Exploring the structure and hydrogen storage capacity of CeHn0/+ clusters.

The unique 4f orbitals and abundant electronic energy levels of rare earth elements enable effective doping and modification to enhance hydrogen storage performance, making it an increasingly prominent focus of research. The structures of neutral and cationic CeHn0/+ (n = 2-20) clusters have been determined using the Crystal Structure AnaLYsis by Particle Swarm Optimization (CALYPSO) method in conjunction with density functional theory (DFT). Interestingly, the CeH13 and CeH14+ exhibit remarkable stability in the doublet state with Cs and C2v symmetry, respectively. The adsorption energy of CeHn0/+ (n = 2-20) suggests a preference for H atoms to chemically adsorb on Ce atoms. The analysis of molecular orbital composition reveals that the stability of both CeH13 and CeH14+ is attributed to the significant hybridization between the H 1s and Ce 4f orbitals. Both CeH13 and CeH14+ demonstrate significant hydrogen storage capacities, with values reaching 8.5 wt% and 9.1 wt%, respectively.

[Genotyping by CRISPR and regional distribution of Yersinia pestis in Qinghai-plateau from 1954 to 2011].

Objective: To investigate the CRISPR genotypes (clusters) and regional distribution of Yersinia pestis in Qinghai-plateau. Methods: One hundred and two isolates of Y. pestis isolated from human plague patients, host animal and insect vectors from Qinghai-plateau were selected. The DNAs were extracted using the traditional sodium dodecyl sulfate decomposition and phenol-chloroform method. Three CRISPR loci YPa, YPb and YPc of 102 isolates of Y. pesits were amplified and sequenced, and then the CRISPR sequence analysis was carried out by comparing the latest published CRISPR spacer dictionary and the NCBI database to identify the spacer and spacer array. CRISPR genotyping of isolates of Y. pesits were finally conducted according to the polymorphism of the spacer arrays and the regional distribution pattern of isolates of Y. pesits in Qinghai-plateau was described. Results: Forty spacers including 22 of YPa, 13 of YPb and 5 of YPc were observed among 102 isolates of Y. pestis in Qinghai-plateau, of which 5 spacers (a1', a103, a104, b4'' and b4''') were firstly identified. Meanwhile, 16, 10, and 5 different spacer arrays were obtained in YPa, YPb and YPc respectively, including 11 new spacer arrays detected in this study. One hundred and two isolates were divided into 24 CRISPR genotypes and classified into 9 CRISPR clusters (Cb4, Cb4', Cb2, Ca37, Ca7, Ca7', CaΔ5', Ca35' and Cc3'). Each dominant cluster presented significant aggregation geographically: Ca7 were found in Yushu, Nangqian, Chenduo, Zaduo, Zhiduo and Qumalai countries. Ca7' were found in Xunhua, Tongren, Zeku, Tongde, Maqin and Guinan countries. CaΔ5' were restricted to Qilian, Gangcha, Menyuan and Datong countries. CaΔ35' were found in Huangyuan, Haiyan, Gangcha, Tianjun, Delingha, Wulan, Doulan, Gonghe, Xinghai, Guide and Tongde countries. Conclusion: CRISPR-based genotyping analyses showed complicated population of Y. pestis in Qinghai-plateau. Four clusters, Ca7, Ca7', CaΔ5' and Ca35' were the most epidemic dominant four clusters and presented obvious regional distribution patterns, which instructed us to strengthen the surveillance and prevention and control by CRISPR-genotyping technique.

The ASSURE study: HIV-1 suppression is maintained with bone and renal biomarker improvement 48 weeks after ritonavir discontinuation and randomized switch to abacavir/lamivudine + atazanavir.

