Circular Reprocessing of Thermoset Polyurethane Foams.

Thermoset polyurethane (PU) foams are widely used in industrial applications, but they cannot be recycled by conventional melt reprocessing because of their cross-linked structures. The introduction of carbamate exchange catalysts converts thermoset PU into covalent adaptable networks (CANs), which are amenable to reprocessing at elevated temperatures. However, this approach has produced solid PU films, which have fewer uses and lower commercial demand. In this work, simultaneous reprocessing and refoaming of thermoset PU foams is demonstrated by leveraging the melt-processability of PU CANs and allowing cell growth by gas generation in a twin-screw extruder. The optimal operating temperature of the refoaming process is determined through chemical, thermal, and structural analysis of PU foam extrudates. The foam-to-foam extrusion process produces controllable, continuous, and uniform foam structures, as characterized by cell diameter and cell number density. Low-density PU foams are obtained through a process simulating injection molding. The compression properties of reprocessed PU foam are compared with as-synthesized PU foam to demonstrate efficacy of the refoaming processes. These results demonstrate that PU foams can be prepared through recycling while maintaining microstructural and chemical integrity. In the future, this strategy may be applied to thermoset PU foams of various chemical compositions and shows promise for scalability.

Miniaturized MR-compatible ultrasound system for real-time monitoring of acoustic effects in mice using high-resolution MRI.

Visualization of focused ultrasound in high spatial and temporal resolution is crucial for accurately and precisely targeting brain regions noninvasively. Magnetic resonance imaging (MRI) is the most widely used noninvasive tool for whole-brain imaging. However, focused ultrasound studies employing high-resolution (> 9.4 T) MRI in small animals are limited by the small size of the radiofrequency (RF) volume coil and the noise sensitivity of the image to external systems such as bulky ultrasound transducers. This technical note reports a miniaturized ultrasound transducer system packaged directly above a mouse brain for monitoring ultrasound-induced effects using high-resolution 9.4 T MRI. Our miniaturized system integrates MR-compatible materials with electromagnetic (EM) noise reduction techniques to demonstrate echo-planar imaging (EPI) signal changes in the mouse brain at various ultrasound acoustic intensities. The proposed ultrasound-MRI system will enable extensive research in the expanding field of ultrasound therapeutics.

Spatiotemporally controlled drug delivery via photothermally driven conformational change of self-integrated plasmonic hybrid nanogels.

BACKGROUND: Spatiotemporal regulation is one of the major considerations for developing a controlled and targeted drug delivery system to treat diseases efficiently. Light-responsive plasmonic nanostructures take advantage due to their tunable optical and photothermal properties by changing size, shape, and spatial arrangement. RESULTS: In this study, self-integrated plasmonic hybrid nanogels (PHNs) are developed for spatiotemporally controllable drug delivery through light-driven conformational change and photothermally-boosted endosomal escape. PHNs are easily synthesized through the simultaneous integration of gold nanoparticles (GNPs), thermo-responsive poly (N-isopropyl acrylamide), and linker molecules during polymerization. Wave-optic simulations reveal that the size of the PHNs and the density of the integrated GNPs are crucial factors in modulating photothermal conversion. Several linkers with varying molecular weights are inserted for the optimal PHNs, and the alginate-linked PHN (A-PHN) achieves more than twofold enhanced heat conversion compared with others. Since light-mediated conformational changes occur transiently, drug delivery is achieved in a spatiotemporally controlled manner. Furthermore, light-induced heat generation from cellular internalized A-PHNs enables pinpoint cytosolic delivery through the endosomal rupture. Finally, the deeper penetration for the enhanced delivery efficiency by A-PHNs is validated using multicellular spheroid. CONCLUSION: This study offers a strategy for synthesizing light-responsive nanocarriers and an in-depth understanding of light-modulated site-specific drug delivery.

Multifocal skull-compensated transcranial focused ultrasound system for neuromodulation applications based on acoustic holography.

