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Find video protocols related to scientific articles indexed in Pubmed.
Smoking and Diabetes: Is the Association Mediated by Adiponectin, Leptin, or C-reactive Protein?
J Epidemiol
PUBLISHED: 11-18-2014
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Background: Although the association between cigarette smoking and risk of type 2 diabetes is well established, its mechanisms are yet to be clarified. This study examined the possible mediating effects of adiponectin, leptin, and C-reactive protein (CRP) concentrations on the smoking-diabetes association.Methods: Between 2002 and 2011, we followed 3338 Japanese workers, aged 35-66 years, who were enrolled in the second Aichi workers' cohort study. We used multivariable-adjusted Cox regression models to determine the hazard ratios and respective 95% confidence intervals (CIs) of the association between smoking status and risk of diabetes. A multiple mediation model with bootstrapping was used to estimate the magnitude and the respective bias-corrected (BC) 95% CIs of the indirect effects of smoking on diabetes through the three biomarkers.Results: Relative to never smokers, the risk of diabetes was significantly elevated in current (hazard ratio 1.75, 95% CI 1.25-2.46) and ex-smokers (hazard ratio 1.54, 95% CI 1.07-2.22). The indirect effects of smoking on diabetes through adiponectin levels were statistically significant among light (point estimate 0.033, BC 95% CI 0.005-0.082), moderate (point estimate 0.044, BC 95% CI 0.010-0.094), and heavy smokers (point estimate 0.054, BC 95% CI 0.013-0.113). In contrast, neither the indirect effects of smoking on diabetes through leptin nor CRP levels were significant, as the corresponding BC 95% CIs included zero.Conclusions: In our analysis, adiponectin concentration appeared to partially mediate the effect of smoking on diabetes, while leptin and CRP levels did not.
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[Expression of CCDC67 mRNA and its role in patients with papillary thyroid carcinoma].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 11-18-2014
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To explore the expression of CCDC67 mRNA between papillary thyroid carcinoma (PTC) and adjacent normal tissues.
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Global Trend in Overweight and Obesity and Its Association With Cardiovascular Disease Incidence.
Circ. J.
PUBLISHED: 11-14-2014
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Although the global prevalence of both the overweight and obese is on the rise, there are variations among regions or countries, and sexes. Approximately half or more than half of the population are overweight/obese defined as body mass index ?25 kg/m(2)in the Americas (61.1%), Europe (54.8%), and Eastern Mediterranean (46.0%) according to the World Health Organization, while a much lower prevalence is observed in Africa (26.9%), South-East Asia (13.7%), and the Western Pacific (25.4%). Females are more likely to be overweight/obese in the Eastern Mediterranean, Africa, South-East Asia and the majority of countries in the Americas and Western Pacific but not in the most of the countries in Europe. These region-sex-ethnicity differences in prevalence may be a clue to the causes of the obesity epidemic. Epidemiological studies done in the USA, Europe, and Asia found that higher BMI was significantly associated with increased incidence of coronary artery disease (CAD) and ischemic stroke, but the association with hemorrhagic stroke incidence was not always consistent. The association of BMI with CAD and ischemic stroke was generally independent of known mediators, which would indicate the importance of controlling or preventing overweight/obesity for the prevention of cardiovascular disease.
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[Role of cardiac magnetic resonance on predicting outcome in patients with hypertrophic obstructive cardiomyopathy undergoing percutaneous transluminal septal myocardial ablation].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 11-13-2014
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To investigate the predictive value of cardiac magnetic resonance (CMR) on outcome of patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing percutaneous transluminal septal myocardial ablation (PTSMA).
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[Clinical characteristics and prognosis comparison of Chinese non ST-segment elevation acute coronary syndrome patients in two different time periods].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 11-13-2014
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To compare the clinical characteristics, treatment methods and outcomes in Chinese non ST-segment elevation acute coronary syndrome (NSTE-ACS) patients from two large clinical trials in different time periods.
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Identification of PI3K regulatory subunit p55? as a novel inhibitor of vascular smooth muscle cell proliferation and neointimal formation.
Cardiovasc. Res.
PUBLISHED: 11-10-2014
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Phosphatidylinositol 3 kinases (PI3Ks) play a pivotal role in vascular physiology and pathophysiology. We aimed to investigate the role of p55?, a regulatory subunit of PI3Ks, in vascular smooth muscle cell (VSMC) proliferation and neointimal formation.
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BiAg Alloy Nanospheres: A New Photocatalyst for H2 Evolution from Water Splitting.
ACS Appl Mater Interfaces
PUBLISHED: 11-08-2014
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We demonstrate for the first time that Bi and BiAg alloy nanospheres, fabricated with a facile hydrothermal method, display evident photocatalytic H2 production activities. Element Bi can serve as an active photocatalyst for both water splitting and photoelectrochemical applications. More interestingly, these activities of Bi can be greatly enhanced by introducing Ag to form BiAg alloy nanoparticles, which may be ascribed to the improved charge separation and enlarged carrier concentration. The constituent of the BiAg alloy can be rationally tuned by varying the amount of Ag nanowires, and it is found that Bi0.7Ag0.3 exhibits the highest photoelectrochemical property.
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Genetic association study of RNF8 and BRDT variants with non-obstructive azoospermia in the Chinese Han population.
Syst Biol Reprod Med
PUBLISHED: 11-07-2014
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Abstract Increasing evidence indicates that polymorphisms in genes relevant to spermatogenesis might modulate the efficiency of reproduction in men. Ring finger protein 8 (RNF8) and bromodomain testis-specific (BRDT) are two candidate genes associated with spermatogenesis. Here, we considered potential associations of 14 single nucleotide polymorphisms (SNPs) in RNF8 and BRDT genes in Chinese patients with non-obstructive azoospermia (NOA). We analyzed 361 men with NOA and 368 fertile controls by using Sequenom iplex technology. Our data did not reveal any variants associated with NOA susceptibility. However, we observed that rs104669 and rs195432 of RNF8 were in strong linkage disequilibrium. Haplotype analysis of the two SNPs indicated that the haplotype AC reduced the risk of NOA and the haplotype TC significantly evaluated the risk of NOA. Moreover, the RNF8 variants rs195432 (C/A p?=?0.030), rs195434 (T/C p?=?0.025), and rs2284922 (T/C p?=?0.034) were correlated with the smaller testis volume.
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Antioxidant and Tyrosinase Inhibitory Effects of Neolignan Glycosides from Crataegus pinnatifida Seeds.
Planta Med.
PUBLISHED: 11-06-2014
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In our efforts to find an inhibitor of melanin formation and develop potential depigmenting agents for skin-protecting cosmetics and medicinal products from natural resources, we focused on the seeds of Crataegus pinnatifida which showed antioxidant and tyrosinase-inhibiting activities. By activity-guided fractionation of an extract of C. pinnatifida seeds, four new neolignan glycosides, pinnatifidaninsides A-D (1-4), along with two known compounds (5-6), were isolated. Their structures were elucidated by spectroscopic analyses, especially 1D, 2D?NMR and CD spectra. The antioxidant and tyrosinase-inhibiting activities of all isolates were assayed. Compound 6 showed good activity against 2,2-diphenyl-1-pikrylhydrazyl, while compounds 1, 2, 5, and 6 exhibited strong 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) free radical scavenging activity, being as effective as, or even more effective than the positive control Trolox. Moreover, compounds 5 and 6 displayed a moderate mushroom tyrosinase inhibitory activity.
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[Soil moisture estimation model based on multiple vegetation index].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 11-01-2014
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Estimating soil moisture conveniently and exactly is a hot issues in water resource monitoring among agriculture and forestry. Estimating soil moisture based on vegetation index has been recognized and applied widely. 8 vegetation indexes were figured out based on the hyper-spectral data measured by portable spectrometer. The higher correlation indexes among 8 vegetation indexes and surface vegetation temperature were selected by Gray Relative Analysis method (GRA). Then, these selected indexes were analyzed using Multiple Linear Regression to establish soil moisture estimation model based on multiple vegetation indexes, and the model accuracy was evaluated. The accuracy evaluation indicated that the fitting was satisfied and the significance was 0.000 (P < 0.001). High correlation was turned out between estimated and measured soil moisture with R2 reached 0.636 1 and RMSE 2.149 9. This method introduced multiple vegetation indexes into soil water content estimating over micro scale by non-contact measuring method using portable spectrometer. The exact estimation could be an appropriate replacement for remote sensing inversion and direct measurement. The model could estimate soil moisture quickly and accurately, and provide theory and technology reference for water resource management in agriculture and forestry.
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Emergence of type I restriction modification system-negative emm1 type Streptococcus pyogenes clinical isolates in Japan.
