Remarkable increase in electrochemiluminescence of isomeric bipyridine-based covalent organic frameworks via regulating the direction of imine linkage for sensing application.

Covalent organic frameworks (COFs) with highly ordered structures and predictable optoelectronic properties provide an ideal platform to investigate the electrochemiluminescence (ECL) performance based on organic materials by atomically varying the molecular construction. Herein, the effect of imine-bond orientation on the ECL performance of COFs is investigated. We report two COFs (NC-COF and CN-COF) with different orientations of imine bonds using pyrene donor units (D) and bipyridine acceptor motifs (A) monomers.

Enzymatic DNA repairing amplification-powered construction of an Au nanoparticle-based nanosensor for single-molecule monitoring of cytosine deaminase activity in cancer cells.

APOBEC3A (A3A) is a cytidine deaminase with critical roles in molecular diagnostics. Herein, we demonstrate the enzymatic DNA repairing amplification-powered construction of an Au nanoparticle-based nanosensor for single-molecule monitoring of A3A activity in cancer cells. Target A3A can convert cytosine (C) in substrate probe to uracil (U), and then the template binds with substrate probe to form a dsDNA containing U/A base pairs.

Elongation and Ligation-Mediated Differential Coding for Label-Free and Locus-Specific Analysis of 8-Oxo-7,8-dihydroguanine in DNA.

Oxidative DNA damage is closely associated with the occurrence of numerous human diseases and cancers. 8-Oxo-7,8-dihydroguanine (8-oxoG) is the most prevalent form of DNA damage, and it has become not only an oxidative stress biomarker but also a new epigenetic-like biomarker. However, few approaches are available for the locus-specific detection of 8-oxoG because of the low abundance of 8-oxoG damage in DNA and the limited sensitivity of existing assays.

Deamination-triggered exponential signal amplification for chemiluminescent detection of cytosine deaminase at the single-cell level.

We construct a sensitive chemiluminescent biosensor for sensitive detection of cytosine deaminase APOBEC3A based on deamination-triggered exponential signal amplification. This biosensor displays good specificity and high sensitivity, and it can screen APOBEC3A inhibitors and measure endogenous APOBEC3A at the single-cell level, with prospective applications in disease diagnostics and therapy.

RNA methylation-driven assembly of fluorescence-encoded nanostructures for sensitive detection of mA modification writer METTL3/14 complex in human breast tissues.

N-methyladenosine (mA) is an ubiquitous post-transcriptional modification catalyzed by METTL3/14 complex in eukaryotic mRNAs. The abnormal METTL3/14 complex activity affects multiple steps of RNA metabolism and may induce various diseases. Herein, we demonstrate the RNA methylation-driven assembly of fluorescence-encoded nanostructures for sensitive detection of mA modification writer METTL3/14 complex in human breast tissues.

Construction of Multiple DNAzymes Driven by Single Base Elongation and Ligation for Single-Molecule Monitoring of FTO in Cancer Tissues.

Fat mass and obesity-associated proteins (FTO) play an essential role in the reversible regulation of N-methyladenosine (mA) epigenetic modification, and the overexpression of FTO is closely associated with the occurrence of diverse human diseases (e.g., obesity and cancers).

Ultrasonic/electrical dual stimulation response nanocomposite bioelectret for controlled precision drug release.

Electret materials have attracted extensive attention because of their permanent polarization and electrostatic effect. However, it is one of problem that needs to be solved in biological application to manipulate the change of surface charge of electret by external stimulation. In this work, a drug-loaded electret with flexibility and no cytotoxicity was prepared under relatively mild conditions.

Controllable assembly of dendritic DNA nanostructures for ultrasensitive detection of METTL3-METTL14 mA methyltransferase activity in cancer cells and human breast tissues.

N-Methyladenosine (mA) is a reversible chemical modification in eukaryotic messenger RNAs and long noncoding RNAs. The aberrant expression of RNA methyltransferase METTL3-METTL14 complex may change the mA methylation level and cause multiple diseases including cancers. The conventional METTL3-METTL14 assays commonly suffer from time-consuming procedures and poor sensitivity.

Entropy-Driven Self-Assembly of Single Quantum Dot Sensor for Catalytic Imaging of Telomerase in Living Cells.

Telomerase is a highly valuable cancer diagnosis biomarker and a promising cancer therapy target. So far, most telomerase assays are limited by the involvement of tedious procedures, multiple enzymes, and complicated reaction schemes. Sensitive monitoring of low-abundant telomerase in living cells remains a challenge.

CRISPR/Cas-Based MicroRNA Biosensors.

