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1.  Nuclear p27 Expression Confers a Favorable Outcome for Nasopharyngeal Carcinoma Patients 
Disease Markers  2013;35(6):925-932.
Objective. The purpose of the present study is to explore the correlation between nuclear expression of cyclin-dependent kinase inhibitor 1B (p27) and clinicopathologic features in nasopharyngeal carcinoma (NPC), including patient survival. Methods. Immunohistochemistry was used to examine the expression of p27 in 130 primary NPC tissues. The relationship between the levels of p27 expression and clinicopathologic characteristics was analyzed. Survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. The significance of various survival variables was analyzed using multivariate Cox proportional hazards model. Results. p27 was expressed in both nuclear and cytoplasmic compartments. Nuclear expression of p27 was inversely correlated with T classification and clinical stage. Patients with nuclear p27 expression had better overall survival rates than those without nuclear expression of p27. Further, we observed that nuclear expression of p27 was positively associated with survival time of NPC patients not only in N0-1 and M0 classifications but also in radiotherapy and chemotherapy treatment groups. Finally, we found that nuclear expression of p27 was not an independent prognostic factor for patients with NPC. Conclusions. Our findings hint that nuclear expression of p27 is a potentially favorable factor in the progression and prognosis of NPC.
doi:10.1155/2013/251209
PMCID: PMC3881392  PMID: 24427780
2.  Metastasis-associated protein 1 induces VEGF-C and facilitates lymphangiogenesis in colorectal cancer 
AIM: To study the correlation between high metastasis-associated protein 1 (MTA1) expression and lymphangiogenesis in colorectal cancer (CRC) and its role in production of vascular endothelial growth factor-C(VEGF-C).
METHODS: Impact of high MTA1 and VEGF-C expression levels on disease progression and lymphovascular density (LVD, D2-40-immunolabeled) in 81 cases of human CRC was evaluated by immunohistochemistry. VEGF-C mRNA and protein expressions in human LoVo and HCT116 cell lines were detected by real-time polymerase chain reaction and Western blotting, respectively, with a stable expression vector or siRNA.
RESULTS: The elevated MTA1 and VEGF-C expression levels were correlated with lymph node metastasis and Dukes stages (P < 0.05). Additionally, high MTA1 expression level was correlated with a large tumor size (P < 0.05). A significant correlation was found between MTA1 and VEGF-C protein expressions in tumor cells (r = 0.371, P < 0.05). Similar to the VEGF-C expression level, high MTA1 expression level was correlated with high LVD in CRC (P < 0.05). Furthermore, over-expression of MTA1 significantly enhanced the VEGF-C mRNA and protein expression levels, whereas siRNAs - knocked down MTA1 decreased the VEGF-C expression level.
CONCLUSION: MTA1, as a regulator of tumor-associated lymphangiogenesis, promotes lymphangiogenesis in CRC by mediating the VEGF-C expression.
doi:10.3748/wjg.v17.i9.1219
PMCID: PMC3063917  PMID: 21448429
Metastasis-associated protein 1; Vascular endothelial growth factor-C; Lymphangiogenesis; Colorectal cancer
3.  Brain magnetic resonance imaging and manganese concentrations in red blood cells of smelting workers: Search for biomarkers of manganese exposure 
Neurotoxicology  2006;28(1):126-135.
The MRI technique has been used in diagnosis of manganism in humans and non-human primates. This cross-sectional study was designed to explore whether the pallidal signal intensity in T1-weighted MRI correlated with Mn levels in the blood compartment among Mn-exposed workers and to understand to what extent the MRI signal could reflect Mn exposure. A group of 18 randomly selected male Mn-exposed workers of which 13 were smelting workers with high exposure (mean of airborne Mn in work place: 1.26 mg/m3; range: 0.31–2.93 mg/m3), and 5 power distribution control workers with low exposure (0.66 mg/m3 and 0.23–0.77 mg/m3) from a ferroalloy factory, and another group of 9 male subjects as controls from a non-smelting factory who were office or cafeteria workers (0.01 mg/m3 and 0–0.03 mg/m3) were recruited for neurological tests, MRI examination, and analysis of Mn in whole blood (MnB), plasma (MnP) or red blood cells (MnRBC). No clinical symptoms and signs of manganism were observed among these workers. MRI data showed average increases of 7.4% (p < 0.05) and 16.1% (p < 0.01) in pallidal index (PI) among low- and high-exposed workers, respectively, as compared to controls. Fourteen out of 18 Mn-exposed workers (78%) had intensified PI values, while this proportion was even higher (85%) among the high Mn-exposed workers. Among exposed workers, the PI values were significantly associated with MnRBC (r = 0.55, p = 0.02). Our data suggest that the workers exposed to airborne Mn, but without clinical symptoms, display an exposure-related, intensified MRI signal. The MRI, as well as MnRBC, may be useful in early diagnosis of Mn exposure.
