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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Electrospun groove shaped fibers with excellent hemocompatibility and highly selective capture of live bacteria from blood

Jianxu Bao,Shifan Chen,Xianda Liu,Ziyue Ling,Chunji Jiang,Zhaoxi Han,Wenjie Wang,Ran Wei,Changsheng Zhao,Weifeng Zhao

Sepsis is a life-threatening systemic inflammatory response syndrome mainly caused by bacterial infection. Directly capturing live bacteria from blood could effectively avoid the activation of pathogen-associated molecular patterns. Despite the availability of numerous materials capable of capturing bacteria, most of these materials will negatively affect blood cells and thus exhibit poor blood compatibility. Given that bacteria are generally smaller than blood cells, we designed a fiber with a groove, where the groove width is larger than bacteria but smaller than blood cells, and trace amounts of positively charged copolymers are loaded into the grooves. This sophisticated design allows the grooved fibers to capture bacteria efficiently as well as maintain good blood compatibility. In vitro experiments show that bacteria could be trapped inside the groove and the fibers can remove over 98% of bacteria. In rabbits’ bacteremia model, these fibers significantly reduce bacterial concentration and endotoxin level, offering a promising therapeutic approach for the treatment of bacteremia. Groove shaped fiber exhibits excellent blood compatibility in both in vitro and in vivo environments. The developed groove shaped fiber opens a new pathway to design functional materials for extracorporeal blood purification.

研究领域: 生物医学工程 · 材料科学 · 感染性疾病研究
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MEDICINAL CHEMISTRY RESEARCH · 2024 · IF 2.6

Identification of α-mangostin as a potent inhibitor of β-lactamase OXA-48

Cheng Wenhui,Zhang Yuejuan,Chen Cheng,Gao Lei,Lv Yuwei,Yu Dian,Chen Bin,Wan Yi

The production of carbapenemases is a significant mechanism contributing to carbapenem resistance in Enterobacteriaceae . Among these carbapenemases, OXA-48 presents a distinct challenge and threat, as most β-lactamase inhibitors do not effectively inhibit its activity. In this study, we investigated the inhibitory potential of α-mangostin against OXA-48 with an IC 50 value of 0.52 μM. Enzyme activity assays demonstrated that α-mangostin inhibited OXA-48 reversibly through a non-competitive and dose-dependent inhibition mode. The docking analysis revealed that the 7-hydroxyl group of α-mangostin formed hydrogen bonds with Thr197 and Trp222, whereas the 5-hydroxyl group and the 4-carbonyl group interacted with Lys116 and Met115. Our study indicates that α-mangostin exhibits significant inhibition against OXA-48 and holds promise as a potential compound for the development of β-lactamase inhibitors.

CAS / MDL: 41906-86-9 96036-03-2
研究领域: 微生物学 · 药理学 · 传染病学
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JOURNAL OF ANTIBIOTICS · 2021 ·Vol. 74 ·期 5 ·330-336 · IF 2.649

Study on the mechanisms of the cross-resistance to TET, PIP, and GEN in Staphylococcus aureus mediated by the Rhizoma Coptidis extracts

Lan Sugui,Li Zhirong,Su Aiqiu,Peng Yanhong,Liao Yanke,Liu Xuemei,Tan Qiang

The purpose of this study was focused on the mechanisms of the cross-resistance to tetracycline (TET), piperacillin Sodium (PIP), and gentamicin (GEN) in Staphylococcus aureus (SA) mediated by Rhizoma Coptidis extracts (RCE). The selected strains were exposed continuously to RCE at the sublethal concentrations for 12 days, respectively. The susceptibility change of the drug-exposed strains was determined by analysis of the minimum inhibitory concentration. The 16S rDNA sequencing method was used to identify the RCE-exposed strain. Then the expression of resistant genes in the selected isolates was analyzed by transcriptome sequencing. The results indicated that RCE could trigger the preferential cross-resistance to TET, PIP, and GEN in SA. The correlative resistant genes to the three kinds of antibiotics were upregulated in the RCE-exposed strain, and the mRNA levels of the resistant genes determined by RT-qPCR were consistent with those from the transcriptome analysis. It was suggested from these results that the antibacterial Traditional Chinese Medicines might be a significant factor of causing the bacterial antibiotic-resistance.

