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T helper 17 (Th17) cells subtype of non-T2 asthma is less responsive (resistant) to inhaled corticosteroids (ICS), so also called severe asthma. Methyl-CpG-binding domain protein 2 (MBD2) regulates the differentiation of the Th17 cells, showing the possibility of a therapeutic target in severe asthma. Androgen tends to show beneficial therapeutic effects and is a “hot research topic,” but its role in the differentiation and expression of Th17 cells via MBD2 is still unknown. The aim of this study was to evaluate how sex hormone interacts with MBD2 and affects the differentiation and expression of Th17 cells in severe asthma. Here, first, we measured the concentration of androgen, estrogen, and androgen estrogen ratio from subjects and correlated it with severe asthma status. Then, we established an animal model and bronchial epithelial cells (BECs) model of severe asthma to evaluate the role of MBD2 in the differentiation and expression of Th17 cells (IL-17), the therapeutic potential of sex hormones in severe asthma, and the effect of sex hormones in BECs regulated Th17 cells differentiation via MBD2 at the cellular level. Increased MBD2 expression and Th17 cells differentiation were noted in the animal and the BECs severe asthma models. Th17 cell differentiation and expression were MBD2 dependent. Androgen attenuated the differentiation of BECs regulated Th17 cells via MBD2 showing BECs as a therapeutic target of androgen, and these findings postulate the novel role of androgen in Th17 cells predominant neutrophilic severe asthma therapy through targeting MBD2.

Apoptosis of alveolar epithelial cells is a critical initial link in the pathogenesis of acute lung injury (ALI), recent studies have revealed that Methyl-CpG binding domain protein 2 (MBD2) was involved in the execution of apoptosis, yet its role in ALI remained unclear. In the present study, we aim to explore the role and mechanism of MBD2 in the pathogenesis of ALI. We have found that MBD2 expression, in parallel to apoptosis, increased in alveolar epithelial cells of mice treated with LPS, knockout of MBD2 reduced apoptosis and protected mice from LPS-induced ALI. In MLE-12 cells, a cell line of murine alveolar epithelial cells, LPS induced MBD2 expression and apoptosis in a dose- and time-dependent manner. Knockdown of MBD2 with shRNA alleviated, while overexpression of MBD2 increased LPS-induced apoptosis. Mechanistically, intracellular zinc level decreased when MLE-12 cells were treated with LPS. MBD2 knockdown restored intracellular zinc level after LPS treatment, and MBD2 overexpression further aggravated LPS-induced intracellular zinc loss. Metal transcription factor 1 (MTF1) is a critical transcription factor in charge of intracellular zinc efflux. LPS treatment induced MTF1 expression both in vivo and in vitro. Inhibition of MTF1 reduced LPS-induced apoptosis in MLE-12 cells. MBD2 could bind to the promoter region of MTF1 and promote MTF1 expression. Collectively, these data indicated that loss of MBD2-ameliorated LPS-induced alveolar epithelial cell apoptosis and ALI in mice via modulating intracellular zinc homeostasis by upregulating MTF1.

With the rapid development of nanotechnology, more and more products need to be etched on the surface of nanomaterials. Due to its own limitations, it is difficult to obtain in-depth and effective ...

Background: Studies have shown that methyl-CpG binding domain protein 2 (MBD2) expression is significantly elevated in a neutrophil-dominant severe asthma mouse model. It also regulates Th17 cell differentiation. The objective of this study was to investigate the relationship between serum MBD2 levels in patients with severe asthma with different endotypes.Methods: Eligible adults with confirmed asthma (n = 63) underwent a clinical assessment, asthma control test and pulmonary function test and were classified as having mild, moderate or severe asthma. Severe asthma endotypes were defined according to the percentage of Th2 and Th17 cells in the peripheral blood and by the type of inflammation. The percentage of Th2 and Th17 cells in the peripheral blood was determined by flow cytometry. Serum MBD2, eosinophilic cationic protein and myeloperoxidase were measured by enzyme-linked immunosorbent assay. Correlations of MBD2 expression with clinical parameters were evaluated using Spearman's rank correlation analysis.Results: Serum MBD2 levels were upregulated in patients with severe asthma compared to healthy controls and patients with mild to moderate asthma. MBD2 was also significantly increased in patients with Th17 severe asthma compared to patients with type 2 severe asthma. Furthermore, MBD2 was positively correlated with MPO and Th17 cells but negatively correlated with ECP and Th2 cells in patients with severe asthma.Conclusions: These findings suggest that serum MBD2 may be a potential new biomarker for identifying severe asthma, Th17 severe asthma and the type of airway inflammation. However, these findings are still preliminary and need to be further investigated.

