High-performance fentanyl molecularly imprinted electrochemical sensing platform designed through molecular simulations.

BACKGROUND: Fentanyl and its derivatives are a type of potent opioid analgesics, with the characteristics of diverse structure, high toxicity, extremely low content, and high fatality rate. Currently, they have become one of the most serious problems in international drug abuse control due to their extensive use in drug production and use. Therefore, the development of a rapid, sensitive, and accurate method for detecting trace fentanyl is of great significance. In this study, in view of its complex structure and trace concentration, a new molecular imprinting electrochemical sensor was developed through molecular simulations followed by experimental validation to detect trace fentanyl. RESULTS: The process consisted of first obtaining the optimal functional monomer and its molar ratio through molecular simulations. The recognition sites of fentanyl-imprinted polymers were predicted to guide the synthesis of imprinted membranes with precision approach to ensure an efficient and accurate reaction process. Reduced graphene oxide (ErGO) was then deposited on glassy carbon electrode surface by electrochemical reduction to yield large numbers of active sites suitable for catalyzing reactions of fentanyl piperidine for promoted efficient electron transfer and amplified sensitivity of the sensor. Accordingly, fentanyl molecularly imprinted film was formed through one-step electropolymerization to yield greatly improved sensing selectivity due to the specific recognition of molecularly imprinted polymer. Under optimal experimental conditions, the fentanyl sensor showed an extended detection range of 3.84 × 10-9 mol L-1-1.72 × 10-6 mol L-1 and a detection limit of 1.28 × 10-9 mol L-1. SIGNIFICANCE: A distinctive feature of this sensor is its molecularly imprinted polymerized membrane, which offers excellent specific recognition, thereby boosting the sensor's selectivity. Throughout the sensor's development process, molecular simulations were employed to steer the synthesis of molecularly imprinted polymers and predict the recognition sites of fentanyl-imprinted polymers. The experimental outcomes proved to align with the simulation data. The final sensor exhibited outstanding selectivity, repeatability, stability, and high sensitivity. The sensor was effectively used to reliably track fentanyl in human serum samples, with acceptable analytical reliability, suggesting its potential for practical applications.

A multicenter clinical AI system study for detection and diagnosis of focal liver lesions.

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

A simple polyarginine membrane electrochemical sensor for the determination of MDMA and MDA.

In this study, a simple electrochemical sensor based on l-arginine membrane (P-L-arg/GCE) was developed for rapid and sensitive detection of MDMA and MDA. A polyarginine membrane was obtained through one-step direct electropolymerization, which provides more reaction sites for the analyte and improves the sensitivity of the sensor. Following the optimized selection parameters, the MDMA detection range was established at 1.0 × 10-7∼3.5 × 10-5 mol L-1, with a detection limit of 3.3 × 10-8 mol L-1. Similarly, the detection range for MDA was established at 1.0 × 10-7∼5.3 × 10-5 mol L-1 with a detection limit of 3.3 × 10-8 mol L-1. Additionally, the potential oxidation mechanism of MDMA and MDA during the REDOX process was analyzed by cyclic voltammetry. Furthermore, the proposed sensor exhibited superior selectivity, excellent reproducibility, and satisfactory stability. The proposed sensors can be used for reliable monitoring of MDMA or MDA in human urine and hair samples, respectively, and it has acceptable analytical reliability and enormous potential for practical applications.

A novel hydrangea-like magnetic composite Fe3O4@MnO2@ZIF-67 for efficient selective adsorption of Pd(II) from metallurgical wastewater.

The selective adsorption of palladium from wastewater is a feasible solution to solving palladium pollution and resource scarcity. Because traditional solvent extraction methods often involve the use of considerable amounts of organic solvents, research is focused on investigating adsorption techniques that can selectively remove palladium from wastewater. In this paper, the magnetic composite Fe3O4@MnO2@ZIF-67 was synthesized and its performance for the adsorption of Pd(II) in acidic water was investigated. Fe3O4@MnO2@ZIF-67 was characterized by various analytical methods such as TEM, SEM, EDS, BET, XRD, FTIR, zeta potential analysis, VSM, and TGA. The effects of palladium ion concentration, contact time, pH, and temperature on adsorption were evaluated. The kinetics were shown to follow the pseudo-second-order kinetic model and Elovich model, and the rate-limiting step was chemisorption. Thermodynamic studies showed that increasing the temperature promoted the adsorption of Pd(II), and the maximum uptake capacity of Fe3O4@MnO2@ZIF-67 for Pd(II) was 531.91 mg g-1. Interestingly, Fe3O4@MnO2@ZIF-67 exhibited superior selectivity for Pd(II) in the presence of Ir(IV), Pt(IV), and Rh(III). The adsorbent can be used repeatedly for selective adsorption of palladium. Even at the fifth cycle, the uptake rate of Pd(II) remained as high as 83.1%, and it showed a favorable adsorption capacity and selectivity for Pd(II) in real metallurgical wastewater. The adsorption mechanism was analyzed by SEM, FTIR, XRD, XPS, and DFT calculations, which indicated that electrostatic interactions and coordination with nitrogen-containing groups were involved. Fe3O4@MnO2@ZIF-67 is a promising adsorbent for the efficient adsorption and selective separation of palladium ions.

