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The dual antimicrobial and immunomodulatory roles of host defense peptides and their applications in animal production 被引量:2
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作者 Di Wu Linglong Fu +1 位作者 Weizhang Wen Na Dong 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2023年第2期501-514,共14页
Host defense peptides(HDPs)are small molecules with broad-spectrum antimicrobial activities against infectious bacteria,viruses,and fungi.Increasing evidence suggests that HDPs can also indirectly protect hosts by mod... Host defense peptides(HDPs)are small molecules with broad-spectrum antimicrobial activities against infectious bacteria,viruses,and fungi.Increasing evidence suggests that HDPs can also indirectly protect hosts by modulating their immune responses.Due to these dual roles,HDPs have been considered one of the most promising antibiotic substitutes to improve growth performance,intestinal health,and immunity in farm animals.This review describes the antimicrobial and immunomodulatory roles of host defense peptides and their recent applications in animal production. 展开更多
关键词 Antimicrobials host defense peptides IMMUNOMODULATION POULTRY RUMINANTS SWINE
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Geographically Distinct Expression Profile of Host Defense Peptides in the Skin of the Chinese Odorous Frog, Odorrana margaretae
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作者 Guiying LING Li LI +3 位作者 Jiuxiang GAO Haining YU Yipeng WANG Jiang ZHOU 《Asian Herpetological Research》 SCIE 2013年第4期288-297,共10页
Odorrana margaretae (Anura: Ranidae) is widely distributed in the southern provinces of China. Previously, 72 antimicrobial peptides (AMPs) belonging to 21 families were identified from the skin of O. margaretae,... Odorrana margaretae (Anura: Ranidae) is widely distributed in the southern provinces of China. Previously, 72 antimicrobial peptides (AMPs) belonging to 21 families were identified from the skin of O. margaretae, which were captured in the Hunan province. In the present study, five O. margaretae frogs were captured from the Guizhou province and a total of 28 cDNAs encoding 17 host defense peptides (HDPs) belonging to 14 families were cloned from the skin cDNA library of O. margaretae. Among the 17 HDPs, only one (brevinin-1-Omar5) had been characterized. The distinct HDP expression profiles for O. margaretae in the previous and present study may be attributed to the environmental differences between the sampling locations and the genetic divergence among O. margaretae populations. Besides, 11 of the 17 HDPs identified in the present study were novel for ranids. In order to understand their roles in host defense reactions, three HDPs (odorranain-H-OM1, odorranain-M-OM and ranatuerin-2-OM), which possess low sequence similarity with the known amphibian HDPs, were selected for further chemical synthesis and functional analysis. Odorranain-H-OM1 showed direct antimicrobial activity against bacteria and fungi. Odorranain-M-OM exhibited concentration-dependent anti-oxidant activity. Ranatuerin-2-OM showed lectin-like activity and could strongly hemagglu -tinate human intact erythrocytes with or without the presence of Ca2+. The diverse activities of HDPs implied that they may play different roles in host defense reactions of O. margaretae. 展开更多
关键词 AMPHIBIAN host defense peptides (HDPs) Odorrana margaretae antimicrobial activity anti-oxidant activity erythrocytes hemagglutinating activity
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Two intestinal microbiota-derived metabolites, deoxycholic acid and butyrate, synergize to enhance host defense peptide synthesis and alleviate necrotic enteritis
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作者 Dohyung M.Kim Jing Liu +3 位作者 Melanie A.Whitmore Isabel Tobin Zijun Zhao Guolong Zhang 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2024年第3期1158-1172,共15页
