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1.  Regulation of Autophagy by miR-30d Impacts Sensitivity of Anaplastic Thyroid Carcinoma to Cisplatin* 
Biochemical pharmacology  2013;87(4):562-570.
miR-30d has been observed to be significantly down-regulated in human anaplastic thyroid carcinoma (ATC), and is believed to be an important event in thyroid cell transformation. In this study, we found that miR-30d has a critical role in modulating sensitivity of ATC cells to cisplatin, a commonly used chemotherapeutic drug for treatment of this neoplasm. Using a mimic of miR-30d, we demonstrated that miR-30d could negatively regulate the expression of beclin 1, a key autophagy gene, leading to suppression of the cisplatin-activated autophagic response that protects ATC cells from apoptosis. A reporter gene assay demonstrated that the binding sequences of miR-30d in the beclin 1-3′ UTR was the region required for the inhibition of beclin 1 expression by this miRNA. We further showed that inhibition of the beclin 1-mediated autophagy by the miR-30d mimic sensitized ATC cells to cisplatin both in vitro (cell culture) and in vivo (animal xenograft model). These results suggest that dysregulation of miR-30d in ATC cells is responsible for the insensitivity to cisplatin by promoting autophagic survival. Thus, miR-30d may be exploited as a potential target for therapeutic intervention in the treatment of ATC.
doi:10.1016/j.bcp.2013.12.004
PMCID: PMC3926201  PMID: 24345332
miR-30d; autophagy; apoptosis; Beclin1; cisplatin; Anaplastic thyroid cancer
2.  A biopolymer-like metal enabled hybrid material with exceptional mechanical prowess 
Scientific Reports  2015;5:8357.
The design principles for naturally occurring biological materials have inspired us to develop next-generation engineering materials with remarkable performance. Nacre, commonly referred to as nature's armor, is renowned for its unusual combination of strength and toughness. Nature's wisdom in nacre resides in its elaborate structural design and the judicious placement of a unique organic biopolymer with intelligent deformation features. However, up to now, it is still a challenge to transcribe the biopolymer's deformation attributes into a stronger substitute in the design of new materials. In this study, we propose a new design strategy that employs shape memory alloy to transcribe the “J-curve” mechanical response and uniform molecular/atomic level deformation of the organic biopolymer in the design of high-performance hybrid materials. This design strategy is verified in a TiNi-Ti3Sn model material system. The model material demonstrates an exceptional combination of mechanical properties that are superior to other high-performance metal-based lamellar composites known to date. Our design strategy creates new opportunities for the development of high-performance bio-inspired materials.
doi:10.1038/srep08357
PMCID: PMC4322361  PMID: 25665501
3.  Evident bacterial community changes but only slight degradation when polluted with pyrene in a red soil 
Understanding the potential for Polycyclic aromatic hydrocarbons (PAH) degradation by indigenous microbiota and the influence of PAHs on native microbial communities is of great importance for bioremediation and ecological evaluation. Various studies have focused on the bacterial communities in the environment where obvious PAH degradation was observed, little is known about the microbiota in the soil where poor degradation was observed. Soil microcosms were constructed with a red soil by supplementation with a high-molecular-weight PAH (pyrene) at three dosages (5, 30, and 70 mg ⋅ kg-1). Real-time PCR was used to evaluate the changes in bacterial abundance and pyrene dioxygenase gene (nidA) quantity. Illumina sequencing was used to investigate changes in diversity, structure, and composition of bacterial communities. After 42 days of incubation, no evident degradation was observed. The poor degradation ability was associated with the stability or significant decrease of abundance of the nidA gene. Although the abundance of the bacterial 16S rRNA gene was not affected by pyrene, the bacterial richness and diversity were decreased with increasing dosage of pyrene and the community structure was changed. Phylotypes affected by pyrene were comprehensively surveyed: (1) at the high taxonomic level, seven of the abundant phyla/classes (relative abundance >1.0%) including Chloroflexi, AD3, WPS-2, GAL5, Alphaproteobacteria, Actinobacteria, and Deltaproteobacteria and one rare phylum Crenarchaeota were significantly decreased by at least one dosage of pyrene, while three phyla/classes (Acidobacteria, Betaproteobacteria, and Gammaproteobacteria) were significantly increased; and (2) at the lower taxonomic level, the relative abundances of twelve orders were significantly depressed, whereas those of nine orders were significantly increased. This work enhanced our understanding of the biodegradation potential of pyrene in red soil and the effect of pyrene on soil ecosystems at the microbial community level.
doi:10.3389/fmicb.2015.00022
PMCID: PMC4311681
PAH pollution; pyrene; biodegradation; bacterial community; 16S rRNA gene; Illumina sequencing; red soil
4.  Simultaneous hydrogen and ethanol production from cascade utilization of mono-substrate in integrated dark and photo-fermentative reactor 
Background
Integrating hydrogen-producing bacteria with complementary capabilities, dark-fermentative bacteria (DFB) and photo-fermentative bacteria (PFB), is a promising way to completely recover bioenergy from waste biomass. However, the current coupled models always suffer from complicated pretreatment of the effluent from dark-fermentation or imbalance between dark and photo-fermentation, respectively. In this work, an integrated dark and photo-fermentative reactor (IDPFR) was developed to completely convert an organic substrate into bioenergy.
