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1.  Identification of Norovirus as the Top Enteric Viruses Detected in Adult Cases with Acute Gastroenteritis 
To elucidate the importance of the norovirus and other enteric viruses, and the difference of the genetic relatedness on norovirus between the outbreak and sporadic cases, a total of 557 stool samples, consisting of 503 sporadic cases and 54 samples of 4 outbreaks were collected and tested for norovirus and other enteric viruses in Beijing, China, July 2007–June 2008. The data showed norovirus, rotavirus, astrovirus, and sapovirus, were detected in 26.6%, 6.1%, 1.8%, and 0.5%, respectively. Norovirus was detected almost throughout the surveillance period, norovirus co-infecting with rotavirus, astrovirus, and sapovirus, respectively, were identified both in outbreak and the sporadic cases. GII.4/2006 was identified as the predominant strain circulating both in outbreak and sporadic cases. The results showed that norovirus was rather the important agent than other enteric viruses affected adults with acute gastroenteritis; no significant genetic relatedness of the dominant strains was found between the outbreak and sporadic cases.
PMCID: PMC2844560  PMID: 20348525
2.  Genomic and transcriptomic analysis of the endophytic fungus Pestalotiopsis fici reveals its lifestyle and high potential for synthesis of natural products 
BMC Genomics  2015;16(1):28.
In recent years, the genus Pestalotiopsis is receiving increasing attention, not only because of its economic impact as a plant pathogen but also as a commonly isolated endophyte which is an important source of bioactive natural products. Pestalotiopsis fici Steyaert W106-1/CGMCC3.15140 as an endophyte of tea produces numerous novel secondary metabolites, including chloropupukeananin, a derivative of chlorinated pupukeanane that is first discovered in fungi. Some of them might be important as the drug leads for future pharmaceutics.
Here, we report the genome sequence of the endophytic fungus of tea Pestalotiopsis fici W106-1/CGMCC3.15140. The abundant carbohydrate-active enzymes especially significantly expanding pectinases allow the fungus to utilize the limited intercellular nutrients within the host plants, suggesting adaptation of the fungus to endophytic lifestyle. The P. fici genome encodes a rich set of secondary metabolite synthesis genes, including 27 polyketide synthases (PKSs), 12 non-ribosomal peptide synthases (NRPSs), five dimethylallyl tryptophan synthases, four putative PKS-like enzymes, 15 putative NRPS-like enzymes, 15 terpenoid synthases, seven terpenoid cyclases, seven fatty-acid synthases, and five hybrids of PKS-NRPS. The majority of these core enzymes distributed into 74 secondary metabolite clusters. The putative Diels-Alderase genes have undergone expansion.
The significant expansion of pectinase encoding genes provides essential insight in the life strategy of endophytes, and richness of gene clusters for secondary metabolites reveals high potential of natural products of endophytic fungi.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-014-1190-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4320822  PMID: 25623211
Genome; Endophyte; Pestalotiopsis fici; Secondary metabolite
3.  Plasmon resonance enhanced multicolour photodetection by graphene 
Nature communications  2011;2:579.
Graphene has the potential for high-speed, wide-band photodetection, but only with very low external quantum efficiency and no spectral selectivity. Here we report a dramatic enhancement of the overall quantum efficiency and spectral selectivity that enables multicolour photodetection, by coupling graphene with plasmonic nanostructures. We show that metallic plasmonic nanostructures can be integrated with graphene photodetectors to greatly enhance the photocurrent and external quantum efficiency by up to 1,500%. Plasmonic nanostructures of variable resonance frequencies selectively amplify the photoresponse of graphene to light of different wavelengths, enabling highly specific detection of multicolours. Being atomically thin, graphene photodetectors effectively exploit the local plasmonic enhancement effect to achieve a significant enhancement factor not normally possible with traditional planar semiconductor materials.
PMCID: PMC4235953  PMID: 22146398
4.  Effects of crowding and sex on fecal cortisol levels of captive forest musk deer 
Biological Research  2014;47(1):48.
Restricted space and close contact with conspecifics in captivity may be stressful for musk deer, as they are highly territorial and solitary in the wild. So we tested the effects of crowding on stress of forest musk deer (Moschus berezovskii) in heterosexual groups, using fecal cortisol analysis as a non-invasive method. 32 healthy adults during non-breeding seasons were chose as our experimental objects. Group 1 was defined as higher crowding condition, with 10-15 m2/deer (6 enclosures, 10♀ and 6♂); group 2 was defined as lower crowding condition, with 23-33 m2/deer (6 enclosures, 10♀ and 6♂). Every enclosure contained 1 male and 3 female. These patterns had been existed for years.