Background Necrotic enteritis(NE)is a major enteric disease in poultry,yet effective mitigation strategies remain elusive.Deoxycholic acid(DCA)and butyrate,two major metabolites derived from the intestinal microbiota,... Background Necrotic enteritis(NE)is a major enteric disease in poultry,yet effective mitigation strategies remain elusive.Deoxycholic acid(DCA)and butyrate,two major metabolites derived from the intestinal microbiota,have independently been shown to induce host defense peptide(HDP)synthesis.However,the potential synergy between these two compounds remains unexplored.Methods To investigate the possible synergistic effect between DCA and butyrate in regulating HDP synthesis and barrier function,we treated chicken HD11 macrophage cells and jejunal explants with DCA and sodium butyrate(NaB),either individually or in combination,for 24 h.Subsequently,we performed RNA isolation and reverse transcrip-tion-quantitative PCR to analyze HDP genes as well as the major genes associated with barrier function.To further determine the synergy between DCA and NaB in enhancing NE resistance,we conducted two independent trials with Cobb broiler chicks.In each trial,the diet was supplemented with DCA or NaB on the day-of-hatch,followed by NE induction through sequential challenges with Eimeria maxima and Clostridium perfringens on d 10 and 14,respectively.We recorded animal mortality after infection and assessed intestinal lesions on d 17.The impact of DCA and NaB on the microbiota in the ileum and cecum was evaluated through bacterial 16S rRNA gene sequencing.Results We found that the combination of DCA and NaB synergistically induced multiple HDP genes in both chicken HD11 cells and jejunal explants.Additionally,the gene for claudin-1,a major tight junction protein,also exhibited synergistic induction in response to DCA and NaB.Furthermore,dietary supplementation with a combination of 0.75 g/kg DCA and 1 g/kg NaB led to a significant improvement in animal survival and a reduction in intestinal lesions compared to either compound alone in a chicken model of NE.Notably,the cecal microbiota of NE-infected chickens showed a marked decrease in SCFA-producing bacteria such as Bacteroides,Faecalibacterium,and Cuneatibacter,with lactobacilli becoming the most dominant species.However,supplementation with DCA and NaB largely restored the intestinal microbiota to healthy levels.Conclusions DCA synergizes with NaB to induce HDP and claudin-1 expression and enhance NE resistance,with potential for further development as cost-effective antibiotic alternatives. 展开更多
关键词 Bile acids host defense peptides METABOLITES MICROBIOME Necrotic enteritis Short-chain fatty acids
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Discovery of natural products capable of inducing porcine host defense peptide gene expression using cell-based high throughput screening 被引量:2
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作者 Jing Wang Wentao Lyu +5 位作者 Wei Zhang Yonghong Chen Fang Luo Yamin Wang Haifeng Ji Guolong Zhang 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2021年第2期598-610,共13页
Background:In-feed antibiotics are being phased out in livestock production worldwide.Alternatives to antibiotics are urgently needed to maintain animal health and production performance.Host defense peptides(HDPs)are... Background:In-feed antibiotics are being phased out in livestock production worldwide.Alternatives to antibiotics are urgently needed to maintain animal health and production performance.Host defense peptides(HDPs)are known for their broad-spectrum antimicrobial and immunomodulatory capabilities.Enhancing the synthesis of endogenous HDPs represents a promising antibiotic alternative strategy to disease control and prevention.Methods:To identify natural products with an ability to stimulate the synthesis of endogenous HDPs,we performed a high-throughput screening of 1261 natural products using a newly-established stable luciferase reporter cell line known as IPEC-J2/pBD3-luc.The ability of the hit compounds to induce HDP genes in porcine IPEC-J2 intestinal epithelial cells,3D4/31 macrophages,and jejunal explants were verified using RT-qPCR.Augmentation of the antibacterial activity of porcine 3D4/31 macrophages against a Gram-negative bacterium(enterotoxigenic E.coli)and a Gram-positive bacterium(Staphylococcus aureus)were further confirmed with four selected