Frontiers in Bioengineering and Biotechnology
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2021
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IF 5.89
Zhang Guangbao,Hu Shuting,Jia Xiaoqiang
Although many whole-cell biosensors (WCBs) for the detection of Cd2+ have been developed over the years, most lack sensitivity and specificity. In this paper, we developed a Cd2+ WCB with a negative feedback amplifier in P. putida KT2440. Based on the slope of the linear detection curve as a measure of sensitivity, WCB with negative feedback amplifier greatly increased the output signal of the reporter mCherry, resulting in 33% greater sensitivity than in an equivalent WCB without the negative feedback circuit. Moreover, WCB with negative feedback amplifier exhibited increased Cd2+ tolerance and a lower detection limit of 0.1 nM, a remarkable 400-fold improvement compared to the WCB without the negative feedback circuit, which is significantly below the World Health Organization standard of 27 nM (0.003 mg/L) for cadmium in drinking water. Due to the superior amplification of the output signal, WCB with negative feedback amplifier can provide a detectable signal in a much shorter time, and a fast response is highly preferable for real field applications. In addition, the WCB with negative feedback amplifier showed an unusually high specificity for Cd2+ compared to other metal ions, giving signals with other metals that were between 17.6 and 41.4 times weaker than with Cd2+. In summary, the negative feedback amplifier WCB designed in this work meets the requirements of Cd2+ detection with very high sensitivity and specificity, which also demonstrates that genetic negative feedback amplifiers are excellent tools for improving the performance of WCBs.
研究领域:
生物技术
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环境科学
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合成生物学
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DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
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2024
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IF 5.6
Ling Zhou,Qingyin Tian,Wenjie Ding,Hongmin Hu,Tingting Shi,Guogui Ning,Lianggui Wang,Yuanzheng Yue,Xiulian Yang
Osmanthus fragrans have a unique aroma, its extracts and its constituents have a wide range of biological activities, making them of great industrial value. β-ionone is a crucial factor in determining the aroma quality of O. fragrans . The synthesis mechanism of β-ionone is essential for studying the aromatic compounds in O. fragrans . This study demonstrated that the OfMYB1R114-OfSDIR1-like- OfCCD4 module regulates β-ionone synthesis in O. fragrans . A MYB-related transcription factor OfMYB1R114 increased β-ionone aroma substance and elevated OfCCD4 expression level through binding to the OfCCD4 promoter and activating its expression; this demonstrated a positive loop in β-ionone synthesis. Screening for interacting proteins using a cDNA library of O. fragrans petals, the interaction pair between OfMYB1R114 and OfSDIR1-like was validated. In addition, OfSDIR1-like negatively regulated β-ionone synthesis by ubiquitinating the OfMYB1R114 protein and decreasing the ability of OfMYB1R114 to activate its downstream target gene OfCCD4 . Interestingly, OfMYB1R114 could directly bind to the OfSDIR1-like promoter and repress its transcription, revealing a negative feedback loop between OfMYB1R114 and OfSDIR1-like. Hence, this suggests that OfSDIR1-like is a new novel regulator that functions in β-ionone synthesis via the OfMYB1R114-mediated aroma pathway. The mechanistic framework revealed by the studies is that the OfMYB1R114-mediated module OfMYB1R114-OfSDIR1-like- OfCCD4 regulates β-ionone synthesis. It sheds light on the molecular mechanisms at the basis of aroma synthesis in O. fragrans and provides theoretical basis and technical guidance for the comprehensive utilisation and industrial development of O. fragrans aroma substance.
研究领域:
植物科学
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分子生物学
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生物化学
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农学
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DOI
高影响因子
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
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2018
·Vol. 20
·期 6
·4347-4350
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IF 3.906
Wei Huang,Yan Zhou,Yuequan Deng,Yi He
We report a negative feedback loop based on proton-driven in situ formation of plasmonic MoO3−x nanosheets. When the concentration of Cu2+ is below a certain level, the reaction of Cu2+ and glutathione (GSH) produces Cu+ and few protons. However, when the concentration of Cu2+ is above a certain threshold, the reaction of GSH and Cu2+ will generate enough protons in the system to initiate the redox reaction of GSH and MoO3 nanosheets, which generates plasmonic MoO3−x nanosheets. This process in turn inhibits the reaction of GSH and Cu2+, which sequesters the excess Cu2+ from the system. The formation of MoO3−x nanosheets lowers the concentration of protons in solution and turns off the production of MoO3−x nanosheets. More importantly, the threshold concentration of Cu2+ can be easily regulated by changing the concentration of MoO3 nanosheets.