APMIS
PUBLISHED: 10-31-2014
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Streptococcus pyogenes emm1 type is the dominant cause of streptococcal toxic shock syndrome (STSS) in Japan and many other developed countries. Recently, the number of STSS patients in Japan was reported to be increasing. Hence, we analyzed the S. pyogenes clinical isolates detected in Japan after 2005. We found that the regions encoding the Spy1908–1910 two-component regulatory system and the adjacent type I restriction modification system were deleted in some emm1 type isolates. The isolates with the deletion were detected only in the emm1 strains that were isolated between 2010 and 2013, but not before 2010. Twenty-six of 46 (56.5%) emm1 type isolates were isolated in 2010–2013, and among these isolates, five of seven (71.4%) emm1 type STSS isolates were shown to have that deletion. PFGE and PCR analysis for the presence of several pyrogenic exotoxin-related genes suggested that the emm1 isolates with and without the deletion shared the same genetic background. The emm1 isolates with the deletion could incorporate exogenous plasmids by experimental electroporation transformation far more efficiently. These results suggested that the novel emm1 isolates have occupied a fairly large part of total emm1 isolates.
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A crosstalk between class A scavenger receptor and receptor for advanced glycation end-products contributes to diabetic retinopathy.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 10-30-2014
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In response to hyperglycemia in patients with diabetes, a plethora of signaling pathways forge extensive dialogues cumulatively contributing to the pathogenesis of diabetic complications including diabetic retinopathy (DR). Excessive production of inflammatory mediators plays an important role in this process. Amadori-glycated albumin (AGA), one of the major forms of advanced glycated end-product (AGE), has been implicated in DR by inducing inflammatory responses in microglia/macrophages. Our goal was to delineate the potential crosstalk between class A scavenger receptor (SR-A) and the receptor for AGE (RAGE) in the context of DR. We show here that SR-A ablation caused an exacerbated form of diabetic retinopathy in STZ-injected C57BL/6J mice as evidenced by fundus imaging and electroretinography. Immunohistochemistry staining and RT-PCR assay suggest that there was augmented activation of pro-inflammatory macrophages with up-regulated synthesis of pro-inflammatory mediators in the retina in Sr-a(-/-) mice. Over-expression of SR-A suppressed RAGE induced MAPK signaling whereas RAGE activation in macrophages favored a pro-inflammatory (M1) phenotype in the absence of SR-A. Mechanistic analysis on BMDMs and HEK293 cell line revealed that SR-A interacted with and inhibited the phosphorylation of MKK7 (Mitogen-activated protein kinase kinase 7), the major kinase in the RAGE-MAPK-NF-?B signaling thereby leading to diminished secretion of pro-inflammatory cytokines. Our findings indicate that the antagonism between SR-A and RAGE contributes to the pathogenesis of DR by nurturing a disease-prone macrophage phenotype. Therefore, specific agonist that boosts SR-A signaling could potential provide benefits in the prevention and/or intervention of diabetic retinopathy.
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A target-triggered exponential amplification-based DNAzyme biosensor for ultrasensitive detection of folate receptors.
Chem. Commun. (Camb.)
PUBLISHED: 10-28-2014
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We develop a new method for ultrasensitive detection of folate receptors (FRs) using a target-triggered isothermally exponential amplification reaction (EXPAR)-based DNAzyme biosensor. This method exhibits excellent specificity and high sensitivity with a detection limit as low as 0.23 fM and a large dynamic range of 6 orders of magnitude from 1 fM to 1 nM. It might be further applied for the detection of various small molecule-binding proteins by simply changing the linked small molecule moiety of the hairpin probes.
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Activation and Regulation of Caspase-6 and Its Role in Neurodegenerative Diseases.
Annu. Rev. Pharmacol. Toxicol.
PUBLISHED: 10-24-2014
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Caspases, a family of cysteine proteases, are major mediators of apoptosis and inflammation. Caspase-6 is classified as an apoptotic effector, and it mediates nuclear shrinkage during apoptosis, but it possesses unique activation and regulation mechanisms that differ from those of other effector caspases. Furthermore, increasing evidence has shown that caspase-6 is highly involved in axon degeneration and neurodegenerative diseases, such as Huntington's disease and Alzheimer's disease. Cleavage at the caspase-6 site in mutated huntingtin protein is a prerequisite for the development of the characteristic behavioral and neuropathological features of Huntington's disease. Active caspase-6 is present in early stages of Alzheimer's disease, and caspase-6 activity is associated with the disease's pathological lesions. In this review, we discuss the evidence relevant to the role of caspase-6 in neurodegenerative diseases and summarize its activation and regulation mechanisms. In doing so, we provide new insight about potential therapeutic approaches that incorporate the modulation of caspase-6 function for the treatment of neurodegenerative diseases. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 55 is January 06, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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Tolerability of selective cyclooxygenase 2 inhibitors used for the treatment of rheumatological manifestations of inflammatory bowel disease.
Cochrane Database Syst Rev
PUBLISHED: 10-24-2014
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Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammatory pain and swelling in inflammatory bowel disease (IBD) patients with rheumatological manifestations. While these drugs effectively reduce musculoskeletal pain and stiffness, long-term use is limited by gastrointestinal (GI) adverse effects (AEs) and disease exacerbation. As an alternative to NSAIDs, selective cyclooxygenase 2 (COX-2) inhibitors were developed to improve GI safety and tolerability. COX-2 inhibitors include drugs such as celecoxib, rofecoxib, valdecoxib, etoricoxib, and lumiracoxib. Rofecoxib and valdecoxib have been withdrawn from the market worldwide due to safety concerns (most importantly for cardiovascular adverse events) and lumiracoxib has been withdrawn in many countries due to liver toxicity. However, celecoxib and etoricoxib continue to be available for use in many countries. Several studies have examined whether COX-2 inhibitors can be safely used for the treatment of rheumatological manifestations of IBD with inconsistent results. Some investigators report acceptable safety profiles associated with these drugs while others found that COX-2 inhibitors are associated with high rates of disease exacerbation.
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[Research on cleaning rate of the C-shaped canal treated by manual or rotary endodontic file combined with ultrasonic rinsing].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 10-24-2014
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To evaluate the cleaning effect of the C-shaped canal treated by manual K file and ProTaper rotary endodontic file combined with ultrasonic cleaning, and find a better cleaning program for the C-shaped root canal.
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Regulator of G Protein Signalling 5 protects against atherosclerosis in apolipoprotein E-deficient mice.
Br. J. Pharmacol.
PUBLISHED: 10-21-2014
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Atherosclerosis is a chronic inflammatory disease, during which "vulnerable plaques" have been recognised as the underlying risk factor for coronary disease. Regulator of G Protein Signalling (RGS) 5 has been demonstrated to regulate endothelial cells functions and inflammation. In this study, we explored the effect of RGS5 on atherosclerosis and the potential mechanism.
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A self-powered AC magnetic sensor based on piezoelectric nanogenerator.
Nanotechnology
PUBLISHED: 10-21-2014
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An AC magnetic field, which is a carrier of information, is distributed everywhere and is continuous. How to use and detect this field has been an ongoing topic over the past few decades. Conventional magnetic sensors are usually based on the Hall Effect, the fluxgate, a superconductor quantum interface or magnetoelectric or magnetoresistive sensing. Here, a flexible, simple, low-cost and self-powered active piezoelectric nanogenerator (NG) is successfully demonstrated as an AC magnetic field sensor at room temperature. The amplitude and frequency of a magnetic field can both be accurately sensed by the NG. The output voltage of the NG has a good linearity with a measured magnetic field. The detected minute magnetic field is as low as 1.2 × 10(-7) tesla, which is 400 times greater than a commercial magnetic sensor that uses the Hall Effect. In comparison to the existing technologies, an NG is a room-temperature self-powered active sensor that is very simple and very cheap for practical applications.
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Palladium-catalyzed coupling of N-tosylhydrazones and ?-bromostyrene derivatives: new approach to 2H-chromenes.
Org. Biomol. Chem.
PUBLISHED: 10-20-2014
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2H-Chromene is an important structural motif that exists in natural products and non-natural compounds possessing interesting biological activities. In this investigation, a highly efficient approach toward 2H-chromenes has been developed based on palladium-catalyzed coupling of N-tosylhydrazones and ?-bromostyrenes. The mechanism of this reaction is proposed that involves the formation of vinyl palladium by carbene migratory insertion and the intramolecular nucleophilic substitution.
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Full vector measurements of converging terahertz beams with linear, circular, and cylindrical vortex polarization.
