Biosensors-Basel
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2024
·Vol. 14
·期 11
·521
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IF 4.9
Linmin Zhong,Huiping Chen,Shuang Cao,Shanwen Hu
Single nucleotide polymorphisms (SNPs) present significant challenges in microbial detection and treatment, further raising the demands on sequencing technologies. In response to these challenges, we have developed a novel barcode-based approach for highly sensitive single nucleotide recognition. This method leverages a dual-head folded complementary template probe in conjunction with DNA ligase to specifically identify the target base. Upon recognition, the system triggers rolling circle amplification (RCA) followed by the self-assembly of CdSe quantum dots onto polystyrene microspheres, enabling a single-particle fluorescence readout. This approach allows for precise base identification at individual loci, which are then analyzed using a bio-barcode array to screen for base changes across multiple sites. This method was applied to sequence a drug-resistant mutation site inHelicobacter pylori(H. pylori), demonstrating excellent accuracy and stability. Offering high precision, high sensitivity, and single nucleotide resolution, this approach shows great promise as a next-generation sequencing method.
研究领域:
分子生物学
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医学检测
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纳米技术
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基因组学
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PubMed
高影响因子
HELICOBACTER
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2019
·Vol. 24
·期 3
·e12577
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IF 3.352
Wanli Yan,Lide Gu,Wei Ren,Xiaoyi Ma,Mingcan Qin,Mingsheng Lyu,Shujun Wang
Background Helicobacter pylori ( H pylori ) is a disease-causing pathogen capable of surviving under acidic conditions of the human stomach. Almost half of the world's population is infected with H pylori , with gastric cancer being the most unsatisfactory prognosis. Although H pylori has been discovered 30 years ago, the effective treatment and elimination of H pylori continue to be problematic. Materials and methods In our study, we screened nucleic acid aptamers using H pylori surface recombinant antigens as targets. Trypsin was used for separating aptamers that were bound to proteins. Following nine rounds of screening, we performed sequence similarity analyses to assess whether the aptamers can recognize the target protein. Two sequences with desirable recognition ability were selected for affinity detection. Aptamer Hp4 with the strongest binding ability to the H pylori surface recombinant antigen was chosen. After optimization of the binding conditions, we conducted specificity tests for Hp4 using Escherichia coli , Staphylococcus aureus, Vibrioanguillarum , and H pylori . Results The data indicated that the aptamer Hp4 had an equilibrium dissociation constant ( K d ) of 26.48 ± 5.72 nmol/L to the target protein. This aptamer was capable of exclusively detecting H pylori cells, without displaying any specificity for other bacteria. Conclusions We obtained a high-affinity aptamer for H pylori, which is expected to serve as a new molecular probe for detection of H pylori .
研究领域:
微生物学
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分子生物学
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医学诊断
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PubMed
高影响因子
WORLD JOURNAL OF GASTROENTEROLOGY
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2021
·
IF 5.742
Xiao-Hua Li,Yong-Yi Huang,Lin-Ming Lu,Li-Juan Zhao,Xian-Ke Luo,Ru-Jia Li,Yuan-Yuan Dai,Chun Qin,Yan-Qiang Huang,Hao Chen
BACKGROUND The drug resistance rate of clinical Helicobacter pylori ( H. pylori ) isolates has increased. However, the mechanism of drug resistance remains unclear. In this study, drug-resistant H. pylori strains were isolated from different areas and different populations of Chinese for genomic analysis. AIM To investigate drug-resistant genes in H. pylori and find the genes for the early diagnosis of clarithromycin resistance. METHODS Three drug-resistant H. pylori strains were isolated from patients with gastritis in Bama County, China. Minimal inhibitory concentrations of clarithromycin, metronidazole, and levofloxacin were determined and complete genome sequencing was performed with annotation. Hp1181 and hp1184 genes were found in these strains and then detected by reverse transcription polymerase chain reaction. The relationships between hp1181 or hp1184 and clarithromycin resistance were ascertained with gene mutant and drug-resistant strains. The homology of the strains with hp26695 was assessed through complete genome detection and identification. Differences in genome sequences, gene quantity, and gene characteristics were detected amongst the three strains. Prediction and analysis of the function of drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the three strains, which was the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains was assessed. RESULTS The strains showing a high degree of homology with hp26695 , hp1181 , and hp1184 genes were found in these strains; the expression of the genes hp1184 and hp1181 was associated with clarithromycin resistance. CONCLUSION Hp1181 and hp1184 mutations may be the earliest and most persistent response to clarithromycin resistance, and they may be the potential target genes for the diagnosis, prevention, and treatment of clarithromycin resistance.
