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Exploring targets for inhibiting androgen receptor (AR) activity is an effective strategy for suppressing the development of castration-resistant prostate cancer (CRPC). Upregulation of histone demethylase JMJD2A activity is an important factor in increasing AR expression in CRPC. Based on our research, we found that the binding affinity between JMJD2A and AR increases in CRPC, while the level of AR histone methylation decreases and the H3K27ac level increases in the AR enhancer region. Further investigations revealed that overexpression of the histone demethylase JMJD2A increased the binding affinity between JMJD2A and AR, decreased AR histone methylation levels, upregulated H3K27ac in the AR enhancer region, and increased AR activity. Conversely, knocking down JMJD2A effectively reversed these effects. Additionally, in CRPC, JMJD2A expression was upregulated, the tumor-intrinsic immune cGAS-STING signaling pathway was suppressed, the tumor microenvironment was altered, and AR expression was upregulated. However, both knocking down JMJD2A and inhibiting the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS-STING) signaling pathway reversed these effects. In summary, our study indicates that in CRPC, JMJD2A can directly bind to AR and activate residual AR enhancers through its demethylation activity, thereby promoting AR expression. Furthermore, upregulation of JMJD2A expression inhibits the innate immune cGAS-STING signaling pathway of the tumor, leading to a decrease in antitumor immune function, and further promoting AR expression.
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Regulación Neoplásica de la Expresión Génica , Histona Demetilasas con Dominio de Jumonji , Proteínas de la Membrana , Nucleotidiltransferasas , Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Transducción de Señal , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Animales , Línea Celular Tumoral , Ratones , Elementos de Facilitación Genéticos , Microambiente Tumoral , Proliferación CelularRESUMEN
Entanglement in bipartite systems has been applied to generate secure random numbers, which are playing an important role in cryptography or scientific numerical simulations. Here, we propose to use multipartite entanglement distributed between trusted and untrusted parties for generating randomness of arbitrary dimensional systems. We show that the distributed structure of several parties leads to additional protection against possible attacks by an eavesdropper, resulting in more secure randomness generated than in the corresponding bipartite scenario. Especially, randomness can be certified in the group of untrusted parties, even when there is no randomness in either of them individually. We prove that the necessary and sufficient resource for quantum randomness in this scenario is multipartite quantum steering when each untrusted party has a choice between only two measurements. However, the sufficiency no longer holds with more measurement settings. Finally, we apply our analysis to some experimentally realized states and show that more randomness can be extracted compared with the existing analysis.
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In recent years, bladder carcinoma (BC) has shown an increasing incidence, with poor patient outcomes. In clinical practice, BC is still mainly treated by surgery combined with chemoradiotherapy. However, as chemotherapy resistance of tumor cells becomes more and more obvious, it is urgent to find more effective BC treatment regimes. With the increasing application and growing attention paid to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in various neoplastic diseases, EGFR-TKIs have been considered as a new treatment direction in the future. In this study, the research team used AG1478, an EGFR-TKI, to intervene with the BC cell line T24. It was found that the cell activity was statistically decreased, the apoptosis was enhanced, and the cells were dominantly arrested in the G0/G1 phase, confirming the future therapeutic potential of EGFR-TKIs in BC. Besides, the research team further observed that AG1478 also promoted pyroptosis in T24 cells, and its mechanism is related to the induction of mitochondrial oxidative stress damage. The findings lay a more reliable foundation for the future application of EGFR-TKIs in BC.
