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1.  Molecular footprints of domestication and improvement in soybean revealed by whole genome re-sequencing 
BMC Genomics  2013;14:579.
Background
Artificial selection played an important role in the origin of modern Glycine max cultivars from the wild soybean Glycine soja. To elucidate the consequences of artificial selection accompanying the domestication and modern improvement of soybean, 25 new and 30 published whole-genome re-sequencing accessions, which represent wild, domesticated landrace, and Chinese elite soybean populations were analyzed.
Results
A total of 5,102,244 single nucleotide polymorphisms (SNPs) and 707,969 insertion/deletions were identified. Among the SNPs detected, 25.5% were not described previously. We found that artificial selection during domestication led to more pronounced reduction in the genetic diversity of soybean than the switch from landraces to elite cultivars. Only a small proportion (2.99%) of the whole genomic regions appear to be affected by artificial selection for preferred agricultural traits. The selection regions were not distributed randomly or uniformly throughout the genome. Instead, clusters of selection hotspots in certain genomic regions were observed. Moreover, a set of candidate genes (4.38% of the total annotated genes) significantly affected by selection underlying soybean domestication and genetic improvement were identified.
Conclusions
Given the uniqueness of the soybean germplasm sequenced, this study drew a clear picture of human-mediated evolution of the soybean genomes. The genomic resources and information provided by this study would also facilitate the discovery of genes/loci underlying agronomically important traits.
doi:10.1186/1471-2164-14-579
PMCID: PMC3844514  PMID: 23984715
Artificial selection; Evolution; Genetic diversity; Population genomics; Soybean
2.  The Bsister MADS Gene FST Determines Ovule Patterning and Development of the Zygotic Embryo and Endosperm 
PLoS ONE  2013;8(3):e58748.
Many homeotic MADS-box genes have been identified as controllers of the floral transition and floral development. However, information regarding Bsister (Bs)-function genes in monocots is still limited. Here, we describe the functional characterization of a Bs-group MADS-box gene FEMALE-STERILE (FST), whose frame-shift mutation (fst) results in abnormal ovules and the complete abortion of zygotic embryos and endosperms in rice. Anatomical analysis showed that the defective development in the fst mutant exclusively occurred in sporophytic tissues including integuments, fertilized proembryos and endosperms. Analyses of the spatio-temporal expression pattern revealed that the prominent FST gene products accumulated in the inner integument, nucellar cell of the micropylar side, apical and base of the proembryos and free endosperm nuclei. Microarray and gene ontology analysis unraveled substantial changes in the expression level of many genes in the fst mutant ovules and seeds, with a subset of genes involved in several developmental and hormonal pathways appearing to be down-regulated. Using both forward and reverse genetics approaches, we demonstrated that rice FST plays indispensable roles and multiple functions during ovule and early seed development. These findings support a novel function for the Bs-group MADS-box genes in plants.
doi:10.1371/journal.pone.0058748
PMCID: PMC3602522  PMID: 23527017
3.  Factors Associated with Myopia in School Children in China: The Beijing Childhood Eye Study 
PLoS ONE  2012;7(12):e52668.
Purpose
To assess factors associated with myopia in school children in rural and urban parts of Greater Beijing.
Methods
The Beijing Pedriatic Eye Study was a population-based cross-sectional study, in which one school of each level (primary, junior high, senior high) was randomly selected from nine randomly selected districts out of 18 districts of Greater Beijing. The children underwent non-cylcoplegic refractometry and their parents an interview.
Results
Of 16,771 eligible students, 15,066 (89.8%) children (7,769 (51.6%) girls) participated, with 8,860 (58.8%) participants living in the rural region. Mean age was 13.2±3.4 years (range:7–18 years). In multivariate analysis, prevalence of myopia (defined as ≤−1.00 diopters) was associated with higher age (Odds ratio(OR):1.37; 95% confidence interval(CI):1.35,1.39), female gender (OR:1.35;95%CI:1.25,1.47), key school type (OR:0.77;95%CI: 0.70,0.85), higher family income (OR:1.04;95%CI:1.01,1.07), parental myopia (OR:1.46;95%CI:1.40,1.53), dim reading illumination (OR:0.93;95%CI: 0.88,0.98), longer daily studying duration (OR:1.10;95%CI:1.06,1.15), shorter duration of watching television (or computer) (OR:0.93;95%CI:0.89,0.97), higher self-reported protein intake (OR:0.94;95%CI:0.90,0.99), feeling well about life and status (OR:0.93;95%CI:0.89,0.98), and feeling tired or dizzy (OR:0.94;95%CI:0.91,0.97). Prevalence of high myopia (defined as ≤−6.00 diopters) was associated with higher age (OR:1.43;95%CI:1.38, 1.48), key school type (OR:0.61;95%CI:0.49,0.74), family income (OR:1.07;95%CI:1.02,1.13), parental myopia (OR:1.65;95%CI:1.54,1.76), dim reading illumination (OR:0.86;95%CI:0.77,0.96), less rest during studying (OR:1.18;95%CI:1.10,1.27), feeling well about life and studying (OR:0.88;95%CI: 0.81,0.96) and feeling dizzy or tired (OR:0.93;95%CI:0.87,0.99). Prevalence of high myopia (defined as ≤−8.00 diopters) was significantly associated with higher age (OR:1.39;95%CI:1.31,1.48;), key school type (OR:0.61;95%CI:0.42,0.88) and parental myopia (OR:1.87;95%CI:1.66,2.12).