doi:10.1016/j.neuro.2006.08.005
PMCID: PMC3983995  PMID: 16978697
Manganese; MRI; Red blood cells; Trace element; Smelting workers; Biomarker
4.  Interferon-γ and interleukin-4 detected in serum and saliva from patients with oral lichen planus 
Our previous salivary study had demonstrated an apparent T helper 2 (Th2)-predominance in saliva of oral lichen planus (OLP) patients and suggested a potential of salivary interleukin-4 (IL-4) as a biomarker for monitoring disease severity. To further determine the consistency of Th1/Th2 bias of OLP, this study investigated the expression profile of interferon-γ (IFN-γ) and IL-4 in serum and the relationship of the serum levels of these cytokines with their saliva partners. Sixty ethnic Chinese patients with OLP (40 of the erythematous/ulcerative form and 20 of the reticular form) were recruited for this study, with 40 age–sex-matched healthy volunteers as control group. IFN-γ and IL-4 levels in serum and paired saliva samples were screened by enzyme-linked immunosorbent assay. OLP patient showed a low-level IFN-γ but high-level IL-4 expression profile in both serum and saliva, with a lower IFN-γ/IL-4 ratio. Serum IL-4 level in the erythematous/ulcerative group was significantly higher than that in the reticular group. Serum levels of IFN-γ and IL-4 were significantly and positively correlated with their saliva partners. These results provided more evidence for Th2 cytokine-predominant immune imbalance in OLP, as well as the potential of IL-4 as the biomarker for monitoring severity of OLP.
doi:10.1038/ijos.2013.74
PMCID: PMC3967304  PMID: 24158143
oral lichen planus; saliva; serum; T helper cytokines
5.  Thalamic GABA Predicts Fine Motor Performance in Manganese-Exposed Smelter Workers 
PLoS ONE  2014;9(2):e88220.
Overexposure to manganese (Mn) may lead to parkinsonian symptoms including motor deficits. The main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is known to play a pivotal role in the regulation and performance of movement. Therefore this study was aimed at testing the hypothesis that an alteration of GABA following Mn exposure may be associated with fine motor performance in occupationally exposed workers and may underlie the mechanism of Mn-induced motor deficits. A cohort of nine Mn-exposed male smelter workers from an Mn-iron alloy factory and 23 gender- and age-matched controls were recruited and underwent neurological exams, magnetic resonance spectroscopy (MRS) measurements, and Purdue pegboard motor testing. Short-echo-time MRS was used to measure N-Acetyl-aspartate (NAA) and myo-inositol (mI). GABA was detected with a MEGA-PRESS J-editing MRS sequence. The mean thalamic GABA level was significantly increased in smelter workers compared to controls (p = 0.009). Multiple linear regression analysis reveals (1) a significant association between the increase in GABA level and the duration of exposure (R2 = 0.660, p = 0.039), and (2) significant inverse associations between GABA levels and all Purdue pegboard test scores (for summation of all scores R2 = 0.902, p = 0.001) in the smelter workers. In addition, levels of mI were reduced significantly in the thalamus and PCC of smelter workers compared to controls (p = 0.030 and p = 0.009, respectively). In conclusion, our results show clear associations between thalamic GABA levels and fine motor performance. Thus in Mn-exposed subjects, increased thalamic GABA levels may serve as a biomarker for subtle deficits in motor control and may become valuable for early diagnosis of Mn poisoning.
doi:10.1371/journal.pone.0088220
PMCID: PMC3913772  PMID: 24505436
6.  How Early Can Myocardial Iron Overload Occur in Beta Thalassemia Major? 
PLoS ONE  2014;9(1):e85379.
Background
Myocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload in a young Chinese population with beta TM.
Methods and Results
We analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload.
Conclusions
The TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old.
doi:10.1371/journal.pone.0085379
PMCID: PMC3899006  PMID: 24465548
7.  The Assessment of the Quality of Reporting of Systematic Reviews/Meta-Analyses in Diagnostic Tests Published by Authors in China 
PLoS ONE  2014;9(1):e85908.
Background
The quality of reporting in systematic reviews (SRs)/meta-analyses (MAs) of diagnostic tests published by authors in China has not been evaluated. The aims of present study are to evaluate the quality of reporting in diagnostic SRs/MAs using the PRISMA statement and determine the changes in the quality of reporting over time.
