Nanopipettes provide a promising confined space that enables advances in electrochemical, optical, and mass spectrometric measurements at the nanoscale. They have been employed to reveal the hidden ...population properties and dynamics of single molecules and single particles. Moreover, new detection mechanisms based on nanopipettes have led to detailed information on single cells at high spatial and temporal resolution. In this Minireview, we focus on the fabrication and characterization of nanopipettes, summarize their wide applications for the analysis of single entities, and conclude with an outlook for advanced practical sensing.
The preparation and characterization of nanopipettes—promising devices for electrochemical, optical, and mass spectrometric measurements at the nanoscale—are the themes of this Minireview. Their application enables the dynamics and properties of single molecules and particles to be uncovered. Furthermore, new detection mechanisms based on nanopipettes have led to detailed information on single cells at high resolution.
Single-molecule measurements have greatly enhanced our understanding of living systems. Biological systems offer nanopores, a sub-class of membrane proteins, the well-defined confined space for ...accommodating a single molecule. The biological nanopore acts as a single-biomolecule interface for capturing and identifying a single molecule of interest, and thus it can be used as a single-molecule sensor. In this Perspective, we focus on biological nanopore-based single-biomolecule interfaces for single-biomolecule detection. First, we outline the design of the nanopore-based single-biomolecule interface, which provides rich stochastic information regarding each biomolecule. Next, we highlight future research directions beyond DNA sequencing, including detection of rare species, identification of hidden intermediates, spectral analysis of covalent/noncovalent interactions, and tracing of the dynamic pathways of single-biopolymer behaviors. The concept of a “single-molecule ionic spectrum” is discussed, which may allow mapping of noncovalent interactions at an atomic level in the future. We also discuss the challenges and goals for the future to make this measurement possible for addressing entirely new types of biological questions, which would be an exciting area of future research.
Gold nanoparticles (AuNPs) have been demonstrated to serve as effective nanomaterial‐based enzyme mimetics (nanozymes) for a number of enzymatic reactions under mild conditions. The intrinsic glucose ...oxidase and peroxidase activities of single AuNPs and Ag–Au nanohybrids, respectively, were investigated by single NP collision electrochemical measurements. A significantly high turnover number of nanozymes was obtained from individual catalytic events compared with the results from the classical, ensemble‐averaged measurements. The unusual enhancement of catalytic activity of single nanozymes is believed to originate from the high accessible surface area of monodispersed NPs and the high activities of carbon‐supported NPs during single‐particle collision at a carbon ultramicroelectrode. This work introduces a new method for the precise characterization of the intrinsic catalytic activities of nanozymes, giving further insights to the design of high‐efficiency nanomaterial catalysts.
Imitation is the sincerest form of flattery: The intrinsic glucose‐oxidase‐ and peroxidase‐mimicking activities of single AuNPs and Ag–Au nanohybrids, respectively, were quantified using stochastic collision electrochemistry, providing new insights for the design of high‐efficiency, nanomaterial‐based catalysts.
Proteins are responsible for the occurrence and treatment of many diseases, and therefore protein sequencing will revolutionize proteomics and clinical diagnostics. Biological nanopore approach has ...proved successful for single‐molecule DNA sequencing, which resolves the identities of 4 natural deoxyribonucleotides based on the current blockages and duration times of their translocations across the nanopore confinement. However, open challenges still remain for biological nanopores to sequentially identify each amino acid (AA) of single proteins due to the inherent complexity of 20 proteinogenic AAs in charges, volumes, hydrophobicity and structures. Herein, we focus on recent exciting advances in biological nanopores for single‐molecule protein sequencing (SMPS) from native protein unfolding, control of peptide translocation, AA identification to applications in disease detection.
Nanopore electrochemistry offers a bright prospect for single‐molecule protein sequencing by measuring specific interactions between amino acids based on their natural structure and chemistry continuity and diversity. This Minireview focusses on recent advances in biological nanopores from protein unfolding, peptide translocation, amino acid identification to diagnostic application.
In this paper, starting from the fusion of audio-visual multisensory vocal music feature representation, the RAE algorithm is used to represent the music lyrics text in vocal singing teaching. Due to ...the heterogeneity of the feature space of the audio modality and the lyrics modality, which makes it exceptionally tricky to directly mine the correlation between these two modalities, it is necessary to optimize the research through the fusion of the audio and the textual modality for the representation of the implicit space of the music. According to the SVM’s optimal classification, hyperplane is not limited by the data dimension. Combined with the kernel function parameters and emotional LFSM fusion, a visual multisensory vocal singing teaching emotion model based on SVM is constructed. The parameter environment and dataset are selected, and the comparison method and evaluation criteria are determined to analyze emotional research on vocal singing teaching in colleges and universities. The results show that in terms of model performance, the SVM model in this paper is 8.5% higher than model 6, reaching the highest 0.873, with stronger emotion extraction and recognition ability, greatly improving the emotion classification results of the model. The multimedia type of audio singing material is the least helpful for expression and physical performance in vocal singing teaching, with a total value of 67. This study provides a more comprehensive understanding of the emotional changes of students in teaching activities so as to identify problems, improve and optimize them, and give more students guidance and support in performing vocal singing.