Transcranial focused ultrasound stimulation is a promising therapeutic modality for human brain disorders because of its noninvasiveness, long penetration depth, and versatile spatial control capability through beamforming and beam steering. However, the skull presents a major hurdle for successful applications of ultrasound stimulation. Specifically, skull-induced focal aberration limits the capability for accurate and versatile targeting of brain subregions. In addition, there lacks a fully functional preclinical neuromodulation system suitable to conduct behavioral studies. Here, we report a miniature ultrasound system for neuromodulation applications that is capable of highly accurate multiregion targeting based on acoustic holography. Our work includes the design and implementation of an acoustic lens for targeting brain regions with compensation for skull aberration through time-reversal recording and a phase conjugation mirror. Moreover, we utilize MEMS and 3D-printing technology to implement a 0.75-g lightweight neuromodulation system and present in vivo characterization of the packaged system in freely moving mice. This preclinical system is capable of accurately targeting the desired individual or multitude of brain regions, which will enable versatile and explorative behavior studies using ultrasound neuromodulation to facilitate widespread clinical adoption.

Calcium-Modified Silk Patch as a Next-Generation Ultrasound Coupling Medium.

There is an increasing interest in developing next-generation wearable ultrasound patch systems because of their wide range of applications, such as home healthcare systems and continuous monitoring systems for physiological conditions. A wearable ultrasound patch system requires a stable interface to the skin, an ultrasound coupling medium, a flexible transducer array, and miniaturized operating circuitries. In this study, we proposed a patch composed of calcium (Ca)-modified silk, which serves as both a stable interface and a coupling medium for ultrasound transducer arrays. The Ca-modified silk patch provided not only a stable and conformal interface between the epidermal ultrasound transducer and human skin with high adhesion but also offered acoustic impedance close to that of human skin. The Ca-modified silk patch was flexible and stretchable (∼400% strain) and could be attached to various materials. In addition, because the acoustic impedance of the Ca-modified silk patch was 2.15 MRayl, which was similar to that of human skin (1.99 MRayl), the ultrasound transmission loss of the proposed patch was relatively low (∼0.002 dB). We also verified the use of the Ca-modified silk patch in various ultrasound applications, including ultrasound imaging, ultrasound heating, and transcranial ultrasound stimulation for neuromodulation. The comparable performance of the Ca-modified patch to that of a commercial ultrasound gel and its durability against various environmental conditions confirmed that the Ca-modified silk patch could be a promising candidate as a coupling medium for next-generation ultrasound patch systems.

Inhibitory role of AMP­activated protein kinase in necroptosis of HCT116 colon cancer cells with p53 null mutation under nutrient starvation.

Simultaneous induction of other types of programmed cell death, alongside apoptosis, in cancer cells may be considered an attractive strategy for the development of more effective anticancer therapies. The present study aimed to investigate the role of AMP­activated protein kinase (AMPK) in nutrient/serum starvation­induced necroptosis, which is a programmed form of necrosis, in the presence or absence of p53. The present study detected higher cell proliferation and lower cell death rates in the HCT116 human colon cancer cell line containing a p53 null mutation (HCT116 p53­/­) compared with in HCT116 cells harboring wild­type p53 (HCT116 p53+/+), as determined using a cell viability assay. Notably, western blot analysis revealed a relatively lower level of necroptosis in HCT116 p53­/­ cells compared with in HCT116 p53+/+ cells. Investigating the mechanism, it was revealed that necroptosis may be induced in HCT116 p53+/+ cells by significantly increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP), whereas little alterations were detected in HCT116 p53­/­ cells. Unexpectedly, a much lower level of ATP was detected in HCT116 p53­/­ cells compared with in HCT116 p53+/+ cells. Accordingly, AMPK phosphorylation on the Thr172 residue was markedly increased in HCT116 p53­/­ cells. Furthermore, western blot analysis and ROS measurements indicated that AMPK inhibition, using dorsomorphin dihydrochloride, accelerated necroptosis by increasing ROS generation in HCT116 p53­/­ cells. However, AMPK activation by AICAR did not suppress necroptosis in HCT116 p53+/+ cells. In conclusion, these data strongly suggested that AMPK activation may be enhanced in HCT116 p53­/­ cells under serum­depleted conditions via a drop in cellular ATP levels. In addition, activated AMPK may be at least partially responsible for the inhibition of necroptosis in HCT116 p53­/­ cells, but not in HCT116 p53+/+cells.

Anticancer activity of gomisin J from Schisandra chinensis fruit.

