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1.  Mandarin Fish Caveolin 1 Interaction with Major Capsid Protein of Infectious Spleen and Kidney Necrosis Virus and Its Role in Early Stages of Infection 
Journal of Virology  2013;87(6):3027-3038.
Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus from the family Iridoviridae. ISKNV is one of the major agents that cause mortality and economic losses to the freshwater fish culture industry in Asian countries, particularly for mandarin fish (Siniperca chuatsi). In the present study, we report that the interaction of mandarin fish caveolin 1 (mCav-1) with the ISKNV major capsid protein (MCP) was detected by using a virus overlay assay and confirmed by pulldown assay and coimmunoprecipitation. This interaction was independent of the classic caveolin 1 scaffolding domain (CSD), which is responsible for interacting with several signaling proteins and receptors. Confocal immunofluorescence microscopy showed that ISKNV MCP colocalized with mCav-1 in the perinuclear region of virus-infected mandarin fish fry (MFF-1) cells, which appeared as soon as 4 h postinfection. Subcellular fractionation analysis showed that ISKNV MCP was associated with caveolae in the early stages of viral infection. RNA interference silencing of mCav-1 did not change virus-cell binding but efficiently inhibited the entry of virions into the cell. Taken together, these results suggested that mCav-1 plays an important role in the early stages of ISKNV infection.
doi:10.1128/JVI.00552-12
PMCID: PMC3592132  PMID: 23283951
2.  Infectious Spleen and Kidney Necrosis Virus (a Fish Iridovirus) Enters Mandarin Fish Fry Cells via Caveola-Dependent Endocytosis 
Journal of Virology  2012;86(5):2621-2631.
Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus from the family Iridoviridae. Megalocytiviruses have been implicated in more than 50 fish species infections and currently threaten the aquaculture industry, causing great economic losses in China, Japan, and Southeast Asia. However, the cellular entry mechanisms of megalocytiviruses remain largely uncharacterized. In this study, the main internalization mechanism of ISKNV was investigated by using mandarin fish fry (MFF-1) cells. The progression of ISKNV infection is slow, and infection is not inhibited when the cells are treated with ammonium chloride (NH4Cl), chloroquine, sucrose, and chlorpromazine, which are inhibitors of clathrin-dependent endocytosis. The depletion of cellular cholesterol by methyl-β-cyclodextrin results in the significant inhibition of ISKNV infection; however, the infection is resumed with cholesterol replenishment. Inhibitors of caveolin-1-involved signaling events, including phorbol 12-myristate 13-acetate (PMA), genistein, and wortmannin, impair ISKNV entry into MFF-1 cells. Moreover, ISKNV entry is dependent on dynamin and the microtubule cytoskeleton. Cofraction analysis of ISKNV and caveolin-1 showed that ISKNV colocates with caveolin-1 during virus infection. These results indicate that ISKNV entry into MFF-1 cells proceeds via classical caveola-mediated endocytosis and is dependent on the microtubules that serve as tracks along which motile cavicles may move via a caveola-caveosome-endoplasmic reticulum (ER) pathway. As a fish iridovirus, ISKNV entry into MFF-1 cells is different from the clathrin-mediated endocytosis of frog virus 3 entry into mammalian cells (BHK-21) at 28°C, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection.
doi:10.1128/JVI.06947-11
PMCID: PMC3302275  PMID: 22171272
3.  The Novel Bacterial N-Demethylase PdmAB Is Responsible for the Initial Step of N,N-Dimethyl-Substituted Phenylurea Herbicide Degradation 
Applied and Environmental Microbiology  2013;79(24):7846-7856.
The environmental fate of phenylurea herbicides has received considerable attention in recent decades. The microbial metabolism of N,N-dimethyl-substituted phenylurea herbicides can generally be initiated by mono-N-demethylation. In this study, the molecular basis for this process was revealed. The pdmAB genes in Sphingobium sp. strain YBL2 were shown to be responsible for the initial mono-N-demethylation of commonly used N,N-dimethyl-substituted phenylurea herbicides. PdmAB is the oxygenase component of a bacterial Rieske non-heme iron oxygenase (RO) system. The genes pdmAB, encoding the α subunit PdmA and the β subunit PdmB, are organized in a transposable element flanked by two direct repeats of an insertion element resembling ISRh1. Furthermore, this transposable element is highly conserved among phenylurea herbicide-degrading sphingomonads originating from different areas of the world. However, there was no evidence of a gene for an electron carrier (a ferredoxin or a reductase) located in the immediate vicinity of pdmAB. Without its cognate electron transport components, expression of PdmAB in Escherichia coli, Pseudomonas putida, and other sphingomonads resulted in a functional enzyme. Moreover, coexpression of a putative [3Fe-4S]-type ferredoxin from Sphingomonas sp. strain RW1 greatly enhanced the catalytic activity of PdmAB in E. coli. These data suggested that PdmAB has a low specificity for electron transport components and that its optimal ferredoxin may be the [3Fe-4S] type. PdmA exhibited low homology to the α subunits of previously characterized ROs (less than 37% identity) and did not cluster with the RO group involved in O- or N-demethylation reactions, indicating that PdmAB is a distinct bacterial RO N-demethylase.
doi:10.1128/AEM.02478-13
PMCID: PMC3837831  PMID: 24123738
4.  Size of solitary pulmonary nodule was the risk factor of malignancy 
Journal of Thoracic Disease  2014;6(6):668-676.