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Apoptosis , Puntos de Control del Ciclo Celular , Receptores ErbB , Mitocondrias , Inhibidores de Proteínas Quinasas , Quinazolinas , Tirfostinos , Neoplasias de la Vejiga Urinaria , Humanos , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidores , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Tirfostinos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Piroptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
The primary challenge in percutaneous coronary interventions for vascular restenosis is the occurrence of restenosis, which is defined by the excessive proliferation of neointimal tissue. Herein, our research team suggests that exosomes obtained from PSC, when paired with quercetin (Q@PSC-E), successfully reduce neointimal hyperplasia in a Sprague-Dawley rat model. Furthermore, the physical properties of the synthesized Q@PSC-E were examined using UV-vis, DLS, and FT-IR characterization techniques. The rats were subjected to balloon injury (BI) utilizing a 2-Fr Fogarty arterial embolectomy balloon catheter. Intimal hyperplasia and the degree of VSMC proliferation were evaluated using histological analysis in the rat groups that received a dosage of Q@PSC-E at 30 mg/kg/d. Significantly, Q@PSC-E inhibited cell proliferation through a pathway that does not include lipoxygenase, as demonstrated by [3H] thymidine incorporation, MTT, and flow cytometry studies. Additionally, the data indicate that Q@PSC-E hinders cell proliferation by targeting particular events that promote cell growth, including the activation of Akt and NF-κB, disruption of cell-cycle progression and also obstructs the ERK signaling pathway.
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Hyperspectral image (HSI) classification is a vital part of the HSI application field. Since HSIs contain rich spectral information, it is a major challenge to effectively extract deep representation features. In existing methods, although edge data augmentation is used to strengthen the edge representation, a large amount of high-frequency noise is also introduced at the edges. In addition, the importance of different spectra for classification decisions has not been emphasized. Responding to the above challenges, we propose an edge-aware and spectral-spatial feature learning network (ESSN). ESSN contains an edge feature augment block and a spectral-spatial feature extraction block. Firstly, in the edge feature augment block, the edges of the image are sensed, and the edge features of different spectral bands are adaptively strengthened. Then, in the spectral-spatial feature extraction block, the weights of different spectra are adaptively adjusted, and more comprehensive depth representation features are extracted on this basis. Extensive experiments on three publicly available hyperspectral datasets have been conducted, and the experimental results indicate that the proposed method has higher accuracy and immunity to interference compared to state-of-the-art (SOTA) method.
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As an important component of the deep tunnel drainage system for dealing with urban waterlogging, the rotating stepped dropshaft has been proposed due to its small air entrainment. However, the hydraulic characteristics inside the shaft still need to be fully studied. In this study, the flow patterns, water velocity, and pressure in the rotating stepped dropshaft under different flow rates and geometric parameters were studied using a three-dimensional numerical model. The results show that increasing the central angle of the step and reducing the step height can both reduce the terminal velocity. A theoretical formula for predicting the terminal velocity was established and well validated. The connection between the shaft and the outlet pipe poses a severe threat to the structural safety due to alternating positive and negative pressures. Wall-attached swirling flow generates a circular high-pressure zone at the bottom of the dropshaft and the larger the flow rate, the greater the pressure gradient at the center of the bottom. By using the momentum theorem and considering the impact pressure range of the swirling flow, the shaft bottom pressure can be predicted reasonably well.
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Agua , Movimiento (Física)RESUMEN
Novel prophylactic drugs and vaccination strategies for protection against influenza virus should induce specific effector T-cell immune responses in pulmonary airways and peripheral lymphoid organs. Designing approaches that promote T-cell-mediated responses and memory T-cell differentiation would strengthen host resistance to respiratory infectious diseases. The results of this study showed that pulmonary delivery of MENK via intranasal administration reduced viral titres, upregulated opioid receptor MOR and DOR, increased the proportions of T-cell subsets including CD8+ T cells, CD8+ TEM cells, NP/PA-effector CD8+ TEM cells in bronchoalveolar lavage fluid and lungs, and CD4+/CD8+ TCM cells in lymph nodes to protect mice against influenza viral challenge. Furthermore, we demonstrated that, on the 10th day of infection, the proportions of CD4+ TM and CD8+ TM cells were significantly increased, which meant that a stable TCM and TEM lineage was established in the early stage of influenza infection. Collectively, our data suggested that MENK administered intranasally, similar to the route of natural infection by influenza A virus, could exert antiviral activity through upregulating T-cell-mediated adaptive immune responses against influenza virus.
