Indoleamine 2,3-dioxygenase (IDO) has emerged as a pivotal enzyme for mediating immune tolerance. Because IDO metabolizes tryptophan into kynurenine, the plasma kynurenine/tryptophan (Kyn/Trp) ratio has been widely used as a marker of systemic IDO. Here, we evaluated the clinical value of using the plasma Kyn/Trp ratio to estimate cell-mediated immune responses to tuberculin skin testing and risk of new bacterial infection. We also compared the Kyn/Trp ratio to a novel IDO marker, the IDO median fluorescence index (MFI) of peripheral blood mononuclear cells, which was determined by flow cytometry. In 228 patients from two hemodialysis centers, the two IDO markers were higher in patients than in healthy controls but were not correlated with each other. In vitro experiments demonstrated that peripheral blood mononuclear cells could not metabolize tryptophan into kynurenine, indicating that the increased Kyn/Trp ratio was IDO-independent. Skin induration diameters of tuberculin skin testing were correlated with the IDO MFI (negatively), but not the Kyn/Trp ratio. Further, in a 24-month prospective cohort, the Kyn/Trp ratio was not correlated with clinical infection. Alternatively, patients with a higher IDO MFI had a lower accumulative infection-free survival rate. Using a Cox proportional hazard model, it was also revealed that a higher IDO MFI was significantly associated with new bacterial infection. Taken together, these results indicate that the Kyn/Trp ratio is not a reliable circulating IDO marker in hemodialysis patients. However, the IDO MFI reflects an immunocompromised state and thus might be a potential clinical marker of bacterial infection.

The simultaneous analysis of diversified biomarkers with high sensitivity and in a point-of-care (POC) manner is of great significance for facile and early cancer diagnosis. Herein, we develop a target amplification-assisted ratiometric fluorescence assay (TARFA) platform integrating the dual-amplification strategy and colorimetric readout technology for sensitive and specific detection of two malignancy-associated biomarkers. Meanwhile, the NIR-excited alkaline-earth sulfide nanodots (ASNDs) with an ultrasmall (<10 nm) diameter and tunable emission wavelength are employed to replace commonly UV/visible light-excited fluorescent labels to minimize background interference from the sample matrix. Unique advantages of the ASNDs, together with superiority of consecutive signal amplification of enzymatic target recycling (ETR) and hybridization chain reaction (HCR), realize the pg/mL-range detection limit in specifically recognizing the vascular endothelial growth factor (VEGF) and soluble interleukin-6 receptors (sIL-6R). The combination detection of the dual analyte exhibits an improved sensitivity for cancer diagnosis. The addition of the target biomarkers leads to an increasingly ratiometric RGB signal, and quantification based on the ratio-dependent signal is more reliable rather than measuring the absolute RGB signals. Moreover, perceptible color transformation makes the TARFA platform competent for visual analysis of the target analytes as convenient as reading the pH indicator strip, and hue-based image analysis also improves the method with fine precision by quantitatively identifying the visual color. This work provides a new kind of NIR-excited aptasensing platform with a low detection limit, high throughput, and great portability, which also highlights the potential of the ASNDs in biomolecular fluorescent labeling.

Abstract:Purpose: T he purpose of this paper is to set up the coordinating mechanism for a decentralized distribution system consisting of a manufacturer and multiple independent retailers by means of contracts. It is in the two-stage supply chain system that all retailers sell an identical product made by the manufacturer and determine their order quantities which directly affect the expected profit of the supply chain with random demand.Design/methodology/approach: First comparison of the optimal order quantities in the centralized and decentralized system shows that the supply chain needs coordination. Then the coordination model is given based on buyback cost and compensation benefit. Finally the coordination mechanism is set up in which the manufacturer as the leader uses a buyback policy to incentive these retailers and the retailers pay profit returns to compensate the manufacturer. Findings:The results of a numerical example show that the perfect supply chain coordination and the flexible allocation of the profit can be achieved in the multi-retailer supply chain by the buyback and compensation contracts. Research limitations:The results based on assumptions might not completely hold in practice and the paper only focuses on studying a single product in two-stage supply chain.-203-Journal of Industrial Engineering and Management -http://dx.doi.org/10.3926/jiem.1303Practical implications: The coordination mechanism is applicable to a realistic supply chain under a private information setting and the research results is the foundation of further developing the coordination mechanism for a realistic multi-stage supply chain system with more products. Originality/value: This paper focused on studying the coordination mechanism for a decentralized multi-retailer supply chain by the joint application of the buyback and compensation contracts. Furthermore the perfect supply chain coordination and the flexible allocation of the profit are achieved.

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