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1.  Psychometric Characteristics of Duke Social Support Index in Young Rural Chinese Population 
Death studies  2012;36(9):858-869.
The study is aimed to examine the psychometric characteristics of Duke Social Support Scale (DSSI) in young rural Chinese individuals (379 suicides, 411 controls) aged 15–34 years. Social support was measured by 23-item DSSI which included Social Interaction Scale, Subjective Social Support and Instrumental Social Support. DSSI had high internal consistency (alphas all over .79), and correlated with hopelessness and anxiety in both samples. Confirmatory factor analysis showed that the structure models of DSSI were basically suitable for the original structure of DSSI but some items should be modified or deleted. Altogether, these findings support that DSSI has high reliability and validity, which makes it an acceptable measure for social support in young Chinese populations. However, further model tests should be carried out by deleting or modifying some items or being used in different populations.
PMCID: PMC3982863  PMID: 24563931
2.  PFOS induced lipid metabolism disturbances in BALB/c mice through inhibition of low density lipoproteins excretion 
Scientific Reports  2014;4:4582.
Male BALB/c mice fed with either a regular or high fat diet were exposed to 0, 5 or 20 mg/kg perfluorooctane sulfonate (PFOS) for 14 days. Increased body weight, serum glucose, cholesterol and lipoprotein levels were observed in mice given a high fat diet. However, all PFOS-treated mice got reduced levels of serum lipid and lipoprotein. Decreasing liver glycogen content was also observed, accompanied by reduced serum glucose levels. Histological and ultrastructural examination detected more lipid droplets accumulated in hepatocytes after PFOS exposure. Moreover, transcripitonal activity of lipid metabolism related genes suggests that PFOS toxicity is probably unrelevant to PPARα's transcription. The present study demonstrates a lipid disturbance caused by PFOS and thus point to its role in inhibiting the secretion and normal function of low density lipoproteins.
doi:10.1038/srep04582
PMCID: PMC3974142
3.  Role of Na+/Ca2+ Exchanger (NCX) in Modulating Postovulatory Aging of Mouse and Rat Oocytes 
PLoS ONE  2014;9(4):e93446.
We studied the role of the Na+/Ca2+ exchanger (NCX) in modulating oocyte postovulatory aging by observing changes in NCX contents and activities in aging mouse and rat oocytes. Whereas the NCX activity was measured by observing oocyte activation following culture with NCX inhibitor or activator, the NCX contents were determined by immunohistochemical quantification. Although NCX was active in freshly-ovulated rat oocytes recovered 13 h post hCG injection and in aged oocytes recovered 19 h post hCG in both species, it was not active in freshly-ovulated mouse oocytes. However, NCX became active when the freshly-ovulated mouse oocytes were activated with ethanol before culture. Measurement of cytoplasmic Ca2+ revealed Ca2+ increases always before NCX activation. Whereas levels of the reactive oxygen species (ROS) and the activation susceptibility increased, the density of NCX member 1 (NCX1) decreased significantly with oocyte aging in both species. While culture with H2O2 decreased the density of NCX1 significantly, culture with NaCl supplementation sustained the NCX1 density in mouse oocytes. It was concluded that (a) the NCX activity was involved in the modulation of oocyte aging and spontaneous activation; (b) ROS and Na+ regulated the NCX activity in aging oocytes by altering its density as well as functioning; and (c) cytoplasmic Ca2+ elevation was essential for NCX activation in the oocyte.
doi:10.1371/journal.pone.0093446
PMCID: PMC3973580  PMID: 24695407
4.  Synthesis and screening of 3-MA derivatives for autophagy inhibitors 
Autophagy  2013;9(4):595-603.
