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Objective: To investigate the role of TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 in the mechanism of asthma combined with obstructive sleep apnea (OSA) in mice., Method: C57BL/6 mice were randomly divided into four groups: control group (NS-RA), asthma group (OVA-RA), OSA group (NS-IH), and asthma combined with OSA group (OVA-IH). After monitoring lung function in each group, the expression levels of TASK-1 and TASK-3 mRNA and protein in lung tissues were measured, and the correlation between the changes of both and lung function was analyzed., Results: A total of 64 male mice were studied. Penh, serum IgE concentrations, and the percentage of eosinophils in bronchoalveolar lavage fluid (BALF) were higher in OVA-RA and OVA-IH mice compared with NS-RA (P < 0.05),while the above indexes were slightly elevated in NS-IH mice compared with NS-RA (P > 0.05), where the Penh and the percentage of eosinophils in BALF was higher in OVA-IH mice than NS-IH (P < 0.05).Increased TASK-3 mRNA expression (P < 0.05) as well as TASK-1 and TASK-3 protein expression (P > 0.05) in lung tissues of OVA-RA and NS-IH mice compared with NS-RA, and TASK-3 mRNA expression was slightly more in the OVA-IH group compared with NS-RA (P > 0.05), but less compared with OVA-RA (P < 0.05) or NS-IH (P > 0.05), while TASK-1 and TASK-3 protein expression was increased in the OVA-IH group compared with the remaining three groups, and TASK-3 protein expression was associated with lung function impairment was positively correlated with the degree of lung function impairment (P < 0.05)., Conclusion: Task-1 and Task-3 may be involved in the pathogenesis of asthma with OSA by affecting lung function., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Previous studies demonstrated that phosphatases play a pivotal role in modulating inflammation-associated signal transduction, particularly in the context of heat shock, where Mitogen-Activated Protein Kinase Phosphatase-1 (MKP-1) appears to have a central role. Recently, Human Antigen R (HuR) has also been identified as a factor that enhances stress-response protein MKP-1 levels. Consequently, we have directed our interest towards elucidating the mechanisms by which heat shock induces MKP-1 mRNA stabilization, dependent on HuR via the p38 MAPK Signaling Cascade. In this study, we subjected Mouse Embryonic Fibroblast (Mef) cells to heat shock treatment, resulting in a potent stabilization MKP-1 mRNA. The RNA-binding protein HuR, known to influence mRNA, was observed to bind to the MKP-1 AU-rich 3 ´untranslated region. Transfection of p38 wild-type Mef cells with a flag-HuR plasmid resulted in a significant increase in MKP-1 mRNA stability. Interestingly, transfection of the siRNA for HuR into Mef cells resulted in diminished MKP-1 mRNA stability following heat shock, inhibition of p38 MAPK activity effectively curtailed heat shock-mediated MKP-1 mRNA stability. Immunofluorescence analyses further revealed that the translocation of HuR was contingent on p38 MAPK Signaling Cascade. Collectively, these findings underscore the regulatory role of heat shock in MKP-1 gene expression at posttranscriptional levels. The mechanisms underlying the observed increased MKP-1 mRNA stability are shown to be partially dependent on HuR through the p38 MAPK Signaling Cascade., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Analyzing the influence of the bed allocation and utilization efficiency in healthcare institutions on the isolation proportion of Multidrug-resistant organisms (MDROs) to provide data to support prevention and control of MDROs. In this study, the provincial panel data from 2014 to 2020 in China on health resource indicators, including the number of beds per 1,000 population, hospital bed utilization rate, and average hospital stay from 2014 to 2020 in China were used to analyze the relationship between bed allocation or utilization efficiency and MDROs by the panel data quantile regression model. It was shown that the number of beds per 1,000 population had a negative effect on the isolation proportion of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, methicillin-resistant coagulase-negative Staphylococcus, and cefotaxime or ceftriaxone resistant Escherichia coli (regression coefficient < 0, P < 0.05). The utilization rate of hospital bed had a positive effect on the isolation proportion of methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative Staphylococcus, vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, cefotaxime or ceftriaxone resistant Escherichia coli, carbapenem-resistant Escherichia coli, cefotaxime or ceftriaxone resistant Klebsiella pneumoniae, carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii (regression coefficient > 0, P < 0.05). The average hospital stay had a positive effect on the isolation proportion for several antibiotic-resistant organisms, including methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative Staphylococcus, vancomycin-resistant Enterococcus faecalis, vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, cefotaxime or ceftriaxone resistant Escherichia coli, carbapenem-resistant Escherichia coli, quinolone-resistant Escherichia coli, cefotaxime or ceftriaxone resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii (regression coefficient > 0, P < 0.05). Bed allocation and utilization efficiency in healthcare institutions may affect the isolation proportion of MDROs in varying degrees., (© 2023. The Author(s).)

The semiconductor white laser light source is used as a light source for underwater illumination. The required standard color temperature of white light is obtained at the underwater target surface. We studied the power compensation of a synthetic white laser source and its application to underwater illumination. First, the power ratios of the red (638 nm), green (520 nm), and blue (450 nm) lasers at a color temperature of 6500 K were obtained by using chromaticity theory. Next, the three-color and synthetic white laser parameters were obtained with transmission distance, according to the exponential attenuation characteristics of different light in clear water and seawater medium. The three-color laser power at the output was compensated, and the underwater target illumination surface reached the standard 6500 K color temperature of the white laser, improving the illumination. Finally, an experimental system for underwater white laser illumination based on power compensation was established. The errors between experimental and theoretical results of color temperature and illuminance are no more than 0.43% and 22.15%. This power-compensated synthetic white laser light source has both the advantages of long-range underwater detection and the spectral advantages of LED white light sources. The white laser light source meets specific requirements by compensating for power and optimizing white light characteristics for underwater lighting applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©2023PublishedbyElsevierLtd.)

Slow dynamics in supercooled and glassy liquids is an important research topic in soft matter physics. Compared to the traditionally focused one-component systems, glassy dynamics in mixture systems adds in a rich set of new complexities, which are fundamentally interesting and also relevant for many technological applications. In this paper, we apply the recently developed self-consistent cooperative hopping theory (SCCHT) to systematically investigate the effects of the size ratio, composition and interparticle interactions on the cooperative activated hopping dynamics of matrix (in larger size) and penetrant (in smaller size) particles in varied binary sphere mixture model systems, with a specific focus on ultrahigh mixture packing fractions that mimic the deeply supercooled glass transition conditions for molecular/polymeric mixture materials. Analysis shows that in these high activation barrier cases, the long-range elastic distortion associated with a matrix particle hopping over its cage confinement always generates an elastic barrier of a nonnegligible magnitude, although the ratio between the elastic barrier and local barrier contribution is sensitively dependent on all three mixture-specific system factors considered in this work. SCCHT predicts two general scenarios of penetrant-matrix cooperative activated hopping dynamics: matrix/penetrant co-hopping (regime 1) or the penetrant mean barrier hopping time shorter than that of the matrix (regime 2). Increasing the penetrant-to-matrix size ratio or the penetrant-matrix cross-attraction strength is found to universally enlarge the composition window of regime 1. Diverse dynamical properties characterising different aspects of the cooperative activated hopping process, including the penetrant and matrix transient localization lengths, penetrant and matrix hopping jump distances, different types of local and elastic activated barriers, and matrix long-time diffusivity, relaxation time and dynamic fragility are quantitatively studied against a wide range of variations over the three system factors. Of particular interest is the universal "anti-plasticization" phenomenon achievable for sufficiently strong cross-attractive interactions. The prospects this work opens for the exploration of a wide variety of polymer-based mixture materials are briefly discussed at the end.

Hyperglycemia-induced myelopoiesis and atherosclerotic progression occur in mice with type I diabetes. However, less is known about the effects of metabolites on myelopoesis in type 2 diabetes. Here, we use fluorescence-activated cell sorting to analyze the proliferation of granulocyte/monocyte progenitors (GMP) in db/db mice. Using targeted metabolomics, we identify an increase in inosine monophosphate (IMP) in GMP cells of 24-week-old mice. We show that IMP treatment stimulates cKit expression, ribosomal S6 activation, GMP proliferation, and Gr-1 + granulocyte production in vitro. IMP activates pAkt in non-GMP cells. In vivo, using an established murine acute pancreatitis (AP) model, administration of IMP-treated bone marrow cells enhances the severity of AP. This effect is abolished in the presence of a pAkt inhibitor. Targeted metabolomics show that plasma levels of guanosine monophosphate are significantly higher in diabetic patients with AP. These findings provid a potential therapeutic target for the control of vascular complications in diabetes., (© 2022. The Author(s).)