Results
In the IDPFR, Ethanoligenens harbinese B49 and Rhodopseudomonas faecalis RLD-53 were separated by a membrane into dark and photo chambers, while the acetate produced by E. harbinese B49 in the dark chamber could freely pass through the membrane into the photo chamber and serve as a carbon source for R. faecalis RLD-53. The hydrogen yield increased with increasing working volume of the photo chamber, and reached 3.38 mol H2/mol glucose at the dark-to-photo chamber ratio of 1:4. Hydrogen production by the IDPFR was also significantly affected by phosphate buffer concentration, glucose concentration, and ratio of dark-photo bacteria. The maximum hydrogen yield (4.96 mol H2/mol glucose) was obtained at a phosphate buffer concentration of 20 mmol/L, a glucose concentration of 8 g/L, and a ratio of dark to photo bacteria of 1:20. As the glucose and acetate were used up by E. harbinese B49 and R. faecalis RLD-53, ethanol produced by E. harbinese B49 was the sole end-product in the effluent from the IDPFR, and the ethanol concentration was 36.53 mmol/L with an ethanol yield of 0.82 mol ethanol/mol glucose.
Conclusions
The results indicated that the IDPFR not only circumvented complex pretreatments on the effluent in the two-stage process, but also overcame the imbalance of growth and metabolic rate between DFB and PFB in the co-culture process, and effectively enhanced cooperation between E. harbinense B49 and R. faecalis RLD-53. Moreover, simultaneous hydrogen and ethanol production were achieved by coupling E. harbinese B49 and R. faecalis RLD-53 in the IDPFR. According to stoichiometry, the hydrogen and ethanol production efficiencies were 82.67% and 82.19%, respectively. Therefore, IDPFR was an effective strategy for coupling DFB and PFB to fulfill efficient energy recovery from waste biomass.
doi:10.1186/s13068-014-0191-x
PMCID: PMC4308915  PMID: 25648915
Hydrogen production; Ethanol production; Dark-fermentation; Photo-fermentation; Integrated dark and photo-fermentative reactor; Kinetics; Membrane
5.  Consolidated bioprocessing performance of Thermoanaerobacterium thermosaccharolyticum M18 on fungal pretreated cornstalk for enhanced hydrogen production 
Background
Biological hydrogen production from lignocellulosic biomass shows great potential as a promising alternative to conventional hydrogen production methods, such as electrolysis of water and coal gasification. Currently, most researches on biohydrogen production from lignocellulose concentrate on consolidated bioprocessing, which has the advantages of simpler operation and lower cost over processes featuring dedicated cellulase production. However, the recalcitrance of the lignin structure induces a low cellulase activity, making the carbohydrates in the hetero-matrix more unapproachable. Pretreatment of lignocellulosic biomass is consequently an extremely important step in the commercialization of biohydrogen, and for massive realization of lignocellulosic biomass as alternative fuel feedstock. Thus, development of a pretreatment method which is cost efficient, environmentally benign, and highly efficient for enhanced consolidated bioprocessing of lignocellulosic biomass to hydrogen is essential.
Results
In this research, fungal pretreatment was adopted for enhanced hydrogen production by consolidated bioprocessing performance. To confirm the fungal pretreatment efficiency, two typical thermochemical pretreatments were also compared side by side. Results showed that the fungal pretreatment was superior to the other pretreatments in terms of high lignin reduction of up to 35.3% with least holocellulose loss (the value was only 9.5%). Microscopic structure observation combined with Fourier transform infrared spectroscopy (FTIR) analysis further demonstrated that the lignin and crystallinity of lignocellulose were decreased with better holocellulose reservation. Upon fungal pretreatment, the hydrogen yield and hydrogen production rate were 6.8 mmol H2 g-1 pretreated substrate and 0.89 mmol L-1 h-1, respectively, which were 2.9 and 4 times higher than the values obtained for the untreated sample.
Conclusions
Results revealed that although all pretreatments could contribute to the enhancement of hydrogen production from cornstalk, fungal pretreatment proved to be the optimal method. It is apparent that besides high hydrogen production efficiency, fungal pretreatment also offered several advantages over other pretreatments such as being environmentally benign and energy efficient. This pretreatment method thus has great potential for application in consolidated bioprocessing performance of hydrogen production.
doi:10.1186/s13068-014-0178-7
PMCID: PMC4296546  PMID: 25648837
Consolidated bioprocessing; Thermoanaerobacterium thermosaccharolyticum M18; Pretreatment; Hydrogen production; Cornstalk
6.  Recognition and Control of the Progression of Age-Related Hearing Loss 
Rejuvenation Research  2013;16(6):475-486.
Abstract
Recent breakthroughs have provided notable insights into both the pathogenesis and therapeutic strategies for age-related hearing loss (ARHL). Simultaneously, these breakthroughs enhance our knowledge about this neurodegenerative disease and raise the question of whether the disorder is preventable or even treatable. Discoveries relating to ARHL have revealed a unique link between ARHL and the underlying pathologies. Therefore, we need to better understand the pathogenesis or the mechanism of ARHL and learn how to take full advantage of various therapeutic strategies to prevent the progression of ARHL.
doi:10.1089/rej.2013.1435
PMCID: PMC3869427  PMID: 23915327
7.  Description of Caenorhabditis sinica sp. n. (Nematoda: Rhabditidae), a Nematode Species Used in Comparative Biology for C. elegans 
PLoS ONE  2014;9(11):e110957.