A promising and highly sensitive electrochemical platform for the detection of fentanyl and alfentanil in human serum.

A novel electrochemical method has been developed, based on a covalent organic framework (COF) and reduced graphene oxide (rGO), to detect fentanyl and alfentanil. COF nanomaterials with chrysanthemum morphology obtained by solvothermal reaction contain rich active sites for electrochemical catalytic reaction, thus improving the detection performance of the designed sensor. Reduced graphene oxide improves the sensor's sensitivity due to enhanced electron transfer. Under optimized experimental conditions, the fabricated electrode presents a linear range of 0.02 to 7.26 µM for alfentanil and 0.1 to 6.54 µM for fentanyl, with detection limits of 6.7 nM and 33 nM, respectively. In addition, the sensor possesses excellent selectivity, outstanding reproducibility, and acceptable stability. The proposed sensor is feasible for the reliable monitoring of fentanyl and alfentanil in human serum samples, with acceptable reliability and high potential in real-world applications. Finally, the electrochemical characteristic fingerprint of fentanyl is investigated by studying the electrochemical behavior of alfentanil and fentanyl on the electrode surface.

An electrochemical sensor for direct and sensitive detection of ketamine.

Ketamine is an organic drug with weak electrochemical activity, which makes it difficult to directly detect by electrochemical methods. Herein, an electrochemical sensor, with excellent detection sensitivity, is proposed for direct detection of ketamine based on a weakly conductive poly-L-cysteine molecularly imprinted membrane. Poly-L-cysteine molecularly imprinted membrane sensor (poly-L-Cys-KT-MIM/GCE) is obtained using L-cysteine as a functional monomer and ketamine as a template molecule based on electropolymerization. The green and highly active cysteine is selected as a functional monomer during electropolymerization, which cannot only achieve specific recognition but also improve detection sensitivity. Furthermore, the oxidation mechanism and fingerprint of ketamine on the electrode surface are established by analyzing the corresponding oxidation products using high/resolution mass spectrometry, which will help to promote the application of electrochemistry in the rapid detection of drugs. Under optimal conditions, the as-designed sensor demonstrated a linear response to ketamine within the range of 5.0 × 10-7 to 2.0 × 10-5 mol L-1 and a detection limit of 1.6 × 10-7 mol L-1. The proposed method exhibited excellent performance from the viewpoints of selectivity, sensitivity and stability. Notably, the sensor rendered excellent reliability and could be used for the detection of target analytes in hair and urine samples with high recovery rates.

A multifunctional adsorbent based on 2,3-dimercaptosuccinic acid/dopamine-modified magnetic iron oxide nanoparticles for the removal of heavy-metal ions.

Overexploitation of nature by humans has led to an increasingly serious issue of heavy-metal water pollution. To reduce the threat of water pollution to humans and the environment, it is imperative to develop or improve the water treatment technology for heavy-metal-containing wastewater. Functionalized Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) have been widely used as effective adsorbents for the removal of heavy-metal ions from water owing to their high efficiency, low cost, selective adsorption ability, and recyclability. In this study, Fe3O4@DA-DMSA magnetic nanoparticles (FDDMs) were prepared by the functionalization of Fe3O4 MNPs with environmentally friendly dopamine (DA) and a heavy-metal detoxifying agent such as 2,3-dimercaptosuccinic acid (DMSA) for the efficient and rapid adsorption of Pb2+, Cu2+, and Cd2+, with maximum adsorption capacities of 187.62, 63.01, and 49.46 mg/g, respectively. FDDMs exhibited the best ability to remove Pb2+ with a maximum adsorption capacity than that of the most reported Fe3O4 MNP-related adsorbents. In actual wastewater and multi-component simulated water samples contaminated with Pb2+, Cu2+, and Cd2+, the as-prepared adsorbent maintained a good removal ability for Pb2+ with low influence by ionic strength and interfering ions, as well as exhibited an excellent selectivity. According to the results of batch experiments and X-ray photoelectron spectroscopy (XPS) analysis of the adsorbent before and after adsorption, the adsorption mechanism of the adsorbent for the removal of heavy-metal ions mainly involves coordination and ion exchange. In addition, the adsorbent exhibited a good regeneration performance. Therefore, FDDMs can be considered as a promising adsorbent for the treatment of heavy-metal wastewater.

