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1.  Predictive performance of ‘Diprifusor’ TCI system in patients during upper abdominal surgery under propofol/fentanyl anesthesia*  
Objective: To evaluate the predictive performance of ‘Diprifusor’ TCI (target-controlled infusion) system for its better application in clinical anesthesia. Methods: The predictive performance of a ‘Diprifusor’ TCI system was investigated in 27 Chinese patients (16 males and 11 females) during upper abdominal surgery under total intravenous anesthesia (TIVA) with propofol/fentanyl. Measured arterial propofol concentrations were compared with the values predicted by the TCI infusion system. Performance was determined by the median performance error (MDPE), the median absolute performance error (MDAPE), the divergence (the percentage change of the absolute PE with time), and the wobble (the median absolute deviation of each PE from the MDPE). Results: The median (range) values of 14.9% (−21.6%~42.9%) for MDPE, 23.3% (6.9%~62.5%) for MDAPE, −1.9% h−1 (−32.7%~23.0% h−1) for divergence, and 18.9% (4.2%~59.6%) for wobble were obtained from 227 samples from all patients. For the studied population, the PE did not increase with time but with increasing target propofol concentration, particularly following induction. Conclusions: The control of depth of anaesthesia was good in all patients undergoing upper abdominal surgical operation and the predictive performance of the ‘Diprifusor’ target controlled infusion system was considered acceptable for clinical purposes. But the relatively bigger wobble showed that the pharmacokinetic model is not so suitable and requires improvement.
PMCID: PMC1390758  PMID: 15593391
Target-controlled infusion (TCI); ‘Diprifusor’ TCI system; Predictive performance assessment; Wobble; Infusion
2.  Image quality and radiation dose of dual-source CT cardiac angiography using prospective ECG-triggering technique in pediatric patients with congenital heart disease 
All studies involving use of ionizing radiation should be performed in accordance with the ALARA (As Low As Reasonably Achievable) principle, especially in children. In this study, the prospective ECG triggering technique with low voltage was used in dual-source computed tomography (DSCT) angiography to investigate if image quality with low radiation dose could be satisfactory in pediatric patients with congenital heart disease.
Sixty pediatric patients with suspected congenital cardiovascular anomalies were enrolled prospectively in the study. They were randomly assigned to two groups for DSCT angiography. Group A were scanned by prospective ECG-triggering computed tomography angiography (CTA) with 80 kV tube voltage, while group B by used non-ECG-gated CTA with the same tube voltage. The anomaly accuracy was evaluated based on the surgical and/or conventional cardiac angiography findings. The overall image quality was assessed on a five-point scale. And the diagnostic accuracy and radiation dose was evaluated in both groups.
There were 127 cardiovascular anomalies in Group A and 108 in Group B. The mean subjective image quality and diagnostic accuracy between these two groups were significantly different (P = 0.007 and 0.011, respectively). The mean effective dose in Group A and Group B was 0.38 ± 0.13 mSv and 0.35 ± 0.17 mSv, respectively. But there was no significant difference between two groups (P = 0.197).
The prospective ECG triggering technique in DSCT scan can offer better image quality and diagnostic accuracy with low radiation exposure in pediatric patients with congenital heart diseases. This technique has potential to become a new clinical routine in pediatric cardiac computed tomography (CT) imaging.
PMCID: PMC4826524  PMID: 27059600
Dual-source CT; Congenital heart disease; Radiation dose
3.  Endocannabinoids in Synaptic Plasticity and Neuroprotection 
Endocannabinoids (eCBs) are endogenous lipid mediators involved in a variety of physiological, pharmacological, and pathological processes. While activation of the eCB system primarily induces inhibitory effects on both GABAergic and glutamatergic synaptic transmission and plasticity through acting on presynaptically-expressed CB1 receptors in the brain, accumulated information suggests that eCB signaling is also capable of facilitating or potentiating excitatory synaptic transmission in the hippocampus. Recent studies show that a long-lasting potentiation of excitatory synaptic transmission at Schaffer collateral (SC)-CA1 synapses is induced by spatiotemporally primed inputs, accompanying with a long-term depression of inhibitory synaptic transmission (I-LTD) in hippocampal CA1 pyramidal neurons. This input-timing-dependent long-lasting synaptic potentiation at SC-CA1 synapses is mediated by 2-arachidonoylglycerol (2-AG) signaling triggered by activation of postsynaptic NMDA receptors, group I metabotropic glutamate receptors (mGluRs), and a concurrent rise in intracellular Ca2+. Emerging evidence now also indicates that 2-AG is an important signaling mediator keeping brain homeostasis by exerting its anti-inflammatory and neuroprotective effects in response to harmful insults through CB1/2 receptor-dependent and/or independent mechanisms. Activation of the nuclear receptor protein peroxisome proliferator-activated receptor-γ (PPARγ) apparently is one of the important mechanisms in resolving neuroinflammation and protecting neurons produced by 2-AG signaling. Thus, the information summarized in this review suggests that the role of eCB signaling in maintaining integrity of brain function is greater than what we thought previously.
