Proteomic analysis reveals activation of platelet- and fibrosis-related pathways in hearts of ApoE-/- mice exposed to diesel exhaust particles.

Air pollution is an environmental risk factor linked to multiple human diseases including cardiovascular diseases (CVDs). While particulate matter (PM) emitted by diesel exhaust damages multiple organ systems, heart disease is one of the most severe pathologies affected by PM. However, the in vivo effects of diesel exhaust particles (DEP) on the heart and the molecular mechanisms of DEP-induced heart dysfunction have not been investigated. In the current study, we attempted to identify the proteomic signatures of heart fibrosis caused by diesel exhaust particles (DEP) in CVDs-prone apolipoprotein E knockout (ApoE-/-) mice model using tandem mass tag (TMT)-based quantitative proteomic analysis. DEP exposure induced mild heart fibrosis in ApoE-/- mice compared with severe heart fibrosis in ApoE-/- mice that were treated with CVDs-inducing peptide, angiotensin II. TMT-based quantitative proteomic analysis of heart tissues between PBS- and DEP-treated ApoE-/- mice revealed significant upregulation of proteins associated with platelet activation and TGFß-dependent pathways. Our data suggest that DEP exposure could induce heart fibrosis, potentially via platelet-related pathways and TGFß induction, causing cardiac fibrosis and dysfunction.

Pressure-Dependent Structure of BaZrO3 Crystals as Determined by Raman Spectroscopy.

The structure of dielectric perovskite BaZrO3, long known to be cubic at room temperature without any structural phase transition with variation in temperature, has been recently disputed to have different ground state structures with lower symmetries involving octahedra rotation. Pressure-dependent Raman scattering measurements can identify the hierarchy of energetically-adjacent polymorphs, helping in turn to understand its ground state structure at atmospheric pressure. Here, the Raman scattering spectra of high-quality BaZrO3 single crystals grown by the optical floating zone method are investigated in a pressure range from 1 atm to 42 GPa. First, based on the analyses of the infrared and Raman spectra measured at atmospheric pressure, it was found that all the observed vibrational modes could be assigned according to the cubic Pm3¯m structure. In addition, by applying pressure, two structural phase transitions were found at 8.4 and 19.2 GPa, one from the cubic to the rhombohedral R3¯c phase and the other from the rhombohedral to the tetragonal I4/mcm phase. Based on the two pressure-induced structural phase transitions, the true ground state structure of BaZrO3 at room temperature and ambient pressure was corroborated to be cubic while the rhombohedral phase was the closest second.

Three-Dimensional Plasmonic Nanocluster-Driven Light-Matter Interaction for Photoluminescence Enhancement and Picomolar-Level Biosensing.

Plasmonic nanoparticle clusters promise to support unique engineered electromagnetic responses at optical frequencies, realizing a new concept of devices for nanophotonic applications. However, the technological challenges associated with the fabrication of three-dimensional nanoparticle clusters with programmed compositions remain unresolved. Here, we present a novel strategy for realizing heterogeneous structures that enable efficient near-field coupling between the plasmonic modes of gold nanoparticles and various other nanomaterials via a simple three-dimensional coassembly process. Quantum dots embedded in the plasmonic structures display ∼56 meV of a blue shift in the emission spectrum. The decay enhancement factor increases as the total contribution of radiative and nonradiative plasmonic modes increases. Furthermore, we demonstrate an ultracompact diagnostic platform to detect M13 viruses and their mutations from femtoliter volume, sub-100 pM analytes. This platform could pave the way toward an effective diagnosis of diverse pathogens, which is in high demand for handling pandemic situations.

Effect of Threading Dislocations on the Electronic Structure of La-Doped BaSnO3 Thin Films.

