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Red blood cell distribution width (RDW) is the coefficient of variation of red blood cell size, considered to be associated with cardiovascular disease (CVD). This study aimed to comprehensively synthesize previous studies on RDW and CVD outcomes through an overall and dose-response meta-analysis. PubMed, Embase and Web of Science were searched systematically for English and Chinese language publications up to November 30, 2015. We extracted data from publications matching our inclusion criteria for calculating pooled hazard ratio (HR), which was used to assess prognostic impact of RDW on CVD. Twenty-seven articles, consisting of 28 studies and 102,689 participants (mean age 63.9 years, 63,703 males/36,846 females, 2,140 gender-unmentioned subjects) were included in the present meta-analysis. The pooled HRs are 1.12 (95% CI = 1.09–1.15) for the association of all-cause mortality (ACM) per 1% increase of RDW, 1.12(95% CI = 1.08–1.17) for major adverse cardiac events (MACEs) per 1% increase of RDW. A dose-response curve relating RDW increase to its effect on CVD outcomes was established (pcurve

Background Flood-related damage can be very severe and include health effects. Among those health impacts, infectious diseases still represent a significant public health problem in China. However, there have been few studies on the identification of the spectrum of infectious diseases associated with floods in one area. This study aimed to quantitatively identify sensitive infectious diseases associated with floods in Guangxi, China. Methods A time-trend ecological design was conducted. A descriptive analysis was first performed to exclude infectious diseases with low incidence from 2005 to 2012 in ten study sites of Guangxi. The Wilcoxon rank-sum test was applied to examine the difference in the ten-day attack rate of infectious diseases between the exposure and control periods with different lagged effects. Negative binomial, zero-inflated Poisson and zero-inflated negative binomial models were used to examine the relationship and odd ratios (ORs) of the risk of floods on infectious diseases of preliminary screening. Results A total of 417,271 infectious diseases were notified. There were 11 infectious diseases associated with floods in the preliminary screening process for flood-sensitive infectious diseases. The strongest effect was shown with a 0–9 ten-day lag in different infectious diseases. Multivariate analysis showed that floods were significantly associated with an increased the risk of bacillary dysentery (odds ratio (OR) = 1.268, 95% confidence interval (CI): 1.072–1.500), acute haemorrhagic conjunctivitis (AHC, OR = 3.230, 95% CI: 1.976–5.280), influenza A (H1N1) (OR = 1.808, 95% CI: 1.721–1.901), tuberculosis (OR = 1.200, 95% CI: 1.036–1.391), influenza (OR = 2.614, 95% CI: 1.476–4.629), Japanese encephalitis (OR = 2.334, 95% CI: 1.119–4.865), and leptospirosis (OR = 1.138, 95% CI: 1.075–1.205), respectively. Conclusion The spectrum of infectious diseases which are associated with floods are bacillary dysentery, AHC, influenza A (H1N1), tuberculosis, influenza, Japanese encephalitis and leptospirosis in Guangxi. Floods can result in differently increased risk of these diseases, and public health action should be taken to control a potential risk of these diseases after floods., Highlights • The health effects of floods on infectious diseases are complex and far-reaching. • First time to quantitatively identify sensitive infectious diseases associated with floods. • Floods have different impacts on sensitive infectious diseases and bring more risk of AHC and influenza.

To investigate the effects of traditional Chinese herbal medicines (TCHM) on hematological parameters and immunity in chickens, Astragalus membranaceus (AM), Angelicae sinensisextract (ASE) and Danggui Buxue San (DBS) were used for the study of immunity and hematinic mechanism in order to provide basis for clinical reference. Three hundred 56-week-old hens were randomized into 10 groups. AM were added into the diets of the animals at the dosage of 5, 10 and 15 mg/kg, respectively from group I to group III; ASE were added from group IV to group VI and DBS were added from VII to group IX in the same way. The hens of group X, as of control, were fed with the diet without TCHM. At 1 day of test, all hens of each group were injected against Newcastle disease virus (NDV)-IV vaccine. The added TCHM period was 15 days. At 8 and 15 days of the test, blood of 1 hen of each group per replication was collected by wing-vein picks to measure the blood index. At 8, 15, 22, and 29 days of the test, blood of 1 hen of each group per replication was collected by wing-vein picks to measure the hens Newcastle disease (ND) and hemagglutination inhibition (HI) antibody titer. The results showed that DBS could significantly increase the count of white blood cell (WBC) (p 0.05); ASE (15 mg/kg) could significantly increase the count of RBC and the content of Hb (p 0.05). At the same time, DBS (10 mg/kg) could significantly decrease the dropping rate of blood cell at 30 (p 0.05). In addition, DBS (10 mg/kg) could improve the antibody level than control group at 8, 15, 22 and 29 days (p 0.05). This indicated that DBS had the ability on improving hemopoietic function and immunity in chickens. At the same time, DBS was added into the diets of the animals at the recommended dosage of 10 mg/kg. Key words: Astragalus membranaceus, Angelicae sinensis extract, chickens, blood cell count, immunity.

A landmark study from the Institute of Medicine reported that the assessment of cognitive difficulties in children with epilepsy is timely and imperative. Anticonvulsant-induced cognitive impairment could influence the quality of life more than seizure itself in patients. Although the monoaminergic system is involved in the regulation of cognitive process, its role in anticonvulsant-induced cognitive impairment remains unclear. Methods: To explore in vivo monoamine receptor binding activity in patients with anticonvulsant-induced cognitive impairment, each patient underwent PET imaging with both monoamine receptor binding agent 11C-N-methylspiperone and glucose metabolic agent 18F-FDG. Tests of intelligence quotient (IQ), including verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ), were performed in each patient. Results: Compared with the patients with monotherapy, patients with polytherapy had significantly lower VIQ, PIQ, and FSIQ (P 0.05). Conclusion: Monoamine receptor PET imaging could be a promising in vivo imaging biomarker for mapping anticonvulsant-induced cognitive impairment.