研究领域:
医学
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微生物学
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基因组学
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PubMed
高影响因子
Advanced Healthcare Materials
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2025
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IF 9.6
Shali Tan,Ruijue Dan,Junfeng Guo,Qinglin Wei,Kaige Xu,Qiang Luo,Yuchen Zhang,Chaoqiang Fan,Xiaoyan Zhao,Donghui Zhu,Quan Wang,Malcolm Xing,Shiming Yang,Yu Huang
Helicobacter pylori ( H. pylori ) infection remains a major challenge in gastric disease treatment, with conventional antibiotic therapies hindered by poor gastric retention, lack of specificity, and the growing threat of bacterial resistance. To address these limitations, we introduce a novel bioengineered robotic system inspired by icebreakers, integrating multi-functional nanomaterials for targeted, autonomous, and efficient H. pylori eradication. Our micro-robots combine a platinum nanozyme-based calcium carbonate complex with chitosan (Cs) modification, gastric epithelial cell membranes (CM) coating, and pronase (P) incorporation, enabling selective targeting and autonomous motility. Upon gastric acid exposure, this system undergoes controlled decomposition, generating carbon dioxide to propel movement, releasing pronase to penetrate and degrade mucus barriers, and deploying Pt nanozymes for deep bacterial eradication. This multi-modal mechanism significantly enhances gastric retention, precision targeting, and therapeutic effectiveness. Our in vitro and in vivo studies validate its superior antibacterial activity, biocompatibility, and its unprecedented ability to mitigate H. pylori -induced inflammation while preserving intestinal microbiota balance. By combining bioengineering, nanotechnology, and autonomous propulsion, this innovation represents a paradigm shift in H. pylori therapy, offering a precise, efficient, and resistance-mitigating alternative to conventional treatments.
研究领域:
纳米医学
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生物医学工程
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微型机器人
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胃肠病学
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抗菌治疗
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药物递送
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Yiqing Zou,Xiaonan Chen,Yingying Sun,Pengyu Li,Mao Xu,Pengchao Fang,Shuqi Zhang,Gang Yuan,Xin Deng,Haiyan Hu
Biofilms and intracellular survival tremendously help Helicobacter pylori ( H. pylori ) escape from antibacterial agents attacking, therefore issuing extreme challenges to clinical therapies. Herein, we constructed fucoidan (FU)-coated nanoparticles (FU/ML-LA/EB NPs) via simple self-assembly of biguanide derivative (metformin-linoleic acid, ML) and linoleic acid (LA), encapsulating urease inhibitor ebselen (EB) instead of antibiotics to take antibacterial effect . Negatively charged FU/ML-LA/EB NPs easily penetrated through the gastric mucus layer to arrive at infection sites, then eradicated extracellular polymeric substances (EPS) to destroy H. pylori biofilms structure. After strengthening bacterial membrane permeability, the nanoparticles could enter H. pylori and kill bacteria by inhibiting the activity of urease. FU/ML-LA/EB NPs also entered H. pylori -infected host cells through receptor-mediated internalization, in which they activated AMPK to recover lysosomal acidification for killing intracellular H. pylori . Additionally, FU/ML-LA/EB NPs alleviated oxidative stress, hence reducing gastric mucosal damage and cutting off the pathways of carcinogenesis. Notably, H. pylori burden after FU/ML-LA/EB NPs treatment was reduced to a great extent in vivo , which was significantly lower than that after treatment with clinical therapy. Antibiotics-free FU/ML-LA/EB NPs improving bacterial eradication and alleviating oxidation stress made it a powerful approach against H. pylori .
