The comprehensive understanding of the mechanisms underlying the interaction of cells with their membrane microenvironment is of great value for fundamental biological research; however,tracking biomolecules on cell surfaces with high temporal and spatial resolution remains ac hallenge. Herein, amodular strategy is presented for the construction of cell surface DNA-based sensors by engineering DNAm otifs and synthetic cofactors.I nt his strategy,astimuli-reactive organic molecule is employed as the cofactor for the DNA motif,and the self-assembly of them forms aFRET-based holo DNA-based sensor.Withthe use of the DNA-based sensors,the versatility of this modular strategy has been demonstrated in the ratiometric imaging of the cellular extrusion process of endogenous signaling molecules,i ncluding sulfur dioxide derivatives and nitric oxide.

The RhoA/ROCK pathway mediates HG-induced cardiomyocyte apoptosis via oxidative stress and activation of p38MAPK and JNK in neonatal rats in vitro. Fasudil effectively ameliorates HG-induced cardiomyocyte apoptosis by suppressing oxidative stress and the p38MAPK and JNK pathways.

The label-free assay has drawn extensive attention because it does not require a labeling step and enables direct interaction and signal transduction between the sensing unit and target analytes. Herein, we demonstrate a proof-of-principle concept of a label-free and visualized nanoplasmonic strategy for silver ions sensing, where only Ti3C2 MXenes are employed by exploring their excellent adsorption affinity and reductive property toward metal ions. Ag+ was adsorbed onto the surface of Ti3C2 MXene nanosheets, followed by the Ti3C2 MXenes mediated in situ silver nanoparticles (Ag NPs) generation without adding any extra stabilizing or reducing agent. The excellent localized surface plasmon resonances at a particular wavelength provide Ag NPs the capability for colorimetric assay with a detection limit of 0.615 μM. With the assistance of a smartphone, RGB analysis exhibited visualized results consistent with the results measured on a UV–vis spectrometer, promising a budget, simple-operating on-site detection. Moreover, the detection of Ag+ in real samples was achieved with satisfactory results meeting the analysis demand for the Drinking Water Standards of the World Health Organization (WHO) and the United States Environmental Protection Agency (U.S. EPA). These results reveal that Ti3C2 MXenes possess great potential in building convenient label-free colorimetry nanoplatforms and may evoke more inspirations to explore strategies for the direct sensing of analytes.

Selective modulation of ligand–receptor interaction is essential in targeted therapy. In this study, we design an intelligent “scan and unlock” DNA automaton (SUDA) system to equip a native protein‐ligand with cell‐identity recognition and receptor‐mediated signaling in a cell‐type‐specific manner. Using embedded DNA‐based chemical reaction networks (CRNs) on the cell surface, SUDA scans and evaluates molecular profiles of cell‐surface proteins via Boolean logic circuits. Therefore, it achieves cell‐specific signal modulation by quickly unlocking the protein‐ligand in proximity to the target cell‐surface to activate its cognate receptor. As a proof of concept, we non‐genetically engineered hepatic growth factor (HGF) with distinct logic SUDAs to elicit target cell‐specific HGF signaling and wound healing behaviors in multiple heterogeneous cell types. Furthermore, the versatility of the SUDA strategy was shown by engineering tumor necrotic factor‐α (TNFα) to induce programmed cell death of target cell subpopulations through cell‐specific modulation of TNFR1 signaling.

Macrophages are key responders of inflammation and are closely related with oxidative stress. Activated macrophages can enhance oxygen depletion, which causes an overproduction of reactive oxygen species (ROS) and leads to further excessive inflammatory response and tissue damage. Agmatine, an endogenous metabolite of L-arginine, has recently been shown to have neuroprotective effects based on its antioxidant properties. However, the antioxidant effects of agmatine in peripheral tissues and cells, especially macrophages, remain unclear. In this study we explored the role of agmatine in mediating antioxidant effects in RAW 264.7 cells and studied its antioxidant mechanism. Our data demonstrate that agmatine is an activator of Nrf2 signaling that markedly enhances Nrf2 nuclear translocation, increases nuclear Nrf2 protein level, up-regulates the expression of the Nrf2 downstream effector HO-1, and attenuates ROS generation induced by Lipopolysaccharide (LPS). We further demonstrated that the agmatine-induced activation of Nrf2 is likely through the PI3K/Akt pathway. LY294002, a specific PI3K/Akt inhibitor, abolished agmatine-induced HO-1 up-regulation and ROS suppression significantly. Inhibiting HO-1 pathway significantly attenuated the antioxidant effect of agmatine which the products of HO-1 enzymatic activity contributed to. Furthermore, the common membrane receptors of agmatine were evaluated, revealing that α2-adrenoceptor, I1-imidazoline receptor or I2-imidazoline receptor are not required by the antioxidant properties of agmatine. Taken together, our findings revealed that agmatine has antioxidant activity against LPS-induced ROS accumulation in RAW 264.7 cells involving HO-1 expression induced by Nrf2 via PI3K/Akt pathway activation.