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1.  Bonding of Resin Cement to Zirconia with High Pressure Primer Coating 
PLoS ONE  2014;9(7):e101174.
Objectives
To investigate the effect of air-drying pressure during ceramic primer coating on zirconia/resin bonding and the surface characteristics of the primed zirconia.
Methods
Two ceramic primers (Clearfil Ceramic Primer, CCP, Kuraray Medical Inc. and Z-Prime Plus, ZPP, Bisco Inc.) were applied on the surface of air-abraded zirconia (Katana zirconia, Noritake) and dried at 4 different air pressures (0.1–0.4 MPa). The primed zirconia ceramic specimens were bonded with a resin-based luting agent (SA Luting Cement, Kuraray). Micro-shear bond strengths of the bonded specimens were tested after 3 days of water storage or 5,000× thermocycling (n = 12). Failure modes of the fractured specimens were examined with scanning electron miscopy. The effects of air pressure on the thickness of the primer layers and the surface roughness (Sa) of primed zirconia were evaluated using spectroscopic ellipsometry (n = 6), optical profilometry and environmental scanning electron microscopy (ESEM) (n = 6), respectively.
Results
Clearfil Ceramic Primer air-dried at 0.3 and 0.4 MPa, yielding significantly higher µSBS than gentle air-drying subgroups (p<0.05). Compared to vigorous drying conditions, Z-Prime Plus air-dried at 0.2 MPa exhibited significantly higher µSBS (p<0.05). Increasing air-drying pressure reduced the film thickness for both primers. Profilometry measurements and ESEM showed rougher surfaces in the high pressure subgroups of CCP and intermediate pressure subgroup of ZPP.
Conclusion
Air-drying pressure influences resin/zirconia bond strength and durability significantly. Higher air-drying pressure (0.3-0.4 MPa) for CCP and intermediate pressure (0.2 MPa) for ZPP are recommended to produce strong, durable bonds between resin cement and zirconia ceramics.
doi:10.1371/journal.pone.0101174
PMCID: PMC4081122  PMID: 24992678
2.  The safety and efficacy of daptomycin versus other antibiotics for skin and soft-tissue infections: a meta-analysis of randomised controlled trials 
BMJ Open  2014;4(6):e004744.
Objective
Daptomycin, a cyclic lipopeptide that exhibits rapid, concentration-dependent bactericidal activity in vitro against a broad spectrum of Gram-positive pathogens, has now, since 2003, been approved in more than 70 countries and regions to treat skin and soft-tissue infections (SSTIs). The purpose of this meta-analysis was to compare the safety and efficacy of daptomycin with other antibiotics, especially with vancomycin which has long been considered the standard therapy for complicated SSTIs.
Design
Meta-analysis of randomised controlled trials (RCTs).
Data sources
We thoroughly searched PubMed, EMBASE, Cochrane Central to identify relevant RCTs. Six RCTs with a total of 1710 patients were included in this meta-analysis.
Results
The results demonstrated that the efficacy of daptomycin was at par with or maybe better than other first-line antibiotics for treating SSTIs as shown by the OR for clinical success (OR=1.05, 95% CI 0.84 to 1.31, p=0.65, I2=0%); daptomycin versus vancomycin subgroup (OR=1.19, 95% CI 0.77 to 1.83, p=0.43, I2=0%); overall microbiological success (OR=1.05, 95% CI 0.61 to 1.79, p=0.86, I2=42%); microbiological success of daptomycin versus comparators for Staphylococcus aureus (SA, OR=1.05, 95% CI 0.61 to 2.60, p=0.53, I2=47%), for methicillin-resistant S. aureus (OR=0.90, 95% CI 0.77 to 1.06, p=0.20, I2=56%). However, daptomycin tended to have a similar treatment-related adverse events (AEs) incidence in comparison with other antibiotics (OR=1.06, 95% CI 0.71 to 1.59, p=0.76, I2=41%). The trend showed that daptomycin might cause less discontinuation due to AEs and death compared with other first-line antibiotics (OR=0.71, 95% CI 0.46 to 1.10, p=0.12, I2=11%). Significantly more patients in the daptomyicn group had creatine phosphokinase elevation than those in the control group; however, it could be reversed when the therapy ended (OR=1.95, 95% CI 1.04 to 3.65, p=0.04, I2=0).
Conclusions
This meta-analysis demonstrated that the safety and efficacy of daptomycin was not inferior to that of other first-line drugs, and daptomycin tended to exhibit superior efficacy when compared with vancomycin or with comparators for SA infections; nevertheless, more high-quality RCTs are needed to draw a more credible conclusion.
doi:10.1136/bmjopen-2013-004744
PMCID: PMC4078778  PMID: 24961714
Epidemiology
3.  Clinical analysis of kasabach-merritt syndrome in 17 neonates 
BMC Pediatrics  2014;14:146.
