Carbonation of a Synthetic CAF Compound by CO2 Absorption and Its Effect on Cement Matrix.

In the field of construction materials, the development of fundamental technologies to reduce energy consumption and CO2 emissions, such as manufacturing process improvement and the expanded use of alternative materials, is required. Technologies for effectively reducing energy consumption and improving CO2 absorption and reduction that can meet domestic greenhouse gas reduction targets are also required. In this study, calcium-aluminate-ferrite (CAF), a ternary system of CaO·Al2O3·Fe2O3, was sintered at a low temperature (1100 °C) to examine the possibility of CO2 adsorption, and excellent CO2 absorption performance was confirmed, as the calcite content was found to be 11.01% after 3 h of the reaction between synthetic CAF (SCAF) and CO2. In addition, the physical and carbonation characteristics were investigated with respect to the SCAF substitution rate for cement (10%, 30%, 50%, 70%, and 100%). It was found that SCAF 10% developed a compressive strength similar to that of ordinary Portland cement (OPC 100%), but the compressive strength tended to decrease as the SCAF substitution rate increased. An increase in the SCAF substitution rate led to the rapid penetration of CO2, and carbonation was observed in all the specimens after 7 days. As carbonation time increased, the CO2 diffusion coefficient tended to decrease. This is because the diffusion of CO2 in the cement matrix follows the semi-infinite model of Fick's second law. SCAF can contribute to reduced energy consumption and CO2 emissions because of the low-temperature sintering and can absorb and fix CO2 when a certain amount is substituted.

The Characteristics of Self-Hydration and Carbonation Reaction of Coal Ash from Circulating Fluidized-Bed Boiler by Absorption of CO2.

The by-products of the circulating fluidized-bed boiler combustion (CFBC) of coal exhibit self-hardening properties due to the calcium silicates generated by the reaction between SiO2 and CaO, and the ettringite generated by the reaction of gypsum and quicklime with activated alumina. These reactions exhibit tendencies similar to that of the hydration of ordinary Portland cement (OPC). In this study, the self-hydration and carbonation reaction mechanisms of CFBC by-products were analyzed. These CFBC by-products comprise a number of compounds, including Fe2O3, free CaO, and CaSO4, in large quantities. The hydration product calcium aluminate (and/or ferrite) of calcium aluminate ferrite and sulfate was confirmed through instrumental analysis. The CFBC by-products attain hardening properties because of the carbonation reaction between calcium aluminate ferrite and CO2. This can be identified as a self-hardening process because it does not require a supply of special ions from the outside. Through this study, it was confirmed that CFBC by-products generate CaCO3 through carbonation, thereby densifying the pores of the hardened body and contributing to the development of compressive strength.

Digital Biomarkers of Gait and Balance in Diabetic Foot, Measurable by Wearable Inertial Measurement Units: A Mini Review.

People with diabetic foot frequently exhibit gait and balance dysfunction. Recent advances in wearable inertial measurement units (IMUs) enable to assess some of the gait and balance dysfunction associated with diabetic foot (i.e., digital biomarkers of gait and balance). However, there is no review to inform digital biomarkers of gait and balance dysfunction related to diabetic foot, measurable by wearable IMUs (e.g., what gait and balance parameters can wearable IMUs collect? Are the measurements repeatable?). Accordingly, we conducted a web-based, mini review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified 20 papers in this mini review. We found preliminary evidence of digital biomarkers of gait and balance dysfunction in people with diabetic foot, such as slow gait speed, large gait variability, unstable gait initiation, and large body sway. However, due to heterogeneities in included papers in terms of study design, movement tasks, and small sample size, more studies are recommended to confirm this preliminary evidence. Additionally, based on our mini review, we recommend establishing appropriate strategies to successfully incorporate wearable-based assessment into clinical practice for diabetic foot care.

Single and Especially Multisport Participation May Increase Physical Fitness in Younger Americans.

