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1.  The Prevalence of Nonalcoholic Fatty Liver Disease and Relationship with Serum Uric Acid Level in Uyghur Population 
The Scientific World Journal  2014;2014:393628.
Objective. To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of serum uric acid level with NAFLD in Uygur people, Xinjiang. Methods. A total of 2241 Uyghur persons (1214 males and 1027 females) were interviewed for physical checkups from 2011 to 2012. The clinical data of questionnaire survey, body mass index (BMI), abdominal circumference, blood pressure, blood sugar, blood lipid, and serum uric acid level were collected for analysis. Results. The prevalence rates of NAFLD determined by abdominal ultrasound examination and hyperuricemia were 43.9% and 8.4%, respectively. The persons with NAFLD had significantly higher serum uric acid levels than those without NAFLD (320 ± 88 versus 254 ± 80 μmol/L; P < 0.001). The prevalence rate of NAFLD was significantly higher in subjects with hyperuricemia than that in those without hyperuricemia (78.19% versus 40.83%; P < 0.001), and the prevalence rate increased with progressively higher serum uric acid levels (P < 0.001). Multiple regression analysis showed that hyperuricemia was associated with an increased risk of NAFLD (odds ratio (OR): 2.628, 95% confidence interval (CI): 1.608–4.294, and P < 0.001). Conclusion. Serum uric acid level was significantly associated with NAFLD, and the prevalence rate of NAFLD increased with progressively higher serum uric acid levels.
PMCID: PMC3910275  PMID: 24516367
2.  Solution NMR Structure of Dsy0195 Homodimer from Desulfitobacterium hafniense: First Structure Representative of the YabP Domain Family of Proteins Involved in Spore Coat Assembly 
Protein domain family YabP (PF07873) is a family of small protein domains that are conserved in a wide range of bacteria and involved in spore coat assembly during the process of sporulation. The 62-residue fragment of Dsy0195 from Desulfitobacterium hafniense, which belongs to the YabP family, exists as a homodimer in solution under the conditions used for structure determination using NMR spectroscopy. The structure of the Dsy0195 homodimer contains two identical 62-residue monomeric subunits, each consisting of five anti-parallel beta strands (β1, 23-29; β2, 31-38; β3, 41-46; β4, 49-59; β5, 69-80). The tertiary structure of the Dsy0195 monomer adopts a cylindrical fold composed of two beta sheets. The two monomer subunits fold into a homodimer about a single C2 symmetry axis, with the interface composed of two anti-parallel beta strands, β1-β1’ and β5b-β5b’, where β5b refers to the C-terminal half of the bent β5 strand, without any domain swapping. Potential functional regions of the Dsy0195 structure were predicted based on conserved sequence analysis. The Dsy0195 structure reported here is the first representative structure from the YabP family.
PMCID: PMC3697068  PMID: 21904870
PF07873; YabP; Dsy0195; Sporulation Protein; Structural Genomics; NMR
3.  Severe Fever with Thrombocytopenia Syndrome Virus among Domesticated Animals, China 
Emerging Infectious Diseases  2013;19(5):756-763.
To investigate the infections of severe fever with thrombocytopenia syndrome virus (SFTSV) in domesticated animals, we sampled a total of 3,039 animals in 2 counties in Shandong Province, People’s Republic of China, from April to November 2011. SFTSV-specific antibodies were detected in 328 (69.5%) of 472 sheep, 509 (60.5%) of 842 cattle, 136 (37.9%) of 359 dogs, 26 (3.1%) of 839 pigs, and 250 (47.4%) of 527 chickens. SFTSV RNA was detected in all sampled animal species, but the prevalence was low, ranging from 1.7% to 5.3%. A cohort study in 38 sheep was conducted to determine when seroconversion to SFTSV occured. SFTSVs were isolated from sheep, cattle, and dogs and shared >95% sequence homology with human isolates from the same disease-endemic regions. These findings demonstrate that natural infections of SFTSV occur in several domesticated animal hosts in disease-endemic areas and that the virus has a wide host range.
PMCID: PMC3647489  PMID: 23648209
severe fever with thrombocytopenia syndrome virus; SFTSV; infection; domesticated animals; host; China; Phlebovirus; family Bunyaviridae; pathogenic disease; transmission; viruses; zoonoses; prevalence
4.  Chemistry and Tumor Cell Growth Inhibitory Activity of 11,20-Epoxy-3Z,5(6)E-diene Briaranes from the South China Sea Gorgonian Dichotella gemmacea 
Marine Drugs  2013;11(5):1565-1582.