In attempting to identify effective anticancer drugs from natural products that are harmless to humans, we found that the gomisin J from Schisandra chinensis fruit has anticancer activity. Schisandra chinensis fruits are used in traditional herbal medicine and gomisin J is one of their chemical constituents. In the present study, we examined the anticancer activity of gomisin J in MCF7 and MDA-MB-231 breast cancer cell lines and in MCF10A normal cell line, in a time- and concentration-dependent manner. Our data revealed that gomisin J exerted a much stronger cytotoxic effect on MCF7 and MDA-MB-231 cancer cells than on MCF10A normal cells. Gomisin J suppressed the proliferation and decreased the viability of MCF7 and MDA-MB-231 cells at relatively low (<10 µg/ml) and high (>30 µg/ml) concentrations, respectively. Our data also revealed that gomisin J induced necroptosis, a programmed form of necrosis, as well as apoptosis. Notably, gomisin J predominantly induced necroptosis in MCF7 cells that are known to have high resistance to many pro-apoptotic anticancer drugs, while MDA-MB-231 exhibited a much lower level of necroptosis but instead a higher level of apoptosis. This data indicated the possibility that it may be used as a more effective anticancer drug, especially in apoptosis-resistant malignant cancer cells. In an extended study, gomisin J exhibited a strong cytotoxic effect on all tested various types of 13 cancer cell lines, indicating its potential to be used against a wide range of different types of cancer cells.

Evidence-based approaches for establishing the 2015 Dietary Reference Intakes for Koreans.

BACKGROUND/OBJECTIVES: The Dietary Reference Intakes for Koreans (KDRIs), a set of reference intake values, have served as a basis for guiding a balanced diet that promotes health and prevents disease in the general Korean population. In the process of developing DRIs, a systematic review has played an important role in helping the DRI committees make evidence-based and transparent decisions for updating the next DRIs. Thus, the 2015 KDRI steering committee applied the systematic review framework to the revision process of the KDRIs. The purpose of this article is to summarize the revision process for the 2015 KDRIs by focusing on the systematic review framework. MATERIALS/METHODS: The methods used to develop the systematic review framework for 2015 KDRIs followed the Agency for Healthcare Research and Quality (AHRQ) and the Tufts Evidence-based Practice Center (EPC). The framework for systematic review of the 2015 KDRIs comprised of the 3 following steps: (1) development of an analytic framework and refinement of key questions and search terms; (2) literature search and data extraction; and, (3) appraisal of the literature and summarizing the results. RESULTS: A total of 203,237 studies were retrieved through the above procedure, with 2,324 of these studies included in the analysis. General information, main results, comments of reviewers, and results of quality assessment were extracted and organized by study design. The average points of quality appraisals were 3.0 (range, 0-5) points for intervention, 6.1 (0-9) points for cohort, 6.0 (3-9) points for nested case-control, 5.4 (1-8) points for case-control, 14.6 (0-22) points for cross-sectional studies, and 7.0 (0-11) points for reviews. CONCLUSIONS: Systematic review helped to establish the 2015 KDRIs as a useful tool for evidence-based approach. Collaborative efforts to improve the framework for systematic review should be continued for future KDRIs.

Anti-cancerous effect of cis-khellactone from Angelica amurensis through the induction of three programmed cell deaths.

Angelica amurensis has traditionally been used to treat various medical problems. In this report, we introduce cis-khellactone as a new anti-cancer agent, which was isolated from the chloroform soluble fraction of the rhizomes of Angelica amurensis. Its anti-cancerous effect was at first tested in MCF7 and MDA-MB-231 breast cell lines, in which MCF7 is well known to be resistant to many anti-cancer drugs; MCF10A normal breast cell line was used as a control. In vitro experiments showed that cis-khellactone suppressed cell growth and proliferation at a relatively low concentrations (<5 µg/ml) and decreased cell viability at high concentrations (>10 µg/ml) in both cancer cell lines in a time- and concentration-dependent manner. This anti-cancerous effect was also checked in additional 16 different types of normal and cancer cell lines. Cis-khellactone treatment significantly suppressed cell proliferation and enhanced cell death in all tested cancer cell lines. Furthermore, Western blot analysis showed that cis-khellactone induced three types of programmed cell death (PCD): apoptosis, autophagy-mediated cell death, and necrosis/necroptosis. Cis-khellactone concentration-dependently decreased cell viability by increasing the level of reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP), which are related to all three types of PCD. Mitochondrial fractionation data revealed that cis-khellactone induced the translocation of BAX and BAK into mitochondria as well as the overexpression of VDAC1, which probably accelerates MMP disruption and finally cell death. Importantly, our extended in vivo studies with xenograft model further confirmed these findings of anti-cancerous effects and showed no harmful effects in normal tissues, suggesting that there would be no side effects in humans.

