Multicyclic Ligation-Driven Self-Assembly of Magnetic Nanobundles for Sensitive Profiling of Multiple Repair Glycosylases in Cancer Cells.

Base excision repair (BER) enzymes are essential for maintaining genomic stability and contribute significantly to disease pathogenesis, but simultaneous monitoring of multiple BER enzymes remains a challenge due to their mechanistic diversity and lack of versatile detection platforms. Herein, we demonstrate for the first time multicyclic ligation-driven self-assembly of magnetic nanobundles for sensitive profiling of multiple repair glycosylases in cancer cells. In this assay, we design two programmable dsDNA substrates with the incorporation of 8-oxo-7,8-dihydroguanine (8-oxoG) and uracil (U) base lesions, which can be cleaved by Fpg and UDG to generate nicking sites, respectively.

Engineering of a multi-modular CRISPR biomachine for ultrasensitive monitoring of β-glucosyltransferase activity.

β: β-Glucosyltransferase (β-GT) is a pivotal enzymatic tool for 5-hydroxymethylcytosine (5-hmC) detection, and it can specifically catalyze the glycosylation of 5-hmC. This enzymatic reaction plays a crucial role in modulating bacteriophage-specific gene expression and facilitating the survival of bacteriophages and parasites within host cells. Herein, we engineer a multi-modular and structurally ordered CRISPR/Cas-based biomachine by integrating 5-hmC glycosylation-triggered palindrome-primed hyperbranched rolling circle amplification (PP-HRCA) for ultrasensitive analysis of exogenous β-GT activity.

Programmable Nanodevice and Amplifier Module-Based DNA Cascaded Logic Circuits for Breast Tumor Cell Subtype Discrimination.

Sensitive analysis of multiple disease-related biomarkers with DNA logic circuits can facilitate accurate discrimination of cell subtypes, which is essential for early disease diagnosis. Nevertheless, the reported DNA logic circuits usually suffer from poor efficiency, single signal output, and low sensitivity. Herein, a series of versatile DNA logic circuits (i.

High-Performance Electrochemiluminescence Imaging Immunosensor for Adeno-Associated Virus Serotype 8 Detection Based on Nanobody-Functionalized Covalent Organic Frameworks and Au@Rh Catalytic Amplification.

Adeno-associated virus serotype 8 (AAV8) is a widely used gene therapy vector with the characteristics of high transduction efficiency and tissue specificity. Reliable detection of AAV8 is crucial for assessing therapeutic efficacy and tracking its in vivo distribution. Herein, we develop a nanobody-based electrochemiluminescence (ECL) imaging immunosensor based on integrating advanced functional materials with spatially resolved signal output for sensitive and visual detection of AAV8.

Integration of AND logic circuit with CRISPR/Cas12a system for sensitive detection of biomarkers and accurate discrimination of breast cancer cells.

Flap endonuclease 1 (FEN1) is a structure-selective nuclease that is of great significance in maintaining genomic stability. FEN1 is up-regulation in various cancers and is regarded as a new biomarker for cancer diagnosis. Herein, we integrate DNA logic circuit with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system for sensitive detection of FEN1 at the cellular level and accurate discrimination of different cell types.

Low-triggering-potential electrochemiluminescence biosensor based on hydrogen-bonded organic framework and luminol-derived carbon dots for α-glucosidase detection.

Low-triggering-potential can decrease electrochemical interference and cross talk of electrochemiluminescence (ECL), significantly improving long-term stability of working electrode. Herein, we develop a ratiometric ECL biosensor with hydrogen organic framework (HOF) and luminol derived carbon dots (Lu-CDs) as the emitters for sensitive detection of α-glucosidase (α-Glu) at a low positive potential range of 0.1-1.

Tumor microenvironment-responsive dynamic self-assembly of DNAzyme nanowires for high-contrast imaging of multiple messenger RNAs and chemotherapy.

Messenger RNAs (mRNAs) are a category of protein-coding RNA, and their dysregulation is closely implicated in diverse cancers. Static DNA nanodevices have been engineered for the imaging and therapy, but they rely on the pre-assembly of DNA components and are limited by the low imaging contrast. Herein, we demonstrate the tumor microenvironment-responsive dynamic self-assembly of DNAzyme nanowires for high-contrast imaging of multiple mRNAs and chemotherapy.

The ballet of nature: the interconvertible isomerisation of natural products.

Covering: up to 2025The diverse interconversion of isomers among natural products (NPs) are shaped by both intrinsic structural characteristics and extrinsic environmental factors, representing a rich source of chemical complexity and biological diversity. Deciphering these intricate interconversion processes holds the potential to unlock a vast array of bioactive compounds, expanding our exploration of the chemical landscape. Identifying the specific conditions and molecular characteristics while accurately predicting 'the ballet of nature' will effectively achieve increased activity, lower toxicity, and superior pharmacokinetics.

