Chloramphenicol (CAP), a broad-spectrum antibiotic derived from Streptomyces, readily persists and accumulates in humans through pathways such as the food chain, leading to significant toxic effects. Herein, a novel electrochemiluminescence (ECL) aptasensor based on the signal “ON–OFF–ON” strategy is proposed for CAP detection in food. We utilized the immobilization capacity and enzyme-mimicking activity of iron-lanthanum doped prussian blue analogue (Fe-La PBA) to catalytically enhance the luminol–H2O2 luminescent system, thereby engineering the composite nanozyme-based luminophore (luminol-Au@Fe-La PBA). Moreover, polydopamine (PDA)-coordinated cadmium sulfide (CdS) decorated with gold nanoparticles (Au@CdS/PDA) serves as an energy acceptor to quench the signal from emitter luminol-Au@Fe-La PBA. Firstly, the luminol-Au@Fe-La PBA emitter was immobilized on a glassy carbon electrode (GCE), providing a strong initial ECL signal and serving as a platform for anchoring cDNA hybridized with the aptamer (Apt). Then the specific quenching probe (Apt-Au@CdS/PDA) was introduced, leading to substantial signal reduction. Upon the action of CAP, the dissociation of the Apt–cDNA hybrid duplex led to the detachment of the quenching probe from the electrode surface, thereby restoring the ECL signal intensity. The aptasensor demonstrated a linear response over a concentration range of 10 to 107 pg mL− 1, and LOD was 1.18 pg mL− 1, exhibiting satisfactory recoveries in various food samples and quality control samples.
Conventional receptor-targeted fluorescent probes have shown promise in tumor imaging, yet achieving a high tumor-to-normal (T/N) tissue ratio in vivo remains challenging due to limited biomarker density on tumor cell membranes. Here, we present an in situ assembly strategy of bioorthogonal-functionalized chimeric artificial receptors (BCARs) that locally constructs BCARs on tumor surfaces, which amplify fluorescence signals and enable high-contrast imaging. Rapid, selective membrane engineering under physiological conditions increases effective receptor density, enhancing fluorophore binding and tumor visualization. Mechanistic studies reveal that BCARs exhibit exceptional membrane retention and spatial precision, sustaining signal amplification in heterogeneous tumor microenvironments. In air-pouch and orthotopic bladder cancer models, BCARs notably improve the T/N imaging ratio and tumor boundary delineation. Translational validation with surgical specimens from 14 patients with bladder cancer confirms clinical feasibility. This work establishes a versatile platform for on-site receptor reprogramming and signal amplification, offering a powerful tool for high-contrast tumor margin detection.
Imatinib (IMA) is crucial for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). However, achieving highly sensitive detection of IMA remains challenging due to the low signal levels of most existing detection platforms and the high cost of instrumentation. In this work, we report a signal-enhanced electrochemiluminescence (ECL) aptasensor based on a Cd-TBAPy metal-organic framework (MOF) composite for sensitive detection of IMA. The enhanced ECL performance of Cd-TBAPy is attributed to the rigid coordination environment and ordered arrangement of H4TBAPy ligands within the MOF framework, which restrict intramolecular motion and reduce non-radiative relaxation pathways. Specific binding of IMA to the aptamer induces dissociation of the aptamer from the surface-confined CP-Apt duplex(dsDNA), thereby exposing the immobilized capture probe. The exposed capture probe subsequently hybridizes with the Cd-TBAPy-labeled signal probe, generating an ECL signal that increases with increasing target concentration. The sensor exhibits a good linear response over the range of 1 nM to 50,000 nM, with a detection limit as low as 0.47 nM, providing a promising basis for further development toward therapeutic drug monitoring of IMA.
