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The genus Primula is extremely diverse in the east Himalaya-Hengduan Mountains (HHM) in China as a result of rapid radiation. In order to overcome the difficulty of morphological classification of this genus, we surveyed three plastid regions (rbcL, matK, and trnH-psbA) and two nuclear markers (ITS and ITS2) from 227 accessions representing 66 Primula species across 18 sections, to assess their discriminatory power as barcodes. We found that ITS alone or combined with plastid regions showed the best discrimination across different infrageneric ranks and at species level. We suggest rbcL + matK + ITS as the first choice at present to barcode Primula plants. Although the present barcoding combination performed poorly in many closely related species of Primula, it still provided many new insights into current Primula taxonomy, such as the underlying presence of cryptic species, and several potential improper taxonomic treatments. DNA barcoding is one useful technique in the integrative taxonomy of the genus Primula, but it still requires further efforts to improve its effectiveness in some taxonomically challenging groups.

It has been demonstrated that exercise is one of the stresses known to increase the aldosterone secretion. Both potassium and angiotensin II (Ang II) levels are shown to be correlated with aldosterone production during exercise, but the mechanism is still unclear. In an in vivo study, male rats were catheterized via right jugular vein (RJV), and divided into four groups namely water immersion, swimming, lactate infusion (13 mg/kg/min) and pyruvate infusion (13 mg/kg/min) groups. Each group was treated for 10 min. Blood samples were collected at 0, 10, 15, 30, 60 and 120 min from RJV after administration. In an in vitro study, rat zona glomerulosa (ZG) cells were challenged by lactate (1-10 mM) in the presence or absence of Ang II (10(-8) M) for 60 min. The levels of aldosterone in plasma and medium were measured by radioimmunoassay. Cell lysates were analyzed by immunoblotting assay. After exercise and lactate infusion, plasma levels of aldosterone and lactate were significantly higher than those in the control group. Swimming for 10 min significantly increased the plasma Ang II levels in male rats. Administration of lactate plus Ang II significantly increased aldosterone production and enhanced protein expression of steroidogenic acute regulatory protein (StAR) in ZG cells. These results demonstrated that acute exercise led to the increase of both aldosterone and Ang II secretion, which is associated with lactate action on ZG cells and might be dependent on the activity of renin-angiotensin system.

BACKGROUND: The aim of this study was to investigate the interaction effects of pri-let-7a-1 rs10739971 with pepsinogen C (PGC) and excision repair cross complementing group 6 (ERCC6) gene polymorphisms and its association with the risks of gastric cancer and atrophic gastritis. We hoped to identify miRNA polymorphism or a combination of several polymorphisms that could serve as biomarkers for predicting the risk of gastric cancer and its precancerous diseases. METHODS: Sequenom MassARRAY platform method was used to detect polymorphisms of pri-let-7a-1 rs10739971 G → A, PGC rs4711690 C → G, PGC rs6458238 G → A, PGC rs9471643 G → C, and ERCC6 rs1917799 in 471 gastric cancer patients, 645 atrophic gastritis patients and 717 controls. RESULTS: An interaction effect of pri-let-7a-1 rs10739971 polymorphism with ERCC6 rs1917799 polymorphism was observed for the risk of gastric cancer (P interaction = 0.026); and interaction effects of pri-let-7a-1 rs10739971 polymorphism with PGC rs6458238 polymorphism (P interaction = 0.012) and PGC rs9471643 polymorphism (P interaction = 0.039) were observed for the risk of atrophic gastritis. CONCLUSION: The combination of pri-let-7a-1 rs10739971 polymorphism and ERCC6 and PGC polymorphisms could provide a greater prediction potential than a single polymorphism on its own. Large-scale studies and molecular mechanism research are needed to confirm our findings.

BACKGROUND: Pepsinogen C (PGC) plays an important role in sustaining the cellular differentiation during the process of gastric carcinogenesis. This study aimed to assess the role of PGC tagSNPs and their interactions with Helicobacter pylori (H. pylori) in the development of gastric cancer and its precursor, atrophic gastritis. METHODS: Four PGC tagSNPs (rs6941539, rs6912200, rs3789210 and rs6939861) were genotyped by Sequenom MassARRAY platform in a total of 2311 subjects consisting of 642 gastric cancer, 774 atrophic gastritis, and 895 healthy control subjects. The mRNA and protein expression levels of PGC in gastric tissues and in serum were respectively measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), immunohistochemistry, and Eenzyme-linked immunoabsorbent assay (ELISA). RESULTS: We found associations between PGC rs3789210 CG/GG genotypes and reduced gastric cancer risk and between PGC rs6939861 A variant allele and increased risks of both gastric cancer and atrophic gastritis. As for the haplotypes of PGC rs6941539-rs6912200-rs3789210-rs6939861 loci, the TTCA and TTGG haplotypes were respectively associated with increased and reduced risks of both gastric cancer and atrophic gastritis; additionally, the CTCA haplotype was associated with increased atrophic gastritis risk. Very interestingly, rs6912200 CT/TT genotypes had a positive interaction with H. pylori, synergistically elevating the gastric cancer risk. Moreover, healthy subjects who carried rs6912200 CT, TT and CT/TT variant genotypes had lower histological and serum expression levels of PGC protein. CONCLUSIONS: Our findings highlight an important role of PGC rs3789210 and rs6939861 in altering susceptibility to atrophic gastritis and/or gastric cancer. Moreover, people who carry rs6912200 variant genotypes exhibit higher gastric cancer risk in case of getting H. pylori infection, which strongly suggest a necessity of preventing and/or eliminating H. pylori infection in those individuals.