研究领域:
材料科学
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化学
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纳米技术
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DOI
PubMed
高影响因子
Synthetic and Systems Biotechnology
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2023
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IF 4.8
Shuting Hu,Guangbao Zhang,Xiaoqiang Jia
In this study, we designed a Cd 2+ whole-cell biosensor with both positive and negative feedback cascade amplifiers in Pseudomonas putida KT2440 (LTCM) based on our previous design with only a negative feedback amplifier (TCM). The results showed that the newly developed biosensor LTCM was greatly improved compared to TCM. Firstly, the linear response range of LTCM was expanded while the maximum linear response range was raised from 0.05 to 0.1 μM. Meanwhile, adding a positive feedback amplifier further increased the fluorescence output signal of LTCM 1.11–2.64 times under the same culture conditions. Moreover, the response time of LTCM for detection of practical samples was reduced from 6 to 4 h. At the same time, LTCM still retained very high sensitivity and specificity, while its lowest detection limit was 0.1 nM Cd 2+ and the specificity was 23.29 (compared to 0.1 nM and 17.55 in TCM, respectively). In summary, the positive and negative feedback cascade amplifiers effectively improved the performance of the biosensor LTCM, resulting in a greater linear response range, higher output signal intensity, and shorter response time than TCM while retaining comparable sensitivity and specificity, indicating better potential for practical applications.
研究领域:
生物技术
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环境科学
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合成生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Mengmeng Nan,Kangle Guo,Tao Jia,Guangtong Wang,Shaoqin Liu
Soft robots have great potential applications in manufacturing, disaster rescue, medical treatment, etc. Artificial muscle is one of the most important components of a soft robot. In previous years, hydrogel actuators that can be controllably deformed by the stimuli of external signals have been developed as good candidates for muscle-like materials. In this article, we successfully prepared a chemical fuel-driven self-resettable bilayer hydrogel actuator mimicking natural muscles with the aid of a new negative feedback reaction network. The actuator can temporarily deform upon the addition of H+ (chemical fuel). Subsequently, H+ accelerated the reaction between BrO3– and Fe(CN)64–, which consume H+. It resulted in the spontaneous recovery of the pH as well as the shape of the actuator. Such an actuator exhibits a great similarity with natural muscles in actuation mechanisms and automaticity in the manipulation compared to the widely reported stimuli-responsive hydrogel actuators. This illustrates that fuel-driven self-resettable hydrogel is a promising dynamic material for mimicking the functions of living creatures.
研究领域:
材料科学
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生物医学工程
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
·
IF 15.1
Zhi Zheng,Jian Sun,Jun Wang,Suisui He,Yun Huang,Xu Yang,Yuqi Zhao,Cui-Yun Yu,Hua Wei
The compromised microenvironment after cartilage injury generally leads to low survival or abnormal differentiation of implanted stem cells for fibrocartilage formation with weak mechanical properties. Suitable and safe bionic materials can provide mechanical properties for cartilage repair while promoting cartilage regeneration effects. However, to our knowledge, mechanical strength modulation of therapeutic peptide-based bionic hydrogels remains relatively unexplored, and further application of peptide-based bionic hydrogels in a negative feedback manner for defective cartilage repair has been seldom reported so far. In this study, we reported the first sophisticated design and fabrication of a dual cross-linked peptide-based hydrogel for promoted cartilage regeneration in a feedback-regulated manner. The integration of multiple supramolecular forces including host–guest interactions and extensive hydrogen bonding endow the resulting hydrogels with excellent self-healing and mechanical strength for highly synergistic lubrication properties and compressive performance. More importantly, the unique integrative peptide VPM-pmTGF-β1 can realize on-demand pmTGF-β1 release that is triggered by the MMP-3-responsive cleavage of a VPM sequence. When the VPM-pmTGF-β1-modified hydrogel system is implanted into the cartilage defect sites in a model of SD rats, MMP-3-triggered on-demand pmTGF-β1 release suppresses IκBα/NF-κB signaling pathway-induced cartilage inflammation in a negative feedback manner while promoting the targeted cartilage differentiation of BMSCs for efficient cartilage regeneration. The novel strategy developed herein contributes to a more comprehensive and in-depth understanding of the biological properties of peptide-based hydrogels for cartilage defect repair and provides a simple yet powerful means for clinical translations.
