Comparative metabolomics reveals the mechanism of avermectin production enhancement by <Emphasis Type="Italic">S</Emphasis>-adenosylmethionine

It was found that S-adenosylmethionine (SAM) could effectively improve avermectin titer with 30–60 μg/mL addition to FH medium. To clearly elucidate the mechanism of SAM on intracellular metabolites of Streptomyces avermitilis, a GC–MS-based comparative metabolomics approach was carried out. First, 230 intracellular metabolites were identified and 14 of them remarkably influenced avermectin biosynthesis were discriminative biomarkers between non-SAM groups and SAM-treated groups by principal components analysis (PCA) and partial least squares (PLS). Based on further key metabolic pathway analyses, these biomarkers, such as glucose, oxaloacetic acid, fatty acids (in soybean oil), threonine, valine, and leucine, were identified as potentially beneficial precursors and added in medium. Compared with single-precursor feeding, the combined feeding of the precursors and SAM markedly increased the avermectin titer. The co-feeding approach not only directly verified our hypothesis on the mechanism of SAM by comparative metabolomics, but also provided a novel strategy to increase avermectin production.     

Neuroprotective Effect of Chitosan Oligosaccharide on Hypoxic-Ischemic Brain Damage in Neonatal Rats

Neonatal hypoxic-ischemic brain damage (HIBD) is one of the leading causes of neonatal mortality and permanent neurological disability worldwide and the effective treatment strategies are not yet available. It has been demonstrated that Chitosan oligosaccharide (COS) exerts protective effect in vitro ischemic brain injury. However, no information is available on possible effects of COS on neonatal HIBD. To investigate the hypothesis of the potential neuroprotective effect of COS on the brain injury due to HIBD, 7-day-old Sprague–Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen (balanced with nitrogen) for 2.5 h at 37?°C. After COS treatment, the cerebral damage was measured by behavior tasks, 2,3,5-triphenyltetrazolium chloride(TTC), Hematoxyline-Eosin(HE), Nissl and Fluoro-Jade B(FJB)staining. In addition, the oxidative stress were assayed with ipsilateral hemisphere homogenates. Immunofluorescence staining were used to examine the activation of the astrocyte and microglia. Expression of inflammatory-related proteins were analyzed by western-blot analysis. In this study we found that administration of COS ameliorated early neurological reflex behavior, significantly reduce brain infarct volume and attenuated neuronal cell injury and degeneration. Furthermore, COS markedly decreased the level of MDA, lactic acid and increased SOD, GSH-Px and T-AOC. COS attenuated hypoxic-ischemic induced up-regulation of expressions of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), meanwhile it dramatically increased the interleukin-10 (IL-10). These results suggest that COS exerts neuroprotection on hypoxic-ischemic brain damage in neonatal rats, it implies COS might be a potential therapeutic for the treatment of HIBD.     

Multi-actor multi-criteria sustainability assessment framework for energy and industrial systems in life cycle perspective under uncertainties. Part 1: weighting method

Purpose

Life cycle sustainability assessment is meaningful for the decision-makers/stakeholders to select the most sustainable option among multiple alternatives; however, there are usually various severe uncertainty problems in sustainability-oriented decision-making, i.e., the vagueness and ambiguity that existed in human judgments and the lack of information. This study aims at developing a novel life cycle multi-criteria sustainability assessment method for helping the decision-makers/stakeholders to determine the sustainability level of the industrial and energy systems. In part 1, an improved interval analytic hierarchy process (AHP) which allows multiple decision-makers/stakeholders to participate in the decision-making was developed to determine the weights of the criteria which were used in life cycle sustainability assessment.

Methods

It is usually difficult for the decision-makers/stakeholders to use the numbers from 1 to 9 and their reciprocals for determining the comparison matrix when using the traditional AHP method for weight calculation, because human judgments usually involve various uncertainties. In order to the overcome this weak point of the traditional AHP, an improved AHP, so-called interval AHP, in which, multiple decision-makers/stakeholders are allowed to participate in the decision-making and allowed to use interval numbers instead of crisp numbers to establish the comparison matrix for determining the weights of the criteria for life cycle sustainability assessment, has been developed.

Results and discussion

The proposed method was used to determine the weights of the four aspects for life cycle sustainability assessment including economic, safety, social, and environmental aspects. Five representative stakeholders were invited to participate in the decision-making. After Monte Carlo simulation, the final weights of the four aspects have been determined with the proposed interval AHP.

