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1.  Superconductivity in Strong Spin Orbital Coupling Compound Sb2Se3 
Scientific Reports  2014;4:6679.
Recently, A2B3 type strong spin orbital coupling compounds such as Bi2Te3, Bi2Se3 and Sb2Te3 were theoretically predicated to be topological insulators and demonstrated through experimental efforts. The counterpart compound Sb2Se3 on the other hand was found to be topological trivial, but further theoretical studies indicated that the pressure might induce Sb2Se3 into a topological nontrivial state. Here, we report on the discovery of superconductivity in Sb2Se3 single crystal induced via pressure. Our experiments indicated that Sb2Se3 became superconductive at high pressures above 10 GPa proceeded by a pressure induced insulator to metal like transition at ~3 GPa which should be related to the topological quantum transition. The superconducting transition temperature (TC) increased to around 8.0 K with pressure up to 40 GPa while it keeps ambient structure. High pressure Raman revealed that new modes appeared around 10 GPa and 20 GPa, respectively, which correspond to occurrence of superconductivity and to the change of TC slop as the function of high pressure in conjunction with the evolutions of structural parameters at high pressures.
doi:10.1038/srep06679
PMCID: PMC4202213  PMID: 25327696
2.  Superconductivity in Topological Insulator Sb2Te3 Induced by Pressure 
Scientific Reports  2013;3:2016.
Topological superconductivity is one of most fascinating properties of topological quantum matters that was theoretically proposed and can support Majorana Fermions at the edge state. Superconductivity was previously realized in a Cu-intercalated Bi2Se3 topological compound or a Bi2Te3 topological compound at high pressure. Here we report the discovery of superconductivity in the topological compound Sb2Te3 when pressure was applied. The crystal structure analysis results reveal that superconductivity at a low-pressure range occurs at the ambient phase. The Hall coefficient measurements indicate the change of p-type carriers at a low-pressure range within the ambient phase, into n-type at higher pressures, showing intimate relation to superconducting transition temperature. The first principle calculations based on experimental measurements of the crystal lattice show that Sb2Te3 retains its Dirac surface states within the low-pressure ambient phase where superconductivity was observed, which indicates a strong relationship between superconductivity and topology nature.
doi:10.1038/srep02016
PMCID: PMC3687246  PMID: 23783511
3.  Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity. 
Journal of Clinical Investigation  1995;96(6):2792-2801.
Glucosamine (Glmn), a product of glucose metabolism via the hexosamine pathway, causes insulin resistance in isolated adipocytes by impairing insulin-induced GLUT 4 glucose transporter translocation to the plasma membrane. We hypothesized that Glmn causes insulin resistance in vivo by a similar mechanism in skeletal muscle. We performed euglycemic hyperinsulinemic clamps (12 mU/kg/min + 3H-3-glucose) in awake male Sprague-Dawley rats with and without Glmn infusion at rates ranging from 0.1 to 6.5 mg/kg/min. After 4h of euglycemic clamping, hindquarter muscles were quick-frozen and homogenized, and membranes were subfractionated by differential centrifugation and separated on a discontinuous sucrose gradient (25, 30, and 35% sucrose). Membrane proteins were solubilized and immunoblotted for GLUT 4. With Glmn, glucose uptake (GU) was maximally reduced by 33 +/- 1%, P < 0.001. The apparent Glmn dose to reduce maximal GU by 50% was 0.1 mg/kg/min or 1/70th the rate of GU on a molar basis. Control galactosamine and mannosamine infusions had no effect on GU. Relative to baseline, insulin caused a 2.6-fold increase in GLUT 4 in the 25% membrane fraction (f), P < 0.01, and a 40% reduction in the 35%f, P < 0.05, but had no effect on GLUT 4 in the 30% f, P= NS. Addition of Glmn to insulin caused a 41% reduction of GLUT 4 in the 25%f, P < 0.05, a 29% fall in the 30%f, and prevented the reduction of GLUT 4 in the 35% f. The 30%f membranes were subjected to a second separation with a 27 and 30% sucrose gradient. Insulin mobilized GLUT 4 away from the 30%f, P < 0.05, but not the 27% f. In contrast, Glmn reduced GLUT 4 in the 27%f, P < 0.05, but not the 30%f. Thus Glmn appears to alter translocation of an insulin-insensitive GLUT 4 pool. Coinfusion of Glmn did not alter enrichment of the sarcolemmal markers 5'-nucleotidase, Na+/K+ATPase, and phospholemman in either 25, 30, or 35% f. Thus Glmn completely blocked movement of Glut 4 induced by insulin. Glmn is a potent inducer of insulin resistance in vivo by causing (at least in part) a defect intrinsic to GLUT 4 translocation and/or trafficking. These data support a potential role for Glmn to cause glucose-induced insulin resistance (glucose toxicity).