BACKGROUND: We sought to examine the associations between sports participation and physical fitness in younger Americans. METHODS: The analytic sample included 1108 Americans aged 6-15 years. Muscular fitness assessments included handgrip strength, leg extension strength, and plank position. Cardiorespiratory fitness was examined with graded treadmill tests. RESULTS: Youth participating in any sports had increased physical fitness performance for each marker: 1.63 kg (CI: 0.91-2.35) for handgrip strength, 6.23 kg (CI: 3.15-9.32) for leg extension strength, 9.41 lbs. (CI: 4.51-14.31) for plank position held, and 3.02 mL/kg/min (CI: 1.23-4.80) for estimated maximal oxygen uptake. Participants engaging in a single sport had increased performance for most fitness markers: 1.52 kg (CI: 0.67-2.38) for handgrip strength, 5.16 kg (CI: 1.50-8.82) for leg extension strength, 5.98 s (CI: 0.17-11.78) for plank position held, and 2.67 mL/kg/min (CI: 0.58-4.77) for estimated maximal oxygen uptake. Youth engaging in multiple sports exhibited even steeper trends: 1.77 kg (CI: 0.83-2.70) for handgrip strength, 7.63 kg (CI: 3.62-11.65) for leg extension strength, 13.89 s (CI: 7.52-20.27) for plank position held, and 3.50 mL/kg/min (CI: 1.15-5.85) for estimated maximal oxygen uptake. CONCLUSIONS: Any sports participation, including single and multiple sports, is linked to increased physical fitness in American youth.

Graphene e-tattoos for unobstructive ambulatory electrodermal activity sensing on the palm enabled by heterogeneous serpentine ribbons.

Electrodermal activity (EDA) is a popular index of mental stress. State-of-the-art EDA sensors suffer from obstructiveness on the palm or low signal fidelity off the palm. Our previous invention of sub-micron-thin imperceptible graphene e-tattoos (GET) is ideal for unobstructive EDA sensing on the palm. However, robust electrical connection between ultrathin devices and rigid circuit boards is a long missing component for ambulatory use. To minimize the well-known strain concentration at their interfaces, we propose heterogeneous serpentine ribbons (HSPR), which refer to a GET serpentine partially overlapping with a gold serpentine without added adhesive. A fifty-fold strain reduction in HSPR vs. heterogeneous straight ribbons (HSTR) has been discovered and understood. The combination of HSPR and a soft interlayer between the GET and an EDA wristband enabled ambulatory EDA monitoring on the palm in free-living conditions. A newly developed EDA event selection policy leveraging unbiased selection of phasic events validated our GET EDA sensor against gold standards.

Highly Sensitive Capacitive Pressure Sensors over a Wide Pressure Range Enabled by the Hybrid Responses of a Highly Porous Nanocomposite.

Past research aimed at increasing the sensitivity of capacitive pressure sensors has mostly focused on developing dielectric layers with surface/porous structures or higher dielectric constants. However, such strategies have only been effective in improving sensitivities at low pressure ranges (e.g., up to 3 kPa). To overcome this well-known obstacle, herein, a flexible hybrid-response pressure sensor (HRPS) composed of an electrically conductive porous nanocomposite (PNC) laminated with an ultrathin dielectric layer is devised. Using a nickel foam template, the PNC is fabricated with carbon nanotubes (CNTs)-doped Ecoflex to be 86% porous and electrically conductive. The PNC exhibits hybrid piezoresistive and piezocapacitive responses, resulting in significantly enhanced sensitivities (i.e., more than 400%) over wide pressure ranges, from 3.13 kPa-1 within 0-1 kPa to 0.43 kPa-1 within 30-50 kPa. The effect of the hybrid responses is differentiated from the effect of porosity or high dielectric constants by comparing the HRPS with its purely piezocapacitive counterparts. Fundamental understanding of the HRPS and the prediction of optimal CNT doping are achieved through simplified analytical models. The HRPS is able to measure pressures from as subtle as the temporal arterial pulse to as large as footsteps.

