The abnormal sustained activation of mesenchymal-epithelial transition factor (Met) dimers on cancer cell membranes is closely associated with malignant tumor progression; however, accurate identification of specific cancer cells and subsequent sensitive monitoring of intercellular signaling pathways activated by membrane Met dimerization within the intricate tumor microenvironments remain significant challenges. Here, an innovative surface-enhanced Raman scattering (SERS)-based AND logic gate was proposed for the highly sensitive imaging of Met protein dimers on target cancer cells, facilitated through the assembly of recognition probes (RPs) and SERS tag network nanostructures (RP-SERS tag NWs) with rich SERS hot spots. The SERS-based AND logic gate, powered by the synergistic interplay of aptamer-targeted cancer cell-triggered localized catalytic hairpin assembly (LCHA) and proximity ligation-induced DNAzyme cleavage, achieves precise identification of specific tumor cells and real-time imaging of membrane Met protein dimerization. Moreover, we successfully employed SERS imaging to visualize the HGF/Met signaling pathway between stromal cells or stem cells and cancer cells within the natural complexity of cellular microenvironments. This approach also allows for real-time evaluation of the antitumor efficacy of drugs targeting receptor dimerization. These results indicated that the proposed AND logic-based SERS strategy holds promise for advancing cancer diagnostics, understanding cellular communication mechanisms, and accelerating the development of more effective therapeutic interventions.

DNA/RNA modifications are crucial for biological processes. To understand their regulatory mechanisms, precise mapping and quantification of these modifications are essential. Although next-generation sequencing can detect the location and stoichiometry of modifications, complex treatments are required, hindering efficiency and long-range analysis. In contrast, nanopore sequencing eliminates the need for additional treatment and PCR amplification, thus preserving DNA/RNA modification information. It enables modifications to be identified and quantified directly at the single-molecule level. Therefore, nanopore sequencing facilitates long-read, real-time modification detection, and has gained widespread applications. This perspective introduces the principles of nanopore sequencing, evaluates its strengths/weaknesses, and critically examines its broader real-world applications. To expand the utility of nanopore sequencing further, we discuss the current challenges and suggest future directions.

Current therapies for Alzheimer's disease (AD) primarily target amyloid-β (Aβ) pathology using monoclonal antibodies, yet their limited efficacy partly results from unintended exacerbation of neural hyperexcitability. This highlights a critical but under-appreciated link between Aβ clearance and neuronal network dysfunction. Here, we designed R@AClipo, a nanotherapeutic platform that codelivers the TREM2 agonist peptide COG1410 and the glutamate modulator riluzole via Angiopep-2-modified liposomes capable of crossing the blood-brain barrier. In AD model mice, R@AClipo upregulated TREM2 expression and enhanced microglial-mediated Aβ clearance. Concurrently, it reduced glutamate accumulation and mitigated neuronal hyperexcitability, as measured by in vivo fiber photometry. Notably, TREM2-driven Aβ clearance alone modestly reduced hyperexcitability, independent of riluzole, contrasting with the excitatory effects frequently associated with antibody-based Aβ therapies. This combinatorial strategy improved cognitive performance and restored neural activity patterns without observable toxicity. Together, these findings support a physiologically compatible strategy that targets the pathological crosstalk between Aβ accumulation and neural hyperexcitability, offering a promising avenue for AD intervention.