Images
PMCID: PMC185989  PMID: 8675649
4.  Single-molecule force measurement via optical tweezers reveals different kinetic features of two BRaf mutants responsible for cardio-facial-cutaneous (CFC) syndrome: errata 
Biomedical Optics Express  2014;6(1):244.
We correct the omission of the construct and protein purification method in our recent paper [Biomed. Opt. Express 4(12), 2835–2845 (2013)].
doi:10.1364/BOE.6.000244
PMCID: PMC4317112  PMID: 25656083
(170.0170) Medical optics and biotechnology; (170.1420) Biology; (170.4520) Optical confinement and manipulation; (350.4855) Optical tweezers or optical manipulation
6.  First birth Caesarean section and subsequent fertility: a population-based study in the USA, 2000–2008 
Human Reproduction (Oxford, England)  2013;28(12):3349-3357.
STUDY QUESTION
Is first birth Caesarean delivery associated with a lower likelihood of subsequent childbearing when compared with first birth vaginal delivery?
SUMMARY ANSWER
In this study of US women whose first delivery was in 2000, those who had a Caesarean delivery were less likely to have a subsequent live birth than those who delivered vaginally.
WHAT IS ALREADY KNOWN
Some studies have reported lower birth rates subsequent to Caesarean delivery in comparison with vaginal delivery, while other studies have reported no difference.
STUDY DESIGN, SIZE, DURATION
We conducted a retrospective cohort study of 52 498 women who had a first singleton live birth in the State of Pennsylvania, USA in 2000 and were followed to the end of 2008 via Pennsylvania birth certificate records to identify subsequent live births during the 8- to 9-year follow-up period.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Birth certificate records of first singleton births were linked to the hospital discharge data for each mother and newborn, and linked to all birth certificate records for each mother's subsequent deliveries which occurred in 2000 to the end of 2008. Poisson regression models were used to evaluate the association between first birth factors and whether or not there was a subsequent live birth during the follow-up period.
MAIN RESULTS AND THE ROLE OF CHANCE
Over an average of 8.5 years of follow-up, 40.2% of women with a Caesarean first birth did not have a subsequent live birth, compared with 33.1% of women with a vaginal first birth (risk ratio (RR): 1.21, 95% confidence interval (CI): 1.18–1.25). Adjustment for the demographic confounders of maternal age, race, education, marital status and health insurance coverage attenuated the RR to 1.16 (95% CI: 1.13–1.19). Specific pregnancy and childbirth-related complications associated with not having a subsequent live birth included diabetes-related disorders, abnormalities of organs and soft tissues of the pelvis, fetal abnormalities, premature or prolonged rupture of membranes, hypertensive disorders, amnionitis, fetal distress and other maternal health problems. However, adjustment for the pregnancy and childbirth complications had little effect on the RR of not having a subsequent live birth (RR = 1.15, 95% CI: 1.11–1.19).
LIMITATIONS, REASONS FOR CAUTION
We were unable to distinguish between women who did not have a subsequent live birth and those who moved out of the state, which may have introduced a selection bias if those who had Caesarean births were more likely to emigrate than those who delivered vaginally. In addition we were unable to measure pre-pregnancy body mass index, weight gain during pregnancy and prior infertility, which would have been helpful in our efforts to reduce selection bias.
WIDER IMPLICATIONS OF THE FINDINGS
The results of this study provide further corroboration of previous studies that have reported reduced fertility subsequent to Caesarean section in comparison with vaginal delivery.
STUDY FUNDING/POTENTIAL COMPETING INTERESTS
This study was funded by the US National Institute of Child Health and Human Development (NICHD, R01-HD052990). No competing interests are declared.
doi:10.1093/humrep/det343
PMCID: PMC3829579  PMID: 24021550
Caesarean section; fertility; parturition; reproduction; pregnancy complications
7.  Expression of insulin-like growth factor-1 receptor in keloid and hypertrophic scar 
Background
Keloid and hypertrophic scar (HS) are two pathological forms of excessive dermal fibrosis, which are due to aberrant wound-healing responses. Accumulating evidence suggests that aberrant activity of growth factors and increased numbers of growth factor receptors play an important role in the formation of pathological scar.