Background
Kasabach-Merritt syndrome (KMS) is characterized by giant hemangiomas and severe thrombocytopenia, which may result in life-threatening multi-organ hemorrhage. This study evaluated the clinical characteristics, treatments, and outcomes in neonates with KMS, in order to find out the optimal therapy.
Methods
The clinical data of 17 patients treated for KMS in the Department of Neonates, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, China from January 2007 to January 2012 were retrospectively analyzed.
Results
The patients were 13 males and 4 females, aged 17 hours to 28 days at admission. Four patients had visceral hemangiomas and 13 had cutaneous hemangiomas. All had thrombocytopenia and coagulation disorders. Intravenous steroid therapy was initially effective in 6 patients (of which 3 relapsed) and ineffective in 11. The 11 patients with a poor response to steroids and the 3 who relapsed underwent arterial embolization therapy, which was effective in 9 patients (of which 1 relapsed), ineffective in 4, and discontinued before completion in 1. Subsequently, four patients in whom arterial embolization therapy was ineffective and one with relapse were treated with vincristine. This was effective in four patients, and the other died of disseminated intravascular coagulation. Steroid therapy was effective in 35.3% of patients, but the relapse rate was 50%. Arterial embolization was effective in 64.3% of patients and vincristine was effective in 80%.
Conclusions
In patients with neonatal KMS, steroid therapy has a low rate of effectiveness and high rate of relapse. Arterial embolization has a good rate of effectiveness. Combined steroid and embolization therapy should be considered for first-line treatment of neonatal KMS. If this approach is ineffective, vincristine may be useful.
doi:10.1186/1471-2431-14-146
PMCID: PMC4088914  PMID: 24920221
Arterial embolization; Steroid therapy; Kasabach-Merritt syndrome; Neonate; Vincristine
4.  B and N isolate-doped graphitic carbon nanosheets from nitrogen-containing ion-exchanged resins for enhanced oxygen reduction 
Scientific Reports  2014;4:5184.
B,N-codoped carbon nanostructures (BNCS) can serve as alternative low-cost metal-free electrocatalysts for oxygen reduction reactions (ORR). However, the compensation effect between the p- (B atoms) and n-type (N atoms) dopants would make the covalent boron-nitride (BN) easily formed during the synthesis of BNCS, leading to a unsatisfactory ORR activity. Therefore, it has been challenging to develop facile and rapid synthetic strategies for highly active BNCS without forming the direct covalent BN. Here, a facile method is developed to prepare B and N isolate-doped graphitic nanosheets (BNGS) by using iron species for saving N element and simultaneous doping the B element from nitrogen-containing ion-exchanged resins (NR). The resulting BNGS exhibits much more onset potential (Eonset) compared with the B-doped graphitic carbon nanosheets (BGS), N-doped graphitic carbon nanosheets (NGS), as well as B,N-codoped disorder carbon (BNC). Moreover, the BNGS shows well methanol tolerance propery and excellent stability (a minimal loss of activity after 5,000 potential cycles) compared to that of commercial Pt/C catalyst. The goog performance for BNGS towards ORR is attributed to the synergistic effect between B and N, and the well electrons transport property of graphitic carbon in BNGS.
doi:10.1038/srep05184
PMCID: PMC4046170  PMID: 24898033
5.  Soil Physicochemical and Biological Properties of Paddy-Upland Rotation: A Review 
The Scientific World Journal  2014;2014:856352.
Paddy-upland rotation is an unavoidable cropping system for Asia to meet the increasing demand for food. The reduction in grain yields has increased the research interest on the soil properties of rice-based cropping systems. Paddy-upland rotation fields are unique from other wetland or upland soils, because they are associated with frequent cycling between wetting and drying under anaerobic and aerobic conditions; such rotations affect the soil C and N cycles, make the chemical speciation and biological effectiveness of soil nutrient elements varied with seasons, increase the diversity of soil organisms, and make the soil physical properties more difficult to analyze. Consequently, maintaining or improving soil quality at a desirable level has become a complicated issue. Therefore, fully understanding the soil characteristics of paddy-upland rotation is necessary for the sustainable development of the system. In this paper, we offer helpful insight into the effect of rice-upland combinations on the soil chemical, physical, and biological properties, which could provide guidance for reasonable cultivation management measures and contribute to the improvement of soil quality and crop yield.
doi:10.1155/2014/856352
PMCID: PMC4060577  PMID: 24995366
6.  A comparative analysis of the statistical properties of large mobile phone calling networks 
Scientific Reports  2014;4:5132.