Objective
The purpose of this study was to analyze the role of the sizes of solitary pulmonary nodules (SPNs) in predicting their potential malignancies.
Methods
A total of 379 patients with pathologically confirmed SPNs were enrolled in this study. They were divided into three groups based on the SPN sizes: ≤10, 11-20, and >20 mm. The computed tomography (CT) findings of these SPNs were analyzed in these three groups to identify the malignant and benign SPNs. The risk factors were analyzed using binary logistic regression analysis.
Results
Of these 379 patients, 120 had benign SPNs and 259 had malignant SPNs. In the ≤10 mm SPN group, air cavity density was the risk factor for malignancy, with the sensitivity, specificity, and accuracy being 77.8%, 75.0%, and 76.3%. In the 11-20 mm SPN group, age, glitches and vascular aggregation were the risk factors for malignancy, with the sensitivity, specificity, and accuracy being 91.3%, 56.9%, and 81.5%. In the >20 mm SPN group, age, lobulation, and vascular aggregation were the risk factors for malignancy, with the sensitivity, specificity, and accuracy being 88.6%, 57.1%, and 79.1%.
Conclusions
According to CT findings of SPNs, age, glitches, lobulation, vascular aggregation, and air cavity density are the risk factors of malignancy, whereas calcification and satellite lesions are the protective factors. During the course of development from small to large nodules, air cavity density could be firstly detected in early stages, followed by glitches and vascular aggregation. Lobulation is associated with relatively large lesions.
doi:10.3978/j.issn.2072-1439.2014.06.22
PMCID: PMC4073405  PMID: 24976989
Solitary pulmonary nodules (SPNs); computed tomography (CT); logistic regression; risk factors
5.  Effect of Lianhuaqingwen Capsules on Airway Inflammation in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease 
Chronic obstructive pulmonary disease (COPD) is characterized by a chronic inflammatory response that is worsened by acute exacerbations. Lianhuaqingwen (LHQW) has anti-inflammatory and immune regulatory functions and may inhibit the airway inflammation that occurs during an acute exacerbation of COPD. In this study, 100 participants were recruited and randomly assigned, 1 : 1, to the LHQW and the conventional groups, which were treated, respectively, with LHQW capsules and conventional Western medicine or only conventional Western medicine. The scores of the CAT scale and levels of inflammatory cytokines in blood and sputum were measured during treatment. In addition, subjects were subdivided into high-risk and low-risk subgroups. The CAT scores in the LHQW group and high-risk subgroup were clearly improved from the 5th day, but the other groups improved only after treatment was completed. Expression levels of IL-8, TNF-α, IL-17, and IL-23 in the sputum and of IL-8 and IL-17 in the blood were significantly decreased after treatment, and similar results were found in subgroups. These data suggested that LHQW capsules can accelerate the improvement of AECOPD patients, especially for the high-risk subgroup, and the mechanism of action may be related to the decreased release of inflammatory mediators.
doi:10.1155/2014/637969
PMCID: PMC4058171  PMID: 24971150
6.  Increased microRNA-155 and decreased microRNA-146a may promote ocular inflammation and proliferation in Graves’ ophthalmopathy 
Graves’ ophthalmopathy is an inflammatory autoimmune disease of the orbit, characterized by inflammation and proliferation of the orbital tissue caused by CD4+T cells and orbital fibroblasts. Despite recent substantial findings regarding its cellular and molecular foundations, the pathogenesis of Graves’ ophthalmopathy remains unclear. Accumulating data suggest that microRNAs play important roles in the pathophysiology of autoimmunity and proliferation. Specifically, microRNA-155 (miR-155) can promote autoimmune inflammation by enhancing inflammatory T cell development. In contrast to miR-155, microRNA-146a (miR-146a) can inhibit the immune response by suppressing T cell activation. Furthermore, miR-155 and miR-146a are involved in cell proliferation, differentiation, and many other life processes. Thus, miR-155 and miR-146a, with opposite impacts on inflammatory responses carried out by T lymphocytes, appear to have multiple targets in the pathogenesis of Graves’ ophthalmopathy. Our previous work showed that the expression of miR-146a was significantly decreased in peripheral blood mononuclear cells from Graves’ ophthalmopathy patients compared with normal subjects. Accordingly, we proposed that the expression of miR-155 increased and the expression of miR-146a decreased in the target cells (CD4+T cells and orbital fibroblasts), thus promoting ocular inflammation and proliferation in Graves’ ophthalmopathy. The proposed hypothesis warrants further investigation of the function of the differentially expressed microRNAs, which may shed new light on the pathogenesis of Graves’ ophthalmopathy and lead to new strategies for its management.
