Excellent Specificity Research Articles

Simultaneous determination of ethylene oxide, 2-chloroethanol and ethylene glycol residues in medical device products by gas chromatography

A gas chromatography-based method was developed for the simultaneous and rapid determination of ethylene oxide (EO), 2-chloroethanol (ECH), and ethylene glycol (EG) residues in medical devices after EO sterilization. A sample weighing 2.5 g was added with 5 mL of ethanol as the extraction medium, and the residual substances in the sample were extracted at 40 ℃ for 4 h. The samples were separated on a DB-WAX capillary column (30 m×0.53 mm×1.0 μm) and determined using a hydrogen flame ionization detector. The temperature was maintained at 40 ℃ for 5 min, increased to 120 ℃ at a rate of 40 ℃/min, held for 5 min, and then increased to 200 ℃ at a rate of 6 ℃/min, held for 2 min. The flow rate of the nitrogen gas was 3 mL/min. The split ratio was 5∶1. The inlet and detector temperatures were 200 and 300 ℃, respectively. The changes in the chromatographic peak areas over time (0.5-10 h) under different temperatures (20, 30, 40, and 50 ℃) were investigated, and the optimal extraction condition was determined to be 40 ℃ for 4 h. In the experiments, quantification was performed using an external standard method. EO, ECH, and EG exhibited good peak shapes and separation effects as well as good linearity within their respective ranges. The linear correlation coefficients for EO, ECH, and EG were greater than 0.99. The limits of detection (LODs) for EO, ECH, and EG were in the range of 0.10-0.40 μg/g, and the limits of quantification (LOQs) were in the range of 0.30-1.20 μg/g. The average recoveries under different spiked levels were in the range of 91.08%-116.08%, and the relative standard deviations (n=6) were in the range of 0.56%-8.45%. EO, ECH, and EG residues were found to exist at different levels in the medical devices tested. In particular, disposable infusion sets must be paid careful attention. ECH and EG were not detected in disposable sterile medical devices made of non-polyvinyl chloride materials, which may be due to the fact that the products themselves did not contain chloride ions, they were not exposed to chlorine-containing substances during their production, sterilization, storage, transportation, use, etc. This study established a method to detect EO residues in disposable medical devices, and has the advantages of simple operation, excellent specificity, accurate quantification, and good reproducibility. It can simultaneously detect three residual substances in medical devices while meeting the actual detection requirements for EO, ECH, and EG residues. The method can be used to scientifically and effectively evaluate the risk of EO residues in single-use medical devices sterilized with EO, and will be helpful for improving the quality of medical devices, ensuring the safety of device use, and providing a reference for regulatory supervision and testing.

Rapid and sensitive detection of staphylococcal enterotoxin E using a time-resolved fluorescence immunochromatography assay

Staphylococcal food poisoning is a significant foodborne illness caused by staphylococcal enterotoxins (SEs). Immunoassays have become the primary method for rapidly detecting harmful bacteria and toxins because of their excellent sensitivity and specificity. However, these assays have limitations in that they cannot differentiate between types of SEs and do not provide rapid, on-site, quantitative testing. In this study, a time-resolved fluorescence immunochromatography assay (TRFICA) was developed specifically for detecting staphylococcal enterotoxin E (SEE), which is commonly found in dairy products. Compared with a double antibody sandwich enzyme-linked immunosorbent assay, which had a detection limit of 0.028 ng/mL, TRFICA demonstrated comparable sensitivity, enabling SEE quantification with a detection limit as low as 0.081 ng/mL in infant formula. Validation by spiking infant formula samples confirmed no cross-reactivity with analogs (recoveries ranged from 93.17% to 128.77%). Furthermore, with an 8-min reaction time and interpretation delivered by a portable TRFICA strip reader, our method demonstrates potential for use in mobile and on-site detection. This study describes a rapid, easy, and reliable method for detecting trace levels of SEE in infant formula, which could serve as an early screening tool toward preventing food poisoning in infants and children.

Transdermal Minimally Invasive Optical Multiplex Detection of Protein Biomarkers by Nanopillars Array-Embedded Microneedles.