Objective: To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways., Methods: Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 β, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis., Results: The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1., Conclusion: LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the combined anti-inflammatory effect of activating blood circulation and detoxifying Chinese medicines in unstable angina (UA) patients., Methods: This study was an open-labeled, randomized controlled trial conducted in 5 centers in Beijing. A total of 154 patients were randomized into two groups at a 1:1 ratio by random numbers. Based on the conventional treatment, patients in the activating blood circulation (ABC) group were treated with Guanxin Danshen Droping Pill (, 0.4 g, thrice daily), and patients in the activating blood circulation and detoxifying (ABCD) group were treated with Guanxin Danshen Droping Pill (0.4 g, thrice daily) and Andrographis tablet (0.2 g, thrice daily) for 4 weeks. The primary outcome was the serum level of high sensitive C reaction protein (hs-CRP), and the secondary outcome index included the serum levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble CD40 ligand (sCD40L), thrombomodulin (TM), the score of angina pectoris, the score of blood stasis syndrome, and the score of Chinese medicine symptoms, observed at week 0 and week 4., Results: A total of 144 patients completed the trial (ABC group, n=70; ABCD group, n=74). There were no significant differences in the clinical baseline characteristics between the two groups. When compared with the ABC group, ABCD group showed better performance in reducing the level of inflammatory factors, especially hs-CRP (P<0.05), IL-6 (P<0.01) and TNF-α (P<0.01). In term of clinical symptoms, ABCD group played a better role in improving the scores of angina pectoris and blood stasis syndrome than ABC group (all P<0.05)., Conclusions: The combination of Guanxin Danshen Dropping Pill and Andrographis tablet exert significant anti-inflammatory effect on UA patients, which is superior to single Guanxin Danshen Dropping Pill. (Registration No. ChiCTR-TRC-13004072)., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The magnetic velocity induction system (MAVIS) is commonly used for velocimetry in shock compression experiment. Due to some discrepancies, the variation in induced voltage amplitude is ambiguous, which makes the simulation of this experiment particularly significant. In this work, we have designed a MAVIS, which was used to determine the induced voltage amplitude and flyer velocity. We built a three-dimensional model of MAVIS and performed the simulations using the Analysis System Electromagnetics Suite. Additionally, we performed some experiments and compared the results of both studies on the basis of flyer thickness, radius, and velocity. It was established that the flyer velocity influenced the induced electromotive force (EMF) in the pick-up coils. The increase in flyer radius led to the increase in the induced EMF. The cut-off radius for flyers was also discussed in detail by computing the lowest induced EMFs at discrete flyer velocities and radii. Due to the eddy current loss, experimental data laid slightly lower than simulations. The simulation data have proved its accuracy within the experimental error range. Thus, it can be applied as an economical framework to calculate projectile velocity precisely, regardless of its geometry, and to estimate the trigger level of the oscilloscope before performing the experiments. In order to enhance the quality of induced voltage, we also proposed a new design consisting of three pick-up coils. This redesigned MAVIS contributed significantly in signal narrowing as well as controlled the loss in amplitude peaks that reduced the experimental uncertainty in flyer velocity <0.4%.

The structure, electronic, and magnetic properties have been investigated by the first-principles calculations for paramagnetic, ferromagnetic, and antiferromagnetic Cu 3 TeO 6 under pressure from 0 to 100 GPa. The calculated lattice parameters at 0 GPa are in excellent agreement with the available calculated and experimental values. With increasing pressure, the lattice parameters and volume decrease, but Cu 3 TeO 6 keeps a stable cubic structure. The electronic calculations show that paramagnetic and ferromagnetic Cu 3 TeO 6 are metallic, and antiferromagnetic Cu 3 TeO 6 is non-metallic with a direct band gap which decreases with the increasing pressure. Under the pressure, their non-locality of density of states enhances and the electrons become more active. Moreover, for antiferromagnetic Cu 3 TeO 6 , the spin moments of Cu atoms are affected obviously by pressures, and Te atoms show nonmagnetic performance. The total magnetic moment, which is mainly contributed by Cu, reaches the maximum at 20 GPa, and decreases with the increasing pressure. The knowledge of these properties will provide reference and guidance for the subsequent study of Cu 3 TeO 6 .

Background: Leptospira is the causative agent of leptospirosis, a zoonotic disease of global importance. To have a better understanding on the host species of Leptospira , we investigated the prevalence of Leptospira species in hedgehogs in Central China. Materials and Methods: Hedgehogs were captured in Hubei Province, China in May and October, 2018. Total DNA was extracted from the kidney tissues of hedgehogs for determining the Leptospira species by PCR amplification of the rrs2 , secY , and flaB genes with genus-specific primers. Results: PCR amplification indicated that the positive rate of hedgehogs to the rrs2 , secY , and flaB genes were 19.5% (8/41), 12.2% (5/41), and 9.8% (4/41), respectively. The homology of the partial sequence of rrs2 , secY , and flaB genes were 99.0-100% among the Leptospira strains from hedgehogs. Phylogenetic analysis revealed that Leptospira species detected in this study clustered together with Leptospira interrogans. Conclusions: We detected L. interrogans from hedgehogs in Central China, suggesting hedgehogs are the hosts of L. interrogans.

Objective: Many studies have explored the effects of individual foods or nutrients on fluorosis, but no studies have focused on dietary patterns. This study examined the relationship between dietary patterns and coal-burning fluorosis in Guizhou, China. Methods: This 1:1 matched case-control study was conducted in Zhijin County of Guizhou province with a sample size of 200 cases of fluorosis and 200 age and gender matched controls. Habitual dietary intake was assessed by face-to-face interviews, using a validated 75-item food frequency questionnaire (FFQ) and various covariates using structured questionnaires. The dietary patterns were identified by factor analysis. Results: The factor analysis identified three major dietary patterns which were labeled healthy, easy-to-roast and high protein. After adjusting for various confounding factors, a decreased risk for fluorosis was observed in the highest tertile of the healthy dietary pattern relative to the lowest tertile (OR = 0.47, 95% CI = 0.27-0.84, P-trend = 0.003) and a positive association was observed between the easy-to-roast dietary pattern and fluorosis risk (OR = 2.05, 95% CI = 1.15-3.66), with a significant linear trend ( P = 0.017). We did not find an association between fluorosis risk and the high protein dietary pattern. The relationships remained significant when the analyses were stratified by gender and fluorosis subtypes. Conclusion: The healthy dietary pattern may lower coal-burning fluorosis risk; in contrast, the easy-to-roast dietary pattern significantly increases the risk of coal-burning fluorosis., (Copyright © 2020 Liu, Yang, Luo, Chen, Ma, Tao, Zhao and Wang.)

Previously, we reported that although the HSPC frequency in bone marrow cells (BMC) was comparable between β2-/- and β2+/+ mice, transplantation of β2-/- BMC into lethally irradiated CD45.1 recipient resulted in more myeloid cell production than β2+/+ BMC. The objective of this study is to address if integrin β2 deficiency skews granulocyte/macrophage progenitor (GMP) proliferation. FACS analysis demonstrated that GMP frequency and cell number were higher and megakaryocyte/erythrocyte progenitor frequency and cell number were lower in β2-/- mice than β2+/+ mice. However, the common myeloid progenitors (CMP) frequency and cell number were similar between the two groups. The increased GMP number was due to GMP proliferation as evidenced by the percentage of BrdU-incorporating GMP. Whole genome transcriptome analysis identified increased FcεRIα expression in β2-/- CMP compared to β2+/+ CMP. FcεRIα expression on β2-/- GMP was detected increased in β2-/- mice by qRT-PCR and FACS. Although transplantation of FcεRIα hi GMP or FcεRIα lo GMP into lethally irradiated CD45.1 recipient resulted in comparable myeloid cell production, transplantation of β2 deficient FcεRIα hi GMP generated more myeloid cells than β2+/+ FcεRIα hi GMP. GATA2 expression was increased in β2-/- GMP. Using a luciferase reporter assay, we demonstrated that mutation of the GATA2 binding site in the FcεRIα promoter region diminished FcεRIα transcription. In vitro, the addition of IgE, the ligand of FcεRIα, promoted GMP expansion, which was abrogated by inhibition of JNK phosphorylation. Integrin β2 deficiency promoted GMP proliferation and myeloid cell production, which was mediated via FcεRIα/IgE-induced JNK phosphorylation in GMP. Stem Cells 2019;37:430-440., (© 2018 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2018.)

