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1.  Smoking-Related Knowledge, Attitude, Social Pressure, and Environmental Constraints among New Undergraduates in Chongqing, China 
Background: Smoking has resulted in numerous deaths in China. Data indicate that 21% of college students in China are smokers. Objective: This study aimed to examine the smoking-related behaviors of undergraduates, as influenced by knowledge, attitude, social pressure, and environmental constraints. Method: A convenience sampling of 412 fresh undergraduates from two universities in the University Town in Chongqing, China was recruited. Chi-square tests were used to compare the smoking-related variables between smokers and non-smokers. Moreover, logistic regression was used to examine the factors that associated with smoking status in undergraduates. Results: Smokers and non-smokers differ in terms of knowledge, attitudes toward smoking, participation in tobacco promotional activities, and sources of social pressure. Logistic regression model identified that sex, living cost, five smoking-related attitudes of “Smoking is pleasurable, Smoking relaxes me, Smoking makes me look strong, Smoking is a waste of money, Smoking can help me study better”, the social pressure “Smoking brings comfort during celebration”, and the environmental constraints “How did you get your cigarettes in the past 30 days?” are significantly associated with smoking. Conclusions: The findings provide a better understanding of the epidemic of smoking among fresh undergraduates in Chongqing, China. This study provides more detailed consideration of the implications for the WHO Framework Convention on Tobacco Control (FCTC) policies, especially on restriction of retail sales outlets and tobacco promotion activities near universities in China.
doi:10.3390/ijerph120100895
PMCID: PMC4306900  PMID: 25607600
undergraduates; smoking; attitude; environmental constraints; knowledge; social pressure
2.  Transmission/Disequilibrium Tests Incorporating Unaffected Offspring 
PLoS ONE  2014;9(12):e114892.
We propose a new method for family-based tests of association and linkage called transmission/disequilibrium tests incorporating unaffected offspring (TDTU). This new approach, constructed based on transmission/disequilibrium tests for quantitative traits (QTDT), provides a natural extension of the transmission/disequilibrium test (TDT) to utilize transmission information from heterozygous parents to their unaffected offspring as well as the affected offspring from ascertained nuclear families. TDTU can be used in various study designs and can accommodate all types of independent nuclear families with at least one affected offspring. When the study sample contains only case-parent trios, the TDTU is equivalent to TDT. Informative-transmission disequilibrium test (i-TDT) and generalized disequilibrium test(GDT) are another two methods that can use information of both unaffected offspring and affected offspring. In contract to i-TDT and GDT, the test statistic of TDTU is simpler and more explicit, and can be implemented more easily. Through computer simulations, we demonstrate that power of the TDTU is slightly higher compared to i-TDT and GDT. All the three methods are more powerful than method that uses affected offspring only, suggesting that unaffected siblings also provide information about linkage and association.
doi:10.1371/journal.pone.0114892
PMCID: PMC4275232  PMID: 25535968
3.  Dual-color labeled anti-mucin 1 antibody for imaging of ovarian cancer: A preliminary animal study 
Oncology Letters  2014;9(3):1231-1235.
To investigate the feasibility of the anti-mucin 1 (anti-MUC1/CD227) antibody in the fluorescent imaging of ovarian cancer, the CD227 antibody and a control IgG antibody were labeled with a near-infrared dye [Cy5.5-N-hydroxysuccinimide (NHS)] and a green dye (fluorescein-NHS). In vivo fluorescence images were obtained at 4, 12 and 36 h after injection of the probes into OVCAR3 tumor-bearing mice. The tumor to background ratios were calculated for both probes. Ex vivo fluorescence images were obtained following sacrifice at 36 h. After conjugation to Cy5.5 and fluorescein, the dual-color labeled CD227 probe (Ab-FL-Cy5.5) could be visualized by both green and near-infrared fluorescence. Uptake by the tumors was higher for the Ab-FL-Cy5.5 than for the IgG-Cy5.5 probe. All tumors could be visualized by in vivo imaging with an acceptable tumor to background ratio. Ex vivo studies demonstrated the advantages of using green fluorescence imaging to guide the resection of tumor tissues. These preliminary data indicate that the Ab-FL-Cy5.5 probe is promising for further tumor imaging applications and clinical translation.
doi:10.3892/ol.2014.2807
PMCID: PMC4315008  PMID: 25663888
fluorescence imaging; ovarian cancer; mucin 1 antibody; CD227 antibody; near-infrared fluorescence
4.  Molecular basis for the selective and ABA-independent inhibition of PP2CA by PYL13 
Cell Research  2013;23(12):1369-1379.