Autophagy is a conserved degradation process, which plays important pathophysiological roles. The lack of effective inhibitors of autophagy has been an obstacle in both basic research and understanding the physiological role of autophagy in disease manifestation. The most widely used inhibitor, 3-methyladenine (3-MA), is poorly soluble at room temperature and is effective only at high concentrations. In this study, we synthesized a library of small compounds by chemically modifying 3-MA and screened this library for autophagy inhibitors. Three 3-MA derivatives generated through this approach showed improved solubility and effectiveness in inhibiting autophagy. We demonstrated that chemical modification of an existing autophagy inhibitor is an effective method to generate improved autophagy inhibitors.
doi:10.4161/auto.23641
PMCID: PMC3627673  PMID: 23412639
autophagy; inhibitor; 3-MA; synthesis; derivatives
6.  C-027 Inhibits IgE-mediated passive sensitization bronchoconstriction and acts as a histamine and serotonin antagonist in human airways 
Atopic asthma is poorly controlled by current therapies. Newer therapies and novel antihistamines are, therefore, required to treat patients whose atopic asthma is not controlled. For the first time, C-027 is shown to antagonize histamine, IgE-mediated and serotonin-induced contraction in human airways and vessels. Human precision-cut lung slices (PCLS, 250 µm thick), containing an airway or blood vessel, were pretreated with either C-027 (2 hours) or with vehicle alone and were contracted with histamine or serotonin. Known antihistamine was used as a comparator in antihistamine studies. Also, human airways were contracted via IgE passive sensitization in the presence or absence of C-027 or fexofenadine. Affinity of C-027 toward human G-protein coupled receptors was also determined, as well as the drug's biodistribution in murine model. C-027 was shown to have the highest affinity toward human histamine and serotonin receptors. Subsequently, C-027 was shown to antagonize histamine- and serotonin-induced airway and vascular smooth muscle contraction, respectively, and histamine-released bronchocontraction mediated by IgE passive sensitization in human small airways. C-027 also inhibited histamine-mediated single-cell calcium ion release. Low levels of C-027 were found in murine brain tissue. Collectively, these data suggest that C-027 markedly inhibits IgE-induced bronchoconstriction and antagonizes histamine and serotonin-contraction with little biodistribution in the brain. The compound may offer a future therapy for allergen-induced airway hyperresponsiveness in patients with asthma.
doi:10.2500/aap.2011.32.3460
PMCID: PMC3968313  PMID: 22195688
Airway smooth muscle; allergy; antagonist; anti-histamine; anti-serotonic; asthma; IgE mediated; novel compound; PCLS; reverse agonist
7.  DelPhi Web Server: A comprehensive online suite for electrostatic calculations of biological macromolecules and their complexes 
Here we report a web server, the DelPhi web server, which utilizes DelPhi program to calculate electrostatic energies and the corresponding electrostatic potential and ionic distributions, and dielectric map. The server provides extra services to fix structural defects, as missing atoms in the structural file and allows for generation of missing hydrogen atoms. The hydrogen placement and the corresponding DelPhi calculations can be done with user selected force field parameters being either Charmm22, Amber98 or OPLS. Upon completion of the calculations, the user is given option to download fixed and protonated structural file, together with the parameter and Delphi output files for further analysis. Utilizing Jmol viewer, the user can see the corresponding structural file, to manipulate it and to change the presentation. In addition, if the potential map is requested to be calculated, the potential can be mapped onto the molecule surface. The DelPhi web server is available from http://compbio.clemson.edu/delphi_webserver.
PMCID: PMC3966485
DelPhi; electrostatics; proteins; continuum models; electrostatic potential; Finite-Difference Poisson-Boltzmann solver
8.  Predictors of the Rate of Change in Disease Activity over Time in LUMINA, a Multiethnic US Cohort of Patients with Systemic Lupus Erythematosus: LUMINA LXX 
Lupus  2010;19(6):727-733.
The objectives of the present study were (1) to clarify and quantify the relationship between age and disease duration with the rate of change in disease activity over time in patients with systemic lupus erythematosus (SLE) and (2) to explore other possible factors associated with this rate of change. To this end, SLE patients from LUMINA were studied if they had ≥3 visits in which disease activity (Systemic Lupus Activity Measure-Revised or SLAM-R) had been ascertained. Variables associated with the rate (slope) of change in disease activity (obtained by regressing the SLAM-R scores against the length of time from diagnosis to last visit) were examined by univariable and multivariable analyses. Five-hundred forty-two of the 632 patients had ≥3 SLAM-R scores. In multivariable analyses Caucasians exhibited the fastest decline in disease activity; Texan Hispanics exhibited the slowest, trailed by the African Americans. Longer disease duration and HLA-DRB1*1503 positivity were associated with a slower decline whereas a greater number of ACR criteria and abnormal laboratory parameters (white blood cell and platelet counts, hematocrit and serum creatinine) were associated with a faster decline. These findings complement existing knowledge on SLE disease activity and are potentially useful to clinicians managing these patients.
doi:10.1177/0961203309359289
PMCID: PMC3964002  PMID: 20118158
Lupus; disease activity; rate of change; ethnicity; cohort
9.  Pressure-induced planar N6 rings in potassium azide 
Scientific Reports  2014;4:4358.