Inflammatory cells in atherosclerotic plaque exclusively originate from hematopoietic stem/progenitor cells (HSPCs). In this study, we investigated whether circulating HSPCs frequency related to coronary stenosis in patients with coronary heart disease (CHD). Coronary angiography was performed in 468 participants who were recruited at Cardiology Centre in LuHe Hospital from March 2016 to May 2017. Among these subjects, 344 underwent echocardiography. Mononuclear cells isolated from peripheral blood were stained with an antibody cocktail containing anti-human CD34, anti-human lineage, anti-human CD38, and anti-human CD45RA. Lineage - CD38 - CD45RA dim CD34 + HSPCs were quantified by flow cytometry. CHD was defined as coronary stenosis ≥50% and the extent of CHD was further categorised by coronary stenosis ≥70%. A p < 0.0031 was regarded statistically significant by the Bonferroni correction. Circulating HSPCs frequency was 1.8-fold higher in CHD patients than non-CHD participants (p = 0.047). Multivariate-adjusted logistic analysis demonstrated that HSPCs was the only marker that was associated with the odds ratio of having mild vs. severe coronary stenosis (2.08 (95% CI, 1.35-3.21), p = 0.0009). Left ventricular ejection fraction was inversely correlated with HSPCs frequency and CRP in CHD patients (p < 0.05 for both). In conclusion, HSPCs frequency in circulation is intimately related to coronary stenoses in CHD patients.

Atherothrombosis is the major cause of acute coronary syndromes and cardiovascular deaths. Platelets participate in the processes of forming and extending atherosclerotic plaques. Therefore, antiplatelet therapy is a milestone in the primary and second prevention of atherothrombotic diseases. Along with the longterm use of antiplatelet agents, the safety and drug resistance has become a big concern in clinic and new drugs possessing higher effectiveness and fewer adverse effects are needed. Abundant recent data support that traditional Chinese herbs may be a good alternative and complementary choice of new antiplatelet drugs. This review highlights the progress of antiplatelet effect of active components derived from traditional Chinese herbs based on their chemical structures.

Background: High-pressure processing is gaining popularity in the food industry. However, its effect on the Maillard reaction during high-pressure-assisted pasteurization and sterilization is not well documented. This study aimed to investigate the effects of high hydrostatic pressure on the Maillard reaction during these processes using amino acid (lysine or arginine)-sugar (glucose or fructose) solution models., Results: High pressure retarded the intermediate and final stages of the Maillard reaction in the lysine-sugar model. For the lysine-glucose model, the degradation rate of Amadori compounds was decelerated, while acceleration was observed in the arginine-sugar model. Increased temperature not only accelerated the Maillard reaction over time but also formed fluorescent compounds with different emission wavelengths. Lysine reacted with the sugars more readily than arginine under the same conditions. In addition, it was easier for lysine to react with glucose, whereas arginine reacted more readily with fructose under high pressure., Conclusion: High pressure exerts different effects on lysine-sugar and arginine-sugar models. © 2017 Society of Chemical Industry., (© 2017 Society of Chemical Industry.)

The geometrical structures, electrical properties, and nonlinear optical (NLO) properties of AlNNT-Li and BNNT-Li nanotube systems were investigated by means of the density functional theory (DFT) method. Frontier molecular orbitals and density of states analyses show that adsorption of the Li atom can significantly narrow the wide HOMO-LUMO gaps of pure AlNNT and BNNT. The results reveal that AlNNT-Li and BNNT-Li systems containing diffuse excess electrons can be regarded as inorganic electrides. The formation of diffuse excess electrons leads to a decrease in transition energies, thereby increasing the first hyperpolarizabilities (β 0 ) of AlNNT-Li and BNNT-Li. This work may contribute to the development of potential high-performance NLO materials. Graphical abstract The structural characteristics and nonlinear optical properties of the AlNNT-Li and BNNT-Li systems were studied by means of density functional theory. Introduction of Li atoms greatly enhances the static first hyperpolarizabilities of AlNNT-Li and BNNT-Li.

Iron (Fe)-homeostasis in the plastids is closely associated with Fe transport proteins that prevent Fe from occurring in its toxic free ionic forms. However, the number of known protein families related to Fe transport in the plastids (about five) and the function of iron in non-green plastids is limited. In the present study, we report the functional characterization of Zea mays Fe deficiency-related 4 (ZmFDR4), which was isolated from a differentially expressed clone of a cDNA library of Fe deficiency-induced maize roots. ZmFDR4 is homologous to the bacterial FliP superfamily, coexisted in both algae and terrestrial plants, and capable of restoring the normal growth of the yeast mutant fet3fet4, which possesses defective Fe uptake systems. ZmFDR4 mRNA is ubiquitous in maize and is inducible by iron deficiency in wheat. Transient expression of the 35S:ZmFDR4-eGFP fusion protein in rice protoplasts indicated that ZmFDR4 maybe localizes to the plastids envelope and thylakoid. In 35S:c-Myc-ZmFDR4 transgenic tobacco, immunohistochemistry and immunoblotting confirmed that ZmFDR4 is targeted to both the chloroplast envelope and thylakoid. Meanwhile, ultrastructure analysis indicates that ZmFDR4 promotes the density of plastids and accumulation of starch grains. Moreover, Bathophenanthroline disulfonate (BPDS) colorimetry and inductively coupled plasma mass spectrometry (ICP-MS) indicate that ZmFDR4 is related to Fe uptake by plastids and increases seed Fe content. Finally, 35S:c-Myc-ZmFDR4 transgenic tobacco show enhanced photosynthetic efficiency. Therefore, the results of the present study demonstrate that ZmFDR4 functions as an iron transporter in monocot plastids and provide insight into the process of Fe uptake by plastids., (© 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.)

Both brown adipocytes (BAC) and beige cells hold therapeutic potential for the treatment of metabolic disorders. Unfortunately, the amount and activity of these cells are limited in adults. Although BAC marker expression has been shown in peri-renal adipose tissues in children and adults, functional assessment is lacking. Furthermore, it is entirely unknown whether adipose progenitors are present in human embryo and able to give rise to BAC in situ during evolution. Therefore, adipose tissues in the interscapular and peri-renal regions were dissected from human embryo and subcutaneous white adipose tissues (sWAT) were obtained from an adult. After subjected to differentiation in vitro, adipocyte progenitors were detected present in all these adipose tissues. When stimulated for adipogenesis, differentiated adipocytes in the intercapular and peri-renal regions showed similar features: (1) induced BAC and beige cell marker expression including UCP1 and PRDM16 and comparable mitochondrion copy number; (2) similar gene expression patterns by RNA-Seq analysis; and (3) similar maximal oxygen consumption rates examined by respirometry. Nevertheless, stimulation of adipocyte progenitors in sWAT induces neither BAC and beige cell marker expression nor any change of oxygen consumption. In conclusion, peri-renal adipocyte progenitors in human embryo hold browning potential for BAC production.

Objective: To explore the mechanism of Bushen Qiangji Granule (, BSQJ) in restraining the osteogenic differentiation of ankylosing spondylitis (AS) fifibroblasts., Methods: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement and healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery as a control. Finite fifibroblast lines were established from these tissue samples to observe the effect of BSQJ on suppressing osteogenic differentiation of fifibroblasts. The expression of osteogenic marker gene corebinding factor a1 (Cbfa1) and Smad family proteins were examined by Western blot and real-time quantitative polymerase chain reaction (qPCR)., Results: The mRNA expression level of Cbfa1 was significantly higher in AS fibroblasts than that in normal fibroblasts and the expression of pSmad1, pSmad5, Smad4 and Cbfa1 in AS fibroblasts was also higher, demonstrating the activation of the BMP/Smads signal pathway in AS fifibroblasts. BSQJ-medicated serum not only restrained the mRNA and protein expression levels of Cbfa1 and inhibited protein expression level of Smad4 but also decreased the expression quantities of pSmad1 and pSmad5., Conclusions: BSQJ can inhibit osteogenic differentiation of AS fifibroblasts in vitro by suppressing the activation of the BMP/Smads signal pathway. This may be the important molecular mechanism of BSQJ in regulating AS ossifification.