Aim
We examined the expression level of insulin-like growth factor-1 receptor (IGF-IR) in keloid, HS and normal skin.
Methods
IGF-IR expression was analyzed by immunohistochemistry, real-time PCR and western blotting on tissues and fibroblasts from 30 patients, comprising 10 patients with keloid and 20 with HS (10 with immature and 10 with mature HS), and from 10 age-matched and sex-matched healthy controls.
Results
Immunoreactivity to IGF-IR was found in dermal fibroblasts of keloid (90%), immature HS, (80%) and mature HS (30%), but not in normal skin. There was no statistically significant difference in immunoreactivity scores between keloid and immature HS, but there was a significant difference (P < 0.01) between mature and immature HS. Real-time PCR and western blot analysis confirmed that there was high expression of IGF-IR in keloid and immature HS fibroblasts, but not in mature HS or normal skin fibroblasts. IGF-IR was expressed in the overlying epidermis, and there was no significant difference between the groups.
Conclusions
IGF-IR may be involved in the pathogenesis of keloid and HS. Given that IGF-IR are predominantly expressed on dermal fibroblasts, targeting of IGF-IR in fibroblasts may be of benefit to prevent scarring.
doi:10.1111/ced.12407
PMCID: PMC4232319  PMID: 25154292
8.  Ribosomal s6 protein kinase 4: a prognostic factor for renal cell carcinoma 
Fan, L | Li, P | Yin, Z | Fu, G | Liao, D J | Liu, Y | Zhu, J | Zhang, Y | Wang, L | Yan, Q | Guo, Y | Shao, C | Huang, G | Wang, Z
British Journal of Cancer  2013;109(5):1137-1146.
Background:
The expression and function of ribosomal s6 protein kinase 4 (RSK4) in renal cell carcinoma (RCC) are unknown.
Methods:
Immunohistochemistry was used to detect the expression of RSK4 in RCC, and the relationship between RSK4 expression and clinicopathological features as well as prognosis of RCC patients was statistically analysed. Ectopic RSK4 expression in RCC cell lines was performed to determine its effect on cell cycle regulation, tumour invasiveness, and metastatic capability.
Results:
RSK4 was overexpressed in RCCs (P=0.003), compared with normal tissues, and the expression varied in different RCC subtypes (P=0.021), especially in two subtypes of papillary RCCs (P=0.001). RSK4 expression was positively correlated with high pT stage (P<0.001), high Fuhrman grade (P<0.001), lymph node involvement (P<0.001), and presence of distant metastasis (P=0.039), and could predict poor outcome in RCC patients. Molecular studies showed that overexpression of RSK4 could promote cell cycle progression and enhance the invasive and metastatic capability of RCC cell lines and vice versa.
Conclusion:
The expression pattern and molecular mechanisms of RSK4 in RCCs indicate that it could be a potential independent prognostic factor and serve as a new potential therapeutic target for RCC patients.
doi:10.1038/bjc.2013.463
PMCID: PMC3778307  PMID: 23942078
ribosomal s6 protein kinase 4; renal cell carcinoma; prognosis; invasion; metastasis
9.  An Optimized Fluorogenic ADAMTS13 Assay with Increased Sensitivity for the Investigation of Patients with Thrombotic Thrombocytopenic Purpura 
Journal of thrombosis and haemostasis : JTH  2013;11(8):10.1111/jth.12319.
Summary
Background
Most ADAMTS13 assays use non-physiological conditions (low ionic strength, low pH, barium chloride), are subject to interference from plasma proteins, hemoglobin and bilirubin, and have limited sensitivity, especially for inhibitors.
Objectives
We addressed these constraints by designing a substrate that can be used in undiluted plasma.
Methods
A polypeptide was expressed in E. coli that corresponds to von Willebrand factor Gln1599-Arg1668, with mutations N1610C and K1617R and an N-terminal Gly. Substrate FRETS-rVWF71 was prepared by modifying Cys1610 with DyLight 633 (abs 638 nm, em 658 nm) and the N-terminus with IRDye QC-1 (abs 500-800 nm). Assays were performed at pH 7.4 in 150 mM NaCl, 10 mM CaCl2.
