Optimal Design of Silicon-based Chips for Piezo-induced Ultrasound Resonances in Embedded Microchannels

AbstractWe present a variational formulation of the governing equations and introduce global indicators to describe the behavior of acoustofluidic devices driven at resonance frequencies by means of a piezoelectric transducer. The individuation of the correct Lagrangian densities for the different parts constituting the device (the piezo transducer, the silicon walls, the fluid-filled microchannel, and the glass lid) allows for the introduction of the weak formulation used in the finite element discretization of the equations describing the system in its oscillatory regime. Additionally, the knowledge of the Lagrangian density leads to the derivation of the correct structure of the Hamiltonian density, i.e. the energy density, which is important for the quantification of the energy content of the whole system and its individual parts. Specifically, the energy content of the embedded microchannel is quantified by means of the acoustofluidic yield η defined as the ratio between the energy in the channel and the total energy. From the standpoint of acoustophoretic application, the introduction of the acoustophoretic mean orientation allows us to identify the frequencies for which an acoustophoretic effect, i.e. the lateral motion of particle dragged by the axial main flow, is particularly strong. Finally, the connection between the mechanical and electrical degrees of freedom of the system is addressed. This is important for proper determination of the dissipated power, and it may lead to the detection of resonance states by means of purely electrical measurements. Numerical simulations and preliminary experimental results show some features of the model introduced

Local behavior of p-harmonic Green's functions in metric spaces

We describe the behavior of p-harmonic Green's functions near a singularity in metric measure spaces equipped with a doubling measure and supporting a Poincar\'e inequality

Targeting lipid rafts as a strategy against coronavirus

Lipid rafts are functional membrane microdomains containing sphingolipids, including gangliosides, and cholesterol. These regions are characterized by highly ordered and tightly packed lipid molecules. Several studies revealed that lipid rafts are involved in life cycle of different viruses, including coronaviruses. Among these recently emerged the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The main receptor for SARS-CoV-2 is represented by the angiotensin-converting enzyme-2 (ACE-2), although it also binds to sialic acids linked to host cell surface gangliosides. A new type of ganglioside-binding domain within the N-terminal portion of the SARS-CoV-2 spike protein was identified. Lipid rafts provide a suitable platform able to concentrate ACE-2 receptor on host cell membranes where they may interact with the spike protein on viral envelope. This review is focused on selective targeting lipid rafts components as a strategy against coronavirus. Indeed, cholesterol-binding agents, including statins or methyl-β-cyclodextrin (MβCD), can affect cholesterol, causing disruption of lipid rafts, consequently impairing coronavirus adhesion and binding. Moreover, these compounds can block downstream key molecules in virus infectivity, reducing the levels of proinflammatory molecules [tumor necrosis factor alpha (TNF-α), interleukin (IL)-6], and/or affecting the autophagic process involved in both viral replication and clearance. Furthermore, cyclodextrins can assemble into complexes with various drugs to form host–guest inclusions and may be used as pharmaceutical excipients of antiviral compounds, such as lopinavir and remdesivir, by improving bioavailability and solubility. In conclusion, the role of lipid rafts-affecting drugs in the process of coronavirus entry into the host cells prompts to introduce a new potential task in the pharmacological approach against coronavirus

Advances in the Pathophysiology of Thrombosis in Antiphospholipid Syndrome. Molecular Mechanisms and Signaling through Lipid Rafts

The pathological features of antiphospholipid syndrome (APS) are related to the activity of circulating antiphospholipid antibodies (aPLs) associated with vascular thrombosis and obstetric complications. Indeed, aPLs are not only disease markers, but also play a determining pathogenetic role in APS and exert their effects through the activation of cells and coagulation factors and inflammatory mediators for the materialization of the thromboinflammatory pathogenetic mechanism. Cellular activation in APS necessarily involves the interaction of aPLs with target receptors on the cell membrane, capable of triggering the signal transduction pathway(s). This interaction occurs at specific microdomains of the cell plasma membrane called lipid rafts. In this review, we focus on the key role of lipid rafts as signaling platforms in the pathogenesis of APS, and propose this pathogenetic step as a strategic target of new therapies in order to improve classical anti-thrombotic approaches with "new " immunomodulatory drugs

The role of cardiolipin as a scaffold mitochondrial phospholipid in autophagosome formation: In vitro evidence

Cardiolipin (CL) is a hallmark phospholipid localized within the inner mitochondrial membrane. Upon several mitochondrial stress conditions, CL is translocated to specialized plat-forms, where it may play a role in signaling events to promote mitophagy and apoptosis. Recent studies characterized the molecular composition of MAM-associated lipid microdomains and their implications in regulating the autophagic process. In this study we analyzed the presence of CL within MAMs following autophagic stimulus and the possible implication of raft-like microdomains enriched in CL as a signaling platform in autophagosome formation. Human 2FTGH fibroblasts and SKNB-E-2 cells were stimulated under nutrient deprivation with HBSS. MAM fraction was obtained by an ultracentrifugation procedure and analyzed by HPTLC immunostaining. CL interactions with mitofusin2 (MFN2), calnexin (CANX) and AMBRA1 were analyzed by scanning confocal microscopy and coimmunoprecipitation. The analysis revealed that CL accumulates in MAMs fractions following autophagic stimulus, where it interacts with MFN2 and CANX. It associates with AMBRA1, which in turn interacts with BECN1 and WIPI1. This study demonstrates that CL is present in MAM fractions following autophagy triggering and interacts with the multimolecular complex (AMBRA1/BECN1/WIPI1) involved in autophagosome formation. It may have both structural and functional implications in the pathophysiology of neurodegenerative disease(s)