A systematic review of the applicability of emergency department assessment of chest pain score-accelerated diagnostic protocol for risk stratification of patients with chest pain.

The emergency department assessment of chest pain score-accelerated diagnostic protocol (EDACS-ADP) are commonly used for risk stratification in undifferentiated patients with acute chest pain. This systematic review aimed to investigate EDACS-ADP for risk stratification of emergency department (ED) patients with chest pain. The PubMed, Web of Science, Medline, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for related studies without restrictions on the publication year. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the risk of bias, and Stata 16.0 was used to determine the combined sensitivity, specificity, positive diagnostic likelihood ratio (DLR), and negative DLR. Twelve studies comprising 14 290 patients were identified. Of these, 7537 (52.74%) patients were considered low risk, and 67 (0.89%) had major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death within 30 days of the patients' ED presentation. EDACS-ADP showed a combined sensitivity of 0.97 (95% confidence interval [CI]: 0.95-0.99); specificity, 0.58 (0.53-0.63); positive DLR, 2.34 (2.08-2.63); negative DLR, 0.04 (0.02-0.09); diagnostic odds ratio, 53.11 (26.45-106.63); and summary receiver operating characteristic area under the curve, 0.83 (0.79-0.86). Despite the large statistical heterogeneity of the results, EDACS-ADP identified a considerable number of low-risk patients for early discharge, with a specificity >50% and an incidence of MACE within 30-days of patients' ED presentation <1%. Thus, it is a useful tool with a potential for clinical application.

Cell-free synthesis system-assisted pathway bottleneck diagnosis and engineering in Bacillus subtilis.

Metabolic engineering is a key technology for cell factories construction by rewiring cellular resources to achieve efficient production of target chemicals. However, the existence of bottlenecks in synthetic pathway can seriously affect production efficiency, which is also one of the core issues for metabolic engineers to solve. Therefore, developing an approach for diagnosing potential metabolic bottlenecks in a faster and simpler manner is of great significance to accelerate cell factories construction. The cell-free reaction system based on cell lysates can transfer metabolic reactions from in vivo to in vitro, providing a flexible access to directly change protein and metabolite variables, thus provides a potential solution for rapid identification of bottlenecks. Here, bottleneck diagnosis of the N-acetylneuraminic acid (NeuAc) biosynthesis pathway in industrially important chassis microorganism Bacillus subtilis was performed using cell-free synthesis system. Specifically, a highly efficient B. subtilis cell-free system for NeuAc de novo synthesis was firstly constructed, which had a 305-fold NeuAc synthesis rate than that in vivo and enabled fast pathway dynamics analysis. Next, through the addition of all potential key intermediates in combination with substrate glucose respectively, it was found that insufficient phosphoenolpyruvate supply was one of the NeuAc pathway bottlenecks. Rational in vivo metabolic engineering of NeuAc-producing B. subtilis was further performed to eliminate the bottleneck. By down-regulating the expression level of pyruvate kinase throughout the growth phase or only in the stationary phase using inhibitory N-terminal coding sequences (NCSs) and growth-dependent regulatory NCSs respectively, the maximal NeuAc titer increased 2.0-fold. Our study provides a rapid method for bottleneck diagnosis, which may help to accelerate the cycle of design, build, test and learn cycle for metabolic engineering.

Effect of water-sediment regulation of the Xiaolangdi reservoir on the concentrations, characteristics, and fluxes of suspended sediment and organic carbon in the Yellow River.

Water-sediment regulation (WSR) of the Xiaolangdi Reservoir in the Yellow River is different from other water conservancy projects, with sediment resuspending along the river downstream of the reservoir during water regulation while some suspended sediment depositing during sediment regulation. In this study, samples were collected before, during, and after WSR to investigate the effect of WSR on the suspended sediment and organic carbon downstream of the reservoir. The suspended sediment concentration ([SPS]) increased with the river flow velocity (V) as a power function ([SPS]=1.348V(2.519)) during the three periods. The suspended sediment grain size decreased along the river during water and sediment regulations and after WSR; they were generally below 200µm with the fine particles (<50µm) of 68.0%-93.7% and positively correlated with the flow velocity. The black carbon content in suspended sediment elevated along the river during both water and sediment regulations, and it increased with 2-50µm fraction during water regulation and with <2µm fraction during sediment regulation, suggesting that black carbon mainly exists in fine particles and is influenced by both suspended sediment source and characteristics. There was no significant difference in dissolved organic carbon (DOC) concentration during water regulation, sediment regulation, and after WSR, inferring that the effect of sediment resuspension/deposition on DOC concentration was insignificant. The contribution of DOC flux (27.3%) during WSR period to the annual flux was comparable to that (22.6%) of water, but lower than the sediment (32.5%) and particulate organic carbon (POC) (49.5%). This study suggests that WSR will exert significant influence on the concentrations, characteristics and fluxes of POC (p<0.05) and sediment (p<0.05) but have no significant influence on DOC (p>0.1) of the Yellow River.