MicroRNA-155 (miR-155) is a critical biomarker implicated in various pathological processes, including cancer progression, immune response, and cardiovascular diseases. Consequently, accurate detection of miR-155 at low concentrations is essential for early diagnosis and effective treatment monitoring. To address this need, this study introduces a novel application of reduced graphene oxide/silver sulfide-gold (rGO/Ag₂S-Au) nanocomposites as signal tracers for the sensitive detection of miR-155. First, Ag₂S-Au nanoparticles were synthesized via in-situ reduction of HAuCl₄ on Ag₂S surfaces and then incorporated into rGO to form the nanocomposites. Subsequently, the composites were hybridized with signal probes to fabricate signal labels. In the detection mechanism, miR-155 triggers local catalytic hairpin assembly (L-CHA) to amplify signals. Finally, the products were immobilized on capture probe-modified electrodes, and electrochemical responses were measured by differential pulse voltammetry (DPV). As a result, the biosensor exhibits a linear detection range from 1 fM to 1 μM, with a detection limit as low as 0.17 fM. Overall, this work advances electrochemical biosensor technology and provides valuable insights for high-performance biosensor design in rapid clinical diagnostics.
Phosphate plays a crucial role in various physiological and pathological processes; however, effective strategies for analyzing diverse phosphates and monitoring phosphate hydrolysis remain limited. Herein, we develop a metal-organic framework wrapped Cu nanoclusters-based (CuNCs@MOF) fluorescent sensor array for high-throughput discrimination of phosphates and real-time monitoring of their enzymatic hydrolysis. Leveraging the confinement effect of zinc-based MOFs, the encapsulated CuNCs exhibited reduced intramolecular vibration and rotation, resulting in enhanced luminescence performance. Due to the distinct affinities of various phosphates toward zinc ions, the sensor array generates differentiated fluorescence responses for seven phosphates, including adenosine triphosphate (ATP), cytidine triphosphate, uridine triphosphate, adenosine diphosphate, adenosine monophosphate, pyrophosphate (PPi), and inorganic phosphate. Subsequently, the fluorescence response signals are processed using the pattern recognition algorithm to generate the unique fingerprint spectra of each phosphate. We demonstrate that the sensor array can not only identify seven distinct phosphates at concentrations as low as 5 mu M and effectively distinguish between their mixtures but also exhibit excellent anti-interference capability and enable dynamic monitoring of ATP and PPi hydrolysis. Notably, the sensor array achieved outstanding performance in complex real-world samples and cellular-level analyses, demonstrating 100% accuracy in blind sample identification. Overall, this work develops a strategy for high-throughput discrimination of phosphates and real-time monitoring of their enzymatic hydrolysis.
A novel ternary electrochemiluminescence (ECL) aptasensor was creatively proposed for florfenicol (FF) detection, on account of the manganese-nitrogen dual-doped carbon dots (Mn-NHCDs) emitter and the facilitation of triethylamine (TEA) by zinc oxide (ZnO). First, Mn-NHCDs with low excitation potentials and excellent electrochemical luminescence properties were synthesized. Then, a newly formulated ZnO with an enlarged specific surface area and an appropriate mesoporous structure was utilized to load Mn-NHCDs, thereby diminishing the leakage of Mn-NHCDs and stabilizing the luminescence within the system. More importantly, ZnO can serve as a new co-reaction accelerator for TEA to improve the reaction rate of Mn-NHCDs with TEA efficiently. Furthermore, owing to the overlap of spectra, we employed an ECL resonance energy transfer (ECL-RET) strategy, with the Mn-NHCDs/ZnO as the donor and black hole quencher (BHQ) as the acceptor. The ECL biosensor illustrates an extremely selective and sensitive determination of FF from 1.00 fg mL⁻1 to 10.0 ng mL⁻1 and a detection Limit of 0.413 fg mL⁻1. We envision that our aptasensor will provide substantial assurance concerning food safety.
Macrophages play a key role in wound healing. Dysfunction of their M0 polarization to M2 leads to disorders of the wound immune microenvironment and chronic inflammation, which affects wound healing. Regulating the polarization of M0 macrophages to M2 macrophages is an effective strategy for treating wound healing. Mesenchymal stem cells (MSCs) deliver endogenous regulatory factors via paracrine extracellular vesicles, which may play a key role in wound healing, and previous studies have shown that apoptotic bodies (ABs) are closely associated with inflammation regression and macrophage polarization. However, the specific regulatory mechanisms involved in ABs remain unknown. In the present study, we designed an MSC-AB (MSC-derived AB)-loaded polycaprolactone (PCL) scaffold, evaluated the macrophage phenotype and skin wound inflammation in vivo and in vitro, and explored the ability of MSC-AB-loaded PCL scaffolds to promote wound healing. Our data suggest that the PCL scaffold regulates the expression of the CCL-1 gene by targeting the delivery of mmu-miR-21a-5p by local sustained-release MSC-ABs, and drives M0 macrophages to program M2 macrophages to regulate inflammation and angiogenesis, thereby synergistically promoting wound healing. This study provides a promising therapeutic strategy and experimental basis for treating various diseases associated with imbalances in proinflammatory and anti-inflammatory immune responses.