Results
Serum and plasma anticoagulated with citrate or heparin had equivalent ADAMTS13 activity with FRETS-rVWF71. Neither bilirubin (≤20 mg/dL) nor hemoglobin (≤20 g/L) interfered with product detection. Assays with FRETS-rVWF71 and FRETS-VWF73 gave similar results (R2 = 0.95) for plasma from 80 subjects with thrombotic microangiopathy, 22 subjects with other causes of thrombocytopenia, and 20 healthy controls. The limit of detection with FRETS-rVWF71 for ADAMTS13 activity was ≤0.3%. Inhibitor assays with FRETS-rVWF71 gave titers ~2.5-fold higher than with FRETS-VWF73 and clearly distinguished patients with and without inhibitors.
Conclusions
FRETS-rVWF71 is suitable for ADAMTS13 assays in minimally diluted plasma or serum without interference from proteins, bilirubin or free hemoglobin in plasma. Optimized detection of ADAMTS13 inhibitors will facilitate the monitoring of antibody responses during the treatment of thrombotic thrombocytopenic purpura.
doi:10.1111/jth.12319
PMCID: PMC3807872  PMID: 23773695
ADAMTS13 protein, human; Purpura, thrombotic thrombocytopenic; von Willebrand factor; Recombinant Fusion Proteins; Kinetics; Substrate Specificity
10.  In Vitro Cadmium-Induced Alterations in Growth and Oxidative Metabolism of Upland Cotton (Gossypium hirsutum L.) 
The Scientific World Journal  2014;2014:309409.
Cadmium (Cd) is a toxic pollutant, which cause both dose- and time-dependent physiological and biochemical alterations in plants. The present in vitro study was undertaken to explore Cd-induced physiological and biochemical changes in cotton callus culture at 0, 550, 700, 850, and 1000 μM Cd for four different stress periods (7, 14, 21, and 28 days). At 1000 μM Cd, mean growth values were lower than their respective control. The cell protein contents decreased only after 7-day and 14-day stress treatment. At 550 μM Cd, malondialdehyde (MDA) contents decreased after various stress periods except 21-day period. Superoxide dismutase (SOD) activity at 1000 μM Cd improved relative to its respective controls in the first three stress regimes. Almost a decreasing trend in the hydrogen peroxide (H2O2) and peroxidase (POD) activities at all Cd levels after different stress periods was noticed. Ascorbate peroxidase (APX) activity descended over its relevant controls in the first three stress regimes except at 700 μM Cd after 14- and 21-day stress duration. Moreover, catalase (CAT) mean values significantly increased as a whole. From this experiment, it can be concluded that lipid peroxidation as well as reactive oxygen species (ROS) production was relatively higher as has been revealed by higher MDA contents and greater SOD, CAT activities.
doi:10.1155/2014/309409
PMCID: PMC4075124  PMID: 25013851
11.  Chromium (VI) Uptake and Tolerance Potential in Cotton Cultivars: Effect on Their Root Physiology, Ultramorphology, and Oxidative Metabolism 
BioMed Research International  2014;2014:975946.
Chromium (Cr) is present in our environment as a toxic pollutant, which needs to be removed using phytoremediation technology. In present study, two transgenic cotton cultivars (J208, Z905) and their hybrid line (ZD14) were used to explore their Cr uptake and tolerance potential using multiple biomarkers approach. Four different levels of Cr (CK, 10, 50, and 100 μM) were applied. Cr caused a significant reduction in root/shoot length, number of secondary roots, and root fresh and dry biomasses at 100 μM. Cr accumulated more in roots and was found higher in hybrid line (ZD14) as compared with its parent lines (J208, Z905) at all Cr stress levels (10, 50, and 100 μM). Cr translocation was less than 1 in all cultivars. Ultrastructural studies at 100 μM Cr showed an increase in number of nuclei and vacuoles and presence of Cr dense granules in dead parts of the cell (vacuoles/cell wall). Malondialdehyde (MDA), hydrogen peroxide (H2O2), total soluble proteins, superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), catalase (CAT), and glutathione reductase (GR) as a whole were upregulated with elevated levels of Cr. Higher Cr uptake by roots, accelerated metabolism, and Cr sequestration in dead parts of the cell indicate that these cotton cultivars can be useful for Cr accumulation and tolerance.
doi:10.1155/2014/975946
PMCID: PMC4053220  PMID: 24955374
12.  The Optimal Solution of a Non-Convex State-Dependent LQR Problem and Its Applications 
PLoS ONE  2014;9(4):e94925.