Mobile phone calling is one of the most widely used communication methods in modern society. The records of calls among mobile phone users provide us a valuable proxy for the understanding of human communication patterns embedded in social networks. Mobile phone users call each other forming a directed calling network. If only reciprocal calls are considered, we obtain an undirected mutual calling network. The preferential communication behavior between two connected users can be statistically tested and it results in two Bonferroni networks with statistically validated edges. We perform a comparative analysis of the statistical properties of these four networks, which are constructed from the calling records of more than nine million individuals in Shanghai over a period of 110 days. We find that these networks share many common structural properties and also exhibit idiosyncratic features when compared with previously studied large mobile calling networks. The empirical findings provide us an intriguing picture of a representative large social network that might shed new lights on the modelling of large social networks.
doi:10.1038/srep05132
PMCID: PMC4038836  PMID: 24875444
7.  Dynamic Evolution of Cross-Correlations in the Chinese Stock Market 
PLoS ONE  2014;9(5):e97711.
The analysis of cross-correlations is extensively applied for the understanding of interconnections in stock markets and the portfolio risk estimation. Current studies of correlations in Chinese market mainly focus on the static correlations between return series, and this calls for an urgent need to investigate their dynamic correlations. Our study aims to reveal the dynamic evolution of cross-correlations in the Chinese stock market, and offer an exact interpretation for the evolution behavior. The correlation matrices constructed from the return series of 367 A-share stocks traded on the Shanghai Stock Exchange from January 4, 1999 to December 30, 2011 are calculated over a moving window with a size of 400 days. The evolutions of the statistical properties of the correlation coefficients, eigenvalues, and eigenvectors of the correlation matrices are carefully analyzed. We find that the stock correlations are significantly increased in the periods of two market crashes in 2001 and 2008, during which only five eigenvalues significantly deviate from the random correlation matrix, and the systemic risk is higher in these volatile periods than calm periods. By investigating the significant contributors of the deviating eigenvectors in different time periods, we observe a dynamic evolution behavior in business sectors such as IT, electronics, and real estate, which lead the rise (drop) before (after) the crashes. Our results provide new perspectives for the understanding of the dynamic evolution of cross-correlations in the Chines stock markets, and the result of risk estimation is valuable for the application of risk management.
doi:10.1371/journal.pone.0097711
PMCID: PMC4035345  PMID: 24867071
8.  Social Determinants of Community Health Services Utilization among the Users in China: A 4-Year Cross-Sectional Study 
PLoS ONE  2014;9(5):e98095.
Background
To identify social factors determining the frequency of community health service (CHS) utilization among CHS users in China.
Methods
Nationwide cross-sectional surveys were conducted in 2008, 2009, 2010, and 2011. A total of 86,116 CHS visitors selected from 35 cities were interviewed. Descriptive analysis and multinomial logistic regression analysis were employed to analyze characteristics of CHS users, frequency of CHS utilization, and the socio-demographic and socio-economic factors influencing frequency of CHS utilization.
Results
Female and senior CHS clients were more likely to make 3–5 and ≥6 CHS visits (as opposed to 1–2 visits) than male and young clients, respectively. CHS clients with higher education were less frequent users than individuals with primary education or less in 2008 and 2009; in later surveys, CHS clients with higher education were the more frequent users. The association between frequent CHS visits and family income has changed significantly between 2008 and 2011. In 2011, income status did not have a discernible effect on the likelihood of making ≥6 CHS visits, and it only had a slight effect on making 3–5 CHS visits.
Conclusion
CHS may play an important role in providing primary health care to meet the demands of vulnerable populations in China. Over time, individuals with higher education are increasingly likely to make frequent CHS visits than individuals with primary school education or below. The gap in frequency of CHS utilization among different economic income groups decreased from 2008 to 2011.
doi:10.1371/journal.pone.0098095
PMCID: PMC4031144  PMID: 24854502
9.  Rare V203I mutation in the PRNP gene of a Chinese patient with Creutzfeldt–Jakob disease 
Prion  2013;7(3):259-262.
Here, we report a Chinese case of Creutzfeldt–Jakob disease (CJD) with a rare mutation in the prion protein gene (PRNP) leading to an exchange of amino acid from valine (Val) to isoleucine (I) at codon 203 (V203I). The 80-y-old male presented with sudden memory loss, rapid loss of vocabulary, inattention and slow responses, accompanied by dizziness, blurred vision and ataxia. Two weeks after admission, he exhibited tremor, myoclonus and bilateral Babinski signs. At the end of the clinical course, he developed severe akinetic mutism. The cerebrospinal fluid (CSF) was positive for 14-3-3 protein. Increased bilateral signal intensity in the frontal and parietal lobes was seen on diffusion-weighted imaging (DWI); periodic activity was recorded on an electroencephalogram (EEG). There was no family history of similar symptoms. The total clinical course was approximately two months.
doi:10.4161/pri.24674
PMCID: PMC3783113  PMID: 23764840
14-3-3 protein; PRNP; Creutzfeldt–Jakob disease; V203I; mutation
10.  A New Lyngbyatoxin from the Hawaiian Cyanobacterium Moorea producens 
Marine Drugs  2014;12(5):2748-2759.