Music can induce different emotions. However, its neural mechanism remains unknown. The aim of this study was to use functional magnetic resonance imaging (fMRI) and position emission tomography (PET) imaging for mapping of neural changes under the most popular music in healthy volunteers. Blood-oxygen-level-dependent (BOLD) fMRI and monoamine receptor PET imaging with 11C-N-methylspiperone (11C-NMSP) were conducted under the popular music Gangnam Style and light music A Comme Amour in healthy subjects. PET and fMRI images were analyzed by using the Statistical Parametric Mapping software (SPM). Significantly increased fMRI BOLD signals were found in the bilateral superior temporal cortices, left cerebellum, left putamen and right thalamus cortex. Monoamine receptor availability was increased significantly in the left superior temporal gyrus and left putamen, but decreased in the bilateral superior occipital cortices under the Gangnam Style compared with the light music condition. Significant positive correlation was found between 11C-NMSP binding and fMRI BOLD signals in the left temporal cortex. Furthermore, increased 11C-NMSP binding in the left putamen was positively correlated with the mood arousal level score under the Gangnam Style condition. Popular music Gangnam Style can arouse pleasure experience and strong emotional response. The left putamen is positively correlated with the mood arousal level score under the Gangnam Style condition. Our results revealed characteristic patterns of brain activity associated with Gangnam Style, and may also provide more general insights into the music-induced emotional processing.

Introduction: The prevalence of deep vein thrombosis (DVT) and its risk factors in patients with cervical spondylotic myelopathy (CSM) before spinal surgery are poorly understood. We investigated this association with a retrospective cross-sectional study. Patients concerns: The study cohort consisted of all consecutive patients with CSM who were scheduled for spinal surgery at our institution from 2013 to 2015. DVT was defined as an intraluminal filling defect in a lower extremity vein identified by Doppler ultrasonography. Outcomes: Of the 396 patients with CSM, 16 (4%) had DVT. Compared with patients without preoperative DVT, patients with preoperative DVT were older (62.75 ± 8.79 vs 53.03 ± 10.95 years, P = 0.001), had higher D-dimer concentrations (2.23 ± 4.15 vs 0.43 ± 0.90 mg/L, P = 0.04), had experienced longer duration of CSM (7.56 ± 7.08 vs 4.01 ± 6.37 months, P = 0.03), had lower Japanese Orthopaedic Association lower limb motor dysfunction scores (1.68 ± 1.25 vs 2.54 ± 0.91, P = 0.01), and had a history of ischemic cardiovascular events (33.3% vs 2.1%, P = 0.02). The area under the curve for the ability of D-dimer levels to predict DVT was 0.858 (95% confidence interval: 0.764–0.951; P

This study reports the synthesis and evaluation studies of 6′-cyclopentadienyl tricarbonyl technetium-99m 6′-oxo-11-(hexanamide)undecanoic acid (1). 1 was prepared with 26.5 ± 4.3% of radiochemical yield and more than 98% of radiochemical purity. Tissue distribution in mice showed that high radioactivity accumulated in the heart with moderate clearance. However, unfortunately, similar to those of other technetium-labeled fatty acid analogs, the biodistribution studies of 1 in mice showed poor heart-to-blood ratios, which suggested that 1 cannot be used as myocardial imaging agent, and it may provide a theoretical basis or a lab experience for corresponding fatty acid tracers studies.

In Escherichia coli, the BAM complex is essential for the assembly and insertion of outer membrane proteins (OMPs). The BAM complex is comprised of an integral β-barrel outer membrane protein BamA and four accessory lipoproteins BamB, BamC, BamD and BamE. Here, the crystal structure of BamB is reported. The crystal of BamB diffracted to 2.0 Å with one monomer in the asymmetric unit and the structure is composed of eight-bladed β-propeller motifs. Pull-down and Western blotting assays indicate that BamB interacts directly with the POTRA 1-3 domain of BamA and the C-terminal region of the POTRA 1-3 domain plays an important role in the interaction, while the POTRA 1-2 domain is not required for the interaction.

Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction.

The outer membrane protein complex (BAM complex) plays an important role in outer membrane protein (OMP) assembly in Escherichia coli. The BAM complex includes the integral β-barrel protein BamA as well as four lipoproteins: BamB, BamC, BamD and BamE. One of these lipoproteins, BamD, is essential for the survival of Escherichia coli. The structure of BamD at 2.6 Å resolution shows that this lipoprotein is composed of ten α-helices that form five tetratricopeptide-repeat (TPR) motifs. The arrangement of the BamD motifs is similar to that in the periplasmic part of BamA. One of the ten α-helices, α10, which has been shown to be important for the assembly of the BAM complex, is located in the very C-terminal region of BamD. A deep groove between TPR domains 4 and 5 is also observed. This groove, as well as the surface around α10, may provide binding sites for other components of the BAM complex. The C-terminal region of BamD serves as a platform for interactions with other components of the BAM complex. The N-terminal region shares structural similarity to other proteins whose functions are related to assistance in or regulation of secretion. Therefore, this region is likely to play an important role in the insertion of other outer membrane proteins.