In spite of great application potential as transparent n-type oxides with high electrical mobility at room temperature, threading dislocations (TDs) often found in the (Ba,La)SnO3 (BLSO) films can limit their intrinsic properties so that their role in the physical properties of BLSO films need to be properly understood. The electrical properties and electronic structure of BLSO films grown on SrTiO3 (001) (STO) and BaSnO3 (001) (BSO) substrates are comparatively studied to investigate the effect of the TDs. In the BLSO/STO films with TD density of ~1.32 × 1011 cm-2, n-type carrier density ne and electron mobility are significantly reduced, as compared with the BLSO/BSO films with nearly no TDs. This indicates that TDs play the role of scattering-centers as well as acceptor-centers to reduce n-type carriers. Moreover, in the BLSO/STO films, both binding energies of an Sn 3d core level and a valence band maximum are reduced, being qualitatively consistent with the Fermi level shift with the reduced n-type carriers. However, the reduced binding energies of the Sn 3d core level and the valence band maximum are clearly different as 0.39 and 0.19 eV, respectively, suggesting that the band gap renormalization preexisting in proportion to ne is further suppressed to restore the band gap in the BLSO/STO films with the TDs.

Engineering Efficient Self-Assembled Plasmonic Nanostructures by Configuring Metallic Nanoparticle's Morphology.

We reveal the significance of plasmonic nanoparticle's (NP) shape and its surface morphology en route to an efficient self-assembled plasmonic nanoparticle cluster. A simplified model is simulated in the form of free-space dimer and trimer nanostructures (NPs in the shape of a sphere, cube, and disk). A ~200% to ~125% rise in near-field strength (gap mode enhancement) is observed for spherical NPs in comparison with cubical NPs (from 2 nm to 8 nm gap sizes). Full-width three-quarter maximum reveals better broad-spectral optical performance in a range of ~100 nm (dimer) and ~170 nm (trimer) from spherical NPs as compared to a cube (~60 nm for dimer and trimer). These excellent properties for sphere-based nanostructures are merited from its dipole mode characteristics.

Characteristics and Electronic Band Alignment of a Transparent p-CuI/n-SiZnSnO Heterojunction Diode with a High Rectification Ratio.

Transparent p-CuI/n-SiZnSnO (SZTO) heterojunction diodes are successfully fabricated by thermal evaporation of a (111) oriented p-CuI polycrystalline film on top of an amorphous n-SZTO film grown by the RF magnetron sputtering method. A nitrogen annealing process reduces ionized impurity scattering dominantly incurred by Cu vacancy and structural defects at the grain boundaries in the CuI film to result in improved diode performance; the current rectification ratio estimated at ±2 V is enhanced from ≈106 to ≈107. Various diode parameters, including ideality factor, reverse saturation current, offset current, series resistance, and parallel resistance, are estimated based on the Shockley diode equation. An energy band diagram exhibiting the type-II band alignment is proposed to explain the diode characteristics. The present p-CuI/n-SZTO diode can be a promising building block for constructing useful optoelectronic components such as a light-emitting diode and a UV photodetector.

Clinical relation among dural adhesion, dural ossification, and dural laceration in the removal of ossification of the ligamentum flavum.

BACKGROUND CONTEXT: Dural laceration frequently occurs during surgery in patients with ossification of the ligamentum flavum (OLF), mainly because of dural adhesion (DA) and dural ossification (DO) between the ligamentum flavum and the dura mater. However, the radiological predictive factors of DA in OLF have rarely been reported. PURPOSE: The objective of this study was to determine the preoperative radiological signs for predicting intraoperative DA in OLF by using preoperative magnetic resonance imaging (MRI) and computed tomography (CT). STUDY DESIGN: This is a retrospective study. PATIENT SAMPLE: This study included 182 patients who underwent decompressive laminectomy and OLF removal from 2005 to 2014. OUTCOME MEASURE: Demographic data, preoperative neurologic status, surgical procedure and results, and intraoperative and postoperative complications were analyzed. Clinical outcome was assessed with the Japanese Orthopaedic Association score. MATERIALS AND METHODS: Depending on the morphologic appearance of OLF in preoperative radiographs, we aimed to investigate the prevalence of intraoperative DA and DO. We used the following factors of representative classifications: (1) surface appearance, (2) "double-layer" or "tram-track" sign, (3) cross-sectional area of the stenosed level, (4) Sato classification as axial classification, (5) Kuh classification as sagittal classification, and (6) high-signal-intensity change on T2-weighted MRI. RESULTS: Intraoperative evidence of DA was observed in 52 patients (29%), and DO was observed in 23 patients (13%). Twenty-seven patients (15%) had dural laceration during surgery. Statistically, DA was closely associated with the non-uniform type of surface appearance (odds ratio 5.396, p=.001) and with the presence of either a double-layer sign or a tram-track sign (odds ratio 11.525, p<.001). In the preoperative CT and MRI, 21 out of 23 patients with DO showed a "double-layer sign" or a "tram-track sign." CONCLUSIONS: This study identified two predictive factors of DA in OLF, which were the non-uniform surface appearance and the presence of a double-layer sign or a tram-track sign. The presence of DO in OLF was closely associated with a double-layer sign or a tram-track sign in the preoperative radiological images.