The objective of this study was to introduce application of the Richards equation on modelling and prediction of stand diameter distribution. The long-term repeated measurement data sets, consisted of 309 diameter frequency distributions from Chinese fir (Cunninghamia lanceolata) plantations in the southern China, were used. Also, 150 stands were used as fitting data, the other 159 stands were used for testing. Nonlinear regression method (NRM) or maximum likelihood estimates method (MLEM) were applied to estimate the parameters of models, and the parameter prediction method (PPM) and parameter recovery method (PRM) were used to predict the diameter distributions of unknown stands. Four main conclusions were obtained: (1) R distribution presented a more accurate simulation than three-parametric Weibull function; (2) the parameters p, q and r of R distribution proved to be its scale, location and shape parameters, and have a deep relationship with stand characteristics, which means the parameters of R distribution have good theoretical interpretation; (3) the ordinate of inflection point of R distribution has significant relativity with its skewness and kurtosis, and the fitted main distribution range for the cumulative diameter distribution of Chinese fir plantations was 0.4∼0.6; (4) the goodness-of-fit test showed diameter distributions of unknown stands can be well estimated by applying R distribution based on PRM or the combination of PPM and PRM under the condition that only quadratic mean DBH or plus stand age are known, and the non-rejection rates were near 80%, which are higher than the 72.33% non-rejection rate of three-parametric Weibull function based on the combination of PPM and PRM.

Glutathione S-transferase P1 (GSTP1) is a critical enzyme in the phase II detoxification pathway. One of the common functional polymorphisms of GSTP1 is A→G at nucleotide 313, which results in an amino acid substitution (Ile105Val) at the substrate binding site and reduced catalytic activity. We evaluated the interaction between GSTP1 Val allele and Helicobacter pylori infection, smoking and alcohol consumption, increasing the risk of gastric cancer among the Chinese population. Information on potential gastric cancer risk factors and blood specimens were collected from 618 incident gastric cancer cases and 1,830 non-cancer controls between March 2002 and December 2011 in Liaoning Province, China. GSTP1 Ile105Val was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism. Serum levels of anti-H. pylori IgG were measured by ELISA. Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate logistic regression, adjusted by sex and age. The risk of gastric cancer was significantly elevated in patients with the GSTP1 Val/Val genotype (adjusted OR = 3.324; 95% CI = 1.790-6.172). An elevated risk of gastric cancer was observed in patients with H. pylori infection, smoking, or alcohol consumption, and together with the GSTP1 Ile/Val +Val/Val genotype (OR = 3.696; 95% CI = 2.475-5.521; OR = 1.638; 95% CI = 1.044-2.571; OR = 1.641; 95% CI = 0.983-2.739, respectively) (p

