Bubble formation in nanopores: a matter of hydrophobicity, geometry, and size

This review focuses on the phase behaviour of liquids in nanoscale confinement, which promotes drying by a combination of hydrophobicity, small size, and high degree of confinement. In these conditions, the vapour phase can form at exceptionally large pressures or low temperatures as compared to bulk vaporisation, giving rise to the unexpected formation of bubbles. A general framework is introduced which allows to understand the main effects of confinement on the thermodynamics and on the kinetics of drying. The relevance of such phenomena is discussed in the realm of biological nanopores, specifically ion channels, and in nanoporous materials. The emergence of nanoscale effects not accounted for in macroscopic theories is discussed together with the open challenges in this rapidly expanding field

Integrated approach including docking, MD simulations, and network analysis highlights the action mechanism of the cardiac hERG activator RPR260243

hERG is a voltage-gated potassium channel involved in the heart contraction whose defections are associated with the cardiac arrhythmia Long QT Syndrome type 2. The activator RPR260243 (RPR) represents a possible candidate to pharmacologically treat LQTS2 because it enhances the opening of the channel. However, the molecular detail of its action mechanism remains quite elusive. Here, we address the problem using a combination of docking, molecular dynamics simulations, and network analysis. We show that the drug preferably binds at the interface between the voltage sensor and the pore, enhancing the canonical activation path and determining a whole-structure rearrangement of the channel that slightly impairs inactivation

Apoptotic effects on HL60 human leukaemia cells induced by lavandin essential oil treatment

Recent scientific investigations have reported a number of essential oils to interfere with intracellular signalling pathways and to induce apoptosis in different cancer cell types. In this paper, Lavandin Essential Oil (LEO), a natural sterile hybrid obtained by cross-breeding L. angustifolia × L. latifolia, was tested on human leukaemia cells (HL60). Based on the MTT results, the reduced cell viability of HL60 cells was further investigated to determine whether cell death was related to the apoptotic process. HL60 cells treated for 24 h with LEO were processed by flow cytometry, and the presence of Annexin V was measured. The activation of caspases-3 was evaluated by western blot and immunofluorescence techniques. Treated cells were also examined by scanning and transmission electron microscopy to establish the possible occurrence of morphological alterations during the apoptotic process. LEO main compounds, such as linalool, linalyl acetate, 1,8-cineole, and terpinen-4-ol, were also investigated by MTT and flow cytometry analysis. The set of obtained results showed that LEO treatments induced apoptosis in a dose-dependent, but not time-dependent, manner on HL60 cells, while among LEO main compounds, both terpinen-4-ol and linalyl acetate were able to induce apoptosis

Two-steps versus one-step solidification pathways of binary metallic nanodroplet

The solidification of AgCo, AgNi, and AgCu nanodroplets is studied by molecular dynamics simulations in the size range of 2-8 nm. All these systems tend to phase separate in the bulk solid with surface segregation of Ag. Despite these similarities, the simulations reveal clear differences in the solidification pathways. AgCo and AgNi already separate in the liquid phase, and they solidify in configurations close to equilibrium. They can show a two-step solidification process in which Co-/Ni-rich parts solidify at higher temperatures than the Ag-rich part. AgCu does not separate in the liquid and solidifies in one step, thereby remaining in a kinetically trapped state down to room temperature. The solidification mechanisms and the size dependence of the solidification temperatures are analyzed, finding qualitatively different behaviors in AgCo/AgNi compared to AgCu. These differences are rationalized by an analytical model

Early thromboelastography in acute traumatic coagulopathy: an observational study focusing on pre-hospital trauma care

Background: Major brain injury and uncontrolled blood loss remain the primary causes of early trauma-related mortality. One-quarter to one-third of trauma patients exhibit trauma-induced coagulopathy (TIC). Thromboelastometry (ROTEM) and thrombelastography (TEG) are valuable alternatives to standard coagulation testing, providing a more comprehensive overview of the coagulation process. Purpose: Evaluating thromboelastographic profile, the incidence of fibrinolysis (defined as Ly30 > 3%) in severe trauma patients, and factors influencing pathological coagulation pattern. Methods: Prospective observational 2\ua0years cohort study on severe trauma patients assisted by Helicopter Emergency Medical System (HEMS) and Level 1 Trauma Center, in a tertiary referral University Hospital. Results: Eighty three patients were enrolled, mean NISS (new injury severity score) 36 (\ub1 13). Mean R value decreased from 7.25 (\ub1 2.6) to 6.19 (\ub1 2.5) min (p 40 groups, changes in R value increased their significance (p = 0.04 and p < 0.03, respectively). Pathological TEG was found in 71 (88.8%) patients at T0 and 74 (92.5%) at T1. Hypercoagulation was present in 57 (71.3%) patients at T0, and in 66(82.5%) at T1. 9 (11.3%) patients had hyperfibrinolysis at T0, 7 (8.8%) patients at T1. Prevalence of StO2 < 75% at T0 was greater in patients whose TEG worsened (7 patients, 46.7%) against whose TEG remained stable or improved (8 patients, 17.4%) from T0 to T1 (p = 0.02). 48 (57.8%) patients received < 1000\ua0mL of fluids, while 35 (42.2%) received 65 1000\ua0mL. The first group had fewer patients with hypercoagulation (20, 41.6%) than the second (6, 17.6%) at T1 (p < 0.03). No differences were found for same TEG pattern at T0, nor other TEG pattern. Conclusion: Our population is representative of a non-hemorrhagic severe injury subgroup. Almost all of our trauma population had coagulation abnormalities immediately after the trauma; pro-coagulant changes were the most represented regardless of the severity of injury. NISS appears to affect only R parameter on TEG. Hyperfibrinolysis has been found in a low percentage of patients. Hypoperfusion parameters do not help to identify patients with ongoing coagulation impairment. Small volume resuscitation and mild hypotermia does not affect coagulation, at least in the early post-traumatic phase

