Intelligent DNA Nanosystem for Broad-Spectrum Oncological Typing and Therapy.

The occurrence of multiple primary cancers in individual patients underscores the need for diagnostic and therapeutic techniques with augmented cancer-targeting selectivity and broad-spectrum antitumor effects. To address this, we develop a quadruple-input-triggered R-ND-ND logic gated oncological nanosystem (OAA). This system employs four cancer-related markers (EpCAM, MUC1, APE1, and miR-21) to generate three distinct fluorescence signals, enabling precise differentiation of various cancer cell lines (MCF-7, HepG2, and HeLa) from normal cells (MCF-10A).

Intelligent Cell Profiling and Precision Release: Multimolecular Marker-Activated Transmembrane DNA Computing Nanosystem.

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion.

Click Conjugation of Zwitterionic Peptide with DNA Strand: An Efficient Antifouling Strategy for Versatile Photoelectrochemical Aptasensor.

Advanced antifouling biosensors have garnered considerable attention for their potential for precise and sensitive analysis in complex human bodily fluids. Herein, a pioneering approach was utilized to establish a robust and versatile photoelectrochemical aptasensor by conjugating a zwitterionic peptide with a DNA strand. Specifically, the branched zwitterionic peptide (BZP) was efficiently linked to complementary DNA (cDNA) through a click reaction, forming the BZP-cDNA conjugate.

Engineered Branching Peptide as Dual-Functional Antifouling and Recognition Probe: Toward a Dual-Photoelectrode Protein Biosensor with High Accuracy.

The building of practical biosensors that have anti-interference abilities against biofouling of nonspecific proteins and biooxidation of reducing agents in actual biological matrixes remains a great challenge. Herein, a robust photoelectrochemical (PEC) biosensor capable of accurate detection in human serum was pioneered through the integration of a new engineered branching peptide (EBP) into a synergetic dual-photoelectrode system. The synergetic dual-photoelectrode system involved the tandem connection of a CN/TiO photoanode and a AuPt/PANI photocathode, while the EBP as a dual-functional antifouling and recognition probe featured an inverted Y-shaped configuration with one recognition backbone and two antifouling branches.

Synergistic Incorporation of Two ssDNA Activators Enhances the Trans-Cleavage of CRISPR/Cas12a.

CRISPR/Cas12a has been believed to be powerful in molecular detection and diagnostics due to its amplified trans-cleavage feature. However, the activating specificity and multiple activation mechanisms of the Cas12a system are yet to be elucidated fully. Herein, a "synergistic activator effect" is discovered, which supports an activation mechanism that a synergistic incorporation of two short ssDNA activators can promote the trans-cleavage of CRISPR/Cas12a, while either of them is too short to work independently.

Promoting sensitive colorimetric detection of hydroquinone and Hg via ZIF-8 dispersion enhanced oxidase-mimicking activity of MnO nanozyme.

Reducing the agglomeration and improving the dispersibility in water of two-dimensional (2D) nanozymes is one of the effective ways to improve their enzyme-like activity. In this work, we propose a method by constructing zeolitic imidazolate framework-8 (ZIF-8)-dispersed 2D manganese-based nanozymes to achieve the specific regulated improvement of oxidase-mimicking activity. By in-situ growth of manganese oxides nanosheets of MnO(1), MnO(2) and MnO on the surface of ZIF-8, the corresponding nanocomposites of ZIF-8 @MnO(1), ZIF-8 @MnO(2), and ZIF-8 @MnO were prepared at room temperature.

Compute-and-Release Logic-Gated DNA Cascade Circuit for Accurate Cancer Cell Imaging.

Accurate identification of cancer cells is an essential prerequisite for cancer diagnosis and subsequent effective curative interventions. The logic-gate-assisted cancer imaging system that allows a comparison of expression levels between biomarkers, rather than just reading biomarkers as inputs, returns a more comprehensive logical output, improving its accuracy for cell identification. To fulfill this key criterion, we develop a compute-and-release logic-gated double-amplified DNA cascade circuit.

Molecular Engineering of Near-Infrared Fluorescent Probes for Cell Membrane Imaging.

Cell membrane (CM) is a phospholipid bilayer that maintains integrity of a whole cell and relates to many physiological and pathological processes. Developing CM imaging tools is a feasible method for visualizing membrane-related events. In recent decades, small-molecular fluorescent probes in the near-infrared (NIR) region have been pursued extensively for CM staining to investigate its functions and related events.

Engineering of a novel D-A type fluorophore with hydrogen bond-induced enhanced emission property for sensitively detecting endogenous HOCl in living cells and tissues.