PMCID: PMC4143501  PMID: 24571856
Monoacylglycerol lipase; Alzheimer’s disease; chronic traumatic encephalopathy; input-timing-dependent plasticity; long-term depression of inhibitory synaptic transmission; PPARγ
4.  Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice 
Brain-derived neurotrophic factor (BDNF) and STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61) have opposing functions in the brain, with BDNF supporting and STEP61 opposing synaptic strengthening. BDNF and STEP61 also exhibit an inverse pattern of expression in a number of brain disorders, including schizophrenia (SZ). NMDAR antagonists such as phencyclidine (PCP) elicit SZ-like symptoms in rodent models and unaffected individuals, and exacerbate psychotic episodes in SZ. Here we characterize the regulation of BDNF expression by STEP61, utilizing PCP-treated cortical culture and PCP-treated mice. PCP-treated cortical neurons showed both an increase in STEP61 levels and a decrease in BDNF expression. The reduction in BDNF expression was prevented by STEP61 knockdown or use of the STEP inhibitor, TC-2153. The PCP-induced increase in STEP61 expression was associated with the inhibition of CREB-dependent BDNF transcription. Similarly, both genetic and pharmacologic inhibition of STEP prevented the PCP-induced reduction in BDNF expression in vivo and normalized PCP-induced hyperlocomotion and cognitive deficits. These results suggest a mechanism by which STEP61 regulates BDNF expression, with implications for cognitive functioning in CNS disorders.
PMCID: PMC4801664  PMID: 26450419
BDNF; Phencyclidine; Schizophrenia; STEP inhibitor; Ubiquitination
5.  Controllable Hysteresis and Threshold Voltage of Single-Walled Carbon Nano-tube Transistors with Ferroelectric Polymer Top-Gate Insulators 
Scientific Reports  2016;6:23090.
Double-gated field effect transistors have been fabricated using the SWCNT networks as channel layer and the organic ferroelectric P(VDF-TrFE) film spin-coated as top gate insulators. Standard photolithography process has been adopted to achieve the patterning of organic P(VDF-TrFE) films and top-gate electrodes, which is compatible with conventional CMOS process technology. An effective way for modulating the threshold voltage in the channel of P(VDF-TrFE) top-gate transistors under polarization has been reported. The introduction of functional P(VDF-TrFE) gate dielectric also provides us an alternative method to suppress the initial hysteresis of SWCNT networks and obtain a controllable ferroelectric hysteresis behavior. Applied bottom gate voltage has been found to be another effective way to highly control the threshold voltage of the networked SWCNTs based FETs by electrostatic doping effect.
PMCID: PMC4793293  PMID: 26980284
6.  Efficient and simple generation of multiple unmarked gene deletions in Mycobacterium smegmatis 
Scientific Reports  2016;6:22922.
Research on mycobacterial genetics relies heavily on techniques for directed gene mutation, but genetic studies are often hampered by the difficulty of generating gene deletions in mycobacteria. We developed an efficient and improved deletion system, described here in detail, which can be used to construct multiple unmarked recombinants in mycobacteria. We tested this system by using it to sequentially delete four pairs of toxin-antitoxin genes in Mycobacterium smegmatis.
PMCID: PMC4789726  PMID: 26972108
7.  miR-33a is downregulated in melanoma cells and modulates cell proliferation by targeting PCTAIRE1 
Oncology Letters  2016;11(4):2741-2746.
