University of Modena and Reggio Emilia
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Targeting monocarboxylate transporter 1 with a copper-chelating coumarin-based bioconjugate: Synthesis and characterization
No full text: Monocarboxylate Transporters (MCTs), particularly MCT1, are increasingly recognized as key regulators of cancer metabolism, facilitating lactate exchange and contributing to tumor aggressiveness. Their overexpression in various malignancies makes them attractive targets for both therapeutic and diagnostic strategies. In this study, we report the design, synthesis, and comprehensive characterization of a novel chimeric bioconjugate, LCPn, integrating a coumarin-based MCT1-targeting moiety with a TACN(1,4,7-triazacyclononane)-containing chelator, optimized for copper radioisotope binding. The synthetic route was refined through strategic modifications, including mono-Boc (tert-butyloxycarbonyl) protecting group protection of the macrocycle and efficient SN2-type coupling via thionyl chloride activation. Structural confirmation was achieved through nuclear magnetic resonance and mass spectrometry. Five protonation constants were determined for LCPn, reflecting contributions from both the chelator and targeting domains. Complexation studies with Cu2+ and Zn2+ confirmed the formation of stable 1:1 metal-to-ligand complexes, while cyclic voltammetry studies indicated a quasi-reversible redox behaviour upon Cu2+ to Cu+ reduction. Docking simulations and cell-based assays demonstrated that the coumarin-based targeting moiety exhibits high affinity for MCT1 and effectively inhibits lactate uptake in prostate cancer models. These findings underscore the dual functionality of LCPn as a selective MCT1-targeting agent and a robust copper-chelating platform, paving the way for future theranostics applications in oncology exploiting inorganic bioconjugates
Il sistema sanzionatorio penale e le intersezioni col sistema dei controlli: diffida, prescrizione estintiva e altri strumenti di estinzione del reato
No full textTransfer Accuracy and Chairside Efficiency of Two Digital Indirect Bonding Techniques: An In Vitro Analysis
No full textBackground: Digital indirect bonding (IB) has emerged as a reliable approach to improving the precision and efficiency of orthodontic bracket placement.Methods: This in vitro study evaluated and compared the positional accuracy and efficiency of two digitally driven indirect bonding (IB) techniques—a rigid single-tooth transfer jig (Leone Jig System) and a flexible three-part transfer tray (IBT Flex Resin)—as well as conventional direct bonding. Ten sets
of 3D-printed resin dental models were randomly allocated to the three bonding protocols. Bracket positions were virtually planned and analyzed by superimposing pre- and postbonding
STL models using landmark- and surface-based registration. Linear discrepancies were measured along the axial, sagittal, and vertical planes, and data were analyzed using repeated-measures ANOVA and Friedman tests (α = 0.05). Results: Both indirect bonding
techniques showed significantly smaller deviations fromthe ideal virtual setup comparedwith direct bonding across all spatial planes (p < 0.001). Mean discrepancieswere consistently below 0.3 mm for the indirect protocols, compared with values exceeding 0.4 mm for direct bonding. The rigid jig demonstrated the highest precision, particularly in the sagittal (0.18 ± 0.06 mm) and vertical (0.21 ± 0.07 mm) planes, while the flexible tray showed slightly higher deviations
(approximately 0.25–0.30 ± 0.08–0.09 mm across planes). Chairside bonding time per full arch was reduced by more than 50% with both IB techniques, with the jig-based system being the most time-efficient. No significant interaction between bonding method and spatial plane was observed. Conclusions: Within the limitations of this in vitro study, digital indirect bonding—especially rigid, patient-specific jigs—demonstrated superior bracket placement accuracy and procedural efficiency compared with direct bonding
Fast ultrasonic-based extraction of peptides from teeth for forensics and archaeological purposes
No full textOxidative Stress as a Central Mechanistic Bridge Between Alzheimer’s and Vascular Pathologies in Mixed Dementia: Emerging Evidence and Therapeutic Perspectives
No full textMixed dementia (MD), characterized by overlapping features of Alzheimer's disease (AD) and vascular dementia (VaD), represents the most prevalent form of late-life cognitive decline. Increasing evidence identifies oxidative stress as a unifying molecular mechanism driving both neurodegenerative and vascular pathologies in MD. Reactive oxygen species (ROS) contribute to amyloid-beta aggregation, tau hyperphosphorylation, endothelial dysfunction, and blood-brain barrier disruption, creating a self-perpetuating cycle of neuronal and vascular injury. Mechanistic models demonstrate how chronic hypoperfusion and mitochondrial dysfunction exacerbate ROS generation and neuroinflammation, while impaired Nrf2-mediated antioxidant defense further amplifies damage. Therapeutically, classical antioxidants show inconsistent efficacy, shifting focus toward mitochondrial protection, Nrf2 activation, and lifestyle-based oxidative load reduction. Therefore, we sought to outline therapeutic approaches capable of broadly targeting these mechanisms, through focused narrative analysis of recent studies employing delivery systems for antioxidant proteins and/or redox-regulating miRNAs. In particular, experimental interventions using mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) demonstrate neuroprotective and anti-inflammatory effects via the Nrf2 pathway, suggesting promising avenues for multimodal treatment. Integrating oxidative, vascular, and neurodegenerative paradigms is essential for advancing diagnostic precision and developing targeted interventions capable of addressing the complex pathophysiology of mixed dementia
Emerging knowledge on the evolution, structure and resource distribution of the northern South China Sea continental margin