OBJECTIVES: HIV treatment guidelines endorse switching or simplification of antiretroviral therapy in therapy-experienced patients with suppressed viraemia; ritonavir discontinuation may also enhance tolerability and reduce long-term adverse events (AEs). This open-label, multicentre, noninferiority study enrolled HIV-1-infected, treatment-experienced adults with confirmed HIV-1 RNA ≤ 75 HIV-1 RNA copies/mL currently receiving tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC + ATV/r) for ≥ 6 months with no reported history of virological failure. METHODS: Participants were randomized 1:2 to continue current treatment or switch to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Endpoints included the proportion of participants with HIV-1 RNA < 50 copies/mL by time to loss of virological response (TLOVR), AEs, fasting lipids, and inflammatory, coagulation, bone and renal biomarkers. RESULTS: After 48 weeks, 76% (152 of 199) of ABC/3TC + ATV-treated and 79% (77 of 97) of TDF/FTC + ATV/r-treated participants had HIV-1 RNA < 50 copies/mL (TLOVR; P = 0.564). Other efficacy analyses yielded similar results. Rates of new grade 2-4 AEs were 45% in both groups, but an excess of hyperbilirubinaemia made the rate of treatment-emergent grade 3-4 laboratory abnormalities higher with TDF/FTC + ATV/r (36%) compared with ABC/3TC + ATV (19%). Most fasting lipid levels remained stable over time; high-density lipoprotein (HDL) cholesterol increased modestly in ABC/3TC + ATV-treated participants. Bone and renal biomarkers improved significantly between baseline and week 48 in participants taking ABC/3TC + ATV and were stable in participants taking TDF/FTC + ATV/r. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups. CONCLUSIONS: The ABC/3TC + ATV treatment-switch group had similar viral suppression rates up to 48 weeks to the TDF/FTC + ATV/r comparator group, with lower rates of moderate- to high-grade hyperbilirubinaemia and improvements in bone and renal biomarkers.

Theophylline: a review of population pharmacokinetic analyses.

WHAT IS KNOWN AND OBJECTIVE: Numerous population pharmacokinetic studies of theophylline have been conducted in paediatric and adult patients. The purpose of this review was to summarize the published studies concerning population pharmacokinetics of theophylline in patients of different ages and discuss factors that might cause the large variability in the pharmacokinetics of theophylline. METHODS: A literature search was conducted in PubMed using the following keywords: 'theophylline', 'population pharmacokinetic(s)' and 'nonlinear mixed effect model'. Additionally, the relevant references listed in the retrieved articles were manually reviewed. All of the studies that reported the population pharmacokinetics of theophylline in humans were included in this review. However, articles were excluded if they were not written in English. RESULTS AND DISCUSSION: Sixteen articles were included in this review. Among them, 11 were conducted on paediatric patients, and five were conducted on adults. A one-compartment model with first-order elimination was employed in most of the included articles. A nonlinear mixed effect modelling approach (NONMEM) was the most commonly used software to develop a population pharmacokinetic model. Body weight and age (post-conceptional age and post-natal age) were the most important factors associated with the clearance (CL) of theophylline in paediatric patients. Body weight (ideal body weight and lean body mass), age and smoking status were most frequently used to estimate the CL of theophylline in adults. The median (range) estimate values of CL for paediatric and adult patients were 0·062 (0·0056-0·0949) L/h/kg and 0·053 (0·0493-0·0517) L/h/kg, respectively. The median values of the interindividual variability of CL were 33·5% in adults and 25·8% in paediatric patients. The mean values of the residual variability were 21% in paediatric patients and 14·3% in adults. WHAT IS NEW AND CONCLUSION: This review concludes that body weight and age were the most important factors associated with the clearance of theophylline in paediatric patients. Body weight, age and smoking were most frequently used to estimate the clearance of theophylline in adults. Future studies are warranted to detect the influence of new factors, such as cytochrome P450 (CYP) 1A2 gene polymorphisms, on the pharmacokinetics of theophylline because some pharmacokinetic variability was not fully explained.

First Report of Powdery Mildew Caused by Erysiphe cruciferarum on Chinese Cabbage in China.