A colloidal gold immunochromatographic assay (CG-ICA) was developed to detect sulfamethazine (SM2) residues in five kinds of meat: namely, chicken, pork, shrimp, beef, and fish. The limit of detection (LOD) of CG-ICA for SM2 detection was 0.104 ng mL−1 within 20 min. CG-ICA exhibited a wide linear range of 0.1 ng mL−1 to 96 ng mL−1 with a reliable correlation coefficient (R2 = 0.9938). The average recoveries of CG-ICA for SM2 detection in chicken, pork, shrimp, beef, and fish were 98.1% ± 4.6%, 86.1% ± 0.5%, 86.2% ± 4.9%, 71.7% ± 1.7%, and 79.2% ± 2.5%, respectively. The matrix effect of the five kinds of meat on CG-ICA was also assessed. The standard curves of the five matrices did not coincide with the standard curve of phosphate buffer saline, indicating that a matrix effect had occurred in CG-ICA for SM2 detection in the five matrices. The strongest matrix effect was elicited by beef, followed by fish, pork, and shrimp, whereas the weakest matrix effect was produced by chicken.

This study was examined the thermal behavior of graphene nanosheets/carbon nanotubes-water nanofluid using the molecular dynamics method. First, the atomic stability in simulated structures was investigated by examining kinetic and potential energies. The results of this part represent the convergence of physical quantities. Also, the simulated samples' atomic and thermal behavior was studied by examining independent variables, including the volume fraction and the dimensions of carbon nanoparticles (graphene nanosheets/carbon nanotubes). The molecular dynamics simulations show that with the addition of carbon nanoparticles (NPs) with optimal value (5%), the phase change time and the thermal conductivity of the simulated nanofluid were converged to 1.10 ns and 0.73 W/mK, respectively. Also, increasing the dimensions of carbon NPs leads to a reduction in the phase change time of the simulated structure. Numerically, by increasing the length of carbon NPs to 1 nm, the phase change time in this sample reduces to 1.02 ns? Generally, these results indicate that the thermal behavior of the water-based fluid improved with the addition of carbon NPs.

The high-temperature oxidation behaviors of Nimonic95 alloy at 800 °C, 900 °C and 1000 °C were studied. The diffusion process of alloying elements in different stages of oxidation was studied and analyzed, and the pre-oxidation process was established. The results showed that multilayer oxide films formed in the air at 800 °C, 900 °C and 1000 °C, the outer layer was mainly Cr2O3 with a small amount of Al2O3, TiO2 and composite oxides such as CrTi spinel. The inner layer was mainly Al2O3. Nimonic95 alloy has excellent oxidation resistance at 800 °C and 900 °C, but poor oxidation resistance at 1000 °C and the oxide film peeled off in a short time. The oxidation resistance of Nimonic95 alloy at 1000 °C can be improved significantly by pre-oxidation at 800 °C for 140 h.

The role of the microalloying process in relaxation behavior and crystallization evolution of Zr20Cu20Ni20Ti20Hf20 high entropy bulk metallic glass (HEBMG) was investigated. We selected Al and Nb elements as minor elements, which led to the negative and positive effects on the heat of mixing in the master HEBMG composition, respectively. According to the results, both elements intensified β relaxation in the structure; however, α relaxation remained stable. By using different frequencies in dynamic mechanical analysis, it was revealed that the activation energy of β relaxation for the Nb-added sample was much higher, which was due to the creation of significant structural heterogeneity under the microalloying process. Moreover, it was found that Nb addition led to a diversity in crystallization stages at the supercooled liquid region. It was suggested that the severe structural heterogeneity in the Nb-added sample provided multiple energy-level sites in the structure for enhancing the crystallization stages.

