Square-planar Tetranuclear Cluster-based Alkaline Earth Metal-organic Frameworks with Enhanced Proton Conductivity.

Alkaline earth (AE) metal complexes have garnered significant interest in various functional fields due to their nontoxicity, low density, and low cost. However, there is a lack of systematic investigation into the structural characteristics and physical properties of AE-metal-organic frameworks (MOFs). In this research, we synthesized isostructural MOFs consisting of AE4(µ4-Cl) clusters bridged by benzo-(1,2;3,4;5,6)-tris(thiophene-2'-carboxylic acid) (BTTC3-) ligands. The resulting structure forms a truncated octahedral cage denoted as [AE4(m4-Cl)]6(BTTC)8, which further linked to a porous three-dimensional framework. Among the investigated AE ions (Ca, Sr, and Ba), the Ca4-MOF demonstrated good chemical stability in water compared to Sr4-MOF and Ba4-MOF. The N2 adsorption and solid-state UV-vis-NIR absorption behaviors were evaluated for all AE4-MOFs, showing similar trends among the different metal ions. Additionally, the proton conduction study revealed that the Ca4-MOF exhibited ultra-high proton conductivity, reaching 3.52×10-2 S cm-1 at 343 K and 98 % RH. Notably, the introduction of LiCl via guest exchange resulted in an improved proton conduction of up to 6.36×10-2 S cm-1 under similar conditions in the modified LiCl@Ca4-MOF. The findings shed light on the regulation of physical properties and proton conductivity of AE-MOFs, providing valuable insights for their potential applications in various fields.

Development of a single-molecule biosensor with an ultra-low background for the simultaneous detection of multiple retroviral DNAs.

Human T-cell lymphotropic virus type I and type II (HTLV-I and HTLV-II) are the two most prevalent subtypes of HTLVs, and they usually infect individuals asymptomatically and may induce various diseases. Herein, we develop a single-molecule biosensor with an ultra-low background for the simultaneous detection of multiple retroviral DNAs. This biosensor is constructed by immobilizing two types of signal probes (i.e., signal probes 1 and 2) onto the surface of magnetic beads (MBs) through specific biotin-streptavidin interactions. The presence of HTLV-I DNA and HTLV-II DNA will initiate the RNase H-assisted cyclic cleavage of signal probes, inducing the release of Cy3 and Cy5 fluorophores from the MBs. After magnetic separation, the Cy3 and Cy5 fluorophores can be directly quantified by single-molecule detection, with the Cy3 signal indicating HTLV-I DNA and the Cy5 signal indicating HTLV-II DNA. This biosensor enables the all-in-one and simultaneous detection of HTLV-I DNA and HTLV-II DNA under isothermal conditions, greatly simplifying the operation procedures and reducing the assay time. Due to the high amplification efficiency of RNase H-assisted target recycling, the ultra-low background resulting from magnetic separation, and the intrinsic high signal-to-noise ratio of single-molecule detection, this biosensor exhibits high sensitivity with a detection limit of 66.1 aM for HTLV-I DNA and 82.8 aM for HTLV-II DNA. Moreover, it can be applied for the discrimination of HTLV-positive cells from HTLV-negative cells, and even simultaneously quantify endogenous HTLV-I DNA and HTLV-II DNA at the single-cell level. Furthermore, this biosensor can be extended to detect other nucleotide molecules by rationally designing signal probes, providing a universal and powerful tool for clinical diagnosis and biomedical research.

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). We design a trifunctional split dumbbell probe that can act as a probe for NAD+ recognition, a template for RCA reaction, and a substrate for SYBR Green I binding. In the presence of target NAD+, it can serve as a cofactor to active E. coli DNA ligase which subsequently catalyzes the ligation of split dumbbell probe to form a circular template for RCA reaction, generating numerous dumbbell probe amplicons which can be easily and label-free monitored by using SYBR Green I as the fluorescent indicator. Due to the high fidelity of NAD+-dependent ligation and high amplification efficiency of RCA amplification, this method exhibits high sensitivity with a detection limit of 85.6 fM and good selectivity with the capability of discriminating target NAD+ from its analogs. Moreover, this method can be applied for accurate and sensitive detection of NAD+ in complex biological samples and cancer cells, holding great potential in NAD+-related biological researches and clinical diagnosis.

Peptide-templated gold nanoparticle nanosensor for simultaneous detection of multiple posttranslational modification enzymes.

We developed a peptide-templated gold nanoparticle (AuNP) nanosensor for simultaneous detection of multiple posttranslational modification (PTM) enzymes with a detection limit of 28 pM for histone deacetylase (HDAC) and 0.8 pM for protein tyrosine phosphatase 1B (PTP1B), and it can be further applied for the screening of PTM enzyme inhibitors and the measurement of PTM enzymes in cancer cells.