Bioinformatics analysis and identification of potential key genes and pathways in the pathogenesis of nonischemic cardiomyopathy.

Nonischemic cardiomyopathy (NICM) is a major cause of advanced heart failure, and the morbidity and mortality associated with NICM are serious medical problems. However, the etiology of NICM is complex and the related mechanisms involved in its pathogenesis remain unclear. The microarray datasets GSE1869 and GSE9128 retrieved from the Gene Expression Omnibus database were used to identify differentially expressed genes (DEGs) between NICM and normal samples. The co-expressed genes were identified using Venn diagrams. Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene ontology enrichment were used to clarify biological functions and signaling pathways. Analysis of protein-protein interaction networks using Search Tool for the Retrieval of Interacting Genes/Proteins online to define the hub genes associated with NICM pathogenesis. A total of 297 DEGs were identified from GSE1869, 261 of which were upregulated genes and 36 were downregulated genes. A total of 360 DEGs were identified from GSE9128, 243 of which were upregulated genes and 117 were downregulated genes. In the 2 datasets, the screening identified 36 co-expressed DEGs. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis showed that DEGs were mainly enriched in pantothenate and CoA biosynthesis, beta-alanine metabolism, kinetochore, G-protein beta/gamma-subunit complex, and other related pathways. The PPI network analysis revealed that DUSP6, EGR1, ZEB2, and XPO1 are the 4 hub genes of interest in the 2 datasets. Bioinformatics analysis of hub genes and key signaling pathways is an effective way to elucidate the mechanisms involved in the development of NICM. The results will facilitate further studies on the pathogenesis and therapeutic targets of NICM.

[Abundance and Fluorescent Components of Dissolved Organic Matter Affected by Land Use in a Drinking Water Source].

Regional concentrations, fluorescent components, and sources of dissolved organic matter (DOM) in a drinking water source in Chaobai River across seasons were investigated here using fluorescence excitation-emission matrices, parallel factor analysis, and fluorescence indexes. Five fluorescent-DOM components were identified, including two microbial humic-like components and one autochthonous tyrosine-like, one reduced quinone-like, and one terrestrial humic-like component. DOM was mainly derived from microorganisms. The farmland-dominated region showed the highest DOM concentration and significantly lower maximum fluorescence intensities (Fmax) of almost all fluorescent components than those in the forest-dominated region. The region dominated by urban lands exhibited obviously lower DOM concentrations than those in the farmland-dominated region and lower Fmax values of fluorescent components than those in the forest-dominated region. No interaction was found between land use and season when considering their effects on DOM. Season had a significant influence on the humification degree of DOM. This study shows that agricultural land use had a greater impact on DOM than that of forests and urban areas, and the increased riverine DOM resulting from farmland was mainly non-fluorescent parts.

Abnormal ankle-brachial index and risk of cardiovascular or all-cause mortality in patients with chronic kidney disease: a meta-analysis.

Prognostic role of ankle-brachial index (ABI) in patients with chronic kidney disease (CKD) is controversial. We aimed to evaluate whether abnormal ABI was an independent predictor of cardiovascular or all-cause mortality in CKD patients with or without hemodialysis by conducting a meta-analysis. We systematically searched Pubmed and Embase databases for prospective observational studies that investigated baseline abnormal ABI and subsequent cardiovascular or all-cause mortality risk in CKD patients with or without hemodialysis. An ABI value of 0.9 to 1.3 was defined as normal. Pooled hazard risk (HR) with 95% confidence interval (CI) was calculated for the abnormal vs. normal ABI category. Six studies enrolling 5820 patients were identified and analyzed. Overall, abnormal ABI was associated with an increased risk of all-cause mortality (HR 2.26; 95% CI 1.60-3.18) and cardiovascular mortality (HR 3.58; 95% CI 2.53-5.06). Subgroup analysis indicated that patients with abnormally low ABI increased by 2.45-fold all-cause mortality and 5.18-fold cardiovascular mortality. Similarly, an abnormally high ABI increased by 1.94-fold all-cause mortality and 4.04-fold cardiovascular mortality. In addition, the effect of abnormal ABI on all-cause mortality was more pronounced among hemodialysis patients (HR 3.06; 95% CI 2.30-4.07) but not in CKD patients (HR 1.42; 95% CI 0.98-2.05). Abnormally low and high ABI are independently associated with cardiovascular or all-cause mortality risk in maintenance hemodialysis patients. This meta-analysis highlighted an U-shaped relationship between ABI and mortality risk in CKD patients undergoing hemodialysis. However, findings of this meta-analysis were undermined by the small number of included studies.

The Antibiosis Action and Rice-Induced Resistance, Mediated by a Lipopeptide from Bacillus amyloliquefaciens B014, in Controlling Rice Disease Caused by Xanthomonas oryzae pv. oryzae.

