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Based on the LAMOST survey and Sloan Digital Sky Survey, we use low-resolution spectra of 130 043 F/G-type dwarf stars to study the kinematics and metallicity properties of the Galactic disc. Our study shows that the stars with poorer metallicity and larger vertical distance from the Galactic plane tend to have a larger eccentricity and velocity dispersion. After separating the sample stars into likely thin-disc and thick-disc sub-samples, we find that there exists a negative gradient of rotation velocity Vφ with metallicity [Fe/H] for the likely thin-disc subsample, and the thick-disc sub-sample exhibits a larger positive gradient of rotation velocity with metallicity. By comparing with model predictions, we consider that the radial migration of stars appears to have influenced the formation of the thin disc. In addition, our results show that the observed thick-disc stellar orbital eccentricity distribution peaks at low eccentricity (e ~ 0.2) and extends to a high eccentricity (e ~ 0.8). We compare this result with four thickdisc formation simulation models, which imply that our result is consistent with the gas-rich merger model. [ABSTRACT FROM AUTHOR]

The ubiquitin- proteasome system is considered to be the key regulator of protein degradation. Bortezomib (BTZ) is the first proteasome inhibitor approved by the US Food and Drug Administration for treatment of relapsed multiple myeloma and mantle cell lymphoma. Recently, BTZ treatment was reported to inhibit right ventricular hypertrophy and vascular remodeling in hypoxia-exposed and monocrotaline-injected rats. However, the underlying mechanisms remain poorly understood. We previously confirmed that hypoxia-elevated basal intracellular Ca2+ concentration ([Ca2+]i) and store-operated Ca2+ entry (SOCE) in pulmonary artery smooth muscle cells (PASMCs) are involved in pulmonary vascular remodeling. In this study we aim to determine whether BTZ attenuates the hypoxia-induced elevation of [Ca2+] in PASMCs and the signaling pathway involved in this mechanism. Our results showed that 1) in hypoxia- and monocrotaline-induced rat pulmonary hypertension (PH) models, BTZ markedly attenuated the development and progression of PH, 2) BTZ inhibited the hypoxiainduced increase in cell proliferation, basal [Ca2+]i, and SOCE in PASMCs, and 3) BTZ significantly normalized the hypoxia-upregulated expression of hypoxia-inducible factor-γ, bone morphogenetic protein 4, canonical transient receptor potential isoforms 1 and 6, and the hypoxia-downregulated expression of peroxisome proliferatoractivated receptor-γ in rat distal pulmonary arteries and PASMCs. These results indicate that BTZ exerts its protective role in the development of PH potentially by inhibiting the canonical transient receptor potential-SOCE-[Ca2+]i signaling axis in PASMCs. [ABSTRACT FROM AUTHOR]

Our laboratory previously showed that sodium tanshinone IIA sulfonate (STS) inhibited store-operated Ca(2+) entry (SOCE) through store-operated Ca(2+) channels (SOCC) via downregulating the expression of transient receptor potential canonical proteins (TRPC), which contribute to the formation of SOCC (Wang J, Jiang Q, Wan L, Yang K, Zhang Y, Chen Y, Wang E, Lai N, Zhao L, Jiang H, Sun Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 48: 125-134, 2013). The detailed molecular mechanisms by which STS inhibits SOCE and downregulates TRPC, however, remain largely unknown. We have previously shown that, under hypoxic conditions, inhibition of protein kinase G (PKG) and peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling axis results in the upregulation of TRPC (Wang J, Yang K, Xu L, Zhang Y, Lai N, Jiang H, Zhang Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 49: 231-240, 2013). This suggests that strategies targeting the restoration of this signaling pathway may be an effective treatment strategy for pulmonary hypertension. In this study, our results demonstrated that STS treatment can effectively prevent the hypoxia-mediated inhibition of the PKG-PPAR-γ signaling axis in rat distal pulmonary arterial smooth muscle cells (PASMCs) and distal pulmonary arteries. These effects of STS treatment were blocked by pharmacological inhibition or specific small interfering RNA knockdown of either PKG or PPAR-γ. Moreover, targeted PPAR-γ agonist markedly enhanced the beneficial effects of STS. These results comprehensively suggest that STS treatment can prevent hypoxia-mediated increases in intracellular calcium homeostasis and cell proliferation, by targeting and restoring the hypoxia-inhibited PKG-PPAR-γ signaling pathway in PASMCs. [ABSTRACT FROM AUTHOR]

