Microbiology Spectrum
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2025
·
IF 3.8
Leisheng Sun,Zonghan Jiang,Dingding Li,Yao Tian,Junqi Liu,Zhiliang Sun
Multi-drug-resistant Aeromonas hydrophila infections are becoming increasingly threatening, and the development of novel antimicrobial drugs is indispensable. Herein, we demonstrate that this novel peptide is highly active against colistin-resistant A. hydrophila strain and shows sustained killing efficacy in vivo. Mechanistic studies showed that D-Q7 interacted with phosphatidylglycerol and lipopolysaccharide in the bacterial cell membrane, with an increase in intracellular ROS as well as a decrease in ATP level, ultimately leading to cell membrane disruption and bacterial death. Importantly, our study identified gene3832 as a potential regulator of membrane permeability, which may act as a potential modulator of bacterial susceptibility to D-Q7. The role of gene3832 was further confirmed by gene knockout and complementation assays. Consistently, we observed that gene3832 was also involved in biofilm formation in the colistin-resistant A. hydrophila strain. Collectively, our study provides an effective antimicrobial strategy with potential targets for the treatment of drug-resistant A. hydrophila infection.
研究领域:
微生物学
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抗生素耐药
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肽类治疗
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感染性疾病
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分子微生物学
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PubMed
高影响因子
Toxics
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2025
·Vol. 13
·期 9
·706
·
IF 4.1
Juntong Gao,Qimeng Yang,Xiarui Fan,Xinwei Zhou,Peng Ren
Toxicological effects of microplastics (MPs) have been confirmed in a variety of microorganisms in aquatic environments, and they are closely correlated with the physicochemical properties of the MPs. In a natural environment, different aging treatments always induce different alterations in the physicochemical properties of MPs, thus influencing their environmental behaviors and biotoxicity. In this work, physicochemical properties and toxicity towardsEscherichia coli(E. coli) were investigated in polystyrene (PS) MPs (3 and 10 μm) before and after aging by UV irradiation and biofilm formation, respectively. The results show that UV irradiation and biofilm formation led to different alterations in the surface morphologies and functional groups of PS. The UV-aged 3 μm PS had the strongest inhibitory effect onE. coligrowth, and the bio-aged 10 μm PS had the strongest beneficial effect onE. coligrowth. Also, the ATPase activity, production of intercellular ROS, and MDA content of theE. coliwere affected differently. UV aging enhanced the toxicity of PS towardsE. coli, while bio-aging had an opposite weakening effect. Overall, our research verified the remarkable differences in the physicochemical properties and biotoxicity of PS induced by UV aging and bio-aging.
研究领域:
环境毒理学
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微生物学
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生态毒理学
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环境科学
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2025
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IF 7.7
Guangxu Fang,Kai Wen,Qixuan Zhao,Yingxuan Chen,Yanbo Wang,Haobo Han,Quanshun Li
Postoperative tissue analysis is essential for the evaluation of surgical outcome in the tumor therapy. The identification of tumor biomarkers represents a supplementary approach to histochemical observation, facilitating the diagnosis of cancers at molecular level. Herein, a biosensor was developed by integrating an ATP-responsive aptazyme and its substrate on the surface of streptavidin magnetic beads to achieve the simultaneous detection of ATP and apurinic/apyrimidinic endonuclease 1 (APE1) within cancer cells. This strategy enabled the biosensor to respond to excessive ATP in cancer cells, thereby generating the primer. Meanwhile, the biosensor contained a double-stranded DNA with apurinic/apyrimidinic site, which allowed it to respond to APE1 and produce a padlock. The released primer and padlock triggered the rolling cycle amplification to yield an amplified fluorescent or colorimetric signal. The biosensor functioned as the “AND”-logic gate, effectively distinguishing cancer and non-cancerous cells. Moreover, the biosensor exhibited high specificity and sensitivity in discriminating the tumor and non-tumor tissues isolated from the patients bearing non-small cell lung cancer. Taken together, the biosensor showed the potential in clinical molecular diagnosis, serving as a promising supplementary approach for the postoperative tissue analysis.
