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Using mesoporous SiO2 to encapsulate CsPbBr3 nanocrystals is one of the best strategies to exploit such materials in devices. However, the CsPbBr3/SiO2 composites produced so far do not exhibit strong photoluminescence emission and, simultaneously, high stability against heat and water. We demonstrate a molten-salts-based approach delivering CsPbBr3/mesoporous-SiO2 composites with high PLQY (89 ± 10%) and high stability against heat, water, and aqua regia. The molten salts enable the formation of perovskite nanocrystals and other inorganic salts (KNO3–NaNO3–KBr) inside silica and the sealing of SiO2 pores at temperatures as low as 350 °C, representing an important technological advancement (analogous sealing was observed only above 700 °C in previous reports). Our CsPbBr3/mesoporous-SiO2 composites are attractive for different applications: as a proof-of-concept, we prepared a white-light emitting diode exhibiting a correlated color temperature of 7692K. Our composites are also stable after immersion in saline water at high temperatures (a typical underground environment of oil wells), therefore holding promise as oil tracers.

Oxidative stress has been implicated as critical pathogenic factors contributing to the etiology of diabetic retinopathy and other retinal diseases. This study investigated antioxidative effect of ascorbic acid and astaxanthin on ARPE-19 cells within an oxidative stress model induced by common biological sources of reactive oxygen species (ROS). Hydrogen peroxide (H2O2) at concentrations of 0.1&ndash, 0.8 mM and 20&ndash, 100 mJ/cm2 of ultraviolet B (UVB) were treated to ARPE-19 cells. Cell viability and intracellular ROS level changes were measured. With the sublethal and lethal dose of each inducers, 0&ndash, 750 &mu, M of ascorbic acid and 0&ndash, 40 &mu, M of astaxanthin were treated to examine antioxidative effect on the model. Ascorbic acid at concentrations of 500 and 750 &mu, M increased the cell viability not only in the UVB model but also in the H2O2 model, but 20 and 40 &mu, M of astaxanthin only did so in the UVB model. The combination of ascorbic acid and astaxanthin showed better antioxidative effect compared to each drug alone, suggesting a synergistic effect.

Introduction: Chlorfenapyr is a pyrrole-based pro-insecticide. The main activity of this agent is the inhibition of adenosine triphosphate synthesis, and it is used in agriculture to control several insects and mites resistant to carbamate, organophosphate and pyrethroid insecticide. The World Health Organization classifies this agent as a class II toxin (moderately hazardous). Case presentation: All previously reported cases of chlorfenapyr poisoning in humans occurred following oral ingestion except one case involving exposure to chlorfenapyr vapour. Discussion: In this report, we describe a case of chlorfenapyr intoxication after skin exposure in a 49-year-old patient who died 5 days after exposure. Conclusion: This case demonstrates that similar to oral ingestion, dermal absorption of chlorfenapyr may also be fatal.

We report a new Mg 2+ , Mn 4+ co-doped red-emitting SrLaMgTaO 6 phosphor for solid state lighting. The phosphor can be efficiently excited in the wavelength range of 250–500 nm, which matches well with the emission wavelengths of blue or NUV chips. The photo-luminescence spectra exhibit the highest emission peak at 692 nm from 2 E g → 4 A 2 spin forbidden transition of Mn 4+ under NUV excitation. The Mg 2+ co-dopant for charge compensation plays a key role in enhancing the luminescence intensity by a factor of 2.8. The incorporation of Mg 2+ ion in the host could not only suppress the energy migration among Mn 4+ ions but also eliminates the charge imbalance in Mn 4+ − Mg 2+ pairs. W-LED fabrication with different mass ratios of yellow emitting YAG: Ce 3+ and red emitting SrLaMgTaO 6 :Mn 4+ /Mg 2+ phosphors is designed to explore its possible application in warm w-LEDs with high CRI. The w-LEDs fabricated with the integration of SrLaMgTaO 6 :Mn 4+ /Mg 2+ red phosphor show changing trends toward warm white light with lower color temperature and higher CRI than that based on single yellow emitting YAG:Ce 3+ phosphors. The results suggest that SrLaMgTaO 6 : Mn 4+ /Mg 2+ phosphor has great potential for the warm w-LEDs application as a suitable red light component.

We report the properties of upconversion photoluminescence (UCPL) on SrLaMgTaO 6 crystal doped with trivalent erbium at concentrations of 1–20 mol% that were synthesized by a solid state reaction method from powder based precursors. The crystal structure, electronic structure, and optical properties of SrLa (1-x) MgTaO 6 :Er x were discussed by using X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), UV–vis spectrophotometer, DFT (density functional theory) calculations and photoluminescence (PL) spectra. Under the excitation of a 975 nm laser diode, the phosphors emitted green ( 2 H 11/2 , 4 S 3/2 → 2 I 15/2 ) and red ( 4 F 9/2 → 2 I 15/2 ) UCPL. Under the 10 mol% concentration of Er 3+ , the intensity of the green UCPL had increased in a linearly proportional to Er 3+ concentration, which was attributed to the UCPL of low concentration of Er 3 and it was mostly generated from ESA process. From higher Er 3+ concentration above 10 mol%, however, as the ETU process had additionally participated in UCPL the intensity of UCPL had decreased. It was attributed to the concentration quenching which was more active than ETU process at higher concentration of Er 3+ in SrLaMgTaO 6 .