Microwave-prepared surface imprinted magnetic nanoparticles based electrochemical sensor for adsorption and determination of ketamine in sewage.

Detection technology for the determination of drugs, such as ketamine (KT), in sewage is of great significance in drug inspection and criminal investigation. Herein, we propose the utilization of ketamine magnetic molecularly imprinted polymers (Fe3O4@MIPs) as a target molecule identification and concentration container coupled with magnetic glassy carbon electrode (mGCE) for KT detection in sewage. Molecular simulations were employed to evaluate the most suitable monomer and ratio of functional monomer to template. Fe3O4@MIPs were prepared using microwave-assisted synthesis and possessed a "shell-core" structure with good recognition ability, superior adsorption capacity and fast kinetics toward KT. Additionally, a novel imprinted electrochemical sensor was constructed based on the magnetism of Fe3O4@MIPs for efficient monitoring of low concentrations of KT. The morphology and properties of Fe3O4@MIPs/mGCE were effectively characterized by element mapping, transmission electron microscopy, cyclic voltammetry and square wave voltammetry. KT detection was performed by square wave voltammetry within the range of 1.0 × 10-12 and 4.0 × 10-4 mol L-1, and the limit of detection was 8.0 × 10-13 mol L-1. Furthermore, Fe3O4@MIPs/mGCE was successfully tested for KT determination in domestic sewage samples.

Sensitive detection of ketamine with an electrochemical sensor based on UV-induced polymerized molecularly imprinted membranes at graphene and MOFs modified electrode.

Ketamine is one of the most widely abused drugs in the world and poses a serious threat to human health and social stability; therefore, the ability to accurately monitor the substance in real-time is necessary. However, several problems still exists towards this goal, such as the generally low concentration of the target molecules disturbed in the complex samples that undergo analysis during criminal investigations. In this work, the sensitive and selective detection of ketamine was accomplished by molecularly imprinted electrochemical sensor. The molecularly imprinted membrane as a biomimetic recognition element was fabricated by the UV-induced polymerization of methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) on a metal-organic framework/graphene nanocomposite (MOFs@G) modified screen-printed electrode. The screen printed electrode (SPE) provided good adhesion for the formation of the imprinted membranes and increased the stability of the sensor. The morphology and performance of the imprinted films were characterized in detail by scanning electron microscopy (SEM), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). The experimental results demonstrated that the imprinted sensor had excellent sensitivity, selectivity, and long-term stability. It offered a low detection limit (4.0 × 10-11 mol L-1) and had a dynamic range from 1.0 × 10-10 mol L-1 to 4.0 × 10-5 mol L-1. Furthermore, the established method was successfully applied for the determination of ketamine in urine and saliva samples.

New reconstruction method for few-view grating-based phase-contrast imaging via dictionary learning.

Grating-based phase-contrast is a hot topic in recent years owing to its excellent imaging contrast capability on soft tissues. Although it is compatible with conventional X-ray tubes and applicable in many fields, long scanning time, and high radiation dose obstruct its wider use in clinical and medical fields, especially for computed tomography applications. In this study, we solve this challenge by reducing the projection views and compensating the loss of reconstruction quality through dual-dictionary learning algorithm. The algorithm is implemented in two steps. First, estimated high-quality absorption images are obtained from the first dual-quality dictionary learning, which uses the correspondence between high-quality images and low-quality ones reconstructed from highly under-sampled data. Then, the second absorption-phase dual-modality dictionary learning is adopted to yield both estimated phase and absorption images, resulting in complementary information for both modality images. Afterwards the absorption and phase images are gradually improved in iterative reconstructions. By using SSIM RMSE measurements and visual assessment for enlarged regions of interest, our proposed method can improve the resolution of these two modality images and recover smaller structures, as compared to conventional methods.

Electrochemical Sensor Based on Rh(III) Ion-Imprinted Polymer as a New Modifying Agent for Rhodium Determination.