The first-principles method and the evolutionary algorithm are used to identify stable high pressure phases of potassium azide (KN3). It has been verified that the stable phase with space group I4/mcm below 22 GPa, which is consistent with the experimental result, will transform into the C2/m phase with pressure increasing. These two phases are insulator with anions. A metallic phase with P6/mmm symmetry is preferred above 40 GPa, and the N atoms in this structure form six-membered rings which are important for understanding the pressure effect on anions and phase transitions of KN3. Above the studied pressure (100 GPa), a polymerization of N6 rings may be obtained as the result of the increasing compactness.
doi:10.1038/srep04358
PMCID: PMC3950634  PMID: 24619232
10.  Optimal Cut-Off Points for Two-Step Strategy in Screening of Undiagnosed Diabetes: A Population-Based Study in China 
PLoS ONE  2014;9(3):e87690.
To identify optimal cut-off points of fasting plasma glucose for two-step strategy in screening of undiagnosed diabetes in Chinese people, data were selected from two cross-sectional studies of Metabolic Syndrome in Zhejiang Province of China, Zhejiang Statistical Yearbook (2010), and published literatures. Two-step strategy was used among 17437 subjects sampled from population to screen undiagnosed diabetes. Effectiveness (proportion of cases identified), costs (including medical and non-medical costs), and efficiency (cost per case identified) of these different two-step screening strategies were evaluated. This study found the sensitivities of all the two-step screening strategies with further Oral Glucose Tolerance Test (OGTT) at different Fasting Plasma Glucose (FPG) cut-off points from 5.0 to 7.0 (mmol/L) ranged from 0.66 to 0.91. For the FPG point of 5.0 mmol/L, 91 percent of undiagnosed cases were identified. The total cost of detecting one undiagnosed diabetes case ranged from 547.1 to 1294.5 CNY/case, and the strategy with FPG at cut-off point of 6.1 (mmol/L) resulted in the least cost. Considering both sensitivity and cost of screening diabetes, FPG cut-off point at 5.4 mmol/L was optimized for the two-step strategy. In conclusion, different optimal cut-off points of FPG for two-step strategy in screening of undiagnosed diabetes should be used for different screening purposes.
doi:10.1371/journal.pone.0087690
PMCID: PMC3946449  PMID: 24609110
11.  Complete Genome Characterization of a Novel Enterovirus Type EV-B106 Isolated in China, 2012 
Scientific Reports  2014;4:4255.
Human enterovirus B106 (EV-B106) is a recently identified member of enterovirus species B. In this study, we report the complete genomic characterization of an EV-B106 strain (148/YN/CHN/12) isolated from an acute flaccid paralysis patient in Yunnan Province, China. The new strain had 79.2–81.3% nucleotide and 89.1–94.8% amino acid similarity in the VP1 region with the other two EV-B106 strains from Bolivia and Pakistan. When compared with other EV serotypes, it had the highest (73.3%) VP1 nucleotide similarity with the EV-B77 prototype strain CF496-99. However, when aligned with all EV-B106 and EV-B77 sequences available from the GenBank database, two major frame shifts were observed in the VP1 coding region, which resulted in substantial (20.5%) VP1 amino acid divergence between the two serotypes. Phylogenetic analysis and similarity plot analysis revealed multiple recombination events in the genome of this strain. This is the first report of the complete genome of EV-B106.
doi:10.1038/srep04255
PMCID: PMC3939458  PMID: 24584702
12.  Clinical features and gene mutational spectrum of CDKL5-related diseases in a cohort of Chinese patients 
BMC Medical Genetics  2014;15:24.