The rapidly accelerated fibrosarcoma (Raf) kinase is canonically activated by growth factors that regulate multiple cellular processes. In this kinase cascade Raf activation ultimately results in extracellular regulated kinase 1/2 (Erk1/2) activation, which requires Ras binding to the Ras binding domain (RBD) of Raf. We recently reported that all-trans retinoic acid (atRA) rapidly (within minutes) activates Erk1/2 to modulate cell cycle progression in stem cells, which is mediated by cellular retinoic acid binding protein 1 (Crabp1). But how atRA-bound Crabp1 regulated Erk1/2 activity remained unclear. We now report Raf kinase as the direct target of atRA-Crabp1. Molecularly, Crabp1 acts as a novel atRA-inducible scaffold protein for Raf/Mek/Erk in cells without growth factor stimulation. However, Crabp1 can also compete with Ras for direct interaction with the RBD of Raf, thereby negatively modulating growth factor-stimulated Raf activation, which can be enhanced by atRA binding to Crabp1. NMR heteronuclear single quantum coherence (HSQC) analyses reveal the 6-strand β-sheet face of Crabp1 as its Raf-interaction surface. We identify a new atRA-mimicking and Crabp1-selective compound, C3, that can also elicit such an activity. This study uncovers a new signal crosstalk between endocrine (atRA-Crabp1) and growth factor (Ras-Raf) pathways, providing evidence for atRA-Crabp1 as a novel modulator of cell growth. The study also suggests a new therapeutic strategy by employing Crabp1-selective compounds to dampen growth factor stimulation while circumventing RAR-mediated retinoid toxicity.

Purpose We aimed to examine the utility of the Poison Severity Score (PSS) and Sequential Organ Failure Assessment (SOFA) score as early prognostic predictors of short-term outcomes in patients with carbon monoxide (CO) poisoning. We hypothesized that both the PSS and the SOFA score would be useful prognostic tools. Methods This was retrospective observational study of patients with CO poisoning who presented to the emergency department and were admitted for more than 24 hours. We calculated PSS, the initial SOFA score, a second (2nd) SOFA score, and a 24-hour delta SOFA score. The primary outcome was reported as the cerebral performance category (CPC) scale score at discharge. We classified those with CPC 1–2 as the good outcome group and those with CPC 3–5 as the poor outcome group. Results This study included 192 patients: 174 (90.6%) belonged to the good outcome group, whereas 18 (9.4%) belonged to the poor outcome group. The PSS (1.00 [0.00, 1.00] vs 3.00 [3.00, 3.00], p < 0.001), initial SOFA (1.00 [0.00, 2.00] vs 4.00 [3.25, 6.00], p < 0.001), 2nd SOFA score (0.00 [0.00, 1.00] vs 4.00 [3.00, 7.00], p < 0.001), and 24-hour delta SOFA score (-1.00 [-1.00, 0.00] vs 0.00 [-1.00, 1.00], p = 0.047) of the good outcome group were significantly higher than those of the poor outcome group. The areas under the receiver operating characteristic curve for PSS and the initial SOFA and 2nd SOFA scores were 0.977 (95% confidence interval [CI] 0.944–0.993), 0.945 (95% CI 0.903–0.973), and 0.978 (95% CI 0.947–0.994), respectively. Conclusion The PSS, initial SOFA score, and 2nd SOFA score predict acute poor outcome accurately in patients with CO poisoning.

PurposeVitreous vitamin C, as an anti-oxidant, is responsible for regulating oxygen tension and oxidative stress in the eye. Oxidative stress and retinal ischemia are implicated in the development of proliferative diabetic retinopathy (PDR). In this study, we aimed to determine whether vitreous level of vitamin C is compromised in patients with PDR and to investigate the association of diabetic macular ischemia and vitamin C.MethodsThis prospective study enrolled forty patients who underwent pars plana vitrectomy for the treatment of PDR (PDR group, n = 20) and idiopathic epiretinal membrane (control group, n = 20). Serum, aqueous humor, and the vitreous were collected for the analysis of vitamin C level by HPLC. Diabetic macular ischemia (DMI) in PDR group was evaluated with fluorescein angiography (FA).ResultsPDR patients (60.4 ± 2.1 y) were younger than non-diabetic control patients (67.4 ± 1.2 y). Serum, aqueous, and vitreous levels of vitamin C in PDR were 38.7%, 22.5%, and 11.1% of non-diabetic control group, respectively. All PDR patients had DMI (grade 1: 25%, grade 2: 30%, grade 3: 30%, grade 4: 15%). DMI grade was inversely correlated with the level of vitreous vitamin C (r = -0.546, P = 0.019), not with HbA1C, serum, or aqueous vitamin C level. In addition, the level of vitreous vitamin C (4.5 ± 2.6 μg/ml) in high DMI group (Gr 3 &4) was lower than that (31.0 ± 9.1 μg/ml) in low DMI group (Gr 1&2) (P = 0.015).ConclusionsVitreous level of vitamin C in PDR patients showed a tenfold decrease, which was associated with the degree of macular ischemia. This suggests that vitreous vitamin C depletion may cause macula ischemia in PDR patients.

We developed a facile synthesis of nanocomposite powders of CsPbX3 nanocrystals (NCs) embedded in silica. The synthesis starts from colloidal Cs4PbX6 NCs that are mixed with tetraethyl orthosilicate in the presence of nitric acid, which triggers the sol-gel reaction yielding the formation of SiOx and the conversion of starting NCs into CsPbX3 ones. The overall reaction delivers CsPbX3 NCs encased in a silica matrix. The resulting CsPbX3/SiOx nano-composite powders exhibited enhanced moisture and thermal stability in air. Also, when mixing different CsPbX3/SiOx samples having diverse anion compositions, no interparticle anion exchange processes were observed, which is a further indication that the silica matrix acts as a robust barrier surrounding the NCs. Finallly, we used these composites as down-converter phosphors on top of a blue light-emitting diode (LED), delivering nearly ideal white light emission with the Commission Internationale de l'Eclairage (CIE) color coordinates (0.32, 0.33).