Precise construction of Pd superstructures with modulated defect properties for solar-driven organic transformation.

Precisely controlling the spatial arrangement of nanostructures offers unique opportunities for tuning physical and chemical properties; however, it remains a great challenge due to the lack of effective synthetic methods. Herein, we present a wet-chemistry strategy for the synthesis of three-dimensional (3D) Pd superstructures (Pd SSs) by manipulating the growth kinetics. The strategy consists of two steps including (1) the formation of a tetrahedron-shaped Pd nanocrystal core and (2) the growth of four legs on each tip of the core.

Flap cleavage-directed promoter reconstitution and transcription reactivation for label-free and sensitive detection of flap endonuclease 1 activity.

Flap endonuclease 1 (FEN1) is crucial for maintaining the stability and integrity of genomes, and it has emerged as a promising therapeutic and diagnostic target in oncology. Herein, we develop a streamlined florescent biosensor for label-free and amplified detection of FEN1 by rationally engineering a target-responsive transcription machinery. In this biosensor, the double-stranded T7 promoter is split into two separate single-stranded DNA segments to block nonspecific transcription reaction.

Engineering of a palindrome-crosslinked DNA nanoaggregate for rapid detection of circular RNA and precise identification of lung cancer.

Circular RNAs (circRNAs) are endogenous covalently closed non-coding RNAs with cell-/developmental-stage-/tissue-specific expression patterns, and they can act as the miRNA sponges and gene transcription regulatory factors to influence numerous biological processes. Herein, we develop a palindrome-crosslinked DNA nanoaggregate system to rapidly detect circRNA and precisely identify lung cancer. We utilize a self-assembled palindromic DNA nanosphere (DS) as the spatial-confinement scaffold to anchor hairpin probes (HP) for the formation of the hybrid assemblies (DSH).

Construction of a Ligation-Controlled Single-Molecule Biosensor for Simultaneous Measurement of Multiple Cancer-Related circRNAs in Clinical Tissues.

Circular RNAs (circRNAs) are noncoding RNAs with covalently closed circular structures that regulate important cellular processes, and their dysregulation is implicated in the pathogenesis and progression of various cancers. Simultaneous and specific detection of multiple circRNAs is of significant importance in the early diagnosis of cancer. Herein, we develop a ligation-controlled single-molecule biosensor for multiplexed measurement of breast cancer-associated circRNAs.

Development of Proximity-Activated Programmable Multicomponent Nucleic Acid Enzymes for Simultaneous Visualization of Multiple mRNA Splicing Variants in Living Cells.

RNA splicing is a key regulatory process of gene expression that can increase the transcriptome complexity. Simultaneous monitoring of multiple splicing variants in living cells is critical for gaining new insight into cell development. Herein, we demonstrate the development of proximity-activated, programmable multicomponent nucleic acid enzymes (MNAzymes) for the simultaneous visualization of multiple RNA splicing variants (i.

Construction of a dual-color fluorescent light-up biosensor based on sequential coding for label-free and sensitive detection of multiple Piwi-interacting RNAs.

We construct a dual-color light-up biosensor for label-free and sensitive detection of multiple piRNAs. This biosensor exhibits high sensitivity with a limit of detection of 3.19 aM for piRNA-36026 and 4.

Enzymatic cascade amplification-modulated Thermus thermophilus Argonaute biosensor for simultaneous monitoring of multiple Piwi-interacting RNAs.

PIWI-interacting RNAs (piRNAs) play critical regulatory roles in a variety of physiological and pathological process, and their aberrant expression levels are implicated in the progression and prognosis of cancers. Herein, we construct an enzymatic cascade amplification-modulated Thermus thermophilus Argonaute (TtAgo) biosensor for simultaneous monitoring of multiple piRNAs (i.e.

Lighting up three-dimensional nanolantern for circular RNA imaging and precise gene therapy.

Circular RNAs (circRNAs) are a category of endogenous single-stranded RNAs with covalently closed head-to-tail topology, and they play a crucial part in regulating gene expression at post-transcriptional and transcriptional levels. Herein, we construct a three-dimensional nanolantern for circRNA imaging and precise gene therapy. This assay involves an integrated multi-functionalized lantern-shaped probe.

Enhanced Electrochemiluminescence of Porphyrin-Based Hydrogen-Bonded Organic Frameworks at Low Positive Potential via Substituent-Induced Outer-Sphere Microenvironment Modulation.

The porphyrin-based hydrogen-bonded organic framework (HOF) offers a superior platform for decoding electrochemiluminescence (ECL) via controlling charge transfer due to its higher solubility, chemical stability, and tunable framework behavior. In this research, three kinds of HOFs including TDPP-HOF, TCPP-HOF, and TCNPP-HOF are synthesized based on a porphyrin tectonic plate decorated with 2,4-diaminotriazinyl (DAT), carboxyl, and nitrile moieties to study their ECL performances. The hydrazine as the coreactant can trigger TDPP-HOF at the low-excited positive potential to generate 15.