Background
Mutations in the cyclin-dependent kinase-like 5 (CDKL5) (NM_003159.2) gene have been associated with early-onset epileptic encephalopathies or Hanefeld variants of RTT(Rett syndrome). In order to clarify the CDKL5 genotype-phenotype correlations in Chinese patients, CDKL5 mutational screening in cases with early-onset epileptic encephalopathies and RTT without MECP2 mutation were performed.
Methods
The detailed clinical information including clinical manifestation, electroencephalogram (EEG), magnetic resonance imaging (MRI), blood, urine amino acid and organic acid screening of 102 Chinese patients with early-onset epileptic encephalopathies and RTT were collected. CDKL5 gene mutations were analyzed by PCR, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). The patterns of X-chromosome inactivation (XCI) were studied in the female patients with CDKL5 gene mutation.
Results
De novo CDKL5 gene mutations were found in ten patients including one missense mutation (c.533G > A, p.R178Q) which had been reported, two splicing mutations (ISV6 + 1A > G, ISV13 + 1A > G), three micro-deletions (c.1111delC, c.2360delA, c.234delA), two insertions (c.1791 ins G, c.891_892 ins TT in a pair of twins) and one nonsense mutation (c.1375C > T, p.Q459X). Out of ten patients, 7 of 9 females with Hanefeld variants of RTT and the remaining 2 females with early onset epileptic encephalopathy, were detected while only one male with infantile spasms was detected. The common features of all female patients with CDKL5 gene mutations included refractory seizures starting before 4 months of age, severe psychomotor retardation, Rett-like features such as hand stereotypies, deceleration of head growth after birth and poor prognosis. In contrast, the only one male patient with CDKL5 mutation showed no obvious Rett-like features as females in our cohort. The X-chromosome inactivation patterns of all the female patients were random.
Conclusions
Mutations in CDKL5 gene are responsible for 7 with Hanefeld variants of RTT and 2 with early-onset epileptic encephalopathy in 71 girls as well as for 1 infantile spasms in 31 males. There are some differences in the phenotypes among genders with CDKL5 gene mutations and CDKL5 gene mutation analysis should be considered in both genders.
doi:10.1186/1471-2350-15-24
PMCID: PMC3938974  PMID: 24564546
CDKL5 mutations; Early-onset epileptic encephalopathy; X chromosome inactivation
13.  Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model 
Background
Sunitinib alone exhibits satisfactory efficacy in several mouse homografts and xenografts but unsatisfactory efficacy in many kinds of solid tumors in clinic. Different from animals, receiving a diagnosis of cancer impacts chronic stress on patients. Here, we examine whether norepinephrine (NE), one of the most potent stress related hormones, leads to the difference in the efficacy of sunitinib between clinical and preclinical trials.
Methods
The influence of NE on mouse melanoma B16F1 cells under sunitinib was evaluated in vitro and in vivo. The β-AR/cAMP/PKA (β-adrenoceptor/cyclic adenosine monophosphate/protein kinase A) signaling pathway was also evaluated in human lung adenocarcinoma cells.
Results
We found that NE upregulated the expression of VEGF, IL-8 and IL-6 in vitro and stimulated tumor growth in vivo, which was mediated by β-AR/cAMP/PKA signaling pathway and could be inhibited by propranolol, a β-blocker for hypertension for decades.
Conclusions
This research indicates exogenous norepinephrine attenuates the efficacy of sunitinib, and a combination of sunitinib and propranolol might be suggested as a new strategy in solid tumor in clinic.
doi:10.1186/1756-9966-33-21
PMCID: PMC3940302  PMID: 24555849
Tumor; Chronic stress; Norepinephrine; Sunitinib; Propranolol
14.  Effects of resveratrol on apoptosis in a rat model of vascular dementia 
Resveratrol is a natural polyphenol widely present in plants, particularly in the skin of red grapes and in wine. It possesses a wide range of biological effects and exhibits neuroprotective effects in numerous diseases. However, data evaluating the effects of resveratrol in vascular dementia (VaD) are lacking. In the present study, the permanent, bilateral common carotid artery occlusion rat model was used to study the effects of resveratrol on VaD. The Morris water maze was used to test the spatial learning and memory performance of the rats. The expression levels of Bax, Bcl-2, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) in the hippocampus were measured. The results showed that resveratrol inhibited memory impairment in the VaD rat model, and attenuated the increases in the expression levels of Bax, cleaved caspase-3 and cleaved PARP and the reductions in the expression levels of Bcl-2 that were induced by VaD. These results provide a novel insight into the neuroprotective effects of resveratrol and its possible therapeutic role in VaD.