The present study aimed to investigate the expression and significance of microRNA-31 (miR-31) in children with acute B-lymphoblastic leukemia (B-ALL). Bone marrow specimens and peripheral blood were collected from children with B-ALL (n=38) and healthy controls (n=18). Total RNA was extracted and the expression levels of miR-31 were measured using quantitative PCR. In addition, a receiver operating characteristic curve was generated, and the area under the curve (AUC) was calculated to evaluate the diagnostic value of miR-31 for the development of B-ALL. miR-31 expression was significantly lower in the B-ALL group compared with in the control group (P

In this work, we have examined the electronic properties and structural stability of gallium nitride/boron selenide (GaN/BSe) van der Waals heterostructures using the density functional theory calculations. Our results revealed that GaN monolayer interacts with BSe nanosheet through van der Waals (vdW) interactions. The negative binding energies indicated that all the patterned GaN/BSe heterostructures are energetically stable. The maximum (most negative) binding energy was found for the AB stacking pattern, representing the most stable binding of GaN over the BSe system. The electronic band structure calculations show an indirect band gap at the G point, suggesting the semiconducting property of the heterostructure systems. The highest energy band gap belongs to AB stacking pattern with the highest structural stability, whereas the lowest band gap belongs to pattern AD. Our results suggested that the hybrid GaN/BSe vdW heterostructure may be a favorable candidate for applications in future nanoelectronic devices.

A novel lateral flow assay (LFA) was developed by introducing Eu (III)-doped polystyrene nanoparticles (EuNPs) for rapid and ultra-sensitive detection of sulfamethazine (SM2) in raw milk. The limit of detection and linear range of the proposed method were 0.0045 and 0.05���10 ng/mL, respectively. The recovery of LFA for the detection of SM2 in raw milk was 96.1���108.2%. The proposed LFA provides a rapid and convenient strategy for fast and ultra-sensitive screening of SM2 in raw milk. EuNP-LFA may be a remarkable method for the detection of other targets at low concentrations to ensure food safety.

Water-soluble CdS quantum dots (QDs) covered with cationic surfactant-cetyltrimethylammonium bromide (CTAB) were deposited on the highly ordered TiO 2 nanotube arrays (TNTAs) by various methods, such as direct current (DC) electrodeposition, cyclic voltammetric (CV) electrodeposition, and successive ionic layer adsorption reaction (SILAR). The morphology measurements show that CTAB capping could well control the QD size and the CV method could effectively prevent the nanoparticle aggregation and uniformly deposit QDs onto TNTAs. Among all the deposition methods studied, the sample prepared by the CV method possesses superior photoelectrical properties and photocatalytic activity. A maximum photoconversion efficiency of 2.81% is achieved for the CdS/TNTAs prepared by CV electrodeposition, which exhibits about 17 times enhancement over the efficiency of the sample prepared by DC electrodeposition. And the photocatalytic degradation of methyl orange under visible-light irradiation demonstrates that the rate constant of the sample prepared by the CV method is almost seven times of that of the untreated TNTAs. Moreover, the underlying mechanism for the improving properties has been discussed.

The dye-sensitized solar cells (DSSCs) have been fabricated using highly ordered TiO2nanotube arrays as photoelectrode and natural dyes as photosensitizers. The natural dyes were extracted from the abundant plants in the tropical region, such asTradescantia zebrina, kapok, and pitaya. The dyes could chemically couple with TiO2nanotubes and effectively convert visible light into electricity in DSSCs. A power conversion efficiency could be achieved up to 0.3% in the solar cell sensitized by the extracts from kapok with a short-circuit current of 0.86 mA/cm2. Furthermore, the influences of the crystal structure of TiO2nanotube arrays on the performance of the natural DSSCs were discussed.