Methods
According to the inclusion and exclusion criteria, we searched five databases including Chinese Biomedical Literature Database, PubMed, EMBASE, the Cochrane Library, and Web of knowledge, to identify SRs/MAs on diagnostic tests. The searches were conducted on July 14, 2012 and the cut off for inclusion of the SRs/MAs was December 31st 2011. The PRISMA statement was used to assess the quality of reporting. Analysis was performed using Excel 2003, RevMan 5.
Results
A total of 312 studies were included. Fifteen diseases systems were covered. According to the PRISMA checklist, there had been serious reporting flaws in following items: structured summary (item 2, 22.4%), objectives (item 4, 18.9%), protocol and registration (item 5, 2.6%), risk of bias across studies (item 15, 26.3%), funding (item 27, 28.8%). The subgroup analysis showed that there had been some statistically significant improvement in total compliance for 9 PRISMA items after the PRISMA was released, 6 items were statistically improved regarding funded articles, 3 items were statistically improved for CSCD articles, and there was a statistically significant increase in the proportion of reviews reporting on 22 items for SCI articles (P<0.050).
Conclusion
The numbers of diagnostic SRs/MAs is increasing annually. The quality of reporting has measurably been improved over the previous years. Unfortunately, there are still many deficiencies in the reporting including protocol and registration, search, risk of bias across studies, and funding. Future Chinese reviewers should address issues on these aspects.
doi:10.1371/journal.pone.0085908
PMCID: PMC3897563  PMID: 24465781
8.  Investigations of the functional states of dendritic cells under different conditioned microenvironments by Fourier transformed infrared spectroscopy 
Background
Dendritic cells are potent and specialized antigen presenting cells, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses. The dendritic cell-based vaccination against cancer has been clinically achieved promising successes. But there are still many challenges in its clinical application, especially for how to identify the functional states.
Methods
The CD14+ monocytes were isolated from human peripheral blood after plastic adherence and purified to approximately 98% with cocktail immunomagnetic beads. The immature dendritic cells and mature dendritic cells were induced by traditional protocols. The resulting dendritic cells were cocultured with normal cells and cancer cells. The functional state of dendritic cells including immature dendritic cells (imDCs) and mature dendritic cells (mDCs) under different conditioned microenvironments were investigated by Fourier transformed infrared spectroscopy (FTIR) and molecular biological methods.
Results
The results of Fourier transformed infrared spectroscopy showed that the gene transcription activity and energy states of dendritic cells were specifically suppressed by tumor cells (P < 0.05 or 0.01). The expression levels of NF-kappa B (NF-κB) in dendritic cells were also specifically inhibited by tumor-derived factors (P < 0.05 or 0.01). Moreover, the ratios of absorption intensities of Fourier transformed infrared spectroscopy at given wave numbers were closely correlated with the expression levels of NF-κB (R2:0.69 and R2:0.81, respectively).
Conclusion
Our results confirmed that the ratios of absorption intensities of Fourier transformed infrared spectroscopy at given wave numbers were positively correlated with the expression levels of NF-κB, suggesting that Fourier transformed infrared spectroscopy technology could be clinically applied to identify the functional states of dendritic cell when performing dendritic cell-based vaccination. It’s significant for the simplification and standardization of dendritic cell-based vaccination clinical preparation protocols.
doi:10.1186/1475-925X-13-2
PMCID: PMC3897965  PMID: 24410930
Dendritic cell; Fourier transformed infrared spectroscopy; Functional states of cells; NF-κB
10.  Exploring the Relationships of Women’s Sexual Assault Disclosure, Social Reactions, and Problem Drinking 
Journal of interpersonal violence  2008;23(9):10.1177/0886260508314298.
The goal of this exploratory study was to examine correlates of sexual assault disclosure and social reactions in female victims with and without drinking problems. An ethnically diverse sample of sexual assault survivors was recruited from college, community, and mental health agencies. Ethnic minority women were less likely to disclose assault, and women with a greater number of traumatic life events disclosed assault more often. Although there were no differences in disclosure likelihood by drinking status; of those disclosing, problem drinkers told more support sources and received more negative and positive social reactions than nonproblem drinkers. Correlates of receiving negative social reactions were similar for normal and problem drinkers; however, negative social reactions to assault disclosure were related to more problem drinking for women with less frequent social interaction. Implications for future research and possible support interventions with problem-drinking victims are provided.
doi:10.1177/0886260508314298
PMCID: PMC3863580  PMID: 18309039
women; sexual assault; disclosure; social reactions; problem drinking
11.  Basic research and clinical applications of bisphosphonates in bone disease: what have we learned over the last 40 years? 