A Formate Dehydrogenase Confers Tolerance to Aluminum and Low pH.

Formate dehydrogenase (FDH) is involved in various higher plant abiotic stress responses. Here, we investigated the role of rice bean (Vigna umbellata) VuFDH in Al and low pH (H(+)) tolerance. Screening of various potential substrates for the VuFDH protein demonstrated that it functions as a formate dehydrogenase. Quantitative reverse transcription-PCR and histochemical analysis showed that the expression of VuFDH is induced in rice bean root tips by Al or H(+) stresses. Fluorescence microscopic observation of VuFDH-GFP in transgenic Arabidopsis plants indicated that VuFDH is localized in the mitochondria. Accumulation of formate is induced by Al and H(+) stress in rice bean root tips, and exogenous application of formate increases internal formate content that results in the inhibition of root elongation and induction of VuFDH expression, suggesting that formate accumulation is involved in both H(+)- and Al-induced root growth inhibition. Over-expression of VuFDH in tobacco (Nicotiana tabacum) results in decreased sensitivity to Al and H(+) stress due to less production of formate in the transgenic tobacco lines under Al and H(+) stresses. Moreover, NtMATE and NtALS3 expression showed no changes versus wild type in these over-expression lines, suggesting that herein known Al-resistant mechanisms are not involved. Thus, the increased Al tolerance of VuFDH over-expression lines is likely attributable to their decreased Al-induced formate production. Taken together, our findings advance understanding of higher plant Al toxicity mechanisms, and suggest a possible new route toward the improvement of plant performance in acidic soils, where Al toxicity and H(+) stress coexist.

Is dynamic autocrine insulin signaling possible? A mathematical model predicts picomolar concentrations of extracellular monomeric insulin within human pancreatic islets.

Insulin signaling is essential for ß-cell survival and proliferation in vivo. Insulin also has potent mitogenic and anti-apoptotic actions on cultured ß-cells, with maximum effect in the high picomolar range and diminishing effect at high nanomolar doses. In order to understand whether these effects of insulin are constitutive or can be subjected to physiological modulation, it is essential to estimate the extracellular concentration of monomeric insulin within an intact islet. Unfortunately, the in vivo concentration of insulin monomers within the islet cannot be measured directly with current technology. Here, we present the first mathematical model designed to estimate the levels of monomeric insulin within the islet extracellular space. Insulin is released as insoluble crystals that exhibit a delayed dissociation into hexamers, dimers, and eventually monomers, which only then can act as signaling ligands. The rates at which different forms of insulin dissolve in vivo have been estimated from studies of peripheral insulin injection sites. We used this and other information to formulate a mathematical model to estimate the local insulin concentration within a single islet as a function of glucose. Model parameters were estimated from existing literature. Components of the model were validated using experimental data, if available. Model analysis predicted that the majority of monomeric insulin in the islet is that which has been returned from the periphery, and the concentration of intra-islet monomeric insulin varies from ~50-300 pM when glucose is in the physiological range. Thus, our results suggest that the local concentration of monomeric insulin within the islet is in the picomolar 'sweet spot' range of insulin doses that activate the insulin receptor and have the most potent effects on ß-cells in vitro. Together with experimental data, these estimations support the concept that autocrine/paracrine insulin signalling within the islet is dynamic, rather than constitutive and saturated.

The range of time delay and the global stability of the equilibrium for an IVGTT model.

Diabetes mellitus has become a prevalent disease in the world. Diagnostic protocol for the onset of diabetes mellitus is the initial step in the treatments. The intravenous glucose tolerance test (IVGTT) has been considered as the most accurate method to determine the insulin sensitivity and glucose effectiveness. It is well known that there exists a time delay in insulin secretion stimulated by the elevated glucose concentration level. However, the range of the length of the delay in the existing IVGTT models are not fully discussed and thus in many cases the time delay may be assigned to a value out of its reasonable range. In addition, several attempts had been made to determine when the unique equilibrium point is globally asymptotically stable. However, all these conditions are delay-independent. In this paper, we discuss the range of the time delay and provide easy-to-check delay-dependent conditions for the global asymptotic stability of the equilibrium point for a recent IVGTT model through Liapunov function approach. Estimates of the upper bound of the delay for global stability are given in corollaries. In addition, the numerical simulation in this paper is fully incorporated with functional initial conditions, which is natural and more appropriate in delay differential equation systems.