Solid-State Reaction Synthesis of Nanoscale Materials: Strategies and Applications.

Nanomaterials (NMs) with unique structures and compositions can give rise to exotic physicochemical properties and applications. Despite the advancement in solution-based methods, scalable access to a wide range of crystal phases and intricate compositions is still challenging. Solid-state reaction (SSR) syntheses have high potential owing to their flexibility toward multielemental phases under feasibly high temperatures and solvent-free conditions as well as their scalability and simplicity. Controlling the nanoscale features through SSRs demands a strategic nanospace-confinement approach due to the risk of heat-induced reshaping and sintering. Here, we describe advanced SSR strategies for NM synthesis, focusing on mechanistic insights, novel nanoscale phenomena, and underlying principles using a series of examples under different categories. After introducing the history of classical SSRs, key theories, and definitions central to the topic, we categorize various modern SSR strategies based on the surrounding solid-state media used for nanostructure growth, conversion, and migration under nanospace or dimensional confinement. This comprehensive review will advance the quest for new materials design, synthesis, and applications.

Atomically Conformal Metal Laminations on Plasmonic Nanocrystals for Efficient Catalysis.

Despite the enormous application potential, methods for conformal few-atomic-layer deposition on colloidal nanocrystals (NCs) are scarce. Similar to the process of lamination, we introduce a "confine and shine" strategy to homogeneously modify the different surface curvatures of plasmonic NCs with ultrathin conformal layers of diverse catalytic noble metals. This self-limited epitaxial skinlike metal growth harvests the localized surface plasmon resonance to induce reduction chemistry directly on the NC surface, confined inside hollow silica. This strategy avoids any kinetic anisotropic metal deposition. Unlike the conventional thick, anisotropic, and dendritic shells, which show severe nonradiative damping, the skinlike metal lamination preserves the key plasmonic properties of the core NCs. Consequently, the plasmonic-catalytic hybrid nanoreactors can carry out a variety of organic reactions with impressive rates.

Au/Pt-Egg-in-Nest Nanomotor for Glucose-Powered Catalytic Motion and Enhanced Molecular Transport to Living Cells.

Nanostructures converting chemical energy to mechanical work by using benign metabolic fuels, have huge implications in biomedical science. Here, we introduce Au/Pt-based Janus nanostructures, resembling to "egg-in-nest" morphology (Au/Pt-ENs), showing enhanced motion as a result of dual enzyme-relay-like catalytic cascade in physiological biomedia, and in turn showing molecular-laden transport to living cells. We developed dynamic-casting approach using silica yolk-shell nanoreactors: first, to install a large Au-seed fixing the silica-yolk aside while providing the anisotropically confined concave hollow nanospace to grow curved Pt-dendritic networks. Owing to the intimately interfaced Au and Pt catalytic sites integrated in a unique anisotropic nest-like morphology, Au/Pt-ENs exhibited high diffusion rates and displacements as the result of glucose-converted oxygen concentration gradient. High diffusiophoresis in cell culture media increased the nanomotor-membrane interaction events, in turn facilitated the cell internalization. In addition, the porous network of Au/Pt-ENs facilitated the drug-molecule cargo loading and delivery to the living cells.

Preparation of Stretchable Nanofibrous Sheets with Sacrificial Coaxial Electrospinning for Treatment of Traumatic Muscle Injury.

Traumatic muscle injury with massive loss of muscle volume requires intramuscular implantation of proper scaffolds for fast and successful recovery. Although many artificial scaffolds effectively accelerate formation and maturation of myotubes, limited studies are showing the therapeutic effect of artificial scaffolds in animal models with massive muscle injury. In this study, improved myotube differentiation is approved on stepwise stretched gelatin nanofibers and applied to damaged muscle recovery in an animal model. The gelatin nanofibers are fabricated by a two-step process composed of co-axial electrospinning of poly(ɛ-caprolactone) and gelatin and subsequent removal of the outer shells. When stepwise stretching is applied to the myoblasts on gelatin nanofibers for five days, enhanced myotube formation and polarized elongation are observed. Animal models with volumetric loss at quadriceps femoris muscles (>50%) are transplanted with the myotubes cultivated on thin and flexible gelatin nanofiber. Treated animals more efficiently recover exercising functions of the leg when myotubes and the gelatin nanofiber are co-implanted at the injury sites. This result suggests that mechanically stimulated myotubes on gelatin nanofiber is therapeutically feasible for the robust recovery of volumetric muscle loss.