It is now 40 years since bisphosphonates (BPs) were first used in the clinic. So, it is timely to provide a brief review of what we have learned about these agents in bone disease. BPs are bone-specific and have been classified into two major groups on the basis of their distinct molecular modes of action: amino-BPs and non-amino-BPs. The amino-BPs are more potent and they inhibit farnesyl pyrophosphate synthase (FPPS), a key enzyme of the mavalonate/cholesterol biosynthetic pathway, while the non-amino-BPs inhibit osteoclast activity, by incorporation into non-hydrolyzable analogs of ATP. Both amino-BPs and non-amino-BPs can protect osteoblasts and osteocytes against apoptosis. The BPs are widely used in the clinic to treat various diseases characterized by excessive bone resorption, including osteoporosis, myeloma, bone metastasis, Legg-Perthes disease, malignant hyperparathyroidism, and other conditions featuring bone fragility. This review provides insights into some of the adverse effects of BPs, such as gastric irritation, osteonecrosis of the jaw, atypical femoral fractures, esophageal cancer, atrial fibrillation, and ocular inflammation. In conclusion, this review covers the biochemical and molecular mechanisms of action of BPs in bone, particularly the discovery that BPs have direct anti-apoptotic effects on osteoblasts and osteocytes, and the current situation of BP use in the clinic.
doi:10.1186/1479-5876-11-303
PMCID: PMC3874605  PMID: 24330728
Bisphosphonate; Pharmacokinetics; Osteoclast; Osteoblast; Osteoporosis
12.  Intrinsic Features in MicroRNA Transcriptomes Link Porcine Visceral Rather than Subcutaneous Adipose Tissues to Metabolic Risk 
PLoS ONE  2013;8(11):e80041.
MicroRNAs (miRNAs) are non-coding small RNA ∼22 nucleotides in length that can regulate the expression of a wide range of coding genes at the post-transcriptional level. Visceral adipose tissues (VATs) and subcutaneous adipose tissues (SATs), the two main fat compartments in mammals, are anatomically, physiologically, metabolically, and clinically distinct. Various studies of adipose tissues have focused mainly on DNA methylation, and mRNA and protein expression, nonetheless little research sheds directly light on the miRNA transcriptome differences between these two distinct adipose tissue types. Here, we present a comprehensive investigation of miRNA transcriptomes across six variant porcine adipose tissues by small RNA-sequencing. We identified 219 known porcine miRNAs, 97 novel miRNA*s, and 124 miRNAs that are conserved to other mammals. A set of universally abundant miRNAs (i.e., miR-148a-3p, miR-143-3p, miR-27b-3p, miR-let-7a-1-5p, and miR-let-7f-5p) across the distinct adipose tissues was found. This set of miRNAs may play important housekeeping roles that are involved in adipogenesis. Clustering analysis indicated significant variations in miRNA expression between the VATs and SATs, and highlighted the role of the greater omentum in responding to potential metabolic risk because of the observed enrichment in this tissue of the immune- and inflammation-related miRNAs, such as the members of miR-17-92 cluster and miR-181 family. Differential expression of the miRNAs between the VATs and SATs, and miRNA target prediction analysis revealed that the VATs-specific enriched miRNAs were associated mainly with immune and inflammation responses. In summary, the differences of miRNA expression between the VATs and SATs revealed some of their intrinsic differences and indicated that the VATs might be closely associated with increased risk of metabolic disorders.
doi:10.1371/journal.pone.0080041
PMCID: PMC3819305  PMID: 24223210
13.  Diversity of Both the Cultivable Protease-Producing Bacteria and Bacterial Extracellular Proteases in the Coastal Sediments of King George Island, Antarctica 
PLoS ONE  2013;8(11):e79668.
Protease-producing bacteria play a vital role in degrading sedimentary organic nitrogen. However, the diversity of these bacteria and their extracellular proteases in most regions remain unknown. In this paper, the diversity of the cultivable protease-producing bacteria and of bacterial extracellular proteases in the sediments of Maxwell Bay, King George Island, Antarctica was investigated. The cultivable protease-producing bacteria reached 105 cells/g in all 8 sediment samples. The cultivated protease-producing bacteria were mainly affiliated with the phyla Actinobacteria, Firmicutes, Bacteroidetes, and Proteobacteria, and the predominant genera were Bacillus (22.9%), Flavobacterium (21.0%) and Lacinutrix (16.2%). Among these strains, Pseudoalteromonas and Flavobacteria showed relatively high protease production. Inhibitor analysis showed that nearly all the extracellular proteases from the bacteria were serine proteases or metalloproteases. These results begin to address the diversity of protease-producing bacteria and bacterial extracellular proteases in the sediments of the Antarctic Sea.
doi:10.1371/journal.pone.0079668
PMCID: PMC3817139  PMID: 24223990
14.  The effects of different doses of estradiol (E2) on cerebral ischemia in an in vitro model of oxygen and glucose deprivation and reperfusion and in a rat model of middle carotid artery occlusion 
BMC Neuroscience  2013;14:118.