Importance Retinal biomarkers reflecting in vivo brain Alzheimer disease (AD) pathologic abnormalities could be a useful tool for screening cognitively normal (CN) individuals at the preclinical stage of AD. Objectives To investigate the association of both functional and structural alterations of the retina with in vivo AD pathologic abnormalities in CN older adults and model a screening tool for detection of preclinical AD. Design, Setting, and Participants This cross-sectional study included a total of 49 CN individuals, and all assessment was done at the Seoul National University Hospital, Seoul, South Korea. All participants underwent complete ophthalmic examination, including swept-source optical coherence tomography (SS-OCT) and multifocal electroretinogram as well as amyloid-β (Aβ) positron emission tomography and magnetic resonance imaging. Data were collected from January 1, 2016, through October 31, 2017, and analyzed from February 1, 2018, through June 30, 2020. Main Outcomes and Measures For structural parameters of the retina, the thickness of the macula and layer-specific thicknesses, including peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer measured by SS-OCT, were used for analysis. For functional parameters of the retina, implicit time and amplitude of rings 1 to 6 measured by multifocal electroretinogram were used. Results Of the 49 participants, 25 were women (51.0%); mean (SD) age was 70.6 (9.4) years. Compared with 33 CN individuals without Aβ deposition (Aβ−CN), the 16 participants with Aβ (Aβ+CN) showed reduced inner nasal macular thickness (mean [SD], 308.9 [18.4] vs 286.1 [22.5] μm;P = .007) and retinal nerve fiber layer thickness, particularly in the inferior quadrant (133.8 [17.9] vs 103.8 [43.5] μm;P = .003). In addition, the Aβ+CN group showed prolonged implicit time compared with the Aβ−CN group, particularly in ring 5 (41.3 [4.0] vs 38.2 [1.3] milliseconds;P = .002). AD-related neurodegeneration was correlated with the thickness of the ganglion cell-inner plexiform layer only (r = 0.41,P = .005). The model to differentiate the Aβ+CN vs Aβ−CN groups derived from the results showed 90% accuracy. Conclusions and Relevance The findings of this study showing both functional as well as structural changes of retina measured by multifocal electroretinogram and SS-OCT in preclinical AD suggest the potential use of retinal biomarkers as a tool for early detection of in vivo AD pathologic abnormalities in CN older adults.

Precipitation and re-precipitation of metal ions has been carried out from original and supernatant solution producing Bi 3+ – Eu 3+ doped Y 2 O 3 :Eu 3+ and Eu 3+ /Tb 3+ doped Y 2 O 3 , respectively. Shorter reaction time is unable to consume all metal ions present in the solution which can be utilized through re-precipitation process. The doping of Bi 3+ – Eu 3+ in Y 2 O 3 helps to absorb maximum UV light. The activation of Y 2 O 3 matrix by Bi 3+ and Eu 3+ ions, together and separately, were studied considering the excitation energy transfer to the luminescence centers. The successful replacement of Y 3+ by RE 3+ ions can help for fine tuning of emission wavelength. Re-precipitation of supernatant solution by adding terbium precursor can successively produce uniform sized Tb 3+ doped Y 2 O 3 :Eu 3+ . The re-precipitation of the supernatant solution ensures maximum consumption of metal ions for higher product yield and possible fine tuning of emission wavelengths.

A phosphor with higher emission efficiency in the visible region can be very helpful in various optoelectronics applications such as solar cells. Effective conversion of UV and NIR radiations to more useful visible and red emissions were carried out through Gd 2 O 3 :Er 3+ nanostructures synthesized by conventional co-precipitation method. The spectroscopic study of Gd 2 O 3 :Er 3+ samples were carried out as a function of dopant concentration under the excitation wavelengths of 378, 975 and 1540 nm, respectively. The doping of erbium show downconversion emission at 561 and 660 nm under 378 nm excitation while upconversion emission under 975 and 1540 nm excitations shows upconversion of NIR photons to 561 and 660 nm visible emissions. The enhanced red emission (660 nm) at higher erbium concentration was observed due to the dominant cross-relaxation processes. The efficiency of upconversion luminescence is highly dependent on the various relaxation and energy transfer processes involved in different energy levels of erbium. The intensity of downconversion and upconversion emission was enhanced by lithium co-doping in Gd 2 O 3 :Er 3+ nanostructures. The incorporation of alkali metal ions in Gd 2 O 3 :Er 3+ shows considerable enhancement in downconversion and upconversion emission intensity making the phosphor more suitable for optoelectronic applications.

Study Objective To investigate whether these properties of reinforced tubes cause difference in insertion depth compared to standard polyvinyl chloride tracheal tubes. Design A randomized controlled trial. Setting Operation room. Materials Standard polyvinyl chloride tracheal tubes, reinforced tubes. Interventions Seventy-six adult patients undergoing surgery under general anesthesia were randomly allocated with standard tube (n=38) or reinforced tube (n=38) intubation. The endotracheal tube was fixed at the right canine with a predetermined insertion depth using the formula: endotracheal tube insertion length (cm)=0.1977 × [body height (cm)] – 12.7423. Measurements The distances between the tracheal tube tip and the carina using fiberoptic bronchoscope. Main Results The mean tip-to-carina distance of reinforced tube was about 1.2cm longer than that of standard tube ( P Conclusions The insertion depth of straight reinforced tracheal tubes can be shorter than that of standard polyvinyl chloride tracheal tubes due to different tube pathways in the upper airway.