HDP-inducing compounds.Results:A total of 48 natural products with a minimum Z-score of 2.0 were identified after high-throughput screening,with 21 compounds giving at least 2-fold increase in luciferase activity in a follow-up dose-response experiment.Xanthohumol and deoxyshikonin were further found to be the most potent in inducing pBD3 mRNA expression,showing a minimum 10-fold increase in IPEC-J2,3D4/31 cells,and jejunal explants.Other compounds such as isorhapontigenin and calycosin also enhanced pBD3 mRNA expression by at least 10-fold in both IPEC-J2 cells and jejunal explants,but not 3D4/31 cells.In addition to pBD3,other porcine HDP genes such as pBD2,PG1-5,and pEP2C were induced to different magnitudes by xanthohumol,deoxyshikonin,isorhapontigenin,and calycosin,although clear gene-and cell type-specific patterns of regulation were observed.Desirably,these four compounds had a minimum effect on the expression of several representative inflammatory cytokine genes.Furthermore,when used at HDP-inducing concentrations,these compounds showed no obvious direct antibacterial activity,but significantly augmented the antibacterial activity of 3D4/31 macrophages(P<0.05)against both Gram-negative and Gram-positive bacteria.Conclusions:Our results indicate that these newly-identified natural HDP-inducing compounds have the potential to be developed as novel alternatives to antibiotics for prophylactic and therapeutic treatment of infectious diseases in livestock production. 展开更多
关键词 Antibiotic alternatives High throughput screening HDP inducers host defense peptides Natural products
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Tissue expression and developmental regulation of chicken cathelicidin antimicrobial peptides 被引量:3
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作者 Mallika Achanta Lakshmi T Sunkara +3 位作者 Gan Dai Yugendar R Bommineni Weiyu Jiang Guolong Zhang 《Journal of Animal Science and Biotechnology》 SCIE CAS 2012年第2期86-92,共7页
Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, hav... Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, have been identified in chickens. As a first step to understand their role in early innate host defense of chickens, we examined the tissue and developmental expression patterns of all four cathelicidins. Real-time PCR revealed an abundant expression of four cathelicidins throughout the gastrointestinal, respiratory, and urogenital tracts as well as in all primary and secondary immune organs of chickens. Fowlicidins 1 to 3 exhibited a similar tissue expression pattern with the highest expression in the bone marrow and lung, while cathelicidin B1 was synthesized most abundantly in the bursa of Fabricius. Additionally, a tissue-specific regulatory pattern was evident for all four cathelicidins during the first 28 days after hatching. The expression of fowlicidins 1 to 3 showed an age-dependent increase both in the cecal tonsil and lung, whereas all four cathelicidins were peaked in the bursa on day 4 after hatching, with a gradual decline by day 28. An abrupt augmentation in the expression of fowlicidins 1 to 3 was also observed in the cecum on day 28, while the highest expression of cathelicidin B1 was seen in both the lung and cecal tonsil on day 14. Collectively, the presence of cathelicidins in a broad range of tissues and their largely enhanced expression during development are suggestive of their potential important role in early host defense and disease resistance of chickens. 展开更多
关键词 Antimicrobial peptides CATHELICIDINS CHICKENS DEVELOPMENT host defense peptides
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Host defense peptide-mimicking peptide polymer-based antibacterial hydrogel enables efficient healing of MRSA-infected wounds 被引量:2
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作者 Zhongqian Qiao Wenjing Zhang +11 位作者 Yueming Wu Weinan Jiang Ning Shao Jiayang Xie Guixue Xia Qimeng Chen Zhefeng Liu Jingcheng Zou Jiawei Gu Shifang Luan Haodong Lin Runhui Liu 《Science China Chemistry》 SCIE EI CAS CSCD 2023年第6期1824-1833,共10页