Biomarkers detection has become essential in medical diagnostics and early detection of life-threatening diseases. Modern-day medicine relies heavily on painful and invasive tests, with the extraction of large volumes of venous blood being the most common tool of biomarker detection. These tests are time-consuming, complex, expensive and require multiple sample manipulations and trained staff. The application of "intradermal" biosensors utilizing microneedles as minimally invasive sensing elements for capillary blood biomarkers detection has gained extensive interest in the past few years as a central point-of-care (POC) detection platform. Herein, we present a diagnosis paradigm based on vertically aligned nanopillar array-embedded microneedles sampling-and-detection elements for the direct optical detection and quantification of biomarkers in capillary blood. We present here a demonstration of the simple fabrication route for the creation of a multidetection-zone silicon nanopillar array, embedded in microneedle elements, followed by their area-selective chemical modification, toward the multiplex intradermal biomarkers detection. The utilization of the rapid and specific antibody-antigen binding, combined with the intrinsically large sensing area created by the nanopillar array, enables the simultaneous efficient ultrafast and highly sensitive intradermal capillary blood sampling and detection of protein biomarkers of clinical relevance, without requiring the extraction of blood samples for the ex vivo biomarkers analysis. Through preliminary in vitro and in vivo experiments, the direct intradermal in-skin blood extraction-free platform has demonstrated excellent sensitivity (low pM) and specificity for the accurate multiplex detection of protein biomarkers in capillary blood.

Evaluating the feasibility of upper arm ECG for cardiac monitoring

Abstract Background Ambulatory electrocardiogram (ECG) monitoring is essential for detecting paroxysmal cardiac events and tracking long-term physiological parameters. However, traditional Holter devices are cumbersome, restrict movement, and can cause skin irritation, resulting in sub-optimal patient compliance during extended monitoring periods. Wearable devices utilizing non-conventional form factors are emerging as promising non-intrusive alternatives for ECG monitoring. Purpose To determine the optimal location for single-lead ECG acquisition on the upper arm and assess the feasibility of using dry electrode armbands for cardiac monitoring when coupled with robust ECG processing software. Methods Stationary ECGs from 20 healthy adult participants were recorded across a two-phase data collection protocol and processed with clinically validated ECG software. In the first phase, the average signal amplitudes of wet-electrode ECGs obtained from 30 different configurations across the mid-brachial and proximal-brachial regions of the upper arm were assessed. In the second, the performance of two proprietary dry-electrode armbands, featuring either a single-point or three-point electrode strap, were evaluated on the optimal upper arm configuration using QRS detection and heart rate (HR) metrics. Comparative analysis was performed throughout using data simultaneously acquired on a gold standard Holter device in modified lead III (MLIII) configuration. Performance metrics were calculated relative to manually generated signal annotations. Results Wet-electrode-acquired ECGs from the proximal-brachial region exhibited significantly higher average signal amplitudes (0.12 ± 0.06 mV) compared to those from the mid-brachial region (0.05 ± 0.04 mV) of the upper arm (p < 0.05). The optimal configuration (A-F), positioned at the lateral and medial extents of the proximal-brachial region, demonstrated comparable average signal amplitudes (0.16 ± 0.07 mV, 0.16 ± 0.06 mV, 0.19 ± 0.08 mV) for single-point dry, three-point dry, and wet-electrode setups, respectively. Upon processing with ECG software, data from optimal dry-electrode configurations showed excellent average QRS sensitivity and specificity of 98.2% and 98.9% for the one-point strap, and 98.9% and 99.8% for the three-point strap, respectively. HR metrics from the optimized dry-electrode setups were comparable in accuracy to those derived from the reference Holter device, with the average HR error being similar across the three-point dry electrode strap (0.57% ± 0.28%), one-point dry electrode strap (1.16% ± 1.46%), and Holter device (0.74% ± 1.50%). Conclusion(s) Optimized upper arm single-lead ECG with dry electrodes can yield signals with sufficient amplitude and quality for automated ECG analysis. Coupled with robust ECG signal processing software, the cardiac metrics obtained from the optimized upper arm setups exhibited comparable performance to those derived from medical Holter data.