Cellular response to DNA damage, including ionizing radiation (IR) and UV radiation, is critical for the maintenance of genomic fidelity. Defects of DNA repair often result in genomic instability and malignant cell transformation. Centrosomal protein Nlp (ninein-like protein) has been characterized as an important cell cycle regulator that is required for proper mitotic progression. In this study, we demonstrate that Nlp is able to improve nucleotide excision repair (NER) activity and protects cells against UV radiation. Upon exposure of cells to UVC, Nlp is translocated into the nucleus. The C-terminus (1030-1382) of Nlp is necessary and sufficient for its nuclear import. Upon UVC radiation, Nlp interacts with XPA and ERCC1, and enhances their association. Interestingly, down-regulated expression of Nlp is found to be associated with human skin cancers, indicating that dysregulated Nlp might be related to the development of human skin cancers. Taken together, this study identifies mitotic protein Nlp as a new and important member of NER pathway and thus provides novel insights into understanding of regulatory machinery involved in NER., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Cecropin A1 (CecA1) promoter from Bombyx mori was cloned and characterized to provide insight into the transcriptional control of this antimicrobial peptide gene upon immune challenges. Reporter gene assays demonstrated that both Escherichia coli and lipopolysaccharide could induce expression in BmE cells but B. bombyseptieus or peptidoglycan failed, and the induction pattern of the reporter gene was coincident with the endogenous CecA1. Analysis of deletion and mutation constructs revealed that the regulatory region was the κB motif located between -176 and -166, and no other predicted elements on CecA1 promoter affected its inducibility. Insertion of additional κB motifs increased the activity of CecA1 promoter. Furthermore, binding of Relish to κB motif was confirmed by electrophoretic mobility shift assay. These findings indicate the regulatory mechanism of CecA1 expression in IMD pathway and suggest an approach of engineering antimicrobial peptide promoter with enhanced activities that may lead to broad applications., (© 2015 Institute of Zoology, Chinese Academy of Sciences.)

Aim: We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME)., Methods: SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses., Results: Pretreatment with the combination of ligustrazine (27 mg·kg(-1)·d(-1)) and berberine (90 mg·kg(-1)·d(-1)) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1β, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg(-1)·d(-1))., Conclusion: The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects.

Omp25 protein, an outer membrane protein of Brucella, can cause damage to the central nervous system. As one type of macrophage, microglial cells play a role in immune surveillance and immune protection in the central nervous system; therefore, they are major targets of bacterial attack. The present study examined BV2 mouse microglial cells that were stimulated with different concentrations of Omp25 recombinant protein, and the secretion of inflammatory cytokines by the BV2 cells as well as their level of apoptosis were observed. The objective of the study was to preliminarily illustrate the possible mechanism that Omp25 uses to damage the central nervous system. Mouse BV2 microglial cells were incubated with different concentrations of Omp25 for 24 h, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of the inflammatory cytokines interleukin (IL)-6, tumour necrosis factor (TNF)-α and HMGB1 (high mobility group box-1 protein); reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of TLR4 (Toll-like receptor 4) mRNA; Annexin V-fluorescein isothiocyanate (FITC) double staining was used to detect apoptosis in the BV2 cells. After the BV2 cells were stimulated with different concentrations of Omp25, the levels of IL-6, TNF-α and HMGB1 was increased, and the difference was statistically significant compared with the control group (P<0.05). The secretion of TNF-α and HMGB1 showed a trend toward an initial increase followed by a decrease. The expression level of TLR4 mRNA was increased. Omp25 protein can inhibit apoptosis in BV2 cells. The outer membrane protein Omp25 of Brucella promotes microglial cells to secrete inflammatory cytokines and inhibit apoptosis. TLR4 may be involved in the immune response of the central nervous system to Brucella infection.

Optimizing the metabolism of the myocardium is a new strategy for patients with ischemic heart disease. Many studies have reported beneficial effects of trimetazidine (TMZ) on the clinical prognosis of patients with ischemic heart disease, but whether these beneficial effects are extended to patients undergoing percutaneous coronary intervention (PCI) remains uncertain. A meta-analysis was performed to evaluate the effect of TMZ on patients undergoing PCI. We conducted an electronic search of PubMed, Cochrane databases, the China National Knowledge Infrastructure, and Chinese Biological Medicine Database to identify randomized controlled trials. Methodological quality was assessed according to the Jadad scale score, and the meta-analysis was performed using Cochrane Collaboration RevMan 5.2 and Comprehensive Meta-Analysis. Dichotomous data were analyzed using relative risk (RR) or odds ratio (OR) with effect size indicated by the 95% confidence interval (CI), and continuous variables were analyzed using weighted mean differences (WMD) with effect size indicated by the 95% CI. Sensitivity analysis was performed by changing the statistical methods and effect model. Nine studies involving a total of 778 patients were included in this meta-analysis. Additional use of TMZ significantly improved the left ventricular ejection fraction (WMD: 3.11, 95% CI: [2.26, 3.96]) and reduced elevated cardiac troponin Ic level (RR: 0.69, 95% CI: [0.48, 0.99]), angina attacks during PCI (OR: 0.16, 95% CI: [0.07, 0.38]), and ischemic ST-T changes on the echocardiogram during PCI (RR: 0.76, 95% CI: [0.59, 0.98]). However, no significant difference was observed in serum BNP level 30 days after PCI between the experimental and control group. Additional use of TMZ for patients undergoing PCI may reduce myocardial injury during the procedure and improve cardiac function.

Objective: To explore the effects of Panax Quinquefolium Saponin (PQS) on phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/Akt) pathway of neonatal rat myocardial cells subjected to hypoxia., Methods: Neonatal rat myocardial cells were cultured in vitro. After the myocardial cell injury was induced by hypoxia, the cells were randomized into 5 groups: the normal group, the model group, the positive control group (Ciclosporin A, 2 µ mol/L), the low-dose PQS group (PQSL, 25mg/L), and the high-dose PQS group (PQSH, 50 mg/L). Morphology and behavior of myocardial cells were observed under an inverted microscope. Apoptosis rate and lactate dehydrogenase (LDH) leakage rate of myocardial cells were determined by colorimetry. Mitochondrial transmembrane potential was assessed using a fluorexon laser. Phospho-glycogen synthase kinase (GSK)-3β and phospho-Akt as well as cytochrome C were determined by Western blot, Results: LDH leakage in the Ciclosporin A group, PQSH group and PQSL group reduced progressively compared with the model group (P<0.05). Akt and GSK-3β was strongly phosphorylated after treatment with Ciclosporin A and PQS compared with the model group (P<0.05, P<0.01). Compared with the model group (16.41±1.74; 35.28±6.30), both the integrated optical density of mitochondrial permeability transition pore (MPTP) and the mitochondrial transmembrane potential significantly increased in the PQSH group (42.74±2.12; 71.36±6.54) and the PQSL group (39.58±1.49; 66.99±5.45; P<0.05, P<0.01). However, the protein of cytochrome C outside the mitochondrion decreased in the PQSH group (273.66±14.61) and the PQSL group (259.62±17.31) compared with the model group (502.41±17.76; P<0.05)., Conclusion: Through activation of the PI3K/Akt pathway and inhibition of the MPTP, PQS might protect the heart against ischemia injury and apoptosis of myocardial cells.

Objective: To explore the effect of drug-containing serum of Chinese herbal compounds [Xiongshao Capsule (XS, for activating blood) and Huanglian Capsule (HL, for dispelling toxin)] on tumor necrosis factor-alpha (TNF-alpha)-induced adherence between human umbilical vein endothelial cells (HUVECs) and polymorphonuclear neutrophils (PMN), inflammatory reaction and expression of related proteins in mitogen-activated protein kinase (MAPK) pathway., Methods: Thirty-two rats were randomly divided into four groups (8 in each group) using random digit table: the blank control group treated with distilled water, the test group I treated with Chinese herbal compound of XS (0.135 g/kg), the test group II treated with Chinese herbal compound of HL (0.135 g/kg), and the test group Ill treated with Chinese herbal compound of XS (0.135 g/kg) and HL (0.135 g/kg). All medication was given by gastrogavage once a day for a week. Rats' blood serum was harvested 1 h after the last administration to prepare drug-containing serum. HUVECs were exposed to TNF-alpha (100 ng/mL) to induce cell injury model and incubated with corresponding drug-containing serum (10%) for 24 h. Normal rats' serum was given to cells in the blank control group and the model group, while XC + HL containing serum was given to cells in the rest 3 groups. The adherence of HUVECs and PMN cells was detected by using rose bengal strain. Levels of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and interleukin-1beta (IL-1P) in the supernatant of cultured HU-VECs were determined by ELISA. Protein expressions of mitogen-activated protein kinases p38 (p38MAPK) and extracellular signal-regulated kinase 1/2 (ERK 12) were determined by Western blot., Results: Compared with the blank control group, HUVECs were seriously injured; PMN adherence amount significantly increased; levels of E-selectin, ICAM-1, and IL-1beta increased; expression levels of p-p38MAPK and p-ERK 1/2 in the supernatant of HUVECs significantly increased in the model group (all P < 0.01). Compared with the model group, HUVECs-PMN adherence amount decreased (P < 0.05); levels of E-selectin, ICAM-1, and IL-1 beta in the supernatant of HUVECs decreased (P < 0.01, P < 0.05); expression levels of p-p38MAPK and p-ERK 1/2 of endothelial cells decreased in the test group I, II, and III (P < 0.01)., Conclusions: Drug-containing serums of activating blood, activating blood and dispelling toxin could attenuate TNF-alpha induced injury of HUVECs, inhibit HUVECs-PMN adherence and the release of adhesion factors. Its mechanism might be involved with protein phosphorylation of p38MAPK and ERK 1/2 in the MAPK pathway.