Lyngbyatoxin A from the marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) is known as the causative agent of “swimmer’s itch” with its highly inflammatory effect. A new toxic compound was isolated along with lyngbyatoxin A from an ethyl acetate extract of M. producens collected from Hawaii. Analyses of HR-ESI-MS and NMR spectroscopies revealed the isolated compound had the same planar structure with that of lyngbyatoxin A. The results of optical rotation and CD spectra indicated that the compound was a new lyngbyatoxin A derivative, 12-epi-lyngbyatoxin A (1). While 12-epi-lyngbyatoxin A showed comparable toxicities with lyngbyatoxin A in cytotoxicity and crustacean lethality tests, it showed more than 100 times lower affinity for protein kinase Cδ (PKCδ) using the PKCδ-C1B peptide when compared to lyngbyatoxin A.
doi:10.3390/md12052748
PMCID: PMC4052313  PMID: 24824022
lyngbyatoxin A; cyanobacteria; Moorea producens; toxicity; protein kinase C
11.  TCMSP: a database of systems pharmacology for drug discovery from herbal medicines 
Background
Modern medicine often clashes with traditional medicine such as Chinese herbal medicine because of the little understanding of the underlying mechanisms of action of the herbs. In an effort to promote integration of both sides and to accelerate the drug discovery from herbal medicines, an efficient systems pharmacology platform that represents ideal information convergence of pharmacochemistry, ADME properties, drug-likeness, drug targets, associated diseases and interaction networks, are urgently needed.
Description
The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) was built based on the framework of systems pharmacology for herbal medicines. It consists of all the 499 Chinese herbs registered in the Chinese pharmacopoeia with 29,384 ingredients, 3,311 targets and 837 associated diseases. Twelve important ADME-related properties like human oral bioavailability, half-life, drug-likeness, Caco-2 permeability, blood-brain barrier and Lipinski’s rule of five are provided for drug screening and evaluation. TCMSP also provides drug targets and diseases of each active compound, which can automatically establish the compound-target and target-disease networks that let users view and analyze the drug action mechanisms. It is designed to fuel the development of herbal medicines and to promote integration of modern medicine and traditional medicine for drug discovery and development.
Conclusions
The particular strengths of TCMSP are the composition of the large number of herbal entries, and the ability to identify drug-target networks and drug-disease networks, which will help revealing the mechanisms of action of Chinese herbs, uncovering the nature of TCM theory and developing new herb-oriented drugs. TCMSP is freely available at http://sm.nwsuaf.edu.cn/lsp/tcmsp.php.
doi:10.1186/1758-2946-6-13
PMCID: PMC4001360  PMID: 24735618
TCM; Systems pharmacology; Drug discovery; ADME
12.  TCMSP: a database of systems pharmacology for drug discovery from herbal medicines 
Background
Modern medicine often clashes with traditional medicine such as Chinese herbal medicine because of the little understanding of the underlying mechanisms of action of the herbs. In an effort to promote integration of both sides and to accelerate the drug discovery from herbal medicines, an efficient systems pharmacology platform that represents ideal information convergence of pharmacochemistry, ADME properties, drug-likeness, drug targets, associated diseases and interaction networks, are urgently needed.
Description
The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) was built based on the framework of systems pharmacology for herbal medicines. It consists of all the 499 Chinese herbs registered in the Chinese pharmacopoeia with 29,384 ingredients, 3,311 targets and 837 associated diseases. Twelve important ADME-related properties like human oral bioavailability, half-life, drug-likeness, Caco-2 permeability, blood-brain barrier and Lipinski’s rule of five are provided for drug screening and evaluation. TCMSP also provides drug targets and diseases of each active compound, which can automatically establish the compound-target and target-disease networks that let users view and analyze the drug action mechanisms. It is designed to fuel the development of herbal medicines and to promote integration of modern medicine and traditional medicine for drug discovery and development.
Conclusions
The particular strengths of TCMSP are the composition of the large number of herbal entries, and the ability to identify drug-target networks and drug-disease networks, which will help revealing the mechanisms of action of Chinese herbs, uncovering the nature of TCM theory and developing new herb-oriented drugs. TCMSP is freely available at http://sm.nwsuaf.edu.cn/lsp/tcmsp.php.
doi:10.1186/1758-2946-6-13
PMCID: PMC4001360  PMID: 24735618
TCM; Systems pharmacology; Drug discovery; ADME
13.  Activated Scavenger Receptor A Promotes Glial Internalization of Aβ 
PLoS ONE  2014;9(4):e94197.
