Impact of random demand on dual-channel supply chain profits.

Impact of random demand on dual-channel supply chain profits.</p

The influence of random demand on the optimal decision price.

The influence of random demand on the optimal decision price.</p

Impact of tariff change and export tax rebate on the profit of the dual-channel supply chain.

Impact of tariff change and export tax rebate on the profit of the dual-channel supply chain.</p

The impact of random demand on dual-channel demand.

The impact of random demand on dual-channel demand.</p

Effect of tariff changes and export tax rebate on the optimal decision price.

Effect of tariff changes and export tax rebate on the optimal decision price.</p

Impact of tariff changes and export tax rebate on dual-channel demand.

Impact of tariff changes and export tax rebate on dual-channel demand.</p

Green synthesis and characterization of gold nanoparticles from <i>Pholiota adiposa</i> and their anticancer effects on hepatic carcinoma

Gold nanoparticles (AuNPs) were successfully fabricated by Pholiota adiposa polysaccharide (PAP-1a) without employing any other chemicals. The physical and chemical properties of PAP-AuNPs were determined using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDXR), Fourier-transform infrared spectroscopy (FT-IR), and atomic force microscopy (AFM). In an attempt to analyze the immune regulation, antitumor effect, and biological safety, the production of NO and TNF-α, IL-12p70, and IL-1β from RAW264.7 as well as the proliferation of RAW264.7 were detected in vitro. Flow cytometry was conducted to determine the ratio of the CD4+/CD8+ cell in peripheral blood and immunohistochemical analysis involving hematoxylin and eosin (H&E) and proliferating cell nuclear antigen (PCNA) staining were conducted in vivo. The results of this study showed that PAP-AuNPs had a significantly improved immune regulation and anti-tumor effect in comparison to PAP-1a alone. PAP-AuNPs showed no toxicity both in vivo and in vitro. This study demonstrates a useful application of PAP-AuNPs as a novel nanomedicine for hepatic carcinoma.</p

Image_3_Alpha-linolenic acid pretreatment alleviates NETs-induced alveolar macrophage pyroptosis by inhibiting pyrin inflammasome activation in a mouse model of sepsis-induced ALI/ARDS.tif

BackgroundNeutrophil extracellular traps (NETs) can cause acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) by inducing macrophage pyroptosis. The purpose of this study was to find out whether pretreatment of alpha-linolenic acid (ALA) could inhibit NETs-induced macrophage pyroptosis in sepsis-induced ALI/ARDS, as well as to identify which inflammasome is involved in this process.MethodsLPS was instilled into the trachea to establish sepsis-induced ALI/ARDS in a mouse model. ​Lung injury was assessed by microscopic examination of lung tissue after hematoxylin and eosin staining, pathology score, and bronchoalveolar lavage fluid (BALF) total protein concentration. The level of NETs in lung tissue was detected by MPO-DNA ELISA. Purified NETs, extracted from peritoneal neutrophils, induced macrophage pyroptosis in vitro. Expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β in the lung tissue and bone marrow-derived macrophages (BMDMs) were determined by western blotting or ELISA. Specks of Pyrin/ASC were examined by confocal immunofluorescence microscopy. Mefv (Pyrin)-/- mice were used to study the role of Pyrin in the process of sepsis-induced ALI/ARDS.ResultsALA alleviated LPS-induced lung injury. ALA reduced the level of NETs, pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC), and IL-1β in the lung tissue of sepsis mice. In vitro, NETs increased the expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β significantly in BMDMs. Pyrin protein was found to be higher and form the inflammasome with ASC in NETs challenged-BMDMs. Knockout of Mefv (Pyrin) gene fully restored the increased expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β in vitro and in vivo. Lung injury was alleviated significantly in Mefv (Pyrin)-/- mice as well.​ ALA suppresses all the NETs-induced changes as mentioned above.ConclusionOur study is the first to demonstrate Pyrin inflammasome driving NETs-induced macrophage pyroptosis, and ALA may reduce ALI/ARDS by inhibiting the activation of the Pyrin inflammasome-driven macrophage pyroptosis.</p

Manufacturing Multienzymatic Complex Reactors <i>In Vivo</i> by Self-Assembly To Improve the Biosynthesis of Itaconic Acid in <i>Escherichia coli</i>

The self-assembly of multienzyme into bioreactors is of extensive interest to spatially regulate valuable reactions. Despite the important progresses achieved, methods to precisely manufacture multienzymatic complex reactors (MECRs) are still poorly proposed both <i>in vivo</i> and <i>in vitro</i>, particularly for more than three biocatalytically relevant enzymes. Here, we developed a sequential self-assembly system to form multitude MECRs involving three enzymes in the itaconic acid (IA) pathway with two pairs of protein–peptide interactions. The MECRs were identified as nanoscale particle-like structures when self-assembled <i>in vitro</i> and produced higher IA production than the unassembled and linearly assembled systems when applied <i>in vivo</i> coupling with CRISPR-Cas9 based metabolic engineering. This work provides novel insights into the construction of multifarious multienzyme complex into bioreactors by the self-assembly strategy for multistep cascades to sequentially control metabolic fluxes inside cells

Image_1_Alpha-linolenic acid pretreatment alleviates NETs-induced alveolar macrophage pyroptosis by inhibiting pyrin inflammasome activation in a mouse model of sepsis-induced ALI/ARDS.tif

BackgroundNeutrophil extracellular traps (NETs) can cause acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) by inducing macrophage pyroptosis. The purpose of this study was to find out whether pretreatment of alpha-linolenic acid (ALA) could inhibit NETs-induced macrophage pyroptosis in sepsis-induced ALI/ARDS, as well as to identify which inflammasome is involved in this process.MethodsLPS was instilled into the trachea to establish sepsis-induced ALI/ARDS in a mouse model. ​Lung injury was assessed by microscopic examination of lung tissue after hematoxylin and eosin staining, pathology score, and bronchoalveolar lavage fluid (BALF) total protein concentration. The level of NETs in lung tissue was detected by MPO-DNA ELISA. Purified NETs, extracted from peritoneal neutrophils, induced macrophage pyroptosis in vitro. Expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β in the lung tissue and bone marrow-derived macrophages (BMDMs) were determined by western blotting or ELISA. Specks of Pyrin/ASC were examined by confocal immunofluorescence microscopy. Mefv (Pyrin)-/- mice were used to study the role of Pyrin in the process of sepsis-induced ALI/ARDS.ResultsALA alleviated LPS-induced lung injury. ALA reduced the level of NETs, pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC), and IL-1β in the lung tissue of sepsis mice. In vitro, NETs increased the expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β significantly in BMDMs. Pyrin protein was found to be higher and form the inflammasome with ASC in NETs challenged-BMDMs. Knockout of Mefv (Pyrin) gene fully restored the increased expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1β in vitro and in vivo. Lung injury was alleviated significantly in Mefv (Pyrin)-/- mice as well.​ ALA suppresses all the NETs-induced changes as mentioned above.ConclusionOur study is the first to demonstrate Pyrin inflammasome driving NETs-induced macrophage pyroptosis, and ALA may reduce ALI/ARDS by inhibiting the activation of the Pyrin inflammasome-driven macrophage pyroptosis.</p