The results showed that females in lower crowding condition (217.1 ± 9.5 ug/g) had significantly higher fecal cortisol levels than those in higher crowding condition (177.2 ± 12.1 ug/g). Interestingly, crowding seemed have no effect on male fecal cortisol levels (148.1 ± 9.1 ug/g and 140.5 ± 13.3 ug/g, respectively). At both groups, cortisol was significantly lower in males than in females.
These results showed that chronic crowding may affect stress status of captive forest musk deer. The captive environment should consider the space need for musk deer.
PMCID: PMC4222733  PMID: 25418206
Captivity; M. berezovskii; Fecal cortisol; Chronic stress; Crowding
5.  Relationship between lipids levels and right ventricular volume overload in congestive heart failure 
The relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechanisms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels.
We collected data of clinical characteristics, echocardiograph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels [including total cholesterol (TCL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area.
There was a significantly inverse correlation between TCL levels and RVEDD (r = −0.34, P < 0.001) and RA (r = −0.36, P < 0.001). Other lipids such as LDL-C, HDL-C, and TG had a similar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use.
Lipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as well as identify a causal relationship, if any.
PMCID: PMC4178509  PMID: 25278966
Lipid levels; Heart failure; Right ventricle; Volume overload; Correlation analysis
6.  Maternal germline mosaicism of kinesin family member 21A (KIF21A) mutation causes complex phenotypes in a Chinese family with congenital fibrosis of the extraocular muscles 
Molecular Vision  2014;20:15-23.
To identify the causative mutation with its possible origin in a Chinese family with congenital fibrosis of extraocular muscles type 1 (CFEOM1) and to characterize the ocular phenotypes and lesions in the corresponding intracranial nerves.
Three affected siblings and their asymptomatic parents underwent comprehensive ophthalmic examinations and neuropathologic analysis involving magnetic resonance imaging (MRI). KIF21A, PHOX2A, and TUBB3 genes were sequenced on the leukocyte-derived DNA to detect variants. The disease-linked haplotype was analyzed using four microsatellite markers across the KIF21A locus.
All three affected individuals displayed typical CFEOM1. MRI revealed complicated but consistent neuromuscular abnormalities in the two patients examined, including hypoplastic oculomotor nerves, complete absence of bilateral superior rectus muscles, and unilateral absence of the abducens nerve with marked atrophy of the corresponding lateral rectus muscle. A heterozygous hotspot mutation KIF21A c.2860C>T was identified in all patients, but it was absent in both parents. Haplotype analysis of the disease locus showed the likely maternal inheritance of the disease-associated haplotype to all three affected offspring, strongly suggesting maternal germline mosaicism of the mutation.
Germline mosaicism of KIF21A c.2860C>T is likely to cause the high occurrence of this mutation in the population. This information may be useful for genetic counseling. KIF21A mutations can affect the abducens nerve and cause complete absence of the bilateral superior rectus muscles. MRI characterization of new CFEOM1 phenotypes would assist clinical management.
PMCID: PMC3888497  PMID: 24426772
7.  Domain Wall Motion in Synthetic Co2Si Nanowires 
Nano letters  2012;12(4):1972-1976.
We report the synthesis of single crystalline Co2Si nanowires, and electrical transport studies of single Co2Si nanowire devices at low temperature. The butterfly-shaped magnetoresistance shows interesting ferromagnetic features including negative magnetoresistance, hysteretic switch fields and step-wise drops in magnetoresistance. The non-smooth step-wise magnetoresistance response is attributed to magnetic domain wall pinning and de-pinning motion in the Co2Si nanowires probably at crystal defects or morphology defects. The temperature dependence of the domain wall de-pinning field is observed and is described by a model based on thermally assisted domain wall de-pinning over a single energy barrier.
PMCID: PMC3493485  PMID: 22469009
nanowires; magnetoresistance; domain wall; de-pinning field
8.  Serum uric acid as an index of impaired renal function in congestive heart failure 
Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure.
We retrospectively assessed clinical characteristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis.
In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P < 0.001) and SCr (r = 0.47, P < 0.001).
