eLife
·
2024
·
IF 6.4
Tian Yuan,Yifan Wang,Yuchen Jin,Hui Yang,Shuai Xu,Heng Zhang,Qian Chen,Na Li,Xinyue Ma,Huifang Song,Chao Peng,Ze Geng,Jie Dong,Guifang Duan,Qi Sun,Yang Yang,Fan Yang,Zhuo Huang
Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the detailed mechanism underlying quinidine’s blockade against KCNT1 (Slack) remains elusive. Here, we report a functional and physical coupling of the voltage-gated sodium channel NaV1.6 and Slack. NaV1.6 binds to and highly sensitizes Slack to quinidine blockade. Homozygous knockout of NaV1.6 reduces the sensitivity of native sodium-activated potassium currents to quinidine blockade. NaV1.6-mediated sensitization requires the involvement of NaV1.6’s N- and C-termini binding to Slack’s C-terminus and is enhanced by transient sodium influx through NaV1.6. Moreover, disrupting the Slack-NaV1.6 interaction by viral expression of Slack’s C-terminus can protect against SlackG269S-induced seizures in mice. These insights about a Slack-NaV1.6 complex challenge the traditional view of ‘Slack as an isolated target’ for anti-epileptic drug discovery efforts and can guide the development of innovative therapeutic strategies for KCNT1-related epilepsy.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
LANGMUIR
·
2014
·
IF 4.384
Dongmei Cui,Li Mi,Xuan Xu,Jusheng Lu,Jing Qian,Songqin Liu
Cytochrome P450 enzymes (cyt P450s) with an active center of iron protoheme are involved in most clinical drugs metabolism process. Herein, an electrochemical platform for the investigation of drug metabolism in vitro was constructed by immobilizing cytochrome P450 2D6 (CYP2D6) with cyt P450 reductase (CPR) on graphene modified glass carbon electrode. Direct and reversible electron transfer of the immobilized CYP2D6 with the direct electron transfer constant of 0.47 s–1 and midpoint potential of -0.483 V was obtained. In the presence of substrate tramadol, the electrochemical-driven CYP2D6 mediated catalytic behavior toward the conversion of tramadol to o-demethyl-tramadol was confirmed. The Michaelis–Menten constant (Kmapp) and heterogeneous reaction rate constant during the metabolism of tramadol were calculated to be 23.85 μM and 1.96 cm s–1, respectively. The inhibition effect of quinidine on CYP2D6 catalyze-cycle was also investigated. Furthermore, this system was applied to studying the metabolism of other drugs.
研究领域:
生物化学
·
药物代谢
·
电化学分析
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Environmental Chemical Engineering
·
2025
·
IF 7.2
Jinli Qiu,Yao Feng,Zhiqin Luo,Xinying Chu,Xiaoxue Pan,Fuqiang Liu
Heterogeneous Electro-Fenton (HEF) technology, which requires only oxygen and electric energy, holds significant potential for organic wastewater treatment due to its high efficiency. In this study, an iron-carbon composite cathode catalyst (Fe 3 C/BC) featuring highly dispersed Fe 3 C active sites on biochar (BC) was designed and synthesized to degrade nitenpyram (NTP), a representative neonicotinoid pesticide. The optimized Fe 3 C/BC-HEF system exhibited remarkable catalytic activity for NTP degradation, along with strong pH tolerance (3.0–9.0) and adaptability to various water matrices. This excellent performance can be attributed not only to its enhanced H 2 O 2 generation capability but also to the obviously faster H 2 O 2 activation efficiency to produce reactive oxygen species (ROS) for NTP degradation. Reactive species quenching experiments and electron paramagnetic resonance (EPR) spectroscopy confirmed that singlet oxygen (¹O 2 ) was the dominant reactive species responsible for NTP degradation. Furthermore, combined with HPLC-MS/MS analysis and Fukui index calculation, the intermediate products and degradation pathway of NTP were verified. The excellent reusability and stability of the cathode could be due to the protective role of BC, which minimized direct contact between Fe₃C active sites and the reaction solution, and thus reducing Fe 3 C corrosion during the HEF process. This study offers important insights into the design of superior metal-carbon hybrid cathode for electrochemical water remediation technologies.
研究领域:
环境科学
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电化学工程
·
农药污染治理
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Li Liu,Maomin Peng,Ke Xu,Hong Xia,Xitian Peng,Lijun Peng,Youxiang Zhou,Jin Z. Zhang
Highly stable and photoluminescent methylammonium lead halide perovskite quantum dots (MAPbBr3 PQDs) have been synthesized and applied for the fluorescence quenching detection of clothianidin in fruit and vegetable samples. Characterizations using different techniques, including photoluminescence (PL), X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and time-resolved PL (TRPL), show that static quenching is the dominant fluorescence quenching mechanism of MAPbBr3 PQDs with clothianidin. Hydrogen bonds or van der Waals forces play major roles in the MAPbBr3 PQDs–clothianidin interaction. Under optimized conditions, the relative PL intensity of MAPbBr3 PQDs is linear to the concentration of clothianidin in the 0.0 and 20.0 mg/L range with a detection limit of 0.17 μg/kg. Excellent recoveries of 79.5–115.4% were acquired for radish and banana samples with a relative standard deviation below 9.4%. These results indicate that PQDs can be used for qualitative and quantitative identification of clothianidin, providing an effective detection method for risk prevention and control of neonicotinoid pesticide residues in agricultural products.