研究领域:
生物医学工程
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分子生物学
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癌症诊断
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分析化学
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DOI
高影响因子
WATER RESEARCH
·
2025
·
IF 12.4
Xiaoming Zou,Baoyin Zhang,Yujiao Jing,Lihui Zong,Ligui Wu,Qunyan Zhou,Yue Fang,Kaifang Shen,Xubiao Luo,Lingling Rong
The pivotal role of plasmid-mediated conjugative transfer in the spread of antibiotic resistance genes (ARGs) is well established, and environmental chemicals exert considerable selective pressure on this process. Oral antidiabetic drugs (OADs) are frequently detected in aquatic environments at concentrations reaching the mg/L range. However, their influence on the conjugative transfer of plasmid remains largely unexplored. Here, we investigated the effects of eight widely used OADs on the transfer of the RP4 plasmid between Escherichia coli strains isolated from representative wastewater sources. The results showed that all tested OADs significantly enhance plasmid transfer ( P < 0.05), albeit with up to a four - fold variation in change. Notably, this phenomenon is independent of OAD degradation profiles, but strongly associated with bacterial biochemical responses ( P < 0.05) such as reactive oxygen species (ROS) production, cell membrane permeability, and ATP synthesis. Mechanistic analyses further identify OAD electrophilicity as a key chemical determinant, modulating both physiological processes (membrane permeability and ATP production) and molecular components—genes ( ybbA, mlaA , and ompF ) and their corresponding proteins (YbbA, MlaA, and OmpF)—involved in conjugative transfer. Furthermore, results demonstrate that OADs consistently increase ARG abundance and diversity in activated sludge systems, an effect strongly correlated with their electrophilicity ( P < 0.05). Collectively, our findings reveal, for the first time, that OAD electrophilicity is a critical driver of ARG dissemination in wastewater treatment systems, thereby providing molecular-level insights and a theoretical foundation for controlling ARG spread.
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Bioactive Materials
·
2024
·
IF 18
Yuan Gao,Mengyao Mu,Yiju Wei,Bowen Yan,Hui Liu,Kai Guo,Mengmeng Zhang,Xiaohui Dai,Xiao Sun,David Tai Leong
Biodegradable two-dimensional nanomaterials could be a significant breakthrough in the field of oncology nanotheranostic agents, which are rapidly emerging as promising candidates for tumor theranostic applications. Herein, a novel biodegradable ferrous sulfide nanosheet (FeS NS) is developed. Compared to the traditional photothermal material, black phosphorus nanosheet (BP NS), FeS demonstrates superior degradability and enhanced photothermal performance, and making it ideal for efficient photothermal therapy (PTT) of tumors. In the acidic tumor microenvironment, FeS degrades and releases H 2 S, which inhibits mitochondrial respiration and ATP production. This process leads to a reduction in heat shock protein expression, lowering the resistance of tumor cells to photothermal stimulation, and improving the efficacy of PTT. The released Fe 2+ exhibits efficient peroxidase activity, triggering ferroptosis in tumor cells. Furthermore, due to its superparamagnetic nature, FeS NSs could accumulate at the tumor site and provide a strong magnetic resonance imaging (MRI) signal for imaging-guided tumor therapy. Overall, as a promising alternative to BP, the FeS NSs are a potentially innovative nanotheranostic agent of tumors, offering a synergistic approach to ferroptosis−PTT with MRI guidance.
研究领域:
纳米技术
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肿瘤学
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诊疗一体化
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材料科学
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PubMed
高影响因子
ANALYST
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2025
·
IF 3.3
Liping Lu,kang chunyu
Nicotinamide adenine dinucleotide (NADH) is a crucial biomolecule that serves as an essential cofactor in numerous biocatalytic reactions and a pivotal regulator of mitochondrial function and cellular physiology. This study developed a SECM platform utilizing a double-mediator system for the real-time, in situ, and non-invasive detection of intracellular NADH at the single living cell level. The system employs 1-methoxy-5-methylphenazinium methyl sulfate (mPMS), which permeates the cell membrane to oxidize intracellular NADH, and ferricyanide ([Fe(CN)₆]³⁻), which shuttles electrons from the reduced mPMS to the SECM tip. This methodology was applied to investigate mitochondrial impairment in human hepatoma (HepG2) cells induced by polycyclic aromatic sulfur heterocycles (PASHs). The metabolic response was corroborated by analyzing poly(ADP-ribose) polymerase (PARP) activity, adenosine triphosphate (ATP) content, and mitochondrial membrane potential (MMP). Results demonstrated that exposure to dibenzothiophene (DBT) activated PARP, leading to severe depletion of NADH and ATP and a significant decline in MMP, thereby confirming comprehensive mitochondrial dysfunction. Comparative analysis with its non-sulfur analog fluorene (Flu) revealed that the sulfur atom in DBT's structure is a critical determinant of its enhanced cytotoxicity. This work establishes a reliable and innovative analytical approach for assessing the subcellular metabolic effects of environmental pollutants, providing a new platform for in-depth cytotoxicity mechanistic studies.