MicroRNA-33a (miR-33a) was previously identified as a lipid regulator that controls the cellular balance between cholesterol and fatty acid metabolism. However, its role in tumor progression is largely unknown. The present study identified that miR-33a acts as a tumor suppressor in melanoma cells. The present study revealed that miR-33a was downregulated in melanoma cells compared with melanocytes. Overexpression of miR-33a suppressed the colony formation of human melanoma SK-MEL-1 and WM-115 cells. Furthermore, a bromodeoxyuridine incorporation assay and anaphase analysis revealed that miR-33a inhibits melanoma cell proliferation. miR-33a overexpression inhibited p27 phosphorylation and upregulated p27 expression. Additionally, the present study demonstrated that PCTAIRE1 was a direct target of miR-33a; miR-33a overexpression suppressed the luciferase activity of a reporter construct containing a 3′-untranslated region of PCTAIRE1 and downregulated PCTAIRE1 in melanoma cells. An overexpression of PCTAIRE1 reversed the miR-33a-induced p27 accumulation and tumor suppressive effects. In summary, the present findings offer novel mechanistic insights into miR-33a and its downstream target in melanoma cells.
PMCID: PMC4812543  PMID: 27073545
miR-33a; PCTAIRE1; melanoma; p27
8.  Human cytomegalovirus-encoded US28 may act as a tumor promoter in colorectal cancer 
World Journal of Gastroenterology  2016;22(9):2789-2798.
AIM: To assess human cytomegalovirus-encoded US28 gene function in colorectal cancer (CRC) pathogenesis.
METHODS: Immunohistochemical analysis was performed to determine US28 expression in 103 CRC patient samples and 98 corresponding adjacent noncancerous samples. Patient data were compared by age, sex, tumor location, histological grade, Dukes’ stage, and overall mean survival time. In addition, the US28 gene was transiently transfected into the CRC LOVO cell line, and cell proliferation was assessed using a cell counting kit-8 assay. Cell cycle analysis by flow cytometry and a cell invasion transwell assay were also carried out.
RESULTS: US28 levels were clearly higher in CRC tissues (38.8%) than in adjacent noncancerous samples (7.1%) (P = 0.000). Interestingly, elevated US28 amounts in CRC tissues were significantly associated with histological grade, metastasis, Dukes’ stage, and overall survival (all P < 0.05); meanwhile, US28 expression was not significantly correlated with age, sex or tumor location. In addition, multivariate Cox regression data revealed US28 level as an independent CRC prognostic marker (P = 0.000). LOVO cells successfully transfected with the US28 gene exhibited higher viability, greater chemotherapy resistance, accelerated cell cycle progression, and increased invasion ability.
CONCLUSION: US28 expression is predictive of poor prognosis and may promote CRC.
PMCID: PMC4778001  PMID: 26973417
Human cytomegalovirus; US28; Colorectal cancer; Prognosis; Proliferation; Invasion
9.  Risk Factors for Border Malaria in a Malaria Elimination Setting: A Retrospective Case-Control Study in Yunnan, China 
A retrospective case-control study was conducted to identify risk factors for border malaria in a malaria elimination setting of Yunnan Province, China. The study comprised 214 cases and 428 controls. The controls were individually matched to the cases on the basis of residence, age, and gender. In addition, statistical associations are based on matched analyses. The frequencies of imported, male, adult, and vivax malaria cases were respectively 201 (93.9%), 194 (90.7%), 210 (98.1%), and 176 (82.2%). Overnight stay in Myanmar within the prior month was independently associated with malaria infection (odds ratio [OR] 159.5, 95% confidence interval [CI] 75.1–338.9). In particular, stays in lowland and foothill (OR 5.5, 95% CI 2.5–11.8) or mid-hill (OR 42.8, 95% CI 5.1–319.8) areas, or near streamlets (OR 15.3, 95% CI 4.3–55.2) or paddy field or pools (OR10.1, 95% CI 4.4–55.8) were found to be independently associated with malaria. Neither forest exposure nor use of vector control measures was associated with malaria. In conclusion, travel to lowland and foothill or mid-hill hyperendemic areas, especially along the waterside in Myanmar, was found to be the highest risk factor for malaria. In considering the limitations of the study, further investigations are needed to identify the major determinants of malaria risk and develop new strategies for malaria elimination on China-Myanmar border.
PMCID: PMC4350546  PMID: 25601994
10.  Magnetic nanoparticle-mediated isolation of functional bacteria in a complex microbial community 
The ISME Journal  2014;9(3):603-614.
