Search

Immunotherapy has recently garnered plenty of attention to improve the clinical outcomes in the treatment of various diseases. However, owing to the dynamic nature of the immune system, this approach has often been challenged by concerns regarding the lack of adequate long-term responses in patients. The development of microneedles (MNs) has resulted in the improvement and expansion of immuno-reprogramming strategies due to the housing of high accumulation of dendritic cells, macrophages, lymphocytes, and mast cells in the dermis layer of the skin. In addition, MNs possess many outstanding properties, such as the ability for the painless traverse of the stratum corneum, minimal invasiveness, facile fabrication, excellent biocompatibility, convenient administration, and bypassing the first pass metabolism that allows direct translocation of therapeutics into the systematic circulation. These advantages make MNs excellent candidates for the delivery of immunological biomolecules to the dermal antigen-presenting cells in the skin with the aim of vaccinating or treating different diseases, such as cancer and autoimmune disorders, with minimal invasiveness and side effects. This review discusses the recent advances in engineered MNs and tackles limitations relevant to traditional immunotherapy of various hard-to-treat diseases. Unlabelled Image • Microneedles are promising devices for painless drug delivery with high bioavailability. • Transdermal microneedle can improve the biological effect of drugs through adjustable drug release. • Facile fabrication and versatility have caused high attraction towards microneedle-based drug delivery. • Microneedles are suggested for immunotherapy due to the high abundance of immune cells under the skin. [ABSTRACT FROM AUTHOR]

Work on thermal pools at Poggetti Vecchi in Grosseto, Italy, exposed an up to 3-meter-thick succession of seven sedimentary units. Unit 2 in the lower portion of the succession contained vertebrate bones, mostly of the straight-tusked elephant, Palaeoloxodon antiquus, commingled with stone, bone, and wooden tools. Thermal carbonates overlying Unit 2 are radiometrically dated to the latter part of the middle Pleistocene. This time span indicates that early Neanderthals produced the human artifacts from Poggetti Vecchi. The elephant bones belong to seven individuals of different ages. Sedimentary facies analysis and paleoecological evidence suggest a narrow lacustrine-palustrine embayment affected by water-level fluctuations and, at times, by hydrothermal water. Cyclic lake-level variations were predominantly forced by the rapid climatic fluctuations that occurred at Marine Isotope Stage (MIS) 6–7 transition and throughout the MIS 6. Possibly an abrupt, intense, and protracted cold episode during the onset of MIS 6 led to the sudden death of the elephants, which formed an unexpected food resource for the humans of the area. The Poggetti Vecchi site adds new information on the behavioral plasticity and food procurement strategies that early Neanderthals were able to develop in Italy during the middle to the late Pleistocene transition. [ABSTRACT FROM PUBLISHER]

Geomorphologic, stratigraphic, faunistic, palynological and 14C analyses were carried out in the area of the mouth of the Garigliano River characterized by two strand plains that are referred to the Eutyrrhenian and the Holocene, rimming two depressed zones separated by the Garigliano River channel. This study depicts the palaeoenvironmental evolution over the last 8200 years and the landscape context at the time of Minturnae Roman colony. Between 8200 and 7500 yr BP, a wet zone occurred in the northern zone, whereas in the southern part, a lagoon developed. During the final transgression stage and the beginning of the sea level still stand (7500–5500 yr BP), a freshwater marsh formed in the northern zone, and the width of the southern lagoon decreased. Between 5500 and 3000 yr BP, the coastal barrier changed into a delta cusp, a freshwater marsh also appeared in the southern part and the river wandered between the twin marshes. Because of local uplift, previously unknown in this area, part of the floor of the southern marsh emerged, and after 4000 yr BP, both marshes became coastal ponds with prevailing clastic sedimentation. A progressive increment in anthropic forcing on the land took place after 3000 yr BP. The Marica sanctuary was built (7th century BC), and the Roman colony of Minturnae was developed beginning the 3rd century BC. The shallow depth of the ponds prevented their use as harbours, and saltwork plants can be ruled out based on the faunal and palynological data. The ongoing infilling of both ponds was never completed, and their reclamation is still in progress. [ABSTRACT FROM AUTHOR]