Novel Approaches for the Early Detection of Glaucoma Using Artificial Intelligence

Background: If left untreated, glaucoma—the second most common cause of blindness worldwide—causes irreversible visual loss due to a gradual neurodegeneration of the retinal ganglion cells. Conventional techniques for identifying glaucoma, like optical coherence tomography (OCT) and visual field exams, are frequently laborious and dependent on subjective interpretation. Through the fast and accurate analysis of massive amounts of imaging data, artificial intelligence (AI), in particular machine learning (ML) and deep learning (DL), has emerged as a promising method to improve the early detection and management of glaucoma. Aims: The purpose of this study is to examine the current uses of AI in the early diagnosis, treatment, and detection of glaucoma while highlighting the advantages and drawbacks of different AI models and algorithms. In addition, it aims to determine how AI technologies might transform glaucoma treatment and suggest future lines of inquiry for this area of study. Methods: A thorough search of databases, including Web of Science, PubMed, and Scopus, was carried out to find pertinent papers released until August 2024. The inclusion criteria were limited to research published in English in peer-reviewed publications that used AI, ML, or DL to diagnose or treat glaucoma in human subjects. Articles were chosen and vetted according to their quality, contribution to the field, and relevancy. Results: Convolutional neural networks (CNNs) and other deep learning algorithms are among the AI models included in this paper that have been shown to have excellent sensitivity and specificity in identifying glaucomatous alterations in fundus photos, OCT scans, and visual field tests. By automating standard screening procedures, these models have demonstrated promise in distinguishing between glaucomatous and healthy eyes, forecasting the course of the disease, and possibly lessening the workload of physicians. Nonetheless, several significant obstacles remain, such as the requirement for various training datasets, outside validation, decision-making transparency, and handling moral and legal issues. Conclusions: Artificial intelligence (AI) holds great promise for improving the diagnosis and treatment of glaucoma by facilitating prompt and precise interpretation of imaging data and assisting in clinical decision making. To guarantee wider accessibility and better patient results, future research should create strong generalizable AI models validated in various populations, address ethical and legal matters, and incorporate AI into clinical practice.

Tuning multispectral fluorescence quantum dot–based identification of short-length amyloid β peptides by applying Cu(II) ions

Currently available methods for detecting amyloid β (Aβ) derivatives are mainly dedicated to determining the long forms Aβ1-42 and Aβ1-40. At the same time, the number of physiologically occurring Aβ analogs is much higher, including those truncated at the N- and C-termini. Their identification using standard methods is challenging due to the structural similarity of various Aβ analogs, but could highly benefit from both biomarkers discovery and pathophysiological studies of Alzheimer’s disease. Therefore a “chemical tongue” sensing strategy was employed for the detection of seven Aβ peptide derivatives: Aβ1-16, Aβ4-16, Aβ4-9, Aβ5-16, Aβ5-12, Aβ5-9, Aβ12-16. The proposed sensing system is based on competitive interactions between quantum dots, Cu(II) ions, and Aβ peptides, providing unique fluorescence fingerprints useful for the identification of analytes. After carefully evaluating the Aβ sample preparation protocol, perfect determination of all studied Aβ peptides was achieved using partial least square–discriminant analysis (PLS-DA). The developed PLS-DA models are characterized by excellent accuracy, sensitivity, precision, and specificity of analyte determination, emphasizing the potential of the proposed sensing strategy.Graphical abstract

Split G-Quadruplex Programmed Recyclable AIE-Biosensor for Label-Free Detection of miRNA in Acute Kidney Injury.

We herein rationally designed a target-recyclable AIE-biosensor based on a split G-quadruplex for label-free detection of miRNA in acute kidney injury. Initially, the PG was in an "OFF" state, and the two split segments (G4-a and G4-b) of G4 were tethered at the two terminals of P1 and far away from each other due to the rigid duplex structure formed by the partially complementary intermediate sequences of P2 and P1, bringing MG with quenched fluorescence. In the presence of target, the 5'-PO4 P2 was displaced from PG probe and competitively hybridized with target, which led to G4-a and G4-b tending to form an intact intermolecular G-quadruplex, providing sites for MG intercalation, thus generating an activated "ON" fluorescence signal due to the restriction of intermolecular motion. Successively, relying on the λ-exonuclease (λ-Exo) cleavage reaction-assisted target recycling, more amounts of targets will be liberated, accompanied by forming more G-quadruplex and binding more MG, resulting in a strong fluorescence signal, further realizing the sensitive detection of the targets. As a proof of concept, miRNA-21 was chosen as the model target. Endowing with the precise target recognition and efficient cleavage activity of λ-Exo, the AIE-biosensor exhibited excellent detection sensitivity and specificity, which could quantitatively detect miRNA-21 down to 10.36 fM with a single mismatch specificity. The results revealed that the distinctive attributes of noninvasive, simple, and efficient in this G-quadruplex-based AIE-biosensor offered promising prospects for extensive applications in AKI screening and early clinical diagnosis.