Although uncultured microorganisms have important roles in ecosystems, their ecophysiology in situ remains elusive owing to the difficulty of obtaining live cells from their natural habitats. In this study, we employed a novel magnetic nanoparticle-mediated isolation (MMI) method to recover metabolically active cells of a group of previously uncultured phenol degraders, Burkholderiales spp., from coking plant wastewater biosludge; five other culturable phenol degraders—Rhodococcus sp., Chryseobacterium sp. and three different Pseudomonas spp.—were also isolated from the same biosludge using traditional methods. The kinetics of phenol degradation by MMI-recovered cells (MRCs) was similar to that of the original sludge. Stable isotope probing (SIP) and pyrosequencing of the 16S rRNA from the ‘heavy' DNA (13C-DNA) fractions indicated that Burkholderiales spp. were the key phenol degraders in situ in the biosludge, consistent with the results of MRCs. Single-cell Raman micro-spectroscopy was applied to probe individual bacteria in the MRCs obtained from the SIP experiment and showed that 79% of them were fully 13C-labelled. Biolog assays on the MRCs revealed the impact of various carbon and nitrogen substrates on the efficiency of phenol degradation in the wastewater treatment plant biosludge. Specifically, hydroxylamine, a metabolite of ammonia oxidisation, but not nitrite, nitrate or ammonia, inhibited phenol degradation in the biosludge. Our results provided a novel insight into the occasional abrupt failure events that occur in the wastewater treatment plant. This study demonstrated that MMI is a powerful tool to recover live and functional cells in situ from a complex microbial community to enable further characterisation of their physiology.
PMCID: PMC4331582  PMID: 25191996
11.  Efficacy and safety of the combination of paclitaxel and platinum in advanced thymic carcinoma 
Thoracic Cancer  2015;7(2):222-225.
This study aimed to assess the efficacy and safety of a combination of paclitaxel and cisplatin/carboplatin for the treatment of advanced thymic carcinoma. Thirty‐seven patients (23 men and 14 women, median age 47 years, performance status score ≤2) with pathologically or cytologically diagnosed advanced thymic carcinoma were recruited. Patients received 175 mg/m2 paclitaxel on day 1 and 75 mg/m2 cisplatin or 300 mg/m2 carboplatin on day 2 of a 21 day cycle for at least two cycles to evaluate efficacy and adverse events. No complete response (CR) was observed; 11 patients had a partial response (PR), 16 patients had no change (NC), and 10 had progressive disease, resulting in an overall response rate of 29.7%, a stable rate of 43.2%, and a disease control rate (CR + PR + NC) of 72.9%. Grade I/II and III/IV neutropenia were observed in 21 (56.7%) and 13 (35.1%) patients, respectively. Four (10.8%) patients developed grade I/II thrombocytopenia. Grade I/II and III/IV nausea and vomiting were observed in 19 (51.2%) and five (13.5%) patients, respectively. Grade I/II liver dysfunction was observed in seven (18.9%) patients. Two patients with grade III liver dysfunction recovered after hepatoprotective treatment. The combination of paclitaxel and platinum was effective and well tolerated in patients with advanced thymic carcinoma.
PMCID: PMC4773309  PMID: 27042225
Carboplatin; cisplatin; paclitaxel; thymic carcinoma
12.  Association between polymorphisms of prokineticin receptor (PKR1 rs4627609 and PKR2 rs6053283) and recurrent pregnancy loss*  
Recurrent pregnancy loss (RPL) is a condition with complex etiologies, to which both genetic and environmental factors may contribute. During the last decade, studies indicated that the expression patterns of the prokineticin receptor (PKR1 and PKR2) are closely related to early pregnancy. However, there are few studies on the role of PKR1 and PKR2 in RPL. In this study, we purpose to investigate the association between polymorphisms of the prokineticin receptor (PKR1 rs4627609 and PKR2 rs6053283) and RPL on a group of 93 RPL cases and 169 healthy controls. Genotyping of the single nucleotide polymorphisms (SNPs) was performed using a Sequenom MassARRAY iPLEX system. The results revealed a significant association between PKR2 rs6053283 polymorphism and RPL (P=0.003), whereas no association was observed between PKR1 rs4627609 polymorphism and RPL (P=0.929) in the Chinese Han population.
PMCID: PMC4794513  PMID: 26984842
Prokineticin receptor 1 (PKR1); PKR2; Polymorphism; Recurrent pregnancy loss
13.  A novel hepatovirus identified in wild woodchuck Marmota himalayana 
Scientific Reports  2016;6:22361.