Wound infections are a compelling health issue caused by the invasion and proliferation of pathogens in wound sites.Antibioticloaded hydrogels are widely used to achieve anti-infectious wound healing.However,due to th... Wound infections are a compelling health issue caused by the invasion and proliferation of pathogens in wound sites.Antibioticloaded hydrogels are widely used to achieve anti-infectious wound healing.However,due to the quick emergence of drugresistant bacteria,such as methicillin-resistant Staphylococcus aureus(MRSA),wound infection has been a formidable challenge to human health.To address MRSA-infected wounds,an antibacterial peptide polymer-loaded hyaluronic acid(HA)hydrogel(Gel-HA@P)is prepared.The peptide polymer is designed to mimic host defense peptides as the antibiotic alternative showing potent antibacterial activity,low susceptibility to drug resistance and good stability against proteolysis.HA is biocompatible and biodegradable hydrogel substrate as a primary constituent of the extracellular matrix and suitable for cell migration and wound healing.Gel-HA@P shows potent activity against MRSA in vitro and in vivo,low toxicity during the treatment and promotes the wound healing in vivo.This design has proven to be an effective and antibiotic-free strategy to enable the healing of MRSA-infected wounds. 展开更多
关键词 peptide polymer wound healing MRSA DRUG-RESISTANCE host defense peptide
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Host defense peptide-mimickingβ-peptide polymer displaying strong antibacterial activity against cariogenic Streptococcus mutans
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作者 Yi Yang Yuxin Qian +6 位作者 Mingxing Zhang Shuang Hao Hui Wang Yongqiang Fan Runhui Liu Dake Xu Fuhui Wang 《Journal of Materials Science & Technology》 SCIE EI CAS CSCD 2023年第2期77-88,共12页
Cariogenic Streptococcus mutans(S.mutans)is a leading cause of bacterial-induced oral diseases.Current strategies to kill bacteria based on Host defense peptide(HDP)mimicking polymers hold promise to treat oral bacter... Cariogenic Streptococcus mutans(S.mutans)is a leading cause of bacterial-induced oral diseases.Current strategies to kill bacteria based on Host defense peptide(HDP)mimicking polymers hold promise to treat oral bacterial infection.Here,we explore the impact of hydrophobic subunit and chain length variation on the antibacterial and antibiofilm activity ofβ-peptide polymers.The physicochemical and biological prop-erties,such as the toxicity,the antibacterial activity,and the effect on bacterial transcription ofβ-peptide polymers,were systematically investigated with numerous techniques.The results exhibited that the op-timalβ-peptide polymer has low toxicity towards human periodontal ligament fibroblasts,andβ-peptide polymers(especially P3)have more excellent antibacterial activity against S.mutans than metronidazole.In addition,β-peptide polymers inhibited the reversible and irreversible bacterial adhesion during the formation of biofilms.The polymer can promote biofilm dispersion by decreasing the hydrophobicity of bacterial cells after adhering to cell surfaces.Analysis of the transcriptome for S.mutans treated withβ-peptide polymers demonstrated thatβ-peptide polymers could reduce the cariogenicity of S.mutans by impacting the transcription of the energy and acid metabolism-related genes.β-peptide polymers are promising antimicrobial agents in clinical dentistry due to their high antibacterial efficiency and low tox-icity. 展开更多
关键词 β-peptide polymers host defense peptide S.mutans RT-QPCR TRANSCRIPTOME
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Dietary modulation of endogenous host defense peptide synthesis as an alternative approach to in-feed antibiotics 被引量:12
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作者 Kelsy Robinson Xi Ma +3 位作者 Yulan Liu Shiyan Qiao Yongqing Hou Guolong Zhang 《Animal Nutrition》 SCIE 2018年第2期160-169,共10页