Opt Express
PUBLISHED: 10-17-2014
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The complete vector information of converging terahertz (THz) beams with linear, circular, and cylindrical vortex polarization are precisely measured by using a THz digital holographic imaging system. The transverse (Ex, Ey) and longitudinal (Ez) polarization components of the THz fields around the focal point are separately obtained utilizing the detection crystals with different crystalline orientations. The measured results are in good agreement with the theoretical expectations. This imaging technique provides an effective way for revealing the vector diffraction properties of the THz electro-magnetic waves.
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Tuning aluminum spatial distribution in ZSM-5 membranes: a new strategy to fabricate high performance and stable zeolite membranes for dehydration of acetic acid.
Chem. Commun. (Camb.)
PUBLISHED: 10-16-2014
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A novel ZSM-5 membrane with a low Si/Al ratio and homogeneous aluminum spatial distribution was achieved from an organic template-free inorganic gel in the presence of both OH(-) and F(-) ions and the obtained ZSM-5 membrane exhibited excellent selectivity and high flux and stability for dehydration of acetic acid in a wide AcOH content range.
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Interferon regulatory factor 7 protects against vascular smooth muscle cell proliferation and neointima formation.
J Am Heart Assoc
PUBLISHED: 10-12-2014
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Interferon regulatory factor 7 (IRF7), a member of the interferon regulatory factor family, plays important roles in innate immunity and immune cell differentiation. However, the role of IRF7 in neointima formation is currently unknown.
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Anti-oxidative and anti-apoptosis effects of egg white peptide, Trp-Asn-Trp-Ala-Asp, against H2O2-induced oxidative stress in human embryonic kidney 293 cells.
Food Funct
PUBLISHED: 10-10-2014
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Peptides derived from egg white protein are well-known for their abundant species and biological properties. The aim of this study was to investigate the anti-oxidative and anti-apoptosis effects of (Trp-Asn-Trp-Ala-Asp) WNWAD, a pentapeptide derived from egg white ovomucin pepsin hydrolysates, against the oxidative stress induced by H2O2 in HEK-293 cells. Oxygen radical absorbance capacity (ORAC) results showed that WNWAD possessed extraordinary oxygen radical absorption capacity (with an ORAC value = 2.91 ?M TE ?M(-1)) in vitro. Then, at the cellular level, MTS assay results displayed that WNWAD dose-dependently inhibited H2O2-induced cellular oxidative stress in HEK-293 cells and fully recovered the oxidative damage induced by 400 ?M H2O2 at a concentration of 1 ?M. The 2',7'-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe assay further proved that WNWAD inhibited cellular oxidative stress by reducing intracellular ROS accumulation in intact HEK-293 cells. In addition, scanning electron microscopy (SEM) images showed that the morphology of HEK-293 cells under H2O2 treatment displayed a cell apoptosis phenotype, while WNWAD pretreatment prevented the development of this phenotype. Furthermore, Western blot results indicated that WNWAD up-regulated the level of the anti-apoptotic protein Bcl-2 and down-regulated the levels of apoptosis executor proteins, cleaved caspase-3 and cleaved PRAP, in H2O2-induced oxidative stress in HEK-293 cells. All the above results suggested that WNWAD protected HEK-293 cells against H2O2-induced oxidative stress by inhibiting intracellular ROS accumulation and blocking the ROS activated mitochondria-mediated cell apoptosis pathway.
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A molecular simulation study of the protection of insulin bioactive structure by trehalose.
J Mol Model
PUBLISHED: 10-09-2014
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Biopharmaceuticals are proteins with a crucial role in the treatment of many diseases. However, these protein medicines are often thermally labile and therefore unsuitable for long-term application and storage, as they tend to lose their activity under ambient conditions. Desiccation is one approach to improving protein stability, but the drying process itself can cause irreversible damage. In the current study, insulin was chosen as an example of a thermally sensitive biopharmaceutical to investigate whether the disaccharide, trehalose, can prevent loss of structural integrity due to drying. The experiment was performed using replica exchange molecular simulation and Gromacs software with a Gromos96 (53a6) force field. The results indicate that trehalose preserves the bioactive structure of insulin during drying, consistent with the use of trehalose as a protectant for thermally sensitive biopharmaceuticals. For instance, at the water content of 1.77 %, insulin without any protectants yields the highest RMSD value as 0.451 nm, then the RMSD of insulin in presence of trehalose only ca. 0.100 nm.
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Computational identification of a new SelD-like family that may participate in sulfur metabolism in hyperthermophilic sulfur-reducing archaea.
BMC Genomics
PUBLISHED: 10-07-2014
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Selenium (Se) and sulfur (S) are closely related elements that exhibit similar chemical properties. Some genes related to S metabolism are also involved in Se utilization in many organisms. However, the evolutionary relationship between the two utilization traits is unclear.
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Ultrasound-induced controllable morphology and growth dimension in a dihydrazide-based self-assembly system.
Soft Matter
PUBLISHED: 10-07-2014
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We have demonstrated ultrasound-induced organogels based on twin-tapered dihydrazide derivatives, oxalyl acid N,N-di(3,4,5-trialkoxybenzoyl)hydrazide (FH-Tn). Ultrasound irradiation has been proved to influence gel properties at micro-levels. Different self-assembled structures from entangled fibers to tube-like structures and nanoparticles can be easily manipulated by tuning irradiation time and water bath temperature. FT-IR spectra exhibit weakened hydrogen bonding interactions, and XRD studies showed different packing modes before and after sonication. In addition, ultrasound can have effects on gel properties at macro-levels. Gels obtained from ultrasound treatment possess different wetting properties, relatively worse rheological properties and thermo-stability. Kinetic studies based on dynamic fluorescence spectra, rheological studies and theoretical calculations suggest that molecular aggregation mode differed from one-dimension to two-dimension for the gel after sonication.
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IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after anti-tuberculosis treatment.
Clin. Vaccine Immunol.
PUBLISHED: 10-03-2014
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The diagnosis of active tuberculosis (TB) disease remains a challenge especially in high-burden settings. Cytokines and chemokines are important in the pathogenesis of TB. Here, we investigate the usefulness of circulating and compartmentalized cytokines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF) and cerebrospinal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 and MIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG to distinguish TB from LTBI. However, IP-10 and MIG in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 and MIG in the PF and CSF showed promising diagnostic values in discriminating TB and non-TB pleural effusion (AUC=0.87 for IP-10, AUC=0.93 for MIG), as well as TB meningitis and non-TB meningitis (AUC=0.9 for IP-10, AUC=0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, G-CSF and IFN-Y decreased, while the levels of MCP-1/CCL2 and Eotaxin-1/CCL11 increased, after successful treatment of TB. Our findings provided a practical methodology for discriminating active TB from LTBI by sequential IGRAs and plasma IP-10 test, while increased IP-10 and MIG at the site of infection (PF or CSF) can be used a marker for distinguishing pleural effusion and meningitis caused by TB from those by non-TB.
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Renin inhibition improves ovariectomy-induced osteoporosis of lumbar vertebra in mice.
Biol. Pharm. Bull.
PUBLISHED: 10-03-2014
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The skeletal renin-angiotensin system (RAS) is involved in the progression of osteoporosis and the active peptide within the RAS, angiotensin II (ANG II), has deleterious effects on bones. This study was performed to investigate whether suppression of the rate-limiting step of the RAS cascade by the renin inhibitor aliskiren has a benefit on trabecular bone in osteoporotic mice. A postmenopausal osteoporosis model was induced by bilateral ovariectomy. The ovariectomized (OVX) mice were treated with a low (5 mg/kg) or high (25 mg/kg) dose of aliskiren for 6 weeks. Micro-computed tomography was performed to detect trabecular bone parameters of lumbar vertebra and to obtain 3-dimensional (3D) images. Treatment with aliskiren markedly increased bone volume over total volume (P < 0.05), trabecular bone number (P < 0.05), connectivity density (P < 0.05), and bone mineral density (P < 0.05) and reduced trabecular bone separation (P < 0.05) compared to vehicle-treated OVX mice. Similarly, the 3D images were consistent with the quantitative data that showed aliskiren could markedly reverse the ovariectomy-induced pathological changes of trabecular bone. Thus, this study indicated that the treatment of estrogen-deficient mice with aliskiren could markedly increase bone mass and improve trabecular bone structure, suggesting its potential application in treating postmenopausal osteoporosis.
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Stent for Life Initiative: leading example in building STEMI systems of care in emerging countries.