In Escherichia coli, the BAM complex is employed to mediate correct folding of the outer membrane (OM) proteins into β-barrels and their insertion into the OM. BamA, which is an essential component of the complex, consists of a C-­terminal transmembrane region and five N-terminal polypeptide transport-associated (POTRA) domains. Although deletion studies have shown that each of the POTRA domains plays an important role in the process of BAM complex formation, only POTRA5 is essential for cell viability. Here, the crystal structure of POTRA4–5 has been determined to 1.50 A resolution with an R factor of 14.7% and an R free of 18.9%.

Posttranslational modifications of histone tails are crucial epigenetic marks that regulate diverse cellular processes. Histone lysine methylation activates or represses transcription, depending on the site and degree of these modifications. Two classes of histone lysine demethylases remove histone methylation. Lysine demethylase 1 (KDM1, also known as LSD1) is a flavin adenine dinucleotide (FAD)-containing enzyme that removes mono-/di-methylation. The Jumonji C-terminal domain (JmjC) family of histone demethylases uses Fe(2+) and α-ketoglutarate as cofactors to remove all methylation states. Structural studies have provided insights into the overall architecture, the catalytic mechanism, and the substrate specificity of histone demethylases. Here, we review these exciting advances in the structure biology of histone demethylases and discuss the general principles applicable to other histone-modifying enzymes.

Objective:Obesity is considered as one of the risk factors of kidney cancer. However, the results are not consistent in reported original studies, as well as in published meta-analysis. This study aims to clarify the relationship between overweight/obesity and kidney cancer by an updated ove

The thermodynamic properties of 75 polyfluorinated dibenzo-p-dioxins (PFDDs) in the ideal gas state at 298.15K and 1.013x10(5) Pa have been calculated at the B3LYP/6-311G* level using Gaussian 03 program. The isodesmic reactions were designed to calculate standard enthalpy of formation (DeltaH(f)(degrees)) and standard free energy of formation (DeltaG(f)(degrees)) of PFDDs congeners. The relations of these thermodynamic parameters with the number and position of fluorine atom substitution (N(PFS)) were discussed, and it was found that there exist high correlations between thermodynamic parameters (entropy (S(degrees)), DeltaH(f)(degrees) and DeltaG(f)(degrees)) and N(PFS). According to the relative magnitude of their DeltaG(f)(degrees), the relative stability order of PFDD congeners was theoretically proposed.

Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylation-state-specific manner. However, how substrate specificity is determined and how the enzymes are regulated were largely unknown. We recently found that ceKDM7A, a PHD- and JmjC domain-containing protein, is a histone demethylase specific for H3K9me2 and H3K27me2, and the PHD finger binding to H3K4me3 guides the demethylation activity in vivo. To provide structural insight into the molecular mechanisms for the enzymatic activity and the function of the PHD finger, we solved six crystal structures of the enzyme in apo form and in complex with single or two peptides containing various combinations of H3K4me3, H3K9me2, and H3K27me2 modifications. The structures indicate that H3K9me2 and H3K27me2 interact with ceKDM7A in a similar fashion, and that the peptide-binding specificity is determined by a network of specific interactions. The geometrical measurement of the structures also revealed that H3K4me3 associated with the PHD finger and H3K9me2 bound to the JmjC domain are from two separate molecules, suggesting a trans-histone peptide-binding mechanism. Thus, our systemic structural studies reveal not only the substrate recognition by the catalytic domain but also more importantly, the molecular mechanism of dual specificity of ceDKM7A for both H3K9me2 and H3K27me2.

Orotate phosphoribosyltransferase (OPRTase) catalyzes the OMP-forming step in de novo pyrimidine-nucleotide biosynthesis. Here, the crystal structure of OPRTase from the caries pathogen Streptococcus mutans is reported at 2.4 A resolution. S. mutans OPRTase forms a symmetric dimer and each monomer binds two sulfates at the active sites. The structural symmetry of the sulfate-binding sites and the missing loops in this structure are consistent with a symmetric catalysis mechanism.

We studied the developmental toxicity and possible mechanisms of bisphenol A (BPA) damage of rat embryos in vitro. Whole-embryo culture was used to study the damage of BPA on visceral yolk sacs (VYSs) and embryos. Micromass culture was used to investigate the effects of BPA on differentiation and proliferation of embryonic midbrain cells. Neutral red staining was used to detect cell death. Immunohistochemistry was used to evaluate the expression of inducible nitric oxide synthase (iNOS) in VYSs and embryos. Our results as following, BPA could cause damage to embryonic development and morphological differentiation in a dose-dependent manner. At the highest dose, 80 and 100 mg/l BPA delayed cardiac tube growth and differentiation of VYSs, and induced various embryonic defects. BPA also induced excessive cell death and inhibited both proliferation and differentiation of rat midbrain cells. Immunohistochemical staining showed that BPA induces abnormal expression of iNOS protein in treated VYSs and embryos. Our results indicated that BPA is a potential teratogen and has toxicity on cultured rat embryo development. BPA-related developmental toxicity is caused by damage to the VYS, excessive cell death, inhibition of cell proliferation and differentiation, and abnormal expression of iNOS.

InEscherichia coli, the Omp85 protein BamA and four lipoproteins (BamBCDE) constitute the BAM complex, which is essential for the assembly and insertion of outer membrane proteins into the outer membrane. Here, the crystal structure of BamB in complex with the POTRA3–4 domains of BamA is reported at 2.1 Å resolution. Based on this structure, the POTRA3 domain is associated with BamBviahydrogen-bonding and hydrophobic interactions. Structural and biochemical analysis revealed that the conserved residues Arg77, Glu127, Glu150, Ser167, Leu192, Leu194 and Arg195 of BamB play an essential role in interaction with the POTRA3 domain.

