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1.  Expression of semaphorin 3A and neuropilin 1 with clinicopathological features and survival in human tongue cancer 
Objective: To investigate the association between semaphorin 3A (SEMA 3A) and its receptor neuropilin 1 (NRP1) and the clinicopathologic characteristics of patients with tongue cancer. Study Design: Forty-three tongue squamous cell carcinoma specimens were included. Immunohistochemical staining of SEMA3A and NRP1 was performed on 15 normal tongue epithelium specimens and the 43 tumour specimens. Immunoreactivity was evaluated based on the staining intensity and distribution score. Statistical analyses were performed using Chi-squared and Spearman tests and Kaplan-Meier analysis. Results: SEMA3A was significantly down-regulated in tongue cancer compared with normal tongue (P=0.025), while NRP1 was over-expressed in tumours (P<0.001). SEMA3A expression inversely correlated with nodal metastasis (P=0.017). NRP1 expression did not correlate with any clinicopathological characteristics. Higher SEMA3A expression strongly predicted longer survival (P=0.005). Scores for the NRP1/SEMA3A ratio of ≥1 predicted shorter survival (P=0.045). Conclusions: Aberrant expression of SEMA3A and its receptor NRP1 might be involved in the development of tongue cancer and might be useful prognostic markers in this tumour type.
Key words:Semaphorin 3A, neuropilin 1, tongue, squamous cell carcinoma.
doi:10.4317/medoral.18168
PMCID: PMC3505717  PMID: 22926477
2.  Toxoplasma gondii Pneumonia in an Immunocompetent Individual 
doi:10.1097/MAJ.0000000000000496
PMCID: PMC4495860  PMID: 26110745
Toxoplasma gondii; shortness of breath and fever; compound sulfamethoxazole; clindamycin phosphate
3.  Atrazine Causes Autophagy- and Apoptosis-Related Neurodegenerative Effects in Dopaminergic Neurons in the Rat Nigrostriatal Dopaminergic System 
Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) is widely used as a broad-spectrum herbicide. Animal studies have demonstrated that ATR exposure can cause cell death in dopaminergic neurons. The molecular mechanisms underlying ATR-induced neuronal cell death, however, are unknown. In this study, we investigated the autophagy and apoptosis induced by ATR in dopaminergic neurons in vivo. Wistar rats were administered with ATR at doses of 10, 50 and 100 mg/kg body weight by oral gavage for three months. In terms of histopathology, the expression of autophagy- and apoptosis-related genes as well as proteins related to the Beclin-1/B-cell lymphoma 2 (Bcl-2) autophagy and apoptosis pathways were examined in the rat nigrostriatal dopaminergic system. We observed degenerative micromorphology indicative of neuronal apoptosis and mitochondrial autophagy by electron microscopy in ATR-exposed rat striatum. The rat ventral mesencephalon in the ATR-exposed groups also showed increased expression of Beclin-1, LC3-II, Bax and Caspase-9, and decreased expression of tyrosine hydroxylase (TH), Bcl-xl and Bcl-2. These findings indicate that ATR may induce autophagy- and apoptosis-related changes in doparminergic neurons. Furthermore, this induction may be regulated by the Beclin-1 and Bcl-2 autophagy and apoptosis pathways, and this may help to better understand the mechanism underlying the neurotoxicity of ATR.
doi:10.3390/ijms160613490
PMCID: PMC4490505  PMID: 26075868
atrazine; autophagy; apoptosis; neurotoxicity; wistar rats; dopaminergic neuron
4.  Berberine reverses abnormal expression of L-type pyruvate kinase by DNA demethylation and histone acetylation in the livers of the non-alcoholic fatty disease rat 
Berberine (BBR) can potentially be used as a drug against non-alcoholic fatty liver disease (NAFLD) and diabetes. Our previous study found that BBR could change the pattern of DNA methylation. But the mechanisms underlying berberine are still far from completely understood. In this study, the function of L-PK in cell metabolism was explored, and high-fat-diet induced SD rats NAFLD models were created. The NAFLD rats were randomly grouped to be oral administration with BBR at a dosage of 200 mg/kg daily. Then DNA methylation and histone acetylation around the L-type Pyruvate Kinase (L-PK) gene were examined. In the results, we found that L-PK had a positive effect on cell proliferation, glucose utilization and triglyceride metabolism. However, the expression of L-PK was reduced in the livers of NAFLD rats, in accord with the decrease of DNA hypermethylation and histone deacetylation in the regulatory regions of L-PK. Notably, BBR treatment can restore the expression of L-PK by the demethylation of L-PK promoter and the increase in acetylation levels of histone H3 and H4 around L-PK, which indicated that BBR may be a potential drug for epigenetic-included diseases.