All-trans Retinoic acid (RA) and its derivatives are potent therapeutics for immunological functions including wound repair. However, the molecular mechanism of RA modulation in innate immunity is poorly understood, especially in macrophages. We found that topical application of RA significantly improves wound healing and that RA and IL-4 synergistically activate Arg1, a critical gene for tissue repair, in M2 polarized macrophages. This involves feed forward regulation of Raldh2, a rate-limiting enzyme for RA biosynthesis, and requires Med25 to coordinate RAR, STAT6 and chromatin remodeler, Brg1 to remodel the +1 nucleosome of Arg1 for transcription initiation. By recruiting elongation factor TFIIS, Med25 also facilitates transcriptional initiation-elongation coupling. This study uncovers synergistic activation of Arg1 by RA and IL-4 in M2 macrophages that involves feed forward regulation of RA synthesis and dual functions of Med25 in nucleosome remodeling and transcription initiation-elongation coupling that underlies robust modulatory activity of RA in innate immunity.

Particulate matter (PM) in the atmosphere has wideranging health, environmental, and climate effects, many of which are attributed to fine-mode secondary organic aerosols. PM concentrations are significantly enhanced by primary particle emissions from traffic sources. Recently, in order to reduce CO2 and increase fuel economy, gasoline direct injected (GDI) engine technology is increasingly used in vehicle manufactures. The popularization of GDI technique has resulted in increasing of concerns on environmental protection. In order to better understand variations in chemical composition of particulate matter from emissions of GDI vehicle versus a port fuel injected (PFI) vehicle, a high time resolution chemical composition of PM emissions from GDI and PFI vehicles was measured at facility of Transport Pollution Research Center (TPRC), National Institute of Environmental Research (NIER), Korea. Continuous measurements of inorganic and organic species in PM were conducted using an Aerodyne high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). The HR-ToF-AMS provides insight into nonrefractory PM composition, including concentrations of nitrate, sulfate, hydrocarbon-like and oxygenated organic aerosol, and organic mass with 20 sec time resolution. Many cases of PM emissions during the study were dominated by organic and nitrate aerosol. An overview of observed PM characteristics will be provided along with an analysis of comparison of GDI vehicle versus PFI vehicle in PM emission rates and oxidation states.

Background Methylene blue is the first-line therapy for methemoglobinemia, but it can be intermittently unavailable due to production issues. For this clinical scenario, alternative treatment options need to be explored. Hyperbaric oxygenation (HBO) is conventionally applied as an adjunctive therapy during the systemic administration of methylene blue. Currently, little is known regarding the effects of HBO monotherapy in methemoglobinemia. We report a case of methemoglobinemia that was successfully treated with HBO monotherapy. Case Report A 41-year-old man presented to the Emergency Department with dyspnea and dizziness subsequent to smoking in a garage filled with motor vehicle exhaust gas. There were no abnormal heart or lung sounds. While administering oxygen flowing at 15 L/min via a mask with a reservoir bag, blood tests revealed high methemoglobin (MetHb) levels at 59.6%. He was treated with HBO monotherapy, and sequential tests showed that the MetHb level decreased significantly to 34.0%, 12.8%, 6.2%, and eventually, 3.5%. He was discharged with stable vital signs the next day. Why Should an Emergency Physician Be Aware of This? HBO monotherapy is an effective alternative treatment for methemoglobinemia when methylene blue is not available.

The experimental and theoretical studies of the optical properties of SrMoO4:Tb3+ phosphors were carried out. The structural, optical, and electronical properties of the phosphors were systematically studied. The phosphor samples were crystallized at different temperatures via a sol–gel method. Excitation spectra of SrMoO4:Tb3+ powder samples exhibited gradual red shift and luminescent intensity changed with increasing the sintering temperature. Such spectral changes depend strongly on the crystallographic properties such as lattice parameters and crystallinity. The shift of the excitation spectra is mainly ascribed to the covalent bond interaction between Mo O bonds. An energy band model was demonstrated to describe the luminescence mechanism in the material.

Background: Cardiac enzymes such as creatine kinase-MB, troponin I, and brain natriuretic peptide (BNP) are thought to be useful prognostic factors in patients with acute ischemic stroke. This study investigated the efficacy of cardiac biomarkers as prognostic factors. Methods: We reviewed patients with acute ischemic stroke whose cardiac biomarkers had been measured and who were admitted to our hospital between January 2012 and December 2013. The cardiac biomarkers were measured within 24 hours after admission to the emergency room. We evaluated the clinical characteristics and compared the outcomes of the patients based on their cardiac biomarkers. Results: The following cardiac biomarkers were measured in 219 patients with acute ischemic stroke: creatine kinase-MB (n=218), troponin I (n=219), and BNP (n=143). Statistically significant differences were observed in older age (68.77±12.42 vs. 74.59±6.68, p

Colchicine poisoning is rare but can cause potentially life-threatening toxic complications such as hypovolemic shock, cardiovascular collapse and multiple organ failure. In this case report, we describe a case of a 20-year-old female who presented to the emergency department after suicidal ingestion of a toxic dose of colchicine. She developed thrombocytopenia, neutropenia and acute respiratory distress syndrome that required blood transfusion and administration of granulocyte colony stimulating factor for the prevention of infectious complications. With regard to the clinical manifestations of colchicine toxicity, we discussed suggested mechanisms.