Interleukin-6 (IL-6) is an important mediator of atherosclerotic disease and is also associated with coronary artery disease (CAD). The growing evidences suggest that polymorphisms in the IL-6 promoter region influence the progression of CAD. This study was performed to update the systematic results of association of IL-6 gene polymorphisms with CAD. PubMed, Embase, and China Biology Medicine were searched systematically for English and Chinese articles published up to October 31, 2014. Data were extracted using standardized forms. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Subgroup analyses were made on ethnicity. A total of 42 studies including 15,145 cases and 21,496 controls were combined in this meta-analysis. IL-6 gene −174G/C polymorphism was associated with an increased risk of CAD (for C allele versus G allele: OR = 1.11, 95 % CI 1.02–1.20; for C/C versus G/G: OR = 1.21, 95 % CI 1.03–1.42; for C/C + C/G versus G/G: OR = 1.14, 95 % CI 1.03–1.27). In the subgroup analyses based on ethnicity, a significant association was found between −174 G/C polymorphism and CAD in Caucasians (for C allele versus G allele: OR = 1.12, 95 % CI 1.03–1.22; for C/C versus G/G: OR = 1.21, 95 % CI 1.02–1.42; for C/C + C/G versus G/G: OR = 1.16, 95 % CI 1.05–1.29). In order to reduce heterogeneity, we removed the outlier studies by a Galbraith plot analysis. As a result, the pooled ORs demonstrated no association of −174G/C polymorphism and CAD (C allele versus G allele: OR = 1.02, 95 % CI 0.97–1.06, p = 0.48; C/C versus G/G: OR = 0.1.03, 95 % CI 0.94–1.13, p = 0.48; C/G + C/C versus G/G: OR = 1.03, 95 % CI 0.96–1.09, p = 0.41; C/C versus C/G + G/G: OR = 1.02, 95 % CI 0.94–1.10, p = 0.70, respectively). The polymorphism of −572 G/C was not associated with CAD significantly (for C allele versus G allele: OR = 0.86, 95 % CI 0.74–1.01; C/C versus G/G: OR = 0.99, 95 % CI 0.43–2.27; C/G + C/C versus G/G: OR = 0.96, 95 % CI 0.80–1.15, respectively). In addition, subgroup analyses showed an association between −572 G/C polymorphism and CAD risk among Chinese (C allele versus G allele: OR = 0.64, 95 % CI 0.48–0.85; C/C versus G/G: OR = 0.38, 95 % CI 0.18–0.81; C/G + C/C versus G/G: OR = 0.47, 95 % CI 0.22–1.00; C/C versus C/G + G/G: OR = 0.58, 95 % CI 0.42–0.81). The C allele of −174G/C polymorphism may associate with increased sensibility to CAD among Caucasians in overall analysis. Nevertheless, the effect is interfered by heterogeneity across the included studies. The C allele of −572G/C polymorphism may decrease the risk of CAD in Chinese.

DNA methylation is an important epigenetic modification(1-3). Ten-eleven translocation (TET) proteins are involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC)(4-8). Here we show that human TET1 and TET2 are more active on 5mC-DNA than 5hmC/5fC-DNA substrates. We determine the crystal structures of TET2-5hmC-DNA and TET2-5fC-DNA complexes at 1.80 angstrom and 1.97 angstrom resolution, respectively. The cytosine portion of 5hmC/5fC is specifically recognized by TET2 in a manner similar to that of 5mC in the TET2-5mC-DNA structure(9), and the pyrimidine base of 5mC/5hmC/5fC adopts an almost identical conformation within the catalytic cavity. However, the hydroxyl group of 5hmC and carbonyl group of 5fC face towards the opposite direction because the hydroxymethyl group of 5hmC and formyl group of 5fC adopt restrained conformations through forming hydrogen bonds with the 1-carboxylate of NOG and N4 exocyclic nitrogen of cytosine, respectively. Biochemical analyses indicate that the substrate preference of TET2 results from the different efficiencies of hydrogen abstraction in TET2-mediated oxidation. The restrained conformation of 5hmC and 5fC within the catalytic cavity may prevent their abstractable hydrogen(s) adopting a favourable orientation for hydrogen abstraction and thus result in low catalytic efficiency. Our studies demonstrate that the substrate preference of TET2 results from the intrinsic value of its substrates at their 5mC derivative groups and suggest that 5hmC is relatively stable and less prone to further oxidation by TET proteins. Therefore, TET proteins are evolutionarily tuned to be less reactive towards 5hmC and facilitate the generation of 5hmC as a potentially stable mark for regulatory functions.

Differences between alloplasmic lines and euplasmic controls indicated consistent beneficial effects of Aegilops crassa cytoplasm on common wheats. In general, the agronomic performance of alloplasmic lines was superior to that of euplasmic controls; the significant differences observed were ascribed to nucleus-cytoplasmic (NC) interactions. A number of useful genetic attributes, for example, high yield, good quality and salt tolerance, were identified. A new NC hybrid variety ‘Xiaoshan 2134’ was bred. Field trials showed that the yield NC heterosis of ‘Xiaoshan 2134’ was 13.9% and the yield of ‘Xiaoshan 2134’ was at least 20% higher than that of a control variety widely grown in North China. The results suggested that Ae. crassa cytoplasm could broaden the genetic base of common wheat and improve common wheat cultivars by utilizing NC heterosis.

Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction remains unclear. Positron emission tomography (PET) is the first technology used for in vivo measurement of components of the dopaminergic system in the human brain. In this article, we review the major findings from PET imaging studies on the involvement of DA in drug addiction, including presynaptic DA synthesis, vesicular monoamine transporter 2, the DA transporter, and postsynaptic DA receptors. These results have corroborated the role of DA in addiction and increased the understanding of its underlying mechanisms.

Background. After initial treatment of breast cancer (BC), monitoring locoregional recurrence and distant metastases is a great clinical challenge.Objective. To evaluate the efficacy of PET/CT in association with serum tumor makers in BC follow-up.Methods. Twenty-six women with a history of modified radical mastectomy were evaluated by18F-FDG PET/CT. The results of PET/CT were compared with those of conventional imaging techniques (CITs) (including mammography, chest radiography, CT, MRI, ultrasound, and bone scintigraphy). Serum tumor markers of CEA, CA 125, and CA 15-3 in the BC patients were also analyzed in association with the results of PET/CT.Results. Compared with CITs, PET/CT was more sensitive to detect the malignant foci and had better patient-based sensitivity and specificity. The mean CA 15-3 serum level was significantly higher in the confirmed positive patients of PET/CT results than in the confirmed negative ones, while there were no significant differences in the serum levels of CEA and CA 125 of both groups.Conclusion. PET/CT is a highly efficient tool for BC follow-up compared with CITs. The high serum levels of CA 15-3 in confirmed positive PET/CT patients indicated the clinical value of CA 15-3 in BC follow-up.

Objectives. This study is to assess the prognostic value of 99mTc-pertechnetate thyroid scintigraphy for predicting the outcomes of fixed low dose of radioiodine therapy (RIT) in a cohort of Chinese Graves' disease (GD) patients. Materials and Methods. This is a retrospective study of GD patients who received RIT with a single dose of radioiodine (5 mCi). All the patients received 99mTc-pertechnetate thyroid scintigraphy prior to RIT. Thyroid mass, 99mTc-pertechnetate uptake, gender, age at diagnosis, duration of the disease, ophthalmopathy, and serum levels of FT4, FT3, TT4, and TT3 prior to RIT were analyzed as potential interference factors for outcomes of RIT. Results. One hundred and eighteen GD patients who completed RIT were followed up for 12 months. The outcomes (euthyroidism, hypothyroidism, and hyperthyroidism) were found to be significantly associated with thyroid mass and 99mTc-pertechnetate uptake. Patients with thyroid mass ≤ 40.1 g or 99mTc-pertechnetate uptake ≤ 15.2% had higher treatment success. Conclusions. A fixed low dose of 5 mCi radioiodine seems to be practical and effective for the treatment of Chinese GD patients with thyroid mass ≤ 40.1 g and 99mTc-pertechnetate uptake ≤ 15.2%. This study demonstrates 99mTc-pertechnetate thyroid scintigraphy is an important prognostic factor for predicting the outcomes of RIT.

Objectives Ventricular septal defect (VSD), one of the most common types of congenital heart disease (CHD), results from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in development of CHD. This study was to characterize the expression of miRNAs that might be involved in the development or reflect the consequences of VSD. Methods MiRNA microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR) were employed to determine the miRNA expression profile from 3 patients with VSD and 3 VSD-free controls. 3 target gene databases were employed to predict the target genes of differentially expressed miRNAs. miRNAs that were generally consensus across the three databases were selected and then independently validated using real time PCR in plasma samples from 20 VSD patients and 15 VSD-free controls. Target genes of validated 8 miRNAs were predicted using bioinformatic methods. Results 36 differentially expressed miRNAs were found in the patients with VSD and the VSD-free controls. Compared with VSD-free controls, expression of 15 miRNAs were up-regulated and 21 miRNAs were downregulated in the VSD group. 15 miRNAs were selected based on database analysis results and expression levels of 8 miRNAs were validated. The results of the real time PCR were consistent with those of the microarray analysis. Gene ontology analysis indicated that the top target genes were mainly related to cardiac right ventricle morphogenesis. NOTCH1, HAND1, ZFPM2, and GATA3 were predicted as targets of hsa-let-7e-5p, hsa-miR-222-3p and hsa-miR-433. Conclusion We report for the first time the circulating miRNA profile for patients with VSD and showed that 7 miRNAs were downregulated and 1 upregulated when matched to VSD-free controls. Analysis revealed target genes involved in cardiac development were probably regulated by these miRNAs.

In some areas of China, citreoviridin (CIT) is considered one of the risk factors for development of cardiovascular disease (CVD). Apoptosis of endothelial cell may induce vascular endothelium injury and atherosclerosis, which result in CVD probably. In this study, we investigated the effect of CIT on apoptosis and proliferation of human umbilical vein endothelial cells (HUVECs). The MTT assay was used to determinate HUVECs proliferation. Distribution of the cell cycle was analyzed by flow cytometry. The Annexin-V/PI staining was used to investigate cell apoptosis. Western blotting analysis was used to indicate changes in the expression level of apoptosis-related proteins. The results indicated that CIT inhibited HUVECs proliferation and the cells were arrested at G0/G1 phase, which is associated with decreased levels of cyclinD1 and increased expression of p53 and p21. The apoptosis rate of HUVECs was improved by CIT. The expression of Bcl-2 were down-regulated after CIT treatment, whereas the levels of Bax was significantly up-regulated. Furthermore, CIT-induced apoptosis was accompanied by the activation of caspase-3, -9. These findings demonstrate that CIT inhibits cell proliferation via DNA synthesis reduction and induces caspase-dependent apoptosis in HUVECs. CIT plays a pivotal role in the process of endothelial cell apoptosis, may thereby play an important role in the improvement of CVD in areas of China that have a high prevalence of CIT contamination.