PMCID: PMC4509242  PMID: 26221297
Berberine; L-type pyruvate kinase; non-alcoholic fatty liver disease; DNA methylation; histone acetylation
5.  Annual Carbon Emissions from Deforestation in the Amazon Basin between 2000 and 2010 
PLoS ONE  2015;10(5):e0126754.
Reducing emissions from deforestation and forest degradation (REDD+) is considered one of the most cost-effective strategies for mitigating climate change. However, historical deforestation and emission rates―critical inputs for setting reference emission levels for REDD+―are poorly understood. Here we use multi-source, time-series satellite data to quantify carbon emissions from deforestation in the Amazon basin on a year-to-year basis between 2000 and 2010. We first derive annual deforestation indicators by using the Moderate Resolution Imaging Spectroradiometer Vegetation Continuous Fields (MODIS VCF) product. MODIS indicators are calibrated by using a large sample of Landsat data to generate accurate deforestation rates, which are subsequently combined with a spatially explicit biomass dataset to calculate committed annual carbon emissions. Across the study area, the average deforestation and associated carbon emissions were estimated to be 1.59 ± 0.25 M ha•yr−1 and 0.18 ± 0.07 Pg C•yr−1 respectively, with substantially different trends and inter-annual variability in different regions. Deforestation in the Brazilian Amazon increased between 2001 and 2004 and declined substantially afterwards, whereas deforestation in the Bolivian Amazon, the Colombian Amazon, and the Peruvian Amazon increased over the study period. The average carbon density of lost forests after 2005 was 130 Mg C•ha−1, ~11% lower than the average carbon density of remaining forests in year 2010 (144 Mg C•ha−1). Moreover, the average carbon density of cleared forests increased at a rate of 7 Mg C•ha−1•yr−1 from 2005 to 2010, suggesting that deforestation has been progressively encroaching into high-biomass lands in the Amazon basin. Spatially explicit, annual deforestation and emission estimates like the ones derived in this study are useful for setting baselines for REDD+ and other emission mitigation programs, and for evaluating the performance of such efforts.
doi:10.1371/journal.pone.0126754
PMCID: PMC4423949  PMID: 25951328
6.  Current rectifying and resistive switching in high density BiFeO3 nanocapacitor arrays on Nb-SrTiO3 substrates 
Scientific Reports  2015;5:9680.
Ultrahigh density well-registered oxide nanocapacitors are very essential for large scale integrated microelectronic devices. We report the fabrication of well-ordered multiferroic BiFeO3 nanocapacitor arrays by a combination of pulsed laser deposition (PLD) method and anodic aluminum oxide (AAO) template method. The capacitor cells consist of BiFeO3/SrRuO3 (BFO/SRO) heterostructural nanodots on conductive Nb-doped SrTiO3 (Nb-STO) substrates with a lateral size of ~60 nm. These capacitors also show reversible polarization domain structures, and well-established piezoresponse hysteresis loops. Moreover, apparent current-rectification and resistive switching behaviors were identified in these nanocapacitor cells using conductive-AFM technique, which are attributed to the polarization modulated p-n junctions. These make it possible to utilize these nanocapacitors in high-density (>100 Gbit/inch2) nonvolatile memories and other oxide nanoelectronic devices.
doi:10.1038/srep09680
PMCID: PMC4389717  PMID: 25853937
7.  Pathogenicity of Five Strains of Toxoplasma gondii from Different Animals to Chickens 
Toxoplasma gondii is a protozoan parasite with a broad range of intermediate hosts. Chickens as important food-producing animals can also serve as intermediate hosts. To date, experimental studies on the pathogenicity of T. gondii in broiler chickens were rarely reported. The objective of the present study was to compare the pathogenicity of 5 different T. gondii strains (RH, CN, JS, CAT2, and CAT3) from various host species origin in 10-day-old chickens. Each group of chickens was infected intraperitoneally with 5×108, 1×108, 1×107, and 1×106 tachyzoites of the 5 strains, respectively. The negative control group was mockly inoculated with PBS alone. After infection, clinical symptoms and rectal temperatures of all the chickens were checked daily. Dead chickens during acute phage of the infection were checked for T. gondii tachyzoites by microscope, while living cases were checked for T. gondii infection at day 53 post-inoculation (PI) by PCR method. Histopathological sections were used to observe the pathological changes in the dead chickens and the living animals at day 53 PI. No significant differences were found in survival periods, histopathological findings, and clinical symptoms among the chickens infected with the RH, CN, CAT2, and CAT3 strains. Histopathological findings and clinical symptoms of the JS (chicken origin) group were similar to the others. However, average survival times of infected chickens of the JS group inoculated with 5×108 and 1×108 tachyzoites were 30.0 and 188.4 hr, respectively, significantly shorter than those of the other 4 mammalian isolates. Chickens exposed to 108 of T. gondii tachyzoites and higher showed acute signs of toxoplasmosis, and the lesions were relatively more severe than those exposed to lower doses. The results indicated that the pathogenicity of JS strain was comparatively stronger to the chicken, and the pathogenicity was dose-dependent.