Aims: Previously we demonstrated that both hypoxia inducible factor-1 (HIF-1) and bone morphogenetic protein-4 (BMP4) up-regulate transient receptor potential canonical (TRPC) 1 and TRPC6, resulting in increased basal intracellular Ca2+ concentration ([Ca2+]i) in pulmonary arterial smooth muscle cells (PASMCs), driving development of chronic hypoxia (CH)-induced pulmonary hypertension (CHPH). This study aims to determine whether HIF-1 regulates BMP4, and whether BMP4 mediates TRPC and basal [Ca2+]i increases in hypoxic PASMCs. Methods and results: The level of BMP4 mature protein was increased for ~183% in distal pulmonary arterial smooth muscle (PA) from CH (10% O2 for 21 days; CH) exposed rats, and 143% in PASMCs cultured under prolonged hypoxia (4% O2 for 60 h). In rat PASMCs, HIF-1a overexpression up-regulated, whereas HIF-1a knockdown under hypoxia decreased BMP4 expression; site-mutation identified two functional HIF-1-binding sites in Bmp4 gene promoter; noggin or BMP4 siRNA treatment blocked hypoxia-induced increases of TRPC1 and TRPC6 expression and basal [Ca2+]i. Likewise, in mice, exposure to CH increased BMP4 expression in distal PA for ~80%, which was absent in HIF-1a heterozygous mutant mice. Comparing with wild-type littermates, BMP4 heterozygous mutant mice exposed to CH displayed lower BMP4 and TRPC levels in PA, decreased basal [Ca2+]i in PASMCs, and attenuated CHPH. In human PASMCs, HIF-1a knockdown attenuated hypoxia-induced BMP4 expression and knockdown of either HIF-1a or BMP4 abolished hypoxia-induced TRPC expression and basal [Ca2+]i. Conclusions: BMP4 acts downstream of HIF-1 and mediates hypoxia-induced up-regulation of TRPC, leading to increased basal [Ca2+]i in PASMCs, promoting CHPH pathogenesis. [ABSTRACT FROM AUTHOR]

To clarify the possible mechanism of cigarette smoke (CS)-induced pulmonary hypertension and furthermore provide effective targets for prevention and treatment, the effects of chronic CS on rat pulmonary arterial smooth muscle in vivo and nicotine treatment on rat pulmonary arterial smooth muscle cells (PASMCs) in vitro were investigated. In this study, we demonstrated that chronic CS exposure led to rat weight loss, right ventricular hypertrophy, and pulmonary arterial remodeling. A fluorescence microscope was used to measure intracellular calcium concentration ([Ca2+]i) in rat distal PASMCs. Results showed that basal [Ca2+]i and store-operated calcium entry (SOCE) levels in PASMCs from 3- and 6-mo CS-exposed rats were markedly higher than those in cells from the unexposed control animals (the increases in 6-mo CS group were more significant than that in 3-mo group), accompanied with increased canonical transient receptor potential 1 (TRPC1) and TRPC6 expression at both mRNA and protein levels in isolated distal PA. Simultaneously, in vitro study showed that nicotine treatment (10 nM) significantly increased basal [Ca2+]i and SOCE and upregulated TRPC1 and TRPC6 expression in cultured rat distal PASMCs. TRPC siRNA knockdown strategies revealed that the elevations of basal [Ca2+]i and SOCE induced by nicotine in PASMCs were TRPC1 and TRPC6 dependent. These results suggested that chronic CS-induced changes in vascular tone and structure in PA and the development of pulmonary hypertension might be largely due to upregulation of TRPC1 and TRPC6 expression in PASMCs, in which nicotine played an important role. [ABSTRACT FROM AUTHOR]