As important post-transcriptional regulators, microRNAs (miRNAs) play irreplaceable roles in diverse cellular functions. Dysregulated miRNA expression is implicated in various diseases including cancers, and thus miRNAs have become the valuable biomarkers for disease monitoring. Recently, clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system has shown great promise for the development of next-generation biosensors because of its precise localization capability, good fidelity, and high cleavage activity.

Activatable Self-Dissociation of Watson-Crick Structures with Fluorescent Nucleotides for Sensing Multiple Human Glycosylases at Single-Cell Level.

Nucleobase oxidation and alkylation can destroy Watson-Crick base-pairing to challenge the genomic integrity. Human 8-oxoguanine glycosylase 1 (hOGG1) and alkyladenine glycosylase (hAAG) are evolved to counter these two cytotoxic lesions through base-excision repair, and their deregulations are implicated with multifactorial diseases and cancers. Herein, we demonstrate activatable self-dissociation of Watson-Crick structures with fluorescent nucleotides for sensing multiple human glycosylases at single-cell level.

Construction of a dual-functional dumbbell probe-based fluorescent biosensor for cascade amplification detection of miRNAs in lung cancer cells and tissues.

We develop a dual-functional dumbbell probe-based fluorescent biosensor for cascade amplification detection of miRNAs in lung cancer cells and tissues by integrating a primer exchange reaction (PER) with the CRISPR-Cas12a system. This biosensor can absolutely quantify the miR-486-5p expression in different lung cancer cells and distinguish non-small cell lung cancer (NSCLC) patients from healthy individuals, holding great potential in biomedical research and clinical diagnosis.

Construction of an APE1-Mediated Cascade Signal Amplification Platform for Homogeneously Sensitive and Rapid Measurement of DNA Methyltransferase in Cells.

DNA methylation is an essential genomic epigenetic behavior in both eukaryotes and prokaryotes. Deregulation of DNA methyltransferase (Dam MTase) can change the DNA methylation level and cause various diseases. Herein, we develop an apurinic/apyrimidinic endonuclease 1 (APE1)-mediated cascade signal amplification platform for homogeneously sensitive and rapid measurement of Dam MTase in cells.

Mismatched fluorescent probes with an enhanced strand displacement reaction rate for intracellular long noncoding RNA imaging.

We design mismatched fluorescent probes to directly monitor the long noncoding RNA (lncRNA) in living cells. The introduction of mismatched bases in the fluorescent probe greatly enhances the strand displacement reaction rate toward the target lncRNA. These mismatched probes can monitor the intracellular lncRNA expression level in various cell lines and discriminate cancer cells from normal cells, holding great potential in fundamental biomedical research and clinical disease diagnosis.

Construction of a Structure-Switchable Toehold Dumbbell Probe for Sensitive and Label-Free Measurement of MicroRNA in Cancer Cells and Tissues.

MicroRNAs (miRNAs) play multiple crucial roles in post-transcriptional regulating gene expression, and the abnormal expression may induce various human diseases. Herein, we demonstrate the construction of a structure-switchable toehold dumbbell probe for sensitive and label-free measurement of microRNA in cancer cells and tissues on the basis of integrating exponential-rolling circle amplification (EXP-RCA) with linear-rolling circle amplification (LRCA). We designed a structure-switchable toehold dumbbell probe with annular and symmetric structure whose either side can hybridize with target miRNA to initiate EXP-RCA, greatly improving the detection sensitivity.

Simultaneous single-molecule detection of the acetyltransferase and crotonyltransferase activities of histone acetylation writer p300.

We demonstrate for the first time the simultaneous measurement of the acetyltransferase (HAT) and crotonyltransferase (HCT) activities of histone acetylation writer p300 by integrating antibody-based fluorescence labeling with single molecule detection. This methods exhibits good specificity and high sensitivity. Moreover, it can accurately evaluate the kinetic parameters of both the HAT and HCT activities of p300 and screen inhibitors.

Construction of a damage site-specific fluorescent biosensor for single-molecule detection of DNA damage.

The 8-oxoguanine (8-oxoG) represents the most common DNA damage type, and it has been regarded as the oxidative stress biomarker, but the reported 8-oxoguanine assays are limited by poor specificity and low sensitivity. Herein, we demonstrate the construction of damage site-specific fluorescent biosensor for 8-oxoG assay by integrating single-molecule detection with hyperbranched signal amplification. In this assay, the 8-oxoG damages in DNA can generate free 3' OH with the assistance of formamidopyrimidine DNA glycosylase (Fpg) and polynucleotide kinase (PNK), which subsequently triggers the incorporation of abundant Cy5-labeled dUTPs via terminal deoxynucleotidyl transferase (TDT)-mediated site-specific hyperbranched nucleic acid amplification.