doi:10.3347/kjp.2015.53.2.155
PMCID: PMC4416365  PMID: 25925173
Toxoplasma gondii; chicken; pathogenicity
8.  High expression of N-myc (and STAT) interactor predicts poor prognosis and promotes tumor growth in human glioblastoma 
Oncotarget  2014;6(7):4901-4919.
Glioma is the most malignant brain tumor and glioblastoma (GBM) is the most aggressive type. The involvement of N-myc (and STAT) interactor (NMI) in tumorigenesis was sporadically reported but far from elucidation. This study aims to investigate roles of NMI in human glioma. Three independent cohorts, the Chinese tissue microarray (TMA) cohort (N = 209), the Repository for Molecular Brain Neoplasia Data (Rembrandt) cohort (N = 371) and The Cancer Genome Atlas (TCGA) cohort (N = 528 or 396) were employed. Transcriptional or protein levels of NMI expression were significantly increased according to tumor grade in all three cohorts. High expression of NMI predicted significantly unfavorable clinical outcome for GBM patients, which was further determined as an independent prognostic factor. Additionally, expression and prognostic value of NMI were associated with molecular features of GBM including PTEN deletion and EGFR amplification in TCGA cohort. Furthermore, overexpression or depletion of NMI revealed its regulation on G1/S progression and cell proliferation (both in vitro and in vivo), and this effect was partially dependent on STAT1, which interacted with and was regulated by NMI. These data demonstrate that NMI may serve as a novel prognostic biomarker and a potential therapeutic target for glioblastoma.
PMCID: PMC4467123  PMID: 25669971
NMI; glioblastoma; prognosis; immunohistochemistry; TCGA
9.  Mechanistic Insight into the Elastin Degradation Process by the Metalloprotease Myroilysin from the Deep-Sea Bacterium Myroides profundi D25 
Marine Drugs  2015;13(3):1481-1496.
Elastases have been widely studied because of their important uses as medicine and meat tenderizers. However, there are relatively few studies on marine elastases. Myroilysin, secreted by Myroides profundi D25 from deep-sea sediment, is a novel elastase. In this study, we examined the elastin degradation mechanism of myroilysin. When mixed with insoluble bovine elastin, myroilysin bound hydrophobically, suggesting that this elastase may interact with the hydrophobic domains of elastin. Consistent with this, analysis of the cleavage pattern of myroilysin on bovine elastin and recombinant tropoelastin revealed that myroilysin preferentially cleaves peptide bonds with hydrophobic residues at the P1 and/or P1′ positions. Scanning electron microscopy (SEM) of cross-linked recombinant tropoelastin degraded by myroilysin showed preferential damages of spherules over cross-links, as expected for a hydrophobic preference. The degradation process of myroilysin on bovine elastin fibres was followed by light microscopy and SEM, revealing that degradation begins with the formation of crevices and cavities at the fibre surface, with these openings increasing in number and size until the fibre breaks into small pieces, which are subsequently fragmented. Our results are helpful for developing biotechnological applications for myroilysin.
doi:10.3390/md13031481
PMCID: PMC4377995  PMID: 25793427
deep sea; elastase; bacteria; degradation mechanism; biotechnological potential
10.  Is Yield Increase Sufficient to Achieve Food Security in China? 
PLoS ONE  2015;10(2):e0116430.