Construction of a Self-Enhanced Electrochemiluminescent Sensor Based on Tandem Signal Amplification and a Self-Luminescent Lanthanide Covalent-Organic Polymer for Ochratoxin A Assay.

Ochratoxin A (OTA) is a type of mycotoxin found in various contaminated foods, and it is highly toxic to the livers and kidneys of humans. Herein, we develop a self-enhanced electrochemiluminescent (ECL) sensor based on tandem signal amplification and a self-luminescent europium covalent-organic polymer (Eu-COP) for OTA assay. Eu-COP is a self-enhanced ECL emitter that is obtained by using 2,4,6-trimethyl-1,3,5-triazine (TMT) and 2,2'-bipyridine-5,5'-dicarbaldehyde (BPA) as the first and second ligands to form a highly conjugated structure for sensitizing the Eu luminescence.

A Programmable Automatic Cascade Machinery for Single-Molecule Profiling of Multiple Noncoding RNAs in Breast Tissues.

Noncoding RNAs (ncRNAs) are identified as critical regulatory molecules in tumorigenesis and progression. Investigating the expression patterns of multiple ncRNAs in living cells and tissues may facilitate the diagnosis of cancers. Herein, we develop a programmable automatic cascade machinery for single-molecule profiling of multiple ncRNAs.

Construction of a hierarchical DNA circuit for single-molecule profiling of locus-specific N-methyladenosine-MALAT1 in clinical tissues.

N-methyladenosine (mA) is the most important internal methylation in eukaryotic RNAs, and it is critically implicated in diverse RNA metabolisms for cancer development. Because epigenetic modifications do not interfere with Watson-Crick base pairing and mA modification is not susceptible to chemical decorations, standard hybridization-based techniques cannot be applied for sensing mA in RNAs. Consequently, the development of new methods for accurate and sensitive profiling of locus-specific mA in RNAs remains a great challenge.

Development of a Single-Molecule Biosensor Based on Polymerization-Transcription-Mediated Target Regeneration for Simultaneously One-Pot Detection of Multiple piRNAs.

PIWI-interacting RNAs (piRNAs) are a class of small noncoding RNAs associated with PIWI proteins within the male germline, and they play significant roles in maintaining genome stability via the modulation of gene expression. The piRNAs are implicated in the progression of various cancers, but the simultaneous monitoring of multiple piRNAs remains a challenge. Herein, we construct a single-molecule biosensor based on polymerization-transcription-mediated target regeneration for the simultaneous one-pot detection of multiple piRNAs.

Construction of a Multiple Cyclic Ligation-Promoted Exponential Recombinase Polymerase Amplification Platform for Sensitive and Simultaneous Monitoring of Cancer Biomarkers Fpg and FEN1.

Formamidopyrimidine DNA glycosylase (Fpg) and flap endonuclease 1 (FEN1) are essential to sustaining genomic stability and integrity, while the abnormal activities of Fpg and FEN1 may lead to various diseases and cancers. The development of simple methods for simultaneously monitoring Fpg and FEN1 is highly desirable. Herein, we construct a multiple cyclic ligation-promoted exponential recombinase polymerase amplification (RPA) platform for sensitive and simultaneous monitoring of Fpg and FEN1 in cells and clinical tissues.

Assembly of Dandelion-Like Nanoprobe for Sensitive Detection of N6-Methyladenosine Demethylase by Single-Molecule Counting.

N6-methyladenosine (m6A) demethylase is essential for enzymatically removing methyl groups from m6A modifications and is significantly implicated in the pathogenesis and advancement of various cancers, which makes it a promising biomarker for cancer detection and research. As a proof of concept, we select the fat mass and obesity-associated protein (FTO) as the target m6A demethylase and develop a dandelion-like nanoprobe-based sensing platform by employing biobar-code amplification (BCA) for signal amplification. We construct two meticulously designed three-dimensional structures: reporter-loaded gold nanoparticles (Reporter@Au NPs) and substrate-loaded magnetic microparticles (Substrate@MMPs), which can self-assemble to form dandelion-like nanoprobes via complementary base pairing.

Recent Advance in Single-Molecule Fluorescent Biosensors for Tumor Biomarker Detection.

The construction of biosensors for specific, sensitive, and rapid detection of tumor biomarkers significantly contributes to biomedical research and early cancer diagnosis. However, conventional assays often involve large sample consumption and poor sensitivity, limiting their further application in real samples. In recent years, single-molecule biosensing has emerged as a robust tool for detecting and characterizing biomarkers due to its unique advantages including simplicity, low sample consumption, ultra-high sensitivity, and rapid assay time.