Beta-amyloid (Aβ) aggregates have a pivotal role in pathological processing of Alzheimer’s disease (AD). The clearance of Aβ monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aβ at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide XD4 activates the class A scavenger receptor (SR-A) on the glia by increasing the binding of Aβ to SR-A, thereby promoting glial phagocytosis of Aβ oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of Aβ monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits Aβ oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-α and IL-1β, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.
doi:10.1371/journal.pone.0094197
PMCID: PMC3981768  PMID: 24718459
14.  mAChRs activation induces epithelial-mesenchymal transition on lung epithelial cells 
Background
Epithelial-mesenchymal transition (EMT) has been proposed as a mechanism in the progression of airway diseases and cancer. Here, we explored the role of acetylcholine (ACh) and the pathway involved in the process of EMT, as well as the effects of mAChRs antagonist.
Methods
Human lung epithelial cells were stimulated with carbachol, an analogue of ACh, and epithelial and mesenchymal marker proteins were evaluated using western blot and immunofluorescence analyses.
Results
Decreased E-cadherin expression and increased vimentin and α-SMA expression induced by TGF-β1 in alveolar epithelial cell (A549) were significantly abrogated by the non-selective mAChR antagonist atropine and enhanced by the acetylcholinesterase inhibitor physostigmine. An EMT event also occurred in response to physostigmine alone. Furthermore, ChAT express and ACh release by A549 cells were enhanced by TGF-β1. Interestingly, ACh analogue carbachol also induced EMT in A549 cells as well as in bronchial epithelial cells (16HBE) in a time- and concentration-dependent manner, the induction of carbachol was abrogated by selective antagonist of M1 (pirenzepine) and M3 (4-DAMP) mAChRs, but not by M2 (methoctramine) antagonist. Moreover, carbachol induced TGF-β1 production from A549 cells concomitantly with the EMT process. Carbachol-induced EMT occurred through phosphorylation of Smad2/3 and ERK, which was inhibited by pirenzepine and 4-DAMP.
Conclusions
Our findings for the first time indicated that mAChR activation, perhaps via M1 and M3 mAChR, induced lung epithelial cells to undergo EMT and provided insights into novel therapeutic strategies for airway diseases in which lung remodeling occurs.
doi:10.1186/1471-2466-14-53
PMCID: PMC3975135  PMID: 24678619
Epithelial-mesenchymal transition (EMT); Lung epithelial cells; Non-neuronal cholinergic system; Signaling pathway
15.  Contralateral microemboli following carotid artery stenting in patients with a contralateral internal carotid artery occlusion 
Journal of vascular surgery  2013;58(3):794-797.
Subclinical microembolization identified on diffusion-weighted magnetic resonance imaging is recognized as an important outcome measure for carotid revascularization procedures. It is generally believed that arch manipulation is the primary reason for developing microemboli in the contralateral hemisphere during carotid artery stenting. However, we identified three patients who developed postprocedure microemboli of the contralateral hemisphere despite a known chronic contralateral internal carotid artery occlusion. Our cases highlight that ipsilateral microemboli may be an underappreciated but an important source of contralateral lesions through patent intracranial collateral pathways.
doi:10.1016/j.jvs.2012.11.114
PMCID: PMC3967720  PMID: 23478504
16.  Balance between a Higher Degree of Heterosis and Increased Reproductive Isolation: A Strategic Design for Breeding Inter-Subspecific Hybrid Rice 
PLoS ONE  2014;9(3):e93122.
The application of heterosis (hybrid vigor) has brought great success to plant breeding, particularly of hybrid rice, achieving significant yield increases. Attempts to explore the heterosis of inter-subspecific hybrids between indica and japonica rice, which result in even greater yield increases, have greatly increased in the past decades. However, because of the reduced seed setting rate in F1 hybrids as a result of increased reproductive isolation, the application of inter-subspecific hybrids in rice has slowed. Understanding the balance between heterosis and the reproductive isolation of inter-subspecific hybrids will facilitate the strategic design of inter-subspecific hybrid breeding. In this study, five indica and seven japonica rice varieties were chosen as the parental lines of a complete diallel mating design. Data from six group traits from all of the hybrids and inbred lines were collected. We found that the grain weight per plant, grain number per panicle, tiller per plant, thousand grain weight and plant height, which reflected increased heterosis, were associated with the genetic divergence index (GDI) of the parents. Meanwhile, owing to the reduced seed setting rate, which was also associated with the parents' GDI, the grain production of the hybrids was negatively affected. After analyzing the relationships between the GDI of indica-japonica parents and the grain weight per plant of the F1 hybrids, an ideal GDI value (0.37) for the two indica-japonica parents that could provide an optimal balance between the inter-subspecific heterosis and reproductive isolation was proposed. Our findings will help in the strategic design of an inter-subspecific hybrid rice breeding program by identifying the ideal indica and japonica parents for a hybrid combination to achieve hybrid rice with an optimal yield. This strategic design of an inter-subspecific hybrid rice breeding program will be time saving and cost effective.