A rapid and visual detection assay for Senecavirus A based on recombinase-aided amplification and lateral flow dipstick

BackgroundSenecavirus A (SVA) is a newly pathogenic virus correlated with the acute death of piglets and vesicular lesions in pigs. The further prevalence of SVA will cause considerable economic damage to the global pig farming industry. Therefore, rapid and accurate diagnostic tools for SVA are crucial for preventing and controlling the disease.MethodsWe designed multiple primer pairs targeting the most conserved region of the SVA 3D gene and selected those with the highest specificity. Nfo-probes were subsequently developed based on the highest specificity primer pairs. Subsequently, the recombinase-assisted amplification (RAA) reaction was completed, and the reaction temperature and duration were optimized. The RAA amplicons were detected using a lateral flow device (LFD). Finally, a rapid and intuitive RAA-LFD assay was established against SVA.ResultsThe SVA RAA-LFD assay can be performed under reaction conditions of 35°C within 17 minutes, with results observable to the naked eye. We then evaluated the performance of this method. It exhibited high specificity and no cross-reaction with the other common swine pathogens. The lowest detectable limits of this method for the plasmid of pMD18-SVA-3D, DNA amplification product, and viral were 3.86×101 copies/µL, 8.76×10-7 ng/µL, and 1×100.25 TCID50/mL, respectively. A total of 44 clinical samples were then tested using the RAA-LFD, PCR, and RT-qPCR methods. The results demonstrated a consistent detection rate between the RAA-LFD and RT-qPCR assays.ConclusionThe SVA RAA-LFD assay developed in our study exhibits excellent specificity, sensitivity, and time-saving attributes, making it ideally suited for utilization in lack-instrumented laboratory and field settings.

Accuracy of MRI in detecting seminal vesicle invasion in prostate cancer: a systematic review and meta-analysis.

To determine the diagnostic test accuracy of multiparametric magnetic resonance imaging (mpMRI) in detecting seminal vesicle invasion (SVI). The Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed, the Excerpta Medica dataBASE (EMBASE) and Cochrane databases were search up to May 2023. We included studies that investigated the accuracy of mpMRI in detecting SVI when compared to radical prostatectomy specimens as the reference standard. Data extraction was performed by two independent reviewers to construct 2 × 2 tables, as well as patient and study characteristics. The methodological quality of the included studies was assessed with the Quality of Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity were pooled and presented graphically with summary receiver operator characteristic (SROC) plots. A total of 27 articles with 4862 patients were included for analysis. The summary sensitivity and specificity were 0.57 (95% confidence interval [CI] 0.45-0.68) and 0.95 (95% CI 0.92-0.99), respectively. Meta-regression indicated that there was no evidence that coil strength (P = 0.079), coil type (P = 0.589), year of publication (P = 0.503) or use of the Prostate Imaging-Reporting and Data System (P = 0.873) significantly influenced these results. The summary diagnostic odds ratio was 28.3 (95% CI 15.0-48.8) and the area under the curve for the SROC curve was 0.87. The I2 statistic was a modest 11.9%. In general, methodological quality was good. The use of mpMRI in detecting SVI has excellent specificity but poor sensitivity. Both endorectal coils and magnetic field strength do not significantly impact the accuracy of MRI. These findings suggest that mpMRI cannot reliably rule out SVI in patients with prostate cancer.