There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.
PMCID: PMC3418902  PMID: 22916059
Serum uric acid; Heart failure; Renal function impairment; Factor analysis
9.  Clinical characteristics of the autumn-winter type scrub typhus cases in south of Shandong province, northern China 
Before 1986, scrub typhus was only found endemic in southern China. Because human infections typically occur in the summer, it is called "summer type". During the autumn-winter period of 1986, a new type of scrub typhus was identified in Shandong and northern Jiangsu province of northern China. This newly recognized scrub typhus was subsequently reported in many areas of northern China and was then called "autumn-winter type". However, clinical characteristics of associated cases have not been reported.
From 1995 to 2006, all suspected scrub typhus cases in five township hospitals of Feixian county, Shandong province were enrolled. Indirect immunofluorescent assay (IFA) was used as confirmatory serodiagnosis test. Polymerase chain reaction (PCR) connected with restriction fragment length polymorphism (RFLP) and sequence analyses were used for genotyping of O. tsutsugamushi DNAs. Clinical symptoms and demography of confirmed cases were analyzed.
A total of 480 scrub typhus cases were confirmed. The cases occurred every year exclusively between September and December with a peak occurrence in October. The case numbers were relatively higher in 1995, 1996, 1997, and 2000 than in other years. 57.9% of cases were in the group aged 21–50. More cases occurred in male (56%) than in female (44%). The predominant occupational group of the cases was farmers (85.0%). Farm work was reported the primary exposure to infection in 67.7% of cases. Fever, rash, and eschar were observed in 100.0%, 90.4%, and 88.5% of cases, respectively. Eschars formed frequently on or around umbilicus, abdomen areas, and front and back of waist (34.1%) in both genders. Normal results were observed in 88.7% (WBC counts), 84.5% (PLT counts), and 89.7% (RBC counts) of cases, respectively. Observations from the five hospitals were compared and no significant differences were found.
The autumn-winter type scrub typhus in northern China occurred exclusively from September to December with a peak occurrence in October, which was different from the summer type in southern China. In comparison with the summer type, complications associated with autumn-winter type scrub typhus were less severe, and abnormalities of routine hematological parameters were less obvious.
PMCID: PMC2703643  PMID: 19493361
10.  Potent diuretic effects of prednisone in heart failure patients with refractory diuretic resistance 
The Canadian Journal of Cardiology  2007;23(11):865-868.
Refractory congestive heart failure (CHF) with diuretic resistance is life-threatening and predicts a short life expectancy. Glucocorticoids have been proven to have potent diuretic effects in animal studies; however, their efficacy in CHF patients with diuretic resistance is not known.
Thirteen CHF patients with significant volume overload and diuretic resistance who failed to respond to a conventional sequential nephron blockade therapeutic strategy; that is, the coad-ministration of a thiazide (hydrochlorothiazide) and spironolactone, in combination with loop diuretics, were studied. Prednisone (1 mg/kg daily) was then added to standard care, with other medications unchanged, to determine diuretic efficacy in these CHF patients. Variables included body weight, urine volume, serum electrolytes and renal function.
Adding prednisone resulted in striking diuresis with a mean (± SD) body weight reduction of 9.39±3.09 kg. Prednisone significantly decreased serum creatinine by 52.21±48.68 μmol/L and increased glomerular filtration rate by 33.63±15.87 mL/min/1.73 m2 compared with baseline. All patients were discharged from hospital with improved clinical status and renal function, and 11 patients remained alive in the long term. The main side effect of prednisone appeared to be hyperglycemia in diabetic patients.
The present study demonstrated that prednisone can rapidly eliminate volume overload and improve clinical status and renal function in CHF patients with diuretic resistance. Further prospective randomized clinical studies are warranted to confirm its clinical efficacy.
PMCID: PMC2651362  PMID: 17876376
Diuretic resistance; Furosemide; Heart failure; Prednisone; Renal function; Spironolactone
11.  Acetylcholinesterase-Catalyzed Hydrolysis Allows Ultrasensitive Detection of Pathogens with the Naked Eye** 
Angewandte Chemie (International ed. in English)  2013;52(52):10.1002/anie.201307952.
This paper describes a rapid diagnostic platform for pathogen detection based on the acetylcholinesterase-catalyzed hydrolysis reaction. Owing to the signal amplification strategies, the sensitivity of this assay is comparable to that of PCR. In addition, the readout of this assay is based on the color change of solutions, which can be easily observed by the naked eye alone.
