth, with pooled sensitivity and specificity for abdominal circumference and estimated fetal weight growth velocity (defined as z-scores divided by interval time in days) of 0.22 (95% CI, 0.09-0.44) and 0.92 (95% CI, 0.92-0.95), and 0.55 (95% CI, 0.53-0.56) and 0.96 (95% CI, 0.96-0.96), respectively (GRADE: low). Slowing fetal growth velocity showed a moderate association with adverse perinatal outcomes: abdominal circumference growth velocity <10th centile was associated with composite adverse perinatal outcome among fetuses predicted to be small-for-gestational-age (pooled odds ratio, 2.47; 95% CI, 1.69-3.82), whereas a fixed centile drop in abdominal circumference/estimated fetal weight ≥50 significantly increased the risk of perinatal death, irrespective of estimated fetal weight (pooled odds ratio, 3.92; 95% CI, 2.03-7.58) (GRADE: moderate). CONCLUSION: Fetal growth velocity might be considered a moderate risk factor for adverse outcomes, but it did not improve prediction over cross-sectional biometry, either at 32 or 36 weeks of gestation, even when implemented in multivariable models. Its clinical utility may lie in complementing third-trimester biometry and maternal/fetal Dopplers in risk stratification. However, standardized definitions and formulas are urgently needed to improve reproducibility and guide implementation in antenatal care
Data mining of molecular data resulting from environmental exposure to xenobiotics
No full textMicroplastic exposure is increasingly recognized as a stressor for human tissues, yet its molecular impact across regulatory layers remains incompletely defined. This thesis characterizes the multi-layer transcriptomic response to polystyrene in airway (BEAS-2B) and liver (HepG2) models across dose (10, 100 μg/ml) and time (24, 48, 72 h), and delivers a portable, auditable analysis workflow. An end-to-end Snakemake pipeline performs acquisition, quality control, trimming, alignment (HISAT2 for long-RNA; a Bowtie1-based, contaminant-depletion then miRNA alignment for small-RNA), differential analysis (DESeq2 with effect-size shrinkage), isoform switch detection (IsoformSwitchAnalyzeR), validated miRNA-target integration, and functional enrichment (clusterProfiler/ReactomePA, ORA and GSEA). Reporting is automated to produce synchronized HTML summaries with full provenance. Biologically, polystyrene elicits a dose- and time-structured remodeling of expression programs. Thousands of differentially expressed transcripts and ~1.6k differentially expressed genes are accompanied by extensive isoform reprogramming (>3,000 significant switches across ~2,300 genes) with predicted consequences that alter coding capacity, intron retention, and nonsense-mediated decay susceptibility. Although significant miRNA changes are concentrated in a subset of high-dose contrasts, the associated validated target networks are large, indicating substantial potential for post-transcriptional control. Enrichment analyses converge on mitochondrial respiration/oxidative phosphorylation, translation and mRNA surveillance (including NMD), stress-activated signaling (MAPK/NF-κB), and p53-aligned checkpoint and DNA-repair programs, with detoxification modules appearing in a context-dependent manner. Cell-type differences align with physiology: BEAS-2B emphasizes innate/epithelial stress programs, whereas HepG2 shows pronounced metabolic, mitochondrial, and translational signatures. Numerous novel isoforms contribute to differential expression and switching, underscoring transcriptome plasticity beyond current annotation. Methodologically, the workflow enforces determinism and comparability: identical code paths, centralized thresholds, uniform backgrounds for enrichment, explicit handling of “empty” branches, and environment-portable resource configuration. Every reported artifact is bound to a file target, enabling re-execution under updated references or parameters and facilitating external audit. Together, the results indicate that polystyrene exposure is not neutral for the tested cell types; rather, it induces coordinated transcriptional, splicing, and miRNA-mediated responses along axes plausibly linked to pathology under sustained or mixed exposures. The pipeline generalizes to other materials and datasets, providing a reusable platform for multi-layer toxicogenomic investigation
Augmented Reality in Cultural Heritage: A Dual-Model Pipeline for 3D Artwork Reconstruction
No full textThis paper presents an innovative augmented reality pipeline tailored for museum environments, aimed at recognizing artworks and generating accurate 3D models from single images. By integrating two complementary pre-trained depth estimation models, i.e., GLPN for capturing global scene structure and Depth-Anything for detailed local reconstruction, the proposed approach produces optimized depth maps that effectively represent complex artistic features. These maps are then converted into high-quality point clouds and meshes, enabling the creation of immersive AR experiences. The methodology leverages state-of-the-art neural network architectures and advanced computer vision techniques to overcome challenges posed by irregular contours and variable textures in artworks. Experimental results demonstrate significant improvements in reconstruction accuracy and visual realism, making the system a highly robust tool for museums seeking to enhance visitor engagement through interactive digital content
Methodologies and Strategies for Cultural Heritage Protection and Conservation Against Climate Changes, Natural and Anthropic Risks
No full textThis open access book offers an overview on the intermediate results obtained in the context of the Italian National Research Programme "Cultural Heritage Active Innovation for Sustainable Society" by the Working Group "Spoke 7", which focuses its research on the development and improvement of strategies and methodologies to protect the cultural heritage against the effects of climate change and of natural and anthropic risks. Topics covered in this book include chapters on digital twins and documentation for cultural heritage as well as on monitoring, assessment, and preventive conservation of heritage. The book also examines restoration and sustainable strategies for heritage preservation and offers advice on green materials and methodologies for conservation.