Chinese cabbage, Brassica rapa ssp. pekinensis (syn. Brassica pekinensis (Lour.) Rupr.), in the Brassicaceae, is an important vegetable grown on about 3 million ha in China. Since 2012, a powdery mildew has been found infecting Chinese cabbage plants (cv. Qingyanchunbai No. 1) after bolting for seed production from autumn through spring 2013 in a greenhouse in Qingdao, China. Symptoms first appeared as circular to irregular white patches on both sides of the leaves, and on stems and pods, often thinly covering the whole surface. A voucher specimen was deposited in the herbarium of Qingdao Agricultural University (Accession No. HMQAU12216). Hyphae were thin-walled, smooth, hyaline, and 4 to 6 µm wide. Appressoria on the mycelia were well developed, lobed, solitary, or in pairs. Conidiophores were erect, cylindrical, 45 to 110 µm long, and comprised 3 to 4 cells. Foot-cells of conidiophores were straight, cylindrical, 16 to 28 µm long, and 7.6 to 10 µm wide. Singly-produced conidia were oblong to cylindrical or somewhat ellipsoid-doliiform, 32 to 56 × 12 to 18 µm, with a length/width ratio of 1.8 to 3.8, with angular/rectangular wrinkling of the outer wall surface, and lacked distinct fibrosin bodies. Germ tubes were produced in the perihilar position of conidia. No chasmothecia were found. These structures are typical of the powdery mildew Pseudoidium anamorph of Erysiphe (2). The specific measurements and characteristics (especially short foot-cells of conidiophores) were consistent with previous records of Erysiphe cruciferarum Opiz ex L. Junell (2,3). To confirm the identification, the complete internal transcribed spacer (ITS) region of rDNA of isolate HMQAU12216 was amplified (4) and sequenced directly. The resulting 649-bp sequence was deposited in GenBank (Accession No. KC878683). A GenBank BLAST search of ITS sequences showed an exact match with those of E. cruciferarum on B. oleracea var. acephala (GU721075) and Oidium sp. on B. pekinensis (AB522714). A pathogenicity test was conducted by gently pressing a symptomatic leaf loaded with conidia onto a leaf of each five, healthy, potted, 40-day-old plants (cv. Qingyanchunbai No. 1). Five non-inoculated plants served as a control treatment. Inoculated plants were isolated from non-inoculated plants in separate rooms in a greenhouse at 20 ± 2°C. Inoculated plants developed signs and symptoms after 10 days, whereas the control plants remained symptomless. The fungus present on the inoculated plants was identical morphologically to that originally observed on diseased plants, thus fulfilling Koch's postulates. Though many Brassica spp. have been known to be infected with E. cruciferarum throughout the world, powdery mildew of Chinese cabbage caused by E. cruciferarum has been reported only in Finland, Germany, and Korea (1,3). To our knowledge, this is the first report of powdery mildew caused by E. cruciferarum on Chinese cabbage in China. Though occurrence of the powdery mildew on Chinese cabbage was noticed in an experimental breeding plot, this finding poses a potential threat to production of this vegetable in China. References: (1) U. Braun. The Powdery Mildews (Erysiphales) of Europe. Gustav Fischer Verlag, Jena, Germany, 1995. (2) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No. 11. CBS, Utrecht, 2012. (3) H. J. Jee et al. Plant Pathol. 57:777, 2008. (4) S. Matsuda and S. Takamatsu. Mol. Phylogen. Evol. 27:314, 2003.

EST-SSR markers from Heterodera glycines Ichinohe.

The soybean cyst nematode Heterodera glycines Ichinohe is a severe agricultural pest for which genetic resources are limited. In this study, 295 simple sequence repeats (SSRs) were identified from 259 expressed sequenced tags (ESTs), Which were selected from 9,443 unigenes. The successful primer pairs were designed against six regions. In total, 30 alleles were identified from 30 individuals using the six markers, with an average of five alleles per locus (range, 4-7). The observed and expected heterozygosities were 0.074-0.900 and 0.266-0.775, respectively. Significant departure from Hardy-Weinberg equilibrium was found at three of the six loci. The EST-based SSR markers developed in this study may contribute to better understanding of the genetic structure of H. glycines populations.

Partial order and finite-temperature phase transitions in Potts models on irregular lattices.

We evaluate the thermodynamic properties of the 4-state antiferromagnetic Potts model on the Union-Jack lattice using tensor-based numerical methods. We present strong evidence for a previously unknown, "entropy-driven," finite-temperature phase transition to a partially ordered state. From the thermodynamics of Potts models on the diced and centered diced lattices, we propose that finite-temperature transitions and partially ordered states are ubiquitous on irregular lattices.

Circ_0056618 promoted cell proliferation, migration and angiogenesis through sponging with miR-206 and upregulating CXCR4 and VEGF-A in colorectal cancer.