PMCID: PMC3874880  PMID: 24155243
acetylcholinesterase-catalyzed hydrolysis; pathogen detection; high-sensitivity; gold nanoparticle; clinical samples
12.  Staphylococcal Enterotoxin H Induced Apoptosis of Bovine Mammary Epithelial Cells in Vitro 
Toxins  2014;6(12):3552-3567.
Staphylococcal enterotoxins (SEs) are powerful superantigenic toxins produced by Staphylococcus aureus (S. aureus). They can cause food poisoning and toxic shock. However, their impact on bovine mammary epithelial cells (bMECs) is still unknown. In this study, the distribution of SE genes was evaluated in 116 S. aureus isolates from bovine mastitis, and the most prevalent genes were seh (36.2%), followed by sei (12.1%), seg (11.2%), ser (4.3%), sec (3.4%), sea (2.6%) and sed (1.7%). To better understand the effect of staphylococcal enterotoxin H (SEH) on bMECs, the seh gene was cloned and inserted into the prokaryotic expression vector, pET28a, and transformed into Escherichia coli BL21 (DE3). The recombinant staphylococcal enterotoxin H (rSEH) was expressed and purified as soluble protein. Bioactivity analysis showed that rSEH possessed the activity of stimulating lymphocytes proliferation. The XTT assay showed that 100 μg/mL of rSEH produced the cytotoxic effect on bMECs, and fluorescence microscopy and flow cytometry analysis revealed that a certain dose of rSEH is effective at inducing bMECs apoptosis in vitro. This indicates that SEs can directly lead to cellular apoptosis of bMECs in bovine mastitis associated with S. aureus.
PMCID: PMC4280547  PMID: 25533519
staphylococcal enterotoxin H; expression; bioactivity; bovine mammary gland epithelial cells; viability; apoptosis
13.  A systematic study of atmospheric pressure chemical vapor deposition growth of large-area monolayer graphene† 
Journal of materials chemistry  2012;22(4):1498-1503.
Graphene has attracted considerable interest as a potential material for future electronics. Although mechanical peel is known to produce high quality graphene flakes, practical applications require continuous graphene layers over a large area. The catalyst-assisted chemical vapor deposition (CVD) is a promising synthetic method to deliver wafer-sized graphene. Here we present a systematic study on the nucleation and growth of crystallized graphene domains in an atmospheric pressure chemical vapor deposition (APCVD) process. Parametric studies show that the mean size of the graphene domains increases with increasing growth temperature and CH4 partial pressure, while the density of domains decreases with increasing growth temperature and is independent of the CH4 partial pressure. Our studies show that nucleation of graphene domains on copper substrate is highly dependent on the initial annealing temperature. A two-step synthetic process with higher initial annealing temperature but lower growth temperature is developed to reduce domain density and achieve high quality full-surface coverage of monolayer graphene films. Electrical transport measurements demonstrate that the resulting graphene exhibits a high carrier mobility of up to 3000 cm2 V−1 s−1 at room temperature.
PMCID: PMC4235958  PMID: 25414547
14.  Dietary Glutamate Supplementation Ameliorates Mycotoxin-Induced Abnormalities in the Intestinal Structure and Expression of Amino Acid Transporters in Young Pigs 
PLoS ONE  2014;9(11):e112357.
The purpose of this study was to investigate the hypothesis that dietary supplementation with glutamic acid has beneficial effects on growth performance, antioxidant system, intestinal morphology, serum amino acid profile and the gene expression of intestinal amino acid transporters in growing swine fed mold-contaminated feed. Fifteen pigs (Landrace×Large White) with a mean body weight (BW) of 55 kg were randomly divided into control group (basal feed), mycotoxin group (contaminated feed) and glutamate group (2% glutamate+contaminated feed). Compared with control group, mold-contaminated feed decreased average daily gain (ADG) and increased feed conversion rate (FCR). Meanwhile, fed mold-contaminated feed impaired anti-oxidative system and intestinal morphology, as well as modified the serum amino acid profile in growing pigs. However, supplementation with glutamate exhibited potential positive effects on growth performance of pigs fed mold-contaminated feed, ameliorated the imbalance antioxidant system and abnormalities of intestinal structure caused by mycotoxins. In addition, dietary glutamate supplementation to some extent restored changed serum amino acid profile caused by mold-contaminated feed. In conclusion, glutamic acid may be act as a nutritional regulating factor to ameliorate the adverse effects induced by mycotoxins.