As one of the most extensively studied glycosaminoglycan lyases, heparinase I has been used in producing low or ultra-low molecular weight heparin. Its' important applications are to neutralize the heparin in human blood and analyze heparin structure in the clinic. However, the low productivity and activity of the enzyme have greatly hindered its applications. In this study, a novel Hep-I from Bacteroides cellulosilyticus (BcHep-I) was successfully cloned and heterologously expressed in E. coli BL21 (DE3) as a soluble protein. The molecular mass and isoelectric point (pI) of the enzyme are 44.42 kDa and 9.02, respectively. And the characterization of BcHep-I after purified with Ni-NTA affinity chromatography suggested that it is a mesophilic enzyme. BcHep-I can be activated by 1 mM Ca2+, Mg2+, and Mn2+, while severely inhibited by Zn2+, Co2+, and EDTA. The specific activity of the enzyme was 738.3 U⋅mg-1 which is the highest activity ever reported. The Km and Vmax were calculated as 0.17 mg⋅mL-1 and 740.58 U⋅mg-1, respectively. Besides, the half-life of 300 min at 30°C showed BcHep-I has practical applications. Homology modeling and substrate docking revealed that Gln15, Lys74, Arg76, Lys104, Arg149, Gln208, Tyr336, Tyr342, and Lys338 were mainly involved in the substrate binding of Hep-I, and 11 hydrogen bonds were formed between heparin and the enzyme. These results indicated that BcHep-I with high activity has great potential applications in the industrial production of heparin, especially in the clinic to neutralize heparin. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the interaction effects of pri-let-7a-1 rs10739971 with pepsinogen C (PGC) and excision repair cross complementing group 6 (ERCC6) gene polymorphisms and its association with the risks of gastric cancer and atrophic gastritis. We hoped to identify miRNA polymorphism or a combination of several polymorphisms that could serve as biomarkers for predicting the risk of gastric cancer and its precancerous diseases. Methods: Sequenom MassARRAY platform method was used to detect polymorphisms of pri-let-7a-1 rs10739971 G→A, PGC rs4711690 C→G, PGC rs6458238 G→A, PGC rs9471643 G→C, and ERCC6 rs1917799 in 471 gastric cancer patients, 645 atrophic gastritis patients and 717 controls. Results: An interaction effect of pri-let-7a-1 rs10739971 polymorphism with ERCC6 rs1917799 polymorphism was observed for the risk of gastric cancer (Pinteraction = 0.026); and interaction effects of pri-let-7a-1 rs10739971 polymorphism with PGC rs6458238 polymorphism (Pinteraction = 0.012) and PGC rs9471643 polymorphism (Pinteraction = 0.039) were observed for the risk of atrophic gastritis. Conclusion: The combination of pri-let-7a-1 rs10739971 polymorphism and ERCC6 and PGC polymorphisms could provide a greater prediction potential than a single polymorphism on its own. Large-scale studies and molecular mechanism research are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the effect of proton pump inhibitors (PPIs) on in vitro antimicrobial activity of tigecycline against several species of clinical pathogens. Clinical non-duplicate isolates of Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis and three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumonia and Enterobacter cloacae) were collected from a tertiary hospital and their MICs of tigecycline alone and in combination with PPIs (omeprazole, lansoprazole and pantoprazole) were determined. With one randomly selected isolate of each bacterial species, an in vitro time–kill study was performed for the confirmation of the effect of PPIs on tigecycline activity. The MIC changes after PPIs addition correlated with the PPIs concentrations in the test media. Compared with tigecycline alone, the addition of 5 mg/L PPIs could increase the MICs of tigecycline by 0 to 2-fold and the addition of 50 mg/L PPIs could increase the MICs of tigecycline by 4 to >128-fold. The time–kill study confirmed that the addition of PPIs could affect the in vitro activity of tigecycline. Even at low concentration (5 mg/L) of omeprazole and pantoprazole, antagonistic effect could be observed in E. cloacae and E. faecalis strains. We conclude that In vitro activity of tigecycline can be influenced by the presence of PPIs in a concentration-dependent manner. [ABSTRACT FROM AUTHOR]

Background: Current and historical events have both affected the current distribution patterns and intraspecific divergence of plants. While numerous studies have focused on the Qinghai-Tibetan Plateau (QTP), the impacts of such events on the flora of subtropical China remain poorly understood. Subtropical China is famous for its highly complex topography and the limited impact from glaciation during the Pleistocene; this may have resulted in a different genetic legacy for species in this region compared to fully glaciated areas. Methodology/Principal Findings: We used plastid and nuclear DNA sequence data and distribution modeling to analyze the divergence patterns and demographic history of Primula obconica Hance, a widespread herbaceous montane species in subtropical China. The phylogenetic analysis revealed two major lineages (lineage A and lineage B), representing a west-east split into the Yunnan and Eastern groups, and the Sichuan and Central groups, respectively. The Eastern and Central groups comprised relatively new derived haplotypes. Nested Clade Analysis and Bayesian Skyline Plot analyses both indicated that P. obconica mainly experienced a gradual expansion of populations. In addition, the simulated distribution of P. obconica during the Last Glacial Maximum was slightly larger than its present-day distribution. Conclusion/Significance: Our results are the first to identify a west-east migration of P. obconica. The gradual expansion pattern and a larger potential distribution range in cold periods detected for P. obconica indicate that the population expansion of this species is consistent with the phalanx model. In addition, the current patterns of genetic differentiation have persisted as a result of the extensive environmental heterogeneity that exists in subtropical China. [ABSTRACT FROM AUTHOR]

Genetic variation and population structure may reflect important information for invasion success of exotic plant species and thus help improve management of invasive plants. Spartina alterniflora is an invasive plant that is a major threat to the economy and environment of the coastal regions in China. We analyzed the genetic structure and diversity of six populations of S. alterniflora differing in invasion histories in Guangxi, China. A total of 176 individuals from the six populations produced 348 AFLP fragments. The average heterozygosity was significantly lower than in the native population. And genetic bottlenecks were also detected in most populations. Standardized FST statistics (Φpt = 0.015) and AMOVA results indicated weak genetic differentiation. Genetic admixture and obviously isolation by distance indicated populations in Guangxi come from a pre-admixed population by a single introduction. High phenotypic variations of S. alterniflora in Guangxi influenced by soil salinity and temperature might be an important reason for the successful invasion.

Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis in childhood. The long-term prognosis of HSP is determined by the degree of renal involvement. The aim of this study is to search novel clinically applicable biomarkers to evaluate renal involvement in HSP patients. 20 bio-indexes in urine samples were simultaneously screened by antibody array assay. We indicated that urinary levels of cystatin C (Cys C) and neutrophil gelatinase-associated lipocalin (NGAL) in HSP patients with renal involvement were significantly higher than those without renal involvement and healthy controls. Furthermore, ELISA was used to analyze urinary Cys C and NGAL levels in HSP patients with or without renal involvement, atopic dermatitis (AD) patients and healthy controls. Our results demonstrated that urinary Cys C and NGAL levels in HSP patients with renal involvement were significantly elevated, when compared with those without renal involvement, AD patients and control subjects. In addition, by receiver operating characteristic (ROC) curve analysis, we demonstrated that the area under the ROC curve of NGAL (0.789) was larger than that of Cys C (0.692). Taken together, we show firstly that urinary Cys C and NGAL levels is abnormally elevated in HSP patients with renal involvement. We suggest that urinary Cys C and NGAL are novel useful biomarkers of renal involvement in HSP patients.

Our previous studies have shown that an active fragment of human tachykinins (hHK-1(4-11)) produced an opioid-independent analgesia after intracerebroventricular (i.c.v.) injection in mice, which has been markedly enhanced by a δ OR antagonist, naltrindole hydrochloride (NTI). In this study, we have further characterized the in vivo analgesia after i.c.v. injection of hHK-1(4-11) in mouse model. Our qRT-PCR results showed that the mRNA levels of several ligands and receptors (e.g. PPT-A, PPT-C, KOR, PDYN and PENK) have not changed significantly. Furthermore, neither transcription nor expression of NK1 receptor, MOR and POMC have changed noticeably. In contrast, both mRNA and protein levels of DOR have been up-regulated significantly, indicating that the enhanced expression of δ opioid receptor negatively modulates the analgesia induced by i.c.v. injection of hHK-1(4-11). Additionally, the combinatorial data from our previous and present experiments strongly suggest that the discriminable distribution sites in the central nervous system between hHK-1(4-11) and r/mHK-1 may be attributed to their discriminable analgesic effects. Altogether, our findings will not only contribute to the understanding of the complicated mechanisms regarding the nociceptive modulation of hemokinin-1 as well as its active fragments at supraspinal level, but may also lead to novel pharmacological interventions.

BACKGROUND: MicroRNAs (miRNAs) negatively regulate the 3' untranslated region (3'-UTR) of coding genes by suppressing translation or degrading mRNAs, and they act as oncogenes or tumor suppressors. Recently, several studies investigated the association between pre-miR-27a rs895819 polymorphism and the risks of various cancers, but the results were inconsistent. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 13 studies that included 6501 cancer cases and 7571 controls to address this association. Overall, this meta-analysis showed that the pre-miR-27a rs895819 A/G polymorphism was not statistically associated with cancers risk in all genetic models. In the stratified analysis by cancer types, when compared with the ancestral A allele, individuals with the variant G allele was consistently associated with reduced risks of breast cancer (OR = 0.92, 95% CI = 0.85-0.99), renal cell cancer (OR = 0.81, 95% CI = 0.67-0.97) and nasopharyngeal cancer (OR = 0.84, 95% CI = 0.72-0.97). Inversely, individuals with the heterozygote AG was associated with an increased risk of digestive tract cancers compared with AA genotype (AG vs. AA: OR = 1.16, 95% CI = 1.01-1.32). In the stratified analysis by ethnicity, the pre-miR-27a rs895819 polymorphism showed statistically significant association with decreased risks of cancers in Caucasians (G vs. A allele: OR = 0.90, 95% CI = 0.83-0.97; AG vs. AA: OR = 0.84, 95% CI = 0.75-0.94; AG/GG vs. AA: OR = 0.85, 95% CI = 0.76-0.94) but not in Asians. CONCLUSION/SIGNIFICANCE: This meta-analysis suggests that the pre-miR-27a rs895819 polymorphism may contribute to the susceptibilities of some specific-type of cancers, including breast cancer, renal cell cancer, nasopharyngeal cancer and digestive tract cancers, as well as the susceptibilities of cancers in Caucasians to some extent.