Aims: Estrogen plays a protective role in atherosclerosis. Our preliminary work demonstrated that the active conformation of Tanshinone IIA(TanIIA) is similar to the 17β-estradiol and it can bind to the estrogen receptor. Here, we hypothesized that Tanshinone IIA might have anti-inflammatory and anti-oxidative effects in atherosclerosis, mediated through estrogen receptor activation., Methods: Subjects for this study were 120 apoE(-/-) female mice and 20 C57/BL female mice. The apoE(-/-) mice were ovariectomized (OVX) and the C57/BL mice were sham ovariectomized. The sham OVX mice were maintained on a normal diet (NOR) group. The OVX apoE(-/-) mice were fed a high fat diet and randomly divided into 6 groups: Model (MOD) group which was fed a high fat diet only, E2 group were given estrogen (E2) 0.13 mg/kg/d; E2+ICI group were given E2:0.13 mg/kg/d and ICI182780:65 mg/kg/m; TLD group (TanIIA low dose) were given TanIIA: 30 mg/kg/d; THD group (TanIIA high dose) were given TanIIA:60 mg/kg/d; and TLD+ICI group were given TanIIA 30 mg/kg/d and ICI182780 65 mg/kg/m. After three months of treatment, the aorta and the blood of the mice from each group was collected. The aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE) and oil red O staining and for testing the expression of p-ERK1/2 by Western blot. The blood was used for testing the serum cholesterol, superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), nuclear factor kappa (NF-κB), soluble intercellular cell adhesion molecule-1 (sICAM-1), activating protein-1 (AP-1), E-selectin and 17β-estradiol in serum., Results: Tanshinone IIA significantly reduced the lipid deposition in aorta, decreased the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), MDA, NF-κB, sICAM-1, AP-1, and E-selectin in serum but increased the levels of high density lipoprotein (HDL) and SOD in serum. Tanshinone IIA also suppressed the expression of p-ERK1/2. Tanshinone IIA had no effect of level of serum 17β-estradiol levels. All of the effects of Tanshinone IIA were similar to estrogen and were inhibited by the estrogen receptor antagonist ICI182780., Conclusion: Tanshinone IIA may play an anti-inflammatory and anti-oxidative stress role in OVX atherosclerotic apoE(-/-) mice by activating the estrogen receptor through the ERK signaling pathway. Therefore, Tanshinone IIA, as a phytoestrogen, could be used for estrogen replacement therapy for cardiovascular disease of postmenopausal women., (© 2015 S. Karger AG, Basel.)

Clinical study of modified Ganmai Dazao decoction in the treatment of yang deficiency climacteric depression and observe the effects of modified Ganmai Dazao decoction on neuroendocrine system in patients with yang deficiency climacteric depression. 86 cases were randomly divided into treatment group treated with modified Ganmai Dazao decoction and control group treated with Deanxit. The curative effect was evaluated with Hamilton's depressive scale (HAMD) and pittsburgh sleep quality scale (PSQI) before and at the end of the two and four weeks of the treatment, the serum levels of serotonin (5-HT), norepinephrine (NE), estradiol (E2), follicle stimulating hormone (FSH), luteotropic hormone (LH) were detected before and after the four weeks of the treatment The results showed that the total effective power of treatment group was 88.4% and the total effective power of control group was 81.4% after four weeks interference, with insignificant difference between the two groups. After two and four weeks of the treatment, the score of HAMD decreased remarkably in both groups (P < 0.01), with insignificant difference between the two groups in same phase. After two and four weeks of the treatment, the total score of PSQI decreased remarkably in both groups (P < 0.05), with significant difference between the two groups after four weeks (P < 0.01). After four weeks of treatment, the serum levels of 5-HT and NE increased (P < 0.01), with insignificant difference between the groups. After four weeks of treatment, the serum levels of E2 increased obviously (P < 0.05), the levels of FSH decreased obviously (P < 0.05), the levels of LH decreased insignificant, with insignificant difference between two groups. This study indicates that modified Ganmai Dazao decoction has obvious therapeutic effects in the treatment of climacteric depression, and showed equivalent efficacy with Deanxit, and modified Ganmai Dazao decoction has better effect on improving the sleep quality in patients than Deanxit, the effect of improved clinical symptoms may be through adjusted levels of 5-HT, NE, E2, FSH and LH of climacteric depression.

Objective: To observe the effect of activating blood circulation drugs or activating blood circulation and detoxication drugs on indices of platelet activation, inflammation, and coagulation status correlated with blood-stasis and toxin in acute myocardial infarction rats., Methods: Totally 100 male SD rats were randomly divided into the sham-operation group, the model group, the activating blood circulation group, the activating blood circulation and detoxication group, and the metoprolol group, 20 in each group. Rats in the activating blood circulation group were administered with Xiongshao Capsule at the daily dose of 0.39 g/kg. Rats in the activating blood circulation and detoxication group were administered with Xiongshao Capsule (at the daily dose of 0.39 g/kg) and Huanglian Capsule (at the daily dose of 0.135 g/kg). Rats in the metoprolol group received metoprolol at the daily dose of 2.25 mg/kg. And rats in the rest two groups were administered with normal saline. All medication lasted for 3 successive weeks. After the last administration, the rat model of acute myocardial infarction was prepared by ligation of left anterior descending artery. No ligation was given to rats in the sham-operation group. Animals were sacrificed 24 h after modeling. Tumor necrosis factor-α (TNF-α), β-thromboglobulin (β-TG), platelet α granule membrane protein-140 (GMP-140), 11 dehydro-thromboxane B2 (11-DH-TXB2), fibrinopeptide A (FPA), antithrombin III (AT-III), and D-dimer (DD) were detected by ELISA. The mRNA expression of TNF-α was tested by RT-PCR., Results: Platelet activation parameters were significantly increased in the model group, when compared with the sham-operation group (P < 0.01). Compared with the model group, all indices (except GMP-140 in the metoprolol group) obviously decreased in each medicated group (P < 0.01, P < 0.05). Besides, β-TG and 11-DH-TXB2 were superior in the activating blood circulation and detoxication group to that of the metoprolol group (P < 0.05). But 11-DH-TXB2 was also obviously superior in the activating blood circulation and detoxication group to that of the activating blood circulation group (P < 0.05). Compared with the sham-operation group, an obviously hypercoagulable state was obviously shown in the AMI model group, with significantly increased FPA and DD (P < 0.05 or 0.01) and significantly decreased AT III (P < 0.01). Compared with the model group, the FPA level significantly decreased in each medicated group (P < 0.01), and the AT III level significantly increased in the activating blood circulation group and the activating blood circulation and detoxication group (both P < 0.01). The level of DD obviously decreased in the activating blood circulation and detoxication group (P < 0.01). Besides, the 3 indices were superior in the activating blood circulation and detoxication group to those of the metoprolol group (P < 0.05). Compared with the sham-operation group, the serum TNF-α level and myocardial TNF-α mRNA expression were significantly increased in the model group (P < 0.05, P < 0.01). Compared with the model group, not only the serum TNF-α level was significantly decreased, but also the TNF-α gene expression in the myocardial tissue was improved in the activating blood circulation and detoxication group (P < 0.01)., Conclusion: Combined use of activating blood circulation and detoxication drugs could play an effective role in treatment of coronary heart disease by fighting against platelet activation, improving the hypercoagulable state, and inhibiting inflammation, which was significantly better than using activating blood circulation and removing stasis drugs alone.