Circulating Small Extracellular Vesicles Activate TYRO3 to Drive Cancer Metastasis and Chemoresistance.

Extracellular vesicles (EV) in the tumor microenvironment have emerged as crucial mediators that promote proliferation, metastasis, and chemoresistance. However, the role of circulating small EVs (csEV) in cancer progression remains poorly understood. In this study, we report that csEV facilitate cancer progression and determine its molecular mechanism. csEVs strongly promoted the migration of cancer cells via interaction with phosphatidylserine of csEVs. Among the three TAM receptors, TYRO3, AXL, and MerTK, TYRO3 mainly interacted with csEVs. csEV-mediated TYRO3 activation promoted migration and metastasis via the epithelial-mesenchymal transition and stimulation of RhoA in invasive cancer cells. Additionally, csEV-TYRO3 interaction induced YAP activation, which led to increased cell proliferation and chemoresistance. Combination treatment with gefitinib and KRCT-6j, a selective TYRO3 inhibitor, significantly reduced tumor volume in xenografts implanted with gefitinib-resistant non-small cell lung cancer cells. The results of this study show that TYRO3 activation by csEVs facilitates cancer cell migration and chemoresistance by activation of RhoA or YAP, indicating that the csEV/TYRO3 interaction may serve as a potential therapeutic target for aggressive cancers in the clinic. SIGNIFICANCE: These findings demonstrate that circulating extracellular vesicles are a novel driver in migration and survival of aggressive cancer cells via TYRO3 activation. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/13/3539/F1.large.jpg.

Connectivity map-based drug repositioning of bortezomib to reverse the metastatic effect of GALNT14 in lung cancer.

Despite the continual discovery of promising new cancer targets, drug discovery is often hampered by the poor druggability of these targets. As such, repurposing FDA-approved drugs based on cancer signatures is a useful alternative to cancer precision medicine. Here, we adopted an in silico approach based on large-scale gene expression signatures to identify drug candidates for lung cancer metastasis. Our clinicogenomic analysis identified GALNT14 as a putative driver of lung cancer metastasis, leading to poor survival. To overcome the poor druggability of GALNT14 in the control of metastasis, we utilized the Connectivity Map and identified bortezomib (BTZ) as a potent metastatic inhibitor, bypassing the direct inhibition of the enzymatic activity of GALNT14. The antimetastatic effect of BTZ was verified both in vitro and in vivo. Notably, both BTZ treatment and GALNT14 knockdown attenuated TGFß-mediated gene expression and suppressed TGFß-dependent metastatic genes. These results demonstrate that our in silico approach is a viable strategy for the use of undruggable targets in cancer therapies and for revealing the underlying mechanisms of these targets.

Culture of neural stem cells on conductive and microgrooved polymeric scaffolds fabricated via electrospun fiber-template lithography.

We developed polymeric scaffolds that can provide both topographical and electrical stimuli on mouse neural stem cells (mNSCs) for potential use in nerve tissue engineering. In contrast to conventional patterning techniques such as imprinting, soft/photolithography, and three-dimensional printing, microgroove patterns were generated by using aligned electrospun fibers as templates, via a process denoted as electrospun fiber-template lithography. The preparation of polyvinylpyrrolidone fibers, followed by the deposition of poly(lactic-co-glycolic acid) (PLGA) and the removal of the fiber template, produced freestanding PLGA scaffolds with microgrooves having widths of 1.72 ± 0.24 µm. The subsequent deposition of polypyrrole (PPy) via chemical oxidative polymerization added conductivity to the microgrooved PLGA scaffolds. The resultant scaffolds were cytocompatible with mNSCs. The microgroove patterns enhanced the alignment and elongation of mNSCs, and the PPy layer promoted the interaction of cells with the surface by forming more and longer filopodia compared with the nonconductive surface. Finally, the neuron differentiation of mNSCs was evaluated by monitoring the Tuj-1 neuronal gene expression. The presence of both microgrooves and the conductive PPy layer enhanced the neuronal differentiation of mNSCs even without electrical stimulation, and the neuronal differentiation was further enhanced by stimulation with a sufficient electrical pulse (1.0 V).