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Virus de la Influenza A , Gripe Humana , Ratones , Animales , Humanos , Linfocitos T CD8-positivos , Encefalina Metionina/farmacología , Células T de Memoria , Memoria Inmunológica , Ratones Endogámicos C57BLRESUMEN
The geometric phase is a fundamental quantity characterizing the holonomic feature of quantum systems. It is well known that the evolution operator of a quantum system undergoing a cyclic evolution can be simply written as the product of holonomic and dynamical components for the three special cases concerning the Berry phase, adiabatic non-Abelian geometric phase, and nonadiabatic Abelian geometric phase. However, for the most general case concerning the nonadiabatic non-Abelian geometric phase, how to separate the evolution operator into holonomic and dynamical components is a long-standing open problem. In this Letter, we solve this open problem. We show that the evolution operator of a quantum system can always be separated into the product of holonomy and dynamic operators. Based on it, we further derive a matrix representation of this separation formula for cyclic evolution, and give a necessary and sufficient condition for a general evolution being purely holonomic. Our finding is not only of theoretical interest itself, but also of vital importance for the application of quantum holonomy. It unifies the representations of all four types of evolution concerning the adiabatic/nonadiabatic Abelian/non-Abelian geometric phase, and provides a general approach to realizing purely holonomic evolution.
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The fact that quantum mechanics predicts stronger correlations than classical physics is an essential cornerstone of quantum information processing. Indeed, these quantum correlations are a valuable resource for various tasks, such as quantum key distribution or quantum teleportation, but characterizing these correlations in an experimental setting is a formidable task, especially in scenarios where no shared reference frames are available. By definition, quantum correlations are reference-frame independent, i.e., invariant under local transformations; this physically motivated invariance implies, however, a dedicated mathematical structure and, therefore, constitutes a roadblock for an efficient analysis of these correlations in experiments. Here we provide a method to directly measure any locally invariant property of quantum states using locally randomized measurements, and we present a detailed toolbox to analyze these correlations for two quantum bits. We implement these methods experimentally using pairs of entangled photons, characterizing their usefulness for quantum teleportation and their potential to display quantum nonlocality in its simplest form. Our results can be applied to various quantum computing platforms, allowing simple analysis of correlations between arbitrary distant qubits in the architecture.
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Rolling circle amplification is a widely used biosensing technique. Although various secondary structures have been employed in RCA, their effects on RCA efficiency have seldom been reported. Here, we find that stems in circular templates can strongly inhibit RCA, and the primer-stem distance is responsible for the inhibition. Based on the results, we propose an initiation inhibition mechanism and present a design principle for a general RCA assay. Inspired by this mechanism, we further propose a new nucleic acid detection method. The results verify that this method can increase RCA detection sensitivity according to the target recycling principle. Besides DNA detection, it can also achieve single mismatch discrimination of miRNA detection after optimization. This method also shows convenient visualization detection. The initiation inhibition of RCA could be helpful for RCA applications as promising detection techniques.
