RESUMO
Tuberculosis (TB), characterized by high mortality and low diagnosis, is caused by a single pathogen, Mycobacterium tuberculosis (Mtb). Imaging tools that can be used to track Mtb without pre-labeling and to diagnose live Mtb in clinical samples can shorten the gap between bench and clinic, fuel the development of novel anti-TB drugs, strengthen TB prevention, and improve patient treatment. In this study, we report an unprecedented novel nitroreductase-responsive cyanine-based fluorescent probe (Cy3-NO2-tre) that rapidly and specifically labels Mtb and detects it in clinical samples. Cy3-NO2-tre generated fluorescence after activation by a specific nitroreductase, Rv3368c, which is conserved in the Mycobacteriaceae. Cy3-NO2-tre effectively imaged mycobacteria within infected host cells, tracked the infection process, and visualized Mycobacterium smegmatis being endocytosed by macrophages. Cy3-NO2-tre also detected Mtb in the sputum of patients with TB and exhibited excellent photostability. Furthermore, the Cy3-NO2-tre/auramine O percentage change within 7 ± 2 days post drug treatment in the sputum of inpatients was closely correlated with the reexamination results of the chest computed tomography, strongly demonstrating the clinical application of Cy3-NO2-tre as a prognostic indicator in monitoring the therapeutic efficacy of anti-TB drugs in the early patient care stage.
Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Dióxido de Nitrogênio , Tuberculose/diagnóstico por imagem , Tuberculose/tratamento farmacológico , Antituberculosos/farmacologia , Mycobacterium smegmatis , Escarro/microbiologiaRESUMO
Transferrin (TRF), recognized as a glycoprotein clinical biomarker and therapeutic target, has its concentration applicable for disease diagnosis and treatment monitoring. Consequently, this study developed boronic acid affinity magnetic surface molecularly imprinted polymers (B-MMIPs) with pH-responsitivity as the "capture probe" for TRF, which have high affinity similar to antibodies, with a dissociation constant of (3.82 ± 0.24) × 10-8 M, showing 7 times of reusability. The self-copolymerized imprinted layer synthesized with dopamine (DA) and 3-Aminophenylboronic acid (APBA) as double monomers avoided nonspecific binding sites and produced excellent adsorption properties. Taking the gold nanostar (AuNS) with a branch tip "hot spot" structure as the core, the silver-coated AuNS functionalized with the biorecognition element 4-mercaptophenylboronic acid (MPBA) was employed as a surface-enhanced Raman scattering (SERS) nanotag (AuNS@Ag-MPBA) to label TRF, thereby constructing a double boronic acid affinity "sandwich" SERS biosensor (B-MMIPs-TRF-SERS nanotag) for the highly sensitive detection of TRF. The SERS biosensor exhibited a detection limit for TRF of 0.004 ng/mL, and its application to spiked serum samples confirmed its reliability and feasibility, demonstrating significant potential for clinical TRF detection. Moreover, the SERS biosensor designed in this study offers advantages in stability, detection speed (40 min), and cost efficiency. The portable Raman instrument for SERS detection fulfills the requirements for point-of-care testing.
Assuntos
Técnicas Biossensoriais , Ácidos Borônicos , Ouro , Análise Espectral Raman , Ácidos Borônicos/química , Técnicas Biossensoriais/métodos , Ouro/química , Humanos , Análise Espectral Raman/métodos , Prata/química , Nanopartículas Metálicas/química , Limite de Detecção , Transferrina/análise , Transferrina/química , Impressão Molecular , Polímeros Molecularmente Impressos/química , Glicoproteínas/sangue , Glicoproteínas/química , Materiais Biomiméticos/química , Dopamina/sangue , Dopamina/análise , Compostos de SulfidrilaRESUMO
High-sensitivity quantitative analysis of sepsis disease markers in circulating blood is essential for sepsis early diagnosis, rapid stratification, and interventional treatment. Herein, a high-sensitivity biosensor combining surface-enhanced Raman spectroscopy (SERS) and functionalized magnetic materials was developed to quantitatively detect interleukin-6 (IL-6), a glycoprotein disease marker closely related to sepsis. First, boronic acid-functionalized magnetic nanomaterials with high adsorption performance were synthesized by utilizing the branched polyethyleneimine to provide many binding sites for boronic acid. Under antibody-free conditions, dendrimer-assisted boronic acid-functionalized magnetic nanomaterials selectively capture glycoproteins in complex biological samples as bio-capture element. Then, a core-shell bimetallic material with plenty of 'hot spots' was designed and synthesized as the enhancement substrate. The 4-Mercaptobenzonitrile (4-MP) with a characteristic peak at 2224 cm-1(Raman-silent region) was embedded as the Raman reporter to form a SERS immune probe with highly efficient electromagnetic enhancement effect, achieving specific recognition and high-sensitivity detection of IL-6 on bio-capture elements. Using this strategy for quantitative analysis of IL-6, a wide detection range (0.5-5000 pg ml-1) and a low detection limit (0.453 pg ml-1) were obtained. Moreover, this method exhibited excellent detection performance for IL-6 in human serum samples, demonstrating its potential promise in screening clinically relevant diseases. The biosensor presented here not only provides a novel and universally applicable sensing strategy for the enrichment and detection of trace glycoprotein disease markers, but also the application of a portable Raman spectrometer provides a more reliable experimental basis for the diagnosis and treatment of major diseases in the clinic or remote and deprived areas.