EuroIntervention
PUBLISHED: 09-27-2014
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This paper describes the opportunities and challenges in building ST-elevation acute myocardial infarction (STEMI) systems of care in Stent for Life affiliated and collaborating so-called emerging countries, namely India, China, South Africa and Mexico, where CAD mortality is increasing and becoming a significant healthcare problem. The Stent for Life model supports the implementation of ESC STEMI Guidelines in Europe and endeavours to impact on morbidity and mortality by improving services and developing regional STEMI systems of care, whereby STEMI patients' timely access to a primary percutaneous coronary intervention (PPCI) is assured. In India, the STEMI India model incorporates a dual approach of combining PPCI with a pharmacoinvasive strategy of reperfusion. The architecture of the system is based on a hub and spoke model with each unit called a STEMI cluster. The project is driven by a private non-profit organisation. In China, the STEMI PCI programme is led by the Chinese College of Cardiovascular Physicians and supported by the national government. Although primary PCI is performed nationwide, a thrombolytic treatment strategy is still the first option in many rural areas because of logistic considerations. Establishing local STEMI transfer networks and then implementing a pharmacoinvasive strategy of reperfusion are being considered and promoted currently. In South Africa, the pharmacoinvasive approach currently dominates as STEMI treatment option in many areas. A pilot study shows that low symptom awareness leads to long patient delays. The education of all role players, from patients to healthcare professionals and including institutions and governmental structures, is needed to achieve prompt diagnosis and treatment. In Mexico, improving the treatment of STEMI requires considering myocardial infarction to be an emergency that must be treated by an entire system and not just by a particular service. Patients need to receive quick treatment from clinical and interventional cardiologists, and the emergency medical system (EMS) must understand the importance of early reperfusion therapy when appropriate. Mexican health authorities have used registries as their main strategy for improving the use of health resources for ACS patients. In general, building regional STEMI systems of care and an EMS system infrastructure are critical success factors in the stepwise development of STEMI systems of care at a national level in emerging countries as they are in Europe. An in-depth understanding of healthcare system-level barriers to timely and appropriate reperfusion therapy facilitates the development of more effective strategies for improving the quality of STEMI care in each region and country.
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[Simultaneous determination of five triterpenoid saponins in different parts of Aralia elata by high performance liquid chromatography-tandem mass spectrometry].
Se Pu
PUBLISHED: 09-27-2014
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A method was developed for the simultaneous determination of congmunoside II, congmunoside IV, congmunoside V, congmunoside X and congmuyenoside II in different parts of Aralia elata by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The chromatographic separation was performed on an Alltima C18 analytical column (250 mm x 4.6 mm, 5 microm) using the mobile phases of acetonitrile and 0.1% (v/v) formic acid aqueous solution with gradient elution. The separated compounds were detected in multiple reaction monitoring (MRM)) mode via positive electrospray ionization (ESI+). The linear ranges of congmunoside II, congmunoside IV, congmunoside V, congmunoside X and congmuyenoside II were 0.17-108 microg/L, 0.53-329 microg/L, 0.77-480 microg/L, 0.77-480 microg/L and 0.82-510 microg/L, respectively. The extraction recoveries varied from 99.0% to 100.2%. The developed method is rapid, accurate and reproducible, and is successfully utilized as a quality control method for Aralia elata. The results indicate that the order of contents of these five saponins in different parts of Aralia elata is root bark > leaves > seeds > buds.
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ElectroTaxis-on-a-Chip (ETC): an integrated quantitative high-throughput screening platform for electrical field-directed cell migration.
Lab Chip
PUBLISHED: 09-23-2014
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Both endogenous and externally applied electrical stimulation can affect a wide range of cellular functions, including growth, migration, differentiation and division. Among those effects, the electrical field (EF)-directed cell migration, also known as electrotaxis, has received broad attention because it holds great potential in facilitating clinical wound healing. Electrotaxis experiment is conventionally conducted in centimetre-sized flow chambers built in Petri dishes. Despite the recent efforts to adapt microfluidics for electrotaxis studies, the current electrotaxis experimental setup is still cumbersome due to the needs of an external power supply and EF controlling/monitoring systems. There is also a lack of parallel experimental systems for high-throughput electrotaxis studies. In this paper, we present a first independently operable microfluidic platform for high-throughput electrotaxis studies, integrating all functional components for cell migration under EF stimulation (except microscopy) on a compact footprint (the same as a credit card), referred to as ElectroTaxis-on-a-Chip (ETC). Inspired by the R-2R resistor ladder topology in digital signal processing, we develop a systematic approach to design an infinitely expandable microfluidic generator of EF gradients for high-throughput and quantitative studies of EF-directed cell migration. Furthermore, a vacuum-assisted assembly method is utilized to allow direct and reversible attachment of our device to existing cell culture media on biological surfaces, which separates the cell culture and device preparation/fabrication steps. We have demonstrated that our ETC platform is capable of screening human cornea epithelial cell migration under the stimulation of an EF gradient spanning over three orders of magnitude. The screening results lead to the identification of the EF-sensitive range of that cell type, which can provide valuable guidance to the clinical application of EF-facilitated wound healing.
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[Research advances of platelet derived growth factor family and its significance in neovascular eye diseases].
Zhonghua Yan Ke Za Zhi
PUBLISHED: 09-23-2014
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Platelet derived growth factor (PDGF) is a family of peliotropic growth factors that regulate cell proliferation and differentiation in an autocrine or paracrine manner through receptor mediated signal transduction pathways. Recent studies have demonstrated that PDGF plays an important role in ocular neovascularization, and the application of PDGF has a broad prospect in treatment of ocular neovascularization. Here, we summarize the current understanding of structure, function and expression of PDGF in the eye; the effects of PDGF on the blood vessel forming cells, as well as the interaction between PDGF and other pro-angiogenic factors. In addition, the role of PDGF in neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, corneal neovascularization, and neovascular glaucoma, is also discussed.
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Cloning and characterization of a novel esterase from Rhodococcus sp. for highly enantioselective synthesis of a chiral cilastatin precursor.
Appl. Environ. Microbiol.
PUBLISHED: 09-21-2014
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A novel non-heme chloroperoxidase (RhEst1), with promiscuous esterase activity for enantioselective hydrolysis of ethyl (S)-2,2-dimethylcylopropanecarboxylate, was identified from the shot-gun library of Rhodococcus sp. ECU1013. RhEst1 was overexpressed in Escherichia coli BL21 (DE3), purified to homogeneity and functionally characterized. Fingerprinting analysis revealed that RhEst1 prefers to para-nitrophenyl (pNP) esters of short-chain acyl groups. pNP esters with a cyclic acyl moiety, especially that with a cyclobutanyl group, were also substrates for RhEst1. The Km values for methyl 2,2-dimethylcyclopropanecarboxylate (DmCpCm) and ethyl 2,2-dimethylcyclopropane carboxylate (DmCpCe) were 0.25 and 0.43 mM, respectively. RhEst1 could serve as an efficient hydrolase for the bioproduction of optically pure (S)-2,2-dimethyl cyclopropane carboxylic acid (DmCpCa) which is an important chiral building block for cilastatin. As much as 0.5 M of DmCpCe was enantioselectively hydrolyzed into (S)-DmCpCa with a molar yield of 47.8% and an enantiomeric excess (ee) of 97.5%, indicating an extremely high enantioselectivity (E = 240) of this novel and unique biocatalyst for green manufacturing of highly valuable chiral chemicals.
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N-Methylation of amine and nitro compounds with CO2/H2 catalyzed by Pd/CuZrOx under mild reaction conditions.
Chem. Commun. (Camb.)
PUBLISHED: 09-20-2014
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An active Pd/ZrCuOx catalyst was prepared for the reductive amination of CO2. The N-methylation of amines and nitro compounds with CO2/H2 can be realized with up to 97% yield under relatively mild reaction conditions. N-Formylation becomes the main reaction if the reaction was performed under milder conditions or using Pd/ZnZrOx as the catalyst.
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The effects of restricting the flexion-extension motion of the first metatarsophalangeal joint on human walking gait.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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The first metatarsophalangeal (MTP) joint is a critical component for normal walking. The present study aimed to investigate the effects of restricting the flexion-extension motion of the first MTP joint on human walking gait. Ten male participants were recruited to perform walking trials under barefoot (BF) and the first MTP joint constraint (FMJC) conditions, respectively. The results showed that there were statistically significant differences in walking speed and stride length. The characteristics of angular displacement in three lower limb joints and ground reaction force (GRF) were almost identical in BF and FMJC. However, maxima, minima and range of motion of three joint angles were significantly different. The utilized coefficient of friction (UCOF) increased significantly after FMJC, indicating that there may be a greater risk of slippage and falling when FMJC.
