Blocking Microglial Proliferation by CSF-1R Inhibitor Does Not Alter the Neuroprotective Effects of Adoptive Regulatory T Cells in 3xTg Alzheimer's Disease Mice.

Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes cognitive impairment. Neuroinflammation induced by activated microglia exacerbates AD. Regulatory T cells (Tregs) play roles in limiting neuroinflammation by converting microglial polarization. Therefore, adoptive Treg therapy is considered an attractive option for neurodegenerative disorders. However, the mechanism underlying Treg therapy via microglial modulation is not fully understood. In this study, we sought to determine whether adoptively transferred Tregs were effective when microglia proliferation was inhibited by using GW2580, which is an inhibitor of CSF1R. We found that inhibition of microglial proliferation during Treg transfer did not alter the therapeutic effects of Tregs on cognitive deficits and the accumulation of Aß and pTAU in 3xTg-AD mice. The expression of pro- and anti-inflammatory markers in the hippocampus of 3xTg mice showed that GW2580 did not affect the inhibition of neuroinflammation by Treg transfer. Additionally, adoptively transferred Tregs were commonly detected in the brain on day 7 after transfer and their levels decreased slowly over 100 days. Our findings suggest that adoptively transferred Tregs can survive longer than 100 days in the brain, suppressing microglial activation and thus alleviating AD pathology. The present study provides valuable evidence to support the prolonged efficacy of adoptive Treg therapy in AD.

Effect of Sample Geometry on Graphitization of Polyacrylonitrile.

In this study, it is analyzed how sample geometry (spheres, nanofibers, or films) influences the graphitization behavior of polyacrylonitrile (PAN) molecules. The chemical bonding and changes in the composition of these three geometries are studied at the oxidation, carbonization, and graphitization stages via scanning electron microscopy (SEM), in situ thermogravimetric-infrared (TGA-IR) analysis, elemental analysis, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The influence of molecular alignment on the graphitization of the three sample geometries is investigated using synchrotron wide-angle X-ray diffraction (WAXD) and transmission electron microscopy (TEM). The effects of molecular alignment at different draw rates during spinning are explored in detail.

Chemisorption of silicon tetrachloride on silicon nitride: a density functional theory study.

We studied the chemisorption of silicon tetrachloride (SiCl4) on the NH2/NH-terminated silicon nitride slab model using density functional theory (DFT) for atomic layer deposition (ALD) of silicon nitride. Initially, two reaction pathways were compared, forming HCl or NH3+Cl- as a byproduct. The NH3+Cl- complex formation was more exothermic than the HCl formation, with an activation energy of 0.26 eV. The -NH2* reaction sites are restored by desorption of HCl from the NH3+Cl- complexes at elevated temperatures of 205 °C or higher. Next, three sequential ligand exchange reactions forming Si-N bonds were modeled and simulated. The reaction energies became progressively less exothermic as the reaction progressed, from -1.31 eV to -0.30 eV to 0.98 eV, due to the stretching of Si-N bonds and the distortion of the N-Si-N bond angles. Also, the activation energies for the second and third reactions were 2.17 eV and 1.55 eV, respectively, significantly higher than the 0.26 eV of the first reaction, mainly due to the additional dissociation of the N-H bond. The third Si-N bond formation is unfavorable due to the endothermic reaction and higher activation energy. Therefore, the chemisorbed species would be -SiCl2* when the surface is exposed to SiCl4.

A theoretical study on the surface reaction of tetrakis(dimethylamino)titanium on titanium oxide.

Tetrakis(dimethylamino)-titanium (TDMAT, Ti(NMe2)4) has been used for the low-temperature atomic layer deposition (ALD) process of titanium oxide (TiO2) films. In this study, the chemisorption of TDMAT on a titanium oxide surface using a slab model was simulated by density functional theory (DFT) calculation. We calculated the activation energy for the chemisorption and predicted the final chemisorbed species. A TiO2 slab model was constructed with the optimized number of -OH surface groups. Three serial ligand exchange reactions between a TDMAT molecule and the TiO2 slab were exothermic with low activation energies of 0.16-0.46 eV, which can explain the low processing temperatures of the ALD TiO2 processes. Our DFT calculation showed that three NMe2 ligands of TDMAT would be released and the surface species of -TiNMe2 would be formed, which is in good agreement with the experimental observation in the literature.