We re-isolated in China a relative of the nematode model Caenorhabditis elegans that was previously referred to informally as C. sp. 5. In spite of its importance for comparative biology, C. sp. 5 has remained morphologically uncharacterized. Therefore, we now provide detailed description of morphology and anatomy, assigning the name of Caenorhabditis sinica sp. n. to this nematode that is found frequently in China. C. sinica sp. n. belongs to the Elegans group in the genus Caenorhabditis, being phylogenetically close to C. briggsae although differing in reproductive mode. The gonochoristic C. sinica sp. n. displays two significantly larger distal parts of uteri filled with sperms in the female/hermaphroditic gonad than does the androdioecious C. briggsae. The new species can be differentiated morphologically from all known Caenorhabditis species within the Elegans group by presenting a uniquely shaped, three-pointed hook structure on the male precloacal lip. The lateral field of C. sinica sp. n. is marked by three ridges that are flanked by two additional incisures, sometimes appearing as five ridges in total. This study ends the prolonged period of the ‘undescribed’ anonymity for C. sinica sp. n. since its discovery and use in comparative biological research. Significant and crossing-direction dependent hybrid incompatibilities in F1 and F2 crossing progeny make C. sinica sp. n. an excellent model for studies of population and speciation genetics. The abundance of nematode species lacking detailed taxonomic characterization deserves renewed attention to address the species description gap for this important yet morphologically ‘difficult’ group of animals.
doi:10.1371/journal.pone.0110957
PMCID: PMC4222906  PMID: 25375770
8.  Boosting Functional Avidity of CD8+ T Cells by Vaccinia Virus Vaccination Depends on Intrinsic T-Cell MyD88 Expression but Not the Inflammatory Milieu 
Journal of Virology  2014;88(10):5356-5368.
ABSTRACT
T-cell functional avidity is a crucial determinant for efficient pathogen clearance. Although recombinant DNA priming coupled with a vaccinia-vectored vaccine (VACV) boost has been widely used to mount robust CD8+ T-cell responses, how VACV boost shapes the properties of memory CD8+ T cells remains poorly defined. Here, we characterize the memory CD8+ T cells boosted by VACV and demonstrate that the intrinsic expression of MyD88 is critical for their high functional avidity. Independent of selection of clones with high-affinity T-cell receptor (TCR) or of enhanced proximal TCR signaling, the VACV boost significantly increased T-cell functional avidity through a decrease in the activation threshold. VACV-induced inflammatory milieu is not sufficient for this improvement, as simultaneous administration of the DNA vaccine and mock VACV had no effects on the functional avidity of memory CD8+ T cells. Furthermore, reciprocal adoptive transfer models revealed that the intrinsic MyD88 pathway is required for instructing the functional avidity of CD8+ T cells boosted by VACV. Taking these results together, the intrinsic MyD88 pathway is required for the high functional avidity of VACV-boosted CD8+ T cells independent of TCR selection or the VACV infection-induced MyD88-mediated inflammatory milieu.
IMPORTANCE Functional avidity is one of the crucial determinants of T-cell functionality. Interestingly, although it has been demonstrated that a DNA prime-VACV boost regimen elicits high levels of T-cell functional avidity, how VACV changes the low avidity of CD8+ T cells primed by DNA into higher ones in vivo is less defined. Here, we proved that the enhancement of CD8+ T cell avidity induced by VACV boost is mediated by the intrinsic MyD88 pathway but not the MyD88-mediated inflammatory milieu, which might provide prompts in vaccine design.
doi:10.1128/JVI.03664-13
PMCID: PMC4019089  PMID: 24554667
9.  Lack of Family-Based Association between Common Variations in WNK1 and Blood Pressure Level 
Background
WNK1 (With No-lysine Kinase 1) modulates numerous sodium transport-related ion channels involved in regulation of blood pressure. Several studies have indicated associations between the common variants of the WNK1 gene and hypertension or blood pressure levels. However, little data exists on Asian populations and normotensive or pre-hypertensive subjects. Our aim was to detect whether the common variations in the WNK1 gene are potential contributors to individual variations in blood pressure in a family-based sample.
Material/Methods
525 individuals from 116 families were selected from a rural community of Northern China. Five single-nucleotide polymorphisms were selected from the WNK1 gene. Single-marker and haplotype analyses were conducted using the Family-Based Association Test program.
Results
Regretful, no associations for the 5 WNK1 SNPs and the constructed haplotype blocks of WNK1 with blood pressure level reached nominal statistical significance.
Conclusions
We conclude that although multiple candidate genes are involved in development of hypertension, the genetic polymorphism in WNK1 is not a major contributor to the observed variability in blood pressure and familial clustering risk of hypertension.
doi:10.12659/MSM.890791
PMCID: PMC4211417  PMID: 25321950
Blood Pressure; Family; Polymorphism; Genetic
10.  The Truncate Mutation of Notch2 Enhances Cell Proliferation through Activating the NF-κB Signal Pathway in the Diffuse Large B-Cell Lymphomas 
PLoS ONE  2014;9(10):e108747.