Hepatitis A virus (HAV) is a hepatotropic picornavirus that causes acute liver disease worldwide. Here, we report on the identification of a novel hepatovirus tentatively named Marmota Himalayana hepatovirus (MHHAV) in wild woodchucks (Marmota Himalayana) in China. The genomic and molecular characterization of MHHAV indicated that it is most closely related genetically to HAV. MHHAV has wide tissue distribution but shows tropism for the liver. The virus is morphologically and structurally similar to HAV. The pattern of its codon usage bias is also consistent with that of HAV. Phylogenetic analysis indicated that MHHAV groups with known HAVs but forms an independent branch, and represents a new species in the genus Hepatovirus within the family Picornaviridae. Antigenic site analysis suggested MHHAV has a new antigenic property to other HAVs. Further evolutionary analysis of MHHAV and primate HAVs led to a most recent common ancestor estimate of 1,000 years ago, while the common ancestor of all HAV-related viruses including phopivirus can be traced back to 1800 years ago. The discovery of MHHAV may provide new insights into the origin and evolution of HAV and a model system with which to explore the pathogenesis of HAV infection.
PMCID: PMC4770319  PMID: 26924426
14.  Synthesis of Nitrogen and Sulfur Co-doped Carbon Dots from Garlic for Selective Detection of Fe3+ 
Garlic was used as a green source to synthesize carbon dots (CDs) with a systematic study of the optical and structure properties. Ethylenediamine was added into the synthesis to improve the photoluminescence quantum yield (PL QY) of the CDs. Detailed structural and composition studies demonstrated that the content of N and the formation of C–N and C=N were critical to improve the PL QY. The as-synthesized CDs exhibited excellent stability in a wide pH range and high NaCl concentrations, rendering them applicable in complicated and harsh conditions. Quenching the fluorescence of the CDs in the presence of Fe3+ ion made these CDs a luminescent probe for selective detection of Fe3+ ion.
Electronic supplementary material
The online version of this article (doi:10.1186/s11671-016-1326-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4770002  PMID: 26924814
Carbon dots; Garlic; Ion detection
15.  Single nucleotide polymorphisms of HSP90AA1 gene influence response of SLE patients to glucocorticoids treatment 
SpringerPlus  2016;5:222.
Heat shock protein 90 (HSP90) is an important glucocorticoid receptor (GR) chaperone protein, and is supposed to be the key factor in regulating glucocorticoids (GCs) effects. The aim of the present study was to explore whether single nucleotide polymorphisms (SNPs) within HSP90AA1 gene affect the response of systemic lupus erythematosus (SLE) patients to GCs treatment. Two hundred and forty-five SLE patients were treated with GCs (prednisone) for 12 weeks. SLE disease activity index (SLEDAI) was used to assess the response of SLE patients to GCs treatment, and patients were classified into sensitive group and insensitive group. HapMap database and Haploview software were used to select tag SNPs. Tag SNPs were genotyped by using multiplex SNaPshot method. Univariate and multivariate logistic regression analyses were used to discriminate the impact of SNPs of HSP90AA1 gene on the response of SLE patients to GCs treatment. Two hundred and thirty three SLE patients finished the 12-week follow-up. Of these patients, 128 patients were included in sensitive group, and 105 patients were included in insensitive group. Seven tag SNPs were selected within HSP90AA1 gene. We detected significant associations for rs7160651 (dominant model: crude OR 0.514, 95 % CI 0.297–0.890, P = 0.018; adjusted OR 0.518, 95 % CI 0.293–0.916, P = 0.024), rs10873531 (dominant model: crude OR 0.516, 95 % CI 0.305–0.876, P = 0.014; adjusted OR 0.522, 95 % CI 0.304–0.898, P = 0.019) and rs2298877 (dominant model: crude OR 0.543, 95 % CI 0.317–0.928, P = 0.026, adjusted OR 0.558, 95 % CI 0.323–0.967, P = 0.037) polymorphisms, but not for other polymorphisms (P > 0.05). The present study demonstrates that HSP90AA1 gene SNPs may affect the response of SLE patients to GCs treatment.
PMCID: PMC4771663  PMID: 27026916
Systemic lupus erythematosus; Glucocorticoids; Heat shock protein 90; Single nucleotide polymorphisms
16.  Dual Energy Spectral CT Imaging for Colorectal Cancer Grading: A Preliminary Study 
PLoS ONE  2016;11(2):e0147756.