Selective etching mechanism of silicon oxide against silicon by hydrogen fluoride: a density functional theory study.

Selective etching of silicon oxide (SiO2) against silicon (Si) using anhydrous hydrogen fluoride (HF) vapor has been used for semiconductor device fabrication. We studied the underlying mechanism of the selective etching by density functional theory (DFT) calculation. We constructed surface slab models of SiO2 or Si with different degrees of fluorination and simulated the four steps of fluorination. The calculations show relatively low activation energies of 0.72-0.79 eV for the four steps of fluorination of SiO2, which are close to ∼0.69 eV observed in the experiment. The four-membered ring structure of -Si-O-H-F- in all transition states stabilized the system, resulting in relatively low activation energies. Thus, continuous etching of SiO2 by HF is plausible at near-room temperature. In contrast, the fluorinations of Si showed relatively high activation energies ranging from 1.22 to 1.56 eV due to the less stable transition state geometries. Thus, negligible etching of silicon by HF is expected by the near-room temperature process. Our calculation results explain well the experimental observation of the selective etching of SiO2 against Si by HF vapor.

The Encapsulation of Natural Organic Dyes on TiO2 for Photochromism Control.

Titanium dioxide (TiO2) plays a pivotal role in photocatalytic reactions and holds great promise for the cosmetic and paint industries due to its white color and high refractive index. However, the original color of TiO2 changes gradually to blue or yellow with UV irradiation, which affects its color realization. We encapsulated TiO2 with several natural organic dye compounds, including purpurin, curcumin, and safflower, to control its photochromism and realize a range of different colors. The chemical reaction between TiO2 and dyes based on their functional group was investigated, and the light absorption was tested via FTIR and UV-Vis spectroscopy. The changes in morphology and size distribution additionally supported their successful encapsulation. The discoloration after UV irradiation was evaluated by measuring the color difference (ΔE) of control TiO2 and dye encapsulated TiO2. The unique structure utilized natural dyes to preserve photochromism based on the physical barrier and automatically controlled the electronic transition of core TiO2. In particular, the color difference values of purpurin and curcumin were 4.05 and 3.76, which is lower than the 5.36 of the control TiO2. Dye encapsulated TiO2 was manipulated into lipstick to verify its color realization and retention.

Influence of postpolymerization time and atmosphere on the mechanical properties, degree of conversion, and cytotoxicity of denture bases produced by digital light processing.

STATEMENT OF PROBLEM: Studies on the effects of postprocessing conditions on the physical properties, degree of conversion (DC), and biocompatibility of denture bases produced by digital light processing are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the effects of the atmosphere during postpolymerization and of postpolymerization time on the flexural strength, Vickers hardness, DC, cytotoxicity, and residual monomer content of denture bases. MATERIAL AND METHODS: Six different groups of bar- and disk-shaped specimens from the denture base resin were produced, considering 2 different atmospheres (air and nitrogen) and 3 different postpolymerization times (5, 10, and 20 minutes). To determine the physical properties, the flexural strength and Vickers hardness were measured. Fourier transform infrared spectrometry was used to calculate DC. Cytotoxicity was assessed from the effect on human gingival fibroblasts. The residual monomer content was determined by using high-performance liquid chromatography. Based on the normality test by the Shapiro-Wilk method, a nonparametric factorial analysis of variances was conducted (α=.05). RESULTS: A significant interaction was detected between the atmosphere and postpolymerization time for hardness (P<.001) but no interaction for strength, DC, or cytotoxicity (P=.826, P=.786, and P=.563, respectively). Hardness was significantly affected by the postpolymerization time in the groups with the nitrogen atmosphere (P<.001). DC was significantly affected by the atmosphere (P=.012), whereas strength and cytotoxicity were not (P=.500 and P=.299, respectively). Cytotoxicity was significantly affected by the postpolymerization time (P<.001), but strength and DC were not (P=.482 and P=.167, respectively). Residual monomers were not detected after ≥10-minute postpolymerization time. CONCLUSIONS: The atmosphere significantly affected hardness and DC, whereas the postpolymerization time significantly affected hardness, DC, cytotoxicity, and residual monomer content. Denture bases produced in a nitrogen atmosphere and with the 10-minute postpolymerization time showed sufficient hardness, DC, and no cytotoxicity.

