ANALYST
·
2020
·Vol. 145
·期 13
·4664-4670
·
IF 3.978
Zhifang Wu,Hui Zhou,Qianjin Han,Xuelian Lin,Dongxue Han,Xun Li
The efficient detection of illicit drugs such as cocaine continues to be important for the fight against drug trafficking. Herein, we report a one-step method for rapid and specific cocaine detection. The method is based on our finding that small-molecule Thioflavin T (ThT) can act as a fluorescence indicator, which can be bonded with the anti-cocaine aptamer (MNS-4.1) to generate an enhanced fluorescence signal. More interestingly, upon cocaine binding, the intercalated ThT can be replaced, causing a drastic fluorescence reduction. We further optimized the sequence of MNS-4.1 and a new anti-cocaine aptamer (coc.ap2-GC) was obtained. This aptamer showed a higher affinity to both ligands, which increased the ThT binding fluorescence intensity and showed the highest quenching efficiency. Based on the fluorescence change induced by competitive binding, cocaine detection could be accomplished by a “mix-and-detect” strategy within seconds. Such a label-free method exhibits high sensitivity to cocaine with a low detection limit of 250 nM. Moreover, the practical sample analysis (2.5% human urine and saliva) also exhibits good precision and high sensitivity.
研究领域:
分析化学
·
毒品检测
·
生物传感器
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROPSYCHOPHARMACOLOGY
·
2021
·Vol. 47
·期 3
·652-663
·
IF 7.855
Manz Kevin M.,Coleman Benjamin C.,Jameson Alexis N.,Ghose Dipanwita G.,Patel Sachin,Grueter Brad A.
Parvalbumin-expressing fast-spiking interneurons (PV-INs) within feedforward microcircuits in the nucleus accumbens (NAc) coordinate goal-directed motivational behavior. Feedforward inhibition of medium spiny projection neurons (MSNs) is initiated by glutamatergic input from corticolimbic brain structures. While corticolimbic synapses onto MSNs are targeted by the psychostimulant, cocaine, it remains unknown whether cocaine also exerts acute neuromodulatory actions at collateralizing synapses onto PV-INs. Using whole-cell patch-clamp electrophysiology, optogenetics, and pharmacological tools in transgenic reporter mice, we found that cocaine decreases thalamocortical glutamatergic drive onto PV-INs by engaging a monoamine-independent mechanism. This mechanism relies on postsynaptic sigma-1 (σ 1 ) activity, leading to the mobilization of intracellular Ca 2+ stores that trigger retrograde endocannabinoid signaling at presynaptic type-1 cannabinoid receptors (CB 1 R). Cocaine-evoked CB 1 R activity occludes the expression of CB 1 R-dependent long-term depression (LTD) at this synaptic locus. These findings provide evidence that acute cocaine exposure targets feedforward microcircuits in the NAc and extend existing models of cocaine action on mesolimbic reward circuits.
研究领域:
神经科学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2017
·Vol. 409
·期 16
·3993-4000
·
IF 3.431
Liu Yingxiong,Zhao Qiang
Development of simple, sensitive, and rapid method for cocaine detection is important in medicine and drug abuse monitoring. Taking advantage of fluorescence anisotropy and aptamer, this study reports a direct fluorescence anisotropy (FA) assay for cocaine by employing an aptamer probe with tetramethylrhodamine (TMR) labeled on a specific position. The binding of cocaine and the aptamer causes a structure change of the TMR-labeled aptamer, leading to changes of the interaction between labeled TMR and adjacent G bases in aptamer sequence, so FA of TMR varies with increasing of cocaine. After screening different labeling positions of the aptamer, including thymine (T) bases and terminals of the aptamer, we obtained a favorable aptamer probe with TMR labeled on the 25th base T in the sequence, which exhibited sensitive and significant FA-decreasing responses upon cocaine. Under optimized assay conditions, this TMR-labeled aptamer allowed for direct FA detection of cocaine as low as 5 μM. The maximum FA change reached about 0.086. This FA method also enabled the detection of cocaine spiked in diluted serum and urine samples, showing potential for applications.