The Notch2 is a critical membrane receptor for B-cell functions, and also displays various biological roles in lymphoma pathogenesis. In this article, we reported that 3 of 69 (4.3%) diffuse large B-cell lymphomas (DLBCLs) exhibited a truncate NOTCH2 mutation at the nucleotide 7605 (G/A) in the cDNA sequence, which led to partial deletion of the C-terminal of PEST (proline-, glutamic acid-, serine- and threonine-rich) domain. The truncate Notch2 activated both the Notch2 and the NF-κB signals and promoted the proliferation of B-cell lymphoma cell lines, including DLBCL and Burkitt's lymphoma cell lines. Moreover, the ectopic proliferation was completely inhibited by ammonium pyrrolidinedithiocarbamate (PDTC), an NF-κB inhibitor. Simultaneously, PDTC also reduced the expression level of Notch2. Based on these results, we conclude that the Notch2 receptor with PEST domain truncation enhances cell proliferation which may be associated with the activation of the Notch2 and the NF-κB signaling. Our results are expected to provide a possible target for new DLBCL therapies by suppressing the Notch2 and the NF-κB signaling.
doi:10.1371/journal.pone.0108747
PMCID: PMC4196756  PMID: 25314575
11.  Structure and domain organization of Drosophila Tudor 
Cell Research  2014;24(9):1146-1149.
doi:10.1038/cr.2014.63
PMCID: PMC4152741  PMID: 24810300
12.  Lead-Free Intravascular Ultrasound Transducer Using BZT-50BCT Ceramics 
This paper reports the fabrication and evaluation of a high-frequency ultrasonic transducer based on a new lead-free piezoelectric material for intravascular imaging application. Lead-free 0.5Ba(Zr0.2Ti0.8)O3−0.5(Ba0.7Ca0.3)TiO3 (BZT-50BCT) ceramic with a high dielectric constant (~2800) was employed to develop a high-frequency (~30 MHz) needle-type ultrasonic transducer. With superior piezoelectric performance (piezoelectric coefficient d33 ~ 600 pC/N), the lead-free transducer was found to exhibit a −6-dB bandwidth of 53% with an insertion loss of 18.7 dB. In vitro intravascular ultrasound (IVUS) imaging of a human cadaver coronary artery was performed to demonstrate the potential of the lead-free transducer for biomedical imaging applications. This is the first time that a lead-free transducer has been used for IVUS imaging application. The experimental results suggest that the BZT-50BCT ceramic is a promising lead-free piezoelectric material for high-frequency intravascular imaging applications.
doi:10.1109/TUFFC.2013.2692
PMCID: PMC4090606  PMID: 25004492
13.  Khz-cp (crude polysaccharide extract obtained from the fusion of Ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis by increasing intracellular calcium levels and activating P38 and NADPH oxidase-dependent generation of reactive oxygen species in SNU-1 cells 
Background
Khz-cp is a crude polysaccharide extract that is obtained after nuclear fusion in Ganoderma lucidum and Polyporus umbellatus mycelia (Khz). It inhibits the growth of cancer cells.
Methods
Khz-cp was extracted by solvent extraction. The anti-proliferative activity of Khz-cp was confirmed by using Annexin-V/PI-flow cytometry analysis. Intracellular calcium increase and measurement of intracellular reactive oxygen species (ROS) were performed by using flow cytometry and inverted microscope. SNU-1 cells were treated with p38, Bcl-2 and Nox family siRNA. siRNA transfected cells was employed to investigate the expression of apoptotic, growth and survival genes in SNU-1 cells. Western blot analysis was performed to confirm the expression of the genes.
Results
In the present study, Khz-cp induced apoptosis preferentially in transformed cells and had only minimal effects on non-transformed cells. Furthermore, Khz-cp was found to induce apoptosis by increasing the intracellular Ca2+ concentration ([Ca2+]i) and activating P38 to generate reactive oxygen species (ROS) via NADPH oxidase and the mitochondria. Khz-cp-induced apoptosis was caspase dependent and occurred via a mitochondrial pathway. ROS generation by NADPH oxidase was critical for Khz-cp-induced apoptosis, and although mitochondrial ROS production was also required, it appeared to occur secondary to ROS generation by NADPH oxidase. Activation of NADPH oxidase was shown by the translocation of the regulatory subunits p47phox and p67phox to the cell membrane and was necessary for ROS generation by Khz-cp. Khz-cp triggered a rapid and sustained increase in [Ca2+]i that activated P38. P38 was considered to play a key role in the activation of NADPH oxidase because inhibition of its expression or activity abrogated membrane translocation of the p47phox and p67phox subunits and ROS generation.
Conclusions
In summary, these data indicate that Khz-cp preferentially induces apoptosis in cancer cells and that the signaling mechanisms involve an increase in [Ca2+]i, P38 activation, and ROS generation via NADPH oxidase and mitochondria.
doi:10.1186/1472-6882-14-236
PMCID: PMC4227278  PMID: 25012725
14.  Peripheral Blood for Epidermal Growth Factor Receptor Mutation Detection in Non-Small Cell Lung Cancer Patients 
Translational Oncology  2014;7(3):341-348.