Antifungal activity, mechanical properties, and accuracy of three-dimensionally printed denture base with microencapsulated phytochemicals on varying post-polymerization time.

BACKGROUND: Studies on the antifungal activity, flexural strength, Vickers hardness, and intaglio surface trueness of three-dimensionally printed (3DP) denture bases with microencapsulated phytochemicals with respect to changes in post-polymerization time (PPT) are lacking. METHODS: Specimens of various shapes and dimensions were fabricated with a 3DP denture base resin mixed with 5 wt% phytoncide-filled microcapsules. Each specimen was subjected to different PPT protocols of 5, 10, 20, and 30 min. Specimens without microcapsules with 5-min PPT were used as the negative control group. Cell colonies were counted to evaluate antifungal activity. Three-point bending and Vickers hardness tests were performed to measure the flexural strengths and hardness of the specimens. Fourier-transform infrared spectrometry was used to inspect the degree of conversion (DC). The intaglio surface trueness was measured using root-mean-square estimates calculated by superimposition analysis. A non-parametric Kruskal-Wallis test or one-way analysis of variance was performed (α = 0.05). RESULTS: The specimens with microcapsules and 10-min PPT showed the highest antifungal activity among the tested groups. Compared with the positive control group (5-min PPT), the specimens with PPTs of 10 min or longer showed significantly higher mean flexural strength, higher DC, greater hardness, and better trueness (all, P < 0.05). Except for the difference in antifungal activity, no statistically significant differences were detected between the specimens subjected to 10-, 20-, and 30-min PPT. CONCLUSION: The 3DP denture base filled with microencapsulated phytoncide showed different antifungal activity and physical properties on changing PPT. The 3DP denture base containing phytoncide-filled microcapsules at 5 wt% concentration and subjected to 10-min PPT exhibited sufficient antifungal activity as well as mechanical properties and accuracy within clinical acceptance.

Macroscopic Assembly of Sericin toward Self-Healable Silk.

Silk contains an adhesive glycoprotein, silk sericin, in which silk fibroins can be enfolded and chemically stabilized. Silk sericin is gaining importance as the material for the creation of functional bioscaffolds. However, the assembly of silk sericin is generally limited to the blend of polymers or proteins due to its inherent poor mechanical strength. Here, we report a simple macroscopic controlled assembly of silk sericin fibers based on their secondary structure via wet-spinning. In addition, plasticization of silk sericin using glycerol immobilized with glutaraldehyde was found to induce dimensional stability, affording stable linear fibers with self-adhesion. Furthermore, cyclo-phenylalanine nanowires were incorporated into the silk sericin dope for a practical demonstration of their potential in artificial silk production with superstructure formation. The physicochemical characteristics of the spun fibers have also been elucidated using Fourier-transform infrared spectroscopy, electron microscopy, tensile test, differential scanning calorimetry, and 2D X-ray diffraction.

Genetic architecture of cardiometabolic risks in people living with HIV.