Eighteen new 11,20-epoxy-3Z,5E-dien briaranes, gemmacolides AA–AR (1–18), were isolated together with three known analogs, dichotellides F (19) and I (20), and juncenolide C (21), from the South China Sea gorgonian Dichotella gemmacea. The structures of the compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configuration was determined based on the ECD experiment. In the in vitro bioassay, compounds 1–3, 5, 6, 8–12, and 14–19 exhibited different levels of growth inhibition activity against A549 and MG63 cell lines. Preliminary structure-activity analysis suggests that 12-O-isovalerate may increase the activity whereas 13- or 14-O-isovalerate may decrease the activity. Contribution of substitutions at C-2 and C-16 remains uncertain.
PMCID: PMC3707162  PMID: 23697947
structure activity relationship; briarane diterpenoids; biological activity; Dichotella gemmacea; gorgonian
5.  Downregulation of Cyclophilin A by siRNA diminishes non-small cell lung cancer cell growth and metastasis via the regulation of matrix metallopeptidase 9 
BMC Cancer  2012;12:442.
Cyclophilin A (CypA) is a cytosolic protein possessing peptidyl-prolyl isomerase activity that was recently reported to be overexpressed in several cancers. Here, we explored the biology and molecular mechanism of CypA in non-small cell lung cancer (NSCLC).
The expression of CypA in human NSCLC cell lines was detected by real-time reverse transcription PCR. The RNA interference-mediated knockdown of CypA was established in two NSCLC cell lines (95C and A549). 239836 CypA inhibitor was also used to suppress CypA activity. Tumorigenesis was assessed based on cellular proliferation, colony formation assays, and anchorage-independent growth assays; metastasis was assessed based on wound healing and transwell assays.
Suppression of CypA expression inhibited the cell growth and colony formation of A549 and 95C cells. CypA knockdown resulted in the inhibition of cell motility and invasion. Significantly, we show for the first time that CypA increased NSCLC cell invasion by regulating the activity of secreted matrix metallopeptidase 9 (MMP9). Likewise, suppression of CypA with 239836 CypA inhibitor decreased cell proliferation and MMP9 activity.
The suppression of CypA expression was correlated with decreased NSCLC cell tumorigenesis and metastasis.
PMCID: PMC3518206  PMID: 23031673
Cyclophilin A; Non-small cell lung cancer; Proliferation; Metastasis; Matrix metallopeptidase 9
6.  Differences in iNOS and Arginase Expression and Activity in the Macrophages of Rats Are Responsible for the Resistance against T. gondii Infection 
PLoS ONE  2012;7(4):e35834.
Toxoplasma gondii infects humans and warm blooded animals causing devastating disease worldwide. It has long been a mystery as to why the peritoneal macrophages of rats are naturally resistant to T. gondii infection while those of mice are not. Here, we report that high expression levels and activity of inducible nitric oxide synthase (iNOS) and low levels of arginase-1 (Arg 1) activity in the peritoneal macrophages of rats are responsible for their resistance against T. gondii infection, due to high nitric oxide and low polyamines within these cells. The opposite situation was observed in the peritoneal macrophages of mice. This discovery of the opposing functions of iNOS and Arg 1 in rodent peritoneal macrophages may lead to a better understanding of the resistance mechanisms of mammals, particularly humans and livestock, against T. gondii and other intracellular pathogens.
PMCID: PMC3338469  PMID: 22558235
7.  Cigarette Smoking and p16INK4α Gene Promoter Hypermethylation in Non-Small Cell Lung Carcinoma Patients: A Meta-Analysis 
PLoS ONE  2011;6(12):e28882.
Aberrant methylation of promoter DNA and transcriptional repression of specific tumor suppressor genes play an important role in carcinogenesis. Recently, many studies have investigated the association between cigarette smoking and p16INK4α gene hypermethylation in lung cancer, but could not reach a unanimous conclusion.