Ginsenoside Rb3 (GRb3) is one of the main components in plasma of Panax quinquefolius Saponin of stem and leaf (PQS), which can be into human plasma. Previous studies have found PQS has estrogen-like vascular protective effects. In the present study, we investigated the estrogen-like protective effect of GRb3 on oxidative stress and dysfunction of endothelial cells induced by oxidized low-density lipoprotein. The activities of SOD, NOS and the contents of MDA in the cell lysate were examined by enzyme method or spectrophotometry. The NO and ET-1 concentrations in the cell culture supernatant were measured by ELISA method. The iNOS and eNOS mRNA expression were measured by real time RT-PCR, while the phosphorylation levels of Akt was measured by Western blotting. The results showed that GRb3 could enhance the activity of SOD, reduce the content of MDA, increase the level of NOS, NO, ET-1 and iNOS mRNA expression while decrease the eNOS mRNA expression and the phosphorylation level of Akt. These effects were blocked by estrogen receptor antagonist ICI182780. GRb3 can play a role in protecting vascular endothelial cells by estrogen receptors, the protective mechanism is similar to 17-β estrodiol.

Channel gating in response to extracellular ATP is a fundamental process for the physiological functions of P2X receptors. Here we identify coordinated allosteric changes in the left flipper (LF) and dorsal fin (DF) domains that couple ATP-binding to channel gating. Engineered disulphide crosslinking or zinc bridges between the LF and DF domains that constrain their relative motions significantly influence channel gating of P2X4 receptors, confirming the essential role of these allosteric changes. ATP-binding-induced alterations in interdomain hydrophobic interactions among I208, L217, V291 and the aliphatic chain of K193 correlate well with these coordinated relative movements. Mutations on those four residues lead to impaired or fully abolished channel activations of P2X4 receptors. Our data reveal that ATP-binding-induced altered interdomain hydrophobic interactions and the concomitant coordinated motions of LF and DF domains are allosteric events essential for the channel gating of P2X4 receptors.

Background: Ovalbumin (OVA) is a major allergen in hen egg. During thermal processing, reducing sugars contained in the hen egg white might easily undergo glycation with OVA, but few studies have been conducted on its corresponding immunoreactivity changes. The aim of the present study was to assess changes of the antigenicity, potential allergenicity and conformation of OVA after glycation in a wet-thermal processing system under different concentrations of sodium carbonate-bicarbonate buffer., Results: IgE binding of the glycated OVA was increased after glycation, and the higher the sodium carbonate-bicarbonate buffer concentration, the higher the IgE binding capacity. The increase in IgE binding of OVA corresponded well with the disruption of the disulfide bond, which exposed the epitopes initially buried. Antigenicity of the glycated OVA was increased, and the amount of the increase varied among samples treated under different buffer concentrations., Conclusion: Glycation increased the allergenic potential for OVA, with the amount of increase varying with different sodium carbonate-bicarbonate buffer concentrations., (© 2013 Society of Chemical Industry.)

Objective: To observe the regulatory effect of Chinese drugs for activating blood circulation (ABC) and for activating blood circulation and detoxifying (ABCD) on indices of thrombosis, inflammatory reaction, and tissue damage in a rabbit model of toxin-heat and blood stasis syndrome., Methods: Fifty-four rabbits were randomized into the normal control group, model group, simvastatin group (simvastatin, 0.93 mg/kg per day), ABC group [Xiongshao Capsule, 0.07 g/kg per day], and ABCD group [Xiongshao Capsule, 0.07 g/kg per day, and Huanglian Capsule, 0.14 g/kg per day]. All except the normal control group received a single injection of bovine serum albumin and were fed with high-fat diets for 6 weeks. At the end of week 4 of giving high-fat diets, a dose of endoxitin was given by ear vein injection, and a randomized 2-week treatment was initiated. At the end of treatment, blood lipids, circulating endothelial cells, and the pathological changes of the aortic arch were assessed. The serum levels of matrix metalloproteinases (MMP-9), tissue inhibitors to metalloproteinase (TIMP-1), granule membrane protein-140 (GMP-140), plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α) were determined., Results: Compared with the model group, ABCD group showed decreased serum triglyceride (TG) level, improvement in the pathological change in the aortic arch, and reduction in the number of circulating endothelial cells (4.00 ± 1.41 per 0.9 μL for ABCD group vs 7.83 ± 1.72 per 0.9 μL for the model group). In addition, the levels of serum GMP-140, PAI-1, and IL-6 in ABCD group were also significantly reduced [0.79 ± 0.20 ng/mL, 5.23 ± 1.39 ng/mL, 40.64 ± 10.11 pg/mL for ABCD group vs 1.08 ± 0.31 ng/mL, 7.28 ± 2.01 ng/mL, 54.44 ± 13.56 pg/mL for the model group, respectively, P < 0.05]. A trend showing improvement in the indices of thrombosis, inflammatory reaction, and tissue damage was observed in the ABC group when compared to the model group, but the changes were not statistically significant (P > 0.05)., Conclusions: Chinese drugs for activating blood circulation and detoxifying have beneficial effects on regulating indices of thrombosis (GMP-140 and PAI-1) and inflammatory reaction (IL-6) in rabbit model with toxic-heat and blood stasis. The effect of the activating blood circulation and detoxifying drugs in regulating the levels of serum GMP-140, PAI-1, and IL-6 was superior to that of the activating blood circulation drugs.

In insulin-secreting cells, expression of NADPH oxidase (NOX), a potent source of ROS, has been reported, along with controversial findings regarding its function. Here, the role of NOXs was investigated: first by expression and cellular localization in mouse and human pancreatic islets, and then by functional studies in islets isolated from Nox isoform-specific knockout mice. Both human and mouse β-cells express NOX, in particular NOX2. With use of Nox isoform-specific knockout mice, functional analysis revealed Nox2 as the predominant isoform. In human islets, NOX2 colocalized with both insulin granules and endosome/lysosome membranes. Nox2-deficient islets stimulated with 22.8 mmol/L glucose exhibited potentiation of insulin release compared with controls, an effect confirmed with in vitro knockdown of Nox2. The enhanced secretory function in Nox2-deficient islets was associated with both lower superoxide levels and elevated cAMP concentrations. In control islets, GLP-1 and other cAMP inducers suppressed glucose-induced ROS production similarly to Nox2 deficiency. Inhibiting cAMP-dependent protein kinase reduced the secretory response in Nox2-null islets, although not in control islets. This study ascribes a new role for NOX2 in pancreatic β-cells as negative modulator of the secretory response, reducing cAMP/PKA signaling secondary to ROS generation. Results also show reciprocal inhibition between the cAMP/PKA pathway and ROS.

Aim: To establish a hepatocellular carcinoma model of BALB/c mouse and to study the expression and potential role of metastasis-associated protein 1 (MTA1) in the carcinogenesis process., Methods: Normal adult male BALB/c mice were induced by the combined dimethylnitrosamine (DEN)/carbon tetrachloride (CCl(4);)/alcohol for 150 d. The morphological changes in liver cells and the expression of MTA1 in the liver lesions were observed by HE and immunohistochemical stainings, respectively., Results: The pathological changes of the survivals' livers in experimental group were liver inflammation, fibrosis and cancer in sequence. The level of MTA1 increased in the carcinogenesis process, and MTA1 was mainly expressed in the cytoplasm of the cells suffering cirrhosis., Conclusion: The changes of the expression sites and quantity of MTA1 in the DEN-induced carcinogenesis of mouse liver indicate that MTA1 may play an important role in the whole process of liver carcinogenesis.

Background: Ischemic postconditioning (IPOC) has been suggested to reduce ischemic reperfusion injury. It remains unclear whether the activation of phosphatidylinositol 3 kinase (PI3K)/Akt is a causal mechanism in the cardioprotection afforded by IPOC, which was examined in the model of percutaneous transluminal coronary angioplasty (PTCA) minipigs., Methods and Results: Minipigs underwent 45-min occlusion of the left anterior descending artery and 24-h reperfusion by PTCA. Postconditioning was elicited by three cycles of 30-s reperfusion followed by 30-s ischemia at the onset of reperfusion. Infarct size was determined by triphenyl tetrazolium chloride staining after 24-h reperfusion, and mRNA and protein expression levels of PI3K were ascertained by reverse transcriptase-PCR and western-blot analysis in biopsies. Infarct size was significantly reduced and myocardial PI3K (Akt and GSK-3β) phosphorylation was significantly increased with IPOC treatment compared with ischemic reperfusion. The administration of the PI3K inhibitor wortmannin (30 µg/kg) attenuated the protection of IPOC in the infarct size and decreased the expression of Akt and GSK-3β phosphorylation compared with IPOC. IPOC had no impact on mRNA expression of AKT and GSK-3β., Conclusion: Our findings show that IPOC is capable of protecting the myocardium against IR injury in the PTCA minipig model. The PI3K/Akt-signaling pathway is involved in the cardioprotective effect of IPOC.