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Técnicas Biossensoriais , Dendrímeros , Nanopartículas de Magnetita , Nanopartículas Metálicas , Humanos , Interleucina-6 , Ácidos Borônicos/química , Nanopartículas de Magnetita/química , Análise Espectral Raman/métodos , Glicoproteínas/análise , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Ouro/químicaRESUMO
A sandwich-structured SERS biosensor has been constructed for simultaneous detection of multiple pathogenic bacteria, consisting of non-interfering SERS probes for bacterial labeling and ConA-functionalizd magnetic nanoparticles for bacteria extraction. A the preparation method of PP3 SERS probe with high Raman activity is reported for the first time. Since the PP3 SERS probe has a very strong Raman peak at 2081 cm-1 in the "Raman silent region," the mixed SERS probe formed with MP1 and DP2 can meet the needs of multiple foodborne pathogen detection. Significantly, S. aureus, E. coli, and P. aeruginosa can be successfully extracted upon external magnetic field, and the limit of detection (LOD) is 1 CFUâ§mL-1, lower than that of the congeneric detectors. This work paves a new way for the construction of a novel detector and absorbent for different bacteria in complex samples by using SERS probe.
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Técnicas Biossensoriais , Nanopartículas de Magnetita , Escherichia coli , Staphylococcus aureus , Técnicas Biossensoriais/métodos , Limite de Detecção , Análise Espectral Raman/métodosRESUMO
Specific recognition and highly sensitive detection of biomarkers play an essential role in identification, early diagnosis and prevention of many diseases. Magnetic molecularly imprinted polymers (MMIPs) have been widely used to capture biomimetic receptors for targets in various complex matrices due to their superior recognition ability, structural stability, and rapid separation characteristics, which overcome the existing deficiencies of traditional recognition elements such as antibodies, aptamers. The integration of MMIPs as recognition elements with chemical sensors opens new opportunities for the development of advanced analytical devices with improved selectivity and sensitivity, shorter analysis time, and lower cost. Recently, MMIPs-chemical sensors (MMIPs-CS) have made significant progress in detection, but many challenges and development spaces remain. Therefore, this review focuses on the research progress of the sensor based on biomarker detection and introduces the surface modification of the magnetic support material used to prepare high selective MMIPs, as well as the selective extraction of target biomarkers by MMIPs from the complex biological sample matrix. Based on the understanding of optical sensors and electrochemical sensors, the applications of MMIPs-optical sensors (MMIPs-OS) and MMIPs-electrochemical sensors (MMIPs-ECS) for biomarker detection were reviewed and discussed in detail. Moreover, it provides an overview of the challenges in this research area and the potential strategies for the rational design of high-performance MMIPs-CS, accelerating the development of multifunctional MMIPs-CS.
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Impressão Molecular , Adsorção , Biomarcadores , Fenômenos Magnéticos , Polímeros Molecularmente Impressos , PolímerosRESUMO
Foodborne diseases caused by pathogenic bacteria pose a serious threat to human health. Early and rapid detection of foodborne pathogens is an urgent task for preventing disease outbreaks. Microfluidic devices are simple, automatic, and portable miniaturized systems. Compared with traditional techniques, microfluidic devices have attracted much attention because of their high efficiency and convenience in the concentration and detection of foodborne pathogens. This article firstly reviews the bio-recognition elements integrated on microfluidic chips in recent years and the progress of microfluidic chip development for pathogen pretreatment. Furthermore, the research progress of microfluidic technology based on optical and electrochemical sensors for the detection of foodborne pathogenic bacteria is summarized and discussed. Finally, the future prospects for the application and challenges of microfluidic chips based on biosensors are presented.