研究领域:
分析化学
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食品安全
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2022
·
IF 5.304
Yanju Wu,Kainan Guo,Junqi Zhao,Qunpeng Duan,Fei Wang,Kui Lu
On the surface of glassy carbon electrode, electrochemically reduced graphene oxide-anionic pillar[6]arene (ErGO-AP6) composite film is directly constructed using a potentiostatic method. This composite film is used as an electrochemical sensing platform for detecting clothianidin (CLO). Studies on the interaction mechanism reveal a higher supramolecular recognition capability between AP6 and CLO, compared to that between β -cyclodextrin ( β -CD) and CLO. Owing to the synergistic effect of ErGO and AP6, the ErGO-AP6 composite film shows an outstanding sensitivity and excellent selectivity towards CLO, superior to that of ErGO- β -CD film. The linear range from 1.0 × 10 −7 to 5.0 × 10 −5 mol L −1 and detection limit of 4.0 × 10 −8 mol L −1 for CLO are achieved. In addition, the presented method is used for fruit and water samples in a recovery test, showing recovery rates between 90.0% and 99.4%. This study provides a promising electrochemical sensing platform for rapid and sensitive analysis of CLO.
研究领域:
分析化学
·
环境科学
·
农业科学
✓ 已验证
产品关联
DOI
高影响因子
Analytical Methods
·
2023
·Vol. 15
·期 24
·2946-2954
·
IF 3.1
Xiong Chen,Yingxue Li,Juying Li,Li Cao,Cheng Yao
A ratiometric nitenpyram (NIT) upconversion luminescence sensor UCNPs–PMOF was fabricated from a metal–porphyrin organic framework (PMOF) and pretreated UCNPs. The reaction between NIT and the PMOF releases the H2TCPP (5,10,15,20-tetracarboxyl phenyl) porphyrin ligand, which enhances the absorption of the system at 650 nm, and reduces the upconversion emission intensity of the sensor at 654 nm through a luminescence resonance energy transfer (LRET) mechanism, thus achieving the quantitative detection of NIT. The detection limit was 0.21 μM. Meanwhile, the emission peak of UCNPs–PMOF at 801 nm does not change with the concentration of NIT, and the emission intensity ratio (I654 nm/I801 nm) is used to achieve the ratiometric luminescence detection of NIT, and the detection limit is 0.22 μM. UCNPs–PMOF has good selectivity and anti-interference to NIT. In addition, it has a good recovery rate in actual sample detection, which indicates that it has high practicability and reliability in NIT detection.
研究领域:
分析化学
·
纳米生物技术
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Dan Tao,Chang Xie,Sinan Fu,Shuang Rong,Shizhen Song,Huarong Ye,Nicole Jaffrezic-Renault,Zhenzhong Guo
How to sensitively detect early biomarkers of Alzheimer's disease (AD) is nowadays, one of the major challenges. In this work, Aβ oligomers (AβO), one of the AD biomarkers, was analyzed using an electrochemical aptasensor , which was prepared based on thionine (Th) - functionalized three - dimensional carbon nanomaterials (reduced graphene oxide (rGO) and multi-wall carbon nanotubes (MWCNTs)) immobilized DNA-aptamer. Th, a positively charged planar aromatic molecule, form many π - π conjugated structures with rGO and MWCNTs, then improving the structural stability, electron transfer and the capacitive properties of Th-rGO-MWCNTs nanocomposites. Under the optimal conditions, differential pulse voltammetry (DPV) current responses decreased with the increase of AβO concentration. The obtained AβO aptasensor presented a wide linear range of 0.0443 pM–443.00 pM and limit of detection (LOD) was 10 fM. Meanwhile, AβO aptasensor displayed remarkable stability and selectivity . It has a great potential for early diagnosis of AD in human real serum samples.
研究领域:
生物化学
·
纳米技术
·
分析化学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Jia-Nuo Zhang,Zhi-Dong Pei,Wen-Yu Wang,Ming-Yue Zhao,Wen-Han Pei,Hui Zhang,Hai-Bo Yin,Tian-Min Wang,Gui-Zhong Xin,Ming Xie,Ting-Guo Kang,Yue-Hua Chen,Hui-Peng Song
Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer’s disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 μM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer’s disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.
研究领域:
药理学
·
分析化学
·
神经科学
·
植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2023
·Vol. 148
·期 6
·1322-1329
·
IF 4.2
Chunyan Zhang,Yifeng Fan,Liangliang Cai,Xiaofei Ma
The discovery of novel chiral selectors always fascinates us. This work describes the chiral separation performances of a new chiral selector (kasugamycin, KAS) in capillary electrophoresis (CE) for six pairs of stereoisomers, including ephedrine and pseudoephedrine, quinine and quinidine, cinchonine and cinchonidine, and amlodipine, promethazine and ofloxacin enantiomers. Kasugamycin, an aminoglycoside antibiotic in agriculture, shows significant biological activity against rice blast with low toxicity. As it turns out, this new chiral selector possesses good CE compatibility and stereoselectivity towards model analytes. In this work, we systematically investigated several separation parameters including kasugamycin concentration, buffer pH, separation voltage and the composition of the buffer solution. A detailed discussion about the chiral recognition mechanism was made based on Statistical Product and Service Solution (SPSS) analysis, NMR experiments (1D and 2D) and molecular modeling. This is the first time that kasugamycin is utilized as a chiral selector in CE, and the development of new chiral selectors from agricultural or veterinary antibiotics deserves more attention.
研究领域:
分析化学
·
药学
·
色谱学
·
农业化学
✓ 已验证
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）