PYR1/PYL/RCAR family proteins (PYLs) are well-characterized abscisic acid (ABA) receptors. Among the 14 PYL members in Arabidopsis thaliana, PYL13 is ABA irresponsive and its function has remained elusive. Here, we show that PYL13 selectively inhibits the phosphatase activity of PP2CA independent of ABA. The crystal structure of PYL13-PP2CA complex, which was determined at 2.4 Å resolution, elucidates the molecular basis for the specific recognition between PP2CA and PYL13. In addition to the canonical interactions between PYLs and PP2Cs, an extra interface is identified involving an element in the vicinity of a previously uncharacterized CCCH zinc-finger (ZF) motif in PP2CA. Sequence blast identified another 56 ZF-containing PP2Cs, all of which are from plants. The structure also reveals the molecular determinants for the ABA irresponsiveness of PYL13. Finally, biochemical analysis suggests that PYL13 may hetero-oligomerize with PYL10. These two PYLs antagonize each other in their respective ABA-independent inhibitions of PP2Cs. The biochemical and structural studies provide important insights into the function of PYL13 in the stress response of plant and set up a foundation for future biotechnological applications of PYL13.
doi:10.1038/cr.2013.143
PMCID: PMC3847573  PMID: 24165892
PYL13; PP2CA; PYL10; zinc finger; abscisic acid; ABA signaling
5.  Short-Term Effects of Continuous Subcutaneous Insulin Infusion Therapy in Perioperative Patients with Diabetes Mellitus 
Diabetes Technology & Therapeutics  2013;15(12):1010-1018.
Abstract
Background: Hyperglycemia is common and hard to control in surgical patients with diabetes. We retrospectively investigated short-term effects of continuous subcutaneous insulin infusion (CSII) in perioperative patients with diabetes.
Patients and Methods: Perioperative patients with diabetes discharged between January 1, 2006 and January 1, 2012 were included. Glucose control and postoperative outcomes were compared between the patients using CSII or non-CSII insulin therapy.
Results: We identified 108 pairs of patients matched by propensity and surgical category who were using CSII therapy (CSII group) or non-CSII insulin therapy (control group). The CSII group had significantly lower fasting glucose levels (on the first postoperative day, 9.06±3.09 mmol/L vs. 11.05±4.19 mmol/L; P=0.003) and lower mean glucose levels (on the operation day, 9.93±2.65 mmol/L vs. 12.05±3.86 mmol/L; P=0.001). The CSII group also had a lower incidence of fever (on the first postoperative day, 30.4% vs. 53.2%; P=0.005). Furthermore, patients in the CSII group experienced significantly shorter postoperative intervals for suture removal (P=0.02) and hospital discharge (P=0.03). No significant difference in the total medical expenditure was observed between the two groups (P=0.47). We also made a comparison between the 30 pairs of patients who were using CSII or multiple daily insulin injection therapy but observed no significant difference between these two therapies in glucose control or postoperative outcomes.
Conclusions: Compared with non-CSII insulin therapy, even short-term implementation of CSII can improve the postoperative control of glucose, reduce the incidence of postoperative fever, and shorten the time for suture removal and discharge in surgical patients with diabetes.
doi:10.1089/dia.2013.0117
PMCID: PMC3868275  PMID: 23971526
6.  Association of red blood cell transfusion and in-hospital mortality in patients admitted to the intensive care unit: a systematic review and meta-analysis 
Critical Care  2014;18(6):515.
Introduction
Previous research has debated whether red blood cell (RBC) transfusion is associated with decreased or increased mortality in patients admitted to the intensive care unit (ICU). We conducted a systematic review and meta-analysis to assess the relationship of RBC transfusion with in-hospital mortality in ICU patients.
Methods
We carried out a literature search on Medline (1950 through May 2013), Web of Science (1986 through May 2013) and Embase (1980 through May 2013). We included all prospective and retrospective studies on the association between RBC transfusion and in-hospital mortality in ICU patients. The relative risk for the overall pooled effects was estimated by random effects model. Sensitivity analyses were conducted to assess potential bias.
Results
The meta-analysis included 28,797 participants from 18 studies. The pooled relative risk for transfused versus nontransfused ICU patients was 1.431 (95% CI, 1.105 to 1.854). In sensitivity analyses, the pooled relative risk was 1.211 (95% CI, 0.975 to 1.505) if excluding studies without adjustment for confounders, 1.178 (95% CI, 0.937 to 1.481) if excluding studies with relative high risk of bias, and 0.901 (95% CI, 0.622 to 1.305) if excluding studies without reporting hazard ratio (HR) or relative risk (RR) as an effect size measure. Subgroup analyses revealed increased risks in studies enrolling patients from all ICU admissions (RR 1.513, 95%CI 1.123 to 2.039), studies without reporting information on leukoreduction (RR 1.851, 95%CI 1.229 to 2.786), studies reporting unadjusted effect estimates (RR 3.933, 95%CI 2.107 to 7.343), and studies using odds ratio as an effect measure (RR 1.465, 95%CI 1.049 to 2.045). Meta-regression analyses showed that RBC transfusion could decrease risk of mortality in older patients (slope coefficient −0.0417, 95%CI −0.0680 to −0.0154).