BACKGROUND: Advances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown. METHODS: We screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Genetic hits found exclusively in the PLWH cohort were tested for association with other traits. We then assessed the predictive value of a series of polygenic risk scores (PRS) recapitulating the genetic burden for lipid levels, type 2 diabetes (T2D), and myocardial infarction (MI) in EA and AA PLWH. RESULTS: We confirmed the impact of previously reported lipid-related susceptibility loci in PLWH. Furthermore, we identified PLWH-specific variants in genes involved in immune cell regulation and previously linked to HIV control, body composition, smoking, and alcohol consumption. Moreover, PLWH at the top of European-based PRS for T2D distribution demonstrated a > 2-fold increased risk of T2D compared to the remaining 95% in EA PLWH but to a much lesser degree in AA. Importantly, while PRS for MI was not predictive of MI risk in AA PLWH, multiethnic PRS significantly improved risk stratification for T2D and MI. CONCLUSIONS: Our findings suggest that genetic loci involved in the regulation of the immune system and predisposition to risky behaviors contribute to dyslipidemia in the presence of HIV infection. Moreover, we demonstrate the utility of the European-based and multiethnic PRS for stratification of PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies.

Surface wrinkle formation by liquid crystalline polymers for significant light extraction enhancement on quantum dot light-emitting diodes.

We propose an optimal outcoupling structure of a quantum-dot light-emitting diode (QLED) and present material properties based on numerical calculations via the ray-tracing method, in which light extraction properties are obtained according to the surface wrinkles on a substrate. After analyzing the designed microstructure elements, the optimal model was derived and applied to the QLEDs; consequently, the outcoupling efficiency enhanced by 31%. The liquid crystalline polymer forming the random surface wrinkles not only achieves an excellent light extraction through plasma crosslinking but also facilitates large-area processes. We propose an optical design rule for high-efficiency QLED design by analyzing the electro-optical efficiency, emission spectrum, and angular radiation pattern of the optical device.

Catalyzed Atomic Layer Deposition of Silicon Oxide at Ultralow Temperature Using Alkylamine.

We report the catalyzed atomic layer deposition (ALD) of silicon oxide using Si2Cl6, H2O, and various alkylamines. The density functional theory (DFT) calculations using the periodic slab model of the SiO2 surface were performed for the selection of alternative Lewis base catalysts with high catalytic activities. During the first half-reaction, the catalysts with less steric hindrance such as pyridine would be more effective than bulky alkylamines despite lower nucleophilicity. On the other hand, during the second half-reaction, the catalysts with a high nucleophilicity such as triethylamine (Et3N) would be more efficient because the steric hindrance is less critical. The in situ process monitoring shows that the calculated atomic charge is a good indicator for expecting the catalyst activity in the ALD reaction. The use of Et3N in the second half-reaction was essential to improving the growth rate as well as the step coverage of the film because the Et3N-catalyzed process deposited a SiO2 film with a step coverage of 98% that is better than 93% of the pyridine-catalyzed process. The adsorption of pyridine, ammonia (NH3), or trimethylamine (Me3N) salts was more favorable than that of Et3N, n-Pr3N, or iPr3N salts. Therefore, Et3N was expected to incorporate less amine salts in the film as compared to pyridine, and the compositional analyses confirmed that the concentrations of Cl and N by the Et3N-catalyzed process were significantly lower than those by the pyridine-catalyzed process.

Metabolic Profiling Regarding Pathogenesis of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease characterized by fibrosis of the lung parenchyma and loss of lung function. IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair process including uncontrolled proliferation of lung (myo) fibroblasts and excessive deposition of extracellular matrix proteins in the interstitial space; however, the pathogenic pathways involved in IPF have not been fully elucidated. In this study, we attempted to characterize metabolic changes of lung tissues involved in the pathogenesis of IPF using gas chromatography-mass spectrometry-based metabolic profiling. Partial least-squares discriminant analysis (PLS-DA) model generated from metabolite data was able to discriminate between the control subjects and IPF patients (R(2)X = 0.37, R(2)Y = 0.613 and Q(2) (cumulative) = 0.54, receiver operator characteristic AUC > 0.9). We discovered 25 metabolite signatures of IPF using both univariate and multivariate statistical analyses (FDR < 0.05 and VIP score of PLS-DA > 1). These metabolite signatures indicated alteration in metabolic pathways: adenosine triphosphate degradation pathway, glycolysis pathway, glutathione biosynthesis pathway, and ornithine aminotransferase pathway. The results could provide additional insight into understanding the disease and potential for developing biomarkers.