doi:10.1371/journal.pone.0093122
PMCID: PMC3965518  PMID: 24667442
17.  Nicotine Activates YAP1 through nAChRs Mediated Signaling in Esophageal Squamous Cell Cancer (ESCC) 
PLoS ONE  2014;9(3):e90836.
Cigarette smoking is an established risk factor for esophageal cancers. Yes-associated protein 1 (YAP1), the key transcription factor of the mammalian Hippo pathway, has been reported to be an oncogenic factor for many cancers. In this study, we find nicotine administration can induce nuclear translocation and activation of YAP1 in ESCC. Consistently, we observed nuclear translocation and activation of YAP1 by knockdown of CHRNA3, which is a negative regulator of nicotine signaling in bronchial and esophageal cancer cells. Nicotine administration or CHRNA3 depletion substantially increased proliferation and migration in esophageal cancer cells. Interestingly, we find that YAP1 physically interacts with nAChRs, and nAChRs-signaling dissociates YAP1 from its negative regulatory complex composed with α-catenin, β-catenin and 14-3-3 in the cytoplasm, leading to upregulation and nuclear translocation of YAP1. This process likely requires PKC activation, as PKC specific inhibitor Enzastaurin can block nicotine induced YAP1 activation. In addition, we find nicotine signaling also inhibits the interaction of YAP1 with P63, which contributes to the inhibitory effect of nicotine on apoptosis. Using immunohistochemistry analysis we observed upregulation of YAP1 in a significant portion of esophageal cancer samples. Consistently, we have found a significant association between YAP1 upregulation and cigarette smoking in the clinical esophageal cancer samples. Together, these findings suggest that the nicotine activated nAChRs signaling pathway which further activates YAP1 plays an important role in the development of esophageal cancer, and this mechanism may be of a general significance for the carcinogenesis of smoking related cancers.
doi:10.1371/journal.pone.0090836
PMCID: PMC3951250  PMID: 24621512
18.  Developing regional genetic counseling for southern Chinese with nonsyndromic hearing impairment: a unique mutational spectrum 
Background
Racial and regional factors are important for the clinical diagnosis of non-syndromic hearing impairment. Comprehensive genetic analysis of deaf patients in different regions of China must be performed to provide effective genetic counseling. To evaluate the mutational spectrum of south Chinese families, we performed genetic analysis for non-syndromic hearing impairment in this population.
Methods
Complete clinical evaluations were performed on 701 unrelated patients with non-syndromic hearing impairment from six provinces in south China. Each subject was screened for common mutations, including SLC26A4 c.IVS7-2A > G, c.2168A > G; mitochondrial DNA m.1555A > G, m.1494C > T, m.7444G > A, m.7445A > G; GJB3 c.538C > T, c.547G > A; and WFS1 c.1901A > C, using pyrosequencing. GJB2 and SLC26A4 coding region mutation detection were performed using Sanger sequencing.
Results
Genetic analysis revealed that among the etiology of non-syndromic hearing impairment, GJB2, SLC26A4, and mitochondrial m.1555A > G mutations accounted for 18.0%, 13.1%, and 0.9%, respectively. Common mutations included GJB2 c.235delC, c.109G > A, SLC26A4 c.IVS7-2A > G, c.1229 T > C, and mitochondrial m.1555A > G. The total mutation rate was 45.1% in all patients examined in south China. Overall, the clear contribution of GJB2, SLC26A4, and mitochondrial m.1555A > G to the etiology of the non-syndromic deafness population in south China was 32.0%.
Conclusions
Our study is the first genetic analysis of non-syndromic hearing impairment in south China, and revealed that a clear genetic etiology accounted for 32.0% of non-syndromic hearing cases in patients from these regions. The mutational spectrum of non-syndromic hearing impairment in the south Chinese population provides useful and targeted information to aid in genetic counseling.
doi:10.1186/1479-5876-12-64
PMCID: PMC3975227  PMID: 24612839
South China; Non-syndromic hearing impairment; GJB2; SLC26A4; Mitochondrial DNA; GJB3; WFS1; Gene mutation
19.  A Splay Tree-Based Approach for Efficient Resource Location in P2P Networks 
The Scientific World Journal  2014;2014:830682.