OBJECTIVE: Growing evidence has revealed that circular RNAs (circRNAs) play important roles in the development of cancers, including colorectal cancer (CRC). In this study, we mainly focused on the expression of circ_0056618 and potential functions of circ_0056618 in CRC patients. PATIENTS AND METHODS: RT-PCR was performed to detect circ_0056618 and miR-206 expressions in CRC tissues and adjacent non-tumor tissues. Correlation analysis was used to analyze the correlation between circ_0056618 and miR-206. Kaplan-Meier method was conducted to analyze the overall survival (OS) for CRC patients. Moreover, CCK-8 assay was used to measure cell proliferation ability and transwell assay was performed to detect cell migration ability. Besides, tube formation assay was performed to measure cell angiogenesis capacity. Western blot (WB) was performed to measure protein levels of tissues samples and CRC cell lines. Notably, the Luciferase reporter assay was performed to prove the binding sites in circ_0056618 with miR-206, miR-206 with CXCR4 and VEGF-A. RESULTS: We found that circ_0056618 was elevated in CRC tumor tissues and CRC cell lines, which was related to poor diagnosis for CRC patients. MiR-206 was reduced in CRC tissues, which was negatively related with circ_0056618. Protein levels of CXCR4 and VEGF-A were elevated in CRC tumor tissues, which were negatively related with miR-206. Circ_0056618 inhibition inhibited proliferation, angiogenesis and migration of HT29 cells, and repressed protein levels of Cyclin D1, VEGF-A and N-cadherin and increased E-cadherin. Notably, Luciferase reporter assay indicated that circ_0056618 could sponge with miR-206, which could directly target at CXCR4 and VEGF-A. Finally, we proved a pathway that circ_0056618 promoted cell proliferation, migration and angiogenesis through sponging with miR-206 and removing the repressing effects of miR-206, thereby upregulating CXCR4 and VEGF-A in CRC. CONCLUSIONS: Above all, this study revealed that circ_0056618 was increased in CRC tissues, which was related with the poor OS of CRC patients. We found that circ_0056618 could promote cell proliferation, migration and angiogenesis through sponging with miR-206 and upregulating CXCR4 and VEGF-A in CRC, which might provide a novel potential therapeutic target for treating CRC.

Power and precision of alternate methods for linkage disequilibrium mapping of quantitative trait loci.

Linkage disequilibrium (LD) analysis in outbred populations uses historical recombinations to detect and fine map quantitative trait loci (QTL). Our objective was to evaluate the effect of various factors on power and precision of QTL detection and to compare LD mapping methods on the basis of regression and identity by descent (IBD) in populations of limited effective population size (N(e)). An 11-cM region with 6-38 segregating single-nucleotide polymorphisms (SNPs) and a central QTL was simulated. After 100 generations of random mating with N(e) of 50, 100, or 200, SNP genotypes and phenotypes were generated on 200, 500, or 1000 individuals with the QTL explaining 2 or 5% of phenotypic variance. To detect and map the QTL, phenotypes were regressed on genotypes or (assumed known) haplotypes, in comparison with the IBD method. Power and precision to detect QTL increased with sample size, marker density, and QTL effect. Power decreased with N(e), but precision was affected little by N(e). Single-marker regression had similar or greater power and precision than other regression models, and was comparable to the IBD method. Thus, for rapid initial screening of samples of adequate size in populations in which drift is the primary force that has created LD, QTL can be detected and mapped by regression on SNP genotypes without recovering haplotypes.

Tamoxifen-bound estrogen receptor (ER) strongly interacts with the nuclear matrix protein HET/SAF-B, a novel inhibitor of ER-mediated transactivation.

The estrogen receptor (ER) is a ligand-dependent transcription factor that acts in a cell- and promoter-specific manner. Evidence suggests that the activity of the ER can be regulated by a number of other stimuli (e.g. growth factors) and that the effects of the ER are modulated by nuclear factors termed coregulators. While the interplay among these factors may in part explain the pleiotropic effects elicited by the ER, there are several other less well described mechanisms of control, such as interactions with the nuclear matrix. Here we report that the nuclear matrix protein/scaffold attachment factor HET/SAF-B is an ER-interacting protein. ER and HET/SAF-B interact in in vitro binding assays, with HET binding to both the ER DNA-binding domain and the hinge region. Coimmunoprecipitation experiments reveal that HET/SAF-B and ER associate in cell lines in the presence or absence of estradiol, but binding is increased by the antiestrogen tamoxifen. HET/SAF-B enhances tamoxifen antagonism of estrogen-induced ER-mediated transactivation, but at high concentrations can inhibit both estrogen and tamoxifen-induced ER activity. HET/SAF-B-mediated repression of ER activity is dependent upon interaction with the ER-DBD. While the existence of high-affinity binding sites for the ER in the nuclear matrix has been known for some time, we now provide evidence of a specific nuclear matrix protein binding to the ER. Furthermore, our data showing that HET/SAF-B binds to ER particularly strongly in the presence of tamoxifen suggests that it may be important for the antagonist effect of tamoxifen.