Traditionally, antibiotics are included in animal feed at subtherapeutic levels for growth promotion and disease prevention.However, recent links between in-feed antibiotics and a rise in antibiotic-resistant pathogen... Traditionally, antibiotics are included in animal feed at subtherapeutic levels for growth promotion and disease prevention.However, recent links between in-feed antibiotics and a rise in antibiotic-resistant pathogens have led to a ban of all antibiotics in livestock production by the European Union in January 2006 and a removal of medically important antibiotics in animal feeds in the United States in January 2017.An urgent need arises for antibiotic alternatives capable of maintaining animal health and productivity without triggering antimicrobial resistance.Host defense peptides(HDP) are a critical component of the animal innate immune system with direct antimicrobial and immunomodulatory activities.While in-feed supplementation of recombinant or synthetic HDP appears to be effective in maintaining animal performance and alleviating clinical symptoms in the context of disease, dietary modulation of the synthesis of endogenous host defense peptides has emerged as a cost-effective,antibiotic-alternative approach to disease control and prevention.Several different classes of smallmolecule compounds have been found capable of promoting HDP synthesis.Among the most efficacious compounds are butyrate and vitamin D.Moreover, butyrate and vitamin D synergize with each other in enhancing HDP synthesis.This review will focus on the regulation of HDP synthesis by butyrate and vitamin D in humans, chickens, pigs, and cattle and argue for potential application of HDP-inducing compounds in antibiotic-free livestock production. 展开更多
关键词 host defense peptides Antibiotic alternatives BUTYRATE Vitamin D ANTIBIOTICS
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Breaking or following the membrane-targeting mechanism:Exploring the antibacterial mechanism of host defense peptide mimicking poly(2-oxazoline)s 被引量:2
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作者 Chengzhi Dai Min Zhou +9 位作者 Weinan Jiang Ximian Xiao Jingcheng Zou Yuxin Qian Zihao Cong Zhemin Ji Longqiang Liu Jiayang Xie Zhongqian Qiao Runhui Liu 《Journal of Materials Science & Technology》 SCIE EI CAS CSCD 2020年第24期220-226,共7页
Peptides exert important biological functions but their application is hindered by their susceptibility to proteolysis and poor stability in vivo.Thus,functional peptide mimics have drawn a great deal of attention to ... Peptides exert important biological functions but their application is hindered by their susceptibility to proteolysis and poor stability in vivo.Thus,functional peptide mimics have drawn a great deal of attention to address this challenge.Poly(2-oxazoline)s,a class of biocompatible and proteolysis-resistant polymer,can work as host defense peptide mimics without following the general membrane-targeting mechanism as shown in our previous work.This observation encouraged us to figure out if poly(2-oxazoline)s are special and break the general membrane-targeting mechanism of host defense peptides and their mimics.In this study,we aimed at the connection between structure and antibacterial mechanism of poly(2-oxazoline)s.A new γ-aminobutyric acid(GABA)-pendent poly(2-oxazoline)was synthesized and investigated to compare with glycine-pendent poly(2-oxazoline)in our previous study,with the former polymer has two extra CH2 groups in the sidechain to increase the hydrophobicity and amphiphilicity.Membrane depolarization assay suggested that incorporating two more CH2 groups into the sidechain of poly(2-oxazoline)resulted in a mechanism switch from DNA-targeting to membrane-targeting,which was supported by the slow time-kill kinetics and slightly distorted and sunken membrane morphology.Besides,GABA-pendent poly(2-oxazoline)showed potent activity against methicillin-resistant S.aureus and low hemolysis on human red blood cells.Moreover,repeated use of the antimicrobial poly(2-oxazoline)did not stimulate bacteria to obtain resistance,which was an obvious advantage of membrane-targeting antimicrobial agents. 展开更多
关键词 Poly(2-oxazoline) host defense peptide Antibacterial mechanism Membrane-targeting Antimicrobial resistance
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Antibiofilm and immunomodulatory resorbable nanofibrous filing for dental pulp regenerative procedures
