Arginine prevents thermal aggregation of hen egg white proteins

The control of aggregation and solubilization of hen egg white protein (HEWP) is an important issue for industrial applications of one of the most familiar food protein sources. Here, we investigated the effects of edible amino acids on heat-induced aggregation of HEWP. The addition of 0.6 M arginine (Arg) completely suppressed the formation of insoluble aggregates of 1 mg mL− 1 HEWP following heat treatment, even at 90 °C for 20 min. In contrast, lysine (Lys), glycine (Gly), and sodium chloride (NaCl) did little to suppress the aggregation of HEWP under the same conditions. SDS-PAGE indicated that Arg suppresses the thermal aggregation of almost all types of HEWP at 1 mg mL− 1. However, Arg did not suppress the thermal aggregation of HEWP at concentrations ≥ 10 mg mL− 1 and prompted the formation of aggregates. Transmission electron micrographs revealed a high-density structure of unfolded proteins in the presence of Arg. These results indicate that Arg exerts a greater suppressive effect on a protein mixture, such as HEWP, than on a single model protein. These observations may propose Arg as a safe and reasonable additive to HEWP for the elimination of microorganisms by allowing an increase in sterilization temperature

Slow oxidation of magnetite nanoparticles elucidates the limits of the Verwey transition

Magnetite (Fe3O4) is of fundamental importance as the original magnetic material and also for the Verwey transition near T_V = 125 K, below which a complex lattice distortion and electron orders occur. The Verwey transition is suppressed by strain or chemical doping effects giving rise to well-documented first and second-order regimes, but the origin of the order change is unclear. Here, we show that slow oxidation of monodisperse Fe3O4 nanoparticles leads to an intriguing variation of the Verwey transition that elucidates the doping effects. Exposure to various fixed oxygen pressures at ambient temperature leads to an initial drop to TV minima as low as 70 K after 45-75 days, followed by recovery to a constant value of 95 K after 160 days that persists in all experiments for aging times up to 1070 days. A physical model based on both doping and doping-gradient effects accounts quantitatively for this evolution and demonstrates that the persistent 95 K value corresponds to the lower limit for homogenously doped magnetite and hence for the first order regime. In comparison, further suppression down to 70 K results from inhomogeneous strains that characterize the second-order region. This work demonstrates that slow reactions of nanoparticles can give exquisite control and separation of homogenous and inhomogeneous doping or strain effects on an nm scale and offers opportunities for similar insights into complex electronic and magnetic phase transitions in other materials.Comment: 24 pages, 13 figures, 2 tables, the manuscript is accepted for publishing at Nature Communication

Heparin-Derived Theranostic Nanoprobes Overcome the Blood-Brain Barrier and Target Glioma in Murine Model

The poor permeability of theranostic agents across the blood-brain barrier (BBB) significantly hampers the development of new treatment modalities for neurological diseases. A new biomimetic nanocarrier is discovered using heparin (HP) that effectively passes the BBB and targets glioblastoma. Specifically, HP-coated gold nanoparticles (HP-AuNPs) are designed that are labeled with three different imaging modalities namely, fluorescein (FITC-HP-AuNP), radioisotope (68)Gallium (Ga-68-HP-AuNPs), and MRI active gadolinium (Gd-HP-AuNPs). The systemic infusion of FITC-HP-AuNPs in three different mouse strains (C57BL/6JRj, FVB, and NMRI-nude) displays excellent penetration and reveals uniform distribution of fluorescent particles in the brain parenchyma (69-86%) with some accumulation in neurons (8-18%) and microglia (4-10%). Tail-vein administration of radiolabeled Ga-68-HP-AuNPs in healthy rats also show Ga-68-HP-AuNP inside the brain parenchyma and in areas containing cerebrospinal fluid, such as the lateral ventricles, the cerebellum, and brain stem. Finally, tail-vein administration of Gd-HP-AuNPs (that displays approximate to threefold higher relaxivity than that of commercial Gd-DTPA) in an orthotopic glioblastoma (U87MG xenograft) model in nude mice demonstrates enrichment of T1-contrast at the intracranial tumor with a gradual increase in the contrast in the tumor region between 1 and 3 h. It is believed, the finding offers the untapped potential of HP-derived-NPs to deliver cargo molecules for treating neurological disorders.Peer reviewe

Giant thermal hysteresis in Verwey transition of single domain Fe3O4 nanoparticles

Most interesting phenomena of condensed matter physics originate from interactions among different degrees of freedom, making it a very intriguing yet challenging question how certain ground states emerge from only a limited number of atoms in assembly. This is especially the case for strongly correlated electron systems with overwhelming complexity. The Verwey transition of Fe3O4 is a classic example of this category, of which the origin is still elusive 80 years after the first report. Here we report, for the first time, that the Verwey transition of Fe3O4 nanoparticles exhibits size-dependent thermal hysteresis in magnetization, 57Fe NMR, and XRD measurements. The hysteresis width passes a maximum of 11 K when the size is 120 nm while dropping to only 1 K for the bulk sample. This behavior is very similar to that of magnetic coercivity and the critical sizes of the hysteresis and the magnetic single domain are identical. We interpret it as a manifestation of charge ordering and spin ordering correlation in a single domain. This work paves a new way of undertaking researches in the vibrant field of strongly correlated electron physics combined with nanoscience.Comment: 13 pages, 4 figure