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Técnicas Biosensibles , ADN , MicroARNs , Técnicas de Amplificación de Ácido Nucleico , ADN/análisis , MicroARNs/análisisRESUMEN
A dual-coil inductive displacement transducer is a non-contact type measuring element for measuring displacement and is widely used in large power equipment systems such as construction machinery and agricultural equipment. However, the effect of the coil excitation method on the performance of dual-coil inductive displacement sensors has not been studied. This paper investigates the impact of different coil excitation methods on the operating performance of displacement transducers. The working principle, electromagnetic characteristics, and electrical characteristics were analyzed by building a mathematical model. A transducer measurement device was used to determine the relationship between core displacement and coil inductance. Three coil excitation methods were proposed, and the effects of the three coil excitation methods on the amplitude variation, phase shift, linearity, and sensitivity of the output signal were studied by simulation based on the AD630 chip as the core of the conditioning circuit. Finally, the study's feasibility was demonstrated by comparing the experiment to the simulation. The results show that, under the uniform magnetic field strength distribution in the coil, the coil voltage variation is proportional to the inductive core displacement. The amplitude variation is the largest for the dual-coil series three-wire (DCSTW) and is the same for the dual-coil series four-wire (DCSFW) and dual-coil parallel differential (DCPD). DCSFW has an enormous phase shift. DCSTW has the best linearity. The research in this paper provides a theoretical basis for selecting a suitable coil excitation, which is conducive to further improving the operating performance of dual-coil inductive displacement transducers.
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A double-coil inductive displacement transducer is a non-contact element for measuring displacement and is widely used in large power equipment systems such as construction machinery and agricultural machinery equipment. The type of coil excitation signal has an impact on the performance of the transducer, but there is little research on this. Therefore, the influence of the coil excitation signal on transducer performance is investigated. The working principle and characteristics of the double-coil inductive displacement transducer are analyzed, and the circuit simulation model of the transducer is established. From the aspects of phase shift, linearity, and sensitivity, the effects of a sine signal, a triangle signal, and a pulse signal on the transducer are compared and analyzed. The results show that the average phase shift, linearity, and sensitivity of the sine signal were 11.53°, 1.61%, and 0.372 V/mm, respectively; the average phase shift, linearity and sensitivity of the triangular signal were 1.38°, 1.56%, and 0.300 V/mm, respectively; and the average phase shift, linearity, and sensitivity of the pulse signal were 0.73°, 1.95%, and 0.621 V/mm, respectively. It can be seen that the phase shift of a triangle signal and a pulse signal is smaller than that of a sine signal, which can result in better signal phase-locked processing. The linearity of the triangle signal is better than the sine signal, and the sensitivity of the pulse signal is better than that of the sine signal.
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Road segmentation is beneficial to build a vision-controllable mission-oriented self-driving bot, e.g., the Self-Driving Sweeping Bot, or SDSB, for working in restricted areas. Using road segmentation, the bot itself and physical facilities may be protected and the sweeping efficiency of the SDSB promoted. However, roads in the real world are generally exposed to intricate noise conditions as a result of changing weather and climate effects; these include sunshine spots, shadowing caused by trees or physical facilities, traffic obstacles and signs, and cracks or sealing signs resulting from long-term road usage, as well as different types of road materials, such as cement or asphalt; all of these factors greatly influence the effectiveness of road segmentation. In this work, we investigate the extension of Primordial U-Net by the proposed EnRDeA U-Net, which uses an input channel applying a Residual U-Net block as an encoder and an attention gate in the output channel as a decoder, to validate a dataset of intricate road noises. In addition, we carry out a detailed analysis of the nets' features and segmentation performance to validate the intricate noises dataset on three U-Net extensions, i.e., the Primordial U-Net, Residual U-Net, and EnRDeA U-Net. Finally, the nets' structures, parameters, training losses, performance indexes, etc., are presented and discussed in the experimental results.