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作者 Mauricio Gonçalves da Costa Sousa Gabriela Conceiçao de Almeida +19 位作者 Danilo Cesar Martins Mota Rosiane Andrade da Costa Simoni Campos Dias Samuel Nunes Limberger Frank Ko Li Ting Lin Evan FHaney Hashem Etayash Beverlie Baquir Michael J.Trimble Ya Shen Zheng Su Markus Haapasalo Daniel Pletzer Letícia Chaves de Souza Glaucia Schuindt Teixeira Renato M.Silva Robert E.W.Hancock Octavio Luiz Franco Taia Maria Berto Rezende 《Bioactive Materials》 SCIE 2022年第10期173-186,共14页
Multifunctional scaffolds with host defense peptides designed for regenerative endodontics are desirable nanobiotechnological tools for dentistry.Here,different scaffolds were tested for use during the pulp revascular... Multifunctional scaffolds with host defense peptides designed for regenerative endodontics are desirable nanobiotechnological tools for dentistry.Here,different scaffolds were tested for use during the pulp revascularization process,including poly(vinyl alcohol)-PVA hydrogels or resins,collagen hydrogels and poly(vinyl alcohol)PVA/Chitosan(PVA/CS)nanofibers.Based on time to degradation(21 days),nanofibers were chosen to be incorporated with ciprofloxacin and IDR-1002(each at 50 mg/g).Nanofibers containing ciprofloxacin and IDR-1002 had anti-biofilm activity against Enterococcus faecalis,Staphylococcus aureus and a multispecies oral biofilm,besides anti-inflammatory activities.The in vivo subcutaneous tissue response to tooth fragments filled with nanofibers demonstrated a pulp-like tissue formation,when compared to empty teeth fragments.Thus,we designed a strong antimicrobial,immunomodulatory and regenerative candidate for pulp revascularization and regeneration procedures. 展开更多
关键词 Regenerative endodontics Scaffolds Nanofibers host defense peptides CIPROFLOXACIN IDR-1002
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Effective and biocompatible antibacterial surfaces via facile synthesis and surface modification of peptide polymers 被引量:6
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作者 Ziyi Lu Yueming Wu +14 位作者 Zihao Cong Yuxin Qian Xue Wu Ning Shao Zhongqian Qiao Haodong Zhang Yunrui She Kang Chen Hengxue Xiang Bin Sun Qian Yu Yuan Yuan Haodong Lin Meifang Zhu Runhui Liu 《Bioactive Materials》 SCIE 2021年第12期4531-4541,共11页
It is an urgent need to tackle drug-resistance microbial infections that are associated with implantable biomedical devices.Host defense peptide-mimicking polymers have been actively explored in recent years to fight ... It is an urgent need to tackle drug-resistance microbial infections that are associated with implantable biomedical devices.Host defense peptide-mimicking polymers have been actively explored in recent years to fight against drug-resistant microbes.Our recent report on lithium hexamethyldisilazide-initiated superfast polymerization on amino acid N-carboxyanhydrides enables the quick synthesis of host defense peptide-mimicking peptide polymers.Here we reported a facile and cost-effective thermoplastic polyurethane(TPU)surface modification of peptide polymer(DLL:BLG=90:10)using plasma surface activation and substitution reaction between thiol and bromide groups.The peptide polymer-modified TPU surfaces exhibited board-spectrum antibacterial property as well as effective contact-killing ability in vitro.Furthermore,the peptide polymer-modified TPU surfaces showed excellent biocompatibility,displaying no hemolysis and cytotoxicity.In vivo study using methicillin-resistant Staphylococcus aureus(MRSA)for subcutaneous implantation infectious model showed that peptide polymer-modified TPU surfaces revealed obvious suppression of infection and great histocompatibility,compared to bare TPU surfaces.We further explored the antimicrobial mechanism of the peptide polymer-modified TPU surfaces,which revealed a surface contact-killing mechanism by disrupting the bacterial membrane.These results demonstrated great potential of the peptide-modified TPU surfaces for practical application to combat bacterial infections that are associated with implantable materials and devices. 展开更多
关键词 Peptide polymer host defense peptide Antimicrobial surface MRSA Subcutaneous infection
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