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Técnicas Biossensoriais , Doenças Transmitidas por Alimentos , Bactérias , Técnicas Biossensoriais/métodos , Doenças Transmitidas por Alimentos/diagnóstico , Humanos , Dispositivos Lab-On-A-Chip , MicrofluídicaRESUMO
Since a novel coronavirus was discovered from a cluster of patients with emerging pneumonia of unknown etiology in Wuhan, China, it has spread rapidly through droplet and contact transmission. Recently, the novel coronavirus pneumonia which was named COVID-19 by the World Health Organization (WHO) has been raised as a worldwide problem. Radiological examinations were confirmed as effective methods for the screening and diagnosis of COVID-19. It is reported that some radiologists and radiological technologists were infected when giving examinations to the patients with COVID-19. In order to reduce the infection risk of medical staff in radiology department, we summarized the experience on prevention and control measures in radiology department for COVID-19, aiming to guide the prevention and practical work for radiologists and radiological technologists. KEY POINTS: ⢠The novel coronavirus spreads rapidly through droplet and contact transmission. ⢠Radiologists and radiological technologists were possibly infected by patients. ⢠Prevention and control measures in radiology department for COVID-19 are important.
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Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Saúde Ocupacional , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Pneumonia Viral/prevenção & controle , Serviço Hospitalar de Radiologia/organização & administração , COVID-19 , Humanos , SARS-CoV-2 , Local de TrabalhoRESUMO
BACKGROUND: Rectus femoris necrosis is a rare but severe complication after anterolateral thigh flap (ALTF) harvesting. It has been previously reported that the blood supply of the rectus femoris (RF) often arises from the same source artery as the ALTF; however, precise descriptions of the relationship remain limited. This article revisits the blood supply of the RF based on computed tomography angiography (CTA) and analyzes the possible influence of the blood supply on the RF during ALTF harvesting. METHODS: Between December 2017 and June 2018, CTA images of the bilateral lower extremities of 25 patients were studied. The RF length, number, and diameter of branches at the entry point into muscle, location, and overall branch vessel origins were recorded. RESULTS: The average ± SD RF length was 384.73 ± 19.28 mm. There were 170 branches (mean ± SD, 3.4 ± 0.96 branches per thigh), mainly arising from the lateral circumflex femoral artery. The average ± SD diameter was 1.90 ± 0.51 mm. The first branch was located at 1/5 of the proximal site of the RF, and 91% of all branches were located above the midpoint. The RF vascularity can be classified into 2 types: type 1 (36% of sides) has branches that arise from a single artery (descending lateral circumflex femoral artery or femoral artery), whereas type 2 (64% of sides) has branches at the 1/5 proximal and 4/5 distal parts, which arise from different arteries. CONCLUSIONS: Preoperative CTA can provide anatomic information about the RF's nutrient vessel(s) and helps to optimize ALTF design.
Assuntos
Angiografia por Tomografia Computadorizada , Músculo Quadríceps , Artéria Femoral , Humanos , Extremidade Inferior , Músculo Quadríceps/diagnóstico por imagem , Retalhos Cirúrgicos , Coxa da Perna/diagnóstico por imagemRESUMO
A Pd-catalyzed ring-opening reaction of 2 H-azirines with carboxylic acids was developed. This reaction undergoes nucleophilic addition between 2,3-diaryl-2 H-azirines and carboxylic acids followed by C-N single-bond cleavage and a subsequent thermal rearrangement. This method enables the rapid construction of valuable α-amido ketone derivatives with high atomic efficiency and superb functional group tolerance.