An atomic force microscopy (AFM) image is acquired by probe tip scanning on the surface of a sample. It is a distorted representation of the sample because of the finite size of the tip. To modify the distorted image and improve the measurement accuracy of the AFM image, it is important to estimate the tip shape. Tip estimation results mainly rely on the sample-dimensional uncertainty and AFM image noise. More reliable data of tip morphology can be collected if there is a suitable tip characteriser to reduce the sample-dimensional uncertainty and improve AFM image accuracy. A new tip characteriser for blind reconstruction of AFM tip morphology has been developed through the fabrication of gold nanorod array structures. Based on template synthesis, the gold film (surface roughness, 162.1 nm) was deposited on porous anodic alumina membrane by magnetron sputtering. The well-ordered nanorod array structures (100-400 nm height, 60 nm diameter, ~20 nm at apex and 80 nm pitch) were obtained. In combination with the blind reconstruction algorithm, the prepared nanostructures were used as the tip characteriser to estimate the morphology of the traditional AFM Si3N4 probe, which can effectively reduce the influence of the sample-dimensional uncertainty and image noise on the result of the tip blind reconstruction. [ABSTRACT FROM AUTHOR]

Chronic hypoxia causes remodeling and alters contractile responses in both pulmonary arteries and pulmonary veins. Although pulmonary arteries have been studied extensively in these disorders, the mechanisms by which pulmonary veins respond to hypoxia and whether these responses contribute to chronic hypoxic pulmonary hypertension remain poorly understood. In pulmonary arterial smooth muscle, we have previously demonstrated that influx of 2+ through store-operated calcium channels (SOCC) thought to be composed of transient receptor potential (TRP) proteins is likely to play an important role in development of chronic hypoxic pulmonary hypertension. To determine whether this mechanism could also be operative in pulmonary venous smooth muscle, we measured intracellular 2+ concentration ([Ca2+]) by fura-2 fluorescence microscopy in primary cultures of pulmonary venous smooth muscle cells (PVSMC) isolated from rat distal pulmonary veins. In cells perfused with 2+ - free media containing cyclopiazonic acid (10 µM) and nifedipine (5 μM) to deplete sarcoplasmic reticulum 2+ stores and block voltage-dependent 2+ channels, restoration of extracellular 2+ (2.5 mM) caused marked increases in [Ca2+], whereas MnCl2 (200 μM) quenched fura-2 fluorescence, indicating store-operated 2+ entry (SOCE). SKF-96365 and NiCl2, antagonists of SOCC, blocked SOCE at concentrations that did not alter 2+ responses to 60 mM KCl. Of the seven known canonical TRP (TRPC1-7) and six vanilloid-related TRP channels (TRPV1-6), realtime PCR revealed mRNA expression of TRPC1 > TRPC6 > TRPC4 > TRPC2 ≈ TRPC5 > TRPC3, TRPV2 > TRPV4 > TRPV1 in distal PVSMC, and TRPC1 > TRPC6 > TRPC3 > TRPC4 ≈ TRPC5, TRPV2 ≈ TRPV4 > TRPV1 in rat distal pulmonary vein (PV) smooth muscle. Western blotting confirmed protein expression of TRPC1, TRPC6, TRPV2, and TRPV4 in both PVSMC and PV. Our results suggest that SOCE through 2+ channels composed of TRP proteins may contribute to 2+ signaling in rat distal PV smooth muscle. [ABSTRACT FROM AUTHOR]