Resource location in structured P2P system has a critical influence on the system performance. Existing analytical studies of Chord protocol have shown some potential improvements in performance. In this paper a splay tree-based new Chord structure called SChord is proposed to improve the efficiency of locating resources. We consider a novel implementation of the Chord finger table (routing table) based on the splay tree. This approach extends the Chord finger table with additional routing entries. Adaptive routing algorithm is proposed for implementation, and it can be shown that hop count is significantly minimized without introducing any other protocol overheads. We analyze the hop count of the adaptive routing algorithm, as compared to Chord variants, and demonstrate sharp upper and lower bounds for both worst-case and average case settings. In addition, we theoretically analyze the hop reducing in SChord and derive the fact that SChord can significantly reduce the routing hops as compared to Chord. Several simulations are presented to evaluate the performance of the algorithm and support our analytical findings. The simulation results show the efficiency of SChord.
doi:10.1155/2014/830682
PMCID: PMC3972854  PMID: 24778602
20.  Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection 
Nature  2013;501(7465):10.1038/nature12416.
Cancer research has been righteously and successfully focused on prevention, early detection and identification of specific molecular targets that distinguish the malignant cells from the neighboring benign cells1. However, a major clinical challenge concerns how we can reduce lethal tissue injury caused by intensive chemoradiotherapy during treatment of late-staged metastatic cancers. Here we tested whether induction of adult stem cells repairs chemoradiation-induced tissue injury and prolongs overall survival. We found that intestinal stem cells (ISCs)2 expressed Slit2 and its single-span transmembrane cell-surface receptor Roundabout 1 (Robo1)3,4. Partial genetic deletion of Robo1 decreased intestinal stem cells (ISCs) and caused villus hypotrophy, whereas Slit2 transgene increased ISCs and triggered villus hypertrophy. During lethal dosages of chemoradiation, administering a short pulse of R-spondin 1 (Rspo1; a Wnt agonist)5–14 plus Slit2 reduced ISC loss, mitigated gut impairment and protected animals from death, without concomitantly decreasing tumor sensitivity to chemotherapy. Rspo1 and Slit2 may thus act as therapeutic adjuvants to enhance host tolerance to aggressive chemoradiotherapy for eradicating metastatic cancers.
doi:10.1038/nature12416
PMCID: PMC3888063  PMID: 23903657
21.  Sonographic measurement of renal size in patients undergoing chronic hemodialysis: Correlation with residual renal function 
Previous studies have reported that renal size may change when the function is compromised. However, it is not known whether sonographically measured renal size reflects the residual renal function (RRF) in patients undergoing chronic hemodialysis. A total of 140 patients undergoing chronic hemodialysis (≥3 months) were investigated in the present study. The patients were divided into two groups according to the daily urine volume: Individuals with RRF (RRF+ group; ≥200 ml; n=65) and without RRF (RRF− group; <200 ml; n=75). Renal sizes were measured using sonography and renal volumes were calculated with the ellipsoid formula. Univariable and multivariable stepwise forward logistic regression analyses were performed to examine the correlation between the presence of RRF and various variables. The results indicated that there were statistically significant differences (P<0.001) between the RRF+ and RRF− groups with regard to renal length, width, thickness and volume of the left (length, 7.9±1.2 vs. 6.8±1.2 cm; volume, 60.0±26.7 vs. 40.2±18.1 ml, respectively) and right (length, 7.6±1.2 vs. 6.7±1.2 cm; volume, 50.2±26.5 vs. 33.9±15.3 ml, respectively) sides of the kidney. Multivariable stepwise forward logistic regression analyses showed that the mean renal length or volume and hemodialysis duration were independent predictors of the presence of RRF. Therefore, renal size assessment by ultrasonography may be useful for RRF evaluation in patients undergoing chronic hemodialysis.
doi:10.3892/etm.2014.1560
PMCID: PMC3991538  PMID: 24940422
renal size; renal length; ultrasonography; residual renal function; end-stage renal disease
22.  Briarane Diterpenes from the South China Sea Gorgonian Coral, Junceella gemmacea 
Marine Drugs  2014;12(2):589-600.
Four new briarane diterpenoids, junceellolides M–P (1–4), were isolated together with seven known analogs (5–11) from the South China Sea gorgonian, Junceella gemmacea. The structures of these compounds were elucidated by detailed spectroscopic analysis and comparison with the reported data. The absolute configuration of compounds 1–3 were determined based on an ECD experiment, while the absolute configuration of compound 4 was genetically determined. All the compounds were isolated for the first time from J. gemmacea. These compounds showed no growth inhibitory activity against A549, MG63 and SMMC-7721 cell lines in an in vitro bioassay.
doi:10.3390/md12020589
PMCID: PMC3944505  PMID: 24473165
Junceella gemmacea; briarane; diterpenoid; junceellolide
23.  Snail Contributes to the Maintenance of Stem Cell-Like Phenotype Cells in Human Pancreatic Cancer 
PLoS ONE  2014;9(1):e87409.