Conclusions
There is lack of strong evidence to support the notion that ICU patients who receive RBC transfusion have an increased risk of in-hospital death. In studies adjusted for confounders, we found that RBC transfusion does not increase the risk of in-hospital mortality in ICU patients. Type of patient, information on leukoreduction, statistical method, mean age of patient enrolled and publication year of the article may account for the disagreement between previous studies.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0515-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s13054-014-0515-z
PMCID: PMC4256753  PMID: 25394759
7.  HERC2-USP20 axis regulates DNA damage checkpoint through Claspin 
Nucleic Acids Research  2014;42(21):13110-13121.
The DNA damage response triggers cell-cycle checkpoints, DNA repair and apoptosis using multiple post-translational modifications as molecular switches. However, how ubiquitination regulates ATR signaling in response to replication stress and single-strand break is still unclear. Here, we identified the deubiquitination enzyme (DUB) USP20 as a pivotal regulator of ATR-related DDR pathway. Through screening a panel of DUBs, we identified USP20 as critical for replication stress response. USP20 is phosphorylated by ATR, resulting in disassociation of the E3 ubiquitin ligase HERC2 from USP20 and USP20 stabilization. USP20 in turn deubiquitinates and stabilizes Claspin and enhances the activation of ATR-Chk1 signaling. These findings reveal USP20 to be a novel regulator of ATR-dependent DNA damage signaling.
doi:10.1093/nar/gku1034
PMCID: PMC4245938  PMID: 25355518
8.  Secular trends in the prevalence of low risk factor burden for cardiovascular disease according to obesity status among Chinese adults, 1993–2009 
BMC Public Health  2014;14(1):961.
Background
Cardiovascular disease (CVD) and obesity are now common among Chinese. We aimed to examine secular trends in the prevalence of low risk profile and to examine whether comparable changes in the prevalence of low risk profile across waist circumference (WC) groups and body mass index (BMI) categories have occurred.
Methods
We used data from the nationwide China Health and Nutrition Survey conducted in 1993, 1997, 2000, 2004, 2006, and 2009. There were 7274, 8368, 9369, 8948, 8786, and 9278 participants included in the analyses across the six study periods. We created an index of low risk factor burden from the following variables: not currently smoking, BMI < 25 kg/m2, WC < 90/80 cm in men/women, untreated systolic/diastolic blood pressure < 120/80 mmHg, and not having been previously diagnosed with diabetes.
Results
During the period of 1993–2009, the age-adjusted prevalence of low risk profile decreased from 16.2 to 11.5% among men and from 46.3 to 34.6% among women (both P < 0.001); Similar significant trends were observed in all age groups, rural/urban settings, education groups, WC status and BMI categories. The change in the prevalence of low risk profile was more striking among obese persons (P for interaction terms cohort *BMI were < 0.001). In 2009, 2.0 and 25.6% among central obese men and women had a low risk profile; Of note, was that 0.1 and 0.3% general obese men and women had a low risk profile.
Conclusions
The prevalence of low risk profile declined considerably over the past 17 years in all demographic groups, WC status, and BMI categories. Public health prevention strategies are urgently needed.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-961) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2458-14-961
PMCID: PMC4189202  PMID: 25228284
Cardiovascular risk factors; Trends; Waist circumference; Body mass index; Epidemiology
9.  Secondhand Smoke Exposure and Maternal Action to Protect Children from Secondhand Smoke: Pre- and Post-Smokefree Legislation in Hong Kong 
PLoS ONE  2014;9(8):e105781.
Background
Smokefree legislation may protect children from secondhand smoke (SHS) in the home from smoking parent(s). We examined the effect of the 2007 smokefree legislation on children’s exposure to SHS in the home and maternal action to protect children from SHS exposure in Hong Kong.
Methods
Families with a smoking father and a non-smoking mother were recruited from public clinics before (2005–2006, n = 333) and after the legislation (2007–2008, n = 742) which led to a major extension of smokefree places in Hong Kong. Main outcomes included children’s SHS exposure in the home, nicotine level in mothers’ and children’s hair and home environment, mothers’ action to protect children from SHS, and their support to the fathers to quit.
Results
Fewer mothers post-legislation reported children’s SHS exposure in the home (87.2% versus 29.3%, p<0.01), which was consistent with their hair nicotine levels (0.36ng/mg versus 0.04ng/mg, p<0.01). More mothers post-legislation in the last month took their children away from cigarette smoke (6.3% versus 92.2%; p<0.01) and advised fathers to quit over 3 times (8.3% versus 33.8%; p<0.01). No significant change was found in the content of smoking cessation advice and the proportion of mothers who took specific action to support the fathers to quit.