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Selective filtering defect at the axon initial segment in Alzheimer's disease mouse models.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-17-2014
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Axon pathology has been widely reported in Alzheimer's disease (AD) patients and AD mouse models. Herein we report that increased miR-342-5p down-regulates the expression of ankyrin G (AnkG), a protein known to play a critical role in establishing selective filtering machinery at the axon initial segment (AIS). Diminished AnkG expression leads to defective AIS filtering in cultured hippocampal neurons from AD mouse models, as monitored by selective exclusion of large macromolecules from the axons. Furthermore, AnkG-deficiency impairs AIS localization of Nav 1.6 channels and confines NR2B to the somatodendritic compartments. The expression of exogenous AnkG improved the cognitive performance of 12-mo-old APP/PS1 mice; thus, our data suggest that AnkG and impairment of AIS filtering may play important roles in AD pathology.
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Factors influencing risky decision-making in patients with cerebral infarction.
Psychol Health Med
PUBLISHED: 09-16-2014
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Numerous studies have found that the framing effect is common in medical scenarios, but few studies have examined the influence of the framing effect upon thrombolytic therapy for cerebral infarction. In this study, 1040 inpatients and outpatients in the department of neurology were recruited to explore whether there is a framing effect in decision-making within thrombolytic therapy, and if so, which factors influence that effect. The findings from Study 1 indicate that the framing effect occurred in patients both with and without cerebral infarction (?(2) = 7.90, p = .005; ?(2) = 5.16, p = .023, respectively), with both groups displaying risk-seeking behavior (thrombolytic therapy) in the positive frame and no risk aversion or risk seeking in the negative frame. The results of Study 2 show that the patients preferred risk seeking in both collaborative and individual decision-making. In the collaborative decision-making group, the patients in the senior group showed the framing effect (?(2) = 5.35, p < .05), with the patients in the positive frame (G) showing more significant risk seeking than both those in the negative frame (H) and those in the other positive frame (A, C, and E). In summary, decision-making about thrombolytic therapy in patients with cerebral infarction is influenced by the framing effect, and some influencing factors should be attended in clinical practice. Further research is necessary to guide the treatment of cerebral infarction.
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Preparation of Multifunctional Nanoprobes for Tumor-Targeted Fluorescent Imaging and Therapy.
Curr Drug Targets
PUBLISHED: 09-15-2014
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Nanoparticles are emerging as versatile nanoplatforms for the construction of multifunctional nanoprobes, which not only can deliver drugs into desired tumor regions but also are able to monitor the delivery, release and biodistribution of drugs in real time. In order to assist drug delivery, fluorescent imaging that can make the transportation viewable is often used. Then, various fluorescent nanoprobes that are composed of fluorescent or non-fluorescent nanocarrier, small-molecular fluorophore, drug, targeting ligand are developed and applied in biomedical applications. In this review paper, we will summarize chemical strategies for the construction of multifunctional nanoprobes and for controlled release of drugs. Then, recent examples on fluorescent nanoprobes, which are based on quantum dots, carbon nanodots, upconversion nanoparticles and other nanomaterials, and their applications in optical-guided drug delivery will be reviewed.
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Application of immunosuppressant facilitates the therapy of optic neuritis combined with Sjögren's syndrome.
Chin. Med. J.
PUBLISHED: 09-06-2014
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Optic neuritis (ON) is often the first symptom of multiple sclerosis (MS) and neuromyelitis optica (NMO) while there has been very little research reported on ON combined with Sjögren's syndrome (SS). The aim of this study is to provide different treatments and services for and NMO patients combined with SS.
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A critical role for interferon regulatory factor 9 in cerebral ischemic stroke.
J. Neurosci.
PUBLISHED: 09-05-2014
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The failure of past efforts to develop effective stroke treatments is at least partially because these treatments often interfered with essential physiological functions, even though they are targeted toward pathophysiological events, such as inflammation, excitotoxicity, and oxidative stress. Thus, the direct targeting of endogenous neuroprotective or destructive elements holds promise as a potential new approach to treating this devastating condition. Interferon regulatory factor 9 (IRF9), a transcription factor that regulates innate immune responses, has been implicated in neurological pathology. Here, we provide new evidence that IRF9 directly mediates neuronal death in male mice. In response to ischemia/reperfusion (I/R), IRF9 accumulated in neurons. IRF9 deficiency markedly mitigated both poststroke neuronal death and neurological deficits, whereas the neuron-specific overexpression of IRF9 sensitized neurons to death. The histone deacetylase Sirt1 was identified as a novel negative transcriptional target of IRF9 both in vivo and in vitro. IRF9 inhibits Sirt1 deacetylase activity, culminating in the acetylation and activation of p53-mediated cell death signaling. Importantly, both the genetic and pharmacological manipulation of Sirt1 effectively counteracted the pathophysiological effects of IRF9 on stroke outcome. These findings indicate that, rather than activating a delayed innate immune response, IRF9 directly activates neuronal death signaling pathways through the downregulation of Sirt1 deacetylase in response to acute I/R stress.
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"Smart" theranostic lanthanide nanoprobes with simultaneous up-conversion fluorescence and tunable T1-T2 magnetic resonance imaging contrast and near-infrared activated photodynamic therapy.
Nanoscale
PUBLISHED: 09-05-2014
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The current work reports a type of "smart" lanthanide-based theranostic nanoprobe, NaDyF4:Yb(3+)/NaGdF4:Yb(3+),Er(3+), which is able to circumvent the up-converting poisoning effect of Dy(3+) ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent.
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Production of carbon occluded in phytolith is season-dependent in a bamboo forest in subtropical China.
PLoS ONE
PUBLISHED: 09-04-2014
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Carbon (C) occluded in phytolith (PhytOC) is a stable form of C; when PhytOC is returned to the soil through litterfall it is stored in the soil which can be an effective way for long-term C sequestration. However, few estimates on the rate of PhytOC input to the soil are available. To better understand the seasonal dynamics of PhytOC production and the annual rate of stable C sequestration through PhytOC input, we quantified the monthly litterfall, phytolith and PhytOC return to the soil over a year in a typical Lei bamboo (Phyllostachys praecox) forest in subtropical China. The monthly litterfall ranged between 14.81 and 131.18 g m(-2), and the phytolith concentration in the monthly litterfall samples ranged between 47.21 and 101.68 g kg(-1) of litter mass, with the PhytOC concentration in the phytolith ranged between 29.4 and 44.9 g kg(-1) of phytolith, equivalent to 1.8-3.6 g kg(-1) of PhytOC in the litterfall (based on litterfall dry mass). The amount of phytolith input to the soil system was 292.21 ± 69.12 (mean ± SD) kg ha(-1) yr(-1), sequestering 41.45 ± 9.32 kg CO2-e ha(-1) yr(-1) of C in the studied Lei bamboo forest. This rate of C sequestration through the formation of PhytOC found in this study falls within the range of rates for other grass-type species reported in the literature. We conclude that return of C occluded in phytolith to the soil can be a substantial source of stable soil C and finding means to increase PhytOC storage in the soil should be able to play a significant role in mitigating the rapidly increasing atmospheric CO2 concentration.
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The Relationship between the Plasma PCSK9 Levels and Platelet Indices in Patients with Stable Coronary Artery Disease.
J. Atheroscler. Thromb.
PUBLISHED: 09-02-2014
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Aim: Recent studies have shown that platelet indices are linked to metabolic and cardiovascular diseases, in addition to being markers of hemostasis. These studies suggested that they could be modified by various biomolecules, including lipids. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a newly-identified member, plays a key role in lipid metabolism and atherosclerosis. Therefore, we evaluated the relationship between the plasma PCSK9 level and platelet indices. Methods: In this cross-sectional study, a total of 330 consecutive, stable coronary artery disease (CAD) patients were enrolled at our center between October 2012 and April 2014. The baseline clinical characteristics were collected, and the plasma PCSK9 levels were determined using an ELISA. The associations between PCSK9 and the platelet indices were investigated. Results: The plasma PCSK9 levels were positively correlated with the platelet (PLT) count and plateletcrit (PCT) (r=0.218, p?0.001; r=0.250, p?0.001; respectively), while no correlation of PCSK9 with either the mean platelet volume (MPV) or platelet distribution width (PDW) was found. The association of PCSK9 with the PLT and PCT remained after adjusting for cardiometabolic risk factors (?=0.300, p?0.001; ?=0.269, p?0.01; respectively), but the latter disappeared when further adjusted for inflammatory markers (?=0.212, p?0.05; ?=0.151, p=NS). Additionally, a correlation analysis performed according to the number of diseased vessels showed that PCSK9 was related to the PLT and PCT in patients with single-, two- or multi-vessel disease, with a particularly strong correlation with two-vessel disease. Conclusions: The plasma PCSK9 levels are positively associated with the PLT count in CAD patients, suggesting a potential link between PCSK9 and platelets that may be involved in atherosclerosis and metabolic disorders.