Methods and Findings
Nineteen cross-sectional studies on the association between cigarette smoking and p16INK4α methylation in surgically resected tumor tissues from non-small cell lung carcinoma (NSCLC) patients were identified in PubMed database until June 2011. For each study, a 2×2 cross-table was extracted. In total, 2,037 smoker and 765 nonsmoker patients were pooled with a fixed-effects model weighting for the inverse of the variance. Overall, the frequency of p16INK4α hypermethylation was higher in NSCLC patients with smoking habits than that in non-smoking patients (OR = 2.25, 95% CI = 1.81–2.80). The positive association between cigarette smoking and p16INK4α hypermethylation was similar in adenocarcinoma and squamous-cell carcinoma. In the stratified analyses, the association was stronger in Asian patients and in the studies with larger sample sizes.
Cigarette smoking is positively correlated to p16INK4α gene hypermethylation in NSCLC patients.
PMCID: PMC3236763  PMID: 22174919
8.  Combining NMR and EPR Methods For Homo-Dimer Protein Structure Determination 
Journal of the American Chemical Society  2010;132(34):11910-11913.
There is a general need to develop more powerful and more robust methods for structural characterization of homo-dimers, homo-oligomers and multi-protein complexes using solution-state NMR methods. In recent years, there has been increasing emphasis on integrating distinct and complementary methodologies for structure determination of multi-protein complexes. One approach not yet widely used is to obtain intermediate and long-range distance constraints from paramagnetic relaxation enhancements (PRE) and EPR-based techniques such as Double Electron Electron Resonance (DEER), which, when used together, can provide supplemental distance constraints spanning to 10-70Å. In this communication, we describe integration of PRE and DEER data with conventional solution-state NMR methods for structure determination of Dsy0195, a homo-dimer (62 amino acids per monomer) from Desulfitobacterium hafniense. Our results indicate that combination of conventional NMR restraints with only one or a few DEER distance constraints and a small number of PRE constraints is sufficient for the automatic NMR-based structure determination program CYANA to build a network of inter-chain NOE constraints that can be used to accurately define both the homo-dimer interface and global homo-dimer structure. The use of DEER distances as a source of supplemental constraints as described here has virtually no upper molecular weight limit, and utilization of the PRE constraints is only limited by the ability to make accurate assignments of the protein amide proton and nitrogen chemical shifts.
PMCID: PMC3057626  PMID: 20698532
9.  catena-Poly[[tetra­aqua­manganese(II)]-μ-5-carboxyl­ato-1-carboxyl­atomethyl-2-oxidopyridinium-κ2 O 5:O 1] 
In the title coordination polymer, [Mn(C8H5NO5)(H2O)4]n, the MnII atom is coordinated by two carboxyl­ate O atoms from two 5-carboxyl­ato-1-carboxyl­atomethyl-2-oxidopyridinium (L 2−) ligands and by four water mol­ecules in a distorted octa­hedral geometry. The L 2− ligands bridge the Mn atoms into an infinite chain motif along [100]; the chains are further inter­linked by O—H⋯O hydrogen bonds into a three-dimensional supra­molecular net.
PMCID: PMC3212127  PMID: 22090829
10.  Construct Optimization for Protein NMR Structure Analysis Using Amide Hydrogen / Deuterium Exchange Mass Spectrometry 
Proteins  2009;76(4):882-894.
Disordered or unstructured regions of proteins, while often very important biologically, can pose significant challenges for resonance assignment and three-dimensional structure determination of the ordered regions of proteins by NMR methods. In this paper, we demonstrate the application of 1H/2H exchange mass spectrometry (DXMS) for the rapid identification of disordered segments of proteins and design of protein constructs that are more suitable for structural analysis by NMR. In this benchmark study, DXMS is applied to five NMR protein targets chosen from the Northeast Structural Genomics project. These data were then used to design optimized constructs for three partially disordered proteins. Truncated proteins obtained by deletion of disordered N- and C-terminal tails were evaluated using 1H-15N HSQC and 1H-15N heteronuclear NOE NMR experiments to assess their structural integrity. These constructs provide significantly improved NMR spectra, with minimal structural perturbations to the ordered regions of the protein structure. As a representative example, we compare the solution structures of the full length and DXMS-based truncated construct for a 77-residue partially disordered DUF896 family protein YnzC from Bacillus subtilis, where deletion of the disordered residues (ca. 40% of the protein) does not affect the native structure. In addition, we demonstrate that throughput of the DXMS process can be increased by analyzing mixtures of up to four proteins without reducing the sequence coverage for each protein. Our results demonstrate that DXMS can serve as a central component of a process for optimizing protein constructs for NMR structure determination.