Objective: To investigate the effects of drug-containing serum of Chinese herbal compound, Xiongshao Capsule (, XS, for activating-blood) and Huanglian Capsule (, HL, for dispellingtoxin) on the oxidized low-density lipoprotein (ox-LDL)-induced inflammatory factors in human umbilical vein endothelial cells (HUVECs)., Methods: Thirty-two rats were randomly divided into four groups: the blank control group treated with distilled water, the positive control group treated with simvastatin (1.8 mg/kg), the test group I treated with Chinese herbal compound of XS (0.135 g/kg), and the test group II treated with Chinese herbal compound of XS (0.135 g/kg) and HL (0.135 g/kg). All the treatments were administered for 7 successive days by gastrogavage. Rats' blood serum was harvested 1 h after the last administration to prepare respective drugcontaining serum. HUVECs were exposed to ox-LDL (100 μg/mL) to induce cell injury model and incubated with corresponding drug-containing serum for 24 h. Untreated HUVECs were set for blank control. Levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and soluble intercellular adhesion molecule-1 (sICAM-1) in supernatant of cultured HUVECs were determined by enzyme-linked immunosorbent assay (ELISA). HUVEC surface expressions of ICAM-1 and E-selectin were determined by flow cytometry., Results: Levels of IL-6, TNF-α, and sICAM-1 in the supernatant of HUVECs as well as the cell surface expressions of ICAM-1 and E-selectin significantly increased after 24-h ox-LDL stimulation (P<0.01), while the abnormal elevations, except sICAM-1 in the test group I, were all reduced in the treated groups (the positive control and the two test groups) significantly (P<0.01 or P<0.05). Besides, the effect in the test group II seemed somewhat higher than that in the test group I but with no statistical significance (P>0.05)., Conclusion: Drug-containing serum of XS plus HL has a certain inhibitory effect on the vascular endothelial inflammation response induced by ox-LDL.

Objective: To explore the correlation between Fc γ RIII A (CD16A) and aortic atherosclerotic plaque destabilization in apoE knockout (apoE KO) mice and the intervention effects of effective components of chuanxiong rhizome and red peony root., Methods: Eight 8-week-old male C57BL/6J mice were selected as the control group. Forty 8-week-old male apoE KO mice were randomly divided into the model group, apoE KO + intraperitoneal injection immunoglobulin group (IVIG), apoE KO + simvastatin group (Sm), apoE KO + high dosage of xiongshao capsule (XSC) group (XSCH), and apoE KO + low dosage of XSC group (XSCL), 8 mice in each group. Mice in the control group were put on a normal diet, and others were fed with a high-fat diet. After 10-week different interventions, monocyte CD16 expression was detected by flow cytometry, aortic matrix metalloproteinase-9 (MMP-9) mRNA expression was detected using reverse transcription polymerase chain reaction, and serum tumor necrosis factor (TNF)-α level was detected using enzyme-linked immunosorbent assay., Results: Compared with the control group, monocyte CD16 expression, aortic MMP-9 mRNA expression, and serum TNF-α level in the model group increased obviously (P<0.01). Injections of apoE KO mice with intraperitoneal immunoglobulin during a 5-day period significantly reduced the monocyte CD16 expression, aortic MMP-9 mRNA expression, and serum TNF-α level (P<0.01 or 0.05) over a 10-week period of high-fat diet. Indices above in the Sm group, XSCH group, and XSCL group decreased in a different degree. Of them, the aortic MMP-9 mRNA expression in XSCH group was lower than that in Sm group (P<0.05) and the monocyte CD16 expression and serum TNF-α level showed no significant difference between XSCH group and Sm group (P>0.05). Correlation analyses suggested positive correlation between monocyte CD16 expression and aortic MMP-9 mRNA expression or serum TNF-α level in IVIG group, XSCH group, and XSCL group., Conclusions: FcγR III A mediates systemic inflammation in the progression of coronary heart disease with blood stasis syndrome. XSC could stabilize atherosclerotic plaque by suppressing inflammation and its target was relative with FcγRIII A.

Background: Peanut allergy is one of the most serious food allergies, and Ara h 2 is one of the most important peanut allergens as it is recognised by serum immunoglobulin E from more than 90% of peanut-allergic individuals. Dynamic high-pressure microfluidisation has been widely used in food processing as a new technology. The aim of this study was to investigate the effect of high-pressure microfluidisation on the antigenicity and structure of Ara h 2. Extracted peanut allergen Ara h 2 was treated under a continuous pressure array of 60, 90, 120, 150 and 180 MPa. Immunoreactivity was measured by indirect enzyme-linked immunosorbent assay with rabbit polyclonal antibodies. Secondary structure was analysed by circular dichroism. Surface hydrophobicity and sulfhydryl groups were assessed via fluorescence and UV absorption spectra respectively., Results: High-pressure microfluidisation treatment decreased the antigenicity of peanut allergen Ara h 2, changed its secondary structure and increased its UV absorption intensity and surface hydrophobicity., Conclusion: The change in conformation contributed to the decrease in antigenicity of Ara h 2, and the spatial conformation of peanut allergen Ara h 2 plays a critical role in its antigenicity., (Copyright © 2011 Society of Chemical Industry.)

Objective: To explore the synergistic protection of Danhong Injection (丹红注射液, DHI) and ischemic postconditioning on myocardial reperfusion injury in minipigs., Methods: Acute myocardial infarction model was made by balloon occlusion in left anterior descending coronary artery (LAD) of minipigs, and then postconditioning was simulated through inflation/deflation of the angioplasty balloon. Minipigs were divided into four groups: the sham operation group (SH group), the ischemia/reperfusion group (I/R group), the ischemic postconditioning group (POC group) and DHI combined with ischemic postconditioning group (PAD group, DHI 20 mL through ear vein), six in each group. After 24-h continuous observation, myocardial infarction size was assessed by triphenyltetrazolium staining (TTC). Morphological changes of ischemic myocardium were observed by light microscopy, and cardiomyocyte ultrastructure was studied with electron microscopy. The superoxide dismutase (SOD) and malondialdehyde (MDA) activity in heart homogenates were measured by a biochemical method., Results: The myocardial infarction size was smaller in the POC group than in the I/R group (0.26 ± 0.02 vs. 0.37 ± 0.09, P<0.05), and the PAD group (0.14 ± 0.08) displayed a significantly reduced infarction size relative to the I/R group (P<0.01) and POC group (P<0.05). The damage of myocardial tissue was severe in the I/R group shown by light and electron microscopy: myocardial fibers disorder, sarcoplasmic dissolution, myofilament fracture, mitochondria swelling and even vacuolization formation and a large number of inflammatory cell infiltrations. Compared with the I/R group, reduction of reperfusion injury in the PAD group included more orderly arranged myocardial fibers, less infiltration of inflammatory cells and maintenance of mitochondrial integrity. Compared with the I/R group, the damage of myocardial tissue in the POC group was improved, but not as significant as that in the PAD group. SOD levels in the POC group and the PAD group were significantly higher than those in the I/R group (96.96 ± 13.43, 112.25 ± 22.75 vs. 76.32 ± 10.63, P<0.05), and MDA was significantly lower in the POC group and the PAD group compared to the I/R group (1.27 ± 0.19, 1.09 ± 0.21 vs. 1.47 ± 0.16, P<0.05)., Conclusion: DHI and ischemic postconditioning show a synergistic cardioprotection on myocardial reperfusion injury in minipigs.