A novel electrochemiluminescence (ECL) immunosensor based on the resonance energy transfer (RET) effect between europium-based metal-organic framework (Eu-MOF, ETM) and GO-PEI/Au was developed for detecting neuron-specific enolase (NSE). First, using 4’,5’-Bis(4-carboxyphenyl)-[1,1’:2’,1”-terphenyl]-4,4”-dicarboxylic acid (TCPB) as the ligand, we synthesized an efficient and stable ECL emitter (ETM) as the signaling substrate. Due to efficient spectral overlap between the ECL emission spectrum of ETM and the UV-vis absorption spectrum of GO-PEI/Au, the ECL emission signal of ETM can be expeditiously quenched. Consequently, the ECL varied with the quenching efficiency of the immunosensor, which correlated with the target analyte concentration, enabling quantitative detection of NSE. The developed straightforward and cost-effective immunosensor exhibited outstanding sensitivity and selectivity in identifying NSE within the 10 fg mL− 1 to 100 ng mL− 1 range with an impressively low limit of detection (LOD) of 1.26 fg mL− 1. The immunosensor was successfully applied to quantify NSE in clinical human serum samples. Furthermore, by substituting the quenching probe, this platform can be readily adapted for detecting diverse biomarkers, demonstrating significant potential utility. To sum up, based on the ECL-RET strategy, a highly sensitive ECL immunosensor for NSE detection was constructed. It incorporated a novel ECL emitter (ETM) and established a new energy donor-acceptor pair, which demonstrated effective preliminary analysis of clinical samples.
The hunt for stable and effective luminous materials has always been a major focus of investigation and research during the development of electrochemiluminescence (ECL). However, numerous challenges persist even in current times. The aggregation-induced emission (AIE) ligand 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene and La3+ were used in this study to create a rod-like metal-organic framework (La-TCBPE-MOF, LTM), which was then constructed into an inventive ECL immunosensor for the ultrasensitive detection of neuron-specific enolase (NSE). LTM showed stronger ECL signals compared to H4TCBPE aggregations, which can be attributed not only to the immobilization of H4TCBPE ligands within the rigid MOF matrix, which restricted free intramolecular rotation and vibration, but also to the reduction of nonradiative transitions. Furthermore, the loading capacity of the H4TCBPE luminophore was significantly boosted by anchoring H4TCBPE into the rigid MOF as a bridging ligand. Consequently, a larger ECL intensity was produced due to the increased amount of H4TCBPE luminophores being stimulated. As anticipated, the fabricated ECL immunosensor exhibited a broad linear range spanning from 100 fg mL(-1) to 100 ng mL(-1), accompanied by an impressively low limit of detection (LOD) of 21.5 fg mL(-1). Moreover, the ECL immunosensor was effectively utilized for measurement in human serum. In summary, this research demonstrated a successful integration of AIE into the field of ECL, enabling rapid, sensitive, and highly precise detection of NSE.