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BMP9 regulates cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells.
Cell Oncol (Dordr)
PUBLISHED: 09-01-2014
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Breast cancer cells frequently metastasize to distant organs, including bone. Interactions between breast cancer cells and the bone microenvironment are known to enhance tumor growth and osteolytic damage. Here we investigated whether BMP9 (a secretary protein) may change the bone microenvironment and, by doing so, regulate the cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells.
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MiR-124 represses vasculogenic mimicry and cell motility by targeting amotL1 in cervical cancer cells.
Cancer Lett.
PUBLISHED: 08-31-2014
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miRNAs have extensive functions in differentiation, metabolism, programmed cell death, and tumor metastasis by post-transcriptional regulation. Vasculogenic mimicry is an important pathway in tumor metastasis. Many factors can regulate vasculogenic mimicry, including miRNAs. In previous studies, miR-124 was found to repress proliferation and metastasis in different types of cancers, but whether it functions in cervical cancer remained unknown. Here, we demonstrate that miR-124 can repress vasculogenic mimicry, migration and invasion in HeLa and C33A cells in vitro. Furthermore, we reveal that the effect of miR-124 on vasculogenic mimicry, migration and invasion results from its interaction with AmotL1. MiR-124 regulates AmotL1 negatively by targeting its 3'untranslated region (3'UTR). We found that miR-124 can repress the EMT process. Together, these results improve our understanding of the function of miR-124 in tumor metastasis and will help to provide new potential target sites for cervical cancer treatment.
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Genome sequence and genetic diversity of the common carp, Cyprinus carpio.
Nat. Genet.
PUBLISHED: 08-29-2014
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The common carp, Cyprinus carpio, is one of the most important cyprinid species and globally accounts for 10% of freshwater aquaculture production. Here we present a draft genome of domesticated C. carpio (strain Songpu), whose current assembly contains 52,610 protein-coding genes and approximately 92.3% coverage of its paleotetraploidized genome (2n = 100). The latest round of whole-genome duplication has been estimated to have occurred approximately 8.2 million years ago. Genome resequencing of 33 representative individuals from worldwide populations demonstrates a single origin for C. carpio in 2 subspecies (C. carpio Haematopterus and C. carpio carpio). Integrative genomic and transcriptomic analyses were used to identify loci potentially associated with traits including scaling patterns and skin color. In combination with the high-resolution genetic map, the draft genome paves the way for better molecular studies and improved genome-assisted breeding of C. carpio and other closely related species.
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Rhodium(III)-Catalyzed Transannulation of Cyclopropenes with N-Phenoxyacetamides through C?H Activation.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-26-2014
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An efficient rhodium(III)-catalyzed synthesis of 2H-chromene from N-phenoxyacetamides and cyclopropenes has been developed. The reaction represents the first example of using cyclopropenes as a three-carbon unit in rhodium(III)-catalyzed C(sp(2) )?H activations.
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Myocardial T2 mapping by cardiovascular magnetic resonance reveals subclinical myocardial inflammation in patients with systemic lupus erythematosus.
Int J Cardiovasc Imaging
PUBLISHED: 08-18-2014
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To evaluate whether T2 mapping techniques can detect myocardial edema in patients with systemic lupus erythematosus (SLE). Twenty-four patients (mean age 54 ± 9 years) with SLE and twelve controls (mean age 50 ± 7 years) underwent cardiac MRI at 1.5 T. Standard cine images were obtained. Single-slice T2 maps and non-contrast T1 maps were acquired in a mid-cavity short-axis plane. Late gadolinium enhancement (LGE) images were obtained 15 min after 0.2 mmol/kg of contrast. SLE patients had low disease activity (mean SLE disease activity index score 0.71 ± 0.8). There were no differences in LV size or function between SLE patients and controls. No subjects had LGE. T2 times were higher in SLE patients (58.2 ± 5.6 vs. 52.8 ± 4.4 ms, p = 0.009). On multivariate analysis including demographic and LV parameters, only the diagnosis of SLE was associated with T2 time (p = 0.01). T1 times trended lower in SLE patients, (981.6 ± 65.5 vs. 963.9 ± 32.5), however, differences were not significant (p = 0.3). Repeated measures were highly correlated by linear regression for both inter- and intraobserver analysis (both R = 0.95, p < 0.001). Inter- and intraobserver bias and limits of agreement were -0.4 ± 3.8 and 1.0 ± 3.3 ms, respectively. T2-mapping identifies increased myocardial T2 times in SLE patients, likely due to subclinical myocardial edema. These findings suggest that even in SLE patients with inactive disease and normal cardiac function, low grade myocardial inflammation can be detected by this novel quantitative and highly reproducible technique.
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Prognostic significance and therapeutic implications of peroxisome proliferator-activated receptor ? overexpression in human pancreatic carcinoma.
Int. J. Oncol.
PUBLISHED: 08-13-2014
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Peroxisome proliferator-activated receptor ? (PPAR?) is a ligand-activated nuclear receptor which has been implicated in carcinogenesis and angiogenesis in a wide range of cancers, including pancreatic carcinoma (PC). We aimed to characterize the prognosis and potential therapeutic implications of PPAR? in PC. Real-time RT-PCR and western blotting were used to quantify PPAR? expression in immortalized pancreatic epithelial cells, PC cell lines and freshly isolated matched tumor and non-tumor tissues. PPAR? protein expression was analyzed by immunohistochemistry (IHC) in archived tumor tissues from 101 PC patients. Furthermore, the effect of PPAR? on the cytotoxic action of gemcitabine (Gem) and 5-fluorouracil (5-FU) in PC cell lines was investigated in vitro using RNA interference techniques. Both PPAR? protein and mRNA were expressed at markedly higher levels in all of the PC cell lines and freshly isolated PC tissues, compared to normal immortalized pancreatic epithelial cells and the matched adjacent non-tumor tissues. High levels of PPAR? expression correlated significantly with tumor-node-metastasis (TNM) staging (P<0.001) and poor overall survival (P<0.001), especially in patients with advanced disease who received postoperative chemotherapy. While silencing of PPAR? significantly inhibit the cytotoxic effects of both gemcitabine and 5-fluorouracil in PC cells in vitro. This study suggests that high levels of PPAR? expression are associated with poor overall survival in PC. Additionally, PPAR? promotes chemoresistance in PC cells, indicating that PPAR? may represent a novel therapeutic target for PC.
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Improved poly(3-hydroxybutyrate) production in Escherichia coli by inactivation of cytochrome bd-II oxidase or/and NDH-II dehydrogenase in low efficient respiratory chains.
J. Biotechnol.
PUBLISHED: 08-13-2014
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In order to redirect more carbon flux from TCA cycle into poly(3-hydroxybutyrate) (PHB) biosynthesis pathway via increasing respiratory efficiency, appB and ndh genes encoding cytochrome bd-II oxidase and NDH-II dehydrogenase were inactivated in Escherichia coli JM109/pBHR68. All appB or/and ndh knockout strains exhibited significantly increased PHB accumulation accompanying with increased NAD(P)H/NAD(P)(+) ratio and intracellular acetyl-CoA pool. Among them, the ?ndh strain could accumulate up to 6.16g/L PHB from 20g/L glucose and 3.5g/L PHB from 20g/L xylose, respectively, a 1.76-fold and 3.43-fold increase compared to the wild-type control. The PHB production of this strain reached 28.23g/L in a 5-L fermentor study, which was 2.70-fold as much as that of the wild-type control. These results indicated that inactivating the cytochrome bd-II oxidase or/and NDH-II dehydrogenase of the aerobic respiratory chain is a simple and effective strategy to improve PHB biosynthesis in E. coli. To date, this is the first time to improve PHB production by inactivation of cytochrome bd-II oxidase or/and NDH-II dehydrogenase in low efficient respiratory chains.
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Cadmium-induced activation of high osmolarity glycerol pathway through its Sln1 branch is dependent on the MAP kinase kinase kinase Ssk2, but not its paralog Ssk22, in budding yeast.
FEMS Yeast Res.
PUBLISHED: 08-04-2014
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Cadmium ions disrupt reactive oxygen species/Ca(2+) homeostasis and subsequently elicit cell death and adaptive signaling cascades in eukaryotic cells. Through a functional genomics approach, we have identified deletion mutants of 106 yeast genes, including three MAP kinase genes (HOG1, SLT2, and KSS1), are sensitive to a sublethal concentration of cadmium, and 64 mutants show elevated intracellular cadmium concentrations upon exposure to cadmium. Hog1 is phosphorylated, reaching a peak 30 min after the cadmium treatment. Both Sln1 and Sho1 upstream branches are involved in the cadmium-induced activation of high osmolarity glycerol (HOG) pathway. Cadmium-induced HOG activation is dependent on the MAP kinase kinase kinase Ssk2, but not its paralog Ssk22, in the Sln1 branch.