研究领域:
微生物学
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纳米技术
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药理学
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胃肠病学
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DOI
PubMed
高影响因子
Foods
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2021
·Vol. 10
·期 10
·2453
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IF 4.35
Jingfei Hu,Xueqing Tian,Tong Wei,Hangjie Wu,Jing Lu,Mingsheng Lyu,Shujun Wang
Helicobacter pyloriis a cause of gastric cancer. We extracted the exopolysaccharide (EPS) ofLactobacillus plajomiPW-7 for antibacterial activity versusH. pylori, elucidating its biological activity and structural characteristics. The minimum inhibitory concentration (MIC) of EPS againstH. pyloriwas 50 mg/mL. Disruption of the cell membranes of pathogenic bacteria by EPS was indicated via the antibacterial mechanism test and confirmed through electron microscopy. EPS also has antioxidant capacity. The IC50of EPS for 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide anions, and hydroxyl radicals were 300 μg/mL, 180 μg/mL, and 10 mg/mL, respectively. The reducing power of EPS was 2 mg/mL, equivalent to 20 μg/mL of ascorbic acid. EPS is a heteropolysaccharide comprising six monosaccharides, with an approximate molecular weight of 2.33 × 104Da. Xylose had a significant effect onH. pylori. EPS fromL. plajomiPW-7 showed potential as an antibacterial compound and antioxidant, laying a foundation for the development of EPS-based foods.Keywords:Helicobacter pylori;Lactobacillus plajomi;exopolysaccharide;antibacterial activity;antioxidant activity
研究领域:
微生物学
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食品科学
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医学
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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2015
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IF 0
Jiaying Han,Yinjing Sun,Jiapeng Hou,Yuyan Wang,Yu Liu,Cao Xie,Weiyue Lu,Jun Pan
This paper reports investigations into the preparation and characterization of surface molecularly imprinted nanoparticles (SMINs) designed to adhere to Helicobacter pylori (H. pylori) . Imprinted nanoparticles were prepared by the inverse microemulsion polymerization method. A fraction of Lpp20, an outer membrane protein of H. pylori known as NQA, was chosen as template and modified with myristic acid to facilitate its localization on the surface of the nanoparticles. The interaction between these SMINs with the template NQA were evaluated using surface plasmon resonance (SPR), change in zeta potential and fluorescence polarization (FP). The results were highly consistent in demonstrating a preferential recognition of the template NQA for SMINs compared with the control nanoparticles. In vitro experiments also indicate that such SMINs are able to adhere to H. pylori and may be useful for H. pylori eradication.
研究领域:
生物医学工程
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微生物学
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纳米医学
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DOI
PubMed
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Jie Yuan,Ting Li,Shuangshuang Gao,Yujing Tang,Shuling Ma,Hai Yen Lee,Kim Ling Chin,Hongzhuan Xuan
Ethnopharmacological relevance Propolis, a resinous mixture from plant exudates, is widely used in traditional ethnomedicine for gastrointestinal infections, implying anti- Helicobacter pylori ( H. pylori ) potential. However, its molecular mechanisms targeting H. pylori urease (HPU), a key virulence factor, remain unclear. Aim of the study This study aimed to characterize the inhibitory activity and kinetic properties of poplar propolis ethanol extract (PPEE) against HPU and jack bean urease (JBU), and to elucidate the underlying molecular mechanisms. Materials and methods UPLC–MS/MS-based metabolomics was used to identify PPEE's potential bioactive candidates. Enzyme activity assays, kinetic analysis, thiol/Ni 2+ protection assays, transcriptional profiling of urease-related genes, and molecular docking were applied for mechanistic exploration. Bacterial growth curve assays and PI staining verified its antibacterial activity. Results PPEE, enriched in flavonoids and phenolic acids, exhibited significant dose-dependent and reversible inhibition on HPU, with superior potency to JBU. Mechanistically, PPEE acted synergistically by competitively binding to HPU's substrate pocket, disrupting thiol-Ni 2+ coordination, inducing slow-binding conformational stabilization, and perturbing tertiary structure. It also downregulated ureA / ureB , nixA , and ureH / ureI , forming a multi-layered mode of “direct enzyme inhibition + blocking synthesis/assembly”. Urease inhibition was the core anti- H. pylori mechanism, with auxiliary urease-independent activity. Molecular docking confirmed stable interactions between PPEE components and HPU's active center/substrate pocket. Experimental validation showed that quercetin and taxifolin inhibited HPU in a dose-dependent manner. Conclusions PPEE specifically inhibits HPU via multi-targeted synergistic mechanisms, providing molecular evidence for propolis-derived anti- H. pylori agents and laying a foundation for subsequent SAR and in vivo studies.