Internet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D2 (D2)/Serotonin 2A (5-HT2A) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D2 receptor and glucose metabolism.Twelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and (11)C-N-methylspiperone ((11)C-NMSP) to assess the availability of D2/5-HT2A receptors and with (18)F-fluoro-D-glucose ((18)F-FDG) to assess regional brain glucose metabolism, a marker of brain function. (11)C-NMSP and (18)F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states.In internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D2 receptors was observed in the striatum, and was correlated to years of overuse. A low level of D2 receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex.For the first time, we report the evidence that D2 receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D2/5-HT2A receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects.

Lipocalin alpha 1-microglobulin (alpha 1M) is a conserved glycoprotein present in plasma and in the interstitial fluids of all tissues. alpha 1M is linked to a heterogeneous yellow-brown chromophore of unknown structure, and interacts with several target proteins, including alpha 1-inhibitor-3, fibronectin, prothrombin and albumin. To date, there is little knowledge about the interaction sites between alpha 1M and its partners. Here, we report the crystal structure of the human alpha 1M. Due to the crystallization occurring in a low ionic strength solution, the unidentified chromophore with heavy electron density is observed at a hydrophobic inner tube of alpha 1M. In addition, two conserved surface regions of alpha 1M are proposed as putative protein-protein interface sites. Further study is needed to unravel the detailed information about the interaction between alpha 1M and its partners. (C) 2013 Elsevier Inc. All rights reserved.

Interior microelectrolysis (IM) as a pretreatment process was effective to treat Reactive Black 5 (RB5) in this study. The removal rates of chemical oxygen demand (COD), total organic carbon (TOC) and color were 46.05, 39.99 and 98.77%, respectively, when this process was conducted under the following optimal conditions: the volumetric ratio between iron scraps and active carbon (AC) (V(Fe)/V(C)) 1.0, pH 2.0, aeration dosage 0.6 L/min, and reaction time 100 min. Contaminants could be further removed by ozonation. After subsequent ozonation for 200 min, the solution could be completely decolorized, and the COD and TOC removal rates were up to 77.78 and 66.51%, respectively. In addition, acute toxicity tests with Daphnia magna showed that pretreatment by IM generated effluents that were more toxic when compared with the initial wastewater, and the toxicity was reduced after subsequent ozonation.

Endothelial adhesion plays an important role in the process of atherosclerosis, which is regulated by endothelial adhesion molecules and chemoattractant molecules. In some areas of China, citreoviridin (CIT) is considered a risk factor for the development of atherosclerosis. Here, we investigated the role of CIT in adhesion of human umbilical vein endothelial cells (HUVECs) together with the stimulation of tumor necrosis factor-α (TNF-α). Adhesion of HUVECs to monocytes was analyzed by coculture experiments using U937 cells labeled with 2,7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethylester. The expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin was determined by Western blot and enzyme-linked immunosorbent assay (ELISA). The expression of monocyte chemoattractant protein-1 (MCP-1) was measured by reverse transcription polymerase chain reaction and ELISA. The activation of nuclear factor-κB (NF-κB) was assessed by Western blot and immunofluorescence staining. CIT markedly increased TNF-α-induced HUVECs adhesion to monocytes and the expression levels of ICAM-1, VCAM-1, E-selectin, and MCP-1. TNF-α-induced nuclear translocation of NF-κB in HUVECs was significantly elevated by CIT. Our study demonstrates that CIT upregulates TNF-α-induced endothelial adhesion via increasing activation of NF-κB, which results in the expression of ICAM-1, VCAM-1, E-selectin, and MCP-1. CIT plays a pivotal role in the process of endothelial cell adhesion and may thereby play an important role in the improvement of atherosclerosis in areas of China that have a high prevalence of CIT contamination and atherosclerosis.

The journal of biological chemistry 288(45), 32414-32423 (2013). doi:10.1074/jbc.M113.502112, RecQ helicases, essential enzymes for maintaining genome integrity, possess the capability to participate in a wide variety of DNA metabolisms. They can initiate the homologous recombination repair pathway by unwinding damaged dsDNA and suppress hyper-recombination by promoting Holliday junction (HJ) migration. To learn how DrRecQ participates in the homologous recombination repair pathway, solution structures of Deinococcus radiodurans RecQ (DrRecQ) and its complexes with DNA substrates were investigated by small angle x-ray scattering. We found that the catalytic core and the most N-terminal HRDC (helicase and RNase D C-terminal) domain (HRDC1) undergo a conformational change to a compact state upon binding to a junction DNA. Furthermore, models of DrRecQ in complexes with two kinds of junction DNA (fork junction and HJ) were built based on the small angle x-ray scattering data, and together with the EMSA results, possible binding sites were proposed. It is demonstrated that two DrRecQ molecules bind to the opposite arms of HJ. This architecture is similar to the RuvAB complex and is hypothesized to be highly conserved in the other HJ migration proteins. This work provides us new clues to understand the roles DrRecQ plays in the RecFOR pathway., Published by Soc., Bethesda, Md.