doi:10.12659/MSM.890686
PMCID: PMC3999163  PMID: 24743332
Autoimmune Disease; Graves’ Ophthalmopathy; MicroRNAs
7.  Establishing and Applying a Schistosomiasis Early Warning Index (SEWI) in the Lower Yangtze River Region of Jiangsu Province, China 
PLoS ONE  2014;9(4):e94012.
Background
China has made remarkable progress in schistosomiasis control over the past decades. Transmission control has replaced morbidity control as the country moves towards the goal of elimination and the current challenge is to find a sensitive measure capable of gauging transmission risk in low-prevalence areas. The study aims to develop a Schistosomiasis Early Warning Index (SEWI) and demonstrate its use in Jiangsu Province along the lower Yangtze River.
Methodology/Principal Findings
The Delphi approach, a structured communication technique, was used to develop the SEWI. Two rounds of interviews with 30 public health experts specialized in schistosomiasis control were conducted using 40 indicators that reflected different aspects of schistosomiasis transmission and control. The necessity, feasibility, and sensitivity of each indicator were assessed and the weight value of each indicator determined based on these experts' judgment. The system included 3 first-order indicators, 7 second-order indicators, and 30 third-order indicators. The 3 first-order indicators were endemic status, control measures, social and environmental factors, with the weight values 0.366, 0.343 and 0.291, respectively. For the 7 second-order indicators, the highest weight value was for control measures for snails (0.175) and the lowest for transmission route (0.110). We estimated and mapped the SEWI for endemic areas at the county scale in Jiangsu Province finding that the majority of the endemic areas were characterized as medium transmission risk (SEWI risk values between 0.3 and 0.6), while areas where transmission interruption had been officially declared showed SEWI values <0.30. A few isolated areas (e.g. endemic islands in the Yangtze River) produced SEWI values >0.60. These estimates are largely in agreement with the endemicity levels based on recent epidemiological surveys.
Conclusions/Significance
The SEWI should be useful for estimation of schistosomiasis transmission surveillance, particularly with reference to the elimination of the disease in China.
doi:10.1371/journal.pone.0094012
PMCID: PMC3976384  PMID: 24705352
8.  Draft Genome Sequence of Sphingobium sp. Strain BHC-A, Revealing Genes for the Degradation of Hexachlorocyclohexane 
Genome Announcements  2014;2(2):e00254-14.
Here, we report the draft genome sequence of Sphingobium sp. strain BHC-A, a lin gene-based hexachlorocyclohexane (HCH)-degrading strain, isolated from soil that suffered long-term HCH contamination in an insecticide factory.
doi:10.1128/genomeA.00254-14
PMCID: PMC3974940  PMID: 24699958
9.  Mutational Signature of Aristolochic Acid Exposure as Revealed by Whole-Exome Sequencing 
Science translational medicine  2013;5(197):197ra102.
In humans, exposure to aristolochic acid (AA) is associated with urothelial carcinoma of the upper urinary tract (UTUC). Exome sequencing of UTUCs from 19 individuals with documented exposure to AA revealed a remarkably large number of somatic mutations and an unusual mutational signature attributable to AA. Most of the mutations (72%) in these tumors were A:T-to-T:A transversions, located predominantly on the nontranscribed strand, with a strong preference for deoxyadenosine in a consensus sequence (T/CAG). This trinucleotide motif overlaps the canonical splice acceptor site, possibly accounting for the excess of splice site mutations observed in these tumors. The AA mutational fingerprint was found frequently in oncogenes and tumor suppressor genes in AA-associated UTUC. The AA mutational signature was observed in one patient’s tumor from a UTUC cohort without previous indication of AA exposure. Together, these results directly link an established environmental mutagen to cancer through genome-wide sequencing and highlight its power to reveal individual exposure to carcinogens.
doi:10.1126/scitranslmed.3006200
PMCID: PMC3973132  PMID: 23926200
10.  Psychotropic Medication Treatment of Adolescents: Results from the National Comorbidity Survey–Adolescent Supplement 
Objective
To examine the 12-month prevalence of psychotropic medication use among adolescents and the match between mental disorder diagnoses and past year antidepressant and stimulant use.
Method
Data are from the National Comorbidity Survey–Adolescent Supplement (2002–2004), a nationally representative survey of 10,123 adolescents ages 13 to 18 years, that assesses DSM-IV disorders using a fully structured diagnostic interview, a modified version of the World Health Organization Composite International Diagnostic Interview (CIDI). Rates of 12-month psychotropic medication use are stratified by respondent socio-demographic characteristics and the distribution of 12-month DSM-IV CIDI disorders is estimated among past 12-month use of antidepressants and stimulants.