研究领域:
分析生物医学
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环境毒理学
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细胞代谢
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分子毒理学
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肿瘤学
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生物电化学
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药理学
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JOURNAL OF ANALYTICAL CHEMISTRY
·
2017
·Vol. 72
·期 4
·437-444
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IF 0.723
Ji Xiaoting,Lv Haoyuan,Zhang Wei,Ding Caifeng
In this paper, an adenosine-5′-triphosphate ( ATP ) controlled-release strategy to construct a fluorescence sensing platform has been designed. In the sensing platform, because of ATP aptamer and singlestranded DNA ( ssDNA )-linked mesoporous silica nanoparticles ( Si-MPs ) were hybridized, the pores of Si-MPs were blocked with Au nanoparticles ( AuNPs ) modified with ATP aptamer. Carboxy fluorescein was plugged in channels of Si-MPs. In the presence of target molecule ATP, the ATP aptamer combined with ATP and the AuNPs got away from the pore of the surface of Si-MPs modified by ssDNA. 5-Carboxyfluorescein molecule was released to allow the fluorescent detection. By monitoring the fluorescence at 518 nm, ATP could be quantitatively detected with a detection limit of 6 × 10 –8 M. The linear response range was 6 × 10 –8 to 1 × 10 –6 M. This assay was also able to discriminate ATP from its analogs. The controlled-release aptamer-based biosensor could have an effective application in human breast cancer MCF-7 cells.
研究领域:
纳米技术
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生物化学
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分析化学
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分子生物学
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癌症研究
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高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Chen Xubo,Zhao Xueyan,Lan Fazhang,Zhou Tao,Cai Hua,Sun Haiying,Kong Weijia,Kong Wen
Studies have reported attenuation of insulin resistance (IR) by improving phosphorylation of the insulin signalling pathway. However, the upstream molecular signalling pathway is still elusive. In this study, Western blot was used to evaluate the phosphorylation level of the insulin signalling pathway and the AMPK pathway. 2-NBDG was used to evaluate glucose uptake. Ca 2+ imaging was used to assess change of intracellular Ca 2+ concentration. We found that NaHS enhanced the intracellular Ca 2+ concentration and glucose uptake and activated the insulin signalling cascade in a palmitic acid (PA)-induced IR model in C2C12 cells. Furthermore, activation of the IRS1/PI3K/AKT pathway and glucose uptake were decreased when AMPK or CaMKKβ was inhibited. Our study also showed that the mitochondrial electron transport chain, ATP production, and intramitochondrial cAMP declined in the IR model but that this effect was reversed by NaHS, an effect that may be mediated by the Ca 2+ /CaMKK2/AMPK and PI3K/AKT pathways. Our data indicate that H 2 S improves activation of the insulin signalling cascade and glucose uptake via activation of the Ca 2+ /CaMKK2/AMPK pathway and mitochondrial metabolism in C2C12 cells. Furthermore, NaHS protects mitochondrial function and maintains normal ATP production by activating the cAMP system and the Ca 2+ /CaMKK2/AMPK and PI3K/ATK pathways.
研究领域:
分子生物学
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细胞代谢
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内分泌学
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糖尿病研究
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PubMed
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
·
2019
·Vol. 126
·期 1
·102-112
·
IF 2.683
Lin W.,Yuan D.,Deng Z.,Niu B.,Chen Q.
ObjectivesIn our previous research, we have developed a new combination disinfectant, glutaraldehyde‐didecyldimethylammonium bromide (GD). It was verified that GD had a strong effect on both Escherichia coli and Staphylococcus aureus. In this work, Candida albicans was selected as an object, and it could be killed by GD. We aimed to investigate the cellular and molecular mechanism of GD effecting on C. albicans.Methods and ResultsThe results of sterilization experiment indicated that GD was effective on C. albicans. Flow cytometry and atomic absorption spectrometry were applied to detect cell membrane damage of C. albicans. Luciferase reaction and Bradford method were carried out to detect ATP content and protein quantitation. Transmission electron microscopy was used for intracellular organelles morphological observation. In order to study changes in mitochondrial membrane potential, Rh 123 was used as an indicator. DNA conformation analysis was performed by molecular modelling and circular dichroism. The results indicated that membrane permeability was increased rapidly owing to GD effect, and the leaked K+ and Mg2+ were about 12·1 and 12·4 times those of the control, respectively, at 10 min after GD treatment. Simultaneously, ATP and protein also leaked rapidly out of the cell. Mitochondrial membrane potential was destroyed, succinic dehydrogenase activity was significantly decreased and DNA conformation was changed because of GD action.ConclusionsGlutaraldehyde‐didecyldimethylammonium bromide disinfected C. albicans through distorting cell membrane integrity and permeability, disturbing the intracellular homeostasis by intracellular substances leakage, especially K+, Mg2+, ATP and protein, causing electrolyte imbalance of mitochondria, changing DNA structure, which finally led to cell death.Significance and Impact of the StudyThis study focused on the cellular and molecular mechanism of GD as a disinfectant against C. albicans. It is important to provide theoretical support to GD against Candida albicans in practical application.