Organic–inorganic halide perovskites are efficient absorbers for solar cells. Nevertheless, the trap states at the surfaces and grain boundaries are a detrimental factor compromising the device ...performance. Here, an organic dye (AQ310) is employed as passivator to reduce the trap states of the perovskites and promote better stability. The results demonstrate that the trap states of perovskite are minimized by the presence of AQ310's COOH group and the formation of coordination with under‐coordinated Pb2+ ions. The resulting carrier recombination time is prolonged and verified by the photoluminescence and open‐circuit voltage decay measurements. Consequently, the best average power conversion efficiency (PCE) of 19.43% is achieved for the perovskite solar cell (PSC) with AQ310 passivation, as compared with a low average PCE of 17.98% for the PSC without AQ310 passivation.
An organic dye (AQ310) with COOH functional group as passivator reduces the trap states of the perovskites and promotes better stability. An average efficiency of 19.43% for the AQ310‐passivated device is achieved as compared with a low average efficiency of 17.98% for the device without AQ310 passivation.
With the development of new instruments and methodologies, the highly dynamic behaviors of nanoparticle at the liquid-solid interface have been studied. However, the dynamic nature of the ...electrochemical behavior of individual nanoparticles on the electrode interface is still poorly understood. Here, we generalize scaling relations to predict nanoparticle-electrode interactions by examining the adsorption energy of nanoparticles at an ultramicroelectrode interface. Based on the theoretical predictions, we investigate the interaction-modulated dynamic electrochemical behaviors for the oxidation of individual Ag nanoparticles. Typically, significantly distinct current traces are observed owing to the adsorption-mediated motion of Ag nanoparticles. Inspired by restraining the stochastic paths of particles in the vicinity of the electrode interface to produce surface-confined current traces, we successfully realize high-resolution size measurements of Ag nanoparticles in mixed-sample systems. This work offers a better understanding of dynamic interactions of nanoparticles at the electrochemical interface and displays highly valuable applications of single-entity electrochemistry.
Cholesterol is an essential component of mammalian cell membranes, constituting up to 50% of plasma membrane lipids. By contrast, it accounts for only 5% of lipids in the endoplasmic reticulum (ER)
. ...The ER enzyme sterol O-acyltransferase 1 (also named acyl-coenzyme A:cholesterol acyltransferase, ACAT1) transfers a long-chain fatty acid to cholesterol to form cholesteryl esters that coalesce into cytosolic lipid droplets. Under conditions of cholesterol overload, ACAT1 maintains the low cholesterol concentration of the ER and thereby has an essential role in cholesterol homeostasis
. ACAT1 has also been implicated in Alzheimer's disease
, atherosclerosis
and cancers
. Here we report a cryo-electron microscopy structure of human ACAT1 in complex with nevanimibe
, an inhibitor that is in clinical trials for the treatment of congenital adrenal hyperplasia. The ACAT1 holoenzyme is a tetramer that consists of two homodimers. Each monomer contains nine transmembrane helices (TMs), six of which (TM4-TM9) form a cavity that accommodates nevanimibe and an endogenous acyl-coenzyme A. This cavity also contains a histidine that has previously been identified as essential for catalytic activity
. Our structural data and biochemical analyses provide a physical model to explain the process of cholesterol esterification, as well as details of the interaction between nevanimibe and ACAT1, which may help to accelerate the development of ACAT1 inhibitors to treat related diseases.
Nanopore‐based techniques, which mimic the functions of natural ion channels, have attracted increasing attention as unique methods for single‐molecule detection. The technology allows the real‐time, ...selective, high‐throughput analysis of nucleic acids through both biological and solid‐state nanopores. In this Minireview, the background and latest progress in nanopore‐based sequencing and detection of nucleic acids are summarized, and light is shed on a novel platform for nanopore‐based detection.
Adopted from nature: The functions of natural ion channels can be mimicked with both biological and solid‐state nanopores, which have attracted increasing attention for their possible use in the detection and sequencing of DNA. In this Minireview, background and latest progress in this area are summarized and a novel platform for nanopore‐based detection is discussed.
Inspired by the biological processes of molecular recognition and transportation across membranes, nanopore techniques have evolved in recent decades as ultrasensitive analytical tools for individual ...molecules. In particular, nanopore-based single-molecule DNA/RNA sequencing has advanced genomic and transcriptomic research due to the portability, lower costs and long reads of these methods. Nanopore applications, however, extend far beyond nucleic acid sequencing. In this Review, we present an overview of the broad applications of nanopores in molecular sensing and sequencing, chemical catalysis and biophysical characterization. We highlight the prospects of applying nanopores for single-protein analysis and sequencing, single-molecule covalent chemistry, clinical sensing applications for single-molecule liquid biopsy, and the use of synthetic biomimetic nanopores as experimental models for natural systems. We suggest that nanopore technologies will continue to be explored to address a number of scientific challenges as control over pore design improves.
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