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Recent Advances in Treatment of Retinitis Pigmentosa.
Curr Stem Cell Res Ther
PUBLISHED: 08-03-2014
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Retinitis pigmentosa (RP)is a group of inherited retinal disorders characterized by the progressive photoreceptors and pigment epithelial cells dysfunction. It is the most common retinal degeneration, responsible for loss of vision of most people worldwide. Until now it is not clear about its exact pathogenesis and etiology. So far there is no approved therapy. New approaches for RP therapy including cell transplantation, gene therapy, cytokine therapy, nutrition therapy , hyperbaric oxygen therapy. Present therapies for retinal degenerative diseases are limited in their efficacy. This paper looks back on the relevant documents, especially recent researches, and reviews advances in the treatment of RP.
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Exploring genomes with a game engine.
Faraday Discuss.
PUBLISHED: 07-31-2014
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More and more evidence indicates that the 3D conformation of eukaryotic genomes is a critical part of genome function. However, due to the lack of accurate and reliable 3D genome structural data, this information is largely ignored and most of these studies have to use information systems that view the DNA in a linear structure. Visualizing genomes in real time 3D can give researchers more insight, but this is fraught with hardware limitations since each element contains vast amounts of information that cannot be processed on the fly. Using a game engine and sophisticated video game visualization techniques enables us to construct a multi-platform real-time 3D genome viewer. The game engine-based viewer achieves much better rendering speed and can handle much larger amounts of data compared to our previous implementation using OpenGL. Combining this viewer with 3D genome models from experimental data could provide unprecedented opportunities to gain insight into the conformation-function relationships of a genome.
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Crystal structure of human Ankyrin G death domain.
Proteins
PUBLISHED: 07-31-2014
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Ankyrins (Ank) are a ubiquitously expressed family of multifunctional membrane adapter proteins. Ankyrin G (AnkG) is critical for assembling and maintenance of the axon initial segment. Here we present the 2.1 Å crystal structure of human AnkG death domain (hAnkG-DD). The core death domain is composed of six ?-helices and three 310 -helices. It forms a hydrophobic pocket on the surface of the molecule. The C-terminal tail of the hAnkG-DD curves back to have the aromatic ring of a phenylalanine residue, Phe100 insert into this pocket, which anchors the flexible tail onto the core domain. Related DDs were selected for structure comparison. The major variations are at the C-terminal region, including the ?6 and the long C-terminal extension. The results of size exclusion chromatography and analytical ultracentrifugation suggest that hAnkG-DD exists as monomer in solution. Our work should help for the future investigation of the structure-function of AnkG. Proteins 2014; 82:3476-3482. © 2014 Wiley Periodicals, Inc.
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Synthesis of Aryldiazoacetates through Palladium(0)-Catalyzed Deacylative Cross-Coupling of Aryl Iodides with Acyldiazoacetates.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-27-2014
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Palladium(0)-catalyzed deacylative cross-coupling of aryl iodides and acyldiazocarbonyl compounds can be achieved at room temperature under mild reaction conditions. The coupling reaction represents a highly efficient and general method for the synthesis of aryldiazocarbonyl compounds, which have found wide and increasing applications as precursors for generating donor/acceptor-substituted metallocarbenes.
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Pharmacokinetics and biodistribution of zinc-enriched yeast in rats.
ScientificWorldJournal
PUBLISHED: 07-21-2014
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Zinc-enriched yeast (ZnY) and zinc sulfate (ZnSO4) are considered zinc (Zn) supplements currently available. The purpose of the investigation was to compare and evaluate pharmacokinetics and biodistribution of ZnY and ZnSO4 in rats. ZnY or ZnSO4 were orally administered to rats at a single dose of 4 mg Zn/kg and Zn levels in plasma and various tissues were determined using inductively coupled plasma-optical emission spectrometry. Maximum plasma concentration values were 3.87 and 2.81 ?g/mL for ZnY and ZnSO4, respectively. Both ZnY and ZnSO4 were slowly eliminated with a half-life of over 7 h and bone had the highest Zn level in all tissues. Compared to ZnSO4, the relative bioavailability of ZnY was 138.4%, indicating that ZnY had a significantly higher bioavailability than ZnSO4.
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Association of single nucleotide polymorphisms in the USF1, GTF2A1L and OR2W3 genes with non-obstructive azoospermia in the Chinese population.
J. Assist. Reprod. Genet.
PUBLISHED: 07-17-2014
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To research the association between the single nucleotide polymorphisms (SNPs) of three spermatogenesis-related genes (USF1, GTF2A1L and OR2W3) and non-obstruction azoospermia (NOA).
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Solid Tryptophan as a Pseudoracemate: Physicochemical and Crystallographic Characterization.
Chirality
PUBLISHED: 07-17-2014
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The crystalline nature of solid tryptophan has been characterized by X-ray single crystal and powder diffraction analyses, differential scanning calorimetry, as well as measurement of solid-liquid equilibrium in water/isopropanol solution. Both the thermodynamic and crystallographic investigations have demonstrated unambiguously that solid tryptophan crystallizes in the form of a pseudoracemate (i.e., solid solution) with maximum melting over the entire enantiomeric composition range. Comparative single-crystal X-ray studies show that the crystal structures of racemic and enantiomeric tryptophan give very similar solid-state packing geometries dictated by hydrogen bonding interactions. Our results indicate that the insignificant difference between homochiral and heterochiral interactions accounts for the formation of a pseudoracemate for this system. Chirality 00:000-000, 2014. © 2014 Wiley Periodicals, Inc.
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Effect of enhanced extracorporeal counterpulsation in patients with non-arteritic anterior ischaemic optic neuropathy.
Graefes Arch. Clin. Exp. Ophthalmol.
PUBLISHED: 07-09-2014
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The purpose is to study the effect of Enhanced Extracorporeal Counterpulsation (EECP) in patients with non-arteritic anterior ischaemic optic neuropathy (NAION).
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Two Novel Exopolysaccharides from Bacillus amyloliquefaciens C-1: Antioxidation and Effect on Oxidative Stress.
Curr. Microbiol.
PUBLISHED: 07-08-2014
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Two odorless, water-soluble exopolysaccharide (EPS) fractions, EPS-1 and EPS-2, were isolated from a newly isolated Bacillus amyloliquefaciens strain C-1 and purified by ion exchange and gel chromatography. The purified EPS-1 contained glucose/mannose/galactose/arabinose in a relative proportion of 15:4:2:1, and possessed a molecular weight of 79.6 kDa, while EPS-2 contained only glucose and mannose in a 3:1 ratio, with the molecular weights of 19.8 kDa. The antioxidant activity results showed that EPS-1 exhibited strong reducing power, superoxide radicals (O(2-)·), and hydroxyl free radicals (OH·) scavenging activities. For the H2O2-induced injury in HepG2 cells, EPS-1 significantly decreased the formation of reactive oxygen species, intracellular malondialdehyde levels, and restored intracellular superoxide dismutase activity. For EPS-2, there had no detectable antioxidant activities. And all these results collectively showed that as a natural antioxidant, only EPS-1 produced by C-1 had considerable potential to be used as medical compounds or functional additives.
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Palladium(0)-catalyzed cross-coupling of 1,1-diboronates with vinyl bromides and 1,1-dibromoalkenes.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-08-2014
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Palladium-catalyzed cross-coupling reactions of 1,1-diboronates with vinyl bromides and dibromoalkenes were found to afford 1,4-dienes and allenes, respectively. These reactions utilize the high reactivities of both 1,1-diboronates and allylboron intermediates generated in the initial coupling.
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miR?494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN.
Int. J. Oncol.
PUBLISHED: 07-04-2014
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Accumulating evidence has shown that micro-RNAs (miRNAs) are involved in multiple processes in cancer development and progression. Upregulation of miRNA?494 (miR?494) has been identified as an oncogenic miRNA and is associated with poor prognosis in several types of human cancer. However, the specific function of miR?494 in colorectal cancer remains unclear. In this study we found that the expression of miR?494 in colorectal cancer tissues and cell lines was much higher than in normal control tissues and cells, respectively. In addition, upregulation of miR?494 more frequently occurred in tissue specimens with adverse clinical stage and the presence of distant metastasis. Moreover, multivariate survival analyses demonstrated that overexpression of miR?494 is an independent prognostic factor for both progression?free and overall survival. In addition miR?494 promoted invasion and migration in colorectal cancer cells, and miR?494 directly inhibited the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression by targeting its 3'?untranslated region (3'?UTR). Moreover, PTEN is down regulated and inversely correlated with miR?494 expression in tissues. Thus, for the first time, we provided convincing evidence that upregulation of miR?494 was associated with tumor aggressiveness and tumor metastasis and promoted cell migration and invasion by targeting PTEN gene in colorectal cancer, and miR?494 is an independent prognostic marker for colorectal cancer patients.