Conclusions
Myopia in school children in Greater Beijing was associated with higher age, female gender, school type, parental myopia, higher socioeconomic background, dim reading illumination, longer daily studying duration, less rest during study, shorter duration of watching television (or computer), higher self-reported protein intake, feeling well about life and status, and feeling tired and dizzy.
doi:10.1371/journal.pone.0052668
PMCID: PMC3531363  PMID: 23300738
4.  Draft Genome Sequence of a Rhodococcus Strain Isolated from Tannery Wastewater Treatment Sludge 
Genome Announcements  2015;3(1):e01463-14.
Rhodococcus sp. Chr-9 can degrade pyridine in the presence of chromate. Its draft genome sequence revealed that strain Chr-9 harbors sets of genes for resistance to heavy metals such as lead, mercury, arsenate, and cobalt, as well as three different gene clusters for metabolizing aromatic compounds, such as phenol, benzoate, and 4-nitrophenol.
doi:10.1128/genomeA.01463-14
PMCID: PMC4319503  PMID: 25635009
5.  MiR-203 Suppresses ZNF217 Upregulation in Colorectal Cancer and Its Oncogenicity 
PLoS ONE  2015;10(1):e0116170.
Zinc finger protein 217 (ZNF217) is essential for cell proliferation and has been implicated in tumorigenesis. However, its expression and exact roles in colorectal cancer (CRC) remain unclear. In this study, we demonstrated that ZNF217 expression was aberrantly upregulated in CRC tissues and associated with poor overall survival of CRC patients. In addition, we found that ZNF217 was a putative target of microRNA (miR)-203 using bioinformatics analysis and confirmed that using luciferase reporter assay. Moreover, in vitro knockdown of ZNF217 or enforced expression of miR-203 attenuated CRC cell proliferation, invasion and migration. Furthermore, combined treatment of ZNF217 siRNA and miR-203 exhibited synergistic inhibitory effects. Taken together, our results provide new evidences that ZNF217 has an oncogenic role in CRC and is regulated by miR-203, and open up the possibility of ZNF217- and miR-203-targeted therapy for CRC.
doi:10.1371/journal.pone.0116170
PMCID: PMC4306553  PMID: 25621839
6.  A Truncated NLR Protein, TIR-NBS2, Is Required for Activated Defense Responses in the exo70B1 Mutant 
PLoS Genetics  2015;11(1):e1004945.
During exocytosis, the evolutionarily conserved exocyst complex tethers Golgi-derived vesicles to the target plasma membrane, a critical function for secretory pathways. Here we show that exo70B1 loss-of-function mutants express activated defense responses upon infection and express enhanced resistance to fungal, oomycete and bacterial pathogens. In a screen for mutants that suppress exo70B1 resistance, we identified nine alleles of TIR-NBS2 (TN2), suggesting that loss-of-function of EXO70B1 leads to activation of this nucleotide binding domain and leucine-rich repeat-containing (NLR)-like disease resistance protein. This NLR-like protein is atypical because it lacks the LRR domain common in typical NLR receptors. In addition, we show that TN2 interacts with EXO70B1 in yeast and in planta. Our study thus provides a link between the exocyst complex and the function of a ‘TIR-NBS only’ immune receptor like protein. Our data are consistent with a speculative model wherein pathogen effectors could evolve to target EXO70B1 to manipulate plant secretion machinery. TN2 could monitor EXO70B1 integrity as part of an immune receptor complex.
Author Summary
Secretory pathways play an important role in the plant immune response by delivering antimicrobial compounds and metabolites to the site of infection. The evolutionarily conserved exocyst complex is involved in exocytosis, the final step in the secretory pathway. We showed that loss of the function of EXO70B1, a subunit of exocyst complex, results in activated defense responses, and enhanced resistance to a range of pathogens. We found that EXO70B1 associates with the SNARE complex protein SNAP33, which is involved in focal secretion of defense-related proteins. Enhanced disease resistance and cell death in the exo70B1 mutant are dependent on TIR-NBS2 (TN2), an atypical intracellular immune receptor-like protein that lacks leucine-rich repeats. TN2 physically associates with EXO70B1, and TN2 transcripts accumulate at much higher levels in the exo70B1 mutant. These data are consistent with a model where activation of a receptor pathway containing TIR-NBS2 is responsible for activated defense responses and cell death in exo70B1. Our data further suggest that this, and possibly other, exocyst components could be targets of effectors that are guarded by immune receptors.
doi:10.1371/journal.pgen.1004945
PMCID: PMC4305288  PMID: 25617755
7.  Employment and financial burden of families with preschool children diagnosed with autism spectrum disorders in urban China: results from a descriptive study 
BMC Psychiatry  2015;15:3.
Background
Autism spectrum disorder (ASD) affects many aspects of family life, such as social and economic burden. Little investigation of this phenomenon has been carried out in China. We designed this study to evaluate the employment and financial burdens of families with ASD-diagnosed preschoolers.