Early secretory antigenic target-6 (ESAT-6) is regarded as the most immunogenic protein produced by Mycobacterium tuberculosis, whose detection is of great clinical significance for tuberculosis diagnosis. However, the detection of the ESAT-6 antigen has been hampered by the expensive cost and complex experimental procedures, resulting in low sensitivity. Herein, we developed a titanium carbide (Ti3C2Tx)-based aptasensor for ESAT-6 detection utilizing a triple-signal amplification strategy. First, acetylene black (AB) was immobilized on Ti3C2Tx through a cross-linking reaction to form the Ti3C2Tx-AB-PAn nanocomposite. Meanwhile, AB served as a conductive bridge, and Ti3C2Tx can synergistically promote the electron transfer of PAn. Ti3C2Tx-AB-PAn exhibited outstanding conductivity, high electrochemical signals, and abundant sites for the loading of ESAT-6 binding aptamer II (EBA II) to form a novel signal tag. Second, N-CNTs were adsorbed on NiMn layered double hydride (NiMn LDH) nanoflowers to obtain NiMn LDH/N-CNTs, exhibiting excellent conductivity and preeminent stability to be used as electrode modification materials. Third, the biotinylated EBA (EBA I) was immobilized onto a streptavidin-coated sensing interface, forming an amplification platform for further signal enhancement. More importantly, as a result of the synergistic effect of the triple-signal amplification platform, the aptasensor exhibited a wide detection linear range from 10 fg mL-1 to 100 ng mL-1 and a detection limit of 4.07 fg mL-1 for ESAT-6. We envision that our aptasensor provides a way for the detection of ESAT-6 to assist in the diagnosis of tuberculosis.
Glucose management is an important part of disease control for diabetes patients, thus the development of a rapid and real-time point of care testing (POCT) device for monitoring blood glucose is of great significance. In this work, a paper-based analytical device (PAD) is constructed by combining acetylene black (AB)-hemin complex modified filter paper as sensing platform with a smartphone as signal detector. Large specific surface area of AB decreases the self-associate and aggregate of hemin in aqueous solution, resulting in improved peroxidase-like activity of hemin. Compared with graphene oxide supported hemin, AB-hemin exhibits superior signal response on paper. Glucose oxidase (GOx) catalyzes the conversion of blood glucose to hydrogen peroxide, and then AB-hemin complex catalyzes the oxidation of colorless 3,3 ',5,5 '-tetramethylbenzidine (TMB) to blue TMB oxidized products (TMB+) in the presence of hydrogen peroxide, thus achieving the visual detection of blood glucose. In optimal conditions, PAD provides an applicable linear range from 0.2 mM to 30 mM and a low limit of detection (LOD) (0.06 mM). Notably, the detection accuracy of the developed paper-based sensor is in good agreement with that of the commercially available blood glucose meter (p > 0.05). Moreover, the proposed PAD presents high recoveries from 95.4% to 112% (RSD <= 3.2%), and therefore holds great potential for glucose monitoring and diabetes diagnosis.
Electrochemical tracers with high signal input are essential for electrochemical sensors to overcome the limitations of imprecise detection outcomes. Herein, Fe-metal organic framework doped polyaniline (Fe-MOF/PANI) was developed for the first time as a high signal input tracer for electrochemical signal generation and amplification. Together with a three-dimensional (3D) DNA walker machine, it enabled the sensitive detection of the target microRNA (miRNA). First, the DNA walkers were initiated by target miRNA-574-5p and powered by the process of Nb.BtsI-mediated digestion. Fe3O4 magnetic beads (MBs) were modified with substrate DNA (S-DNA) to generate 3D DNA tracks. DNA walkers moved independently along 3D DNA tracks powered by the nicking endonuclease. Second, output DNA fragments were produced away from the MBs' surface because S-DNA was cleaved during the movement. Finally, the released output DNA was dropped onto the modified electrode surface of the capture probe and hybridized with high signal input tracers to form a sandwich structure, resulting in a stable and robust current response. The proposed electrochemical biosensor demonstrated exceptional efficacy for amplified detection of miR-574-5P in a wide linear range from 1 fM to 1 mu M, with a limit of detection (LOD) of 0.237 fM under optimum conditions. Moreover, the inherent selectivity of the DNA walker allows the biosensor to accurately identify targets in human serum. Therefore, our work paves the way for the fabrication and design of high signal electrochemical biosensor tracers, which exhibit immense potential for bioanalytical applications.