Fluorescence imaging has been widely employed for biomedical research and clinical diagnostics. With ease of synthesis and excellent photophysical properties, D-A type fluorophores are widely designed for fluorescence imaging. However, traditional D-A type fluorophores are solvatochromic which reduces the fluorescence brightness in the biological system.

A protein enzyme-free strategy for fluorescence detection of single nucleotide polymorphisms using asymmetric MNAzymes.

To establish protein enzyme-free and simple approach for sensitive detection of single nucleotide polymorphisms (SNPs), the nucleic acid amplification reactions were developed to reduce the dependence on protein enzymes (polymerase, endonuclease, ligase). These methods, while enabling highly amplified analysis for the short sequences, cannot be generalized to long genomic sequences. Herein, we develop a protein enzyme-free and general SNPs assay based on asymmetric MNAzyme probes.

Integrating a zwitterionic peptide with a two-photoelectrode system for an advanced photoelectrochemical immunosensing platform.

An ingenious strategy with the integration of a zwitterionic peptide into a two-photoelectrode system was reported to construct an advanced photoelectrochemical immunosensing platform. The strategy has endowed the platform with both excellent photoelectric properties and an antifouling ability, and was capable of accurate and sensitive detection of target biomarkers in biological specimens.

Silver ion-regulated ratiometric fluorescence assay for alkaline phosphatase detection based on carbon dots and o-phenylenediamine.

In this work, a novel silver ion (Ag)-regulated ratiometric fluorescence method for the effective and sensitive determination of alkaline phosphatase (ALP) was established based on carbon dots (CDs) and o-phenylenediamine (OPD). OPD can be oxidized by Ag to generate fluorescent 2, 3-diaminophenazine (DAP). Thus, based on inner-filter effect (IFE) or/and fluorescence resonance energy transfer (FRET) between CDs and DAP, the CDs-Ag-OPD system can generate dual-emission at 454 nm and 570 nm respectively when excited at 360 nm.

A sensitive fluorescence biosensor based on metal ion-mediated DNAzyme activity for amplified detection of acetylcholinesterase.

In this paper, we developed an amplified fluorescence biosensor for acetylcholinesterase (AChE) activity detection by taking advantage of the mercury ion-mediated Mgzyme (Mg-dependent DNAzyme) activity. The catalytic activity of Mgzyme can be inhibited by the formation of T-Hg-T base pairs between the Mgzyme and mercury ions. Therefore, the Mgzyme-Hg complex has no activity on a molecular beacon (MB) substrate, which afforded a very weak fluorescence background for this biosensor.

Selective detection of ozone in inflamed mice using a novel activatable chemiluminescent probe.

We report here an activatable chemiluminescent probe CL-O for the high-contrast imaging of O. CL-O exhibited a high selectivity toward O and was able to evaluate the degree of inflammation in mice by detecting endogenous O levels in acute inflamed mice.

Long-wavelength emission carbon dots as self-ratiometric fluorescent nanoprobe for sensitive determination of Zn.

A novel ratiometric fluorescence nanoprobe based on long-wavelength emission carbon dots (CDs) was designed for high sensitive and selective detection of Zn. The CDs were conveniently prepared by a one-step solvothermal treatment of formamide and glutathione (GSH). Under single excitation wavelength (420 nm), the obtained CDs exhibit three emission peaks at 470, 650, and 685 nm, respectively.

A DNAzyme-based normalized fluorescence strategy for direct quantification of endogenous zinc in living cells.

Taking the maximum fluorescence of an identical fluorophore as a reference, a DNAzyme-based normalized strategy is developed to unify the output signals under external interferences. This makes it possible to directly quantify endogenous zinc in living cells by fluorescence imaging, implying promising potential in fundamental study and early disease diagnosis.

Discovery of new 2-phenyl-1H-benzo[d]imidazole core-based potent α-glucosidase inhibitors: Synthesis, kinetic study, molecular docking, and in vivo anti-hyperglycemic evaluation.

In the present study, a series of 2-phenyl-1H-benzo[d]imidazole-based α-glucosidase inhibitors were synthesized and evaluated for their in vitro and in vivo anti-diabetic potential. Screening of an in-house library revealed a moderated α-glucosidase inhibitor, 6a with 3-(1H-benzo[d]imidazol-2-yl)aniline core, and then the structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased activity than 6a, and the most promising inhibitors were found to be compounds 15o and 22d with IC values of 2.

A novel ratiometric fluorescence nanoprobe for sensitive determination of uric acid based on CD@ZIF-CuNC nanocomposites.

A novel ratiometric fluorescence nanoprobe based on carbon dots (CDs) and Cu nanoclusters (CuNCs) was designed for the label-free determination of uric acid (UA). The metal-organic framework (MOF) encapsulated CuNCs (ZIF-CuNC), and nitrogen-doped CDs can self-assemble into well-defined spherical nanocomposites (CD@ZIF-CuNC) due to physical adsorption. Under the excitation wavelength of 360 nm, the CD@ZIF-CuNC nanocomposites exhibit two evident intrinsic emissions peaked at 460 nm (CDs) and 620 nm (ZIF-CuNC), respectively.