Conclusions and perspectives

An interval AHP method was developed for determining the weights of the criteria for life cycle sustainability assessment; the decision-makers are allowed to use interval numbers to establish the comparison matrix for weight calculation. The weighting coefficients determined by Monte Carlo method can accurately reflect the preferences and willingness of multi-actor comparing with the traditional AHP method. This paper merely presents a novel method to calculate the weights of the criteria for life cycle sustainability assessment, but the method for determining the sustainability performance has been presented in part 2.

     

Splenic gene expression profiling in White Leghorn layer inoculated with the Salmonella enterica serovar Enteritidis

Salmonella enterica serovar Enteritidis (SE) is a foodborne pathogen that can threaten human health through contaminated poultry products. Live poultry, chicken eggs and meat are primary sources of human salmonellosis. To understand the genetic resistance of egg‐type chickens in response to SE inoculation, global gene expression in the spleen of 20‐week‐old White Leghorn was measured using the Agilent 4 × 44 K chicken microarray at 7 and 14 days following SE inoculation (dpi). Results showed that there were 1363 genes significantly differentially expressed between inoculated and non‐inoculated groups at 7 dpi (I7/N7), of which 682 were up‐regulated and 681 were down‐regulated genes. By contrast, 688 differentially expressed genes were observed at 14 dpi (I14/N14), of which 371 were up‐regulated genes and 317 were down‐regulated genes. There were 33 and 28 immune‐related genes significantly differentially expressed in the comparisons of I7/N7 and I14/N14 respectively. Functional annotation revealed that several Gene Ontology (GO) terms related to immunity were significantly enriched between the inoculated and non‐inoculated groups at 14 dpi but not at 7 dpi, despite a similar number of immune‐related genes identified between I7/N7 and I14/N14. The immune response to SE inoculation changes with different time points following SE inoculation. The complicated interaction between the immune system and metabolism contributes to the immune responses to SE inoculation of egg‐type chickens at 14 dpi at the onset of lay. GC, TNFSF8, CD86, CD274, BLB1 and BLB2 play important roles in response to SE inoculation. The results from this study will deepen the current understanding of the genetic response of the egg‐type chicken to SE inoculation at the onset of egg laying.     

Statistical Inference Methods for Two Crossing Survival Curves: A Comparison of Methods

A common problem that is encountered in medical applications is the overall homogeneity of survival distributions when two survival curves cross each other. A survey demonstrated that under this condition, which was an obvious violation of the assumption of proportional hazard rates, the log-rank test was still used in 70% of studies. Several statistical methods have been proposed to solve this problem. However, in many applications, it is difficult to specify the types of survival differences and choose an appropriate method prior to analysis. Thus, we conducted an extensive series of Monte Carlo simulations to investigate the power and type I error rate of these procedures under various patterns of crossing survival curves with different censoring rates and distribution parameters. Our objective was to evaluate the strengths and weaknesses of tests in different situations and for various censoring rates and to recommend an appropriate test that will not fail for a wide range of applications. Simulation studies demonstrated that adaptive Neyman’s smooth tests and the two-stage procedure offer higher power and greater stability than other methods when the survival distributions cross at early, middle or late times. Even for proportional hazards, both methods maintain acceptable power compared with the log-rank test. In terms of the type I error rate, Renyi and Cramér—von Mises tests are relatively conservative, whereas the statistics of the Lin-Xu test exhibit apparent inflation as the censoring rate increases. Other tests produce results close to the nominal 0.05 level. In conclusion, adaptive Neyman’s smooth tests and the two-stage procedure are found to be the most stable and feasible approaches for a variety of situations and censoring rates. Therefore, they are applicable to a wider spectrum of alternatives compared with other tests.     

Three saponins from Oxytropis species.

Three flavonoids and three saponins have been isolated from Oxytropis species. Their structures were determined as isorhamnetin-3-O-beta-D-glucoside, rhamnetin-3-O-beta-D-galactoside, apigenin, 3-O-[alpha-L-rhamnopyranosyl (1----2)-beta-D-glucopyranosyl(1----4)-beta-D-glucuronopyranosyl]+ ++soyasapogenol B, 3-O-[beta-D-glucopyranosyl(1----2)-beta-D-glucuronopyranosyl] azukisapogenol and a new saponin 3-O-[beta-D-glucopyranosyl(1----2)-beta-D-glucopyranosyl]-25-O-alpha-L- rhamnopyranosyl-(20S,24S)-3 beta,16 beta, 20,24,25-pentahydroxy-9,19-cycloanostane.