A process is described for the synthesis of kilogram quantities of homochiral 4-silyloxycyclopentenone (R)-1, a key intermediate useful for the synthesis of a plurality of prostaglandin analogue drugs. Cyclopentenone (R)-1 was synthesized in 14 isolated steps from furfural. Key steps in the synthesis include a Wittig reaction, Piancatelli rearrangement, and an enzymatic resolution featuring in situ recycling of the undesired enantiomer furnishing the desired homochiral alcohol in ≥99.5% ee. As a retort to the unsatisfactory coformation of about 8% at best of the trans-olefin in the Wittig reaction, a change to the order of several steps and the identification of a recrystallisable, amine salt derivative, 2, allowed the unwanted isomer to be controlled to as low as 0.2%.

Free-standing open-ended TiO 2 nanotube membranes were fabricated by raising voltage for a short time at the end of anodization process. Benefiting from its semiconducting nature and distinctive through-hole structure, the applications of open-ended TiO 2 nanotube membranes on flow-through photocatalysis and nanoreactor were demonstrated. As for flow-through photocatalysis, the photocatalytic property of TiO 2 is beneficial to reduce the concentration of RhB solution during RhB molecules diffuse through open-ended TiO 2 nanotube membrane. As for nanoreactor application, CdS@TiO 2 core–shell nanocables were successfully fabricated by a simple paired-cell reaction. A possible formation mechanism for the growth of core–shell structure was discussed on the basis of a series of electron microscopy characterization results. In addition, we evaluated the photocatalytic activity of CdS@TiO 2 samples synthesized at different reaction time through the degradation of rhodamine B under simulated sunlight irradiation. It was found that the CdS@TiO 2 samples synthesized at 24 h exhibited about 100% enhanced photocatalytic activity as compared to bare TiO 2 nanotubes, while the CdS@TiO 2 samples synthesized at 48 h (core–shell nanocables) had the equivalent photocatalytic activity to the bare TiO 2 nanotubes. Such behavior that the photocalytic activity changes with CdS loading amount results from a compromise between a larger amount of light absorption and a lower efficiency of charge separation, as well as limited diffusion by channel blocking higher degree of CdS loading.

The photoelectrical properties of highly ordered TiO2 nanotube (TNT) arrays have been systematically and quantitatively studied and found to be closely related to their geometric and crystal structures. The geometric characteristics, including the nanotube diameter and length, were modified by adjusting the anodization potentials and durations, while the crystal structure was modified by thermal annealing at different temperatures. The nanotube array samples with the mixed crystalline phases possess higher photoconversion efficiency than those with the single anatase or rutile phase. The optimal content of rutile phase is about twice of that of anatase phase. In terms of the influence of the geometric structure, the TNT arrays with larger inner diameters and longer tube lengths have better photoelectrical properties. A geometric roughness factor has been applied to describe the combinative effect of the geometric characteristics. The TNT sample with the geometric roughness factor of 125.32 shows the superior photoconversion efficiency of 13.2%. The underlying mechanism has also been discussed in detail.

N-doped TiO2nanotube arrays were prepared by electrochemical anodization in glycerol electrolyte, followed by electrochemical deposition in NH4Cl solution. An orthogonal experiment was used to optimize the doping conditions. Electrolyte concentration, reaction voltage, and reaction time were the main factors to influence the N-doping effect which was the determinant of the visible range photoresponse. The optimal N-doping conditions were determined as follows: reaction voltage is 3 V, reaction time is 2 h, and electrolyte concentration is 0.5 M. The maximal photocurrent enhanced ratio was 30% under white-light irradiation. About 58% improvement of photocatalytic efficiency was achieved in the Rhodamine B degradation experiment by N doping. The kinetic constant of the N-doped TNT arrays sample was almost twice higher than that of the undoped sample. Further analysis by X-ray photoelectron spectroscopy supported that electrochemical deposition is a simple and efficient method for N doping into TiO2nanotube arrays.