Conclusions
SHS exposure in the home decreased and maternal action to protect children from SHS increased after the 2007 smokefree legislation. Maternal support to fathers to quit showed moderate improvement. Cessation services for smokers and specific interventions for smoking families should be expanded together with smokefree legislation.
doi:10.1371/journal.pone.0105781
PMCID: PMC4148325  PMID: 25166507
10.  Adverse Events of Massage Therapy in Pain-Related Conditions: A Systematic Review 
Pain-related massage, important in traditional Eastern medicine, is increasingly used in the Western world. So the widening acceptance demands continual safety assessment. This review is an evaluation of the frequency and severity of adverse events (AEs) reported mainly for pain-related massage between 2003 and 2013. Relevant all-languages reports in 6 databases were identified and assessed by two coauthors. During the 11-year period, 40 reports of 138 AEs were associated with massage. Author, year of publication, country of occurrence, participant related (age, sex) or number of patients affected, the details of manual therapy, and clinician type were extracted. Disc herniation, soft tissue trauma, neurologic compromise, spinal cord injury, dissection of the vertebral arteries, and others were the main complications of massage. Spinal manipulation in massage has repeatedly been associated with serious AEs especially. Clearly, massage therapies are not totally devoid of risks. But the incidence of such events is low.
doi:10.1155/2014/480956
PMCID: PMC4145795  PMID: 25197310
11.  DEAD-box helicase DP103 defines metastatic potential of human breast cancers 
The Journal of Clinical Investigation  2014;124(9):3807-3824.
Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β–activated kinase-1 (TAK1) phosphorylation of NF-κB–activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB–mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.
doi:10.1172/JCI73451
PMCID: PMC4151228  PMID: 25083991
12.  DNA methyltransferase3a expression is an independent poor prognostic indicator in gastric cancer 
AIM: To explore the alteration of DNA methyltransferase expression in gastric cancer and to assess its prognostic value.
METHODS: From April 2000 to December 2010, 227 men and 73 women with gastric cancer were enrolled in the study. The expression of DNA methyltransferases (DNMTs), including DNMT1, DNMT3a and DNMT3b, in the 300 cases of gastric carcinoma, of which 85 had paired adjacent normal gastric mucus samples, was evaluated by immunohistochemistry using a tissue microarray. Serum anti-Helicobacter pylori (H. pylori) IgG was detected by enzyme-linked immunosorbent assay (ELISA). The relationships between the above results and the clinicopathological characteristics were analyzed. Their prognostic value was evaluated using the Cox proportional hazards model.
RESULTS: In gastric cancer, expression of DNMTs was mainly seen in the nucleus. Weak staining was also observed in the cytoplasm. Expression of DNMT1, DNMT3a and DNMT3b in gastric cancer was significantly higher compared to that in the paired control samples (60.0% vs 37.6%, 61.2% vs 4.7%, and 94.1% vs 71.8%, P < 0.01). The overall survival rate was significantly higher in the DNMT3a negative group than in the DNMT3a positive group in gastric cancer patients (Log-rank test, P = 0.032). No significant correlation was observed between DNMT1 and DNMT3b expression and the overall survival time (Log-rank test, P = 0.289, P = 0.347). Multivariate regression analysis indicated that DNMT3a expression (P = 0.025) and TNM stage (P < 0.001), but not DNMT1 (P = 0.54) or DNMT3b (P = 0.62), were independent prognostic factors in gastric cancer. H. pylori infection did not induce protein expression of DNMTs.
CONCLUSION: The results suggest that expression of DNMT3a is an independent poor prognostic indicator in gastric cancer. DNMT3a might play an important role in gastric carcinogenesis.
doi:10.3748/wjg.v20.i25.8201
PMCID: PMC4081693  PMID: 25009393
DNA methyltransferase; Prognosis; Gastric cancer; Expression; Helicobacter pylori
13.  Fasting Plasma Glucose at 24–28 Weeks to Screen for Gestational Diabetes Mellitus 
Diabetes Care  2013;36(7):2038-2040.
OBJECTIVE
To evaluate the usefulness of a fasting plasma glucose (FPG) at 24–28 weeks’ gestation to screen for gestational diabetes mellitus (GDM).
RESEARCH DESIGN AND METHODS
The medical records and results of a 75-g 2-h oral glucose tolerance test (OGTT) of 24,854 pregnant women without known pre-GDM attending prenatal clinics in 15 hospitals in China were examined.
RESULTS
FPG cutoff value of 5.1 mmol/L identified 3,149 (12.1%) pregnant women with GDM. FPG cutoff value of 4.4 mmol/L ruled out GDM in 15,369 (38.2%) women. With use of this cutoff point, 12.2% of patients with mild GDM will be missed. The positive predictive value is 0.322, and the negative predictive value is 0.928.
CONCLUSIONS
FPG at 24–28 weeks’ gestation could be used as a screening test to identify GDM patients in low-resource regions. Women with an FPG between ≥4.4 and ≤5.0 mmol/L would require a 75-g OGTT to diagnose GDM. This would help to avoid approximately one-half (50.3%) of the formal 75-g OGTTs in China.
doi:10.2337/dc12-2465
PMCID: PMC3687275  PMID: 23536582
14.  Preparation and functional studies of hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody 
OncoTargets and therapy  2014;7:779-787.
Objective
To prepare hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody, and study their characteristics, functions, and mechanisms of action.