Surface-Textured Mixed-Metal-Oxide Nanocrystals as Efficient Catalysts for ROS Production and Biofilm Eradication.

Next-generation catalysts are urgently needed to tackle the global challenge of antimicrobial resistance. Existing antimicrobials cannot function in the complex and stressful chemical conditions found in biofilms, and as a result, they are unable to infiltrate, diffuse into, and eradicate the biofilm and its associated matrix. Here, we introduce mixed-FeCo-oxide-based surface-textured nanostructures (MTex) as highly efficient magneto-catalytic platforms. These systems can produce defensive ROS over a broad pH range and can effectively diffuse into the biofilm and kill the embedded bacteria. Because the nanostructures are magnetic, biofilm debris can be scraped out of the microchannels. The key antifouling efficacy of MTex originates from the unique surface topography that resembles that of a ploughed field. These are captured as stable textured intermediates during the oxidative annealing and solid-state conversion of ß-FeOOH nanocrystals. These nanoscale surfaces will advance progress toward developing a broad array of new enzyme-like properties at the nanobio interface.

Early Skin Test after Anaphylaxis during Induction of Anesthesia: A Case Report.

BACKGROUND: It is recommended that a skin test be performed 4-6 weeks after anaphylaxis. However, there is little evidence about the timing of the skin test when there is a need to identify the cause within 4-6 weeks. CASE REPORT: A 57-year-old woman was scheduled to undergo surgery via a sphenoidal approach to remove a pituitary macroadenoma. Immediately after the administration of rocuronium, pulse rate increased to 120 beats/min and blood pressure dropped to 77/36 mmHg. At the same time, generalized urticaria and tongue edema were observed. Epinephrine was administered and the surgery was postponed. Reoperation was planned two weeks after the event. Four days after the anaphylactic episode, rocuronium was confirmed to be the cause by the skin prick test. Cisatracurium, which showed a negative reaction, was selected as an alternative agent for future procedures. Two weeks later, the patient underwent reoperation without any adverse events. CONCLUSIONS: The early skin test can be performed if there is a need even earlier than 4-6 weeks after anaphylaxis.

Nanocatalosomes as Plasmonic Bilayer Shells with Interlayer Catalytic Nanospaces for Solar-Light-Induced Reactions.

Interest and challenges remain in designing and synthesizing catalysts with nature-like complexity at few-nm scale to harness unprecedented functionalities by using sustainable solar light. We introduce "nanocatalosomes"-a bio-inspired bilayer-vesicular design of nanoreactor with metallic bilayer shell-in-shell structure, having numerous controllable confined cavities within few-nm interlayer space, customizable with different noble metals. The intershell-confined plasmonically coupled hot-nanospaces within the few-nm cavities play a pivotal role in harnessing catalytic effects for various organic transformations, as demonstrated by "acceptorless dehydrogenation", "Suzuki-Miyaura cross-coupling" and "alkynyl annulation" affording clean conversions and turnover frequencies (TOFs) at least one order of magnitude higher than state-of-the-art Au-nanorod-based plasmonic catalysts. This work paves the way towards next-generation nanoreactors for chemical transformations with solar energy.

Single enzyme nanoparticle, an effective tool for enzyme replacement therapy.

The term "single enzyme nanoparticle" (SEN) refers to a chemically or biologically engineered single enzyme molecule. SENs are distinguished from conventional protein nanoparticles in that they can maintain their individual structure and enzymatic activity following modification. Furthermore, SENs exhibit enhanced properties as biopharmaceuticals, such as reduced antigenicity, and increased stability and targetability, which are attributed to the introduction of specific moieties, such as poly(ethylene glycol), carbohydrates, and antibodies. Enzyme replacement therapy (ERT) is a crucial therapeutic option for controlling enzyme-deficiency-related disorders. However, the unfavorable properties of enzymes, including immunogenicity, lack of targetability, and instability, can undermine the clinical significance of ERT. As shown in the cases of Adagen®, Revcovi®, Palynziq®, and Strensiq®, SEN can be an effective technology for overcoming these obstacles. Based on these four licensed products, we expect that additional SENs will be introduced for ERT in the near future. In this article, we review the concepts and features of SENs, as well as their preparation methods. Additionally, we summarize different types of enzyme deficiency disorders and the corresponding therapeutic enzymes. Finally, we focus on the current status of SENs in ERT by reviewing FDA-approved products.