To assess the diagnostic value of dual energy spectral CT imaging for colorectal cancer grading using the quantitative iodine density measurements in both arterial phase (AP) and venous phase (VP).
81 colorectal cancer patients were divided into two groups based on their pathological findings: a low grade group including well (n = 13) and moderately differentiated cancer (n = 24), and a high grade group including poorly differentiated (n = 42) and signet ring cell cancer (n = 2). Iodine density (ID) in the lesions was derived from the iodine-based material decomposition (MD) image and normalized to that in the psoas muscle to obtain normalized iodine density (NID). The difference in ID and NID between AP and VP was calculated.
The ID and NID values of the low grade cancer group were, 14.65±3.38mg/mL and 1.70±0.33 in AP, and 21.90±3.11mg/mL and 2.05± 0.32 in VP, respectively. The ID and NID values for the high grade cancer group were 20.63±3.72mg/mL and 2.95±0.72 in AP, and 26.27±3.10mg/mL and 3.51±1.12 in VP, respectively. There was significant difference for ID and NID between the low grade and high grade cancer groups in both AP and VP (all p<0.001). ROC analysis indicated that NID of 1.92 in AP provided 70.3% sensitivity and 97.7% specificity in differentiating low grade cancer from high grade cancer.
The quantitative measurement of iodine density in AP and VP can provide useful information to differentiate low grade colorectal cancer from high grade colorectal cancer with NID in AP providing the greatest diagnostic value.
PMCID: PMC4747602  PMID: 26859405
17.  Intestinal Microbiota Distinguish Gout Patients from Healthy Humans 
Scientific Reports  2016;6:20602.
Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota.
PMCID: PMC4757479  PMID: 26852926
18.  Genome of Cnaphalocrocis medinalis Granulovirus, the First Crambidae-Infecting Betabaculovirus Isolated from Rice Leaffolder to Sequenced 
PLoS ONE  2016;11(2):e0147882.
Cnaphalocrocis medinalis is a major pest of rice in South and South-East Asia. Insecticides are the major means farmers use for management. A naturally occurring baculovirus, C. medinalis granulovirus (CnmeGV), has been isolated from the larvae and this has the potential for use as microbial agent. Here, we described the complete genome sequence of CnmeGV and compared it to other baculovirus genomes. The genome of CnmeGV is 112,060 base pairs in length, has a G+C content of 35.2%. It contains 133 putative open reading frames (ORFs) of at least 150 nucleotides. A hundred and one (101) of these ORFs are homologous to other baculovirus genes including 37 baculovirus core genes. Thirty-two (32) ORFs are unique to CnmeGV with no homologues detected in the GeneBank and 53 tandem repeats (TRs) with sequence length from 25 to 551 nt intersperse throughout the genome of CnmeGV. Six (6) homologous regions (hrs) were identified interspersed throughout the genome. Hr2 contains 11 imperfect palindromes and a high content of AT sequence (about 73%). The unique ORF28 contains a coiled-coil region and a zinc finger-like domain of 4–50 residues specialized by two C2C2 zinc finger motifs that putatively bound two atoms of zinc. ORF21 encoding a chit-1 protein suggesting a horizontal gene transfer from alphabaculovirus. The putative protein presents two carbohydrate-binding module family 14 (CBM_14) domains rather than other homologues detected from betabaculovirus that only contains one chit-binding region. Gene synteny maps showed the colinearity of sequenced betabaculovirus. Phylogenetic analysis indicated that CnmeGV grouped in the betabaculovirus, with a close relation to AdorGV. The cladogram obtained in this work grouped the 17 complete GV genomes in one monophyletic clade. CnmeGV represents a new crambidae host-isolated virus species from the genus Betabaculovirus and is most closely relative of AdorGV. The analyses and information derived from this study will provide a better understanding of the pathological symptoms caused by this virus and its potential use as a microbial pesticide.
PMCID: PMC4746121  PMID: 26848752
19.  Strategies used for genetically modifying bacterial genome: ite-directed mutagenesis, gene inactivation, and gene over-expression*  
With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators.
PMCID: PMC4757579  PMID: 26834010
Escherichia coli; Corynebacterium glutamicum; DNA manipulation; Site-directed mutagenesis; Gene inactivation; Gene over-expression
20.  rhHMGB1 drives osteoblast migration in a TLR2/TLR4- and NF-κB-dependent manner 
Bioscience Reports  2016;36(1):e00300.