The pattern of gene expression for extracellular matrix metalloproteinase inducer (EMMPRIN) was revealed in the tooth germ of mouse mandibular molars using quantitative real-time PCR. In situ hybridization and immunohistochemical study demonstrated the characteristic distribution of EMMPRIN in the different stages of tooth germ development. To investigate the functional role played by EMMPRIN in tooth germ development, EMMPRIN siRNA interference approach was carried out in cultured mouse mandibles at embryonic day 11.0 (E11.0). The results showed that EMMPRIN siRNA-treated explants exhibited a marked growth inhibition of tooth germ compared to the control and scrambled siRNA-treated explants. Meanwhile, a significant increase in MT1-MMP mRNA expression and a reduction in MMP-2, MMP-3, MMP-9, MMP-13 and MT2-MMP mRNA expression were observed in the mouse mandibles following EMMPRIN abrogation. The current results indicate that EMMPRIN could thus be involved in the early stage of tooth germ development and morphogenesis, possibly by regulating the expression of MMP genes. [ABSTRACT FROM AUTHOR]

Summary: A series of silica gel(SG) supported metal ionic liquid catalysts(x[Bmim]Cl-CrCl3/SG) were synthesized and exploited for the esterification of palmitic acid(PA) with methanol(ML) to produce biodiesel efficiently. The 10%[Bmim]Cl-CrCl3/SG catalyst with high surface area and desirable acidity exhibited the best catalytic performance and reusability after six consecutive running cycles. Based on the response surface analysis, the optimal reaction conditions were obtained as follows: methanol/acid mole ratio = 11:1 mol/mol, catalyst amount = 5.3 wt%, reaction time = 65 min, as well as reaction temperature = 373 K, reaching to a biodiesel yield of 96.1%. Further kinetic studies demonstrated that the esterification of PA with ML obeyed 1.41 order kinetics for acid concentration with the activation energy of 16.88 kJ/mol. [ABSTRACT FROM AUTHOR]

Precise stellar ages of stars are necessary to study the evolution of the Milky Way. The age determination is significantly affected by C and O abundances of stars due to their contribution to the overall metallicity and opacity. On the basis of C and O abundances derived from high-resolution observations, we determine the ages of 148 FGK-type dwarfs in the solar neighborhood by considering C and O enhancements individually. Our results show that using C and O enhancements individually could affect the age determination of the high-α population, especially for stars with [O/α] > 0.2 dex, making them about 1 Gyr younger compared to the results using traditional α-enhanced models. This results in a steeper slope in the age–[α/Fe] relation for the high-α population (changes from 0.0339 ± 0.0075 to 0.0436 ± 0.0086), indicating a higher formation rate. We find no tight relation between age and [α/Fe] or [O/Fe] in the high-α populations. The distribution of space velocity for young α-rich stars shows that they are more likely characterized to the low-α populations. [ABSTRACT FROM AUTHOR]

Since Gaia DR2 was released, many velocity structures in the disk have been revealed, such as large-scale ridge-like patterns in phase space. Both kinematic information and stellar elemental abundances are needed to reveal their evolution history. We have used labels from the APOGEE survey to predict elemental abundances for a huge amount of low-resolution spectra from the Large Sky Area Multi-Object Fibre Spectroscopic Telescope survey. Deep learning with artificial neural networks can automatically draw on physically sensible features in the spectrum for their predictions. Abundances of 12 individual elements, [C/Fe], [N/Fe], [O/Fe], [Mg/Fe], [Al/Fe], [Si/Fe], [S/Fe], [Cl/Fe], [Ca/Fe], [Ti/Fe], [Mn/Fe], and [Ni/Fe], along with basic stellar labels Teff, log g, metallicity ([M/H] and [Fe/H]), and [α/M] for 1,063,386 stars have been estimated. Then, those stars were cross-matched with Gaia DR2 data to obtain kinematic parameters. We present distributions of chemical abundances in the Vϕ versus R coordinate. Our results extend the chemical characterization of the ridges in the (R, Vϕ) plane to about R = 13 kpc toward the anticenter direction. In addition, radial elemental abundance gradients for disk stars with abs(z) < 0.5 kpc are investigated, and we fitted a line for median abundance values of bins of stars with galactocentric distance between R > 7.84 kpc and R < 15.84 kpc. The radial metallicity gradients for disk stars are, respectively, −0.0475 ± 0.0015 for R ≥ 13.09 kpc and −0.0173 ± 0.0028 for R < 13.09 kpc. Gradients for other elemental abundances are also obtained for disk stars: the [α/M] gradient is 0.0030 ± 0.0002; the [Al/Fe] gradient is 0.0030 ± 0.0002; and the [Mn/Fe] gradient is −0.0078 ± 0.0005. [ABSTRACT FROM AUTHOR]