The binding of cocaine to the TMR-labeled aptamer causes conformation change and alteration of the intramolecular interaction between TMR and bases of aptamer, leading to variance of fluorescence anisotropy (FA) of TMR, so direct FA analyis of cocaine is achieved
研究领域:
分析化学
·
药物检测
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2015
·
IF 6.409
Zhonghui Chen,Yue Tan,Kefeng Xu,Lan Zhang,Bin Qiu,Longhua Guo,Zhenyu Lin,Guonan Chen
Mesoporous silica nanoparticles (MSN) based controlled release system had been coupled with diverse detection technologies to establish biosensors for different targets. Chemiluminescence (CL) system of luminol/H 2 O 2 owns the characters of simplicity, low cost and high sensitivity, but the targets of which are mostly focused on some oxidants or which can participate in a chemical reaction that yields a product with a role in the CL reaction. In this study, chemiluminescent detection technique had been coupled with mesoporous silica-based controlled released system for the first time to develop a sensitive biosensor for the target which does not cause effect to the CL system itself. Cocaine had been chosen a model target, the MSN support was firstly loaded with glucose, then the positively charged MSN interacted with negatively charged oligonucleotides (the aptamer cocaine) to close the mesopores of MSN. At the present of target, cocaine binds with its aptamer with high affinity; the flexible linear aptamer structured will become stems structured through currently well-defined non-Waston–Crick interactions and causes the releasing of entrapped glucose into the solution. With the assistant of glucose oxidase (GOx), the released glucose can react with the dissolved oxgen to produce gluconic acid and H 2 O 2 , the latter can enhance the CL of luminol in the NaOH solution. The enhanced CL intensity has a relationship with the cocaine concentration in the range of 5.0–60 μM with the detection limit of 1.43 μM. The proposed method had been successfully applied to detect cocaine in serum samples with high selectivity . The same strategy can be applied to develop biosensors for different targets.
研究领域:
分析化学
·
生物传感
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
TALANTA
·
2016
·
IF 4.035
Juan Meng,Xianghu Tang,Binbin Zhou,Qiwen Xie,Liangbao Yang
A novel and rapid method to detect cocaine in human urine has been developed by using self-assembly ordered two dimensional (2D) gold nanoparticles (GNPs) film as surface-enhanced Raman spectroscopy (SERS) substrates. In order to obtain high sensitivity, uniformity, and reproducibility of SERS platform, quasi-spherical, uniform GNPs were firstly synthesis using seed growth method, in which the GNPs have been functionalized with CTAB to form orderly close-packed GNPs film as SERS substrate. Importantly, the high-performance GNPs on solid substrates can produce a high yield of sub-10-nm gaps which can generate gigantic signals enhancement for analytes adsorbed GNPs surface. In view of the complex component of human urine, we develop a rapid and efficient pretreatment strategy for separation and purification of cocaine by using hexane extraction in real human urine samples within 3 min. With the advantages of better extraction rates (>75%) examined by ultraperformance liquid chromatography (UPLC) and the excellent signal-to-noise ratio detected by SERS, our pretreatment procedure can efficiently lower the interference of complex biological components in urine. To reach on-spot analyzer, a handheld Raman spectrometer was used for feasible SERS detection of cocaine in real human urine. The favorable results demonstrated our pretreatment strategy combined with SERS platform will be a great prospective method toward rapid, reliable, and on-spot cocaine detection for public safety.