In this paper, we reported that rhHMGB1 could significantly enhance the migration of osteoblast without causing cytotoxic effects through the activation of NF-κB via TLR2 or TLR4, indicating a significant functional role for HMGB1 in skeletal development and bone restoration.
Osteoblast migration is significant in skeletal development. Recently, high mobility group box 1 protein (HMGB1) has been shown to highly expressed in cartilage to regulate endochondral ossification. Nevertheless, whether HMGB1 can modulate osteoblast proliferation and migration is poorly understood, as well as the intracellular signalling pathways that are involved in this process. Herein, we examined the effects of recombinant human HMGB1 (rhHMGB1) on the proliferation and migration of rat osteoblasts and investigated whether Toll-like receptor 2 (TLR2)- and TLR4-dependent signalling pathways are involved in the regulation of intracellular signalling. A transwell chamber assay was used to evaluate the migration of osteoblasts and the MTT assay was used to assess osteoblast proliferation. rhHMGB1 could significantly promote the migration of osteoblasts without inhibiting their proliferation. Meanwhile, rhHMGB1 can increase the nuclear translocation of nuclear factor-kappa B (NF-κB) p65. Specific siRNA constructs that target TLR2 or TLR4 could markedly inhibit HMGB1-induced migration of osteoblasts and HMGB1-enhanced activation of NF-κB. Collectively, HMGB1 could significantly enhance the migration of osteoblasts in vitro, and TLR2/TLR4-dependent NF-κB pathways are involved in HMGB1-induced osteoblast migration.
PMCID: PMC4759610  PMID: 26744383
migration; osteoblast; proliferation; recombinant human high mobility group box 1 protein (rhHMGB1); siRNA; skeletal development
21.  A Vehicle Active Safety Model: Vehicle Speed Control Based on Driver Vigilance Detection Using Wearable EEG and Sparse Representation 
In this paper, we present a vehicle active safety model for vehicle speed control based on driver vigilance detection using low-cost, comfortable, wearable electroencephalographic (EEG) sensors and sparse representation. The proposed system consists of three main steps, namely wireless wearable EEG collection, driver vigilance detection, and vehicle speed control strategy. First of all, a homemade low-cost comfortable wearable brain-computer interface (BCI) system with eight channels is designed for collecting the driver’s EEG signal. Second, wavelet de-noising and down-sample algorithms are utilized to enhance the quality of EEG data, and Fast Fourier Transformation (FFT) is adopted to extract the EEG power spectrum density (PSD). In this step, sparse representation classification combined with k-singular value decomposition (KSVD) is firstly introduced in PSD to estimate the driver’s vigilance level . Finally, a novel safety strategy of vehicle speed control, which controls the electronic throttle opening and automatic braking after driver fatigue detection using the above method, is presented to avoid serious collisions and traffic accidents. The simulation and practical testing results demonstrate the feasibility of the vehicle active safety model.
PMCID: PMC4801618  PMID: 26907278
wearable electroencephalographic; vigilance detection; vehicle active safety; vehicle speed control; sparse representation; brain-computer interface
22.  Developmental control of Polycomb subunit composition by GATA factors mediates a switch to non-canonical functions 
Molecular cell  2015;57(2):304-316.
Polycomb Repressive Complex 2 (PRC2) plays crucial roles in transcriptional regulation and stem cell development. However, the context-specific functions associated with alternative subunits remain largely unexplored. Here we show that the related enzymatic subunits EZH1 and EZH2 undergo an expression switch during blood cell development. An erythroid-specific enhancer mediates transcriptional activation of EZH1, and a switch from GATA2 to GATA1 controls the developmental EZH1/2 switch by differential association with EZH1 enhancers. We further examine the in vivo stoichiometry of the PRC2 complexes by quantitative proteomics and reveal the existence of an EZH1-SUZ12 sub-complex lacking EED. EZH1 together with SUZ12 form a non-canonical PRC2 complex, occupy active chromatin, and positively regulate gene expression. Loss of EZH2 expression leads to repositioning of EZH1 to EZH2 targets. Thus, the lineage- and developmental stage-specific regulation of PRC2 subunit composition leads to a switch from canonical silencing to non-canonical functions during blood stem cell specification.