Enzymatic reaction and competitive prereduction enable label-free and separation-free inductively coupled plasma mass spectrometry detection of leukemia cells

The enzyme terminal deoxynucleotidyl transferase (TdT) exhibits significant activity in various leukemia cells, including human acute lymphoblastic leukemia cells (CCRF). It demonstrates substantial potential as a diagnostic biomarker for acute lymphoblastic leukemia (ALL). Herein, a highly sensitive method for the homogeneous quantification of TdT and CCRF cells, without the need for labeling or separation, was established based on inductively coupled plasma mass spectrometry (ICP-MS). The simple sensor relied on the TdT-induced polymerization process, lengthening the DNA strand and producing large amounts of the by-product phosphates of pyrophosphate (PPi). The PPi formed complexes with Cu²⁺, altering its morphology in homogeneous systems. The remaining Cu²⁺ competed with Hg²⁺ in consuming ascorbic acid (AA) through the pre-reduction of Hg²⁺, affecting the ICP-MS signal of Hg²⁺. Under optimal conditions, this approach exhibited excellent specificity and ultrahigh sensitivity, with limits of detection (LODs) as low as 0.05 U/L for TdT and 5 cells/mL for CCRF cells, respectively. The proposed method offers significant advantages, including high sensitivity and precision, operation at room temperature without the involvement of proteases, and the ability to accurately quantify in complex biological matrices. Consequently, the proposed method shows great promise as a valuable tool for TdT-related biological research and leukemia diagnosis.

Amplified Sensitivity in SERS Detection of L1CAM With Silver Plasmonic Mesoporous Silica Capsules on an Imprinted Films

AbstractThis study presents a novel approach for dual detection, leveraging a combination of a Raman reporter‐bearing nanomaterial and molecular imprinting polymers (MIP). A core‐shell Au‐Ag nanoparticles (Au‐Ag NPs) encapsulated in mesoporous silica nanocapsules (Au‐Ag NCs) and a new MIP‐based material targeting L1CAM are used. The MIP prepared via surface imprinting on a carbon screen‐printed electrode (C‐SPE) used thionine (TH) as a monomer. The plasmonic Au‐AgNCs are further functionalized with the Raman reporter 4‐mercaptobenzoic acid (MBA) and anti‐L1CAM for selective detection by surface‐enhanced Raman scattering (SERS) spectroscopy. The biosensor's analytical performance is evaluated using both SERS and electrochemical impedance spectroscopy (EIS). EIS analysis reveals a linear response within the concentration range of 0.1 to 100 ng mL−1 in buffer and serum samples. SERS demonstrates a sensitivity ten times higher than EIS. Selectivity study demonstrates the biosensor's excellent specificity toward L1CAM, with minimal interference from other compounds such as creatinine, glucose, and carbohydrate antigen 19‐9 (CA 19‐9). The Raman signal from the reporter molecule correlates with increasing L1CAM concentrations, reinforcing the analytical findings obtained through electrochemical analysis. Thus, the combination of dual detection and recognition capabilities presents promising potential for detecting diverse biomarkers, especially in critical scenarios where reducing false‐positive or false‐negative errors is crucial.

Characterization of dynamic changes in cardiac microstructure after reperfused ST-elevation myocardial infarction by biphasic diffusion tensor cardiovascular magnetic resonance.

Microstructural disturbances underlie dysfunctional contraction and adverse left ventricular (LV) remodelling after ST-elevation myocardial infarction (STEMI). Biphasic diffusion tensor cardiovascular magnetic resonance (DT-CMR) quantifies dynamic reorientation of sheetlets (E2A) from diastole to systole during myocardial thickening, and markers of tissue integrity [mean diffusivity (MD) and fractional anisotropy (FA)]. This study investigated whether microstructural alterations identified by biphasic DT-CMR: (i) enable contrast-free detection of acute myocardial infarction (MI); (ii) associate with severity of myocardial injury and contractile dysfunction; and (iii) predict adverse LV remodelling. Biphasic DT-CMR was acquired 4 days (n = 70) and 4 months (n = 66) after reperfused STEMI and in healthy volunteers (HVOLs) (n = 22). Adverse LV remodelling was defined as an increase in LV end-diastolic volume ≥ 20% at 4 months. MD and FA maps were compared with late gadolinium enhancement images. Widespread microstructural disturbances were detected post-STEMI. In the acute MI zone, diastolic E2A was raised and systolic E2A reduced, resulting in reduced E2A mobility (all P < .001 vs. adjacent and remote zones and HVOLs). Acute global E2A mobility was the only independent predictor of adverse LV remodelling (odds ratio .77; 95% confidence interval .63-.94; P = .010). MD and FA maps had excellent sensitivity and specificity (all > 90%) and interobserver agreement for detecting MI presence and location. Biphasic DT-CMR identifies microstructural alterations in both diastole and systole after STEMI, enabling detection of MI presence and location as well as predicting adverse LV remodelling. DT-CMR has potential to provide a single contrast-free modality for MI detection and prognostication of patients after acute STEMI.