No full textThe South China Sea (SCS) formed through Cenozoic lithospheric stretching of the south-eastern edge of the Eurasian Plate and is one of the largest marginal seas in the Western Pacific region. In recent years, its northern continental margin has emerged as a global hotspot for geoscientific research, particularly for advancing our understanding of rift evolution and continental margin architecture. An exceptional wealth of new geological and geophysical data from the hydrocarbon exploration industry and recent scientific ocean drilling expeditions has particularly driven this surge. Building on this opportunity, we assembled the Thematic Collection “Emerging knowledge on the tectonics of the South China Sea”, which integrates new results with existing datasets to provide an updated and comprehensive view of the northern SCS continental margin. In this preface, we provide an overview of the collection, which comprises nine original research articles. Collectively, the contributions reveal a complex structural evolution of the continental margin from proximal to distal domains, characterised by punctuated stages of rifting and pronounced along-strike structural variability. Additionally, they document structural and sedimentological controls on potential hydrocarbon resource distribution across the region. These new insights not only advance our knowledge of the northern SCS continental margin but also contribute to deciphering the inherent complexities across plate-edge (marginal sea) rifts worldwide
Cutting Time in slices
No full textDuring the 18th and 19th centuries, the conquest of deep time emerged as a pivotal achievement when geologists recognized that the age of rocks far exceeded earlier age estimates and exhibited a systematic order of deposition. Geological processes were reframed within an immense temporal framework, prompting efforts to identify and correlate strata worldwide using field-observable discontinuities and lithological traits. As Earth's antiquity became accepted, it also became clear that rock layers preserved records of countless biological and geological events. Biological markers-fossils-offered the most reliable data, but stratigraphers debated whether abrupt changes (catastrophism) or gradual processes (uniformitarianism) should define time slices. They refined biozonation by evaluating species' first and last appearances, ranges, abundance, and geographic distributions. Despite sophisticated biostratigraphic schemes, such subdivisions lacked numerical precision. Only with the discovery of radioactivity and development of radioisotopic dating could geologists assign numerical ages to strata, transforming the geological time scale from a relative framework into one anchored by numerical dates. This breakthrough established a rigid time grid, populated by formally defined periods, epochs, and ages, and with dates geologists could establish the rates of biological and geological processes. Later techniques introduced chemical signatures, magnetic reversal records, and orbital cyclicity as new correlation tools. Today, stratigraphers integrate these diverse markers while continually subdividing intervals to enhance the precision, exactness, and reliability of the Phanerozoic timescale. This multifaceted approach promises even more accurate correlations. By dividing time into thinner intervals and uniting various stratigraphical disciplines, geologists are moving towards a global and finely resolved chronostratigraphic framework. Our aim is to synthesize the principal developments that have shaped the conceptualization of geological time, with the purpose of establishing a rigorous foundation for future advances in the subdivision and quantification of temporal intervals
Prevalence, incidence and mortality of interstitial lung disease in patients with Sjogren disease: data from the prospective observational “EMERGE” study
No full textBackground: Interstitial lung disease (ILD) is a severe pulmonary complication of Sjogren disease (SjD), but its prevalence, natural history and survival are not completely understood. Our study aimed to investigate prevalence, incidence, and mortality of SjD-ILD in a cohort of unselected consecutive SjD patients. Methods: all consecutive SjD patients referred to our centre were enrolled in the study. A careful assessment for respiratory symptoms was periodically performed for each patient, and high-resolution computed tomography (HRCT) was requested in case of new-onset dyspnoea, persistent dry cough, or detection of velcro crackles by mean of electronic auscultation (VECTOR). Findings: At enrolment, ILD was detected in 61/257 patients with a prevalence of 23.7 %. During a mean followup of 42.6 + 14.6 months, 3 new cases of ILD were recorded, with an incidence of 0.41 new cases per 100 patients/year. Multivariate analysis showed a direct association between ILD and male sex, age at SjD diagnosis, and erythro-sedimentation rate >40 mm, and an inverse correlation with sicca syndrome. Nonspecific interstitial pneumonia was the most observed HRCT pattern, followed by usual interstitial pneumonia. During the follow-up, 21 patients (8.2 %) died, with a statistically significant difference between the overall survival of patients with (66.5 %+11.7) and without ILD (88.4 %+5.5) (p<0.001). A fibrotic pattern was associated to a worse survival rate, while no difference was observed according to the radiologic pattern. Anti-SSA antibody was a protective factor for death, while the age at diagnosis of SjD, and the extent of ILD at HRCT were directly associated to an increased mortality. Interpretation: ILD can be identified in a high number of SjD patients, inducing a significant impairment in survival. The ILD extent, but not HRCT pattern of ILD, represents the main predictor of mortality. Therefore, careful monitoring, by a multidisciplinary team, should be ensured to all SjD-ILD patients
Exploring dynamic interactions between energy prices and CPI
No full textThis paper aims to shed light on the dynamic interactions between the US Consumer Price
Index and the Bureau of Labor Statistics Producer Price Index component for fuels and related
products and power, using threshold cointegration together with parametric and non-parametric causality tests. This integrated approach not only validates findings across methods but also reveals more nuanced short-term dynamics than any single test could capture. The empirical results show that, in the long-run, disequilibrium states characterized as ‘‘turbulent’’ are mainly detected before 2000. On the other hand, ‘‘normal’’ regimes appear particularly after 2000. In the short-run, we observe a significant feedback relationship in the pre-2000 period, while a tendency of energy prices to cause the Consumer Price Index dominates in the post-2000 sample. This behavior highlights that the transmission of energy price shocks to the Consumer Price Index is asymmetric and evolves over time, providing useful insights for policymakers and market participants