Qikun Cheng,Mingzhi Xie,Hangjie Ying,Cuiyuan Jin,Lijun Yang,Dong Ma,Shumao Cui,Liyun Shi
Although evidence indicates that the incidence of viral pneumonia is causally associated with disturbances in the microbiome and hypoxic status in the gut, there is currently no effective strategy for the co-delivery of probiotics and oxygen through oral administration. We therefore created a spatiotemporal biosystem by preparing Bacillus coagulans (BC) probiotic spores, coating them with a polydopamine/chitosan (PCS) nanocoating, and conjugating them with CaO 2 nanoparticles. CaO 2 @PCS@BC spore rapidly diffused across the mucus layer spatially while released oxygen followed by bacterial proliferation temporally, thereby significantly enhancing the oxygen levels within intestinal epithelial cells by effectively overcoming the barriers posed by mucus layer and oxygen gradient. In a mouse model of H1N1 infection, we demonstrated that oral CaO 2 @PCS@BC spore treatment reversed gut dysbiosis, alleviated intestinal hypoxia, improved metabolism, restored immune balance, and mitigated symptoms of viral pneumonia. Finally, CaO 2 @PCS@BC spore facilitated spatial recovery and preserved the anaerobic environment of the gut lumen, suggesting significant biosafety. In conlusion, we have developed a spatiotemporal biosystem that effectively co-delivers probiotics and oxygen to mitigate intestinal dysbiosis in the treatment of viral pneumonia through the gut-lung axis.
Carbohydrate microarrays provide a powerful tool for high-throughput analysis of carbohydrate-mediated interactions. In this work, they were fabricated on poly(2-hydroxyethyl methacrylate) (pHEMA)-cyanuric chloride (CC)-modified substrates for the analysis of carbohydrate–lectin interactions. The pHEMA polymer provides an anti-fouling surface and the CC linker allows the covalent immobilization of intact carbohydrates. Carbohydrates of different sizes (mannose, glucose, galactose, maltose, and dextran) were successfully immobilized on the proposed substrates and their recognition specificity with concanavalin A (ConA) was highly conserved. Compared with a 4-hydroxyphenylacetic acid (HPA)-CC-based microarray, the proposed pHEMA-CC-based microarray exhibits better anti-nonspecific adsorption ability, higher carbohydrate loading capability, stronger multivalent recognition and a lower limit of detection for carbohydrate and lectin without any further signal amplification. The application of the proposed microarray was validated by studying carbohydrate-influenza A virus H1N1 hemagglutinin interactions and fabricating microarrays containing carbohydrates with different properties. It is possible to extend it to study interactions of more carbohydrates and different lectins, and it will meet the wider needs in bioanalytical and biomedical application.
In order to meet the demand of analyzing low concentrations of DNA with high sensitivity, herein, a magnetic separated-type fluorescent biosensor has been constructed for ultrasensitive DNA assay based on chemically driven redox-cycling system. In this study, the substrate o-phenylenediamine dihydrochlorlde (OPD) could be oxidized to produce 2, 3-diaminophenazine (DAP) with strong fluorescence emission at 555 nm. In the chemically driven redox-cycling system, Cu2+ oxidized OPD to yield DAP and Cu+/Cu0. On one hand, the produced Cu0 could further oxidize OPD to form DAP. But on the other, the generated Cu+ could react with newly imported H2O2 to undergo a Fenton-like reaction to form hydroxyl radicals (•OH) and Cu2+ ion. The reproduced Cu2+ ion and generated •OH could in turn oxidize OPD to form more DAP, which touching off a chemically driven chemical redox-cycling amplification reaction. By leveraging of the magnetic separation-mode, the chemically driven redox-cycling strategy allowed quantitative detection of H1N1, exhibiting a linear ranging from 1 pM to 1 nM with a low limit of detection of 300 fM. The magnetic separation-mode could effectively minimize the background signal to obtain greatly improved sensitivity. It’s promising that the chemically driven redox-cycling strategy would provide a novel way in the fields of biosensing and biological samples assay.
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