Methods
Four hundred and fifty-nine nuclear families of children with ASD, 418 with some other disability (OD) and 424 with typically developing (TD) children were recruited for this study. Employment and financial burdens of families were evaluated using a structured questionnaire; logistic regression was used to examine differences in job change measures by group, and ordinal logistic regression was used to investigate the association between household income and group.
Results
Fifty-eight percent of families with ASD children and 19% of families with OD children reported that childcare problems had greatly affected their employment decisions, compared with 9% of families with TD children (p < 0.001). Age of child, parental education and parental age notwithstanding, having a child with ASD and having a child with OD were both associated with increased odds of reporting that childcare greatly interfered with employment (ASD, OR: 15.936; OD, OR: 2.502; all p < 0.001) and decreased the odds of living in a higher-income household (ASD, estimate = -1.271; OD, estimate = -0.569; all p < 0.001). The average loss of annual income associated with having a child with ASD was Chinese RenMinBi (RMB) 44,077 ($7,226), compared with RMB 20,788 ($3,408) for families of OD children.
Conclusions
ASD is associated with severe employment and financial burdens, much more than for OD, in families with preschool children.
doi:10.1186/s12888-015-0382-4
PMCID: PMC4307683  PMID: 25608486
Employment burden; Financial burden; Autism spectrum disorder; Chinese
8.  Genome Sequence of an Extensively Drug-Resistant Strain of Klebsiella pneumoniae, Strain YN-1, with Carbapenem Resistance 
Genome Announcements  2015;3(1):e01279-14.
The emergence and spread of multidrug-resistant (MDR) Klebsiella pneumoniae has been regarded as one of the major challenges among health care-associated infections worldwide. Here, we report the draft genome sequence of an extensively drug-resistant (XDR) K. pneumoniae strain isolated in 2013 from Yunnan Province, China.
doi:10.1128/genomeA.01279-14
PMCID: PMC4290976  PMID: 25573939
9.  Downregulated Krüppel-Like Factor 8 Is Involved in Decreased Trophoblast Invasion Under Hypoxia–Reoxygenation Conditions 
Reproductive Sciences  2014;21(1):72-81.
Krüppel-like factor 8 (KLF8) is a pivotal transcription factor expressed in the human placenta that can regulate cell invasion. The objective of this study was to assess whether a hypoxia–reoxygenation (H/R) environment affects placental KLF8 expression levels and subcellular localization and to evaluate the relationship between KLF8 levels and trophoblast invasion activity. Human first trimester villous tissues from normal pregnancies and third trimester placentas from pregnancies with or without preeclampsia (PE) were used for the detection of KLF8 expression and correlating its levels with metalloproteinase 9 (MMP-9) expression. In addition, HTR8/SVneo cells were used to mimic the effects of an H/R environment on placentas to study KLF8 expression and trophoblast invasion. The KLF8 levels, MMP-9 levels, and trophoblast invasion were similarly altered; the levels peaked at 8 to 10 weeks of gestation and declined thereafter along with oxygen tension increased from hypoxia to normoxia during early pregnancy, decreased in third trimester placentas from PE pregnancies featured by repeated H/R and HTR8/SVneo cells exposed to H/R compared with the control. Moreover, a visible reduction in KLF8 immunoreactivity was present in the nuclei of cytotrophoblast cells in human villous tissues at 11 weeks, and partial cytoplasmic accumulation of KLF8 was observed in HTR8/SVneo cells treated with H/R. In conclusion, these findings strongly suggest that H/R reduces the expression and nuclear localization of KLF8 to inhibit the trophoblast invasion by downregulating MMP-9 levels. The KLF8 may play a vital role in the pathogenesis of PE as a novel oxygen tension sensor.
doi:10.1177/1933719113488448
PMCID: PMC3857762  PMID: 23703536
hypoxia–reoxygenation; preeclampsia; KLF8; MMP-9; HTR8/SVneo
10.  Moderate Hypothermia Inhibits Brain Inflammation and Attenuates Stroke-induced Immunodepression in Rats 
CNS neuroscience & therapeutics  2013;20(1):10.1111/cns.12160.
Summary
Aims
Stroke causes both brain inflammation and immunodepression. Mild to moderate hypothermia is known to attenuate brain inflammation but its role in stroke-induced immunodepression (SIID) of the peripheral immune system remains unknown. This study investigated the effects in rats of moderate intra-ischemic hypothermia on SIID and brain inflammation.
Methods
Stroke was induced in rats by permanent distal MCA occlusion combined with transient bilateral CCA occlusion while body temperature was reduced to 30°C. Real-time PCR, flow cytometry, in vitro T cell proliferation assays and confocal microscopy were used to study SIID and brain inflammation.
Results
Brief Intra-Ischemic hypothermia helped maintain certain leukocytes in the peripheral blood and spleen, and enhanced T cell proliferation in vitro and delayed-type hypersensitivity in vivo, suggesting that hypothermia reduces SIID. In contrast, in the brain, brief intra-Ischemic hypothermia inhibited mRNA expression of anti-inflammatory cytokine IL-10 and pro-inflammatory cytokines INF-γ, TNF-α, IL-2, IL-1β and MIP-2. Brief intra-Ischemic hypothermia also attenuated the infiltration of lymphocytes, neutrophils (MPO+ cells) and macrophages (CD68+ cells) into the ischemic brain, suggesting that hypothermia inhibited brain inflammation.
