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      Multifunctional carbonized nanogels to treat lethal acute hepatopancreatic necrosis disease

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          Abstract

          Background

          Shrimp aquaculture has suffered huge economic losses over the past decade due to the outbreak of acute hepatopancreatic necrosis disease (AHPND), which is mainly caused by the bacteria Vibrio parahaemolyticus ( V. parahaemolyticus) with the virulence pVA1 plasmid, which encodes a secretory photorhabdus insect-related (Pir) toxin composed of PirA and PirB proteins. The Pir toxin mainly attacks the hepatopancreas, a major metabolic organ in shrimp, thereby causing necrosis and loss of function. The pandemic of antibiotic-resistant strains makes the impact worse.

          Methods

          Mild pyrolysis of a mixture of polysaccharide dextran 70 and the crosslinker 1,8-diaminooctane at 180 ℃ for 3 h to form carbonized nanogels (DAO/DEX-CNGs) through controlled cross-linking and carbonization. The multifunctional therapeutic CNGs inherit nanogel-like structures and functional groups from their precursor molecules.

          Results

          DAO/DEX-CNGs manifest broad-spectrum antibacterial activity against Vibrio parahaemolyticus responsible for AHPND and even multiple drug-resistant strains. The polymer-like structures and functional groups on graphitic-carbon within the CNGs exhibit multiple treatment effects, including disruption of bacterial membranes, elevating bacterial oxidative stress, and neutralization of PirAB toxins. The inhibition of Vibrio in the midgut of infected shrimp, protection of hepatopancreas tissue from Pir toxin, and suppressing overstimulation of the immune system in severe V. parahaemolyticus infection, revealing that CNGs can effectively guard shrimp from Vibrio invasion. Moreover, shrimps fed with DAO/DEX-CNGs were carefully examined, such as the expression of the immune-related genes, hepatopancreas biopsy, and intestinal microbiota. Few adverse effects on shrimps were observed.

          Conclusion

          Our work proposes brand-new applications of multifunctional carbon-based nanomaterials as efficient anti- Vibrio agents in the aquatic industry that hold great potential as feed additives to reduce antibiotic overuse in aquaculture.

          Graphical Abstract

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12951-021-01194-8.

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          This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
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              Food animals and antimicrobials: impacts on human health.

              Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the "precautionary principle." Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans-directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.
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                Author and article information

                Contributors
                huanging@ntou.edu.tw
                hanjia@ntou.edu.tw
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                24 December 2021
                24 December 2021
                2021
                : 19
                : 448
                Affiliations
                [1 ]GRID grid.260664.0, ISNI 0000 0001 0313 3026, Department of Bioscience and Biotechnology, , National Taiwan Ocean University, ; Keelung, 202301 Taiwan
                [2 ]GRID grid.260664.0, ISNI 0000 0001 0313 3026, Doctoral Degree Program in Marine Biotechnology, , National Taiwan Ocean University, ; Keelung, 202301 Taiwan
                [3 ]GRID grid.260664.0, ISNI 0000 0001 0313 3026, Department of Aquaculture, , National Taiwan Ocean University, ; Keelung, 202301 Taiwan
                [4 ]GRID grid.14848.31, ISNI 0000 0001 2292 3357, Department of Chemistry, , Université de Montréal, ; Montreal, QC H3C 3J7 Canada
                [5 ]GRID grid.19188.39, ISNI 0000 0004 0546 0241, Department of Chemistry, , National Taiwan University, ; Taipei, 10617 Taiwan
                [6 ]GRID grid.19188.39, ISNI 0000 0004 0546 0241, Department of Veterinary Medicine, School of Veterinary Medicine, , National Taiwan University, ; Taipei, 10617 Taiwan
                [7 ]GRID grid.260664.0, ISNI 0000 0001 0313 3026, Institute of Marine Biology, , National Taiwan Ocean University, ; Keelung, 202301 Taiwan
                [8 ]GRID grid.260664.0, ISNI 0000 0001 0313 3026, Center of Excellence for the Oceans, , National Taiwan Ocean University, ; Keelung, 202301 Taiwan
                [9 ]GRID grid.412019.f, ISNI 0000 0000 9476 5696, School of Pharmacy, College of Pharmacy, , Kaohsiung Medical University, ; Kaohsiung, 80708 Taiwan
                Author information
                http://orcid.org/0000-0002-0363-1129
                Article
                1194
                10.1186/s12951-021-01194-8
                8710021
                34952588
                f2926e53-f255-4914-8c28-606f71e70e28
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 27 September 2021
                : 8 December 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan;
                Award ID: 110-2221-E-019-001
                Award ID: 110-2811-M-019-501
                Award ID: 107-2627-M-007-007
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Biotechnology
                carbon nanogels,antimicrobial agents,antibiotic overuse,vibrio,toxin neutralization
                Biotechnology
                carbon nanogels, antimicrobial agents, antibiotic overuse, vibrio, toxin neutralization

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