Transparent p-CuI/n-BaSnO3-δ heterojunctions with a high rectification ratio.

Transparent p-CuI/n-BaSnO3-δ heterojunction diodes were successfully fabricated by the thermal evaporation of a (1 1 1) oriented γ-phase CuI film on top of an epitaxial BaSnO3-δ (0 0 1) film grown by the pulsed laser deposition. Upon the thickness of the CuI film being increased from 30 to 400 nm, the hole carrier density was systematically reduced from 6.0 × 1019 to 1.0 × 1019 cm-3 and the corresponding rectification ratio of the pn diode was proportionally enhanced from ~10 to ~106. An energy band diagram exhibiting the type-II band alignment is proposed to describe the behavior of the heterojunction diode. A shift of a built-in potential caused by the hole carrier density change in the CuI film is attributed to the thickness-dependent rectification ratio. The best performing p-CuI/n-BaSnO3-δ diode exhibited a high current rectification ratio of 6.75 × 105 at ±2 V and an ideality factor of ~1.5.

Design for an efficient single photon source based on a single quantum dot embedded in a parabolic solid immersion lens.

We have designed a single photon emitter based on a single quantum dot embedded within a single mode parabolic solid immersion lens (pSIL) and a capping low-index pSIL. Numerical simulations predicted that the emitter performance should exhibit a high photon collection efficiency with excellent far-field emission properties, broadband operation, and good tolerance in its geometric (spatial configuration) parameters. Good geometric tolerance in a single-mode pSIL without yielding significant losses in the photon collection efficiency is advantageous for device fabrication. The low-index top pSIL layer provided this structure with a high photon collection efficiency, even in the case of a small numerical aperture (NA). Photon collection efficiencies of 64% and 78% were expected for NA values of 0.41 and 0.5, respectively. In addition to the benefits listed above, our combined pSIL design provided excellent broadband performance in a 100 nm range.

Regulation of the expression of renal drug transporters in KEAP1-knockdown human tubular cells.

The kidney secretes various xenobiotics through a well-established transport system. The transcription factor NF-E2-related factor 2 (NRF2) up-regulates a subset of genes encoding antioxidant and detoxification proteins. Kelch-like ECH-associated protein 1 (KEAP1) down-regulates NRF2 by facilitating continuous degradation of NRF2 protein. Here, we investigated the role of NRF2 in the expression of renal drug transporters by using a stable KEAP1 knockdown renal tubular HK-2 cell line (shKEAP1). KEAP1 knockdown resulted in a significant increase in the expression of four renal transporters, namely, multidrug resistance protein 1 (MDR1; ABCB1), breast cancer resistance protein (BCRP; ABCG2), multidrug resistance-associated protein 2 (MRP2; ABCC2), and MRP3 (ABCC3). In western blot and immunocytochemical analyses, protein levels of these transporters were also significantly higher in the knockdown group. Consequently, shKEAP1 cells released more Hoechst 33342 fluorescent dye and doxorubicin, and they were more resistant to doxorubicin than the control cells. In addition, cisplatin resistance of shKEAP1 decreased upon co-incubation with a transporter inhibitor. Whereas, a short term incubation (24h) with sulforaphane did not show noticeable changes in the expression of transporter. Collectively, these results indicate that NRF2 regulates the expression of MDR1, BCRP, MRP2, and MRP3 in human tubular epithelial cells. Altered expression of these transporters affects drug secretion in these cells, which may result in the renal cellular damage upon exposure to nephrotoxic xenobiotics.