Conclusions
Brief intra-ischemic hypothermia attenuated SIID and protected against acute brain inflammation.
doi:10.1111/cns.12160
PMCID: PMC3867545  PMID: 23981596
focal cerebral ischemia; hypothermia; inflammation; immunodepression; leukocytes
11.  Association between the Functional Polymorphism of Vascular Endothelial Growth Factor Gene and Breast Cancer: A Meta-Analysis 
The vascular endothelial growth factor (VEGF) gene single-nucleotide polymorphism involved in the regulation of the protein levels has been implicated in breast cancer. However, the published studies have produced contentious and controversial results. Herein, we performed a meta-analysis (from January to October 2013); to further evaluate the association between +936 C/T polymorphism and the risk of breast cancer. By searching the EMBASE, PubMed, and Web of Science databases, we identified a total of 12 case-control studies with 8,979 cancer patients and 9,180 healthy controls. The strength of the association was assessed using Odds Ratios (ORs) with 95% Confidence Intervals (CI). We found no evidence indicating that the allelic model or the genotype models of +936 C/T polymorphism were associated with the risk of breast cancer in total population (ORCC vs. TT=1.01, 95% CI=0.96-1.06, Ph=1.00; ORCC+CT vs. TT=1.00, 95% CI=0.96-1.05, Ph=1.00; ORCC vs. CT+TT=1.02, 95% CI=0.98-1.07, Ph=0.94; OR allele C vs. allele T=1.01, 95% CI=0.98-1.04, Ph=0.99; ORCT vs. TT=1.01, 95% CI=0.93-1.09, Ph=1.00). Such lack of association with breast cancer was also observed in subgroup analyses according to ethnicity as well as in the analysis by source of controls. In conclusion, this meta-analysis suggests that the functionally important +936 C/T polymorphism may not be associated with breast cancer risk. Larger well-designed studies with gene-to-gene and gene-to-environment interactions are clearly required to validate the results further.
PMCID: PMC4300476  PMID: 25649829
Vascular endothelial growth factor A; Breast neoplasms; Polymorphism; Risk
12.  Genome Sequence of a Pandrug-Resistant Pseudomonas aeruginosa Strain, YN-1 
Genome Announcements  2014;2(6):e01280-14.
A highly rampant multidrug-resistant strain of Pseudomonas aeruginosa appeared in a hospital in Yunnan Province, China. Here, we report the genome sequence of the pandrug-resistant (PDR) P. aeruginosa strain recovered from a patient in 2013.
doi:10.1128/genomeA.01280-14
PMCID: PMC4276817  PMID: 25540339
13.  Eosinophilic chronic rhinosinusitis in East Asians 
Chronic rhinosinusitis (CRS) is a common disease worldwide, with a prevalence rate of 5%-15% in the general population. CRS is currently classified into two types: CRS with and without nasal polyps. CRS may also be divided into eosinophilic CRS (ECRS) and non-ECRS subtypes based on the presence of tissue eosinophilic infiltration or not. There are significant geographic and ethnic differences in the tissue eosinophilic infiltration, which is predominant in Western white patients and less common in East Asians, despite an increasing tendency for its prevalence in East Asia countries. ECRS differs significantly from non-ECRS in clinical characteristics, treatment outcomes and strategies, and underlying pathogenic mechanisms. ECRS commonly demonstrates more severe symptoms, polyp diseases with a higher incidence of bilateral polyps and sinonasal diseases on computed tomography, and the increase in blood eosinophils. ECRS is considered a special and recalcitrant subtype of CRS, commonly with poor treatment outcomes compared to non-ECRS. The differentiation of specific subtypes and clinical features of CRS will be important for developing novel treatment strategies and improving treatment outcomes for individual phenotypes of CRS. This review discusses clinical features, diagnosis, treatment and prognosis of ECRS in East Asians.
doi:10.12998/wjcc.v2.i12.873
PMCID: PMC4266836  PMID: 25516863
Chronic rhinosinusitis; Eosinophilic chronic rhinosinusitis; Eosinophils; Chronic rhinosinusitis with nasal polyps; Nasal polyps
14.  Mental wellbeing amongst younger and older migrant workers in comparison to their urban counterparts in Guangzhou city, China: a cross-sectional study 
BMC Public Health  2014;14(1):1280.
Background
There has been a dramatic increase in internal migrant workers in China over recent decades, and there is a recent concern of poor mental health particularly amongst younger or “new generation” migrants who were born in 1980 or later.
Methods
A cross-sectional study was conducted in Guangzhou city between May and July in 2012. Mental wellbeing was measured using the World Health Organization Five-item Well-Being Index Scale and the 36 Item Short Form Health Survey mental health scale. Linear and logistic regression models were used to investigate the differences between migrant workers and their urban counterparts and between younger and older migrants.