Increasing demand for food, driven by unprecedented population growth and increasing consumption, will keep challenging food security in China. Although cereal yields have substantially improved during the last three decades, whether it will keep thriving to meet the increasing demand is not known yet. Thus, an integrated analysis on the trends of crop yield and cultivated area is essential to better understand current state of food security in China, especially on county scale. So far, yield stagnation has extensively dominated the main cereal-growing areas across China. Rice yield is facing the most severe stagnation that 53.9% counties tracked in the study have stagnated significantly, followed by maize (42.4%) and wheat (41.9%). As another important element for production sustainability, but often neglected is the planted area patterns. It has been further demonstrated that the loss in productive arable land for rice and wheat have dramatically increased the pressure on achieving food security. Not only a great deal of the planted areas have stagnated since 1980, but also collapsed. 48.4% and 54.4% of rice- and wheat-growing counties have lost their cropland areas to varying degrees. Besides, 27.6% and 35.8% of them have retrograded below the level of the 1980s. The combined influence (both loss in yield and area) has determined the crop sustainable production in China to be pessimistic for rice and wheat, and consequently no surprise to find that more than half of counties rank a lower level of production sustainability. Therefore, given the potential yield increase in wheat and maize, as well as substantial area loss of rice and wheat, the possible targeted adaptation measures for both yield and cropping area is required at county scale. Moreover, policies on food trade, alongside advocation of low calorie diets, reducing food loss and waste can help to enhance food security.
doi:10.1371/journal.pone.0116430
PMCID: PMC4332688  PMID: 25680193
11.  Deep RNA sequencing reveals a high frequency of alternative splicing events in the fungus Trichoderma longibrachiatum 
BMC Genomics  2015;16(1):54.
Background
Alternative splicing is crucial for proteome diversity and functional complexity in higher organisms. However, the alternative splicing landscape in fungi is still elusive.
Results
The transcriptome of the filamentous fungus Trichoderma longibrachiatum was deep sequenced using Illumina Solexa technology. A total of 14305 splice junctions were discovered. Analyses of alternative splicing events revealed that the number of all alternative splicing events (10034), intron retentions (IR, 9369), alternative 5’ splice sites (A5SS, 167), and alternative 3’ splice sites (A3SS, 302) is 7.3, 7.4, 5.1, and 5.9-fold higher, respectively, than those observed in the fungus Aspergillus oryzae using Illumina Solexa technology. This unexpectedly high ratio of alternative splicing suggests that alternative splicing is important to the transcriptome diversity of T. longibrachiatum. Alternatively spliced introns had longer lengths, higher GC contents, and lower splice site scores than constitutive introns. Further analysis demonstrated that the isoform relative frequencies were correlated with the splice site scores of the isoforms. Moreover, comparative transcriptomics determined that most enzymes related to glycolysis and the citrate cycle and glyoxylate cycle as well as a few carbohydrate-active enzymes are transcriptionally regulated.
Conclusions
This study, consisting of a comprehensive analysis of the alternative splicing landscape in the filamentous fungus T. longibrachiatum, revealed an unexpectedly high ratio of alternative splicing events and provided new insights into transcriptome diversity in fungi.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1251-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-015-1251-8
PMCID: PMC4324775  PMID: 25652134
Alternative splicing; Fungi; RNA-Seq; Intron retention; Transcriptome; Trichoderma longibrachiatum
12.  Relative Localization in Wireless Sensor Networks for Measurement of Electric Fields under HVDC Transmission Lines 
Sensors (Basel, Switzerland)  2015;15(2):3540-3564.
In the wireless sensor networks (WSNs) for electric field measurement system under the High-Voltage Direct Current (HVDC) transmission lines, it is necessary to obtain the electric field distribution with multiple sensors. The location information of each sensor is essential to the correct analysis of measurement results. Compared with the existing approach which gathers the location information by manually labelling sensors during deployment, the automatic localization can reduce the workload and improve the measurement efficiency. A novel and practical range-free localization algorithm for the localization of one-dimensional linear topology wireless networks in the electric field measurement system is presented. The algorithm utilizes unknown nodes' neighbor lists based on the Received Signal Strength Indicator (RSSI) values to determine the relative locations of nodes. The algorithm is able to handle the exceptional situation of the output permutation which can effectively improve the accuracy of localization. The performance of this algorithm under real circumstances has been evaluated through several experiments with different numbers of nodes and different node deployments in the China State Grid HVDC test base. Results show that the proposed algorithm achieves an accuracy of over 96% under different conditions.
doi:10.3390/s150203540
PMCID: PMC4367372  PMID: 25658390
wireless sensor networks; electric field measurement; relative localization; Received Signal Strength Indicator-based (RSSI-based)
13.  Genome-wide analysis of the R2R3-MYB transcription factor genes in Chinese cabbage (Brassica rapa ssp. pekinensis) reveals their stress and hormone responsive patterns 
BMC Genomics  2015;16(1):17.
Background
The MYB superfamily is one of the most abundant transcription factor (TF) families in plants. MYB proteins include highly conserved N-terminal MYB repeats (1R, R2R3, 3R, and atypical) and various C-terminal sequences that confer extensive functions. However, the functions of most MYB genes are unknown, and have been little studied in Chinese cabbage.