Controllable one-step double emulsion formation via phase inversion.

Double emulsions, the simplest form of multiple emulsion, have been intensively utilized in various industries as well as in fundamental research. A variety of strategies to effectively form double emulsions have been developed, but no simple yet controlled and scalable technique has been achieved yet. Herein, we examine the mechanism of the entire process of double emulsion formation by phase inversion, and we propose a universal one-step strategy for the formation of an oil/water/oil double emulsion using oil soluble polymers and hydrophobic silica nanoparticles. We demonstrate that this new approach enables control of both the fraction and the number of inner small droplets; even high internal phase double emulsions could be achieved.

Total Antioxidant Capacity from Dietary Supplement Decreases the Likelihood of Having Metabolic Syndrome in Korean Adults.

This study was conducted to estimate antioxidant vitamin intake and total antioxidant capacity (TAC) from diet and dietary supplements and to examine their association with metabolic syndrome (MetS) in Korean adults. Out of 6308 adults 19~64 years old from the 2010~2011 Korea National Health and Nutrition Examination Survey, 1847 adults were classified as dietary supplement users and the other 4461 adults were classified as non-users. Antioxidant intake and TAC from diet and dietary supplements were estimated using dietary intake data and linked with the antioxidant and TAC database for common Korean foods. The prevalence of MetS was lower in dietary supplement users (odds ratio (OR) = 0.82; 95% confidence interval (CI), 0.68-0.98) than that in non-users. Among dietary supplement users, a lower prevalence of MetS was observed in the highest tertile for vitamin A (OR = 0.72; 95% CI, 0.53-0.99) and vitamin E (OR = 0.74; 95% CI, 0.55- 0.99) intake than that in the lowest tertile among non-users. Subjects in the highest tertile of TAC among dietary supplement users showed a lower prevalence of MetS (OR = 0.72; 95% CI, 0.52-0.99) than non-users. The results imply that intake of vitamin A, vitamin E, and TAC from dietary supplements might have a protective effect on MetS among Korean adults.

Processable high internal phase Pickering emulsions using depletion attraction.

High internal phase emulsions have been widely used as templates for various porous materials, but special strategies are required to form, in particular, particle-covered ones that have been more difficult to obtain. Here, we report a versatile strategy to produce a stable high internal phase Pickering emulsion by exploiting a depletion interaction between an emulsion droplet and a particle using water-soluble polymers as a depletant. This attractive interaction facilitating the adsorption of particles onto the droplet interface and simultaneously suppressing desorption once adsorbed. This technique can be universally applied to nearly any kind of particle to stabilize an interface with the help of various non- or weakly adsorbing polymers as a depletant, which can be solidified to provide porous materials for many applications.

Self-assembly of core-shell structures driven by low doping limit of Ti in LiCoO2: first-principles thermodynamic and experimental investigation.

Introducing additives is a general method of performance improvement in materials engineering, but details regarding whether the additive is doped in the host crystal or present as a secondary phase are usually examined from experimental experience, with a systematic theoretical prediction lacking, which sometimes causes controversy on the role of additives. In this study, the dopability of Ti in crystalline LiCoO2 (LCO) is investigated by a first-principles simulation method, and the doping limit is quantitatively calculated. The probability of Ti substitution for Co is examined and related to point-defect formation in LCO as a function of the general experimental variables of temperature and gas-phase partial pressures, enabling practical use of the theoretical model for real experiments. It was found that Ti substitution for Co, accompanied by the formation of a Li vacancy, is the most probable Ti doping form in LCO, but the doping limit is very low and most Ti would segregate into secondary phases. The theoretical prediction showed good agreement with the experimental results. Based on theoretical predictions, particles having LCO cores and Ti-rich shells are obtained from a simple sol-gel route followed by one-step firing without additional surface treatment. The high-voltage cyclability of LCO is greatly improved. The method demonstrated in this study may be a useful tool for screening suitable coating or doping elements for various material systems and provide a guide for designing simple spontaneous coating processes, as in this study.