Results
Migrant workers (n = 914) showed a small but significant advantage in mental wellbeing compared to their urban counterparts (n = 814). There was some evidence for age modification effect (p for interaction = 0.055-0.095); better mental wellbeing in migrants than urbanites were mainly seen in the older compared to the younger group, and the difference attenuated somewhat after controlling for income satisfaction. Older migrants showed better mental health than younger migrants. Factors that were independently associated with poor mental health in migrants included being male, longer working hours, and income dissatisfaction, whilst older age, factory job, high income, and increased use of social support resources were associated with reduced risk.
Conclusions
Efforts to promote mental health amongst migrant workers may be usefully targeted on younger migrants and include measures aimed to improve working conditions, strengthen the social support network, and address age-specific needs.
doi:10.1186/1471-2458-14-1280
PMCID: PMC4301935  PMID: 25510169
China; Guangzhou; Migration; Mental health; Wellbeing; SF-36; WHO-5
15.  Deficiency of Kruppel-like factor KLF4 in mammary tumor cells inhibits tumor growth and pulmonary metastasis and is accompanied by compromised recruitment of myeloid-derived suppressor cells 
Increasing evidence indicates that myeloid-derived suppressor cells (MDSCs) negatively regulate immune responses during tumor progression, inflammation and infection. However, the underlying molecular mechanisms of their development and mobilization remain to be fully delineated. Kruppel-like factor KLF4 is a transcription factor that has an oncogenic function in breast cancer development, but its function in tumor microenvironment, a critical component for tumorigenesis, has not been examined. By using a spontaneously metastatic 4T1 breast cancer mouse model and an immunodeficient NOD/SCID mouse model, we demonstrated that KLF4 knockdown delayed tumor development and inhibited pulmonary metastasis, which was accompanied by decreased accumulation of MDSCs in bone marrow, spleens and primary tumors. Mechanistically, we found that KLF4 knockdown resulted in a significant decrease of circulating GM-CSF, an important cytokine for MDSC biology. Consistently, recombinant GM-CSF restored the frequency of MDSCs in purified bone marrow cells incubated with conditioned medium from KLF4 deficient cells. In addition, we identified CXCL5 as a critical mediator to enhance the expression and function of GM-CSF. Reduced CXCL5 expression by KLF4 knockdown in primary tumors and breast cancer cells was correlated with a decreased GM-CSF expression in our mouse models. Finally, we found that CXCL5/CXCR2 axis facilitated MDSC migration and that anti-GM-CSF antibodies neutralized CXCL5-induced accumulation of MDSCs. Taken together, our data suggest that KLF4 modulates maintenance of MDSCs in bone marrow by inducing GM-CSF production via CXCL5 and regulates recruitment of MDSCs into the primary tumors through the CXCL5/CXCR2 axis, both of which contribute to KLF4-mediated mammary tumor development.
doi:10.1002/ijc.28302
PMCID: PMC3796127  PMID: 23737434
KLF4; Myeloid-derived suppressor cells; Tumor development; GM-CSF; CXCL5
16.  Fine scale Spatial-temporal cluster analysis for the infection risk of Schistosomiasis japonica using space-time scan statistics 
Parasites & Vectors  2014;7(1):578.
Background
Marching towards the elimination of schistosomiasis in China, both the incidence and prevalence have witnessed profound decline over the past decades, with the strategy shifting from morbidity control to transmission control. The current challenge is to find out hotspots of transmission risk for precise targeted control in low-prevalence areas. This study assessed the risk at the village level, using the spatial and temporal characteristics of Schistosomiasis japonica in Anhui province from 2006 to 2012.
Method
The comprehensive database was generated from annual surveillance data at village level in Anhui province between 2006 and 2012, comprising schistosomiasis prevalence among humans and cattle, occurrence rate of infected environments and incidence rate of acute schistosomiasis. The database parameters were matched with geographic data of the study area and fine scale spatial-temporal cluster analysis based on retrospective space-time scan statistics was used to assess the clustering pattern of schistosomiasis. The analysis was conducted by using SaTScan 9.1.1 and ArcGIS 10.0. A spatial statistical modelling was carried out to determine the spatial dependency of prevalence of human infection by using Geoda 1.4.3.
Result
A pronounced decline was found in the prevalence of human infection, cattle infection, occurrence rate of environment with infected vector snails and incidence rate of acute schistosomiasis from 2006 to 2012 by 48.6%, 71.5%, 91.9% and 96.4%, respectively. Meanwhile, all 4 indicators showed a statistically significant clustering pattern both in time and space, with a total of 16, 6, 8 and 4 corresponding clustering foci found respectively. However, the number of clustering foci declined with time, and none was found after year 2010. All clustering foci were mainly distributed along the Yangtze River and its connecting branches. The result shows that there is a direct spatial relationship between prevalence of human infection and the other indicators.
Conclusion
A decreasing trend in space-time clustering of schistosomiasis endemic status was observed between 2006 and 2012 in Anhui province. Nevertheless, giving the complexity in schistosomiasis control, areas within the upper-stream of Yangtze River in Anhui section and its connecting branches should be targeted for effective implementation of control strategies in the future.
doi:10.1186/s13071-014-0578-3
PMCID: PMC4273478  PMID: 25491192
Fine scale spatial-temporal scan statistics; Schistosomiasis japonica; Infection risk analysis; Anhui province
17.  Bacterial dynamics within the mucus, tissue and skeleton of the coral Porites lutea during different seasons 
Scientific Reports  2014;4:7320.