Hair-growth stimulation by conditioned medium from vitamin D3-activated preadipocytes in C57BL/6 mice.

AIMS: Recently, immature adipocyte lineage cells have been suggested as a potential hair-growth stimulator. Diverse studies have been attempted to find methods for the preconditioning of immature adipocyte lineage cells. The present study investigates the effect of conditioned medium (CM) from vitamin D3 (Vd3) pre-activated preadipocytes on hair-growth ability. MAIN METHODS: To test the effect of CM from Vd3 pre-activated preadipocytes on hair-growth efficiency in mice, we compared the differences in hair regenerated after injecting CM from mouse preadipocytes pre-activated with or without Vd3. Next, to determine the regulating factors, the VEGF level was measured by ELISA and angiogenesis level was evaluated by IHC. Finally, the signaling mechanism was investigated by inhibitor kinase assay and western blotting. KEY FINDINGS: The CM from Vd3 pre-activated preadipocyte injection markedly promoted the ability of hair regeneration in mice. The VEGF levels were increased by Vd3 treatment in vitro and the CM from Vd3 pre-activated preadipocytes significantly increased the angiogenesis in vivo, suggesting the involvement of angiognensis in the hair regeneration induced by CM from pre-activated preadipocytes. In signaling study, Vd3-enhanced VEGF production was reduced by an ERK1/2 inhibitor and the level of ERK1/2 phosphorylation was increased by treatment with Vd3. SIGNIFICANCE: This has been the first report on CM from Vd3 pre-activated preadipocyte displaying stimulatory effects on hair growth via the enhancement of angiogenesis in a hairless-induced C57BL/6 mice.

ERDR1 enhances human NK cell cytotoxicity through an actin-regulated degranulation-dependent pathway.

Erythroid differentiation regulator 1 (ERDR1), which is a stress-related survival factor, exhibits anti-cancer effects against melanoma. However, the function of ERDR1 on immune cells has not been examined. We investigated whether ERDR1 regulates the cytotoxic ability of human natural killer (NK) cells, which are known as innate effector lymphocytes. In this study, treatment with recombinant ERDR1 resulted in enhanced NK cell cytotoxicity through the secretion of lytic granules. Furthermore, actin modulation was involved in the ERDR1-enhanced NK cell cytotoxicity. ERDR1 stimulated actin accumulation at the immunological synapse, which was induced by the activation of Vav-1 in NK cells. These findings suggest new insight into the function of ERDR1 function in the human immune system.

Effect of intraperitoneal administered ginseng total saponins on hyperalgesia induced by repeated intramuscular injection of acidic saline in rats.

The aim of this study was to assess the antinociceptive activity of ginseng total saponins (GTS) on hyperalgesia induced by repeated intramuscular injections of acidic saline in rats and to examine the mechanisms involved. Rats were injected intraperitoneally with a 0.9% saline vehicle or various doses of GTS after the development of hyperalgesia. Rats were then injected with N-methyl-D-aspartate (NMDA) or naloxone 10 min before GTS injection. The mechanical withdrawal threshold (MWT) was assessed with von Frey filaments. The MWT was significantly increased after intraperitoneal injection of 100 mg/kg and 200 mg/kg of GTS when compared with the MWT after the development of hyperalgesia. Injection of GTS with NMDA showed a significant decrease in the MWT when compared with GTS injection. GTS showed an antinociceptive activity against chronic muscle-induced pain, and the effect of GTS may be mediated by NMDA.

Preparation of Ga-68-NOTA as a renal PET agent and feasibility tests in mice.