This study reports the synthesis and evaluation studies of 6'-cyclopentadienyl tricarbonyl technetium-99m 6'-oxo-11-(hexanamide)undecanoic acid (1). 1 was prepared with 26.5 ± 4.3% of radiochemical yield and more than 98% of radiochemical purity. Tissue distribution in mice showed that high radioactivity accumulated in the heart with moderate clearance. However, unfortunately, similar to those of other technetium-labeled fatty acid analogs, the biodistribution studies of 1 in mice showed poor heart-to-blood ratios, which suggested that 1 cannot be used as myocardial imaging agent, and it may provide a theoretical basis or a lab experience for corresponding fatty acid tracers studies.

To investigate the effects of citreoviridin (CIT) on the expression of MCP-1, IL-1beta, IL-6 and IL-8 induced by TNF-alpha in human umbilical vein endothelial cells (HUVECs).HUVECs isolated from the umbilical cord of neonates within 1 hour after birth (informed with consent form) were cultured in DMEM/ F12 media. After 80% of HUVECs were confluent, the cells were divided into four groups and treated with CIT (2 micromol/L) and/or TNF-alpha (10 microg/L). The levels of MCP-1, IL-1beta, IL-6 and IL-8 in the supernatant of cell culture media were measured by ELISA, the activation of NF-kappaB in HUVECs was detected by immunofluorescence staining, and the expression of MCP-1 mRNA was determinated by RT-PCR assay.The levels of MCP-1, IL-1beta, IL-6 and IL-8 in the supernatant and the expression of NF-kappaB P65 and MCP-1 mRNA of HUVECs were higher in TNF-alpha group and TNF-alpha + CIT group than those in the control group (P0.05), and those of TNF-alpha + CIT group was higher than TNF-alpha group (P0.05).The expression of NF-kappaB, MCP-1, IL-1beta, IL-6 and IL-8 in HUVECs up-regulated by TNF-alpha was promoted by CIT.

In this study cyclophosphamide was used to prepare the blood-deficient model. The red blood cell count and hemoglobin content were measured. The experimental chickens presented the symptoms of blood-deficient syndrome, dullness, shrinkinginto oneself, broken winded, loose feather, waxy eyelid, and pale tongue. At the same time, red blood cell count and hemoglobin content decreased significantly. Angelica polysaccharide as the effective component of Angelica Sinensis could significantly increase the red blood cell count and the hemoglobin content of blood-deficient chickens. The results indicated that cyclophosphamide could significantly reduce the red blood count and hemoglobin content, and make the ideal blood-deficient model successfully. Angelica polysaccharide had the function of enriching blood in different ways. On the one hand Angelica polysaccharide enriched he blood directly, increased the number of RBC and hemoglobin; on the other hand it regulated the hematopoietic factors, enriched the blood indirectly.

To investigate the effects of Angelica polysaccharide on erythrocyte immunity and marrow hematopoiesis in chickens, Angelica polysaccharide was used for the study of immunity and hematinic mechanism in order to provide basis for clinical reference. In this experiment, three gradient dosages (50, 100, 150 mg/kg body weight) of Angelica polysaccharide were drenched to the control group and the anemia groups, respectively. The anemia chickling model was made by abdominal injection of cyclophosphamide (CY) for 6 days (80 mg/kg·day).Red blood cell-C3b receptor (RBC-CR1) and red blood cell-immune complex (RBC-IC) rosette rates were measured and analyzed. Ectogenetic semi-solid culture medium of bone marrow hemopoietic progenitor cells was used to observe Angelica polysaccharide and separated serum fromAngelica polysaccharide treatment on the proliferation of colony-forming unit-erythrocyte (CFU-E), burst-forming unit-erythrocyte (BFU-E) and colony-forming unit-granulocyte macrophage (CFU-GM). The results showed that Angelica polysaccharide can significantly increase RBC-CR1 rosette rate in the healthy chicken groups (p 0.05). At the same time, Angelica polysaccharide can restore the RBC- CR1 rosette rate and the RBC-IC rosette rate caused by cyclophosphamide to the normal level. Serum containing Angelica polysaccharide can significantly facilitate the proliferation on CFU-E (p

In recent years, internet addiction disorder (IAD) has become more prevalent worldwide and the recognition of its devastating impact on the users and society has rapidly increased. However, the neurobiological mechanism of IAD has not bee fully expressed. The present study was designed to determine if the striatal dopamine transporter (DAT) levels measured byT99mc-TRODAT-1 single photon emission computed tomography (SPECT) brain scans were altered in individuals with IAD. SPECT brain scans were acquired on 5 male IAD subjects and 9 healthy age-matched controls. The volume (V) and weight (W) of bilateral corpus striatum as well as theT99mc-TRODAT-1 uptake ratio of corpus striatum/the whole brain (Ra) were calculated using mathematical models. It was displayed that DAT expression level of striatum was significantly decreased and theV,W, and Ra were greatly reduced in the individuals with IAD compared to controls. Taken together, these results suggest that IAD may cause serious damages to the brain and the neuroimaging findings further illustrate IAD is associated with dysfunctions in the dopaminergic brain systems. Our findings also support the claim that IAD may share similar neurobiological abnormalities with other addictive disorders.

Multiple benign osteolytic lesions are very hard to differentiate from disseminated bone metastasis. Whole-body bone scintigraphy (WBBS) with technetium-99m methylene diphosphonate (Tc-99m MDP) demonstrates multiple lesions with increased uptake in any bone involved. Even combined with medical history and multiple imaging results, such as MRI and CT, the clinical diagnosis of metastasis lesion remains as a challenge. These clinical characteristics are similar to multiple malignant bone metastases and therefore affect the following treatment procedures. In this paper, we analyzed multiple benign osteolytic lesions, like eosinophilic granuloma (EG), multiple myeloma (MM), disseminated tuberculosis, fibrous dysplasia, or enchondroma, occurring in our daily clinical work and concluded that additional attention should be paid before giving the diagnosis of multiple bone metastases.