Snail, a potent repressor of E-cadherin expression, plays a key role in epithelial-to-mesenchymal transition (EMT) in epithelial cancer. Recently, EMT and stemness programs are found linked together. In the current study, the expression of Snail and its contribution to cancer stem cell (CSC) marker expression, invasiveness, self-renewal, clonogenicity, and tumorigenicity of pancreatic cancer cells were studied. Our results showed that Snail was highly expressed in CSChigh cell line Panc-1. Stable, short hairpin RNA (shRNA)-mediated Snail knockdown decreased invasion in Panc-1 cells, in line with increased E-cadherin expression and its translocation from the nucleus to the membrane. Snail silencing in Panc-1 also inhibited CSC marker ALDH expression, together with decreased sphere and colony forming capacity, which was highly consistent with the expression of stem cell associated transcription factors like Sox2 and Oct4. In mouse xenograft models, knockdown of Snail led to a reduced number of tumor-bearing mice and a reduced average size of tumors, which had a stronger membrane staining of E-cadherin and lighter staining of Oct4. Collectively, these findings implicate Snail is required for the maintenance of stem cell-like phenotype in pancreatic cancer, and inhibition of Snail could be an efficient strategy to treat pancreatic cancer by targeting CSCs.
doi:10.1371/journal.pone.0087409
PMCID: PMC3906155  PMID: 24489910
24.  A Method for the Evaluation of Image Quality According to the Recognition Effectiveness of Objects in the Optical Remote Sensing Image Using Machine Learning Algorithm 
PLoS ONE  2014;9(1):e86528.
Objective and effective image quality assessment (IQA) is directly related to the application of optical remote sensing images (ORSI). In this study, a new IQA method of standardizing the target object recognition rate (ORR) is presented to reflect quality. First, several quality degradation treatments with high-resolution ORSIs are implemented to model the ORSIs obtained in different imaging conditions; then, a machine learning algorithm is adopted for recognition experiments on a chosen target object to obtain ORRs; finally, a comparison with commonly used IQA indicators was performed to reveal their applicability and limitations. The results showed that the ORR of the original ORSI was calculated to be up to 81.95%, whereas the ORR ratios of the quality-degraded images to the original images were 65.52%, 64.58%, 71.21%, and 73.11%. The results show that these data can more accurately reflect the advantages and disadvantages of different images in object identification and information extraction when compared with conventional digital image assessment indexes. By recognizing the difference in image quality from the application effect perspective, using a machine learning algorithm to extract regional gray scale features of typical objects in the image for analysis, and quantitatively assessing quality of ORSI according to the difference, this method provides a new approach for objective ORSI assessment.
doi:10.1371/journal.pone.0086528
PMCID: PMC3904880  PMID: 24489739
25.  Revision of three camaenid and one bradybaenid species (Gastropoda, Stylommatophora) from China based on morphological and molecular data, with description of a new bradybaenid subspecies from Inner Mongolia, China 
ZooKeys  2014;1-16.
We have revised the taxonomy of three camaenid and one bradybaenid species from China and described one new subspecies of the genus Bradybaena (Family Bradybaenidae) from Inner Mongolia, China. The genitalia of three Satsuma (Family Camaenidae) species S. mellea stenozona (Moellendorff, 1884), S. meridionalis (Moellendorff, 1884), comb. n. and S. uncopila (Heude, 1882), comb. n. assigned to the genus Bradybaena previously,lack a dart sac and mucous glands. Moreover, the molecular phylogeny has revealed close relationships between the three species and the genus Satsuma. Two species, S. stenozona (Moellendorff, 1884) from Fuzhou and Ganesella citrina Zilch, 1940 from Wuyi Mountain, are considered as synonymous and should be a subspecies of S. mellea mellea (Pfeiffer, 1866) because of the morphological and molecular similarities. Meanwhile, the other two are placed in the genus Satsuma: S. meridionalis (Moellendorff, 1884), comb. n. and S. uncopila (Heude, 1882), comb. n. G. virgo Pilsbry, 1927 differs from species of the genera Ganesella and Satsuma not only in its shell, but also in anatomical characters, such as having a dart sac and mucous gland, and lacking a flagellum. Additionally, phylogenetic analyses highly support the sister relationship with other Bradybaena species. Thus, placement of G. virgo Pilsbry, 1927 in the genus Bradybaena issuggested.
doi:10.3897/zookeys.372.6581
PMCID: PMC3909801  PMID: 24493955
Satsuma; Ganesella; Bradybaena; revision; new subspecies

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