An intense red-emitting NaY(MoO4)2:Eu3+ nanophosphor was developed using a hydrothermal technique. A highly pure and single-phase NaY(MoO4)2:Eu3+ nanopowder was obtained after sintering the as-prepared sample at 800 degrees C. The crystal structure and photoluminescence properties of this double molybdate were investigated. X-ray diffraction analysis showed that the NaY(MoO4)2 nanoparticles have a scheelite-type tetragonal structure, without mixed phases. Rietveld analysis provided the atomic coordinates and Mo-O-rare-earth angles. The morphology of the molybdate precursor was controlled by adjusting the synthesis conditions. The pH was found to play a crucial role in the particle size and morphology distribution. The crystalline powder phosphor exhibited intense and efficient red emissions attributed to efficient energy-transfer from MoO4(2-) to Eu3+. The chromaticity coordinates (x,y) of the NaY(MoO4)2:Eu3+ phosphor sample correspond to (0.662, 0.337). The NaY(MoO4)2:Eu3+ powder exhibited a deep-red emission under near-ultraviolet (UV) excitation, indicating a promising red phosphor for white-light-emitting diodes based on near-UV light-emitting diodes.

Flufenoxuron is an insect growth regulator which inhibits chitin (exoskeleton) biosynthesis in insect's body. Not much is known about its toxicity to human. This report describes three patients who developed worsening lactic acidosis and hypotension after ingestion of flufenoxuron-containing materials. Two of the three patients received continuous renal replacement therapy and survived. (Hong Kong j.emerg.med. 2014;21:181-184)

The rapidly accelerated fibrosarcoma (Raf) kinase is canonically activated by growth factors that regulate multiple cellular processes. In this kinase cascade Raf activation ultimately results in extracellular regulated kinase 1/2 (Erk1/2) activation, which requires Ras binding to the Ras binding domain (RBD) of Raf. We recently reported that all-trans retinoic acid (atRA) rapidly (within minutes) activates Erk1/2 to modulate cell cycle progression in stem cells, which is mediated by cellular retinoic acid binding protein 1 (Crabp1). But how atRA-bound Crabp1 regulated Erk1/2 activity remained unclear. We now report Raf kinase as the direct target of atRA-Crabp1. Molecularly, Crabp1 acts as a novel atRA-inducible scaffold protein for Raf/Mek/Erk in cells without growth factor stimulation. However, Crabp1 can also compete with Ras for direct interaction with the RBD of Raf, thereby negatively modulating growth factor-stimulated Raf activation, which can be enhanced by atRA binding to Crabp1. NMR heteronuclear single quantum coherence (HSQC) analyses reveal the 6-strand β-sheet face of Crabp1 as its Raf-interaction surface. We identify a new atRA-mimicking and Crabp1-selective compound, C3, that can also elicit such an activity. This study uncovers a new signal crosstalk between endocrine (atRA-Crabp1) and growth factor (Ras-Raf) pathways, providing evidence for atRA-Crabp1 as a novel modulator of cell growth. The study also suggests a new therapeutic strategy by employing Crabp1-selective compounds to dampen growth factor stimulation while circumventing RAR-mediated retinoid toxicity.

Purpose To evaluate the relationship between pericytes and endothelial cells in retinal neovascularization through histological and immunofluorescent studies. Methods C57BL/6J mice were exposed to hyperoxia from postnatal day (P) 7 to P12 and were returned to room air at P12 to induce a model of oxygen-induced retinopathy (OIR). The cross sections of enucleated eyes were processed with hematoxylin and eosin. Immunofluorescent staining of pericytes, endothelial cells, and N-cadherin was performed. Microfluidic devices were fabricated out of polydimethylsiloxane using soft lithography and replica molding. Human retinal microvascular endothelial cells, human brain microvascular endothelial cells, human umbilical vein endothelial cells and human placenta pericyte were mixed and co-cultured. Results Unlike the three-layered vascular plexus found in retinal angiogenesis of a normal mouse, angiogenesis in the OIR model is identified by the neovascular tuft extending into the vitreous. Neovascular tufts and the three-layered vascular plexus were both covered with pericytes in the OIR model. In this pathologic vascularization, N-cadherin, known to be crucial intercellular adhesion molecule, was also present. Further evaluation using the microfluidic in vitro model, successfully developed a microvascular network of endothelial cells covered with pericytes, mimicking normal retinal angiogenesis within 6 days. Conclusions Pericytes covering endothelial cells were observed not only in vasculature of normal retina but also pathologic neovascularization of OIR mouse at P17. Factors involved in the endothelial cell-pericyte interaction can be evaluated as an attractive novel treatment target. These future studies can be performed using microfluidic systems, which can shorten the study time and provide three-dimensional structural evaluation.

All trans retinoic acid (atRA) is one of the most potent therapeutic agents, but extensive toxicity caused by nuclear RA receptors (RARs) limits its clinical application in treating cancer. AtRA also exerts non-genomic activities for which the mechanism remains poorly understood. We determine that cellular retinoic acid binding protein 1 (Crabp1) mediates the non-genomic activity of atRA, and identify two compounds as the ligands of Crabp1 to rapidly and RAR-independently activate extracellular signal regulated kinase 1/2 (ERK1/2). Non-canonically activated ERK activates protein phosphatase 2A (PP2A) and lengthens cell cycle duration in embryonic stem cells (ESC). This is abolished in Crabp1-null ESCs. Re-expressing Crabp1 in Crabp1-negative cancer cells also sensitizes their apoptotic induction by atRA. This study reveals a physiological relevance of the non-genomic action of atRA, mediated by Crabp1, in modulating cell cycle progression and apoptosis induction, and provides a new cancer therapeutic strategy whereby compounds specifically targeting Crabp1 can modulate cell cycle and cancer cell apoptosis in a RAR-independent fashion, thereby avoiding atRA’s toxicity caused by its genomic effects.