3'-Terminal Repair-Powered Dendritic Nanoassembly of Polyadenine Molecular Beacons for One-Step Quantification of Alkaline Phosphatase in Human Serum.

Alkaline phosphatase (ALP) is an important hydrolase with crucial roles in biological processes, and the dysregulation of ALP may cause various human diseases. The conventional ALP assays usually involve cumbersome procedures with poor sensitivity. Herein, taking advantage of intrinsic superiorities of molecular beacons (MBs) and unique features of terminal deoxynucleotidyl transferase (TdT), we demonstrate for the first time the 3'-terminal repair-powered dendritic nanoassembly of polyadenine (A) MBs for one-step quantification of ALP in human serum.

An antibody-like peptidic network for anti-angiogenesis.

Different from chemical (small molecular inhibitor) and biological (monoclonal antibody) drugs, herein, based on angiogenesis-related neuropilin-1 (NRP-1), we develop a biomimetic superstructure drug, i.e. an antibody-like peptidic network (ALPN) to achieve the high-efficient treatment of choroidal neovascularization (CNV).

Simultaneous Enzyme-Free Detection of Multiple Long Noncoding RNAs in Cancer Cells at Single-Molecule/Particle Level.

Aberrant change in long noncoding RNA (lncRNA) is associated with various diseases and cancers. So far, simultaneous detection of lncRNAs has remained a great challenge due to their large size and extensive secondary structure. Herein, we develop an enzyme-free single-molecule/particle detection method for simultaneous detection of multiple lncRNAs in cancer cells based on target-catalyzed strand displacement.

Controllable synthesis of CoFeSe/NiCoSe hybrid nanotubes with heterointerfaces and improved oxygen evolution reaction performance.

The rational construction of heterointerfaces in hollow nanohybrids is considered as a promising and challenging approach for enhancing their electrocatalytic performance. Herein, we demonstrate the synthesis of CoFeSe/NiCoSe hybrid nanotubes (CFSe/NCSe HNTs) with open ends and abundant heterointerfaces. The CFSe/NCSe HNT hybrid nanotubes are obtained by using NiCo-aspartic acid nanofibres (NiCo-Asp NFs) as the templates which can be converted to the CFSe/NCSe HNTs via proton etching, three metal coprecipitation, Kirkendall effect and anion-exchange reaction.

Integration of single-molecule detection with endonuclease IV-assisted signal amplification for sensitive DNA methylation assay.

We demonstrate the development of a new fluorescent biosensor for sensitive DNA methylation assay by integrating single-molecule detection with endo IV-assisted signal amplification. This biosensor possesses the characteristics of good selectivity and high sensitivity with a detection limit of 7.3 × 10 M.

Aptamer-mediated rolling circle amplification for label-free and sensitive detection of histone acetyltransferase activity.

We develop for the first time an aptamer-mediated rolling circle amplification approach for label-free and sensitive detection of histone-modifying enzyme (HME) activity. This method can achieve femtomolar sensitivity for histone acetyltransferase Tip60 assay, which is the most sensitive HME assay reported so far. It can be further applied for inhibitor screening, enzyme kinetic analysis, and endogenous Tip60 measurement in cancer cells.

Label-Free and Template-Free Chemiluminescent Biosensor for Sensitive Detection of 5-Hydroxymethylcytosine in Genomic DNA.

5-Hydroxymethylcytosine (5hmC) is a modified base present at low levels in various mammalian cells, and it plays essential roles in gene expression, DNA demethylation, and genomic reprogramming. Herein, we develop a label-free and template-free chemiluminescent biosensor for sensitive detection of 5hmC in genomic DNAs based on 5hmC-specific glucosylation, periodate (IO) oxidation, biotinylation, and terminal deoxynucleotidyl transferase (TdT)-assisted isothermal amplification strategy, which we term hmC-GLIB-IAS. This hmC-GLIB-IAS exhibits distinct advantages of bisulfite-free, improved sensitivity, and genome-wide analysis of 5hmC at constant reaction temperature without the involvement of either specially labeled nucleic acid probes or specific templates for signal amplification.

A trifunctional split dumbbell probe coupled with ligation-triggered isothermal rolling circle amplification for label-free and sensitive detection of nicotinamide adenine dinucleotide.

The nicotinamide adenine dinucleotide (NAD) is an important small biomolecule that participates in a variety of physiological functions, and it has been regarded as a potential biomarker for disease diagnosis and a promising target for disease treatment. The conventional methods for NAD assay often suffer from complicated procedures, expensive labeling, poor selectivity, and unsatisfactory sensitivity. Herein, we develop a label-free and sensitive method for NAD assay based on the integration of a trifunctional split dumbbell probe with ligation-triggered isothermal rolling circle amplification (RCA).