Mechanistic insights into the release of doxorubicin from graphene oxide in cancer cells

Liposomal doxorubicin (L-DOX) is a popular drug formulation for the treatment of several cancer types (e.g., recurrent ovarian cancer, metastatic breast cancer, multiple myeloma, etc.), but poor nuclear internalization has hampered its clinical applicability so far. Therefore, novel drug-delivery nanosystems are actively researched in cancer chemotherapy. Here we demonstrate that DOX-loaded graphene oxide (GO), GO-DOX, exhibits much higher anticancer efficacy as compared to its L-DOX counterpart if administered to cellular models of breast cancer. Then, by a combination of live-cell confocal imaging and fluorescence lifetime imaging microscopy (FLIM), we suggest that GO-DOX may realize its superior performances by inducing massive intracellular DOX release (and its subsequent nuclear accumulation) upon binding to the cell plasma membrane. Reported results lay the foundation for future exploitation of these new adducts as high-performance nanochemotherapeutic agents

A multi-parameter field monitoring system to investigate the dynamics of large earth slides–earth flows in the Northern Apennines, Italy

Large earth slides and rocks lides evolving into earth flows are quite widespread in the Northern Italian Apennines. Despite being simply referred to as landslides, many of them are, in fact, large complexes of landslides. They evolved through multiple and/or successive movements, undergoing partial and/or total reactivations. The reactivation of pre-existing landslide bodies is the prevalent mechanism for the known landslide events, as the historical records and the technical reports indicate. Landslide reactivation is, indeed, a relevant topic from the perspective of risk assessment and mitigation. A multi-parameter monitoring system was installed on a large complex of landslides that underwent partial or total reactivations after heavy rainfall events, causing damages to buildings and infrastructures. Two clusters of automatic piezometers—each coupled with an inclinometer—and a time-lapse resistivity deployment were the core of the monitoring system. A weather station, collecting data from subsurface thermometers, and a water content probe completed the system. After the construction of a new geological model of the slope, this study aimed at understanding the possible mechanisms leading to the reactivation of the landslide. This goal was achieved by gaining insights into the process of rainfall infiltration into the landslide deposits, by determining the groundwater flow and evaluating the landslide displacements. The monitoring system captured the processes that took place in the landslide bodies and the bedrock in response to a rainfall event in early February 2017, which followed a dry period of eight months. The recorded data provided indications on the variation of the hydraulic head in the groundwater within the landslide and the bedrock, particularly at the sliding surfaces. The electrical conductivity of the groundwater and the resistivity of the terrain varied across the failure surfaces. In particular, a sudden increase in the electrical conductivity was related to the locations of the main sliding surfaces. The joint analysis of time-lapse resistivity, hydraulic heads, and groundwater electrical conductivity helped identify the locations of weaker levels within the landslide masses, which were confirmed by data from inclinometers. This study improved the knowledge of the hydrogeological behaviour of a complex of landslides in heterogeneous low-permeability media. Moreover, the obtained results contributed to the understanding of the role played by different portions of the landslide complex in the evolution of the movement

Beyond the genetics of HDL:why is HDL cholesterol inversely related to cardiovascular disease?

There is unequivocal evidence that high-density lipoprotein (HDL) cholesterol levels in plasma are inversely associated with the risk of cardiovascular disease (CVD). Studies of families with inherited HDL disorders and genetic association studies in general (and patient) population samples have identified a large number of factors that control HDL cholesterol levels. However, they have not resolved why HDL cholesterol and CVD are inversely related. A growing body of evidence from nongenetic studies shows that HDL in patients at increased risk of CVD has lost its protective properties and that increasing the cholesterol content of HDL does not result in the desired effects. Hopefully, these insights can help improve strategies to successfully intervene in HDL metabolism. It is clear that there is a need to revisit the HDL hypothesis in an unbiased manner. True insights into the molecular mechanisms that regulate plasma HDL cholesterol and triglycerides or control HDL function could provide the handholds that are needed to develop treatment for, e.g., type 2 diabetes and the metabolic syndrome. Especially genome-wide association studies have provided many candidate genes for such studies. In this review we have tried to cover the main molecular studies that have been produced over the past few years. It is clear that we are only at the very start of understanding how the newly identified factors may control HDL metabolism. In addition, the most recent findings underscore the intricate relations between HDL, triglyceride, and glucose metabolism indicating that these parameters need to be studied simultaneously

The Lossetti Tower in Beura-Cardezza (Italy): Structural Assessment and Rehabilitation of a Historical Dry Stone Masonry Building

Dry stone masonry (DSM) is an ancient construction method widely used for vernacular and military buildings in rural and mountain regions. The use of this particular method is due to the large availability of natural stone that characterized these areas. The consolidation of DSM buildings is a challenging issue: in fact, this kind of masonry proved to be scarcely reliable under eccentric and horizontal loads and in absence of elements that are long enough to cross the masonry in its thickness. However, there are very few techniques that can preserve the peculiarities of a masonry texture. This paper presents the design approach that was used for the structural rehabilitation of the Lossetti Tower, a medieval DSM watchtower located in Beura-Cardezza (Italy, Piemonte Region). First, a preliminary research on the building was conducted. Secondly, to better understand the masonry quality, both a 3D laser scanning geometric survey and a technological study of the masonry typology and texture of the tower were executed. Thirdly, to evaluate the mechanical behaviour, a diagonal compression test on the DSM specimens was performed. Finally, after a structural assessment, was developed a tailored design of the strengthening intervention by using the technique of continuous basalt fibers stitching. The proposed system consists in creating a mesh of basalt fiber ropes, that passes through the masonry thickness and ties the blocks together. This system also allows to connect the wall in the transverse direction and to improve the monolithic behaviour of masonry panels in perfect compatibility with the original materials and it was preferred to the more invasive ones also for its reversibilit