Reactive oxygen species (ROS) as well as vascular endothelial growth factor (VEGF) play important roles in pathologic retinal neovascularization. We investigated whether betaine inhibits pathologic retinal neovascularization in a mouse model of oxygen induced retinopathy (OIR). Betaine was intravitreally injected in OIR mice at postnatal day (P) 14. At P17, the neovascular tufts area in OIR retina was analyzed. Intravitreal injection of betaine (200μM) effectively reduced the neovascular tufts area in OIR retina (68.0±6.7% of the control eyes, P

In this paper, we report a successful synthesis of CaWO4:Eu3+ phosphor via an ethanol assisted hydrothermal process. X-ray diffraction (XRD) patterns, X-ray photoelectron spectroscopy (XPS) and field emission scanning electron microscope (FE-SEM) were used to investigate the growth of the products. The water and ethanol volume ratio is found to have extraordinary effect on the particle size and morphological appearance. Flower like ~ 1µm superstructures can be obtained with mixed solution of w/e of 50/50 at 120 °C hydrothermal sysnthesis for 12 h. High concentration of ethanol in aqueous solution was discovered to have a tendency in limiting the interaction between the small particles for crystallization. Temperature and time experiments were also performed to further investigate the growth mechanism of the ethanol assisted hydrothermal process. The photoluminescence properties of flower like CaWO4:Eu3+ has also been investigated.

The purpose of this study is to investigate the overall spray behavior characteristics for various injection conditions in a gasoline direct injection(GDI) injector with multi-hole. The spray characteristics, such as the spray penetration, the spray angle, and the injection quantity, were studied through the change of the injection pressure, the ambient pressure, and the energizing duration in a high-pressure chamber with a constant volume. The n-heptane with 99.5% purity was used as the test fuel. In a constant volume chamber, the injected spray was visualized by the spray visualization system, which consisted of the high-speed camera, the metal-halide lamp, the injector control device, and the image analysis system with the image processing program. It was revealed that the injection quantity was mainly affected by the difference between the injection pressure and the ambient pressure. For low injection pressure conditions, the injection quantity was decreased by the increase of the ambient pressure, while it nearly maintained regardless of the ambient pressure at high injection pressure. According to the increase of the ambient pressure in the constant volume chamber, the spray development became slow, consequently, the spray tip penetration decreased, and the spray area increased. In additions, the circular cone area decreased, and the vortex area increased.

The red-emitting phosphor of Eu3+ ions doped CaWO4 and lithium ions co-doped (Ca, Eu) WO4 have been synthesized by the solid-state reaction technology. The introduction of Li+ ions reduced the preparing temperature and the phosphors exhibited a very strong red emission. It is proved by X-ray diffraction and XPS spectrum that the Li+ ion substituted the Ca2+ in the lattice without changing the crystalline. The photoluminescence spectrum showed that after Li+ doping, the dominant emission peak of 5D0–7F2 centered at 617 nm was remarkably improved by a factor of 2.9, and the concentration quenching behavior was weakened until it is observed at 15 mol%. This is assigned to the incorporation of Li+ into host twinning the V ″ Ca and making a Schottky pair for charge compensation. Li+ acting as charge compensator is responsible for the enhancement of luminescent properties. The CIE coordinates were also calculated according to the NTSC system standard to be (0.682, 0.317), thus it is efficient enough to be used as red phosphor for NUV LED chips.

Background During neurosurgical procedures, patients are often exposed to hypoxic and ischemic brain damage. Cerebral ischemia leads to neuronal cell death and eventually causes neurological impairments. Remifentanil is a new ultra-short acting phenylpiperidine opioid analgesic. In this study, we evaluated remifentanil to determine if it exerts an anti-apoptotic effect in the hippocampal dentate gyrus following transient global ischemia in gerbils. Methods Step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemical staining for caspase-3 were performed. Results The numbers of TUNEL-positive cells and caspase-3-positive cells in the dentate gyrus were increased by ransient global ischemia. Latency in the step-down avoidance task was increased by transient global ischemia. Results revealed that apoptotic cell death in the dentate gyrus was increased significantly following transient global ischemia, resulting in memory impairment. However, treatment with remifentanil suppressed ischemia-induced apoptosis in the dentate gyrus, thereby alleviating the memory impairment that was induced by ischemic cerebral injury. Conclusions These results indicate that remifentanil may exert a neuroprotective effect on ischemic brain damage during surgery.

Purpose Lactic acid, the end product of glycolysis, has emerged as an immune-modulating metabolite in various diseases. In this study, we aimed to examine whether lactic acid contributes to the disease pathogenesis of choroidal neovascularization (CNV) and to investigate the role of macrophages in CNV pathogenesis. Methods CNV was induced by laser photocoagulation in C57BL/6J mice. Lactic acid concentration was measured in the RPE-choroid region. Macrophage infiltration and VEGF were quantified by flow cytometry. VEGF-positive areas and CNV lesions were measured by flat-mount immunofluorescence staining. To inhibit lactic acid uptake in vivo, alpha-cyano-4-hydroxycinnamic acid (α-CHC), a monocarboxylate transporter (MCT) blocker, was injected intravitreally 1 day after laser. VEGF productions were measured in ARPE-19, THP-1 cells, and human umbilical vein endothelial cells (HUVECs) by quantitative PCR and ELISA. Angiogenic activity of lactic acid-treated macrophages was assessed by HUVEC tube formation assay. Results Lactic acid was significantly increased in the RPE-choroid region of CNV-induced mice. Lactic acid upregulated VEGFA mRNA and VEGF protein expressions in THP-1 macrophages, but did not in ARPE-19 or HUVECs. THP-1 macrophages treated with lactic acid increased the angiogenesis of endothelial cells independent of MCT activity. Intravitreal injection of α-CHC substantially reduced the VEGF-positive area that colocalized with F4/80-positive macrophages. CNV lesions were also significantly reduced following α-CHC injection compared with vehicle-injected controls. Conclusions To our knowledge, these results show for the first time the role of lactic acid in facilitating neovascularization through macrophage-induced angiogenesis. We suggest that targeting macrophage metabolism can be a promising strategy for CNV treatment.

