Boosted Cross-Linking and Characterization of High-Performing Self-Assembling Peptides

Tissue engineering (TE) strategies require the design and characterization of novel biomaterials capable of mimicking the physiological microenvironments of the tissues to be regenerated. As such, implantable materials should be biomimetic, nanostructured and with mechanical properties approximating those of the target organ/tissue. Self-assembling peptides (SAPs) are biomimetic nanomaterials that can be readily synthesized and customized to match the requirements of some TE applications, but the weak interactions involved in the self-assembling phenomenon make them soft hydrogels unsuited for the regeneration of medium-to-hard tissues. In this work, we moved significant steps forward in the field of chemical cross-linked SAPs towards the goal of stiff peptidic materials suited for the regeneration of several tissues. Novel SAPs were designed and characterized to boost the 4-(N-Maleimidomethyl) cyclohexane-1-carboxylic acid 3-sulpho-N-hydroxysuccinimide ester (Sulfo-SMCC) mediated cross-linking reaction, where they reached G′ values of ~500 kPa. An additional orthogonal cross-linking was also effective and allowed to top remarkable G′ values of 840 kPa. We demonstrated that cross-linking fastened the pre-existing self-aggregated nanostructures, and at the same time, a strong presence of ß-structures is necessary for an effective cross-linking of (LKLK)3-based SAPs. Combining strong SAP design and orthogonal cross-linking reactions, we brought SAP stiffness closer to the MPa threshold, and as such, we opened the door of the regeneration of skin, muscle and lung to biomimetic SAP technology

Structural performance of an IP2 package in free drop test conditions: numerical and experimental evaluations

The casks or packaging systems used for the transportation of nuclear materials, especially spent fuel elements, have to be designed according to rigorous acceptance requirements, like the IAEA ones, in order to provide protection to human beings and environment against radiation exposure and contamination. This study deals with the free drop test of an Italian design packaging system to be used for the transportation of low and intermediate level radioactive wastes. Impact drop experiments were performed in the Lab. Scalbatraio of the DICI - University of Pisa. Dynamic analyses too have been carried out, by refined models of both the cask and target surface to predict the effects of the impact shock (vertical drop) on the package. The experimental tests and numerical analyses are thoroughly compared, presented and discussed. The numerical approach shows to be suitable to reproduce with good reliability the test situations and results

On the Polish doughnut accretion disk via the effective potential approach

We revisit the Polish doughnut model of accretion disks providing a comprehensive analytical description of the Polish doughnut structure. We describe a perfect fluid circularly orbiting around a Schwarzschild black hole, source of the gravitational field, by the effective potential approach for the exact gravitational and centrifugal effects. This analysis leads to a detailed, analytical description of the accretion disk, its toroidal surface, the thickness, the distance from the source. We determine the variation of these features with the effective potential and the fluid angular momentum. Many analytical formulas are given. In particular it turns out that the distance from the source of the inner surface of the torus increases with increasing fluid angular momentum but decreases with increasing energy function defined as the value of the effective potential for that momentum. The location of torus maximum thickness moves towards the external regions of the surface with increasing angular momentum, until it reaches a maximum an then decreases. Assuming a polytropic equation of state we investigate some specific cases.Comment: 33 pages, 28 figures, 1 table. This is a revised version to meet the published articl

The inflammasome in chronic complications of diabetes and related metabolic disorders

Diabetes mellitus (DM) ranks seventh as a cause of death worldwide. Chronic complications, including cardiovascular, renal, and eye disease, as well as DM-associated non-alcoholic fatty liver disease (NAFLD) account for most of the morbidity and premature mortality in DM. Despite continuous improvements in the management of late complications of DM, significant gaps remain. Therefore, searching for additional strategies to prevent these serious DM-related conditions is of the utmost importance. DM is characterized by a state of low-grade chronic inflammation, which is critical in the progression of complications. Recent clinical trials indicate that targeting the prototypic pro-inflammatory cytokine interleukin-1β (IL-1 β) improves the outcomes of cardiovascular disease, which is the first cause of death in DM patients. Together with IL-18, IL-1β is processed and secreted by the inflammasomes, a class of multiprotein complexes that coordinate inflammatory responses. Several DM-related metabolic factors, including reactive oxygen species, glyco/lipoxidation end products, and cholesterol crystals, have been involved in the pathogenesis of diabetic kidney disease, and diabetic retinopathy, and in the promoting effect of DM on the onset and progression of atherosclerosis and NAFLD. These metabolic factors are also well-established danger signals capable of regulating inflammasome activity. In addition to presenting the current state of knowledge, this review discusses how the mechanistic understanding of inflammasome regulation by metabolic danger signals may hopefully lead to novel therapeutic strategies targeting inflammation for a more effective treatment of diabetic complications

Lymphocyte Subsets and Inflammatory Cytokines of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Almost all multiple myeloma (MM) cases have been demonstrated to be linked to earlier monoclonal gammopathy of undetermined significance (MGUS). Nevertheless, there are no identified characteristics in the diagnosis of MGUS that have been helpful in differentiating subjects whose cancer may progress to a malignant situation. Regarding malignancy, the role of lymphocyte subsets and cytokines at the beginning of neoplastic diseases is now incontestable. In this review, we have concentrated our attention on the equilibrium between the diverse lymphocyte subsets and the cytokine system and summarized the current state of knowledge, providing an overview of the condition of the entire system in MGUS and MM. In an age where the therapy of neoplastic monoclonal gammopathies largely relies on drugs capable of acting on the immune system (immunomodulants, immunological checkpoint inhibitors, CAR-T), detailed knowledge of the the differences existing in benign and neoplastic forms of gammopathy is the main foundation for the adequate and optimal use of new drugs