Background
Because neuroprotective effects of estrogen remain controversial, we aimed to investigate the effect of different doses of estradiol (E2) on cerebral ischemia using both in vivo and in vitro experiments.
Results
PC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 μM and 20 μM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu) incorporation and flow cytometric analysis showed that physiological doses of E2 enhanced cell proliferation and pharmacological doses of E2 inhibited cell proliferation. After the cells were exposed to oxygen and glucose deprivation (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, flow cytometric analysis and Western blot analysis showed that physiological doses of E2 enhanced cell viability, reduced cell apoptosis and decreased the expression of pro-apoptotic protein caspase-3. In contrast, pharmacological doses of E2 decreased cell viability and induced cell apoptosis. In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was induced for 2 h using the middle cerebral artery occlusion (MCAO) technique, followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that 6 μg/kg and 20 μg/kg E2 replacement induced an increase in neurological deficit scores, a decrease in the infarct volume and a reduction in the expression of caspase-3 when compared to animals in the OVX group without E2 treatment. However, 50 μg/kg E2 replacement treatment decreased neurological deficit scores, increased the infarct volume and the expression of caspase-3 when compared to animals in the control group and 6 up/kg or 20 μg/kg E2 replacement group.
Conclusion
We conclude that physiological levels of E2 exhibit neuroprotective effects on cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2 have damaging effects on neurons after cerebral ischemia.
doi:10.1186/1471-2202-14-118
PMCID: PMC3851874  PMID: 24106772
Estrogen; Neuroprotection; Ischemia; Middle carotid artery occlusion (MCAO); Oxygen and glucose deprivation (OGD)
15.  Reduced Vancomycin Susceptibility Found in Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Clinical Isolates in Northeast China 
PLoS ONE  2013;8(9):e73300.
Background
Strains of Staphylococcus aureus with an intermediate level of resistance to vancomycin (vancomycin-intermediate S. aureus, or VISA) or which contain subpopulations of mixed susceptibility (heterogeneous VISA, or hVISA) have been reported worldwide. However, the prevalence of VISA and hVISA infections in Northeast China is unknown. From 2007 through 2010, we surveyed the vancomycin susceptibility of methicillin-resistant and methicillin-sensitive S. aureus (MRSA and MSSA, respectively) clinical isolates in Northeast China.
Methods
S. aureus clinical isolates (369 MRSA and 388 MSSA) were screened for hVISA and VISA on brain heart infusion agar containing 3 μg/mL vancomycin, and their identity confirmed using a modified population analysis profile-area under the curve method and broth microdilution. All hVISA and VISA isolates were characterized genotypically and phenotypically.
Results
Ten percent and 0.5 percent of the isolates were hVISA and VISA, respectively. The proportion of hVISA among MSSA isolates for the entire study period was 4.1%, but increased significantly year-by-year, from 1.2% in 2007 to 7.2% in 2010. The predominant sources of hVISA and VISA isolates were sputum (56.3%), pus (18.8%), and blood (8.8%). Molecular typing of hVISA and VISA strains revealed that, taken together, 80% contained the accessory gene regulator (agr) group II, and of these, 85.7% of the MR-hVISA and MR-VISA strains were staphylococcal cassette chromosome mec (SCCmec) type II. The adherence ability of all hVISA and VISA strains was reduced compared with that of vancomycin-susceptible strains, shown by biofilm assay.
Conclusions
The percentage of hVISA strains was high and increased each year. The proportion of hVISA among MSSA specifically also increased significantly each year. In isolates collected from diverse infection sites, hVISA and VISA strains were found predominantly in sputum, pus, and blood, in descending order. Testing for vancomycin susceptibility should include both MRSA and MSSA isolates collected from different clinical sites.
doi:10.1371/journal.pone.0073300
PMCID: PMC3772004  PMID: 24069184
16.  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
17.  Spatiotemporal Patterns of Japanese Encephalitis in China, 2002–2010 
Objective
The aim of the study is to examine the spatiotemporal pattern of Japanese Encephalitis (JE) in mainland China during 2002–2010. Specific objectives of the study were to quantify the temporal variation in incidence of JE cases, to determine if clustering of JE cases exists, to detect high risk spatiotemporal clusters of JE cases and to provide evidence-based preventive suggestions to relevant stakeholders.
Methods
Monthly JE cases at the county level in mainland China during 2002–2010 were obtained from the China Information System for Diseases Control and Prevention (CISDCP). For the purpose of the analysis, JE case counts for nine years were aggregated into four temporal periods (2002; 2003–2005; 2006; and 2007–2010). Local Indicators of Spatial Association and spatial scan statistics were performed to detect and evaluate local high risk space-time clusters.