PMCID: PMC4305004  PMID: 25578878
23.  Factor inhibiting HIF1α (FIH-1) functions as a tumor suppressor in human colorectal cancer by repressing HIF1α pathway 
Cancer Biology & Therapy  2015;16(2):244-252.
Colorectal cancer (CRC) is one of the most common cancers worldwide. The molecular mechanisms underlying CRC development involve a multistep process with the accumulation of both genetic and epigenetic changes. To deeply understand CRC tumorigenesis and progression, advances in identification of novel mechanisms and key factors are therefore in an urgent need. Here, we examined the correlation of factor inhibiting HIF-1α (FIH-1) expression with clinicopathological features of CRC. The finding that FIH-1 was not only significantly decreased in tumor tissue but also was significantly correlated with tumor invading depth, lymph node involvement, and metastasis suggested the role of FIH-1 as a tumor suppressor in CRC development. To further support the above hypothesis, we performed both in vitro and in vivo experiments to identify the role of FIH-1 in CRC development. FIH-1 was found to inhibit CRC cell proliferation, migration, invasion, and colony formation in vitro. FIH-1 was also shown to repress LOVO xenograft tumor growth in vivo. To decipher the mechanism, we examined the expression level of HIF-1α and its target genes. We found that FIH-1 was able to inhibit HIF1α mediated transcription of GLUT1 and VEGF in CRC cells. The above observation points to the possibility that loss or decreased expression of FIH-1 gene may lead to a constitutive activation of HIF1α and an alteration of HIF-1 targets such as GLUT-1 and VEGF. These findings highlight the critical role of FIH-1 in CRC and indicate FIH-1 functions as a tumor suppressor in human CRC by repressing HIF1α pathway.
PMCID: PMC4622465  PMID: 25602156
colorectal cancer; FIH-1; HIF1α pathway; prognosis; progression; tumor suppressor; tumorigenesis
24.  TGF-β-induced epithelial to mesenchymal transition 
Cell research  2009;19(2):156-172.
During development and in the context of different morphogenetic events, epithelial cells undergo a process called epithelial to mesenchymal transition or transdifferentiation (EMT). In this process, the cells lose their epithelial characteristics, including their polarity and specialized cell-cell contacts, and acquire a migratory behavior, allowing them to move away from their epithelial cell community and to integrate into surrounding tissue, even at remote locations. EMT illustrates the differentiation plasticity during development and is complemented by another process, called mesenchymal to epithelial transition (MET). While being an integral process during development, EMT is also recapitulated under pathological conditions, prominently in fibrosis and in invasion and metastasis of carcinomas. Accordingly, EMT is considered as an important step in tumor progression. TGF-β signaling has been shown to play an important role in EMT. In fact, adding TGF-β to epithelial cells in culture is a convenient way to induce EMT in various epithelial cells. Although much less characterized, epithelial plasticity can also be regulated by TGF-β-related bone morphogenetic proteins (BMPs), and BMPs have been shown to induce EMT or MET depending on the developmental context. In this review, we will discuss the induction of EMT in response to TGF-β, and focus on the underlying signaling and transcription mechanisms.
PMCID: PMC4720263  PMID: 19153598
TGF-β; EMT; Smad; transcription; non-Smad signaling
25.  Effect of Body mass index on the performance characteristics of PSA-related markers to detect prostate cancer 
Scientific Reports  2016;6:19034.
To examine whether the predictive performance of prostate-specific antigen (PSA) and PSA-related markers for prostate cancer (PCa) is modified by body mass index (BMI). Patients with a PSA 2–10 ng/mL who underwent multicore prostate biopsies were recruited from three tertiary centers. Serum markers measured included total PSA (tPSA), free-to-total PSA (f/tPSA), p2PSA, percentage of p2PSA (%p2PSA), and prostate health index (PHI). The association between serum markers and PCa risk was assessed by logistic regression. Predictive performance for each marker was quantified using the area under the receiver operator curves (AUC). Among 516 men, 18.2% had PCa at biopsy. For all tested markers, their predictive value on PCa risk was lower in obese patients compared to normal weight patients. We found statistically significant interactions between BMI and tPSA (P = 0.0026) and p2PSA (P = 0.038). PHI achieved an AUC of 0.872 in normal weight patients and 0.745 in obese patients, which outperformed the other predictors regardless of BMI category. In conclusion, PHI achieved the best predictive performance for detecting PCa and was not influenced by BMI.
PMCID: PMC4709513  PMID: 26754552

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