研究领域:
分析化学
·
纳米技术
·
药物检测
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiabin Chen,Yun Zhang,Junsen Tong,Pengfei Ouyang,Xingyu Deng,Jie Zhang,Huan Liu,Yihui Hu,Weixuan Yao,Jiye Wang,Xia Wang,Shurong Hou,Jianzhuang Yao
Enzyme therapy for cocaine detoxification should break down both cocaine and its primary toxic metabolite, benzoylecgonine (BZE), which is also the main form of cocaine contaminant in the environment. An ideal BZE-metabolizing enzyme (BZEase) is expected to be highly efficient and selective in BZE hydrolysis. Here, BZEase4 was engineered from bacterial cocaine esterase (CocE) by our reactant state-based enzyme design theories (RED), which has a 34,977-fold improved substrate discrimination between BZE and the neurotransmitter acetylcholine (ACh), compared with wild-type CocE. Under the physiological concentrations of BZE and ACh, the reaction velocity of BZEase4 against BZE is 2.25 × 10 6 -fold higher than it against ACh, suggesting BZEase4 has extremely high substrate selectivity for BZE over ACh to minimize the potential cholinergic side-effects. This study provides additional evidence supporting the further development of BZEase4 toward a promising therapeutic for cocaine overdose, a potentially effective and eco-friendly enzymatic method for BZE degradation in the environment.
研究领域:
生物化学
·
药物开发
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Tingting Xiao,Weiqiang Wang,Lingyi Zhao,Jian Xie,Weiping Cai
Illicit drug abuse has brought big challenges to public health, because it has caused severe damage to the human central nervous system. The development of a rapid, quantified, and on-site detection of illicit drugs is of key importance for the control of drug abuse. However, it remains challenging due to biological sample interference and difficulties in achieving specific recognition of the drug molecule. Here, we report a molecule-responsive two-component surface-enhanced Raman scattering (SERS) platform for the capture and detection of illicit drugs. Under optimized conditions, the system demonstrates a linear response to cocaine concentrations ranging from 1 ppb to 10 ppm (R2 > 0.99), with an ultralow detection limit of 1.5 ppb. Successful application in spiked bovine serum validates the method’s robustness against complex biological matrices. This work establishes a novel paradigm for detecting trace-level illicit drugs with significant forensic potential. The design principle might be applied to other chemical detection.
研究领域:
分析化学
·
生物传感
·
法医学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
·
2023
·
IF 4.4
Bing-Hui Yan,Qi-Xuan Xu,Xiao Ge,Ming-Tong Gao,Yun Li,Liang Guo,Po Hu,Yang Pan
Benign prostatic hyperplasia (BPH) is a common disease that affects the quality of life of middle-aged and older men. We investigated the therapeutical effects of Chengshi Beixie Fenqing Decoction (CBFD), a classic traditional Chinese medicine prescription, on BPH through in vivo model and network pharmacology. Bioactives in CBFD were detected through UPLC-Q-Tof-MS/MS and GC-MS, and filtered by the modified Lipinski’s rule. Target proteins associated with the filtered compounds and BPH are selected from public databases. Venn diagram identified the overlapping target proteins between the bioactives-interacted target proteins and the BPH-targeted proteins. The bioactive-protein interactive networking of BPH was analyzed through the KEGG pathway on STRING to identify potential ligand-target and visualized the rich factors on the R packet. After that, the molecular docking test (MDT) was performed between bioactives and target proteins. It showed that the mechanism of CBFD against BPH was related to 104 signaling pathways of 42 compounds. AKT1, 6-demethyl-4′-methyl-N-methylcoclaurine and relaxin signaling pathways were selected as a hub target, key bioactivitie and hub signaling pathway, respectively. In addition, three major compounds, 6-demethyl-4′-methyl-N-methylcoclaurine, isoliensinine and liensinine, had the highest affinity on MDT for the three crucial target proteins, AKT1, JUN and MAPK1. These proteins were associated with the relaxin signaling pathway, which regulated the level of nitric oxide and is implicated in both BPH development and CBFD. We concluded that the three key bioactivities found in Plumula nelumbinis of CBFD may contribute to improving BPH condition by activating the relaxin signaling pathways.Communicated by Ramaswamy H. Sarma