OBJECTIVE: It is important to analyze and track Epidermal Growth Factor Receptor (EGFR) mutation status for predicting efficacy and monitoring resistance throughout EGFR-tyrosine kinase inhibitors (TKIs) treatment in non-small cell lung cancer (NSCLC) patients. The objective of this study was to determine the feasibility and predictive utility of EGFR mutation detection in peripheral blood. METHODS: Plasma, serum and tumor tissue samples from 164 NSCLC patients were assessed for EGFR mutations using Amplification Refractory Mutation System (ARMS). RESULTS: Compared with matched tumor tissue, the concordance rate of EGFR mutation status in plasma and serum was 73.6% and 66.3%, respectively. ARMS for EGFR mutation detection in blood showed low sensitivity (plasma, 48.2%; serum, 39.6%) but high specificity (plasma, 95.4%; serum, 95.5%). Treated with EGFR-TKIs, patients with EGFR mutations in blood had significantly higher objective response rate (ORR) and insignificantly longer progression-free survival (PFS) than those without mutations (ORR: plasma, 68.4% versus 38.9%, P = 0.037; serum, 75.0% versus 39.5%, P = 0.017; PFS: plasma, 7.9 months versus 6.1 months, P = 0.953; serum, 7.9 months versus 5.7 months, P = 0.889). In patients with mutant tumors, those without EGFR mutations in blood tended to have prolonged PFS than patients with mutations (19.7 months versus 11.0 months, P = 0.102). CONCLUSIONS: EGFR mutations detected in blood may be highly predictive of identical mutations in corresponding tumor, as well as showing correlations with tumor response and survival benefit from EGFR-TKIs. Therefore, blood for EGFR mutation detection may allow NSCLC patients with unavailable or insufficient tumor tissue the opportunity to benefit from personalized treatment. However, due to the high false negative rate in blood samples, analysis for EGFR mutations in tumor tissue remains the gold standard.
doi:10.1016/j.tranon.2014.04.006
PMCID: PMC4145390  PMID: 25180058
15.  Structural Insights into SraP-Mediated Staphylococcus aureus Adhesion to Host Cells 
PLoS Pathogens  2014;10(6):e1004169.
Staphylococcus aureus, a Gram-positive bacterium causes a number of devastating human diseases, such as infective endocarditis, osteomyelitis, septic arthritis and sepsis. S. aureus SraP, a surface-exposed serine-rich repeat glycoprotein (SRRP), is required for the pathogenesis of human infective endocarditis via its ligand-binding region (BR) adhering to human platelets. It remains unclear how SraP interacts with human host. Here we report the 2.05 Å crystal structure of the BR of SraP, revealing an extended rod-like architecture of four discrete modules. The N-terminal legume lectin-like module specifically binds to N-acetylneuraminic acid. The second module adopts a β-grasp fold similar to Ig-binding proteins, whereas the last two tandem repetitive modules resemble eukaryotic cadherins but differ in calcium coordination pattern. Under the conditions tested, small-angle X-ray scattering and molecular dynamic simulation indicated that the three C-terminal modules function as a relatively rigid stem to extend the N-terminal lectin module outwards. Structure-guided mutagenesis analyses, in addition to a recently identified trisaccharide ligand of SraP, enabled us to elucidate that SraP binding to sialylated receptors promotes S. aureus adhesion to and invasion into host epithelial cells. Our findings have thus provided novel structural and functional insights into the SraP-mediated host-pathogen interaction of S. aureus.
Author Summary
Staphylococcus aureus is an important pathogen that causes a range of human diseases, such as infective endocarditis, osteomyelitis, septic arthritis and sepsis. The increasing resistance of S. aureus to most of the current antibiotics emphasizes the need to develop new approaches to control staphylococcal infections. As a surface-exposed serine-rich repeat glycoprotein (SRRP), S. aureus SraP is involved in the pathogenesis of infective endocarditis via its ligand-binding region (BR) adhering to human platelets. However, little is known about how SraP interacts with its host receptor(s). Through structural and functional analyses of the BR domain, we have discovered a specific binding of SraP to N-acetylneuraminic acid (Neu5Ac), in agreement with a recent report of the trisaccharide ligand of SraP. Further mutagenesis analysis showed that SraP binding to Neu5Ac and the trisaccharide promotes S. aureus adhesion to and invasion into host epithelial cells. These findings increase our knowledge of surface protein mediated interaction of S. aureus with host epithelial cells.
doi:10.1371/journal.ppat.1004169
PMCID: PMC4047093  PMID: 24901708
16.  Screening and Functional Analysis of the Peroxiredoxin Specifically Expressed in Bursaphelenchus xylophilus—The Causative Agent of Pine Wilt Disease 
The pine wood nematode, Bursaphelenchus xylophilus, is the causal agent of pine wilt disease. Accurately differentiating B. xylophilus from other nematodes species, especially its related species B. mucronatus, is important for pine wood nematode detection. Thus, we attempted to identify a specific protein in the pine wood nematode using proteomics technology. Here, we compared the proteomes of B. xylophilus and B. mucronatus using Two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight (MALDI-TOF/TOF-MS) technologies. In total, 15 highly expressed proteins were identified in B. xylophilus compared with B. mucronatus. Subsequently, the specificity of the proteins identified was confirmed by PCR using the genomic DNA of other nematode species. Finally, a gene encoding a specific protein (Bx-Prx) was obtained. This gene was cloned and expressed in E. coli. The in situ hybridisation pattern of Bx-Prx showed that it was expressed strongly in the tail of B. xylophilus. RNAi was used to assess the function of Bx-Prx, the results indicated that the gene was associated with the reproduction and pathogenicity of B. xylophilus. This discovery provides fundamental information for identifying B. xylophilus via a molecular approach. Moreover, the purified recombinant protein has potential as a candidate diagnostic antigen of pine wilt disease, which may lead to a new immunological detection method for the pine wood nematode.
doi:10.3390/ijms150610215
PMCID: PMC4100149  PMID: 24918285
Bursaphelenchus xylophilus; comparative proteomics; 2-DE; in situ hybridization; prokaryotic expression
17.  Plasma Sphingolipids as Potential Indicators of Hepatic Necroinflammation in Patients with Chronic Hepatitis C and Normal Alanine Aminotransferase Level 
PLoS ONE  2014;9(4):e95095.