Atrophy of dorsal root ganglia (DRG) and thinning of dorsal roots (DR) are hallmarks of Friedreich's ataxia (FRDA). Many previous authors also emphasized the selective vulnerability of larger neurons in DRG and thicker myelinated DR axons. This report is based on a systematic reexamination of DRG, DR and ventral roots (VR) in 19 genetically confirmed cases of FRDA by immunocytochemistry and single- and double-label immunofluorescence with antibodies to specific proteins of myelin, neurons and axons; S-100alpha as a marker of satellite and Schwann cells; laminin; and the iron-responsive proteins ferritin, mitochondrial ferritin, and ferroportin. Confocal images of axons and myelin allowed the quantitative analysis of fiber density and size, and the extent of DR and VR myelination. A novel technology, high-definition X-ray fluorescence (HDXRF) of polyethylene glycol-embedded fixed tissue, was used to "map" iron in DRG. Unfixed frozen tissue of DRG in three cases was available for the chemical assay of total iron. Proliferation of S-100alpha-positive satellite cells accompanied neuronal destruction in DRG of all FRDA cases. Double-label visualization of peripheral nerve myelin protein 22 and phosphorylated neurofilament protein confirmed the known loss of large myelinated DR fibers, but quantitative fiber counts per unit area did not change. The ratio of myelinated to neurofilament-positive fibers in DR rose significantly from 0.55 to 0.66. In VR of FRDA patients, fiber counts and degree of myelination did not differ from normal. Pooled histograms of axonal perimeters disclosed a shift to thinner fibers in DR, but also a modest excess of smaller axons in VR. Schwann cell cytoplasm in DR of FRDA was depleted while laminin reaction product remained prominent. Numerous small axons clustered around fewer Schwann cells. Ferritin in normal DRG localized to satellite cells, and proliferation of these cells in FRDA caused wide rims of reaction product about degenerating nerve cells. Mitochondrial ferritin was not detectable. Ferroportin was present in the cytoplasm of normal satellite cells and neurons, and in large axons of DR and VR. In FRDA, some DRG neurons lost their cytoplasmic ferroportin immunoreactivity, whereas the cytoplasm of satellite cells remained ferroportin positive. Ferroportin in DR axons disappeared in parallel with atrophy of large fibers. HDXRF of DRG detected regional and diffuse increases in iron fluorescence that matched ferritin expression in satellite cells. The observations support the conclusions that satellite cells and DRG neurons are affected by iron dysmetabolism; and that regeneration and inappropriate myelination of small axons in DR are characteristic of the disease.

Energy dispersive X-ray fluorescence (EDXRF) is a well-established and powerful tool for nondestructive elemental analysis of virtually any material. It is widely used for environmental, industrial, pharmaceutical, forensic, and scientific research applications to measure the concentration of elemental constituents or contaminants. The fluorescing atoms can be excited by energetic electrons, ions, or photons. A particular EDXRF method, monochromatic microbeam X-ray fluorescence (MμEDXRF), has proven to be remarkably powerful in measurement of trace element concentrations and distributions in a large variety of important medical, environmental, and industrial applications. When used with state-of-the-art doubly curved crystal (DCC) X-ray optics, this technique enables high-sensitivity, compact, low-power, safe, reliable, and rugged analyzers for insitu, online measurements in industrial process, clinical, and field settings. This new optic-enabled MμEDXRF technique is known as high-definition X-Ray fluorescence (HD XRF). Selected applications of HD XRF are described in this paper including air particulate analysis, analysis of body fluid contamination at ppb levels, elemental mapping of brain tissue and bone samples, as well as analysis of toxins in toys and other consumer products.

Chronic or intermittent extravasations of blood into the subarachnoid space, and dissemination of heme by circulating cerebrospinal fluid, are the only established causes of superficial siderosis of the central nervous system (CNS). We studied the autopsy tissues of nine patients by iron histochemistry, immunocytochemistry, single- and double-label immunofluorescence, electron microscopy of ferritin, and high-definition X-ray fluorescence. In one case, frozen brain tissue was available for quantitative assay of total iron and ferritin. Siderotic tissues showed extensive deposits of iron and ferritin, and infiltration of the cerebellar cortex was especially severe. In addition to perivascular collections of hemosiderin-laden macrophages, affected tissues displayed iron-positive anuclear foamy structures in the neuropil that resembled axonal spheroids. They were especially abundant in eighth cranial nerves and spinal cord. Double-label immunofluorescence of the foamy structures showed co-localization of neurofilament protein and ferritin but comparable merged images of myelin-basic protein and ferritin, and ultrastructural visualization of ferritin, did not allow the conclusion that axonopathy was simply due to dilatation and rupture of fibers. Heme-oxygenase-1 (HO-1) immunoreactivity persisted in macrophages of siderotic cerebellar folia. Siderosis caused a large increase in total CNS iron but high-definition X-ray fluorescence of embedded tissue blocks excluded the accumulation of other metals. Holoferritin levels greatly exceeded the degree of iron accumulation. The susceptibility of the cerebellar cortex is likely due to Bergmann glia that serve as conduits for heme; and the abundance of microglia. Both cell types biosynthesize HO-1 and ferritin in response to heme. The eighth cranial nerves are susceptible because they consist of CNS axons, myelin, and neuroglial tissue along their subarachnoid course. The persistence of HO-1 protein implies continuous exposure of CNS to free heme or an excessively sensitive transcriptional response of the HO-1 gene. The conversion of heme iron to hemosiderin probably involves both translational and transcriptional activation of ferritin biosynthesis.