The extracellular domain of the human epidermal growth factor receptor (HER2-ECD) is a breast cancer biomarker. Accurate and sensitive detection of HER2-ECD concentration in serum is crucial in the diagnosis and patient follow-up. Herein, an "off-on" type electrochemiluminescence (ECL) aptasensor based on the resonance energy transfer (RET) between AuPt@ZIF-67 and AuNPs/g-C3N4/PDDA was developed for detecting HER2-ECD. First, AuNP-modified g-C3N4 (AuNPs/g-C3N4/PDDA), as a signal substrate, generates ECL signals under the co-reactant peroxodisulfate (S2O82-) in a specific potential range and shows significantly enhanced signal strength and stability. Then, AuPt@ ZIF-67 expeditiously quenched the ECL signal of AuNPs/g-C3N4/ PDDA because of ECL resonance energy transfer (ECL-RET) between AuPt@ZIF-67 and AuNPs/g-C3N4/PDDA. We designed a new aptasensor detection platform for HER2-ECD detection. After specific binding of the aptamer with HER2-ECD, the AuPt@ZIF-67 content in the system decreased, and the ECL response recovered. The biosensor demonstrated a linear range of HER2-ECD detection between 100 fg/mL and 100 ng/mL under ideal circumstances, with a low detection limit of 17.3 fg/mL. Furthermore, this biosensor was successfully tested in human serum samples. This strategy, as a novel ECL system with satisfactory stability and excellent sensitivity, can realize the detection of other biological molecules by changing the probe, which is a promising method.
Human epididymis protein 4 (HE4) is a highly sensitive and specific biomarker for diagnosing ovarian cancer. In this work, a new electrochemical aptasensor for rapid and sensitive detection of HE4 was constructed. Firstly, metal–organic framework/ketjen black (NH 2 -MIL-53(Al)/KB) composite with abundant amino groups and large specific surface area was prepared as signal amplifier to anchor gold nanoparticles (AuNPs). Subsequently, signal probe (SP) and a large amount of electroactive toluidine blue (Tb) were attached on AuNPs to form the tracer label, producing a distinct electrochemical detection signal. Moreover, Ni 3 (HITP) 2 was modified by poly(diallyldimethylammonium chloride, PDDA) to obtain PDDA/Ni 3 (HITP) 2 , and then it was covered with deposited gold nanocrystals (DpAu) to form the sensing platform, which increased the electrical conductivity, specific surface area and the loading of triple-helix assembled probes (TAP). Target HE4 was bound to its aptamer in the outer layer of the TAP, leaving a separate capture probe (CP) on the electrode surface that can bind with the tracer label. The proposed aptasensor for HE4 detection showed a wide linear range from 1 to 10 nM with a detection limit of 0.41 fM. In addition, the aptasensor has good selectivity, stability and reproducibility. More importantly, this method showed satisfactory results in clinical serum sample analysis compared with ELISA, possessing application prospects in ovarian cancer diagnosis.
In this work, a new non-enzymatic sensor for the determination of glucose was constructed using Fe-doped NiMoO4 nanoparticles (NiFeMoO4). Hydrothermal and calcination techniques were successfully used to synthesis different proportion nanoparticles of Ni1−xFexMoO4 (x = 0, 0.01, 0.03, 0.05). A set of electrochemical measurements demonstrated that all of the Ni1−xFexMoO4 have electrocatalytic properties to glucose. Especially, Ni0.99Fe0.01MoO4 (x = 0.01) displayed the most excellent amperometric response to glucose in the range of 0.01∼13 mM with a limit of detection (LOD) of 0.29 μM (S/N = 3). This amperometric sensor also showed satisfactory anti-interference performance and stability. More significantly, the sensor’s applicability was tested using a glucose assay in actual serum samples with acceptable results.
Pharmacovigilance in China has experienced rapid development in the past 30 years. The implementation of Good Pharmacovigilance Practice in China since the end of 2021 heralds a new era of pharmacovigilance affairs, which puts forward higher requirements for the quantity and quality of pharmacovigilance personnel. This study aimed to preliminarily explore the current career situations of pharmacovigilance professionals working in China for pharmaceutical companies. A questionnaire was adapted from research in the USA and Europe with the help of several pharmacovigilance experts. Snowball sampling was used to conduct an exploratory survey to obtain the frequency of basic demographic information, work status, and career expectations of pharmacovigilance professionals working for pharmaceutical companies. The personnel engaged in pharmacovigilance work for pharmaceutical companies were mainly medical or pharmaceutical undergraduates within 3 years of graduation. Their work intensity and pressure were relatively high. The training provided by their universities and enterprises could not well meet their needs to improve their job competence. Although they were optimistic about pharmacovigilance and will not change their career, most of them were planning to change their employers. There was a gap between the demand and supply of pharmacovigilance personnel. Relevant regulatory authorities and industry associations should guide higher education institutions to collaborate with pharmacovigilance specialists to strengthen pharmacovigilance education for medical or pharmaceutical students, on the basis of which pharmacovigilance certification courses and continuing education courses can be developed. Meanwhile, pharmaceutical enterprises should consider reasonably adjusting work intensity and income to avoid a high turnover rate.