To find new biomarkers by stimulating acupuncture point GB34 (Yangneungcheon) which has neuroprotective effect on the mouse model of Parkinson's disease, analysis of cDNA microarray on mRNAs of the substantia nigra was performed.Male C57BL/6 mice were divided into two groups: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice (MPTP group, n=3); 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and acupuncture (GB34)-treated mice (MPTP + ACU group, n=3). The mice received an intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) once daily for 3 consecutive days. Manual acupuncture was performed 2 hours after every injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The total RNA in the substantia nigra of each mouse was isolated on 3 days after the last 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection. Agilent mouse whole genome 44K chip was used for microarray analysis and the hybridization image was analysed by GenePix Pro 6.0. Data normalization and analysis were performed using GeneSpring GX 7.3.1 program.The acupuncture stimulation revealed 799 genes (424 up- and 375 down-regulated) of which expression levels were changed more than two-folds in the MPTP + ACU group, compared to the MPTP group. The genes selected were classified into several categories based on their functions using DAVID Bioinformatics Resources 2008 (http://david.abcc.ncifcrf.gov/) and KEGG PATHWAY Database (http://www.genome.jp/kegg/pathway.html).Biomarkers in response to acupuncture stimulation to GB34 were identified in a mouse model for Parkinson's disease. These biomarkers might provide a promising clue for understanding the neuroprotective effect of acupuncture in Parkinson's disease.

This paper describes a numerical study for analyzing combustion and emission characteristics and for suggesting optimal operating conditions of homogeneous charge compression ignition (HCCI) engines fueled with dimethyl ether (DME). Numerous calculations for DME HCCI engines were conducted for wide ranges of intake temperatures, equivalence ratios, and boost pressures. On the basis of the results for HCCI engines, engine performance and emissions including CO, HC, NOx, and soot are shown on a peak cycle temperature and equivalence ratio map. In addition, combustion and emission characteristics of DME HCCI engines were compared to those of n-heptane HCCI engines for the same supplied lower heating values. Results of the present study showed that soot, HC, and NOx emissions are decreased but CO emission is increased by using DME instead of n-heptane for HCCI engines. Furthermore, the DME HCCI engine has a wider optimal operating range than the n-heptane HCCI engine.

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondriarelated genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants. Copyright

In this paper we describe the atomization and combustion characteristics of biodiesel fuels in a common-rail diesel engine. To investigate the effect of the mixing ratio of biodiesels on the emission characteristics and engine performance, the experiments were conducted at various mixing ratios of the biodiesel and engine operation conditions. In addition, the physical properties such as kinematic viscosity and cetane number of the biodiesel-blended fuel were analyzed to study relations with the fuel atomization and combustion characteristics. The atomization characteristics of biodiesel-blended fuels were investigated in terms of spray tip penetration, SMD, and mean velocity distributions by using a spray visualization system and phase Doppler particle analyzer. The effect of the mixing ratio on the combustion characteristics was studied on the basis of the results of the combustion pressure obtained from the single-cylinder engine at various experimental conditions. The emission characteristics of HC, N...

NO is an important factor that induces post-translational modifications of proteins by cellular reduction and oxidation mechanism: cysteinyl-nitrosylation or Tyr nitration. Nuclear factor (NF)-κB activity can be rapidly suppressed by sodium nitroprusside, a NO donor. This effect was effectively reversed by peroxynitrite scavenger deferoxamine, suggesting a Tyr nitration-mediated mechanism. Western blot with nitrotyrosine-specific antibody demonstrated that the p65 subunit of NF-κB was predominantly nitrated on Tyr residues. Tyr nitration of p65 induced its dissociation from p50, its association with IκBα, and subsequent sequestration of p65 in the cytoplasm by IκBα-mediated export. Liquid chromatography-coupled nanoelectrospray mass spectrometry revealed specific nitration on Tyr-66 and Tyr-152 residues of p65. Mutation studies confirmed that both Tyr-66 and Tyr-152 residues were important for the direct effects of NO on p65, which resulted in more p65 export and inactivation of NF-κB activity. This study identified a novel and efficient pathway where NO rapidly inactivated NF-κB activity by inducing Tyr nitration on p65.

Modulation of the spontaneous activity of rat medial vestibular nuclear neurons by nitric oxide was investigated using the whole-cell patch-clamp technique. The spike frequency was increased by sodium nitroprusside (SNP), a nitric oxide liberating agent, and it was also increased by another nitric oxide liberating agent, sodium-nitroso-N-acetylpenicillamine. L-Arginine, the substrate of nitric oxide synthase, increased the firing of the neurons. The increased SNP-induced firing was inhibited by 1H-[1,2,4]oxadiazolo[4,3-α]quinozalin-1-one (ODQ), a specific inhibitor of guanylate cyclase. These results suggest that nitric oxide increases the neuronal excitability of the neurons by a cGMP-dependent mechanism. Keywords:: nitric oxide, medial vestibular nucleus, action potential

Renal dipeptidase (RDPase, membrane dipeptidase, dehydropeptidase 1, EC 3.4.13.19) has been widely studied since it was first purified from porcine kidney brush border membrane. It was reported that RDPase activity in urine samples of acute and chronic renal failure patients decreases. Nitric oxide (NO) is a highly reactive free radical involved in a number of physiological and pathological processes. NO is able to act in a dual mode, leading either to induction of apoptosis or to blunted execution of programmed cell death. NO inhibited the RDPase release from porcine renal proximal tubules, which could be blocked by L‐NAME. Chitosan, the linear polymer of D‐glucosamine in β(1?4) linkage, not only reversed the decreased RDPase release by NO but also increased NO production in the proximal tubule cells. The stimulatory effect of NO on RDPase release from proximal tubules in the presence of chitosan must be different from the previously proposed mechanism of RDPase release via NO signaling pathway. Chitosan...