This paper studies a Non-convex State-dependent Linear Quadratic Regulator (NSLQR) problem, in which the control penalty weighting matrix in the performance index is state-dependent. A necessary and sufficient condition for the optimal solution is established with a rigorous proof by Euler-Lagrange Equation. It is found that the optimal solution of the NSLQR problem can be obtained by solving a Pseudo-Differential-Riccati-Equation (PDRE) simultaneously with the closed-loop system equation. A Comparison Theorem for the PDRE is given to facilitate solution methods for the PDRE. A linear time-variant system is employed as an example in simulation to verify the proposed optimal solution. As a non-trivial application, a goal pursuit process in psychology is modeled as a NSLQR problem and two typical goal pursuit behaviors found in human and animals are reproduced using different control weighting . It is found that these two behaviors save control energy and cause less stress over Conventional Control Behavior typified by the LQR control with a constant control weighting , in situations where only the goal discrepancy at the terminal time is of concern, such as in Marathon races and target hitting missions.
doi:10.1371/journal.pone.0094925
PMCID: PMC3991650  PMID: 24747417
13.  The Effect of Thermal Reduction on the Photoluminescence and Electronic Structures of Graphene Oxides 
Scientific Reports  2014;4:4525.
Electronic structures of graphene oxide (GO) and hydro-thermally reduced graphene oxides (rGOs) processed at low temperatures (120–180°C) were studied using X-ray absorption near-edge structure (XANES), X-ray emission spectroscopy (XES) and resonant inelastic X-ray scattering (RIXS). C K-edge XANES spectra of rGOs reveal that thermal reduction restores C = C sp2 bonds and removes some of the oxygen and hydroxyl groups of GO, which initiates the evolution of carbonaceous species. The combination of C K-edge XANES and Kα XES spectra shows that the overlapping π and π* orbitals in rGOs and GO are similar to that of highly ordered pyrolytic graphite (HOPG), which has no band-gap. C Kα RIXS spectra provide evidence that thermal reduction changes the density of states (DOSs) that is generated in the π-region and/or in the gap between the π and π* levels of the GO and rGOs. Two-dimensional C Kα RIXS mapping of the heavy reduction of rGOs further confirms that the residual oxygen and/or oxygen-containing functional groups modify the π and σ features, which are dispersed by the photon excitation energy. The dispersion behavior near the K point is approximately linear and differs from the parabolic-like dispersion observed in HOPG.
doi:10.1038/srep04525
PMCID: PMC3982168  PMID: 24717290
14.  Association of LIPC and advanced age-related macular degeneration 
Eye  2013;27(2):265-271.
Purpose
To determine whether there is an association between hepatic lipase (LIPC) and age-related macular degeneration (AMD) in two independent Caucasian cohorts.
Methods
A discovery cohort of 1626 patients with advanced AMD and 859 normal controls and a replication cohort of 2159 cases and 1150 controls were genotyped for two single-nucleotide polymorphisms (SNPs) in the promoter region of LIPC. The associations between the SNPs and AMD were examined by χ2 tests.
Results
In the discovery cohort, rs493258 and rs10468017 were both associated with advanced AMD (P=9.63E−3 and P=0.048, respectively). The association was corroborated in the replication cohort (P=4.48E−03 for rs493258 and P=0.015 for rs10468017). Combined analysis resulted in even more significant associations (P=1.21E−04 for rs493258 and P=1.67E−03 for rs10468017).
Conclusion
The LIPC promoter variants rs493258 and rs10468017 were associated with advanced AMD in two independent Caucasian populations, confirming that LIPC polymorphisms may be a genetic risk factor for AMD in the Caucasian population.
doi:10.1038/eye.2012.276
PMCID: PMC3574263  PMID: 23348725
LIPC; hepatic lipase; advanced age-related macular degeneration; genetics
15.  Magnetic and structural transitions of SrFe2As2 at high pressure and low temperature 
Scientific Reports  2014;4:3685.