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Xing Li,Jipeng Zhang,Xiangyu Liu,Zijian Wu,Zhipeng Yu,Wen Zhang,Yuanzhi Wang,Zekun Li,Martien A. Cohen Stuart,Leonard M.C. Sagis,Minchun Lv,Jie Xiao,Yuan Li
Helicobacter pylori ( H. pylori ) is a prevalent global pathogen responsible for gastritis and the potential development of gastric cancer. Sulforaphane (SFN), a foodborne compound, exhibits notable antibiotic properties against H. pylori . However, its utility is limited by poor stability and susceptibility to environmental degradation. Here, we developed a gastric-responsive-release microgel for delivering anti- H. pylori SFN. The microgels were prepared by cross-linking α-lactalbumin nanotubes then coated with chitosan (CTS-MGs). SFN was loaded into microgels with a loading rate of 10.73 ± 0.25 %. The CTS-MG showed a strong adhesion to the gastric mucosa, prolonging gastric retention for up to 24 h and responsively releasing SFN in the stomach. Furthermore, CTS-MG/SFN dissociated and released nanotubes/SFN, which could penetrate into the gastric mucus layer and arrive at the deepest mucus sites where most H. pylori were colonized. Our results revealed that CTS-MG/SFN displayed an obvious inhibitory effect against H. pylori . The oral administration of CTS-MG/SFN in H. pylori -infected mice effectively alleviated H. pylori -induced gastritis and modulated gastric microbiota homeostasis. This work demonstrated high potential of CTS-MG microgels for gastric-targeted and oral delivery of antibiotic natural compounds against H. pylori infection.
研究领域:
药学
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微生物学
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生物材料学
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PubMed
高影响因子
BIOMATERIALS
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2025
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IF 12.9
Zishan Zeng,Jingwen Jiang,Yue Sun,Wanzhen Li,Dong Zheng,Huanxin Lin,Chunshun Zhao
Helicobacter pylori ( H. pylori ) is considered as the major pathogenic factor related to multiple digestive diseases. However, the efficacy of first-line treatment containing antibiotics gradually declined. It is urgent to develop treatment with antibiotic reduction/abandonment to combat H. pylori . Based on our previous discovery that Cu(DTC) 2 exhibited stronger bactericidal effect than that of disulfiram or diethyldithiocarbamate (DTC), we constructed an antibiotic-free therapeutic strategy composed of DTC prodrug, Cu 2+ and shikonin (SK) to eliminate H. pylori . DTC was firstly modified with nitroaromatic moiety to acquire DTC prodrug (NTR-DTC), which was further encapsulated into Cu-SK@DOPA to construct nanoprodrug Cu-SK@NTR-DTC to achieve the triple masking of DTC, Cu 2+ and SK for the specificity therapeutics. Cu-SK@NTR-DTC could penetrate mucus layer and mainly detain in the bacteria infection area. In the presence of H. pylori , DTC was released from NTR-DTC to recover activity of copper chelation, and competitively bound Cu 2+ from Cu-SK to form Cu(DTC) 2 . The released SK possessed the bactericidal sensitization effect on Cu(DTC) 2 . The H. pylori -activable dissociation of Cu-SK@NTR-DTC, and the local release of Cu(DTC) 2 and SK seriously destructed the bacterial membranes integrity and induce H. pylori death, which provided a feasible strategy to address the clinical limitations of H. pylori clearance.
