Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study

Objective The relationship between serum uric acid(SUA)levels and glycemic indices,including plasma glucose(FPG),2-hour postload glucose(2 h-PG),and glycated hemoglobin(HbA1 c),remains inconclusive.We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.Methods The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study.A total of 105,922 community-dwelling adults aged≥40 years underwent the oral glucose tolerance test and uric acid assessment.The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.Results A total of 30,941 men and 62,361 women were eligible for the current analysis.Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels,but with different inflection points in men and women.The thresholds for FPG,2 h-PG,and HbA1 c for men and women were 6.5/8.0 mmol/L,11.0/14.0 mmol/L,and 6.1/6.5,respectively(SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes,while the inflection points were reached earlier in men than in women.     

Linear and Interactive Effects of Air Pollution and Diurnal Temperature Range on COPD Mortality in Weifang,China: A Time Series Analysis

Chronic obstructive pulmonary disease (COPD), which is characterized by a long-term, irreversible airway limitation and persistent respiratory symptoms, is common and preventable. Several studies have suggested that particulate matter is associated with the prevalence of COPD and the risk of mortality. At the same time, the diurnal temperature?range?(DTR)?has?been?suggested?to?be an adverse health factor that is especially associated?with?an?increased?risk?of?hospitalization in patients with COPD[1]. DTR represents temperature variability within 1 day and is considered an important indicator of climate change.?A?few?studies?have?shown?that?ambient?air pollutants [particulate matter (PM)], such as PM2.5 and PM10, and high or low temperature have a synergistic effect on COPD[1]. Thus, the current study determined the interaction between particulate matter (PM) and the DTR on COPD mortality and identified the vulnerable population in?Weifang.     

Toxic effect of NiCl2 on development of the bursa of Fabricius in broiler chickens

This study was conducted with objective of evaluating the toxic effects of nickel chloride (NiCl₂) on development of bursa of Fabricius in broilers fed on diets supplemented with 0, 300, 600 and 900 mg/kg of NiCl₂ for 42 days by using the methods of experimental pathology, flow cytometry (FCM), and quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that dietary NiCl₂ in 300 mg/kg and over induced toxic suppression in the bursal development, which was characterized by decreasing lymphocytes histopathologically and relative weight, increasing G₀/G₁ phase (a prolonged nondividing state), reducing S phase (DNA replication) and proliferating index, and increasing percentages of apoptotic cells. Concurrently, the mRNA expression levels of bax, cytochrome c (cyt c), apoptotic peptidase activating factor 1 (Apaf-1), caspase-3, caspase-6, caspase-7 and caspase-9 were increased and the bcl-2 mRNA expression levels were decreased. The toxic suppression of bursal development finally impaired humoral immunity duo to the reduction of B lymphocyte population and B lymphocyte activity in the broiler chicken. This study provides new evidences for further studying the effect mechanism of Ni and Ni compoundson B-cell or bursa of Fabricius.     

Correlations of fascin-1 and cadherin-17 protein expression with clinicopathologic features and prognosis of patients with gastric cancer

Tumor Biology - We aim to explore the associations of fascin-1 and cadherin-17 in gastric cancer (GC) to the clinicopathologic features and prognosis of GC. Case group included 204 GC tissues while...     

Production and sequence validation of a complete full length ORF collection for the pathogenic bacterium Vibrio cholerae

Cholera, an infectious disease with global impact, is caused by pathogenic strains of the bacterium Vibrio cholerae. High-throughput functional proteomics technologies now offer the opportunity to investigate all aspects of the proteome, which has led to an increased demand for comprehensive protein expression clone resources. Genome-scale reagents for cholera would encourage comprehensive analyses of immune responses and systems-wide functional studies that could lead to improved vaccine and therapeutic strategies. Here, we report the production of the FLEXGene clone set for V. cholerae O1 biovar eltor str. N16961: a complete-genome collection of ORF clones. This collection includes 3,761 sequence-verified clones from 3,887 targeted ORFs (97%). The ORFs were captured in a recombinational cloning vector to facilitate high-throughput transfer of ORF inserts into suitable expression vectors. To demonstrate its application, approximately 15% of the collection was transferred into the relevant expression vector and used to produce a protein microarray by transcribing, translating, and capturing the proteins in situ on the array surface with 92% success. In a second application, a method to screen for protein triggers of Toll-like receptors (TLRs) was developed. We tested in vitro-synthesized proteins for their ability to stimulate TLR5 in A549 cells. This approach appropriately identified FlaC, and previously uncharacterized TLR5 agonist activities. These data suggest that the genome-scale, fully sequenced ORF collection reported here will be useful for high-throughput functional proteomic assays, immune response studies, structure biology, and other applications.     

PACAP inhibit the release and cytokine activity of HMGB1 and improve the survival during lethal endotoxemia

The pathogenesis of sepsis is mediated in part by bacterial endotoxin (lipopolysaccharide; LPS), which stimulates macrophages/monocytes to sequentially release early (e.g., TNF-alpha, IL-1beta) and late [e.g., high mobility group box 1 (HMGB1) protein] pro-inflammatory cytokines. Specifically targeting early mediators has not been effective clinically, in part, because peak mediator activity often has passed before therapy can be initiated. Recent discovery of HMGB1 as a late mediator of lethal sepsis has provided a new target for the treatment of septic shock. Here, we demonstrate that pituitary adenylate cyclase-activating polypeptide (PACAP), an endogenous neuropeptide, significantly attenuated circulating HMGB1 levels and increased survival in animals with established endotoxemia, even if treatment began after acute cytokine response has occurred. In vitro, PACAP suppressed LPS-induced HMGB1 release from macrophages/monocytes, even when given 2-4 h after LPS stimulation. PACAP also suppressed HMGB1 release induced by TNF-alpha or IFN-gamma. Moreover, PACAP inhibits HMGB1-induced cytokine release in vitro and in vivo. These results indicate that PACAP inhibits the release and pro-inflammatory activity of HMGB1 and improves survival during lethal endotoxemia, which confirms this peptide as a candidate for therapy of septic shock.     

2-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 1. Structure-activity relationships and optimization of heterocyclic substituents

Previously we have described a novel series of potent and selective A 2A receptor antagonists (e.g., 1) with excellent aqueous solubility. While these compounds are efficacious A 2A antagonists in vivo, the presence of an unsubstituted furyl moiety was a cause of some concern. In order to avoid the potential metabolic liabilities that could arise from an unsubstituted furyl moiety, an optimization effort was undertaken with the aim of replacing the unsubstituted furan with a more metabolically stable group while maintaining potency and selectivity. Herein, we describe the synthesis and SAR of a range of novel heterocyclic systems and the successful identification of a replacement for the unsubstituted furan moiety with a methylfuran or thiazole moiety while maintaining potency and selectivity.