Results
During a one year period, 7.0% of adolescents used at least one psychotropic medication; these medications were most commonly antidepressants (3.9%) followed by stimulants (2.8%), anxiolytics (0.8%), antipsychotics (0.5%) and mood stabilizers (0.4%). Nearly three-quarters (74.1%) of adolescents with any past year psychotropic medication use had at least one CIDI mental disorder and many had disorders for which the specific medication class is clinically indicated. Among adolescents using antidepressants, 48.8% had a past 12 month depressive or anxiety disorder and an additional 20.3% had a lifetime depressive or anxiety disorder. Nearly one half (49.1%) of adolescents using stimulants met past 12 month attention-deficit/hyperactivity disorder (ADHD) criteria and an additional 13.1% met lifetime criteria for ADHD.
Conclusions
Most adolescents who are treated with psychotropic medications have one or more psychiatric disorders and many, though far from all, have mental disorders for which the specific medications are clinically indicated.
doi:10.1016/j.jaac.2012.12.006
PMCID: PMC3664537  PMID: 23582869
psychotropic medications; DSM-IV disorders; National Comorbidity Survey–Adolescent Supplement (NCS-A)
11.  CHRNA3 Polymorphism Modifies Lung Adenocarcinoma Risk in the Chinese Han Population 
Recent genome-wide association studies (GWASs) have identified 15q25.1 as a lung cancer susceptibility locus. Here, we sought to explore the direct carcinogenic effects of genetic variants in this region on the risk of developing lung adenocarcinoma (ADC). Five common SNPs (rs8034191, rs16969968, rs1051730, rs938682, and rs8042374) spanning the 15q25.1 locus were assayed in a case-control study examining a cohort of 301 lung ADCs and 318 healthy controls. Stratification analysis by gender, smoking status, and tumor, node, metastasis (TNM) classification, was performed. In addition, sections from ADC tissue and normal tissue adjacent to tumors were stained with an anti-CHRNA3 (cholinergic receptor nicotinic α3) antibody by immunohistochemistry in 81 cases. Our results demonstrate that rs8042374, a variant of the CHRNA3 gene, is associated with an increased risk of ADC with an OR of 1.76 (95% CI: 1.17–2.65, p = 0.024). This variant was linked to a greater risk of ADC in female nonsmokers (OR (95% CI): 1.81 (1.05–3.12), p = 0.032) and female stage I + II cases (OR (95% CI): 1.92 (1.03–3.57), p = 0.039). Although located within the same gene, rs938682 showed protective effects for smokers, stage III + IV cases, and male stage III + IV cases. Additionally, the CHRNA3 protein level in ADC tissue was slightly higher than in the surrounding normal lung tissue, based on immunohistochemical analysis. Our results suggest that the CHRNA3 polymorphism functions as a genetic modifier of the risk of developing lung ADC in the Chinese population, particularly in nonsmoking females.
doi:10.3390/ijms15045446
PMCID: PMC4013574  PMID: 24686516
lung adenocarcinoma; single nucleotide polymorphism; CHRNA3; female nonsmokers
12.  Mass spectrometry-based serum peptide profiling in hepatocellular carcinoma with bone metastasis 
AIM: To investigate the potential of serum peptides as a diagnostic tool for hepatocellular carcinoma (HCC) with bone metastasis.
METHODS: Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) was used to characterize the serum peptide profile of HCC patients with bone metastasis. Serum samples from 138 HCC patients (66 cases with and 72 cases without bone metastasis) were randomly assigned into a training set (n = 76) and a test set (n = 62). Differential serum peptides were examined using ClinProt magnetic bead-based purification followed by MALDI-TOF-MS. The sequences of differentially expressed serum peptides were identified using liquid chromatography-mass spectrometry. A diagnostic model was established using a learning algorithm of radial basis function neural network verified by a single blind trial. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of the established model.
RESULTS: Ten peptide peaks were significantly different between HCC patients with or without bone metastasis (P < 0.001). Sequences of seven peptides with mass to charge ratios (m/z) of 1780.7, 1866.5, 2131.6, 2880.4, 1532.4, 2489.8, and 2234.3 were successfully identified. These seven peptides were derived from alpha-fetoprotein, prothrombin, serglycin, isoform 2 of inter-alpha-trypsin inhibitor heavy chain H4, isoform 1 of autophagy-related protein 16-2, and transthyretin and fibrinogen beta chains, respectively. The recognition rate and predictive power of a diagnostic model established on the basis of six significant peptides (m/z for these six peptides were 1535.4, 1780.7, 1866.5, 2131.6, 2880.4, and 2901.9) were 89.47% and 82.89%, respectively. The sensitivity and specificity of this model based upon a single blind trial were 85.29% and 85.71%, respectively. ROC analysis found that the AUC (area under the ROC curve) value was 0.911.