A rhodium (III) ion carbon paste electrode (CPE) based on an ion imprinted polymer (IIP) as a new modifying agent has been prepared and studied. Rh(III) ion imprinted polymer was synthesized by copolymerization of acrylamide-Rh(III) complex and ethylene glycol dimethacrylate according to the precipitation polymerization. Acrylamide acted as both functional monomer and complexing agent to create selective coordination sites in a cross-linked polymer. The ion imprinted carbon paste electrode (IIP-CPE) was prepared by mixing rhodium IIP-nanoparticles and graphite powder in n-eicosane as an adhesive and then embedding them in a Teflon tube. Amperometric i-t curve method was applied as the determination technique. Several parameters, including the functional monomer, molar ratio of template, monomer and cross-linking agent, the amounts of IIP, the applied potential, the buffer solution and pH have been studied. According to the results, IIP-CPE showed a considerably higher response in comparison with the electrode embedded with non-imprinted polymer (NIP), indicating the formation of suitable recognition sites in the IIP structure during the polymerization stage. The introduced electrode showed a linear range of 1.00×10-8~3.0×10-5 mol·L-1 and detection limit of 6.0 nmol L-1 (S/N = 3). The IIP-CPE was successfully applied for the trace rhodium determination in catalyst and plant samples with RSD of less than 3.3% (n = 5) and recoveries in the range of 95.5~102.5%.

A Novel Sensitive Electrochemical Sensor for Podophyllotoxin Assay Based on the Molecularly Imprinted Poly-o-Phenylenediamine Film.

An electrochemical sensor for podophyllotoxin (PPT) based on the molecular imprinting polymer (MIP) membranes was constructed. The sensor was prepared by electropolymerizing o-phenylenediamine (o-PD) on a glassy carbon electrode (GCE) in the presence of PPT as template, and then removing the template by immersing the modified GCE in ethanol. Experimental parameters such as the types of monomer, scan cycles, concentration of o-PD and extraction condition were optimized. Under optimal conditions, the sensor exhibits a good selectivity and high sensitivity. A good linearity was obtained in the range of 4 x 10-8 mol · L(-1) to 3.2 x 10(-5) mol · L(-1) with an estimated detection limit of 4.8 x 10(-9) mol · L(-1). The sensor was applied to the determination of PPT in podophyllum hexandrum and human serum samples with satisfactory results.

A novel sensitive electrochemical sensor based on in-situ polymerized molecularly imprinted membranes at graphene modified electrode for artemisinin determination.

To develop a rapid and simple method for sensitive determination of artemisinin (ART) in complicated matrices, a novel electrochemical sensor was constructed by in-situ polymerization of ART-imprinted membranes (ART-MIMs) on the surface of graphene (G) modified glassy carbon electrode (GCE) using acrylamide (AM) as functional monomer, ethylene glycol dimethacrylate (EGDMA) as cross-linking agent after the experimental parameters for the preparation of ART-MIMs such as functional monomer, molar ratio of template, monomer and cross-linking agent together with extraction condition were optimized. Under the optimal conditions, the sensor named as ART-MIM/G/GCE exhibited a good selectivity, high sensitivity and considerably better resistance against some analogs of artemisinin such as dihydroartemisinin (DHA), artemether (ARM) and artesunate (ARTS). The calibration graph for the determination of artemisinin by the sensor was linear in the range of 1.0 × 10(-8)mol L(-1) to 4.0 × 10(-5)mol L(-1) with the detection limit of 2.0 × 10(-9)mol L(-1). Meanwhile, this sensor possessed of good regeneration, stability and practicability. It could retain more than 94% of its original response after used at least 80 times or stored in water at room temperature for 60 days. The obtained sensor was successfully applied to determine the contents of artemisinin in the extract of Artemisia annua L. with the relative standard deviation (RSD) of less than 3.5% (n=5).

Sensitive detection of mercury and copper ions by fluorescent DNA/Ag nanoclusters in guanine-rich DNA hybridization.

In this work, we designed a new fluorescent oligonucleotides-stabilized silver nanoclusters (DNA/AgNCs) probe for sensitive detection of mercury and copper ions. This probe contains two tailored DNA sequence. One is a signal probe contains a cytosine-rich sequence template for AgNCs synthesis and link sequence at both ends. The other is a guanine-rich sequence for signal enhancement and link sequence complementary to the link sequence of the signal probe. After hybridization, the fluorescence of hybridized double-strand DNA/AgNCs is 200-fold enhanced based on the fluorescence enhancement effect of DNA/AgNCs in proximity of guanine-rich DNA sequence. The double-strand DNA/AgNCs probe is brighter and stable than that of single-strand DNA/AgNCs, and more importantly, can be used as novel fluorescent probes for detecting mercury and copper ions. Mercury and copper ions in the range of 6.0-160.0 and 6-240 nM, can be linearly detected with the detection limits of 2.1 and 3.4 nM, respectively. Our results indicated that the analytical parameters of the method for mercury and copper ions detection are much better than which using a single-strand DNA/AgNCs.