Results
JE incidence showed a decreasing trend from 2002 to 2005 but peaked in 2006, then fluctuated over the study period. Spatial cluster analysis detected high value clusters, mainly located in Southwestern China. Similarly, we identified a primary spatiotemporal cluster of JE in Southwestern China between July and August, with the geographical range of JE transmission increasing over the past years.
Conclusion
JE in China is geographically clustered and its spatial extent dynamically changed during the last nine years in mainland China. This indicates that risk factors for JE infection are likely to be spatially heterogeneous. The results may assist national and local health authorities in the development/refinement of a better preventive strategy and increase the effectiveness of public health interventions against JE transmission.
Author Summary
Japanese encephalitis (JE) is a mosquito-borne disease, which primarily occurs in rural and suburban areas of Southeast Asia and the Western Pacific region. JE still remains a significant public health problem in mainland China, with approximately 50% of global cases annually. Few studies have explored the spatiotemporal patterns of JE cases in China. Here we reported the results of Local Indicators of Spatial Association and spatial scan statistics of JE cases in mainland China at the county level during the four periods: 2002; 2003–2005; 2006; 2007–2010. The primary spatiotemporal cluster of JE was detected in Southwestern China between July and August, with the geographical range of JE transmission increasing over the past years. The results of LISA and spatial scan statistics were consistent which indicates that these methods are reliable and could have wider applications in the fields of disease surveillance and management in China, particularly in the surveillance and monitoring of other vector-borne diseases. These findings may assist in informing prevention and control strategies and increase the effectiveness of public health interventions against JE transmission.
doi:10.1371/journal.pntd.0002285
PMCID: PMC3688550  PMID: 23819000
18.  Prevalence of metabolic syndrome among urban community residents in China 
BMC Public Health  2013;13:599.
Background
Metabolic risk factors and abnormalities such as obesity and hypertension are rapidly rising among the Chinese population following China’s tremendous economic growth and widespread westernization of lifestyle in recent decades. Limited information is available about the current burden of metabolic syndrome (MetS) in China.
Methods
We analyzed data on metabolic risk factors among 22,457 adults aged ≥ 32 years participating in the “Zhabei Health 2020” survey (2009–2010), a cross-sectional study of a representative sample of community residents in Zhabei District. We defined MetS using Chinese-specific cut-off points for central obesity according to consensus criteria recently endorsed by several international and national organizations in defining MetS in different populations worldwide. We used a multiple logistic regression model to assess the associations of potential risk factors with MetS.
Results
The unadjusted prevalence of the MetS was 35.1% for men and 32.5% for women according to the consensus criteria for Chinese. The prevalence increased progressively from 12.1% among participants aged 32–45 years to 45.4% among those aged ≥ 75 years. Age, smoking, family history of diabetes, and education are significantly associated with risk of MetS.
Conclusions
The MetS is highly prevalent and has reached epidemic proportion in Chinese urban adult community residents.
doi:10.1186/1471-2458-13-599
PMCID: PMC3734094  PMID: 23786855
Metabolic syndrome; Prevalence; Population-based survey; China
19.  Dual Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Blockade Produces THC-Like Morris Water Maze Deficits in Mice 
ACS Chemical Neuroscience  2012;3(5):369-378.
Acute administration of Δ9-tetrahydrocannabinol (THC) or exposure to marijuana smoke impairs short-term spatial memory in water maze tasks through a CB1 receptor mechanism of action. N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) are endogenous cannabinoids that are predominantly metabolized by the respective enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Although the MAGL inhibitor JZL184 enhances short-term synaptic plasticity, it has yet to be evaluated in the Morris water maze. Previous research demonstrated that simultaneous, complete blockade of FAAH and MAGL produces full blown THC-like effects. Thus, in the following studies we tested whether dual blockade of FAAH and MAGL would impair learning in a repeated acquisition Morris water maze task. Mice treated with the dual FAAH/MAGL inhibitor JZL195 (20 mg/kg) as well as JZL184-treated FAAH −/– mice displayed robust deficits in Morris water maze performance that were similar in magnitude to THC-treated mice. While 20 or 40 mg/kg impaired water maze performance in FAAH −/– mice, only the high dose of JZL184 disrupted performance in FAAH +/+ mice. The memory impairing effects of JZL184 were blocked by the CB1 receptor antagonist rimonabant. Neither JZL184 nor JZL195 impaired performance in a cued version of the water maze task, arguing against the notion that sensorimotor or motivational deficits accounted for the impaired acquisition performance. JZL184 increased 2-AG levels in the hippocampus, prefrontal cortex, and cerebellum to a similar degree in FAAH −/– and +/+ mice. FAAH −/– mice, regardless of drug treatment, possessed elevated AEA levels in each brain region assessed. The results of this study reveal that concomitant increases in AEA and 2-AG disrupt short-term spatial memory performance in a manner similar to that of THC.