The sodium iodide symporter (NIS) present in the membranes of thyroid cells is responsible for the capacity of the thyroid to concentrate iodide. This allows treatment of thyroid cancers with (131)I. We propose to enlarge the therapeutic strategy to hepatocellular carcinomas by using hepatoma-specific promoter and enhancer for targeted radiotherapy. We constructed a recombinant adenovirus encoding hNIS gene under the control of AFP promoter and enhancer (AdPLEN). After being infected with AdPLEN, HepG2 cells (high AFP-expression hepatoma cells) showed 6 times greater perchlorate-sensitive (125)I uptake than did SMMC7721 cells (low/no AFP-expression hepatoma cells), 30 times higher than Hela (human cervix tumor cells), and noninfected HepG2 cells. These results demonstrate that the AdPLEN vector can function in high AFP expression hepatoma cells. In addition, AdPLEN-infected tumor cells were selectively killed by exposure to (131)I, as revealed by clonogenic assays. To assess the efficiency of this target gene therapy strategy in vivo, we injected the AdPLEN vector in human tumors (HepG2 cells) established in nude mice. Western blotting analysis confirmed the expression of the NIS protein in the tumor. Two days after intratumoral injection, AdPLEN-treated tumors could specifically accumulate (131)I, as revealed by imaging experiments. Altogether, these data indicate that AdPLEN is very efficient in triggering and enlarging significant iodide uptake by hepatocellular carcinomas, outlining the potential of this novel cancer gene therapy approach for a targeted radiotherapy.

Objective: To investigate the effect of the active components from Red Paeonia and Rhizoma chuanxiong (in Xiongshao Capsule, XSC) on matrix metalloproteinases (MMPs) in rabbit model of atherosclerosis., Methods: Fifty New Zealand rabbits were randomly divided into the normal control group (A), the model control group (B), the Simvastatin treated group (C), the low-dose XSC treated group (D) and the high-dose XSC treated group (E), 10 in each group. Rabbits in the normal control group were fed with normal diet, while those in the other four groups were fed with high fat diet and duplicated after two weeks feeding into model of abdominal aortic atherosclerosis by balloon angioplasty. In the 6 successive weeks feeding of high fat diet, Simvastatin 2.5 mg/kg, XSC 0.24 g/kg and 0.48 g/kg per day was given respectively to the rabbits in the three treated groups. Blood sample was collected for determining the level of blood lipids; serum MMP-3 and MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) with enzyme-linked immunoassay; and the protein expression of MMP-3 and cluster of differentiation antigen 40 ligand (CD40L) in plaque were detected with immunohistochemical method., Results: Compared with Group B, the serum levels of MMP-3 and MMP-9; the expression of MMP-3 and CD40L in plaque; and the blood content of total cholesterol in the three treated groups were significantly lower (P < 0.05 or P < 0.01). Besides, the content of triglyceride and low-density lipoprotein cholesterol were significantly reduced in Group C, while the TIMP-1 showed no statistical difference among different groups (P > 0.05)., Conclusion: The active components of Red Paeonia and Rhizoma chuanxiong play a definite role in stabilizing the atherosclerotic plaque in rabbits, one of their possible mechanisms may be by way of inhibiting the expressions of MMP-3, MMP-9 in vascular walls and blood serum.

Acute myocardial infarction (AMI) is still the leading factor causing crippling and death in cardiovascular disease. Percutaneous coronary intervention (PCI) can significantly reduce inpatient mortality and incidence of complication. But owing to the existence of restenosis, in-stent thrombosis, etc., recurrent post-PCI cardiovascular events and high repeatability of hospitalization, as well as its crippling rate and mortality, remain a serious threat to the society and the patients' family. Therefore, the appraisal and intervention in post-PCI associated risk factors has presently become one of the foci in clinical research. To improve the near- and long-term prognosis and quality of life in post-PCI AMI patients, further improvement of the evaluation system in risk factors and prognosis is necessary in order to provide a theoretical basis for early application of intervention in high-risk patients in clinical practice. This thesis mainly dissertates some explicit and valuable factors for clinical prognosis evaluation in recent studies, involving C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), Chinese medicine (TCM) syndrome, their correlation with clinical state and course of AMI, and their importance in clinical prognosis.

Objective: To investigate the differential gene expression profiles in coronary heart disease (CHD) patients of blood-stasis syndrome (BSS) by oligonucleotide microarray technique, and the clinical significance of target gene., Methods: Subjects were assigned to CHD patients with BSS (n=8), CHD patients without BSS (n=8), and BSS patients without CHD (n=8) based on coronary angiography and the diagnostic criteria of BSS. The sex- and age-matched healthy volunteers (n=8) were enrolled as the control group. Venous blood samples were collected for RNA extraction; Test-3 chip was employed to examine the quality of samples. Then, the samples were hybridized with Affymetrix U133 Plus 2.0 array to compare the gene expression profiles among the four groups. Gene-array scanner and gene chip operating software were applied to screen out hybridization signals and analyze gene expression, respectively. Based on the comparison of the samples of the four groups, the differential genes related with CHD and BSS were analyzed with Gene Ontology (GO) and pathway, and target genes selected were confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR). Thirty CHD patients with BSS were selected according to the former criteria and 40 healthy as controls. The serum concentration of interleukin-8 (IL-8) was determined by double-antibody sandwich avidin-biotin peroxidase complex enzyme-linked (ABC-ELISA)., Results: A total of 107 differential genes were found being associated with CHD, including 48 up-regulated genes and 59 down-regulated genes. Among these 107 differential genes, 14 genes (13.1%) were found related to inflammatory reaction and immune response through GO analysis. In the pathway analysis, 4 of 15 conspicuous pathways were referred to the inflammation and immune response. Among 48 differential genes related to BSS, 26 genes were up-regulated, and 22 were down-regulated. Five of the 48 genes (10.4%) and 5 of 10 significant pathways were involved in inflammation and immunity. The results of real-time RT-PCR proved the accuracy of the gene chip. The patients have markedly higher level of serum IL-8 compared to the controls (P<0.05)., Conclusion: The correlation of inflammatory- and immune-related genes with CHD patients of BSS was revealed at the level of nucleic acid, and the target gene IL-8 may play a role in the pathobiology of CHD with BSS.

Objective: To investigate the effects of Xuefu Zhuyu Oral Liquid, a compound traditional Chinese herbal medicine for resolving stagnation, on hemorheology in the patients with blood-stasis syndrome due to coronary disease and their relationship with human platelet antigen-3 (HPA-3) polymorphism of membrane glycoprotein IIb (GPIIb)., Methods: Thirty-two patients with blood-stasis syndrome due to coronary disease were selected in this study. Blood-stasis syndrome scoring was performed and hemorheological parameters were measured in all subjects before and after Xuefu Zhuyu Qral Liquid treatment. The genotypes of GPIIb HPA-3 were determined by TaqMan probe technology., Results: The hemorheology was improved in the patients with blood-stasis syndrome due to coronary heart disease after the treatment. There were significant differences in the whole blood viscosity, deformation index of red blood cells and scores of blood-stasis syndrome between the patients carrying AC plus CC and the patients carrying AA after the treatment (P<0.05)., Conclusion: Xuefu Zhuyu Oral Liquid can improve clinical symptoms and hemorheology in the patients with blood-stasis syndrome due to coronary heart disease, which is related to GPIIb HPA-3 polymorphism.

Objective: To investigate the differential gene expression profiles in patients with blood stasis syndrome by oligonucleotide microarray technique., Methods: Sixteen patients with blood stasis syndrome were divided into patients with coronary heart disease (CAD) (n=8) and non-CAD patients (n=8) by using coronary angiography. The sex- and age-matched eight healthy persons were enrolled as control group. Venous bloods were collected for extracting RNA. Test-3 chip was first employed to examine the quality of samples. Then the samples were hybridized with Affymetrix U133 Plus 2.0 array to compare the gene expression profiles among the three groups. Gene-array scanner and gene chip operating software were applied to screen hybridization signals and analyze gene expression respectively. Based on the comparison of the three groups of samples, the differential genes related with blood stasis syndrome were analyzed by Gene Ontology (GO) and pathway, and confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR)., Results: Forty-eight differential genes were found being associated with blood stasis syndrome, including 26 up-regulated genes and 22 down-regulated genes. Five of the forty-eight genes (10.4%) were related to inflammatory reaction and immune response through the GO analysis. In the pathway analysis, five of ten significant pathways were referred to inflammation and immune response. The results of real-time RT-PCR proved the accuracy of the gene chip., Conclusion: Inflammatory- and immune-related genes have a remarkable predominance in blood stasis syndrome gene expression profiles, which may explain the function of inflammation and immune response in the occurrence and development of blood stasis syndrome.

Through summarizing the literatures concerning basic and clinical study on the correlation between blood-stasis syndrome (BSS) and inflammation, reviewing close correlation of BSS with C-reaction protein, serum interleukin-6, tumor necrosis factor and adhesion molecules, it was found that promoting blood circulation and removing stasis approaches could effect vitally in clinical treatment of inflammation, and the inflammation reaction shows certain effect of mediation in animal model of BSS. Accordingly, the important role played by inflammatory reaction in the occurrence and development of BSS is summarized in the paper.