CONCLUSION: Our study suggested that serum peptides may serve as a diagnosis tool for HCC bone metastasis.
doi:10.3748/wjg.v20.i11.3025
PMCID: PMC3961966  PMID: 24659894
Hepatocellular carcinoma; Serum; Peptides; Matrix-assisted laser desorption ionization-time of flight mass spectrometry; Tumor biomarker
13.  Specific Phobia among U.S. Adolescents: Phenomenology and Typology 
Depression and anxiety  2012;29(12):1072-1082.
Background
Investigators have proposed the diagnostic value of a generalized subtype of specific phobia, with classification based upon the number of phobic fears. However, current and future typologies of specific phobia classify the condition by the nature of phobic fears. This study investigated the clinical relevance of these alternative typologies by: (1) presenting the prevalence and correlates of specific phobia separately by the number and nature of phobia types; and (2) examining the clinical and psychiatric correlates of specific phobia according to these alternative typologies.
Methods
The National Comorbidity Survey Replication-Adolescent Supplement (NCS-A) is a nationally representative face-to-face survey of 10,123 adolescents aged 13–18 years in the continental United States.
Results
Most adolescents with specific phobia met criteria for more than one type of phobia in their lifetime, however rates were fairly similar across DSM-IV/5 subtypes. Sex differences were consistent across DSM-IV/5 subtypes, but varied by the number of phobic types, with a female predominance observed among those with multiple types of phobias. Adolescents with multiple types of phobias exhibited an early age of onset, elevated severity and impairment, and among the highest rates of other psychiatric disorders. However, certain DSM-IV/5 subtypes (i.e. blood-injection-injury and situational) were also uniquely associated with severity and psychiatric comorbidity.
Conclusions
Results indicate that both quantitative and DSM-IV/5 typologies of specific phobia demonstrate diagnostic value. Moreover, in addition to certain DSM-IV/5 subtypes, a generalized subtype based on the number of phobias may also characterize youth who are at greatest risk for future difficulties.
doi:10.1002/da.22008
PMCID: PMC3955257  PMID: 23108894
epidemiology; child/adolescent; phobia/phobic disorders; anxiety/anxiety disorders; assessment/diagnosis
14.  Monitoring pH-Triggered Drug Release from Radioluminescent Nanocapsules with X-Ray Excited Optical Luminescence 
ACS nano  2013;7(2):1178-1187.
One of the greatest challenges in cancer therapy is to develop methods to deliver chemotherapy agents to tumor cells while reducing systemic toxicity to non-cancerous cells. A promising approach to localizing drug release is to employ drug-loaded nanoparticles with coatings that release the drugs only in the presence of specific triggers found in the target cells such as pH, enzymes, or light. However, many parameters affect the nanoparticle distribution and drug release rate and it is difficult to quantify drug release in situ. In this work, we show proof of principle for a “smart” radioluminescent nanocapsule with X-ray excited optical luminescence (XEOL) spectrum that changes during release of the optically absorbing chemotherapy drug, doxorubicin. XEOL provides an almost background-free luminescent signal for measuring drug release from particles irradiated by a narrow X-ray beam. We study in vitro pH triggered release rates of doxorubicin from nanocapsules coated with a pH responsive polyelectrolyte multilayer using HPLC and XEOL spectroscopy. The doxorubicin was loaded to over 5 % by weight, and released from the capsule with a time constant in vitro of ~ 36 days at pH 7.4, and 21.4 hr at pH 5.0, respectively. The Gd2O2S:Eu nanocapsules are also paramagnetic at room temperature with similar magnetic susceptibility and similarly good MRI T2 relaxivities to Gd2O3, but the sulfur increases the radioluminescence intensity and shifts the spectrum. Empty nanocapsules did not affect cell viability up to concentrations of at least 250 μ/ml. These empty nanocapsules accumulated in a mouse liver and spleen following tail vein injection, and could be observed in vivo using XEOL. The particles are synthesized with a versatile template synthesis technique which allows for control of particle size and shape. The XEOL analysis technique opens the door to non-invasive quantification of drug release as a function of nanoparticle size, shape, surface chemistry and tissue type.
doi:10.1021/nn304369m
PMCID: PMC3612352  PMID: 23281651
pH triggered drug release; release monitoring; radioluminescent nanocapsules; theranostics
15.  Cucurbitacin IIb Exhibits Anti-Inflammatory Activity through Modulating Multiple Cellular Behaviors of Mouse Lymphocytes 
PLoS ONE  2014;9(2):e89751.