Differential characterization of hepatic tumors in MR imaging by burst-released Mn2+-ions from hollow manganese-silicate nanoparticles in the liver.

Gd3+-based contrast agents monopolize in the clinical MR imaging-based diagnosis of hepatic tumors, however, the inherent toxicity by the released Gd3+-ions triggered an urgent demand for safer alternatives. Here, we demonstrate hollow manganese silicate nanoparticles (HMS), which exert burst-release of Mn2+-ions by switching to physiological acidic condition, exhibiting high effectiveness in hepatic tumor characterization as liver-specific MR contrast agent through the in-depth in vivo MR imaging study and immunohistochemical investigations with three hepatic tumor models (e.g., hepatocellular carcinoma, neuroendocrine carcinoma, adenocarcinoma). Their characteristic time-sequential enhancement patterns in HMS-enhanced MR imaging with improved conspicuity reflect their biological features such as vascularity, cellularity, mitochondrial activity and hepatocellular specificity, and thus allow the disease-specific characterization of various hepatic tumors. HMS-enhanced MR imaging with necrotic hepatocellular carcinoma model suggested the good correlation of the extent of tumor necrosis with residual mitochondrial activity. Such multi-responsive spatio-biological distribution and function of HMS resulting in time-dependent bioimaging coupled with low systemic toxicity sets the clinical potential to accurate diagnosis and therapeutic response in various hepatic tumors.

Metal@SiO2 Core-Shells with Self-Arrested Migrating Core.

Developing easy and customizable strategies for the directional structure modulation of multicomponent nanosystems to influence and optimize their properties are a paramount but challenging task in nanoscience. Here, we demonstrate highly controlled eccentric off-center positioning of metal-core in metal@silica core-shells by utilizing an in situ generated biphasic silica-based intraparticle solid-solid interface. In the synthetic strategy, by including Ca2+-ions in silica-shell and successive oxidative and reductive annealing at high temperature, a unique hairline-biphasic interface is evolved via the heat-induced concentric radial segregation of calcium silicate phase at the interior and normal silica phase at the exterior of core-shell, which can effectively arrest the outwardly migrating metal-core within rubbery calcium silicate phase, affording various eccentric core-shells, where core-positions are flexibly controlled by the annealing time and amounts of initially added Ca2+-ions. In the structure-property correlation study, the strategy allows fine-tuning of dipolar interaction-based blocking temperatures and magnetic anisotropies of different eccentric core-shells as the function of variable off-center distance of magnetic core without changing the overall size of nanoparticles. This work demonstrates the discovery and potential application of biphasic solid-solid media interface in controlling the heat-induced migration of metal nanocrystals and opens the avenues for exploiting the rarely studied high-temperature solid-state nanocrystal conversion chemistry and migratory behavior for directional nanostructure engineering.

Functional Fragments of AIMP1-Derived Peptide (AdP) and Optimized Hydrosol for Their Topical Deposition by Box-Behnken Design.

Aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1)-derived peptide (AdP) has been developed as a cosmeceutical ingredient for skin anti-aging given its fibroblast-activating (FA) and melanocyte-inhibiting (MI) functions. However, a suitable strategy for the topical delivery of AdP was required due to its low-permeable properties. In this study, FA and MI domains of AdP (FA-AdP and MI-AdP, respectively) were determined by functional domain mapping, where the activities of several fragments of AdP on fibroblast and melanocyte were tested, and a hydrosol-based topical delivery system for these AdP fragments was prepared. The excipient composition of the hydrosol was optimized to maximize the viscosity and drying rate by using Box-Behnken design. The artificial skin deposition of FA-AdP-loaded hydrosol was evaluated using Keshary-Chien diffusion cells equipped with Strat-M membrane (STM). The quantification of the fluorescent dye-tagged FA-AdP in STM was carried out by near-infrared fluorescence imaging. The optimized hydrosol showed 127-fold higher peptide deposition in STM than free FA-AdP (p < 0.05). This work suggests that FA- and MI-AdP are active-domains for anti-wrinkle and whitening activities, respectively, and the hydrosol could be used as a promising cosmetic formulation for the delivery of AdPs to the skin.