Nitroalkane oxidase (NAO) catalyzes neutral nitroalkanes to their corresponding aldehydes or ketones, hydrogen peroxide and nitrite. The crystal structure of NAO from Streptomyces ansochromogenes was determined; it consists of two domains, a TIM barrel domain bound to FMN and C-terminal domain with a novel folding pattern. Site-directed mutagenesis of His179, which is spatially adjacent to FMN, resulted in the loss of enzyme activity, demonstrating that this amino acid residue is important for catalysis. The crystal structure of mutant H179D-nitroethane was also analyzed. Interestingly, Sa-NAO shows the typical function as nitroalkane oxidase but its structure is similar to that of 2-nitropropane dioxygenase. Overall, these results suggest that Sa-NAO is a novel nitroalkane oxidase with TIM barrel structure.

The structures of proteins are very essential in understanding the functions of proteins. Protein crystallography is the most wide-used and precious method for structure determination of proteins. This chapter, Protein crystallography for metalloproteins, is divided into four sections. Firstly, we introduce protein crystallography by comparing with other methods for obtaining structure, such as NMR and cryo-EM. And then the general routine for getting structures via crystallography is described, especially the phasing problem in protein structure determination. In Section 3, the most favorite phasing method, MAD, which is suitable for metallloproteins, is presented. Finally, we demonstrate one case of investigating the function of metalloprotein by obtaining the structure.

Previous studies have shown that one of the genetic variants BDNF val66met polymorphism is associated with drug addiction. Age at onset for drugs abuse has also been regularly cited as a factor associated with high genetic predispositions. We conducted an exploratory research to investigate the association of BDNF val66met genetic polymorphism with the ages of onset for heroin abuse in males. Venous blood samples from 96 heroin-dependent persons were analyzed by Real-Time Fluorogenic PCR Assay to determine the genotype of BDNF val66met polymorphism. The effect of BDNF val66met genetic polymorphism on the age of onset for heroin abuse was analyzed in the patients of different genotypes. The observed genotype frequency was 32.29% (val66val; n=31), 45.83% (val66met; n=44), and 21.88% (met66met; n=21), which was similar with the reported results of Asians. The onset age was significantly different among the three genotypic groups, and val66met carriers had earlier onset of heroin abuse than did val66val and met66met carriers. Our findings further illustrate the role of BDNF genetic variants in drug abuse and dependence and this study will help to identify who are at risk of becoming heroin dependence in the future and decide the more appropriate timing that interventions should be taken in the high-risk groups.

Smu.1392c is a protein with 158 residues of uncharacterized function. Bioinformatics studies predict it is a putative acetyltransferase. In order to identify its exact function via structural studies, Smu.1392c gene was amplified from Streptococcus mutans genomic DNA and cloned into expression vector PET28a. Smu.1392c was crystallized and diffracted to a resolution of 3 A in-house. The crystal belongs to R32 space group, with unit cell parameters a= b= 229.10, c= 63.49 A. There are 2 or 3 molecules in the asymmetric unit.

There are two purposes in displaying spatial genetic structure. One is that a visual representation of the variation of the genetic variable should be provided in the contour map. The other is that spatial genetic structure should be reflected by the patterns or the gradients with genetic boundaries in the map. Nevertheless, most conventional interpolation methods, such as Cavalli-Sforza's method in genography, inverse distance-weighted methods, and the Kriging technique, focus only on the first primary purpose because of their arbitrary thresholds marked on the maps. In this paper we present an application of the contour area multifractal model (CAMM) to human population genetics. The method enables the analysis of the geographic distribution of a genetic marker and provides an insight into the spatial and geometric properties of obtained patterns. Furthermore, the CAMM may overcome some of the limitations of other interpolation techniques because no arbitrary thresholds are necessary in the computation of genetic boundaries. The CAMM is built by establishing power law relationships between the area A (> or =rho) in the contour map and the value p itself after plotting these values on a log-log graph. A series of straight-line segments can be fitted to the points on the log-log graph, each representing a power law relationship between the area A (> or =rho) and the cutoff genetic variable value for rho in a particular range. These straight-line segments can yield a group of cutoff values, which can be identified as the genetic boundaries that can classify the map of genetic variable into discrete genetic zones. These genetic zones usually correspond to spatial genetic structure on the landscape. To provide a better understanding of the interest in the CAMM approach, we analyze the spatial genetic structures of three loci (ABO, HLA-A, and TPOX) in China using the CAMM. Each synthetic principal component (SPC) contour map of the three loci is created by using both Han and minority groups data together. These contour maps all present an obvious geographic diversity, which gradually increases from north to south, and show that the genetic differences among populations in different districts of the same nationality are greater than those among different nationalities of the same district. It is surprising to find that both the value of p and the fractal dimension alpha have a clear north to south gradient for each locus, and the same clear boundary between southern and northern Asians in each contour map is still seen in the zone of the Yangtze River, although substantial population migrations have occurred because of war or famine in the last 2,000 or 3,000 years. A clear genetic boundary between Europeans and Asians in each contour map is still seen in northwestern China with a small value of alpha, although the genetic gradient caused by gene flow between Europeans and Asians has tended to show expansion from northwestern China. From the three contour maps another interesting result can be found: The values of alpha north of the Yangtze River are generally less than those south of the Yangtze River. This indicates that the genetic differences among the populations north of the Yangtze River are generally smaller than those in populations south of the Yangtze River.