Alleviation of Atopic Dermatitis Lesions by a Benzylideneacetophenone Derivative via the MAPK Signaling Pathway.

This experiment was conducted to investigate the effects of a benzylideneacetophenone derivative ((2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one (JC3)) on trimellitic anhydride (TMA)-induced atopic dermatitis (AD)-like symptoms in mice. To induce AD, the dorsal skins of mice were treated with 5% TMA on day 0 and both ears were treated with 5% TMA on day 5 and with 2% TMA from day 6 to day 14. JC3 (1, 5, 10 mg/kg, i.p.) was treated once daily from day 9 to day 14 before TMA treatment. Histological analysis was performed and auricular lymph node weights, ear thicknesses, skin water contents, scratching behaviors, and serum immunoglobulin (IgE) and IFN-γ, and interleukin-4 (IL-4) levels in serum and ear tissues were determined. In addition, the anti-AD activity of JC3 was investigated on phorbol 12-myristate 13-acetate (PMA)-stimulated human mast cells (HMC-1 cells) derived from patients. Levels of TNF-α, IL-4, and mitogen-activated protein kinase (MAPK) were investigated after treating cultured cells with JC3. Treating mice with JC3 (10 mg/kg) significantly decreased ear thicknesses, lymph node weights, skin scores, skin water contents, scratching behavior, and IFN-γ, IL-4 cytokine levels, and serum IgE levels. Moreover, treatment with JC3 (10 mg/kg) significantly decreased serum and ear tissues levels of IFN-γ and IL-4 in AD mice. Furthermore, treatment with JC3 at 10 µg/ml reduced TNF-α and IL-4 levels and decreased MAPK phosphorylation in the HMC-1 cells. The results of this study provide a molecular basis for developing new therapeutics for the treatment of various inflammatory diseases, such as, eczema, asthma, and AD.

Morphine Dependence is Attenuated by Treatment of 3,4,5-Trimethoxy Cinnamic Acid in Mice and Rats.

The effect of 3, 4, 5-trimethoxy cinnamic acid (TMCA) against morphine-induced dependence in mice and rats was investigated. Mice were pretreated with TMCA and then morphine was injected intraperitoneally; whereas rats were treated with TMCA (i.p.) and infused with morphine into the lateral ventricle of brain. Naloxone-induced morphine withdrawal syndrome and conditioned place preference test were performed. Moreover, western blotting and immunohistochemistry were used to measure protein expressions. Number of naloxone-precipitated jumps and conditioned place preference score in mice were attenuated by TMCA. Likewise, TMCA attenuated morphine dependent behavioral patterns such as diarrhea, grooming, penis licking, rearing, teeth chattering, and vocalization in rats. Moreover, the expression levels of pNR1and pERK in the frontal cortex of mice and cultured cortical neurons were diminished by TMCA. In the striatum, pERK expression was attenuated despite unaltered expression of pNR1 and NR1. Interestingly, morphine-induced elevations of FosB/ΔFosB+ cells were suppressed by TMCA (50, 100 mg/kg) in the nucleus accumbens sub-shell region of mice. In conclusion, TMCA could be considered as potential therapeutic agent against morphine-induced dependence.

Inhibition of Carrageenan/Kaolin-Induced Arthritis in Rats and of Inflammatory Cytokine Expressions in Human IL-1ß-Stimulated Fibroblast-like Synoviocytes by a Benzylideneacetophenone Derivative.

