How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a ...potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs) are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated
. However, none of current systems for
differentiation of MDSCs have successfully achieved long-term immune tolerance. Herein, we combined dexamethasone (Dex), which is a classic immune regulatory drug in the clinic, with common MDSCs inducing cytokine granulocyte macrophage colony stimulating factor (GM-CSF) to generate MDSCs
. Addition of Dex into GM-CSF system specifically increased the number of CD11b
Gr-1
MDSCs with an enhanced immunosuppressive function
. Adoptive transfer of these MDSCs significantly prolonged heart allograft survival and also favored the expansion of regulatory T cells
. Mechanistic studies showed that inducible nitric oxide sythase (iNOS) signaling was required for MDSCs in the control of T-cell response and glucocorticoid receptor (GR) signaling played a critical role in the recruitment of transferred MDSCs into allograft through upregulating CXCR2 expression on MDSCs. Blockade of GR signaling with its specific inhibitor or genetic deletion of iNOS reversed the protective effect of Dex-induced MDSCs on allograft rejection. Together, our results indicated that co-application of Dex and GM-CSF may be a new and important strategy for the induction of potent MDSCs to achieve immune tolerance in organ transplantation.
Microbial induced carbonate precipitation (MICP) is a natural bio-mediated process, which has been explored for soil stabilization and heavy metals immobilization in soil and groundwater. Previous ...studies have shown that MICP is capable of immobilizing various heavy metals including lead (Pb). However, most studies focus merely on the immobilization of heavy metals with relatively low concentration. This study: (1) presents results of an investigation into the toxic effects of Pb on bacterial activity and immobilization efficiency within a wide range of Pb concentrations; and (2) identifies controlling biotic and abiotic factors of Pb immobilization by MICP. In the first series of tests, bacterial strains (Sporosarcina pasteurii) are inoculated into nutrient solutions containing 0–50 mM Pb(NO3)2 and incubated at 30 °C. Biochemical parameters are measured over time, which include pH, electrical conductivity, urease activity, and viable cell number. In the second series of tests, grown bacterial strains are mixed with urea, calcium salts and Pb(NO3)2 in solution. Viable cell number, produced ammonium concentration, aqueous Pb concentration of the mixed solution, and total precipitation mass are measured. The results show that the presence of Pb has marginal effect on bacterial growth and associated urease activity at Pb concentration < 30 mM. The calcium source and initial bacteria concentration are found to remarkably influence Pb immobilization efficiency in terms of Pb removal percentage. Supplementary geochemical simulation results indicate that the Pb immobilization mechanisms includes abiotic precipitation, biotic precipitation and bio-sorption.
Display omitted
•Pb contaminants are immobilized by microbial induced carbonate precipitation.•Pb has toxic effects on bacterial activity and immobilization efficiency.•Abiotic and biotic precipitation and bio-sorption are immobilization mechanisms.
Inflammation is a complex physiological process that poses a serious threat to people's health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is ...lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/β and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.
The selection of renewable energy storage technology has important significance for maintaining the supply and demand balance of renewable energy, reducing the application cost of new energy and ...accelerating the pace of the new energy revolution. Different from the existing research which regards the selection of energy storage technology as a multi-criteria decision-making problem, it is called as a multi-criteria group decision-making problem in this study. This paper defines the dual hesitant Pythagorean fuzzy linguistic term sets and proposes a multi criteria decision support framework for renewable energy storage technology selection from the perspective of group decision-making. Then, the empirical example considers the case of energy storage technology selection in Jiangsu Province, China. The proposed method is exploited to analyze the robustness of the results and its comparison to other methods. The case study shoes that it can help the managers scientifically choose more suitable renewable energy storage technology alternatives.
Display omitted
•Dual hesitant Pythagorean fuzzy linguistic term sets are defined and applied for information expression.•The group decision consensus approach for dual hesitant Pythagorean fuzzy linguistic term sets is proposed.•Renewable energy storage technologies are assessed.•Technical, economic, environmental and social criteria are considered.•A multi-component composite energy storage system is recommended to users.
To ensure the safe operation of highway traffic lines, given the imperfect feature extraction of existing road pit defect detection models and the practicability of detection equipment, this paper ...proposes a lightweight target detection algorithm with enhanced feature extraction based on the YOLO (You Only Look Once) algorithm. The BIFPN (Bidirectional Feature Pyramid Network) network structure is used for multi-scale feature fusion to enhance the feature extraction ability, and Varifocal Loss is used to optimize the sample imbalance problem, which improves the accuracy of road defect target detection. In the evaluation test of the model in the constructed PCD1 (Pavement Check Dataset) dataset, the mAP@.5 (mean Average Precision when IoU = 0.5) of the BV-YOLOv5S (BiFPN Varifocal Loss-YOLOv5S) model increased by 4.1%, 3%, and 0.9%, respectively, compared with the YOLOv3-tiny, YOLOv5S, and B-YOLOv5S (BiFPN-YOLOv5S; BV-YOLOv5S does not use the Improved Focal Loss function) models. Through the analysis and comparison of experimental results, it is proved that the proposed BV-YOLOv5S network model performs better and is more reliable in the detection of pavement defects and can meet the needs of road safety detection projects with high real-time and flexibility requirements.
Sepsis remains a leading cause of death worldwide, despite advances in critical care, and understanding of the pathophysiology and treatment strategies. No specific therapy or drugs are available for ...sepsis. Neutrophils play a critical role in controlling infection under normal conditions, and it is suggested that their migration and antimicrobial activity are impaired during sepsis which contribute to the dysregulation of immune responses. Recent studies further demonstrated that interruption or reversal of the impaired migration and antimicrobial function of neutrophils improves the outcome of sepsis in animal models. In this review, we provide an overview of the associated mediators and signal pathways involved which govern the survival, migration and antimicrobial function of neutrophils in sepsis, and discuss the potential of neutrophils as a target to specifically diagnose and/or predict the outcome of sepsis.
Green technology innovation is an important means to break out of the constraints of resources and the environment, enhance the competitiveness of enterprises, and achieve the upgrading of industrial ...structures, and promote high-quality economic growth. In order to realize the overall improvement of the green technology innovation capability of Chinese enterprises, it is necessary to measure the efficiency of industrial enterprises' green technology innovation and explore their regional differences. In this paper, from the perspective of a two-stage innovation value chain, by introducing the industrial carbon emissions per unit of Gross Domestic Product (GDP) and the "three wastes" pollutants into the research framework of green technology innovation efficiency, we established a novel green innovation efficiency evaluation indicator system for industrial enterprises. Furthermore, we used a two-stage network DEA with shared input to measure the efficiency of regional enterprises' green technology innovation and explored the regional differences in industrial enterprises' green technology R&D and the efficiency of green technology achievement transformation. Finally, we provide some suggestions for improving China's industrial enterprises' green innovation efficiency, so that they can ameliorate the significant regional imbalances and differences and realize high-quality economic growth.
PDF