A Root-Based Combination Supplement Containing Pueraria lobata and Rehmannia glutinosa and Exercise Preserve Bone Mass in Ovariectomized Rats Fed a High-Fat Diet.

The aim of this study was to evaluate the effects of a supplement containing Pueraria lobata/Rehmannia glutinosa (PR) root extracts on bone turnover in ovariectomized (OVX) rats (a model for postmenopausal osteoporosis). Female Sprague-Dawley rats (8 weeks old) were randomized into eight groups: sham-operated rats with low-fat control diet + vehicle, OVX rats with low-fat control diet + vehicle, OVX rats with high-fat diet (HFD) + vehicle, OVX rats with HFD + vehicle + exercise, OVX rats with HFD + PR (400 mg/kg body weight/day p.o.), OVX rats with HFD + PR + exercise, OVX rats with HFD + 17ß-estradiol (0.5 mg/kg body weight/day p.o.), OVX rats with HFD + 17ß-estradiol + exercise. Bone microarchitecture, bone turnover markers (e.g., plasma alkaline phosphatase and osteocalcin), expressions of osteogenic and resorptive gene markers in the bone were measured. Eight weeks of PR and/or aerobic exercise improved cortical microarchitecture of the femur and decreased markers of bone turnover and expression of skeletal osteoclastogenic genes in the femur. PR supplementation combined with exercise preserved bone loss induced by estrogen deficiency and should be investigated further as an alternative to hormone replacement therapy for preventing osteoporosis in postmenopausal women.

Role of Atypical Pathogens and the Antibiotic Prescription Pattern in Acute Bronchitis: A Multicenter Study in Korea.

The role of atypical bacteria and the effect of antibiotic treatments in acute bronchitis are still not clear. This study was conducted at 22 hospitals (17 primary care clinics and 5 university hospitals) in Korea. Outpatients (aged ≥ 18 yr) who had an acute illness with a new cough and sputum (≤ 30 days) were enrolled in 2013. Multiplex real-time polymerase chain reaction (RT-PCR) was used to detect five atypical bacteria. A total of 435 patients were diagnosed as having acute bronchitis (vs. probable pneumonia, n = 75), and 1.8% (n = 8) were positive for atypical pathogens (Bordetella pertussis, n = 3; B. parapertussis, n = 0; Mycoplasma pneumoniae, n = 1; Chlamydophila pneumoniae, n = 3; Legionella pneumophila, n = 1). Among clinical symptoms and signs, only post-tussive vomiting was more frequent in patients with atypical pathogens than those without (P = 0.024). In all, 72.2% of the enrolled patients received antibiotic treatment at their first visits, and ß-lactams (29.4%) and quinolones (20.5%) were the most commonly prescribed agents. In conclusion, our study demonstrates that the incidence of atypical pathogens is low in patients with acute bronchitis, and the rate of antibiotic prescriptions is high.

Two-minute assembly of pristine large-area graphene based films.

We report a remarkably rapid method for assembling pristine graphene platelets into a large area transparent film at a liquid surface. Some 2-3 layer pristine graphene platelets temporally solvated with N-methyl-2-pyrrolidone (NMP) are assembled at the surface of a dilute aqueous suspension using an evaporation-driven Rayleigh-Taylor instability and then are driven together by Marangoni forces. The platelets are fixed through physical binding of their edges. Typically, 8-cm-diameter circular graphene films are generated within two minutes. Once formed, the films can be transferred onto various substrates with flat or textured topologies. This interfacial assembly protocol is generally applicable to other nanomaterials, including 0D fullerene and 1D carbon nanotubes, which commonly suffer from limited solution compatibility.

Molybdenum sulfide/N-doped CNT forest hybrid catalysts for high-performance hydrogen evolution reaction.