Lessons learned from the development of health applications in a tertiary hospital.

BACKGROUND: Adoption of smart devices for hospital use has been increasing with the development of health applications (apps) for patient point-of-care and hospital management. To promote the use of health apps, we describe the lessons learned from developing 12 health apps in the largest tertiary hospital in Korea. MATERIALS AND METHODS: We reviewed and analyzed 12 routinely used apps in three categories-Smart Clinic, Smart Patient, and Smart Hospital-based on target users and functions. The log data for each app were collected from the date of release up until December 2012. RESULTS: Medical personnel accessed a mobile electronic medical record app classified as Smart Clinic an average of 452 times per day. Smart Hospital apps are actively used to communicate with each other. Patients logged on to a mobile personal health record app categorized as Smart Patient an average of 222 times per day. As the mobile trend, the choice of supporting operating system (OS) is more difficult. By developing these apps, a monitoring system is needed for evaluation. CONCLUSIONS: We described the lessons learned regarding OS support, device choice, and developmental strategy. The OS can be chosen according to market share or hospital strategic plan. Smartphones were favored compared with tablets. Alliance with an information technology company can be the best way to develop apps. Health apps designed for smart devices can be used to improve healthcare. However, to develop health apps, hospitals must define their future goals and carefully consider all the aspects.

Lysophosphatidylcholine activates adipocyte glucose uptake and lowers blood glucose levels in murine models of diabetes.

Glucose homeostasis is maintained by the orchestration of peripheral glucose utilization and hepatic glucose production, mainly by insulin. In this study, we found by utilizing a combined parallel chromatography mass profiling approach that lysophosphatidylcholine (LPC) regulates glucose levels. LPC was found to stimulate glucose uptake in 3T3-L1 adipocytes dose- and time-dependently, and this activity was found to be sensitive to variations in acyl chain lengths and to polar head group types in LPC. Treatment with LPC resulted in a significant increase in the level of GLUT4 at the plasma membranes of 3T3-L1 adipocytes. Moreover, LPC did not affect IRS-1 and AKT2 phosphorylations, and LPC-induced glucose uptake was not influenced by pretreatment with the PI 3-kinase inhibitor LY294002. However, glucose uptake stimulation by LPC was abrogated both by rottlerin (a protein kinase Cdelta inhibitor) and by the adenoviral expression of dominant negative protein kinase Cdelta. In line with its determined cellular functions, LPC was found to lower blood glucose levels in normal mice. Furthermore, LPC improved blood glucose levels in mouse models of type 1 and 2 diabetes. These results suggest that an understanding of the mode of action of LPC may provide a new perspective of glucose homeostasis.

Lysophosphatidylserine regulates blood glucose by enhancing glucose transport in myotubes and adipocytes.

Lysophosphatidylserine (LPS) is known to have diverse cellular effects, but although LPS is present in many biological fluids, its in vivo effects have not been elucidated. In the present study, we investigated the effects of LPS on glucose metabolism in vivo, and how skeletal muscle cells respond to LPS stimulation. LPS enhanced glucose uptake in a dose- and time-dependent manner in L6 GLUT4myc myotubes, and this effect of LPS on glucose uptake was mediated by a Galpha(i) and PI 3-kinase dependent signal pathway. LPS increased the level of GLUT4 on the cell surface of L6 GLUT4myc myotubes, and enhanced glucose uptake in 3T3-L1 adipocytes. In line with its cellular functions, LPS lowered blood glucose levels in normal mice, while leaving insulin secretion unaffected. LPS also had a glucose-lowering effect in STZ-treated type 1 diabetic mice and in obese db/db type 2 diabetic mice. This study shows that LPS-stimulated glucose transport both in skeletal muscle cells and adipocytes, and significantly lowered blood glucose levels both in type 1 and 2 diabetic mice. Our results suggest that LPS is involved in the regulation of glucose homeostasis in skeletal muscle and adipose tissue.