Identification and interaction analysis of molecular markers in myocardial infarction by bioinformatics and next-generation sequencing data analysis

BackgroundCardiovascular diseases are prevalent worldwide with any age, and it is characterized by sudden blockage of blood flow to heart and permanent damage to the heart muscle, whose cause and underlying molecular mechanisms are not fully understood. This investigation aimed to explore and identify essential genes and signaling pathways that contribute to the progression of MI.MethodsThe aim of this investigation was to use bioinformatics and next-generation sequencing (NGS) data analysis to identify differentially expressed genes (DEGs) with diagnostic and therapeutic potential in MI. NGS dataset (GSE132143) was downloaded from the Gene Expression Omnibus (GEO) database. DEGs between MI and normal control samples were identified using the DESeq2 R bioconductor tool. The gene ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed using g:Profiler. Next, four kinds of algorithms in the protein–protein interaction (PPI) were performed to identify potential novel biomarkers. Next, miRNA-hub gene regulatory network analysis and TF-hub gene regulatory network were constructed by miRNet and NetworkAnalyst database, and Cytoscape software. Finally, the diagnostic effectiveness of hub genes was predicted by receiver operator characteristic curve (ROC) analysis and AUC more than 0.800 was considered as having the capability to diagnose MI with excellent specificity and sensitivity.ResultsA total of 958 DEGs were identified, consisting of 480 up-regulated genes and 478 down-regulated genes. The enriched GO terms and pathways of the DEGs include immune system, neuronal system, response to stimulus and multicellular organismal process. Ten hub genes (namely cftr, cdk1, rps13, rps15a, rps27, notch1, mrpl12, nos2, ccdc85b and atn1) were obtained via protein–protein interaction analysis results. MiRNA-hub gene regulatory network and TF-hub gene regulatory network showed that hsa-mir-409-3p, hsa-mir-3200-3p, creb1 and tp63 might play an important role in the MI.ConclusionsAnalysis of next-generation sequencing dataset combined with global network information and validation presents a successful approach to uncover the risk hub genes and prognostic markers of MI. Our investigation identified four risk- and prognostic-related gene signatures, including cftr, cdk1, rps13, rps15a, rps27, notch1, mrpl12, nos2, ccdc85b and atn1. This gene sets contribute a new perspective to improve the diagnostic, prognostic, and therapeutic outcomes of MI.

Effects of insertion of an h-AlN monolayer spacer in Pt-WSe2-Pt field-effect transistors

The growth of two-dimensional hexagonal aluminum nitride (h-AlN) on transition metal dichalcogenide (TMD) monolayers exhibits superior uniformity and smoothness compared to HfO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_{2}$$\\end{document} on silicon substrate. This makes an h-AlN monolayer an ideal spacer between the gate oxide material and the WSe2 monolayer in a two-dimensional field effect transistor (FET). From first principles approaches, we calculate and compare the transmission functions and current densities of Pt–WSe2–Pt nanojunctions without and with the insertion of an h-AlN monolayer as a spacer in the gate architecture. The inclusion of h-AlN can alter the characteristics of the Pt–WSe2–Pt FET in response to the gate voltage (Vg\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$V_\ ext {g}$$\\end{document}). The FET without (or with) h-AlN exhibits the characteristics of a P-type (or bipolar) transistor: an on/off ratio of around 2.5×106\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$2.5 \ imes 10^{6}$$\\end{document} (or 1.7×106\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$1.7 \ imes 10^{6}$$\\end{document}); and an average subthreshold swing (S.S.) of approximately 109 mV/dec.\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {dec.}$$\\end{document} (or 112 mV/dec.\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {dec.}$$\\end{document}), respectively. We observe that Vg\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$V_\ ext {g}$$\\end{document} shifts the profile of the transmission function by an energy of α(eVg)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha (e V_{\ ext {g}})$$\\end{document}, where α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha$$\\end{document} represents the gate-controlling efficiency. We observed that αin=83%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha _{\ ext {in}}=83\\%$$\\end{document} and αout=33%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha _{\ ext {out}}=33\\%$$\\end{document}, corresponding to whether the Fermi energy is located inside or outside the band gap. Therefore, we construct an effective gate model based on the Landauer formula, with the transmission function at Vg=0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$V_\ ext {g}=0$$\\end{document} as the baseline. Our model generates results that are consistent with those obtained through first principles calculations. The relative error in current densities between model and first-principles calculations is within [ln(10)S.S.]|ΔVGeff|\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$[\\frac{ln(10)}{S.S.}] | \\Delta V_{\ ext {G}}^{\ ext {eff}} |$$\\end{document}. The 2D atomistic FETs show excellent device specifications and the ability to compete with existing transistors based on traditional silicon technology. Our findings could help advance the design of TMD-based FETs.