研究领域:
医学
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药学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Zhixiang Zhu,Yuanjing Zou,Ling Ou,Meiyun Chen,Yujiang Pang,Hui Li,Yajie Hao,Bingmei Su,Yuqian Lai,Liping Zhang,Junwei Jia,Ruixia Wei,Guimin Zhang,Meicun Yao,Zhong Feng
Background: Triphala, is a composite of three individual botanical drugs: Terminalia chebula, Terminalia bellirica, and Emblica officinalis. It exhibits properties such as heatclearing, anti-inflammatory, anti-fatigue, antioxidant, and antibacterial effects,making it extensively utilized in India and Tibet. It has been found to exhibitinhibitory effects on Helicobacter pylori (H. pylori); however, further comprehensive research is still needed to elucidate its specific antibacterial mechanism. The present study investigates the in vitro antibacterial activity and antibacterial mechanism of Triphala against H. pylori.Methods: Ours research investigates the in vitro inhibitory activity of Triphala on multiple standard and clinical strains using microdilution broth method, time-kill curve, time-bactericidal curve and scanning electron microscopy (SEM). Furthermore, the antibacterial mechanism of Triphala is further explored through experiments on urease activity, biofilm formation, anti-adhesion properties, virulence actor assays using RT-qPCR and Western Blotting techniques.Results: The research findings indicate that Triphala exhibits a minimum inhibitory concentration of 80–320 μg/mL against both standard and clinical strains of H. pylori. Triphala exerts its anti-H. pylori effect by perturbing the microstructure of H. pylori, downregulating adhesion-associated genes (alpA, alpB, babA), urease-related genes (ureA, ureB, ureE, ureF), and flagellar genes (flaA, flaB); inhibiting bacterial adhesion, biofilm formation, urease activity as well as CagA protein expression.Discussion: These findings suggest that Triphala exerts inhibitory effects on H. pylori activity through multiple mechanisms, underscoring its potential as a new drug for the prevention and treatment of H. pylori infection.
研究领域:
药理学
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微生物学
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传统医学
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PubMed
高影响因子
ACS Omega
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2021
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IF 3.512
Hangjie Wu,Lide Gu,Xiaoyi Ma,Xueqing Tian,Shihui Fan,Mingcan Qin,Jing Lu,Mingsheng Lyu,Shujun Wang
Helicobacter pylori was first isolated from gastritis patients by Barry J. Marshall and J. Robin Warren in 1982, and more than 90% of duodenal ulcers and about 80% of gastric ulcers are caused by H. pylori infection. Most detection methods require sophisticated instruments and professional operators, making detection slow and expensive. Therefore, it is critical to develop a simple, fast, highly specific, and practical strategy for the detection of H. pylori. In this study, we used H. pylori as a target to select unique aptamers that can be used for the detection of H. pylori. In our study, we used random ssDNA as an initial library to screen nucleic acid aptamers for H. pylori. We used binding rate and the fluorescence intensity to identify candidate aptamers. One DNA aptamer, named HPA-2, was discovered through six rounds of positive selection and three rounds of negative selection, and it had the highest affinity constant of all aptamers tested (Kd = 19.3 ± 3.2 nM). This aptamer could be used to detect H. pylori and showed no specificity for other bacteria. Moreover, we developed a new sensor to detect H. pylori with the naked eye for 5 min using illumination from a hand-held flashlight. Our study provides a framework for the development of other aptamer-based methods for the rapid detection of pathogenic bacteria.
研究领域:
微生物学
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生物技术
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分子生物学
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DOI
PubMed
高影响因子