One of key issues in studying iron based superconductors is to understand how the magnetic phase of the parent compounds evolves. Here we report the systematic investigation of paramagnetic to antiferromagnetic and tetragonal to orthorhombic structural transitions of “122” SrFe2As2 parent compound using combined high resolution synchrotron Mössbauer spectroscopy and x-ray diffraction techniques in a cryogenically cooled high pressure diamond anvil cell. It is found that although the two transitions are coupled at 205 K at ambient pressure, they are concurrently suppressed to much lower temperatures near a quantum critical pressure of approximately 4.8 GPa where the antiferromagnetic state transforms into bulk superconducting state. Our results indicate that the lattice distortions and magnetism jointly play a critical role in inducing superconductivity in iron based compounds.
doi:10.1038/srep03685
PMCID: PMC3890939  PMID: 24418845
16.  Cadmium-Induced Upregulation of Lipid Peroxidation and Reactive Oxygen Species Caused Physiological, Biochemical, and Ultrastructural Changes in Upland Cotton Seedlings 
BioMed Research International  2013;2013:374063.
Cadmium (Cd) toxicity was investigated in cotton cultivar (ZMS-49) using physiological, ultrastructural, and biochemical parameters. Biomass-based tolerance index decreased, and water contents increased at 500 μM Cd. Photosynthetic efficiency determined by chlorophyll fluorescence and photosynthetic pigments declined under Cd stress. Cd contents were more in roots than shoots. A significant decrease in nutrient levels was found in roots and stem. A significant decrease in nutrient levels was found in roots and stems. In response to Cd stress, more MDA and ROS contents were produced in leaves than in other parts of the seedlings. Total soluble proteins were reduced in all parts except in roots at 500 μM Cd. Oxidative metabolism was higher in leaves than aerial parts of the plant. There were insignificant alterations in roots and leaves ultrastructures such as a little increase in nucleoli, vacuoles, starch granules, and plastoglobuli in Cd-imposed stressful conditions. Scanning micrographs at 500 μM Cd showed a reduced number of stomata as well as near absence of closed stomata. Cd depositions were located in cell wall, vacuoles, and intracellular spaces using TEM-EDX technology. Upregulation of oxidative metabolism, less ultrastructural modification, and Cd deposition in dead parts of cells show that ZMS-49 has genetic potential to resist Cd stress, which need to be explored.
doi:10.1155/2013/374063
PMCID: PMC3888702  PMID: 24459668
17.  The Effect of Terminal Cleaning on Environmental Contamination Rates of Multidrug-Resistant Acinetobacter baumannii 
American journal of infection control  2012;40(10):10.1016/j.ajic.2012.05.027.
We evaluated the prevalence of multidrug-resistant Acinetobacter baumannii environmental contamination before and after discharge cleaning in rooms of infected/colonized patients. 46.9% of rooms and 15.3% of sites were found contaminated at baseline. 25% of rooms, 5.5% of sites, were found contaminated post cleaning. Cleaning significantly decreased environmental contamination of A. baumannii, however, persistent contamination represents a significant risk factor for transmission. Further studies on this and more effective cleaning methods are needed.
doi:10.1016/j.ajic.2012.05.027
PMCID: PMC3855251  PMID: 23199726
18.  Tanshinone-1 induces tumor cell killing, enhanced by inhibition of secondary activation of signaling networks 
Cell Death & Disease  2013;4(11):e905-.
Tumor multidrug resistance (MDR) can result from overexpression of drug transporters and deregulation of cellular signaling transduction. New agents and strategies are required for overcoming MDR. Here, we report that tanshinone-1, a bioactive ingredient in traditional Chinese medicine, directly killed MDR tumor cells and their corresponding parental cells, which was potentiated by inhibition of secondary activation of signaling networks. Tanshinone-1 was slightly more potent at inducing cytotoxicity and apoptosis in MDR cells than in corresponding parental cells. Tanshinone-1-induced MDR cell killing was independent of the function and expression of drug transporters but was partially correlated with the phosphatase-dependent reduction of phospho-705-Stat3, which secondarily activated p38-, AKT-, and ERK-involved signaling networks. Cotreatments with p38, AKT, and ERK inhibitors potentiated the anti-MDR effects of tanshinone-1. Our study presents a model for MDR cell killing using a compound of natural origin. This model could lead to new therapeutic strategies for targeting signaling network(s) in MDR cancers as well as new strategies for multitarget design.