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Objective: To evaluate the effect of butylphthalide combined with oxiracetam on cognitive function, intellectual recovery and serum inflammatory factors in patients with cognitive impairment after cerebral infarction. Methods: This is a Clinical comparative study. A total of 80 patients with cognitive impairment after cerebral infarction who visited Renmin Hospital, Hubei University of Medicine from January 2020 to January 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with oral oxiracetam combined with routine treatment. Patients in the study group were given butylphthalide combined with oxiracetam on the basis of routine treatment. Compare the clinical effect, cognitive function and intellectual recovery, inflammatory factor level changes, CBV, CBF, MTT and other cerebral blood flow perfusion indicators, as well as post-treatment incidence of adverse drug reactions in the two groups of patients. Results: The efficacy of the study group was significantly higher than that of the control group (p=0.03). After treatment, the levels of CBV and CBF in the study group were higher than those in the control group, the levels of TNF-α, CRP and IL-6 were significantly lower than those of the control group, while MTT was shorter than that in the control group, with statistically significant difference (p=0.00). Furthermore, there was a statistically significant difference that the MMSE score and MOCA score of the study group were higher than those of the control group (p=0.00). Conclusion: Butylphthalide combined with oxiracetam has an obvious curative effect in the treatment of patients with cognitive impairment after cerebral infarction. It is a safe and effective therapeutic option that can significantly recover cognitive function and intelligence, improve cerebral blood flow perfusion and reduce inflammatory factors, without an obvious increase in adverse reactions.
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Infundibulicybe trachyspora is described as a new species from northeastern China. The species is characterized by clitocyboid to omphalioid habit, carneous, greyish-yellow to brownish pileus, brown to dark reddish-brown, longitudinally fibrillose-striate stipe, non-amyloid, non-smooth spores, the absence of cystidia and the presence of clamp connections. A comprehensive description of the species is provided together with photo-illustrations and comparisons with phenotypically similar and phylogenetically related species. The nuclear ribosomal internal transcribed spacer (ITS) region and the nuclear, large subunit rDNA (nrLSU) region of the new species was sequenced and analyzed. The phylogenetic analysis supported the novelty of the species and its placement within the genus. Furthermore, a discussion on the proposal to establish a new section is made, and a key is provided for the Infundibulicybe species reported from China.
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Agaricales , ADN de Hongos/genética , ADN Espaciador Ribosómico/genética , Filogenia , Análisis de Secuencia de ADNRESUMEN
Bladder cancer (BC) is a primary source of malignancy-associated death, and the mortality rate is high due to its prevalence of metastasis. Corilagin (CLG), a bioactive constituent of numerous medicinal plants, exerts assorted pharmacological actions comprising anti-cancer, apoptotic, anti-inflammatory, and hepatoprotective. CLG possesses a substantial anti-tumor prospective and less noxiousness in normal cells in vitro. However, the molecular mechanisms of CLG on BC cells are not studied well. The current research explored the molecular process intricate in the anticancer and anti-proliferative actions of CLG on the relocation of BC cells T24 and TSGH 8301. The cytotoxicity, apoptosis, adhesion, and migration of CLG on BC cells T24 and TSGH 8301 were evaluated by MTT assay, DAPI, Rh-123, cell adhesion, and cell migration assay. The results point out that CLG inhibits the viability, adhesion, movement, incursion, and inflammation, whereas persuades BC cells apoptosis in a concentration-dependent mode. Besides, CLG treated with T24 and TSGH-8301 cells subdue inflammatory and PI3K/Akt signaling pathways. CLG is accomplished of impeding BC cell migration, invasion, and metastasis through the repression of the NF-κB mediated P13K/Akt signaling. Our findings offer a unique vision into the demonstration of the anti-cancer potential of CLG on BC cells.
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FN-kappa B , Neoplasias de la Vejiga Urinaria , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Glucósidos , Humanos , Taninos Hidrolizables , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Estudios Prospectivos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Small defects on the rails develop fast under the continuous load of passing trains, and this may lead to train derailment and other disasters. In recent years, many types of wireless sensor systems have been developed for rail defect detection. However, there has been a lack of comprehensive reviews on the working principles, functions, and trade-offs of these wireless sensor systems. Therefore, we provide in this paper a systematic review of recent studies on wireless sensor-based rail defect detection systems from three different perspectives: sensing principles, wireless networks, and power supply. We analyzed and compared six sensing methods to discuss their detection accuracy, detectable types of defects, and their detection efficiency. For wireless networks, we analyzed and compared their application scenarios, the advantages and disadvantages of different network topologies, and the capabilities of different transmission media. From the perspective of power supply, we analyzed and compared different power supply modules in terms of installation and energy harvesting methods, and the amount of energy they can supply. Finally, we offered three suggestions that may inspire the future development of wireless sensor-based rail defect detection systems.