doi:10.3892/etm.2014.1542
PMCID: PMC3961111  PMID: 24660032
vascular dementia; resveratrol; apoptosis; caspase-3; poly(ADP-ribose) polymerase
15.  Establishment and Evaluation of Stable Cell Lines Inhibiting Foot-and-Mouth Disease Virus by RNA Interference 
BioMed Research International  2014;2014:109428.
RNA interference (RNAi) has been proved to be a powerful tool for foot-and-mouth disease virus FMDV inhibition in vitro and in vivo. We established five stable baby hamster kidney 21 cell lines (BHK-21) containing five short hairpin RNAs (shRNAs) expression plasmids (p3D1shRNA, p3D2shRNA, p3D3shRNA, p3D4shRNA, and p3D5shRNA) targeting 3D gene of FMDV. Immunofluorescent assay, virus titration, and real-time quantitative reverse transcription polymerase chain reaction (Q-RT-PCR) were conducted to detect the effect of shRNAs on FMDV replication. After challenged with FMDV of O/CHA/99, two cell lines (p3D1shRNA and p3D4shRNA) showed a significant reduction in the synthesis of viral protein and RNA, accompanied by a sharp decrease in viral yield, and the inhibition could last for at least thirty passages. We developed an efficient procedure for the establishment and evaluation of stable cell lines for anti-FMDV research based on RNAi technology, which can be a candidate method for anti-FMDV research.
doi:10.1155/2014/109428
PMCID: PMC3934452
16.  The Rice Semi-Dwarf Mutant sd37, Caused by a Mutation in CYP96B4, Plays an Important Role in the Fine-Tuning of Plant Growth 
PLoS ONE  2014;9(2):e88068.
Plant cytochrome P450 has diverse roles in developmental processes and in the response to environmental cues. Here, we characterized the rice (Oryza sativa L ssp. indica cultivar 3037) semi-dwarf mutant sd37, in which the gene CYP96B4 (Cytochrome P450 96B subfamily) was identified and confirmed as the target by map-based cloning and a complementation test. A point mutation in the SRS2 domain of CYP96B4 resulted in a threonine to lysine substitution in the sd37 mutant. Examination of the subcellular localization of the protein revealed that SD37 was ER-localized protein. And SD37 was predominantly expressed in the shoot apical meristem and developing leaf and root maturation zone but not in the root apical meristem. The sd37 leaves, panicles, and seeds were smaller than those of the wild type. Histological analysis further revealed that a decrease in cell number in the mutant, specifically in the shoots, was the main cause of the dwarf phenotype. Microarray analysis demonstrated that the expression of several cell division-related genes was disturbed in the sd37 mutant. In addition, mutation or strongly overexpression of SD37 results in dwarf plants but moderate overexpression increases plant height. These data suggest that CYP96B4 may be an important regulator of plant growth that affects plant height in rice.
doi:10.1371/journal.pone.0088068
PMCID: PMC3912173  PMID: 24498428
17.  Analysis of BRCA1 Variants in Double-Strand Break Repair by Homologous Recombination and Single-Strand Annealing 
Human mutation  2012;34(3):439-445.
Missense substitutions of uncertain clinical significance in the BRCA1 gene are a vexing problem in genetic counseling for women who have a family history of breast cancer. In this study, we evaluated the functions of 29 missense substitutions of BRCA1 in two DNA repair pathways. Repair of double-strand breaks by homology-directed recombination (HDR) had been previously analyzed for 16 of these BRCA1 variants, and 13 more variants were analyzed in this study. All 29 variants were also analyzed for function in double-strand break repair by the single-strand annealing (SSA) pathway. We found that among the pathogenic mutations in BRCA1, all were defective for DNA repair by either pathway. The HDR assay was accurate because all pathogenic mutants were defective for HDR, and all nonpathogenic variants were fully functional for HDR. Repair by SSA accurately identified pathogenic mutants, but several nonpathogenic variants were scored as defective or partially defective. These results indicated that specific amino acid residues of the BRCA1 protein have different effects in the two related DNA repair pathways, and these results validate the HDR assay as highly correlative with BRCA1-associated breast cancer.