Benchmark dose approach for low-level lead induced haematogenesis inhibition and associations of childhood intelligences with ALAD activity and ALA levels.

Lead (Pb) levels, delta-aminolevulinic acid dehydratase (ALAD) activities, zinc protoporphyrin (ZPP) levels in blood, and urinary delta-aminolevulinic acid (ALA) and coproporphyrin (CP) concentrations were measured for 318 environmental Pb exposed children recruited from an area of southeast China. The mean of blood lead (PbB) levels was 75.0µg/L among all subjects. Benchmark dose (BMD) method was conducted to present a lower PbB BMD (lower bound of BMD) of 32.4µg/L (22.7) based on ALAD activity than those based on the other three haematological indices, corresponding to a benchmark response of 1%. Childhood intelligence degrees were not associated significantly with ALAD activities or ALA levels. It was concluded that blood ALAD activity is a sensitive indicator of early haematological damage due to low-level Pb exposures for children.

Adverse health effects of lead exposure on children and exploration to internal lead indicator.

Our research on adverse effects of lead exposures on physical and neurobehavioral health of children aged 6-12years in 4 villages, labeled as K, M, L, and X, in rural China, was reported in this article. Lead in blood (PbB), urine (PbU), hairs (PbH), and nails (PbN) were measured by graphite furnace atomic absorption spectrometry. Abbreviated Symptom Questionnaire of Conner's instruments and Revised Raven's Standard Progressive Matrices were applied to evaluate childhood attention deficit/hyperactivity disorders (ADHD) and intelligences. Geometric means (SD) of PbB, PbU, PbH and PbN concentrations were 71.2 microg/L (1.56), 11.7 microg/g (1.75), 12.5 microg/g (2.82), and 25.3 microg/g (2.79), respectively. 54 (17.0%) children had PbB levels of > or =100 microg/L. Boys, 6-10 years old, and living in village K were 2.11, 2.48, and 9.16 times, respectively, more likely to be poisoned by lead than girls, aged 11-12 years, and residing in X. 18 (5.7%) and 37 (11.7%) subjects had ADHD and mental retardations, respectively. Inverse relationships between intelligences and natural log transformed PbU and PbH levels were observed with respective odds ratios (95%CI) of 1.79 (1.00-3.22) and 1.46 (1.06-2.03) or 1.28 (1.04-1.58) and 1.73 (1.18-2.52) by binary or ordinal logistic regression modeling. ADHD prevalence was different by gender and age of subjects. PbU, PbH, and PbN related to PbB positively with respective correlation coefficients of 0.530, 0.477, and 0.181. Receiver operating characteristic (ROC) curves of the three measurements revealed areas under curves (AUCs) being 0.829, 0.758, and 0.687, respectively. In conclusion, children had moderate levels of lead exposures in this rural area. Intelligence declines were associated with internal lead levels among children. ROC analysis suggests PbU an internal lead indicator close to PbB.

Forkhead homologue in rhabdomyosarcoma functions as a bifunctional nuclear receptor-interacting protein with both coactivator and corepressor functions.

In a search for novel transcriptional intermediary factors for the estrogen receptor (ER), we used the ligand-binding domain and hinge region of ER as bait in a yeast two-hybrid screen of a cDNA library derived from tamoxifen-resistant MCF-7 human breast tumors from an in vivo athymic nude mouse model. Here we report the isolation and characterization of the forkhead homologue in rhabdomyosarcoma (FKHR), a recently described member of the hepatocyte nuclear factor 3/forkhead homeotic gene family, as a nuclear hormone receptor (NR) intermediary protein. FKHR interacts with both steroid and nonsteroid NRs, although the effect of ligand on this interaction varies by receptor type. The interaction of FKHR with ER is enhanced by estrogen, whereas its interaction with thyroid hormone receptor and retinoic acid receptor is ligand-independent. In addition, FKHR differentially regulates the transactivation mediated by different NRs. Transient transfection of FKHR into mammalian cells dramatically represses transcription mediated by the ER, glucocorticoid receptor, and progesterone receptor. In contrast, FKHR stimulates rather than represses retinoic acid receptor- and thyroid hormone receptor-mediated transactivation. Most intriguingly, overexpression of FKHR dramatically inhibits the proliferation of ER-dependent MCF-7 breast cancer cells. Therefore, FKHR represents a bifunctional NR intermediary protein that can act as either a coactivator or corepressor, depending on the receptor type.