doi:10.1038/cddis.2013.443
PMCID: PMC3847321  PMID: 24201804
tanshinone-1; multidrug resistance; Stat3; p38; AKT; ERK
19.  Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac muscle cells 
Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.
doi:10.1590/1414-431X20132936
PMCID: PMC3854426  PMID: 24036910
Macrophage migration inhibitory factor; HL-1 cells; Hydrogen peroxide; Atrial fibrillation; Protein kinases
20.  Active DNA Demethylation in Plants and Animals 
Active DNA demethylation regulates many vital biological processes, including early development and locus-specific gene expression in plants and animals. In Arabidopsis, bifunctional DNA glycosylases directly excise the 5-methylcytosine base and then cleave the DNA backbone at the abasic site. Recent evidence suggests that mammals utilize DNA glycosylases after 5-methylcytosine is oxidized and/or deaminated. In both cases, the resultant single-nucleotide gap is subsequently filled with an unmodified cytosine through the DNA base excision repair pathway. The enzymatic removal of 5-methylcytosine is tightly integrated with histone modifications and possibly noncoding RNAs. Future research will increase our understanding of the mechanisms and critical roles of active DNA demethylation in various cellular processes as well as inspire novel genetic and chemical therapies for epigenetic disorders.
doi:10.1101/sqb.2012.77.014936
PMCID: PMC3657592  PMID: 23197304
21.  320-detector CT coronary angiography with prospective and retrospective electrocardiogram gating in a single heartbeat: comparison of image quality and radiation dose 
The British Journal of Radiology  2012;85(1015):945-951.
Objectives
To compare the image quality, radiation dose and diagnostic accuracy of 320-detector CT coronary angiography with prospective and retrospective electrocardiogram (ECG) gating in a single heartbeat.
Methods
Two independent reviewers separately scored image quality of coronary artery segment for 480 cardiac CT studies in a prospective group and a retrospective group (240 patients with a heart rate <65 beats per minute in each group). The two groups matched well for clinical characteristics and CT parameters. There was good agreement for image quality scores of coronary artery segment between the independent reviewers (κ = 0.73). Of the 7023 coronary artery segments, the image quality scores of the prospective group and retrospective group were not significantly different (p>0.05). The mean radiation dose was 10.0±3.5 mSv (range 6.2–21.6 mSv) for prospective ECG gating at 65–85% of R–R interval (the interval between the R-wave of one heartbeat to the R-wave of the next). The mean radiation dose for retrospective ECG-triggered modulated scans was 23.2±3.4 mSv (range 17–27.4 mSv). The mean radiation dose was 57% lower for prospective gating than for retrospective gating (p<0.01).
Results
Compared with coronary angiography, the results for prospective vs retrospective ECG gating were 92% vs 90% for sensitivity (p = 0.23), 89% vs 91% for specificity (p = 0.19), 90% vs 93% for positive predictive value (p = 0.25) and 92% vs 95% for negative predictive value (p = 0.21) for lesions with ≥50% stenosis, respectively.
Conclusion
320-detector CT coronary angiography performed with prospective ECG gating has similar subjective image quality scores, but a 57% lower radiation dose than retrospective ECG gating in a single heartbeat.
doi:10.1259/bjr/29901700
PMCID: PMC3474068  PMID: 22745204
22.  A novel compound heterozygous mutation in the BEST1 gene causes autosomal recessive Best vitelliform macular dystrophy 
Eye  2012;26(6):866-871.
Purpose
To determine the genetic basis of early onset autosomal recessive Best vitelliform macular dystrophy (arBVMD) in a family with three affected children.
Design
Clinical and family-based genetic study.
Methods
Seven subjects making up a family with three children affected by Best vitelliform macular dystrophy were studied. Standard ophthalmic exam with dilated ophthalmoscopy and imaging were performed in each individual. The eleven exons of BEST1were directly sequenced.
Results
All three affected children have the clinical characteristic features of Best vitelliform macular dystrophy: large macular vitelliform lesions, scattered vitelliform lesions along the arcades and in the peripheral retina, and an accumulation of serous retinal fluid. A novel compound heterozygous mutation in the BEST1gene was found in the three affected individuals (L41P and I201T). The unaffected parents and children only harbor one heterozygous mutation.