doi:10.1021/cn200130s
PMCID: PMC3382457  PMID: 22860205
Cannabinoid; memory; N-arachidonoylethanolamine (anandamide); 2-arachidonoylglycerol (2-AG); fatty acid amide hydrolase (FAAH); monoacylglycerol lipase (MAGL)
20.  Identification of a Genomic Region Containing a Novel Promoter Resistant to Glucose Repression and Over-Expression of β-Glucosidase Gene in Hypocrea orientalis EU7-22 
A high concentration of glucose in the medium could greatly inhibit the expression of cellulase in filamentous fungi. The aspartic protease from fungus Hypocrea orientalis EU7-22 could efficiently express under both induction condition and glucose repression condition. Based on the sequence of structure gene of aspartic protease, the upstream sequence harboring the putative promoter proA for driving the expression of aspartic protease was obtained by genome walking. The upstream sequence contained the typical promoter motifs “TATA” and “CAAT”. The β-glucosidase gene (Bgl1) from H. orientalis was cloned and recombined with promoter proA and terminator trpC. The expression cassette was ligated to the binary vector to form pUR5750-Bgl1, and then transferred into the host strain EU7-22 via Agrobacterium tumefaciens mediated transformation (ATMT), using hygromycin B resistance gene as the screening marker. Four transformants Bgl-1, Bgl-2, Bgl-3 and Bgl-4 were screened. Compared with the host strain EU7-22, the enzyme activities of filter paper (FPA) and β-glucosidase (BG) of transformant Bgl-2 increased by 10.6% and 19.1% under induction condition, respectively. The FPA and BG activities were enhanced by 22.2% and 700% under 2% glucose repression condition, respectively, compared with the host strain. The results showed that the putative promoter proA has successfully driven the over-expression of Bgl1 gene in H. orientalis under glucose repression condition.
doi:10.3390/ijms14048479
PMCID: PMC3645756  PMID: 23594998
Hypocrea orientalis EU7-22; promoter proA; β-glucosidase gene; over-expression; glucose repression; enzyme activity
21.  Porous 3D graphene-based bulk materials with exceptional high surface area and excellent conductivity for supercapacitors 
Scientific Reports  2013;3:1408.
Until now, few sp2 carbon materials simultaneously exhibit superior performance for specific surface area (SSA) and electrical conductivity at bulk state. Thus, it is extremely important to make such materials at bulk scale with those two outstanding properties combined together. Here, we present a simple and green but very efficient approach using two standard and simple industry steps to make such three-dimensional graphene-based porous materials at the bulk scale, with ultrahigh SSA (3523 m2/g) and excellent bulk conductivity. We conclude that these materials consist of mainly defected/wrinkled single layer graphene sheets in the dimensional size of a few nanometers, with at least some covalent bond between each other. The outstanding properties of these materials are demonstrated by their superior supercapacitor performance in ionic liquid with specific capacitance and energy density of 231 F/g and 98 Wh/kg, respectively, so far the best reported capacitance performance for all bulk carbon materials.
doi:10.1038/srep01408
PMCID: PMC3593215  PMID: 23474952
22.  Conditional Expression of Parkinson disease-related Mutant α-synuclein in the Midbrain Dopaminergic Neurons causes Progressive Neurodegeneration and Degradation of Transcription Factor Nuclear Receptor Related 1 
α-synuclein(α-syn) plays a prominent role in the degeneration of midbrain dopaminergic (mDA) neurons in Parkinson disease (PD). However, only a few studies on α-syn have been carried out in the mDA neurons in vivo, which may be attributed to a lack of α-syn transgenic mice that develop PD-like severe degeneration of mDA neurons. To gain mechanistic insights into the α-syn-induced mDA neurodegeneration, we generated a new line of tetracycline-regulated inducible transgenic mice that overexpressed the PD-related α-syn A53T missense mutation in the mDA neurons. Here we show that the mutant mice developed profound motor disabilities and robust mDA neurodegeneration, resembling some key motor and pathological phenotypes of PD. We further systematically examined the subcellular abnormalities appeared in the mDA neurons of mutant mice, and observed a profound decrease of dopamine release, the fragmentation of Golgi apparatus, and impairments of autophagy/lysosome degradation pathways in these neurons. To further understand the specific molecular events leading to the α-syn-dependent degeneration of mDA neurons, we found that over-expression of α-syn promoted a proteasome-dependent degradation of nuclear receptor related 1 protein (Nurr1); while inhibition of Nurr1 degradation ameliorated the α-syn-induced loss of mDA neurons. Given that Nurr1 plays an essential role in maintaining the normal function and survival of mDA neurons, our studies suggest that the α-syn-mediated suppression of Nurr1 protein expression may contribute to the preferential vulnerability of mDA neurons in the pathogenesis of PD.
doi:10.1523/JNEUROSCI.1731-12.2012
PMCID: PMC3417246  PMID: 22764233
23.  Two-dimensional ultrathin gold film composed of steadily linked dense nanoparticle with surface plasmon resonance 
Nanoscale Research Letters  2012;7(1):683.