Cost effective hydrogen evolution reaction (HER) catalyst without using precious metallic elements is a crucial demand for environment-benign energy production. Molybdenum sulfide is one of the promising candidates for such purpose, particularly in acidic condition, but its catalytic performance is inherently limited by the sparse catalytic edge sites and poor electrical conductivity. We report synthesis and HER catalysis of hybrid catalysts composed of amorphous molybdenum sulfide (MoSx) layer directly bound at vertical N-doped carbon nanotube (NCNT) forest surface. Owing to the high wettability of N-doped graphitic surface and electrostatic attraction between thiomolybdate precursor anion and N-doped sites, ∼2 nm scale thick amorphous MoSx layers are specifically deposited at NCNT surface under low-temperature wet chemical process. The synergistic effect from the dense catalytic sites at amorphous MoSx surface and fluent charge transport along NCNT forest attains the excellent HER catalysis with onset overpotential as low as ∼75 mV and small potential of 110 mV for 10 mA/cm(2) current density, which is the highest HER activity of molybdenum sulfide-based catalyst ever reported thus far.

Novel approach for analysis of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS-based lipidomics: lipid levels in asthmatics and corticosteroid-treated asthmatic patients.

To better understand the respiratory lipid phenotypes of asthma, we developed a novel method for lipid profiling of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS with an internal spectral library and high-throughput lipid-identifying software. The method was applied to BALF from 38 asthmatic patients (18 patients with nonsteroid treated bronchial asthma [NSBA] and 20 patients with steroid treated bronchial asthma [SBA]) and 13 healthy subjects (NC). We identified 69 lipids, which were categorized into one of six lipid classes: lysophosphatidylcholine (LPC), phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylserine (PS), sphingomyelin (SM) and triglyceride (TG). Compared with the NC group, the individual quantity levels of the six classes of lipids were significantly higher in the NSBA subjects. In the SBA subjects, the PC, PG, PS, SM, and TG levels were similar to the levels observed in the NC group. Using differentially expressed lipid species (p value < 0.05, FDR < 0.1 and VIP score of PLS-DA > 1), 34 lipid biomarker candidates with high prediction performance between asthmatics and controls were identified (AUROC > 0.9). These novel findings revealed specific characteristics of lipid phenotypes in asthmatic patients and suggested the importance of future research on the relationship between lipid levels and asthma.

The Clinical Usability Evaluation of an Attachable Video Laryngoscope in the Simulated Tracheal Intubation Scenario: A Manikin Study.

The aim of this study was to assess the usefulness of an attachable video laryngoscope (AVL) by attaching a camera and a monitor to a conventional Macintosh laryngoscope (CML). Normal and tongue edema airway scenarios were simulated using a manikin. Twenty physicians performed tracheal intubations using CML, AVL, Pentax Airwayscope® (AWS), and McGrath MAC® (MAC) in each scenario. Ten physicians who had clinical experience in using tracheal intubation were designated as the skilled group, and another ten physicians who were affiliated with other departments and had little clinical experience using tracheal intubation were designated as the unskilled group. The time required for intubation and the success rate were recorded. The degree of difficulty of use and glottic view assessment were scored by participants. All 20 participants successfully completed the study. There was no difference in tracheal intubation success rate and intubation time in the normal airway scenario in both skilled and unskilled groups. In the experienced group, AWS had the highest success rate (100%) in the tongue edema airway scenario, followed by AVL (60%), MAC (60%), and CML (10%) (p = 0.001). The time required to intubate using AWS was significantly shorter than that with AVL (10.2 s vs. 19.2 s) or MAC (10.2 s vs. 20.4 s, p = 0.007). The difficulty of using AVL was significantly lower than that of CML (7.8 vs. 2.8; p < 0.001). For the experienced group, AVL was interpreted as being inferior to AWS but better than MAC. Similarly, in the unskilled group, AVL had a similar success rate and tracheal intubation time as MAC in the tongue edema scenario, but this was not statistically significant. The difficulty of using AVL was significantly lower than that of CML (8.8 vs. 3.3; p < 0.001). AVL may be an alternative for VL.