We determined the chemical and kinematic properties of the Galactic thin and thick disk using a sample of 307,246 A/F/G/K-type giant stars from the LAMOST spectroscopic survey and Gaia DR2 survey. Our study found that the thick disk globally exhibits no metallicity radial gradient, but the inner disk (R ≤ 8 kpc) and the outer disk (R > 8 kpc) have different gradients when they are studied separately. The thin disk also shows two different metallicity radial gradients for the inner disk and the outer disk, and has a steep metallicity vertical gradient of dex kpc−1, which becomes flat when it is measured at increasing radial distance. The metallicity radial gradient on the other hand becomes weaker with increasing vertical distance. Adopting a Galaxy potential model, we derived the orbital eccentricity of sample stars and found a downtrend of average eccentricity with increasing metallicity for the thick disk. The variation of the rotation velocity with the metallicity shows a positive gradient for the thick disk stars and a negative one for the thin disk stars. Comparisons of our observed results with models of disk formation suggest that radial migration could have influenced the chemical evolution of the thin disk. The formation of the thick disk could be affected by more than one process: the accretion model could play an indispensable role, while other formation mechanisms, such as the radial-migration or disk-heating model could also have a contribution. [ABSTRACT FROM AUTHOR]

We study the radial metallicity gradient Δ[M/H]/ΔRg as a function of [Mg/Fe] and with the help of a guiding radius based on the Apache Point Observatory Galactic Evolution Experiment and Gaia and then analyze the radial migration effect on the radial metallicity gradient and metallicity-rotation gradient between the Galactic thin and thick disks. The derived trend of gradient Δ[M/H]/ΔRg versus [Mg/Fe] shows a transition at [Mg/Fe] ∼0.18 dex, below which the gradient is negative and varies a little as [Mg/Fe] increases; however, it changes sharply in [Mg/Fe] ranges of 0.16–0.18, above which the gradient increases linearly with increasing [Mg/Fe], being a positive value at [Mg/Fe] ≳ 0.22 dex. These positive gradients in the high-[Mg/Fe] populations are found at kpc, and there are nearly no gradients toward higher . By comparing the metallicity distributions, the radial metallicity gradients Δ[M/H]/ΔR, and the metallicity-rotation gradients between the total sample and subsample (or subsample), we find that, for the thick disk, blurring flattens the gradient Δ[M/H]/ΔR and favors metal-poor high-eccentricity stars. These stars are responsible for the measured positive metallicity-rotation gradient of the thick disk. [ABSTRACT FROM AUTHOR]