doi:10.1002/humu.22251
PMCID: PMC3906639  PMID: 23161852
BRCA1; homologous recombination; single-strand annealing; centrosome; VUS
18.  Unraveling the Hidden Heterogeneities of Breast Cancer Based on Functional miRNA Cluster 
PLoS ONE  2014;9(1):e87601.
It has become increasingly clear that the current taxonomy of clinical phenotypes is mixed with molecular heterogeneity, which potentially affects the treatment effect for involved patients. Defining the hidden molecular-distinct diseases using modern large-scale genomic approaches is therefore useful for refining clinical practice and improving intervention strategies. Given that microRNA expression profiling has provided a powerful way to dissect hidden genetic heterogeneity for complex diseases, the aim of the study was to develop a bioinformatics approach that identifies microRNA features leading to the hidden subtyping of complex clinical phenotypes. The basic strategy of the proposed method was to identify optimal miRNA clusters by iteratively partitioning the sample and feature space using the two-ways super-paramagnetic clustering technique. We evaluated the obtained optimal miRNA cluster by determining the consistency of co-expression and the chromosome location among the within-cluster microRNAs, and concluded that the optimal miRNA cluster could lead to a natural partition of disease samples. We applied the proposed method to a publicly available microarray dataset of breast cancer patients that have notoriously heterogeneous phenotypes. We obtained a feature subset of 13 microRNAs that could classify the 71 breast cancer patients into five subtypes with significantly different five-year overall survival rates (45%, 82.4%, 70.6%, 100% and 60% respectively; p = 0.008). By building a multivariate Cox proportional-hazards prediction model for the feature subset, we identified has-miR-146b as one of the most significant predictor (p = 0.045; hazard ratios = 0.39). The proposed algorithm is a promising computational strategy for dissecting hidden genetic heterogeneity for complex diseases, and will be of value for improving cancer diagnosis and treatment.
doi:10.1371/journal.pone.0087601
PMCID: PMC3907466  PMID: 24498150
19.  An integrated genetic map based on four mapping populations and quantitative trait loci associated with economically important traits in watermelon (Citrullus lanatus) 
BMC Plant Biology  2014;14:33.
Background
Modern watermelon (Citrullus lanatus L.) cultivars share a narrow genetic base due to many years of selection for desirable horticultural qualities. Wild subspecies within C. lanatus are important potential sources of novel alleles for watermelon breeding, but successful trait introgression into elite cultivars has had limited success. The application of marker assisted selection (MAS) in watermelon is yet to be realized, mainly due to the past lack of high quality genetic maps. Recently, a number of useful maps have become available, however these maps have few common markers, and were constructed using different marker sets, thus, making integration and comparative analysis among maps difficult. The objective of this research was to use single-nucleotide polymorphism (SNP) anchor markers to construct an integrated genetic map for C. lanatus.
Results
Under the framework of the high density genetic map, an integrated genetic map was constructed by merging data from four independent mapping experiments using a genetically diverse array of parental lines, which included three subspecies of watermelon. The 698 simple sequence repeat (SSR), 219 insertion-deletion (InDel), 36 structure variation (SV) and 386 SNP markers from the four maps were used to construct an integrated map. This integrated map contained 1339 markers, spanning 798 cM with an average marker interval of 0.6 cM. Fifty-eight previously reported quantitative trait loci (QTL) for 12 traits in these populations were also integrated into the map. In addition, new QTL identified for brix, fructose, glucose and sucrose were added. Some QTL associated with economically important traits detected in different genetic backgrounds mapped to similar genomic regions of the integrated map, suggesting that such QTL are responsible for the phenotypic variability observed in a broad array of watermelon germplasm.