Accurate estimation of hepatic necroinflammation caused by chronic hepatitis C (CHC) is crucial for prediction of prognosis and design of therapeutic strategy, which is particularly true for CHC patients with normal alanine aminotransferase (ALT) level. Recent studies have shown that sphingolipids have a close relationship with hepatitis C virus infection. The present study aimed to identify plasma sphingolipids related to hepatic necroinflammation. We included 120 treatment-naïve CHC patients and 64/120 had normal ALT levels (<40 U/L). CHC patients who underwent liver biopsies were subjected to Scheuer scoring analysis for scope of hepatic inflammation. Plasma sphingolipids were detected by high-performance liquid chromatography tandem mass spectrometry. Our results showed 44 plasma sphingolipids were detected altogether. Of all detected sphingolipids, hexosylceramide (HexCer) (d18∶1/22∶0) and HexCer (d18∶1/24∶0) showed a significant difference among G0/G1, G2, and G3/G4 (P<0.05). For identifying hepatic necroinflammation (G≥2), after adjusting other factors, the odds ratio (OR) of HexCer (d18∶1/22∶0) reached 1.01 (95% confidence interval [CI]: 1.00–1.02). Furthermore, the area under the curve (AUC) of HexCer (d18∶1/22∶0) was 0.7 (P = 0.01) and approached that of ALT (AUC = 0.78). However, in CHC patients with normal ALT, HexCer (d18∶1/22∶0) was an independent factor (OR: 1.02, 95% CI: 1.01–1.03) to identify the hepatic necroinflammation (G≥2). HexCer (d18∶1/22∶0) not only showed the largest AUC (0.78, P = 0.001), but also exhibited the highest specificity of all indicators. These results indicate that plasma HexCer (d18∶1/22∶0) is a potential indicator to distinguish hepatic necroinflammation in CHC patients. For CHC with normal ALT, the ability of HexCer (d18∶1/22∶0) to distinguish hepatic necroinflammation might be superior to conventional serum indicators.
doi:10.1371/journal.pone.0095095
PMCID: PMC3988168  PMID: 24736528
18.  Geographic Mapping of Crohn's Disease and Its Relation to Affluence in Jiangsu Province, an Eastern Coastal Province of China 
Background. Geographical variation in the incidence of Crohn's disease (CD) has been reported in Europe and North American. However, there are no comparable data in mainland China. Methods. We retrospectively identified incident cases of CD patients registered in Jinling hospital during 2003 to 2012. The standardized incidence ratio (SIR) was calculated for each area of Jiangsu province and a thematic map of CD was made according to the local SIR. The association between incidence and local economic status was revealed by correlation between SIR of CD and different local economic indicators. Results. A total of 653 CD patients (male-to-female ratio, 1.8 : 1) from Jiangsu province were included. A steady increase was observed in the number of CD patients over the period of observation. Disease map of SIR showed a pronounced geographic concentration of CD in the south part of Jiangsu province. Spearman correlation analysis showed a positive correlation between local SIR of CD and local economic indicators. Conclusions. There is a marked geographic variability in CD incidence across Jiangsu province. CD incidence in affluent areas seems to be higher than that in less affluent areas. Further multicenter population-based studies are needed to assess the real disease map of CD.
doi:10.1155/2014/590467
PMCID: PMC4009246  PMID: 24839438
19.  Fusion-Expressed CTB Improves Both Systemic and Mucosal T-Cell Responses Elicited by an Intranasal DNA Priming/Intramuscular Recombinant Vaccinia Boosting Regimen 
Journal of Immunology Research  2014;2014:308732.
Previous study showed that CTB (Cholera toxin subunit B) can be used as a genetic adjuvant to enhance the systemic immune responses. To further investigate whether it can also be used as a genetic adjuvant to improve mucosal immune responses, we constructed DNA and recombinant Tiantan vaccinia (rTTV) vaccines expressing OVA-CTB fusion antigen. Female C57BL/6 mice were immunized with an intranasal DNA priming/intramuscular rTTV boosting regimen. OVA specific T-cell responses were measured by IFN-γ ELISPOT and specific antibody responses were determined by ELISA. Compared to the nonadjuvant group (pSV-OVA intranasal priming/rTTV-OVA intramuscular boosting), pSV-OVA-CTB intranasal priming/rTTV-OVA-CTB intramuscular boosting group significantly improved the magnitudes of T-cell responses at spleen (1562 ± 567 SFCs/106 splenocytes versus 330 ± 182 SFCs/106 splenocytes, P < 0.01), mesenteric LN (96 ± 83 SFCs/106 lymphocytes versus 1 ± 2 SFCs/106 lymphocytes, P < 0.05), draining LNs of respiratory tract (109 ± 60 SFCs/106 lymphocytes versus 2 ± 2 SFCs/106 lymphocytes, P < 0.01) and female genital tract (89 ± 48 SFCs/106 lymphocytes versus 23 ± 21 SFCs/106 lymphocytes, P < 0.01). These results collectively demonstrated that fusion-expressed CTB could act as a potent adjuvant to improve both systemic and mucosal T-cell responses.
doi:10.1155/2014/308732
PMCID: PMC3988707  PMID: 24741585
20.  L-Serine Treatment May Improve Neurorestoration of Rats after Permanent Focal Cerebral Ischemia Potentially Through Improvement of Neurorepair 
PLoS ONE  2014;9(3):e93405.