PMCID: PMC2739808  PMID: 19306341
DXMS; hydrogen-deuterium exchange; mass spectrometry; NMR; partially disordered proteins; protein construct optimization; structural genomics
11.  Bis(μ-5-carboxyl­ato-1-carboxyl­ato­methyl-2-oxidopyridinium)-κ2 O 5:O 1;κ2 O 1:O 5-[diaqua­(phenan­throline-κ2 N,N′)manganese(II)] dihydrate 
The centrosymmetric binuclear title complex, [Mn2(C8H5NO5)2(C12H8N2)2(H2O)4]·2H2O, was obtained by the reaction of manganese chloride with 5-carb­oxy-1-carboxy­methyl-2-oxidopyridinium and 1,10-phenanthroline. The MnII atom is coordinated by two N atoms from the 1,10-phenanthroline ligand, two O atoms from two 5-carboxyl­ato-1-carboxyl­atomethyl-2-oxidopyridinium ligands and two water mol­ecules, leading to a distorted octahedral MnN2O4 environment. Inter­molecular O—H⋯O hydrogen bonds link neighbouring mol­ecules into a layer structure parallel to (001).
PMCID: PMC2969745  PMID: 21583018
12.  Interaction of methylenetetrahydrofolate reductase C677T, cytochrome P4502E1 polymorphism and environment factors in esophageal cancer in Kazakh population 
AIM: To evaluate the association and interaction of genetic polymorphisms in methylenetetrahydrofolate reductase (MTHER) and cytochrome P4502E1 (CYP4502E1), environment risk factors with esophageal cancer (EC) in Kazakh, a high EC incidence area of Xinjiang Uygur Autonomous Region, China.
METHODS: A 1:2 matched case-control study was conducted with 120 cases of EC and 240 population- or hospital-based controls. The controls were matched for sex, nationality, area of residence and age within a 5-year difference. MTHER and CYP4502E1 genotypes were identified by PCR-based restriction fragment length polymorphism (RFLP). A conditional logistic regression model was established to identify risk factors. The strata method was adopted in interaction analysis.
RESULTS: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) were found to be the risk factors for EC. Individuals with the MTHFR677 (C/T + T/T) genotype had a 2.62-fold (95% CI: 1.61-4.28) risk of developing EC compared with those who carried the C/C genotype. Individuals with the CYP4502E1C1/C1 genotype had a 3.00-fold (95% CI: 1.82-4.96) risk compared with those who carried the CYP4502E1 (C1/C2 + C2/C2) genotype. Gene-environment interaction analysis showed that MTHFR677 gene polymorphism was correlated with consumption of green vegetables and fresh fruit, while CYP4502E1 C1/C1 was correlated with alcohol drinking and unsafe drinking water. MTHFR and CYP4502E1 analysis of gene-gene interaction showed that individuals with the MTHFR677 (C/T + T/T) and CYP4502E1C1/C1 genotypes had a 7.41-fold (95% CI: 3.60-15.25) risk of developing EC compared with those who carried the MTHFR677C/C and CYP4502E1 RsaI C1/C2 + C2/C2 genes, and the interaction rate was higher than that of the two factors alone.
CONCLUSION: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) and polymorphisms in MTHFR and CYP4502E1 genes are important risk factors for EC. There is a synergistic interaction among polymorphisms in MTHFR and CYP4502E1 genes and environment factors. MTHFR and CYP4502E1 genes can be used as biomarkers for prevention of EC in Kazakh, Xinjiang Uygur Autonomous Region, China.
PMCID: PMC2773864  PMID: 19058336
Kazakh; Esophageal Cancer; Methylenetetrahydrofolate reductase C677T; Cytochrome P4502E1; Genetic polymorphism; Environment risk factors; Interaction; Case control study
13.  Tetra­aqua­bis(5-hydroxy­nicotinato-κN)cadmium(II) 
The title compound, [Cd(C6H4NO3)2(H2O)4], was obtained by the reaction of cadmium chloride with 5-hydroxy­nicotinic acid. The CdII atom is located on an inversion centre and is coordinated by two N atoms from two 5-hydroxy­nicotinic acid ligands and four water mol­ecules in a distorted octa­hedral geometry. The structure is stabilized by inter­molecular O—H⋯O hydrogen bonds, forming a three-dimensional network.
PMCID: PMC2960042  PMID: 21581135

Results 1-13 (13)