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A submerged elevation located off the coast of Le Castella, a small village on the Ionian Coast of Calabria (Italy) populated for thousands of years that features notable archaeological remains from the Great Greece (Magna Graecia) and the Middle Ages, was investigated through in-depth, multidisciplinary, geoarchaeological research. This submarine elevation, once aligned with the marine terrace MIS 3 of Le Castella and still completely emerged between 10 and 8 ka years ago, slowly sank due to erosion and local tectonic-structural subsidence and was also favoured by a submerged normal fault that cuts the terrace in two. The dismantling and sinking of this part of the marine terrace has significantly changed the Late Holocene shorelines, with notable consequences on a topographic and archaeological level. In fact, one of the consequences of the sinking of this ancient promontory was the disappearance of two small islands that were reported to be right in front of Le Castella by numerous historical and cartographic sources. In the last decades, there has been a scientific debate over the existence of these islets, but no convincing evidence has been found about their actual presence up until now. This research, funded by the Marine Protected Area “Capo Rizzuto”, was conducted by means of underwater archaeological and geological surveys, geophysical seabed mapping systems, and both direct and instrumental optical surveys made with an Autonomous Surface Vehicle. The outcomes allow us to confirm the presence of these two partially emerged rock bodies up to half a millennium ago. In addition, the presence of anthropogenic extrabasinal materials in a marine area corresponding to one of the highest points of the submerged elevation allows us to define the exact position of one of the two islets. These archaeological findings have been subject, for the first time ever, to a thorough topographical and architectural analysis, then compared with other near and very similar submerged structures. On the basis of these comparisons, the findings should be attributed to the Byzantine Age or, at most, to the Middle Ages. In-depth archival research on portolan charts and navigation maps, in many cases unpublished and dating from the Middle Ages to the early 18th century, supports the results of our marine investigations from a historical point of view.

Inflammation is a tightly coordinated response of the host immune system to bacterial and viral infections, triggered by the production of inflammatory cytokines. Sepsis is defined as a systemic inflammatory response followed by immunosuppression of the host and organ dysfunction. This imbalance of the immune response increases the risk of mortality of patients with sepsis, making it a major problem for critical care units worldwide. The P2X7 receptor plays a crucial role in activating the immune system by inducing the activation of peripheral blood mononuclear cells. In this study, we analyzed a cohort of abdominal origin septic patients and found that the expression of the P2X7 receptor in the plasma membrane is elevated in the different subsets of lymphocytes. We observed a direct relationship between the percentage of P2X7-expressing lymphocytes and the early inflammatory response in sepsis. Additionally, in patients whose lymphocytes presented a higher percentage of P2X7 surface expression, the total lymphocytes populations proportionally decreased. Furthermore, we found a correlation between elevated soluble P2X7 receptors in plasma and inflammasome-dependent cytokine IL-18. In summary, our work demonstrates that P2X7 expression is highly induced in lymphocytes during sepsis, and this correlates with IL-18, along with other inflammatory mediators such as IL-6, IL-8, and procalcitonin., Competing Interests: HM-B, CG-P, LM-A, AG-L, A-BM, PP, and JM-G are co-founders of Viva in vitro diagnostics SL. PP also serves as the scientific consultant of Viva in vitro diagnostics SL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Martínez-Banaclocha, García-Palenciano, Martínez-Alarcón, Amores-Iniesta, Martín-Sánchez, Ercole, González-Lisorge, Fernández-Pacheco, Martínez-Gil, Padilla-Rodríguez, Baroja-Mazo, Pelegrín and Martínez-García.)

Sepsis is characterized by a systemic inflammatory response followed by immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.