The present study was conducted to clarify whether treatment with L-serine can improve the brain repair and neurorestoration of rats after permanent middle cerebral artery occlusion (pMCAO). After pMCAO, the neurological functions, brain lesion volume, and cortical injury were determined. GDNF, NGF, NCAM L1, tenascin-C, and Nogo-A levels were measured. Proliferation and differentiation of the neural stem cells (NSCs) and proliferation of the microvessels in the ischemic boundary zone of the cortex were evaluated. Treatment with L-serine (168 mg/kg body weight, i.p.) began 3 h after pMCAO and was repeated every 12 h for 7 days or until the end of the experiment. L-Serine treatment: 1) reduced the lesion volume and neuronal loss; 2) improved the recovery of neurological functions; 3) elevated the expression of nerve growth-related factors; and 4) facilitated the proliferation of endogenous NSCs and microvessels activated after pMCAO and increased the number of new-born neurons. 5) D-cycloserine, an inhibitor of serine hydroxymethyltransferase, blunted the effects of L-serine on NSC proliferation, differentiation, microvascular proliferation. In conclusions, L-serine treatment in pMCAO rats can reduce brain injury and facilitate neurorestoration which is partly associated with the improvement of proliferation of NSCs and microvessels, reconstruction of neurovascular units and resultant neurorepair. The effects of L-serine on endogenous NSC proliferation and microvascular proliferation are partly mediated by the action of L-serine as a substrate for the production of one-carbon groups used for purine and pyrimidine synthesis and modulation of the expression of some nerve growth-related factors.
doi:10.1371/journal.pone.0093405
PMCID: PMC3966884  PMID: 24671106
21.  Transperitoneal Approach versus Retroperitoneal Approach: A Meta-Analysis of Laparoscopic Partial Nephrectomy for Renal Cell Carcinoma 
PLoS ONE  2014;9(3):e91978.
Objective
To compare the efficiency and safety of the transperitoneal approaches with retroperitoneal approaches in laparoscopic partial nephrectomy for renal cell carcinoma and provide evidence-based medicine support for clinical treatment.
Methods
A systematic computer search of PUBMED, EMBASE, and the Cochrane Library was executed to identify retrospective observational and prospective randomized controlled trials studies that compared the outcomes of the two approaches in laparoscopic partial nephrectomy. Two reviewers independently screened, extracted, and evaluated the included studies and executed statistical analysis by using software STATA 12.0. Outcomes of interest included perioperative and postoperative variables, surgical complications and oncological variables.
Results
There were 8 studies assessed transperitoneal laparoscopic partial nephrectomy (TLPN) versus retroperitoneal laparoscopic partial nephrectomy (RLPN) were included. RLPN had a shorter operating time (SMD = 1.001,95%confidence interval[CI] 0.609–1.393,P<0.001), a lower estimated blood loss (SMD = 0.403,95%CI 0.015–0.791,P = 0.042) and a shorter length of hospital stay (WMD = 0.936 DAYS,95%CI 0.609–1.263,P<0.001) than TLPN. There were no significant differences between the transperitoneal and retroperitoneal approaches in other outcomes of interest.
Conclusions
This meta-analysis indicates that, in appropriately selected patients, especially patients with intraperitoneal procedures history or posteriorly located renal tumors, the RLPN can shorten the operation time, reduce the estimated blood loss and shorten the length of hospital stay. RLPN may be equally safe and be faster compared with the TLPN.