Cucurbitacin IIb (CuIIb) is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A)-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27Kip1 and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3+ T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65), it blocked the nuclear translocation of NF-κB (p65). In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.
doi:10.1371/journal.pone.0089751
PMCID: PMC3934946  PMID: 24587010
16.  Few-Layer MoSe2 Possessing High Catalytic Activity towards Iodide/Tri-iodide Redox Shuttles 
Scientific Reports  2014;4:4063.
Due to the two-dimensional confinement of electrons, single- and few-layer MoSe2 nanostructures exhibit unusual optical and electrical properties and have found wide applications in catalytic hydrogen evolution reaction, field effect transistor, electrochemical intercalation, and so on. Here we present a new application in dye-sensitized solar cell as catalyst for the reduction of I3− to I− at the counter electrode. The few-layer MoSe2 is fabricated by surface selenization of Mo-coated soda-lime glass. Our results show that the few-layer MoSe2 displays high catalytic efficiency for the regeneration of I− species, which in turn yields a photovoltaic energy conversion efficiency of 9.00%, while the identical photoanode coupling with “champion” electrode based on Pt nanoparticles on FTO glass generates efficiency only 8.68%. Thus, a Pt- and FTO-free counter electrode outperforming the best conventional combination is obtained. In this electrode, Mo film is found to significantly decrease the sheet resistance of the counter electrode, contributing to the excellent device performance. Since all of the elements in the electrode are of high abundance ratios, this type of electrode is promising for the fabrication of large area devices at low materials cost.
doi:10.1038/srep04063
PMCID: PMC3924216  PMID: 24525919
17.  Magnetic and optical properties of multifunctional core-shell radioluminescence nanoparticles 
Journal of materials chemistry  2012;22(25):12802-12809.
When X-rays irradiate radioluminescence nanoparticles, they generate visible and near infrared light that can penetrate through centimeters of tissue. X-ray luminescence tomography (XLT) maps the location of these radioluminescent contrast agents at high resolution by scanning a narrow X-ray beam through the tissue sample and collecting the luminescence at every position. Adding magnetic functionality to these radioluminescent particles would enable them to be guided, oriented, and heated using external magnetic fields, while their location and spectrum could be imaged with XLT and complementary magnetic resonance imaging. In this work, multifunctional monodispersed magnetic radioluminescent nanoparticles were developed as potential drug delivery carriers and radioluminescence imaging agents. The particles consisted of a spindle-shaped magnetic γ-Fe2O3 core and a radioluminescent europium-doped gadolinium oxide shell. Particles with solid iron oxide cores displayed saturation magnetizations consistent with their ~13% core volume, however, the iron oxide quenched their luminescence. In order to increase the luminescence, we partially etched the iron oxide core in oxalic acid while preserving the radioluminescent shell. The core size was controlled by the etching time which in turn affected the particles’ luminescence and magnetic properties. Particles with intermediate core sizes displayed both strong magnetophoresis and luminescence properties. They also served as MRI contrast agents with relaxivities of up to 58 mM−1s−1 (r2) and 120 mM−1s−1 (r2*). These particles offer promising multimodal MRI/fluorescence/X-ray luminescence contrast agents. Our core-shell synthesis technique offers a flexible method to control particle size, shape, and composition for a wide range of biological applications of magnetic/luminescent nanoparticles.
doi:10.1039/C2JM15444G
PMCID: PMC3918467  PMID: 24520183
18.  Body Mass Index and Breast Cancer Defined by Biological Receptor Status in Pre-Menopausal and Post-Menopausal Women: A Multicenter Study in China 
PLoS ONE  2014;9(1):e87224.
Background
Few studies have investigated the association between body mass index (BMI) and breast cancer with consideration to estrogen/progesterone/human epidermal growth factor type 2 receptor status (ER/PR/HER2) in the breast tissue among Chinese pre- and post-menopausal women.
Methods
Four thousand two hundred and eleven breast cancer patients were selected randomly from seven geographic regions of China from 1999 to 2008. Demographic data, risk factors, pathologic features, and biological receptor status of cases were collected from the medical charts. Chi-square test, fisher exact test, rank-correlation analysis, and multivariate logistic regression model were adopted to explore whether BMI differed according to biological receptor status in pre- and post-menopausal women.
Results
Three thousand two hundred and eighty one eligible cases with BMI data were included. No statistically significant differences in demographic characteristics were found between the cases with BMI data and those without. In the rank-correlation analysis, the rates of PR+ and HER2+ were positively correlated with increasing BMI among post-menopausal women (rs BMI, PR+ = 0.867, P = 0.001; rs BMI, HER2+ = 0.636, P = 0.048), but the ER+ rates did not vary by increasing BMI. Controlling for confounding factors, multivariate logistic regression models with BMI<24 kg/m2 as the reference group were performed and found that BMI≥24 kg/m2 was only positively correlated with PR+ status among post-menopausal breast cancer cases (adjusted OR = 1.420, 95% CI: 1.116–1.808, Wald = 8.116, P = 0.004).