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Redes de Comunicación de Computadores , Tecnología Inalámbrica , Recolección de Datos , Suministros de Energía EléctricaRESUMEN
Geo-sensory time series, such as the air quality and water distribution, are collected from numerous sensors at different geospatial locations in the same time interval. Each sensor monitors multiple parameters and generates multivariate time series. These time series change over time and vary geographically; hence, geo-sensory time series contain multi-scale spatial-temporal correlations, namely inter-sensor spatial-temporal correlations and intra-sensor spatial-temporal correlations. To capture spatial-temporal correlations, although various deep learning models have been developed, few of the models focus on capturing both correlations. To solve this problem, we propose simultaneously capture the inter- and intra-sensor spatial-temporal correlations by designing a joint network of non-linear graph attention and temporal attraction force(J-NGT) consisting two graph attention mechanisms. The non-linear graph attention mechanism can characterize node affinities for adaptively selecting the relevant exogenous series and relevant sensor series. The temporal attraction force mechanism can weigh the effect of past values on current values to represent the temporal correlation. To prove the superiority and effectiveness of our model, we evaluate our model in three real-world datasets from different fields. Experimental results show that our model can achieve better prediction performance than eight state-of-the-art models, including statistical models, machine learning models, and deep learning models. Furthermore, we conducted experiments to capture inter- and intra-sensor spatial-temporal correlations. Experimental results indicate that our model significantly improves performance by capturing both inter- and intra-sensor spatial-temporal correlations. This fully shows that our model has a greater advantage in geo-sensory time series prediction.
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Engineered nanopipette tools have recently emerged as a powerful approach for electrochemical nanosensing, which has major implications in both fundamental biological research and biomedical applications. Herein, we describe a generic method of target-triggered assembly of aptamers in a nanopipette for nanosensing, which is exemplified by sensitive and rapid electrochemical single-cell analysis of adenosine triphosphate (ATP), a ubiquitous energy source in life and important signaling molecules in many physiological processes. Specifically, a layer of thiolated aptamers is immobilized onto a Au-coated interior wall of a nanopipette tip. With backfilled pairing aptamers, the engineered nanopipette is then used for probing intracellular ATP via the ATP-dependent linkage of the split aptamers. Due to the higher surface charge density from the aptamer assembly, the nanosensor would exhibit an enhanced rectification signal. Besides, this ATP-responsive nanopipette tool possesses excellent selectivity and stability as well as high recyclability. This work provides a practical single-cell nanosensor capable of intracellular ATP analysis. More generally, integrated with other split recognition elements, the proposed mechanism could serve as a viable basis for addressing many other important biological species.
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Adenosina Trifosfato/análisis , Aptámeros de Nucleótidos/química , Técnicas Biosensibles , Técnicas Electroquímicas , Análisis de la Célula Individual , Células Cultivadas , Oro/química , HumanosRESUMEN
Though significant advances are made in the arena of single-cell electroanalysis, quantification of intracellular amino acids of human cells remains unsolved. Exemplified by l-histidine (l-His), this issue is addressed by a practical electrochemical nanotool synergizing the highly accessible nanopipette with commercially available synthetic DNAzyme. The fabricated nanotools are screened before operation of a single-use manner, and the l-His-provoked cleavage of the DNA molecules can be sensibly transduced by the ionic current rectification response, the intrinsic property of nanopipette governed by its interior surface charges. Regional distribution of cytosolic l-His level in human cells is electrochemically quantified for the first time, and time-dependent drug treatment effects are further revealed. This work unveils the possibility of electrochemistry for quantification of cytosolic amino acids of a spatial- and time-based manner and ultimately enables a better understanding of amino acid-involved events in living cells.