A buried paleovalley system, up to 2 km wide and exceeding 50 m in relief, made up of multiple cross-cutting depressions incised into the Lower Pleistocene bedrock, is reported from the central Adriatic coastal plain at the mouth of Biferno River. Through a multi-proxy approach that included geomorphological, stratigraphic, sedimentological and paleontological (benthic foraminifers, ostracods and molluscs) investigations, the facies architecture of distinct, superposed valley fills is reconstructed and their relative chronology established along a transverse profile with extremely high data density (average borehole spacing 75 m). Regional tectonic uplift appears as the major controlling factor of initial (Middle Pleistocene) river down-cutting and paleovalley formation. In contrast, glacio-eustatic fluctuations drove fluvial-system response over the last 120 ky, when valley incision was primarily induced by the last glacial base-level lowering and climatic forcing. A fragmented record of coastal and shallow-marine deposits is available for the lower paleovalley fill, which is penetrated by a limited borehole dataset. Multiple erosion phases probably related to the post-MIS 5e sea-level fall are reconstructed from the upper paleovalley fill, where a buried fluvial terrace succession is identified a few tens of meters below the ground surface. The flat surfaces of two buried fluvial terraces suggest longer-term, stepped relative sea-level fall, and are correlated with fluvial incisions that took place possibly at the MIS 5/4 transition and at the MIS 3/2 transition, respectively. A laterally extensive gravel body developed on the valley floor during the Last Glacial Maximum. During the ensuing latest Pleistocene–early Holocene sea-level rise the Biferno paleovalley was transformed into an estuary. Upstream from the maximum shoreline ingression, the vertical succession of well-drained floodplain, poorly-drained floodplain, and swamp deposits evidences increasing marine influence in the estuary, in response to continuing sea-level rise. The interfluves were drowned around 8 cal. ky BP, when brackish conditions developed in the study area. Decreasing marine influence in the uppermost 15 m of the paleovalley fill suggests the onset of the modern delta: when the rate of sea-level rise was overwhelmed by sediment supply, delta progradation took place. [ABSTRACT FROM AUTHOR]

Abstract: Late Miocene brackish ostracods and molluscs collected in three Italian basins show noticeable differences in their taxonomic composition, despite their capability of dispersing across wide geographic areas. In the Venetian-Friulian Basin (northern Italy), the upper Tortonian sediments contain oligotypic ostracod assemblages including Hemicyprideis dacica dacica, Hemicytheria pejinovicensis, and Loxoconcha cf. L. josephi and few gastropods referable to Planorbidae and Stenothyroides, which are typical of the central Paratethys. In central Italy, the brackish ostracods and molluscs recovered from upper Tortonian-lower Messinian deposits from four Tuscan basins (Volterra-Radicondoli, Velona, Baccinello-Cinigiano, and Valdelsa) display high affinity at a generic level but strong endemicity at a specific level. At Cessaniti (southern Italy), the upper Tortonian unit contains oligotypic brackish ostracods and molluscs: Mediocytherideis (Sylvestra) posterobursa, Cyprideis ruggierii, Loxoconcha cf. L. biformata, and Zonocypris membranae quadricella characterise the ostracod fauna, while Granulolabium bicinctum and Hydrobia frauenfeldi are the dominant molluscs. The recovered ostracods have a strong affinity with brackish species from central and eastern Palaeo-Mediterranean areas, whereas the molluscs present a Paratethyan origin. Despite the fact that the basins are all brackish and partly coeval, the systematics of these assemblages highlights the absence of common species among the three studied areas. Geochemical analyses (stable isotopes and trace elements) are performed on ostracods, and 87Sr/86Sr ratios are established in molluscs and echinoids. The results suggest brackish environments with different compositions and origins of solutes in the three different areas. The Tuscan basins are characterised by brackish waters, with NaCl-enriched waters coming from aquifers of Triassic evaporite bedrock. The brackish deposits of the Venetian-Friulian Basin and Cessaniti are true marginal marine environments, although the northern basin may have been influenced by both the Paratethyan Sava Basin and the northern portion of the Palaeo-Mediterranean water bodies. [Copyright &y& Elsevier]