Materials and methods
The anti-human death receptor 5 single-chain antibody was constructed and expressed. Protein-loaded hydroxyethyl chitosan nanoparticles were prepared, and their size, morphology, particle-size distribution and surface zeta potential were measured by scanning electron microscopy and laser particle-size analysis. Mouse H22 hepatocellular carcinoma cells were cultured, and growth inhibition was examined using the CellTiter-Blue cell-viability assay. Flow cytometry and Hoechst 33342 were employed to measure cell apoptosis. Kunming mice with H22 tumor models were treated with protein-loaded hydroxyethyl chitosan nanoparticles, and their body weight and tumor size were measured, while hematoxylin and eosin staining was used to detect antitumor effects in vivo and side effects from tumors.
Results
The protein-loaded hydroxyethyl chitosan nanoparticles had good stability; the zeta potential was −24.2±0.205, and the dispersion index was 0.203. The inhibition of the protein-loaded hydroxyethyl chitosan nanoparticles on H22 growth was both time- and dose-dependent. Increased expressions of active caspase 8, active caspase 3, and BAX were detected following treatment. The average weight gain, tumor weight, and mean tumor volume of the protein and protein-loaded hydroxyethyl chitosan nanoparticle groups were significantly different (P<0.05) compared with the phosphate-buffered saline group.
Conclusion
The protein-loaded hydroxyethyl chitosan nanoparticles effectively suppressed tumor growth, indicating that nanotechnology has the potential for broad application in cancer therapy.
doi:10.2147/OTT.S59872
PMCID: PMC4039402  PMID: 24899816
anticancer effect; DR5; GCS-aDR5ScFv; H22
15.  Concurrent alterations of RAGE, RECK, and MMP9 protein expression are relevant to Epstein-Barr virus infection, metastasis, and survival in nasopharyngeal carcinoma 
This study aimed to concurrently investigate the expressions of receptor for advanced glycation end products (RAGE), reversion inducing cysteine-rich protein with Kazal motifs (RECK) and matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and their correlations with clinicopathological properties. Using immunohistochemistry, we found that RECK expression was downregulated in NPC tissues compared with chronic nasopharyngitis (CNT) tissues, while RAGE and MMP9 expressions were upregulated. We further found that RECK expression level was inversely correlated with MMP9 expression level in NPC, whereas RAGE expression level was positively correlated with MMP9 expression level. Moreover, aberrant expressions of these proteins had a positive correlation with the titers of EBVCA-IgA, lymphatic metastasis, recurrence and survival. Together, these findings suggest that dysregulations of RECK and RAGE expressions may be collectively involved in tumor progression of NPC by regulating MMP9 expression and that they may be a good prognostic predictors for NPC.
PMCID: PMC4097239  PMID: 25031745
Nasopharyngeal carcinoma; RAGE; RECK; MMP9
16.  Identification and Characterization of ABA Receptors in Oryza sativa 
PLoS ONE  2014;9(4):e95246.
Abscisic acid (ABA) is an essential phytohormone that regulates plant stress responses. ABA receptors in Arabidopsis thaliana (AtPYLs) have been extensively investigated by structural, biochemical, and in vivo studies. In contrast, relatively little is known about the ABA signal transduction cascade in rice. Besides, the diversities of AtPYLs manifest that the information accumulated in Arabidopsis cannot be simply adapted to rice. Thus, studies on rice ABA receptors are compulsory. By taking a bioinformatic approach, we identified twelve ABA receptor orthologs in Oryza sativa (japonica cultivar-group) (OsPYLs), named OsPYL1–12. We have successfully expressed and purified OsPYL1–3, 6 and 10–12 to homogeneity, tested the inhibitory effects on PP2C in Oryza sativa (OsPP2C), and measured their oligomerization states. OsPYL1–3 mainly exhibit as dimers and require ABA to inhibit PP2C’s activity. On the contrary, OsPYL6 retains in the monomer-dimer equilibrium state and OsPYL10–11 largely exist as monomers, and they all display an ABA-independent phosphatase inhibition manner. Interestingly, although OsPYL12 seems to be a dimer, it abrogates the phosphatase activity of PP2Cs in the absence of ABA. Toward a further understanding of OsPYLs on the ABA binding and PP2C inhibition, we determined the crystal structure of ABA-OsPYL2-OsPP2C06 complex. The bioinformatic, biochemical and structural analysis of ABA receptors in rice provide important foundations for designing rational ABA-analogues and breeding the stress-resistant rice for commercial agriculture.