Results
Here, we analyzed 256 (55.2% of total MYBs) R2R3-MYB genes from Chinese cabbage (Brassica rapa ssp. pekinensis) and anchored them onto the 10 chromosomes and three subgenomes. The R2R3-, 3R- and atypical MYB proteins in Chinese cabbage formed 45 subgroups based on domain similarity and phylogenetic topology. Organization and syntenic analysis revealed the genomic distribution and collinear relationships of the R2R3-BrMYBs. Synonymous nucleotide substitution (Ka/Ks) analysis showed that the Chinese cabbage MYB DNA-binding domain is under strong purifying selection. Moreover, RNA-seq data revealed tissue-specific and distinct R2R3-BrMYB expression profiles, and quantitative real-time PCR (qPCR) analysis in leaves showed stress responsive expression and crosstalk with ABA-auxin signaling cascades.
Conclusions
In this study, we identified the largest MYB gene family in plants to date. Our results indicate that members of this superfamily may be involved in plant development, stress responses and leaf senescence, highlighting their functional diversity.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1216-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-015-1216-y
PMCID: PMC4334723  PMID: 25613160
Genome-wide analysis; R2R3-MYB transcription factor; Stress responses; Hormone signals; Chinese cabbage
14.  Effects of Electroacupuncture Stimulation at “Zusanli” Acupoint on Hepatic NO Release and Blood Perfusion in Mice 
The study is to observe the influence of electroacupuncture (EA) stimulation at “Zusanli” (ST36) on the release of nitric oxide (NO) and blood perfusion (BP) in the liver and further explore whether the hepatic blood perfusion (HBP) changes were regulated by EA ST36 induced NO in nitric oxide synthase inhibited mice. The HBP change of the mice was detected by laser speckle perfusion imaging (LSPI) before and after being given interventions, and the NO in liver tissue was detected by nitric acid reductase in each group. The NO levels and HBP in the L-NAME group were significantly lower than those in the control group (P < 0.01). The NO level and HBP increase in EA group were significantly higher than those in control group (P < 0.05). The NO level in the L-NAME EA group was slightly higher than that in the L-NAME group. The HBP increase in the L-NAME EA group was not statistically significant. These results showed that EA could accelerate the synthesis of NO and thereby increase HBP via vasodilation in liver tissue.
doi:10.1155/2015/826805
PMCID: PMC4306412  PMID: 25649678
15.  Impact of Water Content and Temperature on the Degradation of Cry1Ac Protein in Leaves and Buds of Bt Cotton in the Soil 
PLoS ONE  2015;10(1):e115240.
Determining the influence of soil environmental factors on degradation of Cry1Ac protein from Bt cotton residues is vital for assessing the ecological risks of this commercialized transgenic crop. In this study, the degradation of Cry1Ac protein in leaves and in buds of Bt cotton in soil was evaluated under different soil water content and temperature settings in the laboratory. An exponential model and a shift-log model were used to fit the degradation dynamics of Cry1Ac protein and estimate the DT50 and DT90 values. The results showed that Cry1Ac protein in the leaves and buds underwent rapid degradation in the early stage (before day 48), followed by a slow decline in the later stage under different soil water content and temperature. Cry1Ac protein degraded the most rapidly in the early stage at 35°C with 70% soil water holding capacity. The DT50 values were 12.29 d and 10.17 d and the DT90 values were 41.06 d and 33.96 d in the leaves and buds, respectively. Our findings indicated that the soil temperature was a major factor influencing the degradation of Cry1Ac protein from Bt cotton residues. Additionally, the relative higher temperature (25°C and 35°C) was found to be more conducive to degradation of Cry1Ac protein in the soil and the greater water content (100%WHC) retarded the process. These findings suggested that under appropriate soil temperature and water content, Cry1Ac protein from Bt cotton residues will not persist and accumulate in soil.
doi:10.1371/journal.pone.0115240
PMCID: PMC4283960  PMID: 25559638
16.  A Pilot Study on Effects of Acupuncture and Moxibustion by Hyperspectral Imaging Technique 
This study was to observe the effects of acupuncture and moxibustion on spectrum features of acupoint using hyperspectral imaging (HSI) technique. HSI of the Neiguan (PC6) in the acupuncture groups, moxibustion groups, and control groups was scanned by the hyperspectral imager to analyze the spectrum features and the variations within the wavelength of 400–1000 nm and explore the relationship between the spectral characteristics and effects of acupuncture and moxibustion. The light absorption intensity was slightly reduced within the wave band of 540–590 nm after acupuncture. The absorption intensity of PC6 before moxibustion was significantly higher than that after moxibustion, and the maximum reduction was found at the wavelength of 580 nm with 20.5% reduction, P < 0.05. There was no significant change of the spectrum of palm and PC6 and the spectrum curves of the acupoint were basically identical in control group. The light absorption intensity of PC6 of human body was weakened after Acu-mox. Specific wavelengths were all exhibited at 580 nm and the effect of moxibustion was more significant. HSI technique can be used to measure the spectral characteristics of the acupoint areas. This first time research would be significant and beneficial for study on the effect of acupuncture and moxibustion.
