ABSTRACT
DNA origami is capable of spatially organizing molecules into sophisticated geometric patterns with nanometric precision. Here we describe a reconfigurable, two-dimensional DNA origami with geometrically patterned CD95 ligands that regulates immune cell signalling to alleviate rheumatoid arthritis. In response to pH changes, the device reversibly transforms from a closed to an open configuration, displaying a hexagonal pattern of CD95 ligands with ~10 nm intermolecular spacing, precisely mirroring the spatial arrangement of CD95 receptor clusters on the surface of immune cells. In a collagen-induced arthritis mouse model, DNA origami elicits robust and selective activation of CD95 death-inducing signalling in activated immune cells located in inflamed synovial tissues. Such localized immune tolerance ameliorates joint damage with no noticeable side effects. This device allows for the precise spatial control of cellular signalling, expanding our understanding of ligand-receptor interactions and is a promising platform for the development of pharmacological interventions targeting these interactions.
Subject(s)
Arthritis, Rheumatoid , DNA , Immune Tolerance , Signal Transduction , fas Receptor , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Animals , DNA/chemistry , DNA/immunology , Mice , fas Receptor/metabolism , fas Receptor/immunology , Fas Ligand Protein/metabolism , Fas Ligand Protein/immunology , HumansABSTRACT
Chinese horse bean-chili-paste (CHCP), a fermented condiment in China, is traditionally manufactured through naturally spontaneous semi-solid fermentation procedures without intentionally inoculated microorganisms. The aim of this study was to investigate the effect on microbiota and quality variations during CHCP fermentation by inoculation of selected autochthonous microorganisms Bacillus amyloliquefaciens and Candida versatilis. The results showed that relative abundance of Bacillus in the samples inoculated with B. amyloliquefaciens were increased from about 0.6% to almost 25%, and the batches bio-augmented with C. versatilis exhibited clearly 0.7 Lg copies/g higher biomass than that of the other samples. By bio-augmentation, six enzyme activities, namely acid protease, leucine aminopeptidase, α-amylase, cellulose, ß-glucosidase and esterase, were considerably enhanced. As a result, inoculation of these two strains exhibited significant effect on the volatile profiles of CHCP. B. amyloliquefaciens herein was found to contribute mainly to the accumulation of acids, sulfur-containing compounds and pyrazines, whereas C. versatilis was considerably associated with the formation of alcohols, esters and phenols. This study proved that combination of B. amyloliquefaciens and C. versatilis could obtain more extensive aroma profiles, especially for the enrichment of miso-like and fruity flavors, which could provide a guideline for the tailored control of CHCP fermentation process.
Subject(s)
Bacillus amyloliquefaciens/metabolism , Flavoring Agents/metabolism , Microbiota , Saccharomycetales/metabolism , Vicia faba/microbiology , China , Condiments/analysis , Condiments/microbiology , Fermentation , Flavoring Agents/analysis , Odorants/analysis , Volatile Organic Compounds/analysis , Volatile Organic Compounds/metabolismABSTRACT
BACKGROUND: Esters are indispensable aroma compounds and contribute significantly to the fruity aromas in fermented condiments. The ester synthesis activity and pathways of Bacillus licheniformis, Candida etchellsii, and Zygosaccharomyces rouxii, isolated from Chinese horse bean chili-paste (CHCP), were investigated. Chemical buffer models containing esterification and alcoholysis systems inoculated with extracellular extracts of these three strains were established. RESULTS: The ester synthesis activity of C. etchellsii was stronger than that of the other two strains. Zygosaccharomyces rouxii could synthesize acetate esters via esterification, whereas the biosynthesis pathways of B. licheniformis and C. etchellsii were esterification and alcoholysis. Esterification exhibited relatively high activity at pH 4, whereas alcoholysis activity improved with an increase in the pH from 4 to 8. Candida etchellsii could synthesize C6 -C8 of acetate esters, and its activity improved with the number of alcohol carbon atoms. These three strains could synthesize C10 -C18 of ethyl esters. Their ethyl ester synthesis activity decreased with the aliphatic acid carbon number. CONCLUSION: Candida etchellsii has the potential to be used in CHCP fermentation to accumulate esters and improve flavor compared with the other two strains. This research is helpful in explaining the mechanism of ester synthesis in fermented condiments. © 2021 Society of Chemical Industry.