doi:10.1371/journal.pone.0095246
PMCID: PMC3990689  PMID: 24743650
17.  Aberrant SATB1 expression is associated with Epstein-Barr virus infection, metastasis and survival in human nasopharyngeal cells and endemic nasopharyngeal carcinoma 
Special AT-rich sequence-binding protein 1 (SATB1) has been identified as a key factor in the progression of some cancers, functioning as a global genome organizer and chromatin regulator. We examined the levels of SATB1 mRNA expression in NPC cell lines 5-8F (high metastasis) and 6-10B (low metastasis) and immortalized human nasopharyngeal epithelial cells NP69-SV40T by quantitative real-time PCR. We also examined the protein expression levels of SATB1 in 72 cases of nasopharyngeal carcinoma (NPC) tissues and 30 cases of normal nasopharyngeal (NNP) tissues by immunohistochemistry, and then assessed the correlations between SATB1 expression and clinicopathological factors. The expression level of SATB1 mRNA in 5-8F was much higher than those in 6-10B and NP69-SV40T (P < 0.05). The expression level of SATB1 mRNA in 6-10B was higher than in NP69-SV40T, but the difference was not statistically significant (P > 0.05). The positive expression rates of SATB1 protein in NPC (38/72, 52.8%) were significantly higher than in NNP (4/30, 13.3%) (P < 0.05). SATB1 protein levels in NPC were not associated with gender, age, and T stage (P > 0.05), but positively correlated with the titers of EBVCA-IgA, metastasis (N and M stage), recurrence, and survival (P < 0.05). Multivariate analysis showed that the overexpression of SATB1 protein is an independent prognostic factor for NPC. The expression levels of SATB1 were obviously upregulated in primary NPC tissues and human NPC cell lines. Therefore, SATB1 may be a valuable predictor in assessing the metastasis, recurrence, and prognosis of NPC.
PMCID: PMC4069958  PMID: 24966956
Nasopharyngeal carcinoma; SATB1; immunohistochemistry; quantitative real-time PCR; prognosis
18.  Phenethyl Isothiocyanate inhibits STAT3 activation in prostate cancer cells 
This study was undertaken to investigate the mechanism by which phenethyl isothiocyanate (PEITC), a natural compound from cruciferous vegetables, exhibits antitumor effect on prostate cancer cells. Cell proliferation, cell cycle, western blot, gene transfer and reporter assays were used to test the effects of PEITC on the growth and IL6/JAK/STAT3 pathway in prostate cancer. The result showed that PEITC significantly inhibited DU145 cell proliferation in a dose-dependent manner and induced the cell arrest at G2-M phase. PEITC inhibited both constitutive and interleukin 6 (IL-6)-induced STAT3 activity in DU145 cells. IL-6-stimulated phosphorylation of JAK2, an STAT3 upstream kinase, was also attenuated by PEITC. Moreover, an antioxidant reagent, N-acetyl-l-cysteine (NAC) which suppresses reactive oxygen species (ROS) generation, reversed the early inhibitory effects of PEITC on cell proliferation, constitutive or IL-6-mediated JAK-STAT3 phosphorylation in PCa cells. Taken together, our data demonstrated that PEITC can inhibit the activation of the JAK-STAT3 signal-cascade in prostate cancer cells and the underlying mechanism may be partially involved with blocking cellular ROS production during the early stage of the signaling activation by IL-6.
doi:10.1002/mnfr.200800253
PMCID: PMC3964815  PMID: 19437484
Phenethyl isothiocyanate; IL-6; STAT3; Androgen independent growth
19.  Radiation Dose in the Thyroid and the Thyroid Cancer Risk Attributable to CT Scans for Pediatric Patients in One General Hospital of China 
Objective: To quantify the radiation dose in the thyroid attributable to different CT scans and to estimate the thyroid cancer risk in pediatric patients. Methods: The information about pediatric patients who underwent CT scans was abstracted from the radiology information system in one general hospital between 1 January 2012 and 31 December 2012. The radiation doses were calculated using the ImPACT Patient Dosimetry Calculator and the lifetime attributable risk (LAR) of thyroid cancer incidence was estimated based on the National Academies Biologic Effects of Ionizing Radiation VII model. Results: The subjects comprised 922 children, 68% were males, and received 971 CT scans. The range of typical radiation dose to the thyroid was estimated to be 0.61–0.92 mGy for paranasal sinus CT scans, 1.10–2.45 mGy for head CT scans, and 2.63–5.76 mGy for chest CT scans. The LAR of thyroid cancer were as follows: for head CT, 1.1 per 100,000 for boys and 8.7 per 100,000 for girls; for paranasal sinus CT scans, 0.4 per 100,000 for boys and 2.7 per 100,000 for girls; for chest CT scans, 2.1 per 100,000 for boys and 14.1 per 100,000 for girls. The risk of thyroid cancer was substantially higher for girls than for the boys, and from chest CT scans was higher than that from head or paransal sinus CT scans. Conclusions: Chest CT scans caused higher thyroid dose and the LAR of thyroid cancer incidence, compared with paransal sinus or head CT scans. Therefore, physicians should pay more attention to protect the thyroid when children underwent CT scans, especially chest CT scans.
doi:10.3390/ijerph110302793
PMCID: PMC3987004  PMID: 24608902
cancer risk; pediatric CT; radiation dose
20.  Association between Soy Isoflavone Intake and Breast Cancer Risk for Pre- and Post-Menopausal Women: A Meta-Analysis of Epidemiological Studies 
PLoS ONE  2014;9(2):e89288.