Background
Noble metallic nanoparticles have prominent optical local-field enhancement and light trapping properties in the visible light region resulting from surface plasmon resonances.
Results
We investigate the optical spectral properties and the surface-enhanced Raman spectroscopy of two-dimensional distinctive continuous ultrathin gold nanofilms. Experimental results show that the one- or two-layer nanofilm obviously increases absorbance in PEDOT:PSS and P3HT:PCBM layers and the gold nanofilm acquires high Raman-enhancing capability.
Conclusions
The fabricated novel structure of the continuous ultrathin gold nanofilms possesses high surface plasmon resonance properties and boasts a high surface-enhanced Raman scattering (SERS) enhancement factor, which can be a robust and cost-efficient SERS substrate. Interestingly, owing to the distinctive morphology and high light transmittance, the peculiar nanofilm can be used in multilayer photovoltaic devices to trap light without affecting the physical thickness of solar photovoltaic absorber layers and yielding new options for solar cell design.
doi:10.1186/1556-276X-7-683
PMCID: PMC3552831  PMID: 23259927
Ultrathin gold film; Surface plasmon resonance; SERS
24.  Tunable spin-dependent Andreev reflection in a four-terminal Aharonov-Bohm interferometer with coherent indirect coupling and Rashba spin-orbit interaction 
Nanoscale Research Letters  2012;7(1):670.
Using the nonequilibrium Green’s function method, we theoretically study the Andreev reflection(AR) in a four-terminal Aharonov-Bohm interferometer containing a coupled double quantum dot with the Rashba spin-orbit interaction (RSOI) and the coherent indirect coupling via two ferromagnetic leads. When two ferromagnetic electrodes are in the parallel configuration, the spin-up conductance is equal to the spin-down conductance due to the absence of the RSOI. However, for the antiparallel alignment, the spin-polarized AR occurs resulting from the crossed AR (CAR) and the RSOI. The effects of the coherent indirect coupling, RSOI, and magnetic flux on the Andreev-reflected tunneling magnetoresistance are analyzed at length. The spin-related current is calculated, and a distinct swap effect emerges. Furthermore, the pure spin current can be generated due to the CAR when two ferromagnets become two half metals. It is found that the strong RSOI and the large indirect coupling are in favor of the CAR and the production of the strong spin current. The properties of the spin-related current are tunable in terms of the external parameters. Our results offer new ways to manipulate the spin-dependent transport.
doi:10.1186/1556-276X-7-670
PMCID: PMC3575254  PMID: 23228047
Aharonov-Bohm interferometer; Double quantum dot; Andreev reflection; Rashba spin-orbit interaction; Coherent indirect coupling; 73.63.Kv; 73.23.-b; 72.25.-b
25.  Evaluation of an IgY-Based Immunomagnetic Enzyme-Linked Immunosorbent Assay System for Detection of Circulating Schistosoma japonicum Antigen in Serum Samples from Patients in China 
We have developed a novel egg yolk antibody (IgY)–coated magnetic beads antigen-capture immunoassay for detection of a circulating antigen of Schistosoma japonicum in serum samples of patients in schistosomiasis-endemic areas of China. This IgY-based immunomagnetic bead enzyme-linked immunosorbent assay (IgY-IMB-ELISA) uses polyclonal IgY-coated magnetic beads as a capture antibody, and a monoclonal IgG as a detection antibody. The sensitivity of the magnetic immunoassay was 100% (40 of 40) in cases of acute infection and 91.5% (107 of 117) in chronic cases of schistosomiasis, and no positive reaction was found in 0 of 49 healthy persons. Cross-reactivity was 3.3% (1 of 33) with clonorchiasis and 0% (0 of 20) with paragonimiasis. There was a significant correlation between ELISA absorbance value and egg count (eggs per gram feces) and a correlation coefficient of 0.88 in a small sample of 14 patients. The results demonstrated that the IgY-IMB-ELISA is a sensitive and specific assay for detection of human schistosomiasis japonica.
doi:10.4269/ajtmh.2011.11-0051
PMCID: PMC3225151  PMID: 22144443

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