The benzylideneacetophenone derivative JC3 [(2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one] (JC3) was synthesized by modifying yakuchinone B obtained from the seeds of Alpinia oxyphylla, a member of the ginger family (Zingiberaceae), which are widely used as a folk remedy and as an anti-inflammatory. The aim of this study was to investigate the anti-arthritic effects of JC3 in rat models of carrageenan-induced paw pain and carrageenan/kaolin-induced knee arthritis. The anti-nociceptive effect of JC3 was assessed by measuring paw withdrawal pressure thresholds using an analgesy-meter. Arthritic symptoms in our monoarthritic rat model were evaluated using weight distribution ratios (WDR), paw thicknesses, and serum prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and vascular endothelial growth factor (VEGF) levels (determined by ELISA). Histological analyses of knee joints were performed after injecting JC3 intraperitoneally into rats before carrageenan treatment at 5 or 10 mg/kg/day for 6 days. The anti-inflammatory effects of JC3 were investigated in vitro using interleukin-1beta (IL-1ß)-stimulated fibroblast-like synoviocytes (FLS) derived from arthritis patients. PGE2, IL-6, and IL-8 levels were measured after treating FLS with JC3. In arthritis-induced rats, JC3 treatment significantly decreased nociceptive and arthritic symptoms at days 5 to 6 after carrageenan/kaolin injection. Histological staining of knee tissue showed that JC3 significantly reduced inflammatory areas in the knee joints. Furthermore, JC3 inhibited the expressions of IL-6 and IL-8 in FLS cells at concentrations of 5-10 µg/ml and decreased PGE2 levels in FLS cells. These findings suggest JC3 has anti-arthritic effects in in vivo and in vitro, and that it might be useful for the treatment of arthritis.

Large-scale pharmacogenomics based drug discovery for ITGB3 dependent chemoresistance in mesenchymal lung cancer.

Even when targets responsible for chemoresistance are identified, drug development is often hampered due to the poor druggability of these proteins. We systematically analyzed therapy-resistance with a large-scale cancer cell transcriptome and drug-response datasets and predicted the candidate drugs based on the gene expression profile. Our results implicated the epithelial-mesenchymal transition as a common mechanism underlying resistance to chemotherapeutic drugs. Notably, we identified ITGB3, whose expression was abundant in both drug resistance and mesenchymal status, as a promising target to overcome chemoresistance. We also confirmed that depletion of ITGB3 sensitized cancer cells to conventional chemotherapeutic drugs by modulating the NF-κB signaling pathway. Considering the poor druggability of ITGB3 and the lack of feasible drugs to directly inhibit this protein, we took an in silico screening for drugs mimicking the transcriptome-level changes caused by knockdown of ITGB3. This approach successfully identified atorvastatin as a novel candidate for drug repurposing, paving an alternative path to drug screening that is applicable to undruggable targets.

Selective Elimination of Culture-Adapted Human Embryonic Stem Cells with BH3 Mimetics.

The selective survival advantage of culture-adapted human embryonic stem cells (hESCs) is a serious safety concern for their clinical application. With a set of hESCs with various passage numbers, we observed that a subpopulation of hESCs at late passage numbers was highly resistant to various cell death stimuli, such as YM155, a survivin inhibitor. Transcriptome analysis from YM155-sensitive (YM155S) and YM155-resistant (YM155R) hESCs demonstrated that BCL2L1 was highly expressed in YM155R hESCs. By matching the gene signature of YM155R hESCs with the Cancer Therapeutics Response Portal dataset, BH3 mimetics were predicted to selectively ablate these cells. Indeed, short-course treatment with a sub-optimal dose of BH3 mimetics induced the spontaneous death of YM155R, but not YM155S hESCs by disrupting the mitochondrial membrane potential. YM155S hESCs remained pluripotent following BH3 mimetics treatment. Therefore, the use of BH3 mimetics is a promising strategy to specifically eliminate hESCs with a selective survival advantage.

Drug Repositioning for Cancer Therapy Based on Large-Scale Drug-Induced Transcriptional Signatures.