Investigation of the response of coral microbial communities to seasonal ecological environment at the microscale will advance our understanding of the relationship between coral-associated bacteria community and coral health. In this study, we examined bacteria community composition from mucus, tissue and skeleton of Porites lutea and surrounding seawater every three months for 1 year on Luhuitou fringing reef. The bacterial communities were analyzed using pyrosequencing of the V1-V2 region of the 16S rRNA gene, which demonstrated diverse bacterial consortium profiles in corals. The bacterial communities in all three coral compartments studied were significantly different from the surrounding seawater. Moreover, they had a much more dynamic seasonal response compared to the seawater communities. The bacterial communities in all three coral compartments collected in each seasonal sample tended to cluster together. Analysis of the relationship between bacterial assemblages and the environmental parameters showed that the bacterial community correlated to dissolved oxygen and rainfall significantly at our study site. This study highlights a dynamic relationship between the high complexity of coral associated bacterial community and seasonally varying ecosystem parameters.
doi:10.1038/srep07320
PMCID: PMC4256709  PMID: 25475855
18.  Intervention-induced enhancement in intrinsic brain activity in healthy older adults 
Scientific Reports  2014;4:7309.
This study examined the effects of a multimodal intervention on spontaneous brain activity in healthy older adults. Seventeen older adults received a six-week intervention that consisted of cognitive training, Tai Chi exercise, and group counseling, while 17 older adults in a control group attended health knowledge lectures. The intervention group demonstrated enhanced memory and social support compared to the control group. The amplitude of low frequency fluctuations (ALFF) in the middle frontal gyrus, superior frontal gyrus, and anterior cerebellum lobe was enhanced for the intervention group, while the control group showed reduced ALFF in these three regions. Moreover, changes in trail-making performance and well-being could be predicted by the intervention-induced changes in ALFF. Additionally, individual differences in the baseline ALFF were correlated with intervention-related changes in behavioral performance. These findings suggest that a multimodal intervention is effective in improving cognitive functions and well-being and can induce functional changes in the aging brain. The study extended previous training studies by suggesting resting-state ALFF as a marker of intervention-induced plasticity in older adults.
doi:10.1038/srep07309
PMCID: PMC4255189  PMID: 25472002
19.  Mental health training program for community mental health staff in Guangzhou, China: effects on knowledge of mental illness and stigma 
Background
In order to reduce the huge treatment gap in mental health, WHO has called for integrating mental health into primary care. The purposes of this study are to provide a training course to improve the community mental health staff’s knowledge of mental health and reduce stigma related to mental illness, as well as to evaluate the impact of this training on knowledge and stigma.
Methods
The training intervention was a one day course for community mental health staff in Guangzhou, China. Evaluation questionnaires were given before and after the training session. Mental health knowledge was assessed using two vignettes. Stigma was evaluated by the Mental Illness: Clinicians’ Attitudes Scale (MICA) and the Reported and Intended Behavior Scale (RIBS).
Results
A total of 99 community mental health staff from eight regions in Guangzhou, China were recruited for the study. The training course did not lead to a significant improvement of participants’ levels of mental health knowledge. The mean score of MICA decreased from 47.92 ± 8.63 to 43.53 ± 9.61 after the training (t = 6.64, P < 0.001). As for the RIBS, the mean scores increased from (14.12 ± 3.90) to (15.38 ± 3.41) at post-test (t = -5.44, P < 0.001), indicating a significant improvement.
Conclusions
The results from this study show that the training course is an effective way to improve community mental health staff’s attitudes toward people with mental illness in the short term, as well as to lessen the social distance between staff and people with mental illness.
doi:10.1186/1752-4458-8-49
PMCID: PMC4268793  PMID: 25520750
Training course; Stigma; Community mental health staff
20.  Dihydroartemisinin inhibits cell proliferation via AKT/GSK3β/cyclinD1 pathway and induces apoptosis in A549 lung cancer cells 
Lung cancer is the most common cause of cancer-related death in the world. The main types of lung cancer are small cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC); non small cell lung carcinoma (NSCLC) includes squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma, Non small cell lung carcinoma accounts for about 80% of the total lung cancer cases. Dihydroartemisinin (DHA) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of DHA on cell growth and proliferation in lung cancer cells remain to be elucidated. Here, we demonstrate that DHA inhibited cell proliferation in the A549 lung cancer cell line through suppression of the AKT/Gsk-3β/cyclin D1 signaling pathway. DHA significantly inhibited cell proliferation of A549 cells in a concentration and time dependent manner as determined by MTS assay. Flow cytometry analysis demonstrated that DHA treatment of A549 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. These results suggest that DHA is a potential natural product for the treatment of lung cancer.
PMCID: PMC4314032
Dihydroartemisinin; cell proliferation; cell cycle; cyclinD1
21.  Multilocus microsatellite markers for molecular typing of Candida tropicalis isolates 
BMC Microbiology  2014;14(1):245.