Monitoring of mercury ion in environmental media and biological systems using a red emissive fluorescent probe with a large Stokes shift

The development of practical fluorescent probe for detecting toxic mercury ions (Hg2+) is desirable for environmental assurance and public health. In this study, a new red emissive fluorescent probe (KJL) was designed and synthesized for monitoring trace Hg2+ both in vitro and in vivo with distinct features including ideal response rate (within 4 min), red emission (596 nm), large Stokes shift (162 nm), highly sensitivity (LOD = 4.79 nM) and excellent specificity. KJL also validated the good capability for accurately monitoring trace Hg2+ levels in actual samples (faucet water, drinking water, river water, lake water, urine and serum) and possessed the eye-catching ability in visualization of Hg2+ under environmental/biological conditions, which revealed the great potential of this red-emitting fluorescent probe for practical applications in complex environmental and biological systems.

Construction of in-situ self-assembled agent for NIR/PET dual-modal imaging and photodynamic therapy for hepatocellular cancer

Hepatocellular cancer (HCC) remained a life-threatening carcinoma. Agents for HCC imaging and therapy were expected to possess different intratumoral retention time. To construct an agent with different intratumoral retention time when applied for tumor imaging or therapy remained great values. A lasialoglycoprotein receptor (ASGPR) targeted lactobionic acid derivative (LABO) was constructed for fluorescent imaging and photodynamic therapy of HCC. 18F labeled LABO (18F-LABO) was developed for PET imaging of HCC. LABO and 18F-LABO showed similar molecular structure. LABO exhibited characteristic of viscosity and concentration-induced intratumoral in-situ self-assembly to expand the intratumoral retention. LABO was non-fluorescent at free stage, but emitted NIR fluorescence and generated irradiation-induced ROS after self-assembly for fluorescent imaging and photodynamic therapy. ASGPR specificity of LABO and 18F-LABO was confirmed using HepG2 cell. Biodistribution and fluorescent imaging confirmed the different tumor retention time of LABO and 18F-LABO when used for photodynamic therapy and PET imaging. PET imaging and photodynamic therapy were performed on HepG2 tumor bearing mice, which revealed that 18F-LABO/LABO could specifically accumulated in the HepG2 tumor for tumor location/inhibition. LABO/18F-LABO with excellent HCC specificity but different intratumoral behaviors showed great values for the PET/NIR imaging and photodynamic therapy for HCC.Graphical

A study on fast detection methods for tetracycline antibiotic residues based on magnetic nanoparticles and electrochemical aptasensors

This study presents the development of novel electrochemical aptasensors utilizing magnetic nanomaterials for rapid and sensitive detection of tetracycline (TET) antibiotic residues. Two types of nanocomposites, Cu2O@Au octahedral nanoparticles and rGO-Fe3O4, were synthesized and characterized for aptasensor fabrication. The Cu2O@Au-based aptasensor demonstrated a linear detection range from 1 nM to 1 μM, with a limit of detection (LOD) of 0.3 nM. The rGO-Fe3O4/sodium alginate-based aptasensor exhibited a linear range of 5 nM to 500 nM, with an LOD of 1.5 nM. Both aptasensors showed excellent specificity towards TET, good reproducibility (RSD < 5.6 %), and stability (>90 % response after 2 weeks). The practical applicability of the aptasensors was validated through TET detection in spiked milk samples, achieving recoveries between 88.6 % and 107.8 % with RSDs below 7.2 %. These aptasensors offer advantages such as rapid response, simple fabrication, and potential for on-site detection, making them promising tools for food safety monitoring and environmental surveillance.