doi:10.1371/journal.pone.0091978
PMCID: PMC3962363  PMID: 24658032
22.  The sequence and de novo assembly of the giant panda genome 
Li, Ruiqiang | Fan, Wei | Tian, Geng | Zhu, Hongmei | He, Lin | Cai, Jing | Huang, Quanfei | Cai, Qingle | Li, Bo | Bai, Yinqi | Zhang, Zhihe | Zhang, Yaping | Wang, Wen | Li, Jun | Wei, Fuwen | Li, Heng | Jian, Min | Li, Jianwen | Zhang, Zhaolei | Nielsen, Rasmus | Li, Dawei | Gu, Wanjun | Yang, Zhentao | Xuan, Zhaoling | Ryder, Oliver A. | Leung, Frederick Chi-Ching | Zhou, Yan | Cao, Jianjun | Sun, Xiao | Fu, Yonggui | Fang, Xiaodong | Guo, Xiaosen | Wang, Bo | Hou, Rong | Shen, Fujun | Mu, Bo | Ni, Peixiang | Lin, Runmao | Qian, Wubin | Wang, Guodong | Yu, Chang | Nie, Wenhui | Wang, Jinhuan | Wu, Zhigang | Liang, Huiqing | Min, Jiumeng | Wu, Qi | Cheng, Shifeng | Ruan, Jue | Wang, Mingwei | Shi, Zhongbin | Wen, Ming | Liu, Binghang | Ren, Xiaoli | Zheng, Huisong | Dong, Dong | Cook, Kathleen | Shan, Gao | Zhang, Hao | Kosiol, Carolin | Xie, Xueying | Lu, Zuhong | Zheng, Hancheng | Li, Yingrui | Steiner, Cynthia C. | Lam, Tommy Tsan-Yuk | Lin, Siyuan | Zhang, Qinghui | Li, Guoqing | Tian, Jing | Gong, Timing | Liu, Hongde | Zhang, Dejin | Fang, Lin | Ye, Chen | Zhang, Juanbin | Hu, Wenbo | Xu, Anlong | Ren, Yuanyuan | Zhang, Guojie | Bruford, Michael W. | Li, Qibin | Ma, Lijia | Guo, Yiran | An, Na | Hu, Yujie | Zheng, Yang | Shi, Yongyong | Li, Zhiqiang | Liu, Qing | Chen, Yanling | Zhao, Jing | Qu, Ning | Zhao, Shancen | Tian, Feng | Wang, Xiaoling | Wang, Haiyin | Xu, Lizhi | Liu, Xiao | Vinar, Tomas | Wang, Yajun | Lam, Tak-Wah | Yiu, Siu-Ming | Liu, Shiping | Zhang, Hemin | Li, Desheng | Huang, Yan | Wang, Xia | Yang, Guohua | Jiang, Zhi | Wang, Junyi | Qin, Nan | Li, Li | Li, Jingxiang | Bolund, Lars | Kristiansen, Karsten | Wong, Gane Ka-Shu | Olson, Maynard | Zhang, Xiuqing | Li, Songgang | Yang, Huanming | Wang, Jian | Wang, Jun
Nature  2009;463(7279):311-317.
Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
doi:10.1038/nature08696
PMCID: PMC3951497  PMID: 20010809
23.  An Integrated Thermal Compensation System for MEMS Inertial Sensors 
Sensors (Basel, Switzerland)  2014;14(3):4290-4311.
An active thermal compensation system for a low temperature-bias-drift (TBD) MEMS-based gyroscope is proposed in this study. First, a micro-gyroscope is fabricated by a high-aspect-ratio silicon-on-glass (SOG) process and vacuum packaged by glass frit bonding. Moreover, a drive/readout ASIC, implemented by the 0.25 μm 1P5M standard CMOS process, is designed and integrated with the gyroscope by directly wire bonding. Then, since the temperature effect is one of the critical issues in the high performance gyroscope applications, the temperature-dependent characteristics of the micro-gyroscope are discussed. Furthermore, to compensate the TBD of the micro-gyroscope, a thermal compensation system is proposed and integrated in the aforementioned ASIC to actively tune the parameters in the digital trimming mechanism, which is designed in the readout ASIC. Finally, some experimental results demonstrate that the TBD of the micro-gyroscope can be compensated effectively by the proposed compensation system.
doi:10.3390/s140304290
PMCID: PMC4003944  PMID: 24599191
MEMS; gyroscope; silicon-on-glass; temperature bias drift; delta-sigma modulation; thermal compensation
24.  MiR-182 is up-regulated and targeting Cebpa in hepatocellular carcinoma 
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that repress their targets at post transcriptional level. Existing studies have shown that miRNAs are important regulatory genes in hepatocellular carcinoma (HCC), as either tumor suppressors or oncogenes. MiR-122 is normally downregulated in HCC and regarded as a tumor suppressor. Recently miR-122 has been reported to be regulated by CEBPA, which is then involved in a novel pathway to influence proliferation of tumor cells. However it is unknown whether CEBPA is regulated by miRNAs in HCC. In this study, we find that miR-182 is upregulated in HCC model rat, and represses CEBPA in both rat and human. This further improves the current CEBPA/miR-122 pathway that controls the proliferation of tumor cells. These results suggest that miR-182 is a potential oncogene in HCC and could be used as a diagnostic marker and drug target of HCC.
doi:10.3978/j.issn.1000-9604.2014.01.01
PMCID: PMC3937760  PMID: 24653623
miR-182; Cebpa; miR-122; hepatocellular carcinoma (HCC); oncogene
25.  ASDCD: Antifungal Synergistic Drug Combination Database 
PLoS ONE  2014;9(1):e86499.
Finding effective drugs to treat fungal infections has important clinical significance based on high mortality rates, especially in an immunodeficient population. Traditional antifungal drugs with single targets have been reported to cause serious side effects and drug resistance. Nowadays, however, drug combinations, particularly with respect to synergistic interaction, have attracted the attention of researchers. In fact, synergistic drug combinations could simultaneously affect multiple subpopulations, targets, and diseases. Therefore, a strategy that employs synergistic antifungal drug combinations could eliminate the limitations noted above and offer the opportunity to explore this emerging bioactive chemical space. However, it is first necessary to build a powerful database in order to facilitate the analysis of drug combinations. To address this gap in our knowledge, we have built the first Antifungal Synergistic Drug Combination Database (ASDCD), including previously published synergistic antifungal drug combinations, chemical structures, targets, target-related signaling pathways, indications, and other pertinent data. Its current version includes 210 antifungal synergistic drug combinations and 1225 drug-target interactions, involving 105 individual drugs from more than 12,000 references. ASDCD is freely available at http://ASDCD.amss.ac.cn.
doi:10.1371/journal.pone.0086499
PMCID: PMC3901703  PMID: 24475134

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