Monochromatic imaging can provide better contrast and resolution than conventional broadband radiography. In broadband systems, low energy photons do not contribute to the image, but are merely absorbed, while high energy photons produce scattering that degrades the image. By tuning to the optimal energy, one can eliminate undesirable lower and higher energies. Monochromatization is achieved by diffraction from a single crystal. A crystal oriented to diffract at a particular energy, in this case the characteristic line energy, diffracts only those photons within a narrow range of angles. The resultant beam from a divergent source is nearly parallel, but not very intense. To increase the intensity, collimation was performed with polycapillary x-ray optics, which can collect radiation from a divergent source and redirect it into a quasi parallel beam. Contrast and resolution measurements were performed with diffracting crystals with both high and low angular acceptance. Testing was first done at 8 keV with an intense copper rotating anode x-ray source, then 17.5 keV measurements were made with a low power molybdenum source. At 8 keV, subject contrast was a factor of five higher than for the polychromatic case. At 17.5 keV, monochromatic contrast was two times greater than the conventional polychromatic contrast. The subject contrasts measured at both energies were in good agreement with theory. An additional factor of two increase in contrast, for a total gain of four, is expected at 17.5 keV from the removal of scatter. Scatter might be simply removed using an air gap, which does not degrade resolution with a parallel beam.

CdS-sensitized TiO2nanotube arrays have been fabricated using the method of successive ionic layer adsorption and reaction and used as a photoanode for quantum-dot-sensitized solar cells. Before being coated with CdS, the surface of TiO2nanotube arrays was treated with TiCl4, nitric acid (HNO3), potassium hydroxide (KOH), and methyltrimethoxysilane (MTMS), respectively, for the purpose of reducing the interface transfer resistance of quantum-dot-sensitized solar cells. The surfaces of the modified samples represented the characteristics of superhydrophilic and hydrophobic which directly affect the power conversion efficiency of the solar cells. The results showed that surface modification resulted in the reduction of the surface tension, which played a significant role in the connectivity of CdS and TiO2nanotube arrays. In addition, the solar cells based on CdS/TiO2electrode treated by HNO3achieved a maximum power conversion efficiency of 0.17%, which was 42% higher than the reference sample without any modification.

Determination of the microdistribution of trace elements in bone at low concentrations has previously been performed with proton induced X-ray emission (PIXE), high-energy synchrotron source X-ray fluorescence (XRF) and laser ablation - inductively coupled plasma mass spectrometry (LA-ICP-MS). Several commercial benchtop XRF systems with micrometer-scale resolution are currently available. While providing convenient, non-destructive mapping capability, they appear to lack the sensitivity required for detection of trace elements in biological tissues such as bone. We investigated the application of a prototype benchtop XRF system for the measurement of strontium and lead at physiological levels in bone. Detection of several elements of interest, including Sr and Pb was achieved with an experimental set up based on focused monochromatic microbeam X-ray fluorescence (Mµ-XRF) instrumentation with a low power source (45 W molybdenum tube) coupled to doubly curved crystal (DCC) optics. A cross-section of bone about 5 mm × 8 mm size was mapped with 80-µm resolution showing heterogeneous distribution of Sr and Pb. The data showed that Mµ-XRF coupled to DCC is powerful method for measurement of the spatial distribution of trace elements in bone.