The accurate identification and sensitive quantification of heavy metal ions are of great significance, considering that pose a serious threat to environment and human health. Most array-based sensing platforms, to date, utilize nanozymes as sensing elements, but few studies have explored the application of the peroxidase-like activity of clusterzymes in identification of multiple analytes. Herein, for the first time, we developed a clusterzyme sensor array utilizing gold nanoclusters (AuNCs) as sensing elements for five heavy metal ions identification including Hg2+, Pb2+, Cu2+, Cd2+ and Co2+. The heavy metal ions can differentially regulate the peroxidase-like activity of AuNCs, and that can be converted into colorimetric signals with 3,3 ',5,5 '-tetramethylbenzidine (TMB) as the chromogenic substrate. Subsequently, the generated composite responses can be interpreted by combining pattern recognition algorithms. The developed clusterzyme sensor array can identify five heavy metal ions at concentrations as low as 0.5 mu M and their multi-component mixtures. Especially, we demonstrated the successful identification of multiple heavy metal ions in tap water and traditional Chinese medicine, with an accuracy of 100% in blind test. This study provided a simple and effective method for identification and quantification of heavy metal ions, rendering a promising technique for environmental monitoring and drug safety assurance.
目的 探讨模拟教育结合标准化病人在临床药学专业临床药物治疗学实验教学中的应用效果.方法 将该校120名临床药学随机分为2组,单数组采用模拟教育结合标准化病人教学法进行授课,偶数组采用传统的理论教学法进行授课.结果 采用模拟教育结合标准化病人教学法的临床药学生较采用传统教学具有更好的笔试成绩和临床技能考核成绩.结论 模拟教育结合标准化病人教学能有效提升学生解决临床实际问题的能力.
文章以重庆医科大学药学院为例,首先分析了药学硕士专业学位研究生培养现状,然后论述了药学硕士专业学位研究生"产学研用"一体化培养模式,包括深化实践教学改革,为"产学研用"一体化培养模式奠定基础;夯实基础,建立完善的专业学位培养课程体系;由单变双,采取校企合作的"双导师制";建立高校与企业的桥梁,充分实施"产学研用"一体化培养模式.
目的:了解非甾体抗炎药(NSAIDs)相关不良反应(ADRs)的发生情况及特点,为临床提供参考.方法:采用回顾性研究方法,调取2008~2019年解放军药品不良反应监测中心ADR数据库中所有NSAIDs相关ADRs自发报告,对其中5 597例有效自发报告中的患者性别、年龄,可疑NSAIDs分类、给药途径,以及ADRs类型、诱导期和累及系统/器官等进行统计分析,比较不同性别患者各个年龄段的构成比差异.结果:5 597例NSAIDs相关自发报告中,新的一般的ADR报告404例,严重的ADR报告428例,新的严重的ADR报告47例.ADRs报告中男性2 965例(52.97%),女性2 632例(47.03%);年龄1~116(56.53±19.37)岁,大于60岁年龄段构成比最高;40岁以下年龄段男性多于女性,>40岁年龄段女性多于男性(P<0.01);且各年龄段男女构成比差异均有统计学意义(P<0.001).5 597例ADRs涉及NSAIDs十大类别,给药途径以静脉给药为主;ADR诱导期≤1 h例数最多;累及多个系统/器官,以胃肠系统损害(26.02%)和皮肤及皮肤附件损害(23.05%)为多见;严重ADR构成比最高为肝胆系统损害(17.67%);例数最多的品种为氟比洛芬酯,共686例(12.26%),相关严重ADR主要为肝功能异常等.结论:临床使用中应重视NSAIDs安全性问题,及时识别并处理ADR;有必要开展氟比洛芬酯相关用药风险评价研究.