PMCID: PMC4236086  PMID: 25405987
15.  Draft Genome Sequence of Bacillus subtilis Strain NKYL29, an Antimicrobial-Peptide-Producing Strain from Soil 
Genome Announcements  2014;2(6):e01140-14.
Bacillus subtilis strain NKYL29 is an antimicrobial-peptide-producing strain isolated from the soil of Ranzhuang Tunnel in Hebei Province, China. Here, we present the draft genome of this strain, which provides the genetic basis for application of the antimicrobial peptide.
PMCID: PMC4223466  PMID: 25377715
16.  Thermally assisted electric field control of magnetism in flexible multiferroic heterostructures 
Scientific Reports  2014;4:6925.
Thermal and electrical control of magnetic anisotropy were investigated in flexible Fe81Ga19 (FeGa)/Polyvinylidene fluoride (PVDF) multiferroic heterostructures. Due to the large anisotropic thermal deformation of PVDF (α1 = −13 × 10−6 K−1 and α2 = −145 × 10−6 K−1), the in-plane uniaxial magnetic anisotropy (UMA) of FeGa can be reoriented 90° by changing the temperature across 295 K where the films are magnetically isotropic. Thus, the magnetization of FeGa can be reversed by the thermal cycling between 280 and 320 K under a constant magnetic field lower than coercivity. Moreover, under the assistance of thermal deformation with slightly heating the samples to the critical temperature, the electric field of ± 267 kV cm−1 can well align the UMA along the two orthogonal directions. The new route of combining thermal and electrical control of magnetic properties realized in PVDF-based flexible multiferroic materials shows good prospects in application of flexible thermal spintronic devices and flexible microwave magnetic materials.
PMCID: PMC4220272  PMID: 25370605
17.  An Obligatory Role of NF-κB in Mediating Bone Marrow Derived Endothelial Progenitor Cell Recruitment and Proliferation Following Endotoxemic Multiple Organ Injury in Mice 
PLoS ONE  2014;9(10):e111087.
Recruitment of bone marrow derived endothelial progenitor cells (BMDEPCs) alleviates multiple organ injury (MOI) and improves outcomes. However, mechanisms mediating BMDEPC recruitment following septic MOI remain largely unknown. This study characterized the kinetics of BMDEPC recruitment and proliferation and defined the role of NF-κB in regulating BMDEPC recruitment and proliferation.
Methods and Main Findings
Chimeric mice with an intact or disrupted NF-κB p50 gene and BMDEPC-restricted expression of green fluorescent protein were created and injected with LPS (2 mg/kg, i.p.). BMDEPC recruitment and proliferation in multiple organs were quantified. BMDEPC recruitment and proliferation are highly organ-dependent. Lungs had the highest number of BMDEPC recruitment, whereas heart, liver and kidney had only a small fraction of the number of BMDEPCs in lungs. Number of proliferating BMDEPCs was several-fold higher in lungs than in other 3 organs. Kinetically, BMDEPC recruitment into different organs showed different time course profiles. NF-κB plays obligatory roles in mediating BMDEPC recruitment and proliferation. Universal deletion of NF-κB p50 gene inhibited LPS-induced BMDEPC recruitment and proliferation by 95% and 69% in heart. However, the contribution of NF-κB to these regulations varies significantly between organs. In liver, universal p50 gene deletion reduced LPS-induced BMDEPC recruitment and proliferation only by 49% and 35%. NF-κB activities in different tissue compartments play distinct roles. Selective p50 gene deletion either in stromal/parenchymal cells or in BM/blood cells inhibited BMDEPC recruitment by a similar extent. However, selective p50 gene deletion in BM/blood cells inhibited, but in stromal/parenchymal cells augmented BMDEPC proliferation.
BMDEPC recruitment and proliferation display different kinetics in different organs following endotoxemic MOI. NF-κB plays obligatory and organ-dependent roles in regulating BMDEPC recruitment and proliferation. NF-κB activities in different tissue compartments play distinct roles in regulating BMDEPC proliferation.
PMCID: PMC4205081  PMID: 25333282
18.  Positive temperature coefficient of magnetic anisotropy in polyvinylidene fluoride (PVDF)-based magnetic composites 
Scientific Reports  2014;4:6615.