Conclusions
Post-menopausal women with high BMI (≥24 kg/m2) have a higher proportion of PR+ breast cancer. In addition to effects mediated via the estrogen metabolism pathway, high BMI might increase the risk of breast cancer by other routes, which should be examined further in future etiological mechanism studies.
doi:10.1371/journal.pone.0087224
PMCID: PMC3906138  PMID: 24489874
19.  The Prevalence and Endemic Nature of Dengue Infections in Guangdong, South China: An Epidemiological, Serological, and Etiological Study from 2005–2011 
PLoS ONE  2014;9(1):e85596.
Objectives
Frequent outbreaks of dengue are considered to be associated with an increased risk for endemicity of the disease. The occurrence of a large number of indigenous dengue cases in consecutive years indicates the possibility of a changing dengue epidemic pattern in Guangdong, China.
Methods
To have a clear understanding of the current dengue epidemic, a retrospective study of epidemiological profile, serological response, and virological features of dengue infections from 2005–2011 was conducted. Case data were collected from the National Notifiable Infectious Diseases Reporting Network. Serum samples were collected and prepared for serological verification and etiological confirmation. Incidence, temporal and spatial distribution, and the clinical manifestation of dengue infections were analyzed. Pearson's Chi-Square test was used to compare incidences between different age groups. A seroprevalence survey was implemented in local healthy inhabitants to obtain the overall positive rate for the specific immunoglobulin (Ig) G antibody against dengue virus (DENV).
Results
The overall annual incidence rate was 1.87/100000. A significant difference was found in age-specific incidence (Pearson's Chi-Square value 498.008, P<0.001). Children under 5 years of age had the lowest incidence of 0.28/100000. The vast majority of cases presented with a mild manifestation typical to dengue fever. The overall seroprevalence of dengue IgG antibody in local populations was 2.43% (range 0.28%–5.42%). DENV-1 was the predominant serotype in circulation through the years, while all 4 serotypes were identified in indigenous patients from different outbreak localities since 2009.
Conclusions
A gradual change in the epidemic pattern of dengue infection has been observed in recent years in Guangdong. With the endemic nature of dengue infections, the transition from a monotypic to a multitypic circulation of dengue virus in the last several years will have an important bearing on the prevention and control of dengue in the province and in the neighboring districts.
doi:10.1371/journal.pone.0085596
PMCID: PMC3900419  PMID: 24465613
20.  Risk Factors for Breast Cancer Among Chinese Women: A 10-Year Nationwide Multicenter Cross-Sectional Study 
Journal of Epidemiology  2014;24(1):67-76.
Background
The characteristics of established risk factors for breast cancer may vary among countries. A better understanding of local characteristics of risk factors may help in devising effective prevention strategies for breast cancer.
Methods
Information on exposures to risk factors was collected from the medical charts of 4211 women with breast cancer diagnosed during 1999–2008. The distributions of these exposures among regions, and by menopausal status and birth period, were compared with the χ2 test. Crude associations between the selected factors and breast cancer were estimated using the cases in the present study and a representative control population, which was selected from qualified published studies.
Results
As compared with cases from less developed regions, those from more developed regions were significantly more likely to be nulliparous, had fewer childbirths (P < 0.05), and were less likely to have breastfed (P = 0.08). As compared with premenopausal cases, postmenopausal cases were more likely to be overweight and to have breastfed and had more childbirths (P < 0.05). The number of live births and rate of breastfeeding decreased in relation to birth period (P for trends <0.001). Overweight, late menopause, and family history of breast cancer were significantly associated with breast cancer among Chinese women.
Conclusions
Breast cancer incidence was associated with nulliparity and history of breastfeeding. Population attributable risks should be assessed, especially for more developed areas and young women. The effects of body mass index, age at menopause, and family history of breast cancer should be given priority during assessment of breast cancer risk among Chinese women.
doi:10.2188/jea.JE20120217
PMCID: PMC3872527  PMID: 24270059
breast cancer; risk factors; nationwide; multicenter
21.  Characterization of Four Novel Caspases from Litopenaeus vannamei (Lvcaspase2-5) and Their Role in WSSV Infection through dsRNA-Mediated Gene Silencing 
PLoS ONE  2013;8(12):e80418.
