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Fe3O4 magnetic nanoparticles (Fe3O4-MNPs) have been widely used in clinical diagnosis. Hemocompatibility of the nanoparticles is usually evaluated by hemolysis. However, hemolysis assessment does not measure the dysfunctional erythrocytes with pathological changes on the unbroken cellular membrane. The aim of this study is to evaluate the use of suicidal death of erythrocytes (i.e. eryptosis indices) as a novel predictive and prognostic parameter, and to determine the impact of Fe3O4-MNPs on cellular membrane structure and the rheology properties of blood in circulation. Our results showed that phosphatidylserine externalization assessment was significantly more sensitive than classical hemolysis testing in evaluating hemocompatibility. Although no remarkable changes of histopathology, hematology and serum biochemistry indices were observed in vivo, Fe3O4-MNPs significantly affected hemorheology indices including erythrocyte deformation index, erythrocyte rigidity index, red blood cell aggregation index, and erythrocyte electrophoresis time, which are related to the mechanical properties of the erythrocytes. Oxidative stress induced calcium influx played a critical role in the eryptotic activity of Fe3O4-MNPs. This study demonstrated that Fe3O4-MNPs cause eryptosis and changes in flow properties of blood, suggesting that phosphatidylserine externalization can serve as a predictive parameter for hemocompatibility assay.

Abstract(K,Na)NbO3 based ceramics are considered to be one of the most promising lead-free ferroelectrics replacing Pb(Zr,Ti)O3. Despite extensive studies over the last two decades, the mechanism for the enhanced piezoelectricity in multi-elements doped (K,Na)NbO3 ceramics has not been fully understood. Here, we combine temperature-dependent synchrotron x-ray diffraction and property measurements, atomic-scale scanning transmission electron microscopy, and first-principle and phase-field calculations to establish the dopant–structure–property relationship for multi-elements doped (K,Na)NbO3 ceramics. Our results indicate that the dopants induced tetragonal phase and the accompanying high-density nanoscale heterostructures with low-angle polar vectors are responsible for the high dielectric and piezoelectric properties. This work explains the mechanism of the high piezoelectricity recently achieved in (K,Na)NbO3 ceramics and provides guidance for the design of high-performance ferroelectric ceramics, which is expected to benefit numerous functional materials.

Advances in nanotechnology have empowered the design of bionanomaterials by assembling different types of natural biomolecules (e.g., nucleic acids, proteins, and lipids) as building blocks into nanoparticles (NPs) of 1−100 nm in diameter. Such bionanomaterials form the basis of useful nanomedicine applications, such as targeted delivery, gene regulation, molecular diagnostics, and immunomodulation. To achieve optimal performance in these applications, it is imperative that the NPs be delivered effectively to the organs, tissues, and cells of interest. A rational approach to facilitating the delivery of NPs is to develop a detailed and comprehensive understanding in their fundamental interactions with the biological system (or nano−bio interactions). Rigorous nano−bio research can provide mechanistic insights for circumventing the bottlenecks associated with inefficient and nonspecific delivery of NPs, catalyzing the clinical translation of nanomedicines. Cationic liposomes and lipid NPs are conventional carriers of therapeutic cargoes into cells due to their high ability to penetrate the cell membrane, a barrier comprised by an anionic phospholipid bilayer. Yet, cationic NPs tend to cause cytotoxicity and immune responses that may hamper their clinical translation. Contrary to cationic NPs, non-cationic NPs (be they near-neutral or anionic in surface charge) generally exhibit higher biocompatibility but enter mammalian cells in much less pronounced amounts. Intriguingly, some types of non-cationic NPs exhibit high biocompatibility and cellular uptake properties, all attractive features for intracellular delivery. In this Account, we present our studies of the interactions of non-cationic bionanomaterials with cells (or nano−cell interactions). To start with, we introduce the use of near-neutral poly(ethylene glycol)-coated NPs for probing the roles of two rarely explored physicochemical parameters on cellular uptake, namely, extracellular compression and alkylation. We next present the nano−cell interactions of two representative types of anionic bionanomaterials that effectively enter mammalian cells and have found widespread applications in the past decade, including DNA-coated NPs and polydopamine (PDA)-coated NPs. In our cell-based studies, we dissect the route of intracellular trafficking, pathway proteins that dictate cellular uptake, and trafficking of NPs. We further touch on our recent quantitative analysis of the cellular-level distribution of NPs in various organs and tissues of diseased animal models. Our results offer important design rules of NPs for achieving effective intracellular delivery and may even guide us to explore nanomedicine applications that we did not conceive before, such as using DNAcoated NPs for targeting atherosclerotic plaques and PDA-coated plasmonic nanoworms for photothermal killing of cancer cells. We conclude with our perspectives in elucidating nano−bio interactions via a reductionist approach, calling for closer attention to the role of functional groups and more refined...

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Perventricular device closure of pmVSDs appears safe and effective with symmetric and asymmetric occluders. However, the lower residual shunt disappearance and higher branch block incidence rates for asymmetric occluders would favour more proactive conversion to surgical repair immediately when residual shunt is present intraoperatively.

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