In the present study, a lipopeptide (named AXLP14) antagonistic to Xanthomonas oryzae pv. oryzae (Xoo) was obtained from the culture supernatant of Bacillus amyloliquefaciens B014. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis demonstrated that AXLP14 consisted of surfactin homologs. The minimum inhibition concentration and minimum bactericidal concentration of AXLP14 against Xoo were determined to be 1.25 and 2.50 mg/ml, respectively. At a concentration of 0.613 mg/ml, AXLP14 strongly inhibited the formation of Xoo biofilm. AXLP14 also inhibited the motility of Xoo in a concentration-dependent manner. Applying AXLP14 to rice seedlings significantly reduced the incidence and severity of disease caused by Xoo. In Xoo-infected rice seedlings, AXLP14 strongly and continuously up-regulated the expression of both OsNPR1 and OsWRKY45. In addition, AXLP14 effectively inhibited the Xoo-induced up-regulation of the expression of the abscisic acid biosynthesis gene OsNECD3 and the abscisic acid signalingresponsive gene OsLip9, indicating that AXLP14 may protect rice against Xoo-induced disease by enhancing salicylic acid defense and interfering with the abscisic acid response to virulence.

Fibrin sheath formation and intimal thickening after catheter placement in dog model: role of hemodynamic wall shear stress.

PURPOSE: To investigate the role of wall shear stress in aspects of the formation of fibrin sheath and intimal thickening in a dog model. METHODS: Tunneled silicone 14.5-F catheters were inserted into the left internal jugular vein in eight dogs. The dogs were separated into two groups according to catheter indwelling time of 14 and 28 days. All dogs underwent extracorporeal circulation three times a week. Multidetector computed tomography venography (MDCTV) examination was used to examine the catheter tip thrombus. After the animals were sacrificed, histological and immunohistochemistry evaluations were performed to confirm specific cell populations. We used computer modeling to generate wall shear stress profiles for the blood flow through the catheter. RESULTS: Catheter-related sheaths were identified in all catheter specimens, but there was no fibrin sheath around the catheter tip. There were also differences in wall shear stress between the different venous wall sites. Differences in vein wall thickening at different sites have been found at both 14 days (intima to media (I/M) ratio S1 vs S2: p = 0.01, S3 vs S4: p<0.01) and 28 days (I/M ratio S1 vs S2: p<0.01, S3 vs S4: p<0.05). CONCLUSIONS: After catheter placement, fibrin sheath formation partially covered the catheter. Meanwhile, focal areas of intimal thickening were also seen in the venous wall adjacent to the sites of high wall shear stress. These findings indicate an important role of wall shear stress profiles in fibrin sheath formation and intimal thickening.

Nonsense mutations in the PAX3 gene cause Waardenburg syndrome type I in two Chinese patients.

BACKGROUND: Waardenburg syndrome type I (WS1) is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmental abnormalities of the eye, hair and skin, and dystopia canthorum. The gene mainly responsible for WS1 is PAX3 which is involved in melanocytic development and survival. Mutations of PAX3 have been reported in familiar or sporadic patients with WS1 in several populations of the world except Chinese. In order to explore the genetic background of Chinese WS1 patients, a mutation screening of PAX3 gene was carried out in four WS1 pedigrees. METHODS: A questionnaire survey and comprehensive clinical examination were conducted in four Chinese pedigrees of WS1. Genomic DNA from each patient and their family members was extracted and exons of PAX3 were amplified by PCR. PCR fragments were ethanol-purified and sequenced in both directions on an ABI_Prism 3100 DNA sequencer with the BigDye Terminator Cycle Sequencing Ready Reaction Kit. The sequences were obtained and aligned to the wild type sequence of PAX3 with the GeneTool program. RESULTS: Two nonsense PAX3 mutations have been found in the study population. One is heterozygous for a novel nonsense mutation S209X. The other is heterozygous for a previously reported mutation in European population R223X. Both mutations create stop codons leading to truncation of the PAX3 protein. CONCLUSIONS: This is the first demonstration of PAX3 mutations in Chinese WS1 patients and one of the few examples of an identical mutation of PAX3 occurred in different populations.

[Large-scale screening of mtDNA A1555G mutation in China and its significance in prevention of aminoglycoside antibiotic induced deafness].

OBJECTIVE: To explore the necessity of large-scale screening of mtDNA A1555G mutation in prevention of aminoglycoside antibiotic induced deafness (AAID) and to develop a feasible method to prevent AAID. METHODS: A total of 1836 patients with non-syndromic hearing impairment (NSHI), 1352 students of schools for deaf-mutes in 11 provinces and municipality in China, 413 out-patients, and 71 persons from the families with maternal relatives suffering from AAID, underwent questionnaire survey and/or PCR for A-to-G mutation at nucleotide 1555 of the mitochondrial genome. RESULTS: Sixty three patients with mtDNA A1555G mutation were found among the 1836 NSHI patients. Fifty-two maternal pedigrees were identified. 536 cases with normal hearing from these pedigrees were informed to avoid using aminoglycoside antibiotics (AmAn). CONCLUSION: Large-scale screening of mtDNA A1555G mutation and relevant health education to avoid use of AmAn are effective to prevent ototoxicity in the A1555G carriers and their maternal relatives.