研究领域:
生物材料
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组织工程
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再生医学
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生物力学
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分子生物学
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产品关联
DOI
高影响因子
CARCINOGENESIS
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2023
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IF 4.7
Han Sijia,Jin Xueying,Hu Tianyu,Chi Feng
Downregulation of ARHGAP25 was found in the tumor samples from breast cancer patients and five breast cancer cell lines. However, its precise role and molecular mechanisms in breast cancer remain completely unknown. Herein, we found that knockdown of ARHGAP25 in breast cancer cells promoted proliferation, migration and invasion of breast cancer cells. Mechanistically, ARHGAP25 silence facilitated the activation of the Wnt/β-catenin pathway and the upregulation of its downstream molecules (including c-Myc, Cyclin D1, PCNA, MMP2, MMP9, Snail, and ASCL2) by directly regulating Rac1/PAK1 in breast cancer cells. In vivo xenograft experiments indicated ARHGAP25 silence promoted tumor growth and activated the Wnt/β-catenin pathway. In contrast, overexpression of ARHGAP25 in vitro and in vivo impeded all of the above cancer properties. Intriguingly, ASCL2, a downstream target of the Wnt/β-catenin pathway, transcriptionally repressed the expression of ARHGAP25 and therefore constituted a negative feedback loop. Moreover, bioinformatics analysis indicated that ARHGAP25 is significantly correlated with tumor immune cell infiltration and the survival of patients with different immune cell subgroups in breast cancer. Collectively, our work revealed that ARHGAP25 suppressed tumor progression of breast cancer. It provides a novel insight for the treatment of breast cancer.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
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IF 12.8
Xiao Zheng,Ying Liu,Yiqiong Liu,Jie Zang,Kun Wang,Zichen Yang,Nana Chen,Jiuyuan Sun,Li Huang,Yan Li,Liangyi Xue,Hui Zhi,Xiaoyou Zhang,Min Yu,Shiyu Chen,Haiqing Dong,Yongyong Li
Repolarizing the tumor-associated macrophages (TAMs) towards the antitumoral M1-like phenotype has been a promising approach for cancer immunotherapy . However, the anti-cancer immune response is severely limited mainly by the repolarized M1-like macrophages belatedly returning to the M2-like phenotype (i.e., negative feedback). Inspired by nitric oxide (NO) effectively preventing repolarization of inflammatory macrophages in inflammatory diseases, herein, we develop an arginine assembly, as NO nano-donor for NO generation to prevent the negative feedback of the macrophage repolarization. The strategy is to first apply reversible tagging of hydrophobic terephthalaldehyde to create an arginine nano-assembly, and then load a toll-like receptor 7/8 agonist resiquimod (R848) (R848@Arg). Through this strategy, a high loading efficiency of 40 % for the arginine and repolarization characteristics for TAMs can be achieved. Upon the macrophage repolarization by R848, NO can be intracellularly generated from the released arginine by the upregulated inducible nitric oxide synthase. Mechanistically, NO effectively prevented the negative feedback of the repolarized macrophage by mitochondrial dysfunction via blocking oxidative phosphorylation . Notably, R848@Arg significantly increased the tumor inhibition ratio by 3.13-fold as compared to the free R848 by maintaining the M1-like phenotype infiltrating into tumor. The Arg-assembly as NO nano-donor provides a promising method for effective repolarization of macrophages.
研究领域:
癌症免疫学
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药理学
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纳米技术
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免疫治疗
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）