Background
Conclusions drawn from meta-analyses on the association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women are not fully consistent. These meta-analyses did not explore the influence of different study designs on the pooled results on the basis of distinguishing between pre- and post-menopausal women.
Methodology and Principal Findings
We performed a meta-analysis of 35 studies which reported results of association between soy isoflavone intake and breast cancer risk for pre- and/or post-menopausal women, calculated pooled odds ratios and their 95% confidence intervals of pre- and post-menopausal women respectively, and further explored soy isoflavone-breast cancer association on the basis of considering different study regions and designs. Summary results suggested that soy isoflavone intake has a protective effect against breast cancer for both pre- and post-menopausal women. However, they are influenced by study design and region. Pooled ORs of studies carried out in Asian countries suggested that soy isoflavone’s protective effect exist in both pre- and post-menopausal women (OR = 0.59, 95%CI: 0.48–0.69 for premenopausal women; OR = 0.59, 95%CI: 0.44–0.74 for postmenopausal women). However, there are some differences between the results pooled from different study designs for women in Asian countries (test for consistency, P = 0.04). Pooled OR of studies on postmenopausal women in Western countries suggested that soy isoflavone intake has a marginally significant protective effect (OR = 0.92; 95%CI: 0.83∼1.00), but further analyses stratifying by study design found no statistically significant association.
Conclusions
We meta-analyzed more and newer research results, and separated women according to menopausal status to explore soy isoflavone-breast cancer association. We founded that soy isoflavone intake could lower the risk of breast cancer for both pre- and post-menopausal women in Asian countries. However, for women in Western countries, pre- or post-menopausal, there is no evidence to suggest an association between intake of soy isoflavone and breast cancer.
doi:10.1371/journal.pone.0089288
PMCID: PMC3930722  PMID: 24586662
21.  Decreased Galectin-9 and Increased Tim-3 Expression Are Related to Poor Prognosis in Gastric Cancer 
PLoS ONE  2013;8(12):e81799.
Introduction
Galectin-9 (Gal-9) induces adhesion and aggregation of certain cell types and inhibits the metastasis of tumor cells. T-cell immunoglobulin–and mucin domain-3–containing molecule 3 (TIM-3) plays a pivotal role in immune regulation. The aim of this study is to investigate Gal-9 and TIM-3 alterations in gastric cancer and their prognostic values.
Methods
Gal-9 and Tim-3 expression was evaluated using a tissue microarray immunohistochemistry method in 305 gastric cancers, of which 84 had paired adjacent normal samples. Cell lines SGC-7901, BGC-823, MGC-803, MKN45 and GES-1 were also stained. Correlations were analyzed between expression levels of Gal-9 and Tim-3 protein and tumor parameters or clinical outcomes.
Results
Gal-9 and Tim-3 stained positive on tumor cells in 86.2% (263/305), and 60.0% (183/305) patients with gastric cancer, respectively. Gal-9 expression was significantly higher in cancer than in normal mucosa (P<0.001). Reduced Gal-9 expression was associated with lymph-vascular invasion, lymph node metastasis, distant metastasis and worse TNM staging (P = 0.034, P = 0.009, P = 0.002 and P = 0.043, respectively). In contrast, Tim-3 expression was significantly lower in cancer than in control mucosa (P<0.001). Patients with lymph-vascular invasion had higher expression levels of Tim-3 (P<0.001). Moreover, multivariate analysis shows that both high Gal-9 expression and low Tim-3 expression were significantly associated with long overall survival (P = 0.002, P = 0.010, respectively); the combination of Gal-9 and Tim-3 expression was an independent prognostic predictor for patients with gastric cancer (RR: 0.43; 95%CI: 0.20–0.93). H.pylori infection status was not associated with Gal-9 and Tim-3 expression (P = 0.102, P = 0.565).
Conclusion
The results suggest that expression of Gal-9 and Tim-3 in tumor cells may be a potential, independent prognostic factor for patients with gastric cancer. Gal-9 and TIM-3 may play an important part in the gastric carcinogenesis.
doi:10.1371/journal.pone.0081799
PMCID: PMC3858245  PMID: 24339967
22.  Recognition of methylated DNA by TAL effectors 
Cell Research  2012;22(10):1502-1504.
doi:10.1038/cr.2012.127
PMCID: PMC3463267  PMID: 22945353
23.  Peptidomic Analyses of Mouse Astrocytic Cell Lines and Rat Primary Cultured Astrocytes 
Journal of proteome research  2012;11(8):3965-3973.