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Activated carbon supported nano zero-valent iron material (NZVI/AC) was prepared and added to an anaerobic digestion tank to reduce the toxicity inhibition of phenols and increase the methane yield of phenol-containing organic wastewater (POW). The anaerobic digestion (AD) characteristics, including conversion rate of organic substances, removal rate of phenol, and methane yield of POW with different concentrations of phenol were studied, and moreover, the enhancing effects of NZVI/AC on the AD of POW were focused. When the concentration of phenol was below 500â¯mg/L, the methane yield from AD of POW was 387.5â¯mL, which was 10.71% higher than that from control organic water without phenol, however, phenol concentrations greater than 1000â¯mg/L severely inhibited AD, and methane yield was only 50% of the control sample. Indicating that anaerobic microorganisms had a certain degree of tolerance to phenol, and low concentration of phenol could promote AD of organic water although the phenol with high concentration showed severe inhibition. The methane yield increased due to the probable conversion of phenol to methane by microbial actions. In the AD of POW with 500â¯mg/L phenol, the conversion rate of organic substances increased from 37.49% (control group without any accelerant) to 66.56% after adding NZVI/AC. The removal rate of phenol also increased from 39.03% to 81.32%. Cumulative methane yield increased by 145.5%-810â¯mL compared with the control group. The AC carrier in NZVI/AC exerted a good adsorption effect on phenols, reducing the concentration of phenols in the solution and thus minimizing their toxic effects on microbial activity. The NZVI loaded on AC particles strengthened the electron transfer between methanogens by its good electrical conductivity, and then promoted the AD performance of organic matter. Furthermore, NZVI exerted a micro-electrolytic effect on phenolic substances, which could increase the removal rate of phenol. Therefore, NZVI/AC could be used as an efficient accelerant for the AD of POW to enhance the AD process.
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Carvão Vegetal , Águas Residuárias , Anaerobiose , Ferro , Fenol , Fenóis , EsgotosRESUMO
A series of structurally new diheteroaryl thioether analogs was designed, prepared and screened toward MGC-803, MKN-45, EC-109 and H1650. Most of the target compounds displayed moderate to potent antiproliferative activities. Among them, compound 5 showed the best antiproliferative activity against the tested cell lines with the half maximal inhibitory concentration (IC50) values below 10µM. In addition, flow cytometry analysis showed that compound 5 increased Bax expression, down-regulated expression of Bcl-2, cleaved caspases-3/9, finally inducing apoptosis of MKN-45 cells as well asarrested the cell cycle at G2/M phase. This study suggests that the diheteroaryl thioethers are a class of emerging chemotypes for developing antitumor agents or biological probes, and compound 5 could serve as a good starting point to design new apoptosis inducers.
Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Sulfetos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Sulfetos/síntese química , Sulfetos/químicaRESUMO
Contrast-enhanced computed tomography scans (CECT) are routinely used in the evaluation of different clinical scenarios, including the detection and characterization of hepatocellular carcinoma (HCC). Quantitative medical image analysis has been an exponentially growing scientific field. A number of studies reported on the effects of variations in the contrast enhancement phase on the reproducibility of quantitative imaging features extracted from CT scans. The identification and labeling of phase enhancement is a time-consuming task, with a current need for an accurate automated labeling algorithm to identify the enhancement phase of CT scans. In this study, we investigated the ability of machine learning algorithms to label the phases in a dataset of 59 HCC patients scanned with a dynamic contrast-enhanced CT protocol. The ground truth labels were provided by expert radiologists. Regions of interest were defined within the aorta, the portal vein, and the liver. Mean density values were extracted from those regions of interest and used for machine learning modeling. Models were evaluated using accuracy, the area under the curve (AUC), and Matthew's correlation coefficient (MCC). We tested the algorithms on an external dataset (76 patients). Our results indicate that several supervised learning algorithms (logistic regression, random forest, etc.) performed similarly, and our developed algorithms can accurately classify the phase of contrast enhancement.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Aprendizado de Máquina , AlgoritmosRESUMO
Surface-enhanced Raman scattering (SERS) is an ultra-sensitive vibration spectroscopy technology, with the advantages of multi-index and non-destructive quantitative detection, has attracted much attention in the joint detection of biomarkers. A novel SERS biosensor with multisite capture and interference-free quantification was designed for the joint detection of the sepsis biomarker interleukin-6 (IL-6) and procalcitonin (PCT). This biosensor had two interference-free core-shell SERS probes with highly efficient electromagnetic enhancement and a multisite functionalized magnetic nanomaterial with high adsorption capacity. They formed sandwich structure with the targets through boronic affinity and immunoreaction, and the multi-target quantitative analysis of biomarkers in serum was performed using a portable Raman spectrometer in the Raman-silent region. The SERS biosensor was exhibited highly sensitive with detection limits of 0.584 and 2.99 pg/mL for IL-6 and PCT, respectively. In addition, it exhibited excellent selectivity and specificity even with the interference of other proteins. As this SERS method showed excellent performance in the detection of sepsis, it has great potential for multi-index detection in clinical diagnosis of major diseases.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Nanoestruturas , Sepse , Humanos , Interleucina-6 , Biomarcadores/análise , Análise Espectral Raman/métodos , Sepse/diagnóstico , Fenômenos Magnéticos , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Ouro/químicaRESUMO
We report a low-cost and highly sensitive label-free SERS biosensor for pathogen detection. Herein, this study prepared 4-formylphenylboric acid (FPBA) functionalized magnetic nanoparticles to adsorb pathogenic bacteria through boric acid affinity principle, and used aptamer modified Au@AgNPs as SERS substrate to specifically combine with pathogenic bacteria to form a sandwich structure. The pathogenic bacteria were detected by portable Raman spectrometer for SERS detection, and the fingerprint signals of pathogenic bacteria were analyzed by principal component analysis (PCA) to achieve the purpose of classification and identification of pathogenic bacteria. Under the optimized conditions, the SERS detection of Staphylococcus aureus (S. aureus) was 102 â¼ 106 CFU/mL (R2 = 0.9925), and the limit of detection (LOD) was 34 CFU/mL. The linear range of Escherichia coli (E. coli) showed a good linear relationship in the range of 102 â¼ 106 CFU/mL (R2 = 0.9993), and the LOD was 18 CFU/mL. The whole detection process was used the portable Raman spectrometer, which makes it suitable for the application of point-of-care testing (POCT).