We study the metallicity distribution and kinematic properties of 4680 A/F/G/K-type giant stars with 5 kpc selected from the LAMOST spectroscopic survey. The metallicity distribution of giant stars with kpc can be described by a three-peak Gaussian model with peaks at [Fe/H] ∼ −0.6 ± 0.1, −1.2 ± 0.3 and −2.0 ± 0.2, corresponding to the ratio of 19%, 74%, and 7%, respectively. The [α/Fe] is used to associate the three peaks with the thick-disk, inner-halo and outer-halo components of the Galaxy. The metallicity distribution of these giant stars, which is fit with Gaussians corresponding to the three components, show a growing fraction of inner-halo components and declining fraction of the thick-disk components with increasing distance from the Galactic plane. Adopting a galaxy potential model, we also derive the orbital parameters of the sample stars, such as orbit eccentricity and rotation velocity. The peak values of derived orbital eccentricity for stars covering different metallicity regions maintain e ∼ 0.75, independent of height above the plane, within the range 15 kpc. By comparing the MDFs of stars in different rotation velocity intervals, we find that the majority of the retrograde stars are more metal-poor than the prograde stars. [ABSTRACT FROM AUTHOR]

We present a statistical study of the planet–metallicity (P–M) correlation by comparing the 744 stars with candidate planets (SWPs) in the Kepler field that have been observed with LAMOST, and a sample of distance-independent, fake “twin” stars in the Kepler field with no planet reported (CKSNPs) yet. With well-defined and carefully selected large samples, we find for the first time a turnoff P–M correlation of Δ[Fe/H]SWPs–SNPs, which on average increases from ∼0.00 ± 0.03 dex to 0.06 ± 0.03 dex, and to 0.12 ± 0.03 for stars with Earth-, Neptune-, and Jupiter-sized planets successively, and then declines to ∼−0.01 ± 0.03 dex for more massive planets or brown dwarfs. Moreover, the percentage of those systems with positive Δ[Fe/H] has the same turnoff pattern. We also find that FG-type stars follow this general trend, but K-type stars are different. Moderate metal enhancement (∼0.1–0.2 dex) for K-type stars with planets of radii between 2 and 4 R⊕, compared to CKSNPs is observed, which indicates much higher metallicities are required for Super-Earths and Neptune-sized planets to form around K-type stars. We point out that the P–M correlation is actually metallicity-dependent, i.e., the correlation is positive at solar and supersolar metallicities, and negative at subsolar metallicities. No steady increase of Δ[Fe/H] against planet sizes is observed for rocky planets, excluding the pollution scenario as a major mechanism for the P–M correlation. All these clues suggest that giant planets probably form differently from rocky planets or more massive planets/brown dwarfs, and the core accretion scenario is highly favored, and high metallicity is a prerequisite for massive planets to form. [ABSTRACT FROM AUTHOR]

A total of 120 patients admitted to affiliated hospitals of the North Sichuan Medical College between September 2020 and June 2022 were recruited for this study and received percutaneous transhepatic cholangial drainage. Patients in the control group received parenteral nutrition support, whereas patients in the treatment group received parenteral and combined enteral nutrition support. Compared to the control group, the time of first exhaustion and defecation in the treatment group was faster, and the postoperative activity time and hospital stay were shorter. Serum albumin and prealbumin levels in both groups decreased on the 1st day after surgery and recovered on the 7th day, with the treatment group reaching higher levels. After surgery, the decline in alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin levels was higher in the treatment group. CD4+, CD8+ levels, and CD4+/CD8+ ratios in both groups were elevated, with the treatment group showing higher levels. The occurrence of complications in the treatment group was lessened relative to the control group. In summary, enteral combined parenteral nutrition support for patients with malignant obstructive jaundice after surgery can promote faster recovery of gastrointestinal function, improve nutritional status, facilitate the recovery of liver function, and promote immune function. [ABSTRACT FROM AUTHOR]

Metformin is the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. Although accumulated evidence has shed light on the consequences of metformin action, the precise mechanisms of its action, especially in the pancreas, are not fully understood. Aquaporin 7 (AQP7) acts as a critical regulator of intraislet glycerol content, which is necessary for insulin production and secretion. The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets. We used an in vivo model of high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic β-cells (INS-1 cells) damaged by hyperglycemia and hyperlipidemia. Our data showed that AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in vivo and in vitro in response to hyperglycemia and hyperlipidemia. T2DM rats treated with metformin demonstrated a reduction in blood glucose levels and increased regeneration of pancreatic β-cells. In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro. Overexpression of AQP7 increased glycerol influx into INS-1 cells, whereas inhibition of AQP7 reduced glycerol influx, thereby decreasing subsequent insulin secretion. Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression and promoting glycerol influx into pancreatic β-cells and subsequent insulin secretion in T2DM. [ABSTRACT FROM AUTHOR]