Conclusion
arBVMD can be caused by the compound heterozygous mutation L41P and I201T in the BEST1gene.
doi:10.1038/eye.2012.27
PMCID: PMC3376281  PMID: 22422030
autosomal recessive Best vitelliform macular dystrophy; BEST1 gene; genetics
23.  Clinical analysis of prophylactic central neck dissection for papillary thyroid carcinoma 
Purpose
The need of prophylactic central neck dissection (PCND) in patients with papillary thyroid carcinoma (PTC) is still controversial. The major restriction of PCND is the potential complications. We undertook a retrospective study to discuss its necessity in PTC patients.
Methods
A total of 188 patients with PTC who underwent total thyroidectomy and PCND were involved. In all of these, central lymph nodes were pathologic examined. Univariate and multivariate analyses were performed based on tumor location and size, etc.
Results
Overall, node metastases were found in 44.1 % (83/188) of patients. Tumor size was the independent positive predictor for lymph node metastasis, while gender, age, tumor multifocality, tumor location, and capsular infiltration were not independent predictors of central lymph node metastases. Postoperative complications happened in 5.3 % (10/188) of patients, which 4.8 % (9/188) had temporary hypocalcemia and 0 % (0/188) had permanent hypocalcemia. Rates of temporary and permanent recurrent laryngeal nerve injury were 0.5 % (1/188) and 0 % (0/188), respectively.
Conclusions
PCND is recommended in all patients with PTC.
doi:10.1007/s12094-013-1038-9
PMCID: PMC3884135  PMID: 23606353
Thyroid carcinoma; Papillary; cN0; Central lymph node; Prophylactic; Central neck dissection
24.  IL-10 Treatment Is Associated with Prohibitin Expression in the Crohn's Disease Intestinal Fibrosis Mouse Model 
Mediators of Inflammation  2013;2013:617145.
Prohibitin, which can inhibit oxidative stress and mitochondrial dysfunction, has been shown to have significant anti-inflammatory activities. Here, we investigate the effects of altering prohibitin levels in affected tissues in the interleukin-10 knockout (IL-10KO) mouse model with intestinal fibrosis. The aim of this study is to investigate the effects of IL-10 on prohibitin and the role of prohibitin in intestinal fibrosis of murine colitis. After the mice were treated with IL-10, prohibitin expression and localization were evaluated in IL-10KO and wild-type (WT, 129/SvEv) mice. The colon tissue was then investigated and the potential pathogenic molecular mechanisms were further studied. Fluorescence-based quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry assays revealed a significant upregulation of prohibitin with IL-10 treatment. Furthermore, IL-10 decreases inflammatory cytokines and TGF-β1 in the IL-10KO model of Crohn's disease and demonstrates a promising trend in decreasing tissue fibrosis. In conclusion, we hypothesize that IL-10 treatment is associated with increased prohibitin and would decrease inflammation and fibrosis in an animal model of Crohn's disease. Interestingly, prohibitin may be a potential target for intestinal fibrosis associated with inflammatory bowel disease (IBD).
doi:10.1155/2013/617145
PMCID: PMC3649775  PMID: 23690666
25.  The organization of two novel cortical interneuronal circuits 
Nature neuroscience  2013;16(2):210-218.
Deciphering interneuronal circuitry is central to understanding brain functions yet remains as a challenging task in neurobiology. Using simultaneous quadruple-octuple in vitro and dual in vivo whole-cell recordings, we found two previously unknown interneuronal circuits that link cortical layer 1–3 (L1-3) interneurons and L5 pyramidal neurons in the rat neocortex. L1 single-bouquet cells (SBCs) preferentially form unidirectional inhibitory connections on L2/3 interneurons that inhibit the entire dendritic-somato-axonal axis of ~1% of L5 pyramidal neurons located within the same column. In contrast, L1 elongated neurogliaform cells (ENGCs) frequently form mutual inhibitory and electric connections with L2/3 interneurons, and these L1-3 interneurons inhibit the distal apical dendrite of >60% of L5 pyramidal neurons across multiple columns. Functionally, SBC→L2/3 interneuron→L5 pyramidal neuronal circuits disinhibit and ENGC↔L2/3 interneuron→L5 pyramidal neuronal circuits inhibit the initiation of dendritic complex spikes in L5 pyramidal neurons. As dendritic complex spikes can serve coincidence detection, these cortical interneuronal circuits may be essential for salience selection.
doi:10.1038/nn.3305
PMCID: PMC3589105  PMID: 23313910

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