doi:10.1155/2014/135212
PMCID: PMC4269316  PMID: 25544851
17.  Three new species of the myrmecophilous genus Doryloxenus from China (Coleoptera, Staphylinidae, Aleocharinae) 
ZooKeys  2014;75-83.
Three new species of the pygostenine genus Doryloxenus Wasmann, viz., Doryloxenus aenictophilus sp. n. (from Zhejiang), Doryloxenus tangliangi sp. n. (from Zhejiang), and Doryloxenus songzhigaoi sp. n. (from Yunnan), are described, illustrated and distinguished from the Asian congeners. An identification key to the Chinese species is given.
doi:10.3897/zookeys.456.8584
PMCID: PMC4329400  PMID: 25709522
Pygostenini; Doryloxenus; myrmecophilous; army ant; new species; China
18.  Vitamin C treatment attenuates hemorrhagic shock related multi-organ injuries through the induction of heme oxygenase-1 
Background
Vitamin C (VitC) has recently been shown to exert beneficial effects, including protecting organ function and inhibiting inflammation, in various critical care conditions, but the specific mechanism remains unclear. Induction of heme oxygenase (HO)-1, a heat shock protein, has been shown to prevent organ injuries in hemorrhagic shock (HS) but the relationship between VitC and HO-1 are still ill-defined so far. Here we conducted a systemic in vivo study to investigate if VitC promoted HO-1 expression in multiple organs, and then tested if the HO-1 induction property of VitC was related to its organ protection and anti-inflammatory effect.
Methods
Firstly, to determine the HO-1 induction property of VitC, the HO-1 level were measured in tissues including kidney, liver and lung of the normal and HS model of Sprague–Dawley (SD) rats after VitC treatment (100 mg/kg body weight). Secondly, to testify if VitC prevented HS related organ injuries via inducing HO-1, the HS model of rats were separately pre- and post-treated with VitC, and some of them also received Zinc protoporphyrin (Znpp), a specific HO-1 inhibitor. The HO-1 activity in tissues was tested; the organ injuries (as judged by histological changes in tissues and the biochemical indicators level in serum) and inflammatory response in tissues (as judged by the level of pro-inflammatory cytokines Tumor necrosis factor-α and Interleukin-6 ) were analyzed.
Results
The HO-1 mRNA and protein level in kidney, liver, and lung were highly induced by VitC treatement under normal and HS conditions. The HO-1 activity in tissues was enhanced by both VitC pre- and post-treatment, which was shown to improve the organ injuries and inhibit the inflammatory response in the HS model of rats. Of note, the beneficial effects of VitC were abolished after HO-1 activity was blocked by Znpp.
Conclusions
VitC led to a profound induction of HO-1 in multiple organs including the kidney, liver and lung, and this property might be responsible for the organ protection and inflammation inhibitory effects of both pre- and post-treatment with VitC in HS.
doi:10.1186/1472-6882-14-442
PMCID: PMC4246491  PMID: 25387896
19.  Relationship between single nucleotide polymorphisms in the 3’-untranslated region of the vascular endothelial growth factor gene and susceptibility to diabetic peripheral neuropathy in China 
Archives of Medical Science : AMS  2013;10(5):1028-1034.
Introduction
This study is to elucidate the relationship between a 936C/T mutation at the 3’-untranslated region of the human vascular endothelial growth factor (VEGF) gene and diabetic peripheral neuropathy (DPN).
Material and methods
All subjects recruited in this study were divided into DM (diabetes without neuropathy, retinopathy or nephropathy), DPN (diabetes with peripheral neuropathy only) and healthy control groups. The gene polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism, as well as other clinical methods including serum VEGF by ELISA.