Evaluation of a plasma cell-free DNA methylation test for colorectal cancer diagnosis: a multicenter clinical study.

A blood-based diagnostic test is a promising strategy for colorectal cancer (CRC). The MethyDT test (IColohunter), which detects methylation levels of NTMT1 and MAP3K14-AS1, exhibited potential in discriminating CRC, but its clinical performance needs to be validated in large-scale populations. A multicenter, double-blinded, cross-sectional study that enrolled 1194 participants was performed. Plasma samples were collected to detect methylation levels of NTMT1 and MAP3K14-AS1 using quantitative methylation-specific PCR with the MethyDT test, and the accuracy was further evaluated by Sanger sequencing. The sensitivities of the MethyDT test for detecting CRC, early stages of CRC (I and II), advanced adenoma (AA), and high-grade intraepithelial neoplasia (HGIN) were 91.2% (95% confidence interval [CI], 88.4-94.0), 87.4% (95% CI, 82.5-92.2), 43.5% (95% CI, 35.7-51.4), and 72.7% (95% CI, 57.5-87.9), respectively. The specificities for participants with non-AA, interfering diseases (ID), and no evidence of disease (NED) were 85.0% (95% CI, 78.8-91.3), 93.7% (95% CI, 91.4-95.9) and 97.3% (95% CI, 90.5-99.7), respectively, and its overall specificity for all-controls was 92.4% (95% CI, 90.3-94.4). The consistency of the MethyDT test with pathology for CRC was high with a kappa value of 0.830 (95% CI, 0.795-0.865). Additionally, the MethyDT test was comparable to Sanger sequencing for detecting methylation with kappa values > 0.97. The MethyDT test demonstrates excellent sensitivity and specificity for CRC and high consistency with Sanger sequencing for methylation, suggesting it may serve as a potential noninvasive diagnostic tool for the detection of CRC. This clinical trial has been registered in ClinicalTrials.gov (NCT05508503).

Rational Molecular Design of a Fluorescent Probe for Selectively Sensing Human Cytochrome P450 2D6.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme that mediates the metabolism of various drugs and endogenous substances in humans. However, its biological role in drug-drug interactions especially mechanism-based inactivation (MBI), and various diseases remains poorly understood, owing to the lack of molecular tools suitable for selectively monitoring CYP2D6 in complex biological systems. Herein, using a tailored molecular strategy, we developed a fluorescent probe BDPM for CYP2D6. BDPM exhibits excellent specificity and imaging capability for CYP2D6, making it suitable for the real-time monitoring of endogenous CYP2D6 activity in living bio-samples. Therefore, our tailored strategy proved useful for constructing the highly selective and enzyme-activated fluorescent probes. BDPM as a molecular tool to explore the critical roles of CYP2D6 in the pathogenesis of diseases, high-throughput screening of inhibitors and intensive investigation of CYP2D6-induced MBI in natural systems.

Co-freezing localized CRISPR-Cas12a system enables rapid and sensitive nucleic acid analysis

Rapid and sensitive nucleic acid detection is vital in disease diagnosis and therapeutic assessment. Herein, we propose a co-freezing localized CRISPR-Cas12a (CL-Cas12a) strategy for sensitive nucleic acid detection. The CL-Cas12a was obtained through a 15-minute co-freezing process, allowing the Cas12a/crRNA complex and hairpin reporter confined on the AuNPs surface with high load efficiency, for rapid sensing of nucleic acid with superior performance to other localized Cas12a strategies. This CL-Cas12a based platform could quantitatively detect targets down to 98 aM in 30 min with excellent specificity. Furthermore, the CL-Cas12a successful applied to detect human papillomavirus infection and human lung cancer-associated single-nucleotide mutations. We also achieved powerful signal amplification for imaging Survivin mRNA in living cells. These findings highlight the potential of CL-Cas12a as an effective tool for nucleic acid diagnostics and disease monitoring.Graphical abstract