Assuntos
Aptâmeros de Nucleotídeos , Nanopartículas de Magnetita , Nanopartículas Metálicas , Animais , Nanopartículas Metálicas/química , Escherichia coli , Leite/microbiologia , Staphylococcus aureus , Análise Espectral Raman , Bactérias , Aptâmeros de Nucleotídeos/química , Ouro/químicaRESUMO
Objective: To explore the microstructural changes of white matter in children with pediatric autism by using diffusion kurtosis imaging (DKI), and evaluate whether the combination of tract-based spatial statistics (TBSS) and back-propagation neural network (BPNN)/support vector machine (SVM)/logistic regression (LR) was feasible for the classification of pediatric autism. Methods: DKI data were retrospectively collected from 32 children with autism and 27 healthy controls (HCs). Kurtosis fractional anisotropy (FAK), mean kurtosis (MK), axial kurtosis (KA), radial kurtosis (RK), fractional anisotropy (FA), axial diffusivity (DA), mean diffusivity (MD) and Radial diffusivity (DR) were generated by iQuant workstation. TBSS was used to detect the regions of parameters values abnormalities and for the comparison between these two groups. In addition, we also introduced the lateralization indices (LI) to study brain lateralization in children with pediatric autism, using TBSS for additional analysis. The parameters values of the differentiated regions from TBSS were then calculated for each participant and used as the features in SVM/BPNN/LR. All models were trained and tested with leave-one-out cross validation (LOOCV). Results: Compared to the HCs group, the FAK, DA, and KA values of multi-fibers [such as the bilateral superior longitudinal fasciculus (SLF), corticospinal tract (CST) and anterior thalamic radiation (ATR)] were lower in pediatric autism group (p < 0.05, TFCE corrected). And we also found DA lateralization abnormality in Superior longitudinal fasciculus (SLF) (the LI in HCs group was higher than that in pediatric autism group). However, there were no significant differences in FA, MD, MK, DR, and KR values between HCs and pediatric autism group (P > 0.05, TFCE corrected). After performing LOOCV to train and test three model (SVM/BPNN/LR), we found the accuracy of BPNN (accuracy = 86.44%) was higher than that of LR (accuracy = 76.27%), but no different from SVM (RBF, accuracy = 81.36%; linear, accuracy = 84.75%). Conclusion: Our proposed method combining TBSS findings with machine learning (LR/SVM/BPNN), was applicable in the classification of pediatric autism with high accuracy. Furthermore, the FAK, DA, and KA values and Lateralization index (LI) value could be used as neuroimaging biomarkers to discriminate the children with pediatric autism or not.
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Tuberculosis is a chronic lethal infectious disease caused by a single pathogen, Mycobacterium tuberculosis (Mtb). Previous studies developed nitrofuranyl calanolide (NFC) compounds as new class of Mtb diagnostic reagent, such as NFC-Tre-5. Through structure-fluorescence relationships (SFR) investigation, in this article, a new fluorescent probe, 3-vinylcoumarin (17a) with a 20-fold increase in the fluorescent fold change (FFC) value, was gained. Taking the advantage of specific trehalose metabolic mechanism of Mtb, 17a was further cooperated with a trehalose motif through modification of 4-propyl group to obtain 17a-Tre. The 17a-Tre could label the live infected mycobacteria in signal murine macrophage such as M. smeg, specifically mark the living Mtb in single cell from other typical species of bacteria, and detect the Mtb cells under microscope from the sputum of patients.