Intrathecal baclofen, a GABAB receptor agonist, inhibits the expression of p-CREB and NR2B in the spinal dorsal horn in rats with diabetic neuropathic pain.

This study aimed to investigate the effect of baclofen, a γ-aminobutyric acid B (GABAB) receptor agonist, on the expression of p-CREB and NR2B in the spinal dorsal horn of rats with diabetic neuropathic pain (DNP). The DNP rats, which were successfully induced with streptozocin, were distributed among 3 groups that were treated with saline (D1 group), baclofen (D2 group), or CGP55845 + baclofen (D3 group) continuously for 4 days. The rats induced with saline and subsequently treated with saline were used as controls (C group). The times for the paw withdrawal threshold and thermal withdrawal latency of the D1 group were lower than those for the C group, and were significantly increased after baclofen treatment, but not when GABA receptor was pre-blocked with CGP55845 (D3 group). Increased protein expression levels of NR2B and p-CREB and mRNA levels of NR2B were found in the D1 group when compared with the controls. Baclofen treatment significantly suppressed their expression, bringing it close to the levels of controls. However, in the D3 group, the expression of p-CREB and NR2B were still significantly higher than that of the controls. Activation of GABAB receptor by baclofen attenuates diabetic neuropathic pain, which may partly be accomplished via down-regulating the expression of p-CREB and NR2B.

Activation of spinal GABAB receptors normalizes N-methyl-D-aspartate receptor in diabetic neuropathy.

N-methyl-D-aspartate receptor (NMDAR) activity is increased, while GABAB receptor is downregulated in the spinal cord dorsal horn in diabetic neuropathy. In this study, we determined the interaction of NMDARs and GABAB receptors in streptozotocin (STZ)-induced diabetic neuropathy. The paw withdrawal threshold (PWT) was significantly lower in STZ-treated rats than in vehicle-treated rats. Intrathecal injection of baclofen, a GABAB receptor agonist, significantly increased the PWT in STZ-treated rats, an effect that was abolished by pre-administration of the GABAB receptor specific antagonist CGP55845. Spinal NR2B, an NMDA receptor subunit, protein and mRNA expression levels were significantly higher in STZ-treated rats than in vehicle-treated rats. Intrathecal baclofen significantly reduced the NR2B protein and mRNA expression levels in STZ-treated rats. Intrathecal administration of CGP55845 eliminated baclofen-induced reduction of NR2B protein and mRNA levels in STZ-treated rats. In addition, the phosphorylated cAMP response element-binding (CREB) protein level was significantly higher in the spinal cord dorsal horn in STZ-treated rats compared with vehicle-treated rats. Intrathecal injection of baclofen significantly decreased phosphorylated CREB protein level in STZ-treated rats; an effect was blocked by CGP55845. These data suggest that activation of GABAB receptors in the spinal cord dorsal horn normalizes NMDAR expression level in diabetic neuropathic pain.

A reagentless amperometric immunosensor for alpha-1-fetoprotein based on gold nanowires and ZnO nanorods modified electrode.

A novel strategy for the preparation of reagentless immunosensor for rapid determination of alpha-1-fetoprotein (AFP) in human serum has been developed. The immunosensor was prepared by immobilizing alpha-1-fetoprotein antibody (AFP Ab) onto the glassy carbon electrode modified by gold nanowires (Au NWs) and ZnO nanorods (ZnO NRs) composite film. Gold nanowires and ZnO nanorods were produced by an electrodeposition strategy using nanopore polycarbonate (PC) membrane. A sandwich immunoassay format was employed to detect AFP with horseradish peroxidase (HRP)-labeled AFP as tracer. The morphology of the Au NWs and ZnO NRs composite film has been investigated by scanning electron microscopy (SEM) and energy disperse spectroscopy (EDS) analysis. The resulting immunosensor offered an excellent amperometric response for AFP ranging from 0.5 to 160.0ngmL(-1) with a detection limit of 0.1ngmL(-1). Because of the combination of the biocompatibility of ZnO NRs and the direct electron-transfer of Au NWs between HRP and electrode, the proposed immunosensor displayed a direct electrochemical response of HRP to the reduction of H(2)O(2) with high sensitivity, quick response, good repeatability and long-term stability.