Results
The C allele frequency and CC genotype frequency in the DPN group were higher than those in the NC group and DM group. The T allele frequency and CT+TT genotype (carrying the T allele) frequency in the DPN group were lower than those in the NC group (χ2 = 19.051 and 18.533, both p < 0.001) and DM group (χ2 = 11.117 and 11.156, both p = 0.001). However, there was no statistically significant difference in the three genotype (CC/CT+TT) frequencies and allele (C/T) frequencies between the DM group and the NC group. The multivariate logistic regression analysis showed that the levels of glycated hemoglobin (HbA1c), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and plasma VEGF positively correlated with DPN, while the 936C/T gene polymorphism of VEGF negatively correlated with DPN.
Conclusions
Allele 936C of VEGF may serve as a genetic marker susceptible to DPN, while allele 936T may be a protective genetic marker of DPN.
doi:10.5114/aoms.2013.39381
PMCID: PMC4223128  PMID: 25395956
vascular endothelial growth factor; polymorphisms; type 2 diabetes mellitus; diabetic peripheral neuropathy
20.  Association between non-alcoholic fatty liver disease and arterial stiffness in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population 
Background and objective: Non-alcoholic fatty liver disease (NAFLD) is associated with arterial stiffness in the general population. Age, obesity, hypertension, and diabetics are risk factors for arterial stiffness. In this study, we aimed to investigate the association between NAFLD and arterial stiffness as measured by brachial-ankle pulse wave velocity (baPWV) in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population. Methods: A cross-sectional study with 1296 non-obese, non-hypertensive, and non-diabetic young and middle-aged (20–65 years) subjects undergoing routine medical check-ups in the International Health Care Center of the Second Affiliated Hospital of School of Medicine of Zhejiang University was carried out. Fatty liver was diagnosed by ultrasonography, and baPWV was measured using an automatic waveform analyzer. The subjects were classified into two groups according to the presence of NAFLD, and divided into a further two groups according to their baPWV. Results: The overall incidence of NAFLD was 19.0%, and NAFLD patients had a significantly higher level of baPWV than the controls ((1321±158) cm/s vs. (1244±154) cm/s; P<0.001). The incidence of NAFLD was clearly higher in the increased baPWV group than in the normal baPWV group (29.3% vs. 16.9%; P<0.001), and the incidence increased in line with the increase of baPWV quartiles in the normal range as well as with the severity of arterial stiffness (both P for trend <0.001). Multiple linear logistic regression analysis showed that the presence of NAFLD was positively and independently associated with baPWV. Conclusions: Our results suggest that the presence of NAFLD is associated with arterial stiffness as measured by baPWV in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population.
doi:10.1631/jzus.B1400028
PMCID: PMC4201316  PMID: 25294377
Non-alcoholic fatty liver disease; Arterial stiffness; Brachial-ankle pulse wave velocity; Risk factor
21.  Sample size requirements for training high-dimensional risk predictors 
Biostatistics (Oxford, England)  2013;14(4):639-652.
A common objective of biomarker studies is to develop a predictor of patient survival outcome. Determining the number of samples required to train a predictor from survival data is important for designing such studies. Existing sample size methods for training studies use parametric models for the high-dimensional data and cannot handle a right-censored dependent variable. We present a new training sample size method that is non-parametric with respect to the high-dimensional vectors, and is developed for a right-censored response. The method can be applied to any prediction algorithm that satisfies a set of conditions. The sample size is chosen so that the expected performance of the predictor is within a user-defined tolerance of optimal. The central method is based on a pilot dataset. To quantify uncertainty, a method to construct a confidence interval for the tolerance is developed. Adequacy of the size of the pilot dataset is discussed. An alternative model-based version of our method for estimating the tolerance when no adequate pilot dataset is available is presented. The model-based method requires a covariance matrix be specified, but we show that the identity covariance matrix provides adequate sample size when the user specifies three key quantities. Application of the sample size method to two microarray datasets is discussed.
doi:10.1093/biostatistics/kxt022
PMCID: PMC3770001  PMID: 23873895
Conditional score; Cox regression; High-dimensional data; Risk prediction; Sample size; Training set
22.  Prognostic role of microRNA-145 in various human malignant neoplasms: a meta-analysis of 18 related studies 
Background
Recent studies show that microRNA-145 (miR-145) might be an attractive tumor biomarker of considerable prognostic value. To clarify the preliminary predictive value of miR-145 for prognosis in various malignant neoplasms, we conducted a meta-analysis of 18 relevant studies.
Methods
Eligible studies were identified by searching the online databases PubMed, EMBASE, and Web of Science up to March 2014. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for patient survival and disease progress were calculated to investigate the association with miR-145 expression.