The impact of climate change on cultural heritage accelerates the effects of natural hazards as well as those caused by human actions: these phenomena raise new research questions and open new challenges for modern societies, thus requiring a broad multidisciplinary approach towards problem solving. Relevant case studies will be identified with a multi-scale approach to encompass different scenarios and to address both general and specific issues to finally deliver innovative solutions to mitigate the effects of climate change, natural and anthropic risks on cultural heritage
Traduzione annotata e analisi de Qike song di Wu Li: i sette vizi capitali in versi classici cinesi
No full textIl contributo offre una traduzione annotata di tre poesie tratte da Qike song 七克頌 (Lodi delle sette vittorie) del poeta, pittore e missionario gesuita cinese Wu Li 吳歷 (1632-1718). Queste poesie sono significative per il tentativo di fondere la dottrina cattolica dei sette vizi con la forma poetica cinese e l'etica confuciana, rappresentando un precoce esempio di dialogo interculturale tra Oriente e Occidente durante la prima fase
della dinastia Qing (1644-1700). Dopo aver contestualizzato il percorso biografico e spirituale di Wu Li, il genere delle poesie Tianxue shi
天學詩 (poesie dell’apprendimento del Cielo) e il concetto di ke 克 (do-
minare), lo studio, nel tradurre tre poesie de Qike song, evidenzia le
strategie retorico-linguistiche adottate da Wu Li e come il poeta abbia
trasfigurato la dottrina cattolica nella forma poetica cinese
L’impatto della digitalizzazione sul contesto scolastico: il ruolo dell’autovalutazione nella scuola
No full textQuesto lavoro si configura come un’indagine teorico-empirica sulle competenze digitali dei docenti della scuola secondaria di secondo grado, esplorata non come insieme di abilità tecniche misurabili, ma come dimensione emergente e situata dell’identità professionale. La trasformazione digitale, infatti, non si riduce alla sola adozione di strumenti, ma richiede un ripensamento profondo dei modi in cui gli insegnanti progettano, valutano e attribuiscono significato alle proprie pratiche educative. In contrasto con gli approcci valutativi tradizionali, spesso centrati su logiche standardizzate, questa ricerca propone un modello di autovalutazione generativa, costruito attraverso l’integrazione tra Theory-Based Evaluation e Positive Thinking Evaluation. Tale modello consente non solo di rilevare i livelli di competenza digitale dei docenti, ma anche di far emergere le condizioni, gli apprendimenti inattesi e i processi riflessivi che ne sostengono lo sviluppo professionale. L’analisi delle pratiche didattiche permette di interpretare la competenza digitale come una configurazione articolata lungo più dimensioni interconnesse – consapevolezza digitale, pratiche di insegnamento, formazione e sviluppo professionale, collaborazione digitale e cittadinanza digitale. L’attivazione di queste dimensioni non segue traiettorie lineari, ma dipende da fattori quali la cultura organizzativa, le risorse disponibili e il tipo di supporto formativo offerto nei contesti scolastici. In particolare, i casi positivi emersi si rivelano leve cruciali per l’innovazione didattica e la crescita professionale, anche in contesti complessi. I risultati confermano che la valutazione, quando concepita come pratica generativa aperta alla scoperta, può costituire uno strumento strategico di empowerment professionale. In questa prospettiva, la scuola digitale non è definita dalla sola adozione di tecnologie, ma dalla capacità dei docenti di progettare, riflettere e apprendere dall’esperienza, attivando consapevolezza critica e potenziale trasformativo
Emergent Carotid Stenting for Acute Anterior Circulation Ischemic Stroke With Tandem Lesions