研究领域:
微生物学
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分子生物学
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细胞生物学
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Tiange Ma,Xingjiang Li,Manuel Montalbán-López,Xuefeng Wu,Zhi Zheng,Dongdong Mu
Lactococcus lactis is a crucial food-grade cell factory for secreting valuable peptides and proteins primarily via the Sec-dependent pathway. YidC, a membrane insertase, facilitates protein insertion into the lipid membrane for the translocation. However, the mechanistic details of how YidC affects protein secretion in L. lactis remain elusive. This study investigates the effects of deleting yidC1/yidC2 on L. lactis phenotypes and protein secretion. Compared to the original strain, deleting yidC2 significantly decreased the relative biomass, electroporation efficiency, and F-ATP activity by 25%, 47%, and 33%, respectively, and weakened growth and stress resistance, whereas deleting yidC1 had a minimal impact. The absence of either yidC1 or yidC2 reduced target proteins secretion. Meanwhile, there is a considerable alteration in the transcription levels of genes involved in the secretion pathway, with secY transcription increasing over 135-fold. Our results provide a theoretical foundation for further improving target protein secretion and investigating the YidC function.
研究领域:
微生物学
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生物技术
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蛋白质工程
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高影响因子
BIOLOGY AND FERTILITY OF SOILS
·
2020
·Vol. 56
·期 5
·619-631
·
IF 5.521
Zhou Xiaoyu,Chen Lin,Xu Jianming,Brookes Philip C.
The regulatory gate hypothesis considers that soil organic C mineralization is a two-step process, where stable C is firstly transformed abiotically and is only then a microbially available substrate. The mechanisms involved in the abiotic conversion of non-microbially available to available soil organic C remain largely unknown. We conducted a perfusion experiment using a repeated fumigated-incubated soil and the corresponding fresh soil. We found that repeated fumigation-incubation significantly decreased soil microbial ATP to 0.22 nmol g −1 soil, 10% of that in the fresh soil, and significantly destroyed microbial composition and diversity. However, it had little influence on the soil CO 2 -C evolution rate after the flush of fumigant-killed dead biomass (8 μg CO 2 -C g −1 soil day −1 ) or dissolved organic C (DOC) concentration (about 7 μg C g −1 soil) and composition during long-term perfusion. We conclude that soil CO 2 evolution rate and DOC generation were not regulated by the size or composition of the soil microbial communities. This is in support of the regulatory gate hypothesis. We suggest that abiotic processes in soil organic C mineralization need to be considered more and studied further.
Graphical abstract
研究领域:
土壤学
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微生物学
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环境科学
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高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Qichao Hu,Yuan Chen,Wenwen Zhang,Yubing Li,Xinyu Deng,Lisheng Chen,Zongyuan Zhou,Xiao Ma,Jinhao Zeng,Yanling Zhao
Background Acute gastric injury, a common and recurring global digestive disorder, significantly impairs patient quality of life and overall health. Dehydroevodiamine (DHE), a bioactive natural product derived from Tetradium ruticarpum ( A. Juss. ) Hartley, shows potential therapeutic effects on acute gastric injury. This study investigates the underlying mechanisms of DHE's alleviating effects on acute gastric injury. Methods The gastric mucosal protective effect of DHE was confirmed through in vivo and in vitro acute gastric injury models. Biotin pulldown MS and molecular dynamics simulations identified DHE's target. CETSA and SPR assays validated DHE's affinity for IKKβ. Protein site mutation validation and MST pinpointed the direct binding sites of DHE on IKKβ. Additionally, the potential mechanism by which DHE ameliorates acute gastric injury was elucidated using WB, IHC, and IF methods, and further confirmed by rescue experiments. Results DHE effectively ameliorated IDO-induced gastric injury in GES-1 cells and rat gastric mucosa, both in vitro and in vivo . Biotin pulldown MS identified IKKβ as the target of DHE in alleviating gastric injury. CETSA and SPR assays confirmed DHE's direct binding to IKKβ. Molecular dynamics simulations, protein mutation experiments, and MST results pinpointed GLU-149, GLU-49, and ASP-103 in the ATP-binding pocket as the binding sites of DHE on IKKβ. Notably, DHE was found to competitively bind to IKKβ with ATP. Mechanistically, DHE attenuated IDO-induced gastric injury by inhibiting the IKKβ-p65/NLRP3 signaling pathway. Importantly, exogenous activation of IKKβ reversed the therapeutic effect of DHE, indicating that DHE's efficacy depends on IKKβ. Conclusion DHE attenuated IDO-induced gastric injury by inhibiting the IKKβ-p65/NLRP3 signaling pathway. Notably, DHE is a novel ATP-competitive IKKβ inhibitor that prevents phosphorylation by targeting GLU-149, GLU-49, and ASP-103 in the ATP-binding pocket. This study reveals new targets of action for DHE, providing a new molecular basis for using DHE in treating inflammation-related diseases.
研究领域:
药理学
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胃肠病学
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分子生物学
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生物化学
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PubMed
高影响因子
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