Astrocytes play an active role in the modulation of synaptic transmission by releasing cell-cell signaling molecules in response to various stimuli that evoke a Ca2+ increase. We expand on recent studies of astrocyte intracellular and secreted proteins by examining the astrocyte peptidome in mouse astrocytic cell lines and rat primary cultured astrocytes, as well as those peptides secreted from mouse astrocytic cell lines in response to Ca2+-dependent stimulations. We identified 57 peptides derived from 24 proteins with LC–MS/MS and CE–MS/MS in the astrocytes. Among the secreted peptides, four peptides derived from elongation factor 1, macrophage migration inhibitory factor, peroxiredoxin-5, and galectin-1, were putatively identified by mass-matching to peptides confirmed to be found in astrocytes. Other peptides in the secretion study were mass-matched to those found in prior peptidomics analyses on mouse brain tissue. Complex peptide profiles were observed after stimulation, suggesting that astrocytes are actively involved in peptide secretion. Twenty-six peptides were observed in multiple stimulation experiments but not in controls and thus appear to be released in a Ca2+-dependent manner. These results can be used in future investigations to better understand stimulus-dependent mechanisms of astrocyte peptide secretion.
doi:10.1021/pr201066t
PMCID: PMC3434970  PMID: 22742998
glia; astrocytes; secreted peptides; peptidomics; LC–MS; CE–MS; Ca2+-dependent stimulation
24.  High Duty Cycle to Low Duty Cycle: Echolocation Behaviour of the Hipposiderid Bat Coelops frithii 
PLoS ONE  2013;8(5):e62938.
Laryngeally echolocating bats avoid self-deafening (forward masking) by separating pulse and echo either in time using low duty cycle (LDC) echolocation, or in frequency using high duty cycle (HDC) echolocation. HDC echolocators are specialized to detect fluttering targets in cluttered environments. HDC echolocation is found only in the families Rhinolophidae and Hipposideridae in the Old World and in the New World mormoopid, Pteronotus parnellii. Here we report that the hipposiderid Coelops frithii, ostensibly an HDC bat, consistently uses an LDC echolocation strategy whether roosting, flying, or approaching a fluttering target rotating at 50 to 80 Hz. We recorded the echolocation calls of free-flying C. frithii in the field in various situations, including presenting bats with a mechanical fluttering target. The echolocation calls of C. frithii consisted of an initial narrowband component (0.5±0.3 ms, 90.6±2.0 kHz) followed immediately by a frequency modulated (FM) sweep (194 to 113 kHz). This species emitted echolocation calls at duty cycles averaging 7.7±2.8% (n = 87 sequences). Coelops frithii approached fluttering targets more frequently than did LDC bats (C.frithii, approach frequency  = 40.4%, n = 80; Myotis spp., approach frequency  = 0%, n = 13), and at the same frequency as sympatrically feeding HDC species (Hipposideros armiger, approach rate  = 53.3%, n = 15; Rhinolophus monoceros, approach rate  = 56.7%, n = 97). We propose that the LDC echolocation strategy used by C. frithii is derived from HDC ancestors, that this species adjusts the harmonic contents of its echolocation calls, and that it may use both the narrowband component and the FM sweep of echolocations calls to detect fluttering targets.
doi:10.1371/journal.pone.0062938
PMCID: PMC3663840  PMID: 23717396
25.  Increasing trends in central obesity among Chinese adults with normal body mass index, 1993–2009 
BMC Public Health  2013;13:327.
Background
Central obesity is thought to be more pathogenic than overall obesity and studies have shown that the association between waist circumference (WC) and mortality was strongest in those with a normal body mass index (BMI). The objective of our study was to determine secular trends in the prevalence of central obesity (WC ≥ 90 cm for men and ≥ 80 cm for women) among Chinese adults with normal BMI from 1993 to 2009 and to examine the impact of performance of combined BMI and WC on the prevalence of obesity in Chinese adults.
Methods
We used data from the China Health and Nutrition Survey (CHNS) conducted from 1993 to 2009. From which we included a total of 52023 participants aged ≥ 18 years.
Results
The age-standardized prevalence of central obesity among Chinese adults with BMI < 25 kg/m2 increased from 11.9% in 1993 to 21.1% in 2009 (P for linear trend <0.001). The upward trends were noted in both genders, all ages, rural/urban settings, and education groups (all P for linear trend <0.001), with greater increments in men, participants aged 18–64 years, and rural residents (P for interaction terms survey × sex, survey × age, and survey × rural/urban settings were 0.042, 0.003, and < 0.001, respectively). Trends in the prevalence of central obesity were similar when a more stringent BMI < 23 kg/m2 cut point (Asian cut point) was applied. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. More than 65% individuals with obesity would be missed if solely BMI was measured.
Conclusions
We observed an upward trend in the prevalence of central obesity among participants with normal BMI irrespective of sex, age, rural/urban settings, and education level. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. Approximately two thirds of the individuals with obesity would be missed if WC was not measured. It is, therefore, urgent to emphasize the importance of WC as a measure to monitor the prevalence of obesity.
doi:10.1186/1471-2458-13-327
PMCID: PMC3626835  PMID: 23575244
Body mass index; Waist circumference; Central obesity; General obesity; CHNS

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