Dysfunctional mitochondria accumulate in a skeletal muscle knockout model of Smn1, the causal gene of spinal muscular atrophy

The approved gene therapies for spinal muscular atrophy (SMA), caused by loss of survival motor neuron 1 (SMN1), greatly ameliorate SMA natural history but are not curative. These therapies primarily target motor neurons, but SMN1 loss has detrimental effects beyond motor neurons and especially in muscle. Here we show that SMN loss in mouse skeletal muscle leads to accumulation of dysfunctional mitochondria. Expression profiling of single myofibers from a muscle specific Smn1 knockout mouse model revealed down-regulation of mitochondrial and lysosomal genes. Albeit levels of proteins that mark mitochondria for mitophagy were increased, morphologically deranged mitochondria with impaired complex I and IV activity and respiration and that produced excess reactive oxygen species accumulated in Smn1 knockout muscles, because of the lysosomal dysfunction highlighted by the transcriptional profiling. Amniotic fluid stem cells transplantation that corrects the SMN knockout mouse myopathic phenotype restored mitochondrial morphology and expression of mitochondrial genes. Thus, targeting muscle mitochondrial dysfunction in SMA may complement the current gene therapy

In vitro comparative study on the mechanical behavior of Zirconia and Polyetheretherketone in applied dental sciences

OBJECTIVE: Recently, Zirconia and polyaryletherketone (PEEK) have attracted increasing interest as reliable and safe materials in dental applications, mainly because of their good biomechanical characteristics. The aim of this study was to investigate the response to different loads by prosthetic frameworks for supported fixed partial dentures (FPDs), thus simulating osseointegrated implants. MATERIALS AND METHODS: The specimens were divided into two groups (n= 5 each). Group A: FDPs in zirconia-ceramic; Group B: FDPs in PEEK-composite. These 2 groups were subjected to vertical loads so to evaluate structural deformation; then, they have been analyzed by scanning electron microscopy (SEM) at different magnifications. RESULTS: In tested samples, different types of mechanical failures have been observed. In Zirconia-specimens, chipping is the main failure noticed in this study, mostly in distal margins of the structure. Also, peek-specimens show failure and fracture. CONCLUSIONS: Zirconia and PEEK could be considered both good materials, but several investigations are needed to use these materials as an alternative to metals for fixed partial dentures

Deletion of small ankyrin 1 (SANK1) isoforms results in structural and functional alterations in aging skeletal muscle fibers

Muscle-specific ankyrins 1 (sAnk1) are a group of small ankyrin 1 isoforms, of which sAnk1.5 is the most abundant. sAnk1 are localized in the sarcoplasmic reticulum (SR) membrane from where they interact with obscurin, a myofibrillar protein. This interaction appears to contribute to stabilize the SR close to the myofibrils. Here we report the structural and functional characterization of skeletal muscles from sAnk1 knockout mice (KO). Deletion of sAnk1 did not change the expression and localization of SR proteins in 4- to 6-mo-old sAnk1 KO mice. Structurally, the main modification observed in skeletal muscles of adult sAnk1 KO mice (4\u20136 mo of age) was the reduction of SR volume at the sarcomere A band level. With increasing age (at 12\u201315 mo of age) extensor digitorum longus (EDL) skeletal muscles of sAnk1 KO mice develop prematurely large tubular aggregates, whereas diaphragm undergoes significant structural damage. Parallel functional studies revealed specific changes in the contractile performance of muscles from sAnk1 KO mice and a reduced exercise tolerance in an endurance test on treadmill compared with control mice. Moreover, reduced Q\u3b3 charge and L-type Ca2+ current, which are indexes of affected excitation-contraction coupling, were observed in diaphragm fibers from 12- to 15-mo-old mice, but not in other skeletal muscles from sAnk1 KO mice. Altogether, these findings show that the ablation of sAnk1, by altering the organization of the SR, renders skeletal muscles susceptible to undergo structural and functional alterations more evident with age, and point to an important contribution of sAnk1 to the maintenance of the longitudinal SR architecture