Background
Candida tropicalis is considered to be the leading pathogen causing nosocomial fungemia and hepatosplenic fungal infections in patients with cancer, particularly those with leukemia. Microsatellite-based typing methods using sets of genetic markers have been developed and reported for population structure analysis of C. albicans, C. glabrata, and C. parapsilosis, but no studies have been published for genetic analysis of C. tropicalis. The objective of this study was to develop new microsatellite loci that have the ability to distinguish among C. tropicalis isolates.
Results
DNA sequences containing over 10 bi- or tri-nucleotide repeats were selected from the C. tropicalis genome database. Thirty PCR primers sets specific for the microsatellite loci were designed and tested using eight clinically independent isolates. According to the amplification efficiency, specificity, and observed polymorphisms, eight markers were selected for further population structure analysis and molecular typing. Sixty-five independent C. tropicalis isolates were genotyped using these 8 markers. Based on these analyses, six microsatellite loci were confirmed, although two loci were found to be with unstable flanking areas. The six polymorphic loci displayed 4–22 alleles and 7–27 genotypes. The discriminatory power of the six loci ranged from 0.70 to 0.95. Genotyping results obtained by microsatellite analysis were compared to PCR-fingerprinting and multi-locus sequence typing (MLST). The comparisons showed that microsatellite analysis and MLST had the similar discriminatory power for C. tropicalis, which were more powerful than PCR-fingerprinting.
Conclusions
This is the first attempt to develop new microsatellite loci for C. tropicalis. These newly developed markers will be a valuable resource for the differentiation of C. tropicalis isolates. More C. tropicalis isolates will need to be sequenced and analyzed in order to fully show the potential of these newly developed microsatellite markers.
doi:10.1186/s12866-014-0245-z
PMCID: PMC4247128  PMID: 25410579
Candida tropicalis; Microsatellite markers; Population structure; Molecular typing
22.  Lack of association of matrix metalloproteinase-3 gene polymorphism with susceptibility to rheumatoid arthritis: a meta-analysis 
Background
Epidemiological studies have investigated the association between matrix metalloproteinase-3(MMP-3) gene-1171 5A/6A polymorphism and rheumatoid arthritis (RA), but the results were inconsistent. To evaluate the specific relationship, we performed a meta-analysis to clarify the controversies.
Methods
The relevant literatures dated to December 07th 2013 were retrieved from PubMed, EMBASE and the China National knowledge Infrastructure (CNKI) databases. The number of the alleles and genotypes for MMP-3 were obtained. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between MMP-3 5A/6A promoter polymorphism and RA. All of the statistical analyses were conducted by STATA11.0 software.
Results
A total of 6 case-control studies covering 1451 cases and 1239 controls were included in the final meta-analysis. There was no significant association between MMP-3 5A/6A promoter polymorphism and RA in all genetic models (for 6A versus 5A: OR = 1.19, 95% CI = 0.91-1.56, P = 0.203; 5A/6A versus 5A/5A: OR = 1.31, 95% CI = 0.89-1.92, P = 0.174; 6A/6A versus 5A/5A: OR = 1.78, 95% CI = 0.68-4.61, P = 0.238; the recessive model: OR = 1.48, 95% CI = 0.88-2.47, P = 0.141; and the dominant model: OR = 1.46, 95% CI = 0.71-3.00, P = 0.299). In the subgroup analysis by ethnicity, we obtained the similar results.
Conclusions
We systematically investigate the association between MMP-3-1171 5A/6A polymorphism and RA susceptibility; however, the results show a lack of correlation. Considering the small sample size and the selection bias existed in some studies, further studies are needed to confirm the findings.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2474-15-376) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2474-15-376
PMCID: PMC4247749  PMID: 25403368
Rheumatoid arthritis; Matrix metalloproteinase; Polymorphism; Susceptibility; Meta-analysis
23.  Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: A meta-analysis 
World Journal of Gastroenterology : WJG  2014;20(42):15899-15909.
AIM: To investigate the associations of interleukin-17 (IL-17) genetic polymorphisms and serum levels with ulcerative colitis (UC) risk.
METHODS: Relevant articles were identified through a search of the following electronic databases, excluding language restriction: (1) the Cochrane Library Database (Issue 12, 2013); (2) Web of Science (1945-2013); (3) PubMed (1966-2013); (4) CINAHL (1982-2013); (5) EMBASE (1980-2013); and (6) the Chinese Biomedical Database (1982-2013). Meta-analysis was conducted using STATA 12.0 software. Crude odds ratios and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated. All of the included studies met all of the following five criteria: (1) the study design must be a clinical cohort or a case-control study; (2) the study must relate to the relationship between IL-17A/F genetic polymorphisms or serum IL-17 levels and the risk of UC; (3) all patients must meet the diagnostic criteria for UC; (4) the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels; and (5) the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium (HWE). The Newcastle-Ottawa Scale (NOS) criteria were used to assess the methodological quality of the studies. The NOS criteria included three aspects: (1) subject selection: 0-4; (2) comparability of subjects: 0-2; and (3) clinical outcome: 0-3. NOS scores ranged from 0 to 9, with a score ≥ 7 indicating good quality.