Conclusions
The integrated map described herein enhances the utility of genomic tools over previous watermelon genetic maps. A large proportion of the markers in the integrated map are SSRs, InDels and SNPs, which are easily transferable across laboratories. Moreover, the populations used to construct the integrated map include all three watermelon subspecies, making this integrated map useful for the selection of breeding traits, identification of QTL, MAS, analysis of germplasm and commercial hybrid seed detection.
doi:10.1186/1471-2229-14-33
PMCID: PMC3898567  PMID: 24443961
Watermelon; Integrated genetic map; QTL; Sugar content
20.  Study on the Trend and Disease Burden of Injury Deaths in Chinese Population, 2004–2010 
PLoS ONE  2014;9(1):e85319.
Injuries are a growing public health concern in China, accounting for more than 30% of all Person Years of Life Lost (PYLL) due to premature mortality. This study analyzes the trend and disease burden of injury deaths in Chinese population from 2004 to 2010, using data from the National Disease Surveillance Points (DSPs) system, as injury deaths are classified based on the International Classification of Disease-10th Revision (ICD-10). We observed that injury death accounted for nearly 10% of all deaths in China throughout the period 2004–2010, and the injury mortality rates were higher in males than those in females, and higher in rural areas than in urban areas. Traffic crashes (33.79–38.47% of all injury deaths) and suicides (16.20–22.01%) were the two leading causes of injury deaths. Alarmingly, suicide surpassed traffic crashes as the leading cause of injury mortality in rural females, yet adults aged 65 and older suffered the greatest number of fatal falls (20,701 deaths, 2004–2010). The burden of injury among men (72.11%) was about three times more than that of women's (28.89%). This study provides indispensible evidence that China Authority needs to improve the surveillance and deterrence of three major types of injuries: Traffic-related injury deaths should be targeted for injury prevention activities in all population, people aged 65+ should be encouraged to take individual fall precautions, and prevention of suicidal behavior in rural females should be another key priority for the government of China.
doi:10.1371/journal.pone.0085319
PMCID: PMC3894968  PMID: 24465534
21.  miR-203 inhibits tumor cell migration and invasion via caveolin-1 in pancreatic cancer cells 
Oncology Letters  2014;7(3):658-662.
Pancreatic cancer is one of the most lethal malignant diseases with the poorest prognosis and is the fourth leading cause of tumor-associated mortality in the industrialized world. microRNAs (miRNAs or miRs) are small noncoding RNAs of approximately 22 nucleotides long that are able to function as oncogenes or tumor suppressors in human cancer. In our study, overexpression of miR-203 in Panc-1 cells is sufficient to reduce migratory ability and invasiveness, and to induce upregulation of epithelial markers (Snail, ZO-1 and β-catenin) followed by a decrease of mesenchymal marker expression (Zeb-1, vimentin and fibronectin). We also found that the caveolin-1 mRNA or protein levels are modulated by miR-203 in Panc-1 cells. We found that exogenous miR-203 altered the level of cell migration and invasion, and the expression of associated proteins following caveolin-1 knockdown by small interfering RNA. These results demonstrate that miR-203 inhibits cell migration and invasion via caveolin-1 in pancreatic cancer cells, suggest that miR-203 expression may be a useful indicator of the metastatic potential and provide a new therapeutic target in this common malignancy.
doi:10.3892/ol.2014.1807
PMCID: PMC3919932  PMID: 24520289
pancreatic cancer; miR-203; caveolin-1
22.  microRNA-155 acts as an oncogene by targeting the tumor protein 53-induced nuclear protein 1 in esophageal squamous cell carcinoma 
MicroRNA-155 (miR-155) is overexpressed in many human cancers; however, the function of miR-155 is largely unknown in esophageal squamous cell carcinoma (ESCC). In the present study, we found that miR-155 is dramatically increased in ESCC tissues compared with the paired adjacent normal tissues, which suggested that miR-155 acts as an oncogene in ESCC. We predicted that tumor protein p53-induced nuclear protein 1 (TP53INP1) is a candidate target gene of miR-155 given that miR-155 expression decreased mRNA and protein levels of TP53INP1 as determined by RT-PCR and Western blot analysis. In addition, miR-155 and TP53INP1 showed a negative relation in ESCC tissues. Dual luciferase-based reporter assay indicated direct regulation of TP53INP1 by miR-155. Furthermore, we demonstrated that RNA interference of TP53INP1 increased the proliferation and colonies formation of EC-1 cells. Up-regulation of TP53INP1 abrogated miR-155 induced growth in EC-1 cells and mutation of TP53INP1 in 3’-UTR restored the effects when co-transfected with miR-155. We also indicated that overexpression of miR-155 significantly promoted the proliferation of EC-1 cells in vitro and the development of tumors in nude mice. Taken together, our study reveals that miR-155 acts as an oncogene by targeting TP53INP1 in ESCC.