INTRODUCTION: Positron emission tomography (PET) may provide more accurate quantification of kidney function such as glomerular filtration rate (GFR) than gamma imaging. The purpose of these experiments was to prepare and evaluate Ga-68 complexes as potential PET agents for measurement of GFR. METHODS: We labeled EDTA, DTPA, DOTA, and NOTA with Ga-68 obtained from a Ge-68/Ga-68-generator and measured the binding to serum and red blood cells. Biodistribution study was performed in male BALB/c mice after intravenous injection together with Cr-51-EDTA as the standard for glomerular filtration rate (GFR) measurement. Animal-PET study was performed using BALB/c mice. RESULTS: All the tested chelating agents except DTPA showed quantitative labeling yields (>99%). Among them, Ga-68-NOTA showed consistently low binding to both human and mouse RBC and serum protein. Biodistribution study showed no significant difference between Ga-68-NOTA and Cr-51-EDTA groups by one-way analysis of variance (ANOVA) (p>0.05). Furthermore, the GFR values obtained by Ga-68-NOTA and Cr-51-EDTA were almost same (0.26±0.04 and 0.25±0.04mL/min, respectively). Animal-PET study showed almost the same GFR (0.25mL/min) with the values obtained by biodistribution study. CONCLUSION: We proved that an easy-to-prepare agent Ga-68-NOTA is ideal for renal PET as well as for GFR measurement.

Quantum confinement effect of CdSe induced by nanoscale solvothermal reaction.

We report a novel method, nanoscale solvothermal reaction (NSR), to induce the quantum confinement effect of CdSe on nanostructured TiO(2) by solvothermal route. The time-dependent growth of CdSe is observed in solution at room temperature, which is found to be accomplished instantly by heat-treatment in the presence of solvent at 1 atm. However, no crystal growth occurs upon heat-treatment in the absence of solvent. The nanoscale solvothermal growth of CdSe quantum dot is realized on the nanocrystalline oxide surface, where Cd(NO(3))(2)·4H(2)O and Na(2)SeSO(3) solutions are sequentially spun on nanostructured TiO(2), followed by heat-treatment at temperatures ranging from 100 °C to 250 °C. Size of CdSe increases from 4.4 nm to 5.3 nm, 8.7 nm and 14.8 nm, which results in decrease in optical band gap from 2.19 eV to, 1.95 eV, 1.74 eV and 1.75 eV with increasing the NSR temperature from 100 °C to 150 °C, 200 °C and 250 °C, respectively, which is indicative of the quantum confinement effect. Thermodynamic studies reveal that increase in the size of CdSe is related to increase in enthalpy, for instance, from 3.77 J mg(-1) for 100 °C to 8.66 J mg(-1) for 200 °C. Quantum confinement effect is further confirmed from the CdSe-sensitized solar cell, where onset wavelength in external quantum efficiency spectra is progressively shifted from 600 nm to 800 nm as the NSR temperature increases, which leads to a significant improvement of power conversion efficiency by a factor of more than four. A high photocurrent density of 13.7 mA cm(-2) is obtained based on CdSe quantum dot grown by NSR at 200 °C.

Patterns of epidural venous varicosity in lumbar stenosis.

OBJECTIVE: Epidural venous varicosity (congestion of the epidural vein) is rarely introduced as an influential factor of clinical symptoms. However, there are several studies suggesting that epidural venous varicosity results in neurologic symptoms. We would like to highlight evidence that epidural venous varicosity results in neurologic symptoms and the relation between epidural venous varicosity and neural structure observed during the surgery. Based on our experiences, we also propose a new classification of epidural venous varicosity. METHODS: 29 patients with symptomatic lumbar stenosis received microsurgical decompression via partial hemilaminectomy. The authors retrospectively reviewed all recorded intraoperative pictures and categorized patterns of venous varicosities with relationship to neural structures. RESULTS: Type A is conditions in which epidural veins are dilated but located parallel to the nerve root on the lateral side of the nerve root and thus do not compress the nerve root. Type B is conditions in which varices are located on the anterior lateral side of the nerve root to compress the nerve root. Type C is conditions in which varices are encircled around the nerve root and compressing the nerve root. CONCLUSION: Epidural venous varicosity is observed in most lumbar stenosis patients with clinical symptoms. Of the types, the types of epidural venous varicosity compressing nerve structures were Type B and Type C. All epidural venous varicosities were removed regardless of classification during operations. Most patients showed relief in clinical symptoms after the operation. We thought to epidural venous varicosity as a factor that causes clinical symptoms of lumbar stenosis.