Apoptosis plays an important role in white spot syndrome virus (WSSV) pathogenesis, and caspases are central players in apoptosis. Here, we cloned four novel caspases (Lvcaspase2-5) from the Pacific white shrimp Litopenaeus vannamei, and investigated their potential roles in WSSV replication using dsRNA-mediated gene silencing. Lvcaspase2-5 have the typical domain structure of caspase family proteins, with the conserved consensus motifs p20 and p10. Lvcaspase2 and Lvcaspase5 were highly expressed in muscle, while Lvcaspase3 was highly expressed in hemocytes and Lvcaspase4 was mainly expressed in intestine. Lvcaspase2-5 could also be upregulated by WSSV infection, and they showed different patterns in various tissues. When overexpressed in Drosophila S2 cells, Lvcaspase2-5 showed different cellular localizations. Using dsRNA-medicated gene silencing, the expression of Lvcaspase2, Lvcaspase3, and Lvcaspase5 were effectively knocked down. In Lvcaspase2-, Lvcaspase3- or Lvcaspase5-silenced L. vannamei, expression of WSSV VP28 gene was significantly enhanced, suggesting protective roles for Lvcaspase2, Lvcaspase3 and Lvcaspase5 in the host defense against WSSV infection.
doi:10.1371/journal.pone.0080418
PMCID: PMC3871164  PMID: 24376496
22.  Right lung upper lobe carcinoma radical excision plus superior vena cava angioplasty 
Journal of Thoracic Disease  2013;5(6):873-874.
An elderly male patient was found to be with “nodule in upper lobe of right lung” during his health examination, although without any symptom. Chest CT at admission showed that the nodules were close to the superior vena cava, and CT reconstruction displayed an adipose space between the nodules and the superior vena cava. However, bronchoscopy showed negative results. Pre-operative exploration showed that the right upper lung nodules were tightly attached to the surface of superior vena cava and could not be effectively divided; an invasion could not be ruled out. The surgery was performed in a distal-proximal manner. The pulmonary fissure, bronchi, and arteries were divided firstly, followed by veins and the surrounding tissues of the lung. After the surrounding spaces of the tumor were sufficiently disassociated, superior vena cava angioplasty was performed using a stapler. The surgery was performed completely under thoracoscopy, during which the surgical incision was not enlarged. The main operation port was about 4 cm in diameter. Two axillary operation ports (about 1.2 and 0.6 cm in diameter, respectively) were also used. All the surgical equipment were used smoothly, and thus the surgery was completed with lowest invasion.
doi:10.3978/j.issn.2072-1439.2013.11.22
PMCID: PMC3886809  PMID: 24409370
Lung cancer; superior vena; angioplasty; VATS
23.  Ligand-Enabled Methylene C(sp3)–H Bond Activation with A Pd(II) Catalyst 
Journal of the American Chemical Society  2012;134(45):18570-18572.
Pd(II)-Insertion into β-methylene C(sp3)–H bonds was enabled by a mutually-repulsive and electron-rich quinoline ligand. Ligand tuning has led to the development of a method that allows for installation of an aryl group on a range of acyclic and cyclic amides containing β-methylene C(sp3)–H bonds.
doi:10.1021/ja309325e
PMCID: PMC3500088  PMID: 23116159
24.  Preferential Scattering by Interfacial Charged Defects for Enhanced Thermoelectric Performance in Few-layered n-type Bi2Te3 
Scientific Reports  2013;3:3212.
Over the past two decades several nano-structuring methods have helped improve the figure of merit (ZT) in the state-of-the art bulk thermoelectric materials. While these methods could enhance the thermoelectric performance of p-type Bi2Te3, it was frustrating to researchers that they proved ineffective for n-type Bi2Te3 due to the inevitable deterioration of its thermoelectric properties in the basal plane. Here, we describe a novel chemical-exfoliation spark-plasma-sintering (CE-SPS) nano-structuring process, which transforms the microstructure of n-type Bi2Te3 in an extraordinary manner without compromising its basal plane properties. The CE-SPS processing leads to preferential scattering of electrons at charged grain boundaries, and thereby increases the electrical conductivity despite the presence of numerous grain boundaries, and mitigates the bipolar effect via band occupancy optimization leading to an upshift (by ~ 100 K) and stabilization of the ZT peak over a broad temperature range of ~ 150 K.
doi:10.1038/srep03212
PMCID: PMC3827612  PMID: 24225424
25.  Rectal adenocarcinoma metastatic to the tonsil; PET-CT observations with pathological confirmation: A case report 
Oncology Letters  2013;7(1):153-155.
Metastasis of rectal adenocarcinoma develops by lymphatic or hematogenous spread. The usual sites of metastasis from rectal adenocarcinoma include local and distant lymph nodes, the liver and the lungs. The current case report presents a unique case of a mass that was identified in the tonsil by positron emission tomography-computed tomography (PET-CT), indicating a metastasis from rectal adenocarcinoma. Metastatic tumor to the tonsil is extremely rare and to the best of our knowledge, no previous studies have reported a case of tonsil metastasis from rectal adenocarcinoma. PET-CT scanners represent an important evolution in technology that is helping to bring anatomical imaging togeother with functional imaging in cancer diagnosis and therapy. Written informed consent was obtained from the patient.
doi:10.3892/ol.2013.1671
PMCID: PMC3861609  PMID: 24348839
tonsil; metastasis; rectal adenocarcinoma

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