PMCID: PMC3925904  PMID: 24551280
ESCC; TP53INP1; miR-155
23.  PDGF, NT-3 and IGF-2 in Combination Induced Transdifferentiation of Muscle-Derived Stem Cells into Schwann Cell-Like Cells 
PLoS ONE  2014;9(1):e73402.
Muscle-derived stem cells (MDSCs) are multipotent stem cells with a remarkable long-term self-renewal and regeneration capacity. Here, we show that postnatal MDSCs could be transdifferentiated into Schwann cell-like cells upon the combined treatment of three neurotrophic factors (PDGF, NT-3 and IGF-2). The transdifferentiation of MDSCs was initially induced by Schwann cell (SC) conditioned medium. MDSCs adopted a spindle-like morphology similar to SCs after the transdifferentiation. Immunocytochemistry and immunoblot showed clearly that the SC markers S100, GFAP and p75 were expressed highly only after the transdifferentiation. Flow cytometry assay showed that the portion of S100 expressed cells was more than 60 percent and over one fourth of the transdifferentiated cells expressed all the three SC markers, indicating an efficient transdifferentiation. We then tested neurotrophic factors in the conditioned medium and found it was PDGF, NT-3 and IGF-2 in combination that conducted the transdifferentiation. Our findings demonstrate that it is possible to use specific neurotrophic factors to transdifferentiate MDSCs into Schwann cell-like cells, which might be therapeutically useful for clinical applications.
doi:10.1371/journal.pone.0073402
PMCID: PMC3891637  PMID: 24454677
24.  Seroprevalence of Antipolio Antibodies among Children <15 Years of Age in Border Provinces in China 
Despite remarkable progression toward polio eradication worldwide, wild poliovirus (WPV) importation has been a great challenge for China, as it shares borders with countries where WPV is endemic. The objective of this study was to estimate poliovirus antibody seroprevalence among children <15 years of age in 3 border provinces (Yunnan Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region) in China. A cross-sectional, hospital-based study was undertaken in 3 border provinces in 2010. Individuals <15 years old who visited hospitals at the prefecture level or above to have their blood drawn for any reason were invited to participate in our study. Neutralizing antibody titers to polio serotypes 1 (P1), P2, and P3 were assayed according to the World Health Organization manual for the virological investigation of polio. Antibody titers of ≥8 were considered positive. Among the 1,360 subjects enrolled, 1,220 (89.7%), 1,259 (92.6%), and 1,112 (81.8%) were seropositive to P1, P2, and P3, respectively, and 1,051 (77.3%) subjects were seropositive to all three serotypes. The highest seropositive rates were observed in Xinjiang Uygur Autonomous Region. By age, 3- to 5-year-old subjects had the highest rate of seropositivity, and seropositivity decreased significantly with increasing age. The risk of WPV importation will continue until WPV transmission has been interrupted worldwide. Consistent with the Global Polio Eradication Initiative's polio endgame strategy, China must maintain its polio-free status by ensuring adequate population immunity against polio. Because immunity wanes with increasing age, a booster dose with bivalent type 1 and 2 oral poliovirus vaccine could be considered for teenagers in China.
doi:10.1128/CVI.00092-13
PMCID: PMC3697440  PMID: 23677325
25.  Formation of bicyclic pyrroles from the catalytic coupling reaction of 2,5-disubstituted pyrroles with terminal alkynes, involving the activation of multiple C–H bonds† 
Substituted bicyclic pyrroles are produced directly from the coupling reaction of 2,5-disubstituted pyrroles with terminal alkynes, involving the activation of multiple C–H bonds and regioselective cyclisation.
doi:10.1039/b804263b
PMCID: PMC3876409  PMID: 18473066

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