The mouse kappa-opioid receptor (KOR) gene is expressed in mouse embryonal carcinoma P19 cells and induced by retinoic acid (RA) within 24 h. An RA-responsive cis-acting element is identified within promoter I of the KOR gene. This element contains a GC box, a putative binding site for transcription factor Sp1. Enhanced binding of Sp1 to this GC box correlates with RA induction of KOR gene. Phosphatase inhibitor (sodium pyrophosphate) decreases RA induction of this promoter, whereas hypophosphorylation of Sp1 results in an increase in its DNA binding affinity to this promoter as demonstrated by in vitro gel retardation and in vivo chromatin immunoprecipitation assays. Consistently, the inhibitor of MEK, PD98058, dose-dependently enhances RA induction of this promoter, suggesting that the ERK signaling pathway is negatively involved in the RA induction of mouse KOR gene activities. Collectively, enhanced binding of Sp1 to promoter I of the KOR gene as a result of inhibiting the ERK pathway contributes to RA induction of this gene in P19.

NO is related to the pathological condition acute renal failure, in which we previously observed that the level of soluble dipeptidase in urine was decreased. In this study the role of NO in the shedding of the glycosylphosphatidylinositol (GPI)-anchored form of renal dipeptidase (RDPase) was examined. The NO donors sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine rapidly inhibited the release of RDPase from porcine kidney proximal tubules. The substrate of NO synthase, l-Arg, also inhibited the release of RDPase, and this effect was reversed by the NO synthase inhibitor N(omega)-nitro-l-arginine methyl ester. Western-blot analyses using antibodies raised against porcine RDPase and the inositol-1,2-cyclic monophosphate moiety formed on phospholipase C cleavage of the GPI anchor demonstrated that SNP mediated its inhibitory effect on the release of RDPase via a GPI-specific phospholipase C (GPI-PLC). Peroxynitrite scavengers (deferoxamine and superoxide dismutase) or reducing agent (dithiothreitol) did not affect SNP's inhibition of the release of RDPase. Exposure to the G-protein activator AlF(-)(4) mimicked the l-Arg effect in the presence of a low concentration of l-Arg, and the effect was completely reversed by {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122, an intracellular phosphatidylinositol-specific PLC (PI-PLC) inhibitor. These results suggest a signal-transduction pathway involving NO, which is produced by NO synthase(s) following activation of a G-protein-coupled PI-PLC, resulting in inhibition of the GPI-PLC that cleaves and releases RDPase. Therefore, this indicates a role for NO as an inhibitory regulator of the shedding of the GPI-anchored RDPase in acute renal failure.

The incubation of porcine renal proximal tubules (PTs) resulted in the release of the glycosylphosphatidylinositol (GPI)-anchored renal dipeptidase (RDPase, EC 3. 4. 13. 19) from the membrane after a lag period of approximately 6 hours. This spontaneous release of RDPase from the membrane was inhibited by antibiotics. When the incubation supernatant was added back to fresh PTs, both the antibiotic inhibition of RDPase release and the lag period disappeared. The released RDPase reacted with an anti-cross reacting determinant antibody indicating the presence of the Ins (1,2-cyc)P moiety. These results suggest that bacteria in the PTs, when incubated, grow and secrete a phosphatidylinositol-specific phospholipase C (PI-PLC). This enzyme then hydrolyses the GPI-anchored RDPase and is transferable. RDPase was purified following its release from the membrane by this simple and inexpensive method which may also be applied to other GPI-anchored proteins.

The release mechanism of the glycosyl-phosphatidylinositol (GPI)-anchored renal dipeptidase (EC 3.4.13.19) in vivo has been investigated. Triton X-114 phase separation indicated that the dipeptidase is exclusively present as a hydrophilic form in urine from porcine, rat, rabbit and human. Western blot analysis of human and porcine purified dipeptidase and the urine concentrates with anti-(cross-reacting determinant) serum demonstrated the presence of inositol 1,2-cyclic monophosphate indicating that the renal dipeptidase had been released from the membrane by the action of a phospholipase C. This is the first direct evidence for cleavage of a human GPI-anchored protein by a responsible phospholipase C in vivo.

It is known that an excess or deficiency of selenium (Se) causes abnormalities in hair. We evaluated changes in the hair follicles associated with Se imbalance in a C57BL/6 mouse model to better understand the role of Se in hair growth. Fifteen C57BL/6 mice were assigned to diets providing excessive, adequate, or deficient amounts of Se. Alopecia with poliosis was observed in the groups receiving either excessive or deficient selenium. Skin biopsy from alopecia patches showed increased telogen hair follicles with epidermal atrophy. There was a significant decrease of anti-apoptotic Bcl-2 and an increase of pro-apoptotic Bax in the excessive-Se group compared with the adequate group. We suggest that alopecia with poliosis is caused by changes in the hair follicle cycle due to the imbalance of Se and partially influenced by the decrease of the ratio of Bcl-2/Bax, which is associated with induction of apoptosis of keratinocytes.