An in silico chemical genomics approach is developed to predict drug repositioning (DR) candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i) a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii) rich information on drug's mode-of-action. First, the drug-induced expression profile is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity.

A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity.

The present work describes the construction and validation of a human scFv library with a novel design approach to synthetic complementarity determining region (CDR) diversification. The advantage of synthetic antibody libraries includes the possibility of exerting fine control over factors like framework sequences, amino acid and codon usage, and CDR diversity. However, random combinatorial synthesis of oligonucleotides for CDR sequence diversity also produces many clones with unnatural sequences and/or undesirable modification motifs. To alleviate these issues, we designed and constructed a novel semi-synthetic human scFv library with non-combinatorial, pre-designed CDR diversity and a single native human framework each for heavy, kappa, and lambda chain variable domains. Next-generation sequencing analysis indicated that the library consists of antibody clones with highly nature-like CDR sequences and the occurrence of the post-translational modification motifs is minimized. Multiple unique clones with nanomolar affinity could be isolated from the library against a number of target antigens, validating the library design strategy. The results demonstrate that it is possible to construct a functional antibody library using low, non-combinatorial synthetic CDR diversity, and provides a new strategy for the design of antibody libraries suitable for demanding applications.

Identification of a cell cycle-dependent duplicating complex that assembles basal bodies de novo in Naegleria.

During the differentiation of the amoeba Naegleria pringsheimi into a flagellate, a transient complex containing γ-tubulin, pericentrin-like protein, and myosin II (GPM complex) is formed, and subsequently a pair of basal bodies is assembled from the complex. It is not understood, however, how a single GPM is formed nor how the capability to form this complex is acquired by individual cells. We hypothesized that the GPM is formed from a precursor complex and developed an antibody that recognizes Naegleria (Ng)-transacylase, a component of the precursor complex. Immunostaining of differentiating cells showed that Ng-transacylase is concentrated at a site in the amoeba and that γ-tubulin is transiently co-concentrated at the site, suggesting that the GPM is formed from a precursor, GPMp, which contains Ng-transacylase and is already present in the amoeba. Immunostaining of growing N. pringsheimi with Ng-transacylase antibody revealed the presence of one GPMp in interphase cells, but two GPMps in mitotic cells, suggesting that N. pringsheimi maintains one GPMp per cell by duplicating and segregating the complex according to its cell cycle. Our results demonstrate the existence of a cell cycle-dependent duplicating complex that provides a site for the de novo assembly of the next generation of basal bodies.

NgUNC-119, Naegleria homologue of UNC-119, localizes to the flagellar rootlet.

The UNC-119 family of proteins is ubiquitous in animals. The expression of UNC-119 is prominent in neural tissues including photoreceptor cells. Homologues of UNC-119 are also found in ciliated (or flagellated) single-celled organisms; however, the cellular distribution of this protein in protists is unknown. We cloned and characterized a homologue of unc-119 from the ameboflagellate Naegleria gruberi (Ngunc-119) and identified the cellular distribution of the protein. The Ngunc-119 open reading frame contained 570 nucleotides encoding a protein of 189 amino acids with a predicted molecular weight of 22.1 kDa, which is similar to that of Paramecium UNC-119 and Trypanosoma UNC-119. These three proteins are 46-48% identical in their amino acid sequences. The smaller NgUNC-119 corresponds to the conserved C-terminal 3/4 of the UNC-119 from multi-cellular organisms. The amino acid sequence of NgUNC-119 is 43-50% identical to that of the conserved C-terminal regions. NgUNC-119 was not found in growing amoebae but accumulated rapidly after the initiation of differentiation into flagellates. Indirect immunofluorescence staining of differentiating N. gruberi showed that NgUNC-119 begins to concentrate at a spot near the nucleus of differentiating cells and then elongates into a filamentous structure. Purification and indirect immunofluorescence staining of the Naegleria flagellar rootlet suggested that NgUNC-119 is a component of the flagellar rootlet.