Results
In total, 18 eligible studies were included in this meta-analysis. Our results showed that upregulated miR-145 significantly predicted a favorable overall survival (OS) (HR = 0.47, 95% CI 0.31 to 0.72), but failed to show a significant relation with disease prognosis. In stratified analyses, high miR-145 expression predicted favorable OS in both Whites and Asians but the intensity of the association in Whites (HR = 0.67, 95% CI 0.47 to 0.95) was not as strong as in Asians (HR = 0.35, 95% CI 0.19 to 0.64). High miR-145 expression also predicted better progression-free survival (PFS) in Asians (HR = 0.43, 95% CI 0.21 to 0.89), but not in Whites. In addition, a significantly favorable OS associated with upregulated miR-145 expression was observed in both squamous cell (SCC) (HR = 0.34, 95% CI 0.13 to 0.93) and glioblastoma (HR = 0.72, 95% CI 0.52 to 0.99).
Conclusions
Our findings indicate that high miR-145 expression is better at predicting patient survival rather than disease progression for malignant tumors, especially for SCC and glioblastoma in Asians. Considering the insufficient evidence, further investigations and more studies are needed.
doi:10.1186/1477-7819-12-254
PMCID: PMC4249768  PMID: 25106061
Malignant neoplasm; miR-145; Prognosis; Overall survival; Progression-free survival
23.  Prophylactic Cranial Irradiation May Impose a Detrimental Effect on Overall Survival of Patients with Nonsmall Cell Lung Cancer: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(7):e103431.
Purpose
To determine the role of brain metastases (BM) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) by performing a meta-analysis of the RCTs (randomized controlled clinical trials) and non-RCTs (non-randomized controlled clinical trials) published in the literature.
Methods
A meta-analysis was performed using trials identified through PubMed, EMBASE and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included BM, OS, median survival (MS), response rate (RR), Hazard ratios (HRs) and odds ratios (ORs), and their 95% confidence intervals (CIs) were pooled using ReMan software.
Results
Twelve trials (6 RCTs and 6 non-RCTs) involving 1,718 NSCLC patients met the inclusion criteria. They were grouped on the basis of study design for separate Meta-analyses. The results showed that prophylactic cranial irradiation (PCI) reduced the risk of BM as compared with non-PCI in NSCLC patients (OR = 0.30, 95% [CI]: 0.21–0.43, p<0.00001). However, HRs for OS favored non-PCI (HR = 1.19, 95% [CI]: 1.06–1.33, p = 0.004), without evidence of heterogeneity between the studies.
Conclusion
Our results suggest that although PCI decreased the risk of BM, it may impose a detrimental effect on OS of NSCLC patients.
doi:10.1371/journal.pone.0103431
PMCID: PMC4114791  PMID: 25072281
24.  Investigation of Hepatic Blood Perfusion by Laser Speckle Imaging and Changes of Hepatic Vasoactive Substances in Mice after Electroacupuncture 
The study was conducted to observe the effect of electroacupuncture (EA) on hepatic blood perfusion (HBP) and vascular regulation. We investigated 60 male anesthetized mice under the following 3 conditions: without EA stimulation (control group); EA stimulation at Zusanli (ST36 group); EA stimulation at nonacupoint (NA group) during 30 min. The HBP was measured using the laser speckle perfusion imaging (LSPI). The level of nitric oxide (NO), endothelin-1 (ET-1), and noradrenaline (NE) in liver tissue was detected by biochemical methods. Results were as follows. At each time point, HBP increase in ST36 group was higher than that in the NA group in anesthetized mice. HBP gradually decreased during 30 min in control group. The level of NO in ST36 group was higher than that in NA group. The level of both ET-1 and NE was the highest in control group, followed by NA group and ST36 group. It is concluded that EA at ST36 could increase HBP possibly by increasing the blood flow velocity (BFV), changing vascular activity, increasing the level of NO, and inhibiting the level of ET-1 in liver tissue.
doi:10.1155/2014/715316
PMCID: PMC4129169  PMID: 25140188
25.  Descriptions of three new species of the Termitophilous tribe Termitopaediini in China (Coleoptera, Staphylinidae, Aleocharinae) 
ZooKeys  2014;91-100.
Three new species belonging to two genera of the aleocharine tribe Termitopaediini Seevers, viz., Dioxeuta rara Song & Li, sp. n., D. yunnanensis Song & Li, sp. n., and Termitopulex sinensis Song & Li, sp. n. from Baihualing Natural Reserve (Southwest China: Yunnan) are described and illustrated. This is the first record of Termitopulex Fauvel, 1899 from China.
doi:10.3897/zookeys.424.7670
PMCID: PMC4106102  PMID: 25061397
Termitopaediini; Dioxeuta; Termitopulex; termitophily; taxonomy; new species; China; Oriental region

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