研究领域:
药理学
·
中医
·
泌尿科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
·
IF 4.2
Elham Ghashghaei,Minghui Wang,Ahmed Mijiyawa,Hai Lin
Amino acids in the brain modulate eating behavior and energy balance. The aim of the present study was to investigate the effects of DL-methionine (DL-Met), L-lysine monohydrochloride (L-Lys-HCl), and taurine (Tau) on feed intake and the mRNA expression levels of appetite-related hypothalamic neuropeptides in chicks. DL-Met, L-Lys-HCl, or Tau was intracerebroventricularly (ICV) administered to 5-day-old layer-type chicks, and the feed intake was recorded until 1 h post-injection. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of neuropeptide Y ( NPY ) and its receptors, agouti-related protein ( AgRP ), pro-opiomelanocortin ( POMC ), cocaine- and amphetamine-regulated transcript ( CART ), and melanocortin receptors. Our results indicated that injection time and treatment have a significant effect on food intake. Food intake decreased significantly at 30 and 60 minutes after ICV administration of DL-Met (1.678 μmol), L-Lys-HCl (6.856 μmol), and Tau (5.006 μmol) compared to the control group ( P > 0.05). On the contrary, a high dose of each amino acid did not alter feed intake ( P > 0.05). The result showed that ICV injection of DL-Met (1.678 μmol) significantly decreased the mRNA expressions of NPY , NPY4R , and NPY6R ( P < 0.05), but had no significant effect on the mRNA expressions of NPY1R, NPY5R, and AgRP in the hypothalamus ( P > 0.05). Similarly, ICV injection of L-Lys-HCl (6.856 μmol) and Tau (5.006 μmol) significantly decreased mRNA levels of NPY, NPY4R, and NPY6R ( P < 0.05), without affecting the mRNA expressions of NPY1R, NPY5R, and AgRP ( P > 0.05). DL-Met had no effect on anorexigenic gene expression ( P > 0.05). L-Lys-HCl upregulated MC1R ( P < 0.05), and Tau upregulated POMC and MC3R ( P < 0.05), and both had no influence on CART, MC4R , or MC5R ( P > 0.05). The result suggests that both orexigenic and anorexigenic neuropeptide genes are involved in the effects of DL-Met, L-Lys-HCl, and Tau. The effect of DL-Met, L-Lys-HCl, and Tau acts in a dose-dependent manner in the hypothalamus to influence feed intake.
研究领域:
动物科学
·
神经生物学
·
营养学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Analysis and Testing
·
2022
·Vol. 6
·期 2
·120-128
·
IF 0
Jing Le,Xie Chong-Yu,Li Qian-Qian,Yao Hui-Fang,Yang Mei-Qing,Li Hui,Xia Fan,Li Shao-Guang
The sandwich-type lateral flow assays relying on dual aptamers with high sensitivity and specificity have been broadly explored. However, it is unlikely to match a pair of specific aptamers that can bind a small molecular target (e.g., cocaine) simultaneously due to the steric hindrance. In response, we herein introduced the strategy of “one divides into two” into the construction of sandwich-type lateral flow strip assay (LFSA). Specifically, we split a single cocaine-recognizing aptamer into two segments, either of which was conjugated with gold nanoparticles (AuNPs) or labeled with biotin, serving as signal probe and capture probe, respectively. Upon the presence of the target molecule, a ternary sandwich complex comprised of the two halves of the aptamer and the target formed. Such sandwich-type LFSA exhibited an excellent nonlinear logarithmic response in the range from 10 μmol/L to 5 mmol/L with R 2 = 0.9994. The sensitive on-site detection of cocaine in artificial biological samples including urine and sweat was achieved within 15 min, with the visual limit of detection as low as 50 μmol/L for urine and 200 μmol/L for sweat, and the recovery rates of 83.6–107.4%.
研究领域:
分析化学
·
纳米技术
·
现场检测
·
毒品检测
✓ 已验证
产品关联
DOI
危险品化学品经营许可证（带存储）