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Comparative subproteome analysis of three representative Leptospira interrogans vaccine strains reveals cross-reactive antigens and novel virulence determinants.
J Proteomics
PUBLISHED: 07-02-2014
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Pathogenic Leptospira spp. causes leptospirosis in China and throughout the world. Here, we have sequenced two L. interrogans moderately virulent vaccine strains JDL03 (serovar Canicola) and JDL10 (serovar Hebdomadis) used in China. We selected a subproteomic approach to identify surface-exposed proteins including OMPs and extracellular proteins of these two strains plus a highly virulent vaccine strain 56601 (serovar Lai). Comparative surface-exposed proteome among the three strains indicated 81 cores, 61 dispensable and 122 unique surface-exposed proteins. Finally, the 10 highly conserved surface-exposed or subsurface proteins included two known cross-reactive antigens (LipL32 and LA_3469) and another two novel antigens (LA_0136 and LA_0505) displaying conserved immunoreactivity among 15 Chinese epidemic serovars. Furthermore, many potential virulence factors were detected in these identified surface-exposed proteins, such as Loa22, LipL32, LenC, LenF and OmpL37. Interestingly, LipL45, ClpA and ClpB, exhibiting obvious amino acid mutations among str.56601, str.JDL03 and JDL10, might contribute to virulence differences observed among these strains. Additionally, specific surface-exposed proteins in virulent str.56601 were considered to be key virulence determinants, such as Zn-dependent protease, cholesterol oxidase precursor, and so on. In all, we had relatively complete surface-exposed subproteomes of L. interrogans, which will enhance our understanding of leptospiral pathogenesis and key virulence determinants.
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Life Cycle Assessment of Bioethanol Production from Woodchips with Modifications in the Pretreatment Process.
Appl. Biochem. Biotechnol.
PUBLISHED: 06-17-2014
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Pretreatment as a crucial step in the process of ethanol production has significant influences on the process efficiency and on the environmental performance of the bioethanol production from lignocellulosic biomass. In present life cycle analysis (LCA) study, two cases for pretreatment of woodchips were considered as the focal point of the ethanol plant. One was assumed as base scenario whereas the second is the proposed alternative by implementation of modifications on the base design. In the first stage, LCA results of pretreatment unit showed lower environmental impacts in respiratory inorganics and land use than in new scenario, while the base scenario revealed better performance in fossil fuels. The results of the second stage of LCA study demonstrated improvement in proposed design in most categories of environmental impacts such as 18.5 % in land use as well as 17 % improvement in ecosystem quality.
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Cell culture isolation and sequence analysis of genetically diverse US porcine epidemic diarrhea virus strains including a novel strain with a large deletion in the spike gene.
Vet. Microbiol.
PUBLISHED: 06-17-2014
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The highly contagious and deadly porcine epidemic diarrhea virus (PEDV) first appeared in the US in April 2013. Since then the virus has spread rapidly nationwide and to Canada and Mexico causing high mortality among nursing piglets and significant economic losses. Currently there are no efficacious preventive measures or therapeutic tools to control PEDV in the US. The isolation of PEDV in cell culture is the first step toward the development of an attenuated vaccine, to study the biology of PEDV and to develop in vitro PEDV immunoassays, inactivation assays and screen for PEDV antivirals. In this study, nine of 88 US PEDV strains were isolated successfully on Vero cells with supplemental trypsin and subjected to genomic sequence analysis. They differed genetically mainly in the N-terminal S protein region as follows: (1) strains (n=7) similar to the highly virulent US PEDV strains; (2) one similar to the reportedly US S INDEL PEDV strain; and (3) one novel strain most closely related to highly virulent US PEDV strains, but with a large (197aa) deletion in the S protein. Representative strains of these three genetic groups were passaged serially and grew to titers of ?5-6log10 plaque forming units/mL. To our knowledge, this is the first report of the isolation in cell culture of an S INDEL PEDV strain and a PEDV strain with a large (197aa) deletion in the S protein. We also designed primer sets to detect these genetically diverse US PEDV strains.
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Benchmarking mutation effect prediction algorithms using functionally validated cancer-related missense mutations.
Genome Biol.
PUBLISHED: 06-13-2014
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BackgroundMassively parallel sequencing studies have led to the identification of a large number of mutations present in a minority of cancers of a given site. Hence, methods to identify the likely pathogenic mutations that are worth exploring experimentally and clinically are required. We sought to compare the performance of 15 mutation effect prediction algorithms and their agreement. As a hypothesis-generating aim, we sought to define whether combinations of prediction algorithms would improve the functional effect predictions of specific mutations.ResultsLiterature and database mining of single nucleotide variants (SNVs) affecting 15 cancer genes was performed to identify mutations supported by functional evidence or hereditary disease association to be classified either as non-neutral (n¿=¿849) or neutral (n¿=¿140) with respect to their impact on protein function. These SNVs were employed to test the performance of 15 mutation effect prediction algorithms. The accuracy of the prediction algorithms varies considerably. Although all algorithms perform consistently well in terms of positive predictive value, their negative predictive value varies substantially. Cancer-specific mutation effect predictors display no-to-almost perfect agreement in their predictions of these SNVs, whereas the non-cancer-specific predictors showed no-to-moderate agreement. Combinations of predictors modestly improve accuracy and significantly improve negative predictive values.ConclusionsThe information provided by mutation effect predictors is not equivalent. No algorithm is able to predict sufficiently accurately SNVs that should be taken forward for experimental or clinical testing. Combining algorithms aggregates orthogonal information and may result in improvements in the negative predictive value of mutation effect predictions.
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A PH Domain in ACAP1 Possesses Key Features of the BAR Domain in Promoting Membrane Curvature.
Dev. Cell
PUBLISHED: 06-10-2014
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The BAR (Bin-Amphiphysin-Rvs) domain undergoes dimerization to produce a curved protein structure, which superimposes onto membrane through electrostatic interactions to sense and impart membrane curvature. In some cases, a BAR domain also possesses an amphipathic helix that inserts into the membrane to induce curvature. ACAP1 (Arfgap with Coil coil, Ankyrin repeat, and PH domain protein 1) contains a BAR domain. Here, we show that this BAR domain can neither bind membrane nor impart curvature, but instead requires a neighboring PH (Pleckstrin Homology) domain to achieve these functions. Specific residues within the PH domain are responsible for both membrane binding and curvature generation. The BAR domain adjacent to the PH domain instead interacts with the BAR domains of neighboring ACAP1 proteins to enable clustering at the membrane. Thus, we have uncovered the molecular basis for an unexpected and unconventional collaboration between PH and BAR domains in membrane bending.
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Delay in Diagnosis and Treatment of Symptomatic Breast Cancer in China.
Ann. Surg. Oncol.
PUBLISHED: 06-07-2014
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Delay in diagnosis and treatment of cancer may lead to advanced tumor characteristics and poor prognosis. Research and investigation from economically developing countries such as China are warranted to support these conclusions, so we studied the impact on prognosis of delays and factors predicting delay in symptomatic breast cancer patients in China.
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Interferon regulatory factor 9 is critical for neointima formation following vascular injury.
Nat Commun
PUBLISHED: 06-02-2014
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Interferon regulatory factor 9 (IRF9) has various biological functions and regulates cell survival; however, its role in vascular biology has not been explored. Here we demonstrate a critical role for IRF9 in mediating neointima formation following vascular injury. Notably, in mice, IRF9 ablation inhibits the proliferation and migration of vascular smooth muscle cells (VSMCs) and attenuates intimal thickening in response to injury, whereas IRF9 gain-of-function promotes VSMC proliferation and migration, which aggravates arterial narrowing. Mechanistically, we show that the transcription of the neointima formation modulator SIRT1 is directly inhibited by IRF9. Importantly, genetic manipulation of SIRT1 in smooth muscle cells or pharmacological modulation of SIRT1 activity largely reverses the neointima-forming effect of IRF9. Together, our findings suggest that IRF9 is a vascular injury-response molecule that promotes VSMC proliferation and implicate a hitherto unrecognized 'IRF9-SIRT1 axis' in vasculoproliferative pathology modulation.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.