Background: Exposure to ambient ozone (O3) increases the susceptivity to allergens and triggers exacerbations in patients with asthma. However, the detailed mechanisms of action for O3 to trigger asthma exacerbations are still unclear.Methods: An ovalbumin (OVA)-established asthmatic mouse model was selected to expose to filtered air (OVA-model) or 1.0 ppm O3 (OVA-O3 model) during the process of OVA challenge. Next, the possible involvements of p38 MAPK and oxidative stress in the ozone actions on the asthma exacerbations were investigated on the mice of OVA-O3 model by treating them with SB239063 (a p38 MAPK inhibitor), and/or the α-tocopherol (antioxidant). Biological measurements were conducted including airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL), inflammation in the airway lumen and lung parenchyma, the phosphorylation of p38 MAPK and heat shock protein (HSP) 27 in the tracheal tissues, and the malondialdehyde (MDA) content and the glutathione peroxidase (GSH-Px) activity in lung tissues.Results: In OVA-allergic mice, O3 exposure deteriorated airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL) and pulmonary inflammation, accompanied by the increased oxidative stress in lung tissues and promoted p38 MAPK and HSP27 phosphorylation in tracheal tissues. Administration of SB239063 (a p38 MAPK inhibitor) on OVA-O3 model exclusively mitigated the Raw, the CL, and the BAL IL-13 content, while α-tocopherol (antioxidant) differentially reduced the BAL number of eosinophils and macrophages, the content of BAL hyaluronan, the peribronchial inflammation, as well as the mRNA expression of TNF-α and IL-5 in the lung tissues of OVA-O3 model. Administration of these two chemical inhibitors similarly inhibited the AHR, the BAL IFN-γ and IL-6 production, the perivascular lung inflammation and the lung IL-17 mRNA expression of OVA-O3 model. Interestingly, the combined treatment of both compounds together synergistically inhibited neutrophil counts in the BALF and CXCL-1 gene expression in the lung.Conclusions: O3 exposure during the OVA challenge process promoted exacerbation in asthma. Both p38 MAPK and oxidative stress were found to play a critical role in this process and simultaneous inhibition of these two pathways significantly reduced the O3-elicited detrimental effects on the asthma exacerbation. [ABSTRACT FROM AUTHOR]

[Figure: see text].

Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disorder with distinctive deposition of calcium phosphate microliths in the lungs. Mutation of the SLC34A2 gene was proved to be responsible for PAM. Here, we report the study of a family affected by PAM in China. Two daughters of an inbred family whose parents are cousins and are affected by PAM. Mutation analysis of the SLC34A2 gene by polymerase chain reaction (PCR) amplification and direct sequencing in both patients revealed that exon 5 was deleted on both alleles. Both parents of the patients are proved to be carriers of the mutated allele. Gap-PCR was performed to determine the breakpoints and a homologous deletion of 1152 bp encompassing exon 5 of the SLC34A2 gene (c.IVS4+1452&#95;IVS5+660del) was confirmed. A 4-bp fragment of TGGG was located on the edge of both upstream and downstream breakpoints. The upstream breakpoint lies in the same region as the breakpoint of a fused gene SLC34A2-ROS1 , which encodes a constitutive kinase in the lung cancer cell line HCC78 and nonsmall-cell lung cancer (NSCLC), suggesting that the deletion in this family is a hot spot for recombination, not only in cancer samples with somatic mutation, but also in PAM patients with germline genetic defects of SLC34A2 .