Tumor-Specific Multipath Nucleic Acid Damages Strategy by Symbiosed Nanozyme@Enzyme with Synergistic Self-Cyclic Catalysis.

The high proliferation efficiency, redox imbalance, and elevated nucleic acid repair capabilities of tumor cells severely restrict the theranostic efficacy. Selectively interference chaotic tumors with devastating nucleic acid damages (NUDs) properties are expected to overcome theranostic barriers. Here, an exquisite catalytic-based strategy with comprehensive NUDs mechanisms is demonstrated.

Covalent Amide-Bonded Nanoflares for High-Fidelity Intracellular Sensing and Targeted Therapy: A Superstable Nanosystem Free of Nonspecific Interferences.

A nanoflare, a conjugate of Au nanoparticles (NPs) and fluorescent nucleic acids, is believed to be a powerful nanoplatform for diagnosis and therapy. However, it highly suffers from the nonspecific detachment of nucleic acids from the AuNP surface because of the poor stability of Au-S linkages, thereby leading to the false-positive signal and serious side effects. To address these challenges, we report the use of covalent amide linkage and functional Au@graphene (AuG) NP to fabricate a covalent conjugate system of DNA and AuG NP, label-rcDNA-AuG.

Ratiometric Semiconducting Polymer Nanoparticle for Reliable Photoacoustic Imaging of Pneumonia-Induced Vulnerable Atherosclerotic Plaque in Vivo.

Acute pneumonia can greatly increase the vulnerable risk of atherosclerotic plaque and contribute to the mortality of cardiovascular disease. To accurately assess the rupture risk caused by acute pneumonia, we developed a novel kind of ratiometric semiconducting polymer nanoparticle (RSPN) for photoacoustic imaging of vulnerable plaque in apolipoprotein E-deficient mice complicated with pneumonia. Specifically, RSPN can react with O and exhibit the enhanced photoacoustic signals at about 690 nm, while 800 nm is regarded as an internal photoacoustic reference.

Rational design of a HA-AuNPs@AIED nanoassembly for activatable fluorescence detection of HAase and imaging in tumor cells.

Aggregation induced emission (AIE) dots have gained broad attention in fluorescence bioimaging and biosensors in virtue of their distinctive optical properties of splendid biocompatibility, high brightness and good photostability. However, the application of AIE dots in sensing and imaging of enzymes in cells remains at an early stage and needs to be further explored. In this report, we proposed a novel AIE-dot-based nanoprobe for hyaluronidase (HAase) detection using a simple electrostatic self-assembly of AIE dots with gold nanoparticles functionalized using hyaluronic acid (HA-AuNPs), named HA-AuNPs@AIEDs.

Bacterial community composition of internal circulation reactor at different heights for large-scale brewery wastewater treatment.

This study analyzed bacterial community structure for large-scale brewery wastewater treatment at different heights in internal circulation (IC) reactor. Proteobacteria, Bacteroidetes and Chloroflexi were dominant bacteria, which accounted for 64.17%, 64.

A Transparent Vessel-on-a-Chip Device for Hemodynamic Analysis and Early Diagnosis of Intracranial Aneurysms by CFD and PC-MRI.

Hemodynamics plays a critical role in early diagnosis and investigating the growth mechanism of intracranial aneurysms (IAs), which usually induce hemorrhagic stroke, serious neurological diseases, and even death. We developed a transparent blood vessel-on-a-chip (VOC) device for magnetic resonance imaging (MRI) to provide characteristic flow fields of early IAs as the reference for early diagnosis. This VOC device takes advantage of the transparent property to clearly exhibit the internal structure and identify the needless air bubbles in the biomimetic fluid experiment, which significantly affects the MRI image quality.

Peroxidase-like Au@Pt nanozyme as an integrated nanosensor for Ag detection by LSPR spectroscopy.

Here we report the peroxidase-like Au@Pt nanozyme as an integrated nanosensor for selective detection of silver ions (Ag), where the nanozyme plays the roles as both the signal trigger and reporter simultaneously. This method relies on two critical chemical reactions, including (1) the unique inhibitory effect of Ag on the nanozyme triggered HO decomposition at weak acid environment and (2) HO induced Ag reduction onto the nanozyme surface at basic environment, leading to a blueshift in the localized surface plasmonic resonance wavelength (LSPR λ) of the nanosensor. With this simple strategy, we demonstrated the sensitive and selective detection of Ag over a dynamic range from 0.