No full textBACKGROUND AND OBJECTIVES: The management of anterior circulation tandem lesion stroke remains controversial, given its under-representation in randomized thrombectomy trials and uncertainty regarding optimal extracranial carotid intervention. We aimed to determine whether emergent carotid stenting (eCAS) during endovascular thrombectomy (EVT) for anterior circulation tandem lesions improves 90-day functional outcomes compared with a no-stenting strategy. METHODS: We conducted an international multicenter longitudinal retrospective cohort study (CERES-TANDEM, NCT06965036) of consecutive adults treated at 49 comprehensive stroke centers in Europe, North America, and Singapore for anterior circulation acute ischemic stroke due to tandem lesions from January 1, 2018, to December 31, 2024. Exclusion criteria were primary hemorrhagic stroke, absence of intracranial occlusion, presentation >24 hours from symptom onset, and age younger than 18 years. We compared 90-day modified Rankin Scale (mRS) scores between participants receiving eCAS and those receiving no stenting during EVT. The primary estimand was mRS shift, analyzed by stabilized inverse probability of treatment weighting (IPTW)-weighted ordinal regression. Additional estimands were direct-effect estimand adjusting for successful recanalization (defined as Thrombolysis in Cerebral Infarction grade 2b or higher) and symptomatic intracranial hemorrhage (sICH) (estimand 2) and stratum estimand restricting to never-crossers (estimand 3). RESULTS: Of 4,053 patients (mean age 70 years, 65.5% female), 2,522 underwent eCAS and 1,531 received no stenting. After IPTW, eCAS was associated with an improved 90-day functional outcome (common odds ratio (OR) 1.31; 95% CI 1.17-1.47;p < 0.001) and higher odds of mRS score 0-1 (OR 1.27; 95% CI 1.08-1.50; p = 0.005) and mRS score 0-2 (OR 1.30; 95% CI 1.13-1.51; p < 0.001), without a significant increase in sICH (OR 1.21; 95% CI 0.93-1.56; p = 0.15). Findings were consistent in direct-effect (common OR 1.17; 95% CI 1.04-1.31; p = 0.008) and stratum (common OR 1.37; 95% CI 1.21-1.55; p < 0.001) estimands. There was no interaction for intracranial occlusion site, IV thrombolysis, sedation technique, EVT approach, or access site. Sensitivity analysis including recanalization in IPTW-weighted estimand 1 framework confirmed the association of eCAS with improved 90-day functional outcomes (common OR 1.14, 95% CI1.02-1.27, p = 0.008). DISCUSSION: In this large real-world cohort, eCAS during EVT for anterior circulation tandem lesions was associated with superior 90-day functional recovery without increased hemorrhagic risk. These findings support consideration of eCAS in clinical practice and warrant confirmation in randomized trials. TRIAL REGISTRATION INFORMATION: Registered in clinicaltrials.gov, NCT06965036. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with stroke due to anterior circulation tandem lesions, eCAS during EVT improves 90-day functional outcomes compared with EVT alone
Structure-Guided Design of Temporin-Derived Peptides Reveals Potent Dual-Mechanism Inhibitors of SARS-CoV-2
No full text: The study investigates temporin-derived antimicrobial peptides as broad-spectrum antiviral candidates against SARS-CoV-2. Surface plasmon resonance screening shows that temporin G (TG), temporin L (TL), and the nonhemolytic analog Pro3-TL bind the trimeric Spike protein with high affinity, following a two-state binding model. NMR confirms TG-Spike interactions and identifies Phe2 as critical for binding. Docking simulations place the interaction at the NTD-RBD interface and reveal a cation-π interaction between TG Phe2 and Spike Arg357. These insights informed the design of the chimeric analog RB-142 and four derivatives (RB-143 to RB-146) incorporating bulkier aromatic residues. All analogs exhibit submicromolar binding affinities. Biological assays show low cytotoxicity and potent virucidal activity, with RB-146 demonstrating the strongest effect and a high therapeutic index. Mechanistic analyses indicate that RB-146 disrupts viral attachment and damages the viral envelope. The findings position RB-146 as a promising dual-mechanism antiviral candidate
L’Antagonismo digitale. Conflitto politico e democrazia nella post-modernità
No full textLa ricerca ricostruisce il fenomeno dell’ “antagonismo digitale” inteso come forma di attivismo socio-politico espressa attraverso strumenti digitali e, in particolare, tecniche di hacking; lo studio vuole esplorare l’eterogeneità della categoria, rilevandone la trasversalità a più contesti socio-politici nonché il carattere evolutivo che lo ha portato a diventare una componente ricorrente nel repertorio delle proteste sociali contemporanee.
La trattazione guarda a diverse direttrici di ricerca tra cui le radici culturali inerenti l’etica hacker e la cultura cyberpunk, nonché le convergenze tra hacktivismo e i movimenti di protesta di matrice anti-globalista e anti-capitalist