The magnetic anisotropy is decreased with increasing temperature in normal magnetic materials, which is harmful to the thermal stability of magnetic devices. Here, we report the realization of positive temperature coefficient of magnetic anisotropy in a novel composite combining β-phase polyvinylidene fluoride (PVDF) with magnetostrictive materials (magnetostrictive film/PVDF bilayer structure). We ascribe the enhanced magnetic anisotropy of the magnetic film at elevated temperature to the strain-induced anisotropy resulting from the anisotropic thermal expansion of the β-phase PVDF. The simulation based on modified Stoner-Wohlfarth model and the ferromagnetic resonance measurements confirms our results. The positive temperature coefficient of magnetic anisotropy is estimated to be 1.1 × 102 J m−3 K−1. Preparing the composite at low temperature can enlarge the temperature range where it shows the positive temperature coefficient of magnetic anisotropy. The present results may help to design magnetic devices with improved thermal stability and enhanced performance.
PMCID: PMC4196102  PMID: 25311047
19.  NF-κB-to-AP-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury to Repair in Endotoxemic Mice 
Scientific Reports  2014;4:5543.
Endothelial barrier disruption is a hallmark of multiple organ injury (MOI). However, mechanisms governing the restoration of endothelial barrier function are poorly understood. Here, we uncovered an NF-κB-to-AP-1 switch that regulates the transition from barrier injury to repair following endotoxemic MOI. Endothelial NF-κB mediates barrier repair by inhibiting endothelial cell (EC) apoptosis. Blockade of endothelial NF-κB pathway activated the activator protein (AP)-1 pathway (NF-κB-to-AP-1 switch), which compensated for the anti-apoptotic and barrier-repair functions of NF-κB. The NF-κB-to-AP-1 switch occurred at 24 hours (injury to repair transition phase), but not at 48 hours (repair phase) post-LPS, and required an inflammatory signal within the endothelium. In the absence of an inflammatory signal, the NF-κB-to-AP-1 switch failed, resulting in enhanced EC apoptosis, augmented endothelial permeability, and impeded transition from barrier injury to recovery. The NF-κB-to-AP-1 switch is a protective mechanism to ensure timely transition from endothelial barrier injury to repair, accelerating barrier restoration following MOI.
PMCID: PMC4078303  PMID: 24986487
20.  Chlorogenic Acid Decreases Intestinal Permeability and Increases Expression of Intestinal Tight Junction Proteins in Weaned Rats Challenged with LPS 
PLoS ONE  2014;9(6):e97815.
Chlorogenic acid, a natural phenolic acid present in fruits and plants, provides beneficial effects for human health. The objectives of this study were to investigate whether chlorogenic acid (CHA) could improve the intestinal barrier integrity for weaned rats with lipopolysaccharide (LPS) challenge. Thirty-two weaned male Sprague Dawley rats (21±1 d of age; 62.26±2.73 g) were selected and randomly allotted to four treatments, including weaned rat control, LPS-challenged and chlorogenic acid (CHA) supplemented group (orally 20 mg/kg and 50 mg/kg body). Dietary supplementation with CHA decreased (P<0.05) the concentrations of urea and albumin in the serum, compared to the LPS-challenged group. The levels of IFN-γ and TNF-α were lower (P<0.05) in the jejunal and colon of weaned rats receiving CHA supplementation, in comparison with the control group. CHA supplementation increased (P<0.05) villus height and the ratio of villus height to crypt depth in the jejunal and ileal mucosae under condictions of LPS challenge. CHA supplementation decreased (P<0.05) intestinal permeability, which was indicated by the ratio of lactulose to mannitol and serum DAO activity, when compared to weaned rats with LPS challenge. Immunohistochemical analysis of tight junction proteins revealed that ZO-1 and occludin protein abundances in the jejunum and colon were increased (P<0.05) by CHA supplementation. Additionally, results of immunoblot analysis revealed that the amount of occludin in the colon was also increased (P<0.05) in CHA-supplemented rats. In conclusion, CHA decreases intestinal permeability and increases intestinal expression of tight junction proteins in weaned rats challenged with LPS.
PMCID: PMC4041575  PMID: 24887396
21.  Urinary soluble urokinase receptor levels are elevated and pathogenic in patients with primary focal segmental glomerulosclerosis 
BMC Medicine  2014;12:81.
Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease. Recent studies have proposed that plasma soluble urokinase receptor (suPAR) might be a causative circulating factor but this proposal has caused controversy. This study aimed to measure urinary suPAR levels in patients with primary FSGS and its significance in the pathogenesis of FSGS.
Sixty-two patients with primary FSGS, diagnosed between January 2006 and January 2012, with complete clinical and pathologic data were enrolled, together with disease and normal controls. Urinary suPAR levels were measured using commercial ELISA kits and were corrected by urinary creatinine (Cr). The associations between urinary suPAR levels and clinical data at presentation and during follow up were analyzed. Conditionally immortalized human podocytes were used to study the effect of urinary suPAR on activating β3 integrin detected by AP5 staining.
The urinary suPAR level of patients with primary FSGS (500.56, IQR 262.78 to 1,059.44 pg/μmol Cr) was significantly higher than that of patients with minimal change disease (307.86, IQR 216.54 to 480.18 pg/μmol Cr, P = 0.033), membranous nephropathy (250.23, IQR 170.37 to 357.59 pg/μmol Cr, P <0.001), secondary FSGS (220.45, IQR 149.38 to 335.54 pg/μmol Cr, P <0.001) and normal subjects (183.59, IQR 103.92 to 228.78 pg/μmol Cr, P <0.001). The urinary suPAR level of patients with cellular variant was significantly higher than that of patients with tip variant. The urinary suPAR level in the patients with primary FSGS was positively correlated with 24-hour urine protein (r = 0.287, P = 0.024). During follow up, the urinary suPAR level of patients with complete remission decreased significantly (661.19, IQR 224.32 to 1,115.29 pg/μmol Cr versus 217.68, IQR 121.77 to 415.55 pg/μmol Cr, P = 0.017). The AP5 signal was strongly induced along the cell membrane when human differentiated podocytes were incubated with the urine of patients with FSGS at presentation, and the signal could be reduced by a blocking antibody specific to uPAR.
Urinary suPAR was specifically elevated in patients with primary FSGS and was associated with disease severity. The elevated urinary suPAR could activate β3 integrin on human podocytes.
Please see related article
PMCID: PMC4064821  PMID: 24884842
Focal segmental glomerulosclerosis; Urinary soluble urokinase receptor; Podocyte
22.  Development of a New Risk Score for Incident Type 2 Diabetes Using Updated Diagnostic Criteria in Middle-Aged and Older Chinese 
PLoS ONE  2014;9(5):e97042.
Type 2 diabetes mellitus (T2DM) reaches an epidemic proportion among adults in China. However, no simple score has been created for the prediction of T2DM incidence diagnosed by updated criteria with hemoglobin A1c (HbA1c) ≥6.5% included in Chinese. In a 6-year follow-up cohort in Beijing and Shanghai, China, we recruited a total of 2529 adults aged 50–70 years in 2005 and followed them up in 2011. Fasting plasma glucose (FPG), HbA1c, and C-reactive protein (CRP) were measured and incident diabetes was identified by the recently updated criteria. Of the 1912 participants without T2DM at baseline, 924 were identified as having T2DM at follow-up, and most of them (72.4%) were diagnosed using the HbA1c criterion. Baseline body mass index, FPG, HbA1c, CRP, hypertension, and female gender were all significantly associated with incident T2DM. Based upon these risk factors, a simple score was developed with an estimated area under the receiver operating characteristic curve of 0.714 (95% confidence interval: 0.691, 0.737), which performed better than most of existing risk score models developed for eastern Asian populations. This simple, newly constructed score of six parameters may be useful in predicting T2DM in middle-aged and older Chinese.
PMCID: PMC4018395  PMID: 24819157
23.  MCPIP1 Negatively Regulates Toll-like Receptor 4 Signaling and Protects Mice from LPS-induced Septic Shock 
Cellular signalling  2013;25(5):1228-1234.