研究领域: 微生物学 · 药理学 · 分子生物学
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JOURNAL OF CHROMATOGRAPHY A · 2022 · IF 4.601

Simultaneous determination of eight carbapenems in milk by modified QuEChERS and ultra high performance liquid chromatography coupled with high-field quadrupole-orbitrap high-resolution mass spectrometry

Suo Decheng,Fan Xia,Xiao Zhiming,Liyang,Wang Peilong

A simple and accurate method of ultra high performance liquid chromatography (UHPLC) coupled with quadrupole-high field Orbitrap high-resolution mass spectrometry (QE HF HRMS) has been developed for analyzing 8 trace-level (µg/L) carbapenems in milk. Mass spectrometry conditions, chromatographic conditions, extraction solvent and QuEChERS procedures were optimized for determination of 8 carbapenems in milk. Samples were extracted and purified by modified QuEChERS procedure. Good separation for 8 carbapenems s was achieved with a PFP column at 8 min. Method validation results showed the linear ranges are 1–100 µg/L to 10–1,000 µg/L, the correlation coefficients are more than 0.995, and the recoveries of spiked samples are 79.3%–104% with a relative standard deviation less than 15%. This method successfully applied to monitor residue of carbapenems in real milk, four kinds of carbapenems have been detected in 8 sample of 79 collected milks with concentration ranged between 15 µg/L∼3,325 µg/L.

CAS / MDL: 96036-03-2
研究领域: 分析化学 · 食品安全 · 药理学
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ELECTROCHIMICA ACTA · 2023 · IF 6.6

A highly sensitive electrochemical sensor derived from peptide amphiphilic inspired self-assembled, ordered gold nanoparticles for determination of 22 β-lactams

Yexuan Mao,Yichao Fan,Ran Yang,Youyi Wang,Qingyue Li,Meng Dang,Xianqing Huang,Lianjun Song,Pingan Zhang,Miao Song,Liang Liu,Linli Wang,Shun Yu,Qiuyan Zhao,Xiya Zhang

Achieving ordered arrangement of gold nanoparticles (AuNPs) on an electrode can further improve the signal intensity of an electrochemical immunosensor. This ordered AuNPs self-assembly can be inspired by peptide amphiphile (PA). The rational design of hydrophobic chains in PA is a crucial step when the range of hydrophobic alkane chain from 14 to 18 carbons. As arginine (R) can combine specifically with Au surface plane (111), four PAs, i.e., C 15 H 23 CO-RR (C16R2), C 15 H 23 CO-RRR (C16R3), C 15 H 23 CO-RRRR (C16R4), and C 15 H 23 CO-RRRRR (C16R5), in this work are designed to investigate the extent of ordered AuNPs self-assembly. The results indicate that C16R4 presented a dominant electron donating ability and can inspire the self-assembly of AuNPs to form a mono-dispersed raspberry-like structure (C16R4-AuNPs) to obtain the largest ΔI (15.4 μA). In the detection system, C16R4-AuNPs firstly capture and immobilize anti-β-lactam receptor monoclonal antibodies (mAb) by electrostatic adsorption, and the anti-β-lactam receptor mAb possess antigen-antibody binding sites away from the active site of the receptors. Then, they capture β-lactam receptors through an antigen-antibody reaction to form a ternary complex (C16R4-AuNPs-mAb-β-lactam receptors). Based on this indirect-labeling process, the receptor active sites have been exposed completely, facilitating ligand recognition, which greatly further improves the sensitivity of the present method. Finally, a highly sensitive electrochemical immunosensor based on the ternary complex is developed to achieve the determination of 22 β-lactam antibiotics, which is more sensitive and applicable than other reported electrochemical sensors.

研究领域: 分析化学 · 生物医学工程 · 纳米技术
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Advanced Science · 2023 ·Vol. 11 ·期 9 ·2307173 · IF 15.1

Synergistic D-Amino Acids Based Antimicrobial Cocktails Formulated via High-Throughput Screening and Machine Learning

Jingzhi Yang,Yami Ran,Shaopeng Liu,Chenhao Ren,Yuntian Lou,Pengfei Ju,Guoliang Li,Xiaogang Li,Dawei Zhang

Antimicrobial resistance (AMR) from pathogenic bacterial biofilms has become a global health issue while developing novel antimicrobials is inefficient and costly. Combining existing multiple drugs with enhanced efficacy and/or reduced toxicity may be a promising approach to treat AMR. D-amino acids mixtures coupled with antibiotics can provide new therapies for drug-resistance infection with reduced toxicity by lower drug dosage requirements. However, iterative trial-and-error experiments are not tenable to prioritize credible drug formulations, owing to the extremely large number of possible combinations. Herein, a new avenue is provide to accelerate the exploration of desirable antimicrobial formulations via high-throughput screening and machine learning optimization. Such an intelligent method can navigate the large search space and rapidly identify the D-amino acid mixtures with the highest anti-biofilm efficiency and also the synergisms between D-amino acid mixtures and antibiotics. The optimized drug cocktails exhibit high antimicrobial efficacy while remaining non-toxic, which is demonstrated not only from in vitro assessments but also the first in vivo study using a lung infection mouse model.

研究领域: 药理学 · 微生物学 · 机器学习 · 生物技术
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