RESULTS: Of the initial 177 articles, only 16 case-control studies met all of the inclusion criteria. A total of 1614 UC patients and 2863 healthy controls were included in this study. Fourteen studies were performed on Asian populations, and two studies on Caucasian populations. Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models (P < 0.001 for all). The results also showed that UC patients had higher serum IL-17 levels than healthy controls (SMD = 5.95, 95%CI: 4.25-7.65, P < 0.001). Furthermore, serum IL-17 levels significantly correlated with the severity of UC (moderate vs mild: SMD = 2.59, 95%CI: 0.03-5.16, P < 0.05; severe vs mild: SMD = 7.09, 95%CI: 3.96-10.23, P < 0.001; severe vs moderate: SMD = 5.84, 95%CI: 5.09-6.59, P < 0.001). The NOS score was ≥ 5 for all of the included studies. Based on the sensitivity analysis, no single study influenced the overall pooled estimates. Neither the Begger’s funnel plots nor Egger’s test displayed strong statistical evidence for publication bias (IL-17A/F genetic polymorphisms: t = -2.60, P = 0.019; serum IL-17 levels: t = -1.54, P = 0.141).
CONCLUSION: The findings strongly suggest that IL-17A/F genetic polymorphisms and serum IL-17 levels contribute to the development and progression of UC.
doi:10.3748/wjg.v20.i42.15899
PMCID: PMC4229557  PMID: 25400476
Ulcerative colitis; Interleukin-17; Polymorphism; Serum; Meta-analysis
24.  Comparative Hair Restorer Efficacy of Medicinal Herb on Nude (Foxn1nu) Mice 
BioMed Research International  2014;2014:319795.
Eclipta alba (L.) Hassk, Asiasarum sieboldii (Miq.) F. Maek (Asiasari radix), and Panax ginseng C. A. Mey (red ginseng) are traditionally acclaimed for therapeutic properties of various human ailments. Synergistic effect of each standardized plant extract was investigated for hair growth potential on nude mice, as these mutant mice genetically lack hair due to abnormal keratinization. Dried plant samples were ground and extracted by methanol. Topical application was performed on the back of nude mice daily up to completion of two hair growth generations. The hair density and length of Eclipta alba treated mice were increased significantly (P > 0.001) than control mice. Hair growth area was also distinctly visible in Eclipta alba treated mice. On the other hand, Asiasari radix and Panax ginseng treated mice developing hair loss were recognized from the abortive boundaries of hair coverage. Histomorphometric observation of nude mice skin samples revealed an increase in number of hair follicles (HFs). The presence of follicular keratinocytes was confirmed by BrdU labeling, S-phase cells in HFs. Therefore, Eclipta alba extract and/or phytochemicals strongly displayed incomparability of hair growth promotion activity than others. Thus, the standardized Eclipta alba extract can be used as an effective, alternative, and complementary treatment against hair loss.
doi:10.1155/2014/319795
PMCID: PMC4247959  PMID: 25478567
25.  Clinical and molecular characteristics of invasive community-acquired Staphylococcus aureus infections in Chinese children 
BMC Infectious Diseases  2014;14(1):582.
Background
This study aims to investigate the clinical features of invasive community-acquired Staphylococcus aureus (CA-SA) infection in Chinese children and analyze its molecular features.
Methods
Clinical data and invasive CA-SA isolates were prospectively collected. Pediatric risk of mortality (PRISM) score was used for disease severity measurement. Molecular typing was then performed, followed by expression analysis for virulence genes.
Results
Among 163 invasive CA-SA infection cases, 71 (43.6%) were methicillin-resistant SA (MRSA) infections and 92 (56.4%) were methicillin-susceptible SA (MSSA). A total of 105 (64.4%) children were younger than 1 year old, and 79.7% (129/163) were under 3 years age. Thirteen kinds of diseases were observed, in which bacteremia and pneumonia accounted for 65.6% (107/163) and 52.8% (86/163), respectively. A total of 112 (68.1%) patients had two or more infective sites simultaneously, and four cases (2.5%) died. CA-MSSA more frequently caused multi-sites infections, bacteremia, and musculoskeletal infection than MRSA. A total of 25 sequence types (STs) were detected. MRSA mainly comprised ST59 (49/71, 69%), whereas the most frequent clonotypes were ST88 (15/92, 16.3%), ST25 (13/92, 14.1%), ST7 (13/92, 14.1%), ST2155 (12/92, 13%), and ST188 (9/92, 9.8%) for MSSA. Seven STs were common to both MSSA and MRSA groups. No differences in clinical presentation or PRISM score were found between the two groups or among different ST. The expression levels of the four known virulence genes varied among the six main ST clones.
Conclusions
Invasive CA-SA infections were characterized by high incidence and multi-site infections in young children in China. The clinical manifestations of CA-MSSA were more frequently associated with multi-site infections, bacteremia and musculoskeletal infection than those of CA-MRSA. Isolated genotypes may be relevant to the expressions of virulence genes, but not to clinical manifestations.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-014-0582-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-014-0582-4
PMCID: PMC4225039  PMID: 25377600
Staphylococcus aureus; Community-acquired; Invasive infection; Child; Molecular epidemiology

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