Sudden onset of cauda equina syndrome resulting from posterior migration of lumbar herniated disc without significant previous neurological signs.

While extruded disc fragments are known to migrate anteriorly, posteriorly, or laterally to the theca sac, posterior migration of the fragments is relatively rare and sudden onset of cauda equina syndrome (CES) caused by the migration is extremely rare. The authors experienced a case of CES that was manifested abruptly with sudden paraplegia caused by posterior migration of the lumbar intervertebral disc. A 74-year old man, who had no prior significant neurologic signs or trauma history, visited our emergency center with paraplegia of both lower extremities occurring suddenly when awakened. On magnetic resonance image (MRI) findings, we could detect ruptured disc herniation with severe lumbar stenosis at the L2-3 level. We performed an emergent decompression, and the right posterior migrated disc fragments at L2-3 were intraoperatively observed. The patient was fully recovered himself on the follow up after 3 months of the operation. In conclusion, early operation can result in better outcome in acute paraplegia caused by the posterior migrated disc fragments.

A new PEG-lipid conjugate micelle for encapsulation of CdSe/ZnS quantum dots.

A new polymer conjugate of poly(ethylene glycol) (PEG) and 10,12-pentacosadiynoic acid (PCDA), PEG-PCDA conjugate, was synthesized by coupling reaction between carboxyl group of PCDA and hydroxyl group of PEG. Luminescent CdSe/ZnS QDs were encapsulated in the polymer micelles of mixtures of PEG-PCDA and PCDA using solid dispersion method to prepare water-soluble and biocompatible QD micelles. Upon UV-irradiation, the core of QD micelles was further stabilized by intramicellar crosslinking between neighboring PCDA moieties. The polymer conjugate was characterized by 1H-NMR, FT-IR, and GPC measurements, and thereof QD micelles observed using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The QD micelles were spherical with diameters in the range of 30-190 nm. The encapsulated QDs in polymer micelles are water-soluble and have the high potential for applications in biomedical imaging and detection due to their good colloidal stability and biocompatible surface.

Preparation and characterization of CdSe/ZnS quantum dots encapsulated in poly(ethylene glycol)-b-poly(D,L-lactide) micelle nanoparticles.

The final goal of this study is to develop multi-functional organic/inorganic hybrid nanoparticles, which can be utilized as biomedical imaging probes and drug delivery carriers. As an initial step toward this goal, we encapsulated CdSe/ZnS quantum dots (QDs) into poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) micelles using a solid dispersion method. The size and fluorescent intensity of QDs encapsulated in PEG-PLA micelles depended on the amount of incorporated QDs. For example, when the amount of QDs increased from 0.1 to 1.0 microg, the mean diameter increased from 24.2 +/- 6.0 to 211.2 +/- 6.5 nm and the fluorescent intensity changed from 10.2 +/- 1.0 to 469.9 +/- 15.6 (RFU). Stability studies showed that the size and zeta-potential (ZP) of QDs encapsulated in PEG-PLA micelles (QEMs) did not change significantly in response to a change in pH conditions or under a 10% serum condition. We also tested the cytotoxicity and cellular uptake of the QEMs. The viability of HeLa cells treated with micelles for 24 h was 80-100% in various concentration ranges of micelles. Confocal laser scanning microscopic images showed that the QEMs penetrated into the cells, particularly into the cytosolic compartments. Our results suggest that the QEMs may be a promising multi-functional nanocarrier for biomedical imaging and drug delivery.