Assuntos
Corantes Fluorescentes , Mycobacterium tuberculosis , Piranocumarinas , Tuberculose , Animais , Humanos , Camundongos , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Trealose , Tuberculose/diagnóstico , Corantes Fluorescentes/química , Análise de Célula ÚnicaRESUMO
Amphetamine (AMP), as a psychiatric drug acting on the central nervous system, and has become one of the most common drugs of abuse in the illegal market at present, which adversely affects social public safety. We developed a SERS magnetic immunoassay with high sensitivity, specificity, and rapid and quantitative detection of AMP. We synthesized a high SERS intensity substrate (Au-XP013@Ag) using the "hot spot" effect and combined it with antibodies to form SERS immunotags (Au-XP013@Ag-AMP-mAb). Subsequently, the carboxyl magnetic beads were linked to label antigens as functional magnetic beads (carboxyl magnetic beads-AMP-BSA). Using the principle of competitive immunoassay, the Raman response value of the immune complex formed with SERS tags and functional magnetic beads was detected to realize the quantitative detection of AMP. The detection limit of this method for AMP was 2.28 ng mL-1. More importantly, a portable Raman instrument was used in this study, which can meet the requirements of point-of-care testing (POCT). Therefore, this SERS-based magnetic immunoassay can provide a favorable scientific basis for the control of drug abuse, monitoring by law enforcement agencies, and determination of drug users.
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Ouro , Análise Espectral Raman , Monofosfato de Adenosina , Anfetamina , Imunoensaio/métodos , Fenômenos MagnéticosRESUMO
Glycoproteins are a class of proteins with significant biological functions and clinical implications. Due to glycoproteins' reliability for the quantitative analysis, they have been used as biomarkers and therapeutic targets for disease diagnosis. We propose a sandwich structure-based boronate affinity biosensor that can separate and detect target glycoproteins by magnetic separation and Surface-enhanced Raman scattering (SERS) probes. The biosensor relies on boronic acid affinity magnetic molecularly imprinted polymer (MMIPs) with pH response as "capturing probe" for glycoproteins, and Au-MPBA@Ag modified with 4-mercaptophenylboronic acid (MPBA) as SERS probes, among which, MPBA has both strong SERS activity and can specifically recognize and bind to glycoproteins. MMIPs ensured specific and rapid analysis, and SERS detection provided high sensitivity. The proposed boronate affinity SERS strategy exhibited universal applicability and provided high sensitivity with limit of detection of 0.053 ng/mL and 0.078 ng/mL for horseradish peroxidase and acid phosphatase, respectively. Ultimately, the boronate affinity SERS strategy was successfully applied in detection of glycoprotein in spiked serum sample with recovery between 90.6% and 103.4%, respectively. In addition, this study used a portable Raman meter, which can meet the requirements of point-of-care testing. The biosensor presented here also has advantages in terms of cost-effectiveness, stability, and detection speed.
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Técnicas Biossensoriais , Impressão Molecular , Biomimética , Glicoproteínas , Fenômenos Magnéticos , Polímeros , Reprodutibilidade dos Testes , Análise Espectral RamanRESUMO
A new Mtb fluorescent probe, NFC-Tre-5, was reported that could label single cells of Mtb under various stress conditions via a unique fluorescence off-on feature by a Rv2466c-mediated reductive mechanism. This probe effectively facilitates the rapid and specific detection of Mtb in the host cell during infection and the detection of Mtb in sputum samples from patients.
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Corantes Fluorescentes/química , Mycobacterium tuberculosis/isolamento & purificação , Nitrorredutases/metabolismo , Piranocumarinas/química , Trealose/química , Corantes Fluorescentes/metabolismo , Humanos , Estrutura Molecular , Piranocumarinas/metabolismo , Escarro/microbiologia , Trealose/metabolismoRESUMO
Histone lysine specific demethylase 1 (LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound 8a (IC50 = 3.93⯵mol/L) and further medicinal chemistry efforts, leading to the generation of compound 15u (IC50 = 49â¯nmol/L, and K i = 16â¯nmol/L), which inhibited LSD1 reversibly and competitively with H3K4me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency of compound 15u. Compound 15u also showed strong antiproliferative activity against four leukemia cell lines (OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC50 values of 1.79, 1.30, 0.45, 1.22 and 1.40⯵mol/L, respectively. In THP-1 cell line, 15u significantly inhibited colony formation and caused remarkable morphological changes. Compound 15u induced expression of CD86 and CD11b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation. The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazole-fused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1A inhibitors.