Septic shock is one of leading causes of morbidity and mortality in hospital patients. However, genetic factors predisposing to septic shock are not fully understood. Our previous work showed that MCP-induced protein 1 (MCPIP1) was induced by lipopolysaccharides (LPS), which then negatively regulates LPS-induced inflammatory signaling in vitro. Here we report that although MCPIP1 was induced by various toll-like receptor (TLR) ligands in macrophages, MCPIP1-deficient mice are extremely susceptible to TLR4 ligand (LPS)-induced septic shock and death, but not to the TLR2, 3, 5 and 9 ligands-induced septic shock. Consistently, LPS induced tumor necrosis factor α (TNFα) production in MCPIP1-deficient mice was 20-fold greater than that in their wild-type littermates. Further analysis revealed that MCPIP1-deficient mice developed severe acute lung injury after LPS injection and JNK signaling was highly activated in MCPIP1-deificient lungs after LPS stimulation. Finally, macrophage-specific MCPIP1 transgenic mice were partially protected from LPS-induced septic shock, suggesting that inflammatory cytokines from sources other than macrophages may significantly contribute to the pathogenesis of LPS-induced septic shock. Taken together, these results suggest that MCPIP1 selectively suppresses TLR4 signaling pathway and protects mice from LPS-induced septic shock.
PMCID: PMC3622792  PMID: 23422584
MCPIP1; Toll-like receptor; LPS; Septic shock; TNF
24.  Genetic Structure of Chinese Indigenous Goats and the Special Geographical Structure in the Southwest China as a Geographic Barrier Driving the Fragmentation of a Large Population 
PLoS ONE  2014;9(4):e94435.
China has numerous native domestic goat breeds, however, extensive studies are focused on the genetic diversity within the fewer breeds and limited regions, the population demograogic history and origin of Chinese goats are still unclear. The roles of geographical structure have not been analyzed in Chinese goat domestic process. In this study, the genetic relationships of Chinese indigenous goat populations were evaluated using 30 microsatellite markers.
Methodology/Principal Findings
Forty Chinese indigenous populations containing 2078 goats were sampled from different geographic regions of China. Moderate genetic diversity at the population level (HS of 0.644) and high population diversity at the species level (HT value of 0.737) were estimated. Significant moderate population differentiation was detected (FST value of 0.129). Significant excess homozygosity (FIS of 0.105) and recent population bottlenecks were detected in thirty-six populations. Neighbour-joining tree, principal components analysis and Bayesian clusters all revealed that Chinese goat populations could be subdivided into at least four genetic clusters: Southwest China, South China, Northwest China and East China. It was observed that the genetic diversity of Northern China goats was highest among these clusters. The results here suggested that the goat populations in Southwest China might be the earliest domestic goats in China.
Our results suggested that the current genetic structure of Chinese goats were resulted from the special geographical structure, especially in the Western China, and the Western goat populations had been separated by the geographic structure (Hengduan Mountains and Qinling Mountains-Huaihe River Line) into two clusters: the Southwest and Northwest. It also indicated that the current genetic structure was caused by the geographical origin mainly, in close accordance with the human’s migration history throughout China. This study provides a fundamental genetic profile for the conservation of these populations and better to understand the domestication process and origin of Chinese goats.
PMCID: PMC3981790  PMID: 24718092
25.  Chloride intracellular channel 1 regulates colon cancer cell migration and invasion through ROS/ERK pathway 
AIM: To investigate the mechanisms of chloride intracellular channel 1 (CLIC1) in the metastasis of colon cancer under hypoxia-reoxygenation (H-R) conditions.
METHODS: Fluorescent probes were used to detect reactive oxygen species (ROS) in LOVO cells. Wound healing assay and transwell assay were performed to examine the migration and invasion of LOVO cells. Expression of CLIC1 mRNA and protein, p-ERK, MMP-2 and MMP-9 proteins was analyzed by reverse transcription-polymerase chain reaction and Western blot.
METHODS: H-R treatment increased the intracellular ROS level in LOVO cells. The mRNA and protein expression of CLIC1 was elevated under H-R conditions. Functional inhibition of CLIC1 markedly decreased the H-R-enhanced ROS generation, cell migration, invasion and phosphorylation of ERK in treated LOVO cells. Additionally, the expression of MMP-2 and MMP-9 could be regulated by CLIC1-mediated ROS/ERK pathway.
CONCLUSION: Our results suggest that CLIC1 protein is involved in the metastasis of colon cancer LOVO cells via regulating the ROS/ERK pathway in the H-R process.
PMCID: PMC3934477  PMID: 24587680
Colon cancer; Intracellular chloride channel 1; Hypoxia-reoxygenation; Reactive oxygen species; Extracellular signal-regulated kinase; Cancer invasion

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