Physiological impact of nanoporous acupuncture needles: Laser Doppler perfusion imaging in healthy volunteers

Background Recently, porous acupuncture (PA), which is anodized to increase its surface area for higher stimulation intensity, was developed and showed significantly improved therapeutic effects with more comfort as compared with original acupuncture (OA) in vivo. However, the impact of PA on the change of local blood flow as well as its efficacy and acceptability has not yet been confirmed in a clinical trial. In a randomized, controlled crossover clinical trial, we investigated the effects of PA on the change in local blood flow using laser Doppler perfusion imaging and considered the sensation of pain intensity and discomfort severity using a visual analogue scale (VAS) to explore its physiological impact and the possibility of PA in clinical use. Methods Twenty-one healthy participants were randomly treated with PA or OA on one side of Zusanli (ST36) and each participant served as his or her own control. Baseline local blood flow and galvanic skin response (GSR) were obtained for 5 min and acupuncture interventions were subsequently performed. Next, local blood flow and GSR were subsequently obtained for 10 min after insertion, 10 min after manipulation, and 5 min after the withdrawal of acupuncture. At the end of the experiment, participants were asked to indicate the sensation of pain intensity at each session of insertion, retention, manipulation, and withdrawal as well as the overall pain intensity and discomfort severity. Results PA significantly increased the local blood flow as compared with OA and there was no significant difference in GSR between patients treated with PA versus OA in each phase of insertion and manipulation. No significant difference in pain intensity or discomfort severity was found during manipulation, retention, or withdrawal of acupuncture. Conclusions These results indicate that PA increases local blood flow, which can be closely related to the observed enhanced performance, without any associated discomfort or pain, suggesting its applicability in clinical practice. © 2019 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.1

Polymeric Micelles with pH-Responsive Cross-Linked Core Enhance In Vivo mRNA Delivery

Messenger RNA (mRNA) is emerging as a promising therapeutic modality for a variety of diseases. Because of the fragility and limited intracellular access of mRNA, the development of delivery technologies is essential for promoting the applicability of mRNA-based treatments. Among effective nanocarriers, polymeric micelles loading mRNA by polyion complex (PIC) formation with block catiomers have the potential to meet the delivery needs. Since PICs are relatively unstable in in vivo settings, herein, we constructed mRNA-loaded micelles having pH-responsive cross-linked cores by complexing mRNA with cis-aconitic anhydride-modified poly(ethylene glycol)-poly(l-lysine) (PEG-pLL(CAA)) block copolymers. The micelles were stable at physiological pH (pH 7.4) but achieved the complete release of the mRNA at endosomal pH (pH 5.5–4.5). The cross-linking also enhanced the stability of the micelles against disassembly from polyanions and protected the loaded mRNA from degradation by nucleases. Thus, the cross-linked micelles increased the delivery of mRNA to cancer cells, promoting protein expression both in vitro and in vivo. Our results highlight the potential of PEG-pLL(CAA)-based micelles for mRNA delivery

mRNA Structuring for Stabilizing mRNA Nanocarriers and Improving Their Delivery Efficiency

For in vivo application of mRNA therapeutics, the development of mRNA nanocarriers that protect mRNA from enzymatic degradation is needed. While current nanocarrier development focuses on fine-tuning the chemical structure of its components, including lipids and polymers, herein, we propose a novel strategy to design stable mRNA nanocarriers by structuring mRNA inside the nanocarriers. Firstly, several mRNA strands were crosslinked with each other using RNA crosslinkers that hybridize to mRNA strands, to prepare mRNA nanoassemblies (NAs). Then, we mixed NAs with poly(ethylene glycol) (PEG)-polycation block copolymers to prepare core–shell-structured polyplex micelles (PMs), composed of PEG shell and mRNA-containing core. Notably, PM-loading NAs (NA/m) exhibited enhanced stability against enzymatic attack and polyion exchange reaction compared to that loading naïve mRNA (naïve/m). According to mechanistic analyses, NA/m possessed a shell with a denser PEG layer and a core with more condensed mRNA compared to naïve/m. As a result, NA/m induced more efficient protein expression after introduction to cultured cells and mouse brain, compared to naïve/m. While newly developed materials need long processes before their clinical approval, our strategy is effective in improving stability and the mRNA introduction efficiency of existing mRNA nanocarriers just by structuring mRNA without the use of additional materials

An all-joint-control master device for single-port laparoscopic surgery robots

Purpose: Robots for single-port laparoscopic surgery (SPLS) typically have all of their joints located inside abdomen during surgery, whereas with the da Vinci system, only the tip part of the robot arm is inserted and manipulated. A typical master device that controls only the tip with six degrees of freedom (DOFs) is not suitable for use with SPLS robots because of safety concerns. Methods: We designed an ergonomic six-DOF master device that can control all of the joints of an SPLS robot. We matched each joint of the master, the slave, and the human arm to decouple all-joint motions of the slave robot. Counterbalance masses were used to reduce operator fatigue. Mapping factors were determined based on kinematic analysis and were used to achieve all-joint control with minimal error at the tip of the slave robot. Results: The proposed master device has two noteworthy features: efficient joint matching to the human arm to decouple each joint motion of the slave robot and accurate mapping factors, which can minimize the trajectory error of the tips between the master and the slave. Conclusions: We confirmed that the operator can manipulate the slave robot intuitively with the master device and that both tips have similar trajectories with minimal error. © 2016, CARS.