Xihua University

Synaptic dysfunction and loss are central drivers of cognitive decline in Alzheimer's disease (AD), yet current therapeutic approaches targeting amyloid-β or tau pathology have largely failed to rescue synaptic function. Neural oscillations and synaptic plasticity are tightly coupled and underpin functional brain networks, suggesting that modulating oscillatory dynamics may offer new therapeutic avenues. Here, we developed a strategy for precise, non-genetic neuromodulation using focused ultrasound and piezoelectric Ba_0.85Ca_0.15Zr_0.1Ti_0.9O₃ (BCZT) nanoparticles to generate targeted, gamma-frequency electromagnetic fields in the hippocampal CA3 subregion of early-stage AD mouse models. This rhythmic stimulation effectively restored impaired gamma oscillations, enhanced synaptic plasticity, and remodeled memory-related network connectivity, as validated by local field potential recordings, patch-clamp electrophysiology, and functional MRI. Mechanistically, we demonstrate that NF-κB transcription factor activation during rhythmic stimulation regulates AMPAR trafficking by balancing synaptic internalization and delivery, with concurrent upregulation of P300-mediated histone acetylation. Our findings establish a novel paradigm for spatially precise, periodic neuromodulation that restores hippocampal information processing and network function in early AD, highlighting the therapeutic potential of piezoelectric nanomaterials for neural circuit repair in AD and other neurodegenerative diseases characterized by impaired neural rhythms.

While stents are cornerstone treatments for atherosclerosis, in-stent restenosis remains a challenge. Engineering stent surfaces with specific biochemical signals can prevent this by promoting the crucial and timely regeneration of the endothelium. In this work, Ac-SDKP (N-Acetyl-Ser-Asp-Lys-Pro), an anti-inflammatory and endothelial homeostasis-regulating peptide, was incorporated into a blood-compatible PAMAM (poly-amidoamine) platform to yield pro-endothelial repair nanoassemblies. Ac-SDKP nanoassemblies attenuated macrophage activity and TNF α secretion, as well as neutrophil myeloperoxidase release. Simultaneously, the modified surface enhanced endothelial cell (EC) activity, proliferation and protection. The immobilized Ac-SDKP suppressed both extrinsic (caspase 8 pathway) and intrinsic (cytochrome c pathway) apoptotic signal, along with caspase-1-mediated inflammatory death, while also activating PI3K pathway to exert an anti-death effect. Furthermore, the nanoassemblies also suppressed the transmission of EC dysfunction signals by inhibiting the IKKα-RELB pathway, including monocyte chemoattractant protein-1 (linked to inflammation) and tissue factor (promoting coagulation), thereby helping to protect endothelial function. Collectively, this novel modification strategy promoted endothelial regeneration, suppressed neointimal hyperplasia, and reduced inflammatory cell infiltration in Sprague Dawley rats. In summary, constructing Ac-SDKP nanoassemblies on a PAMAM framework promotes endothelial recovery through anti-inflammatory and endothelial protection mechanisms, offering a potential approach for preventing post-implantation complications.

In this work, covalent organic framework (COF)-derived magnetic nanocomposites (Fe₃O₄@PDA@COF_TABP), comprising Fe₃O₄ as the magnetic core, polydopamine (PDA) as the hydrophilic interlayer, and COF_TABP as the outer shell, were first constructed and utilized as the powerful adsorbents for the magnetic solid-phase extraction (MSPE) of pyrethroids (PYRs). The introduction of the PDA coating facilitated the growth of the COF_TABP shell and simultaneously provided additional adsorption sites, thereby enhancing the extraction efficiency. Molecular docking simulations revealed that Fe₃O₄@PDA@COF_TABP exhibited excellent affinity toward PYRs through synergistic π-π stacking, hydrogen bonding, and hydrophobic interactions. The developed MSPE method coupled with GC-μECD exhibited excellent linearity (R² ≥ 0.9988), low limits of detection (0.025-0.064 μg kg^-1), satisfactory recoveries (82.4 %-106.8 %), and low relative standard deviations (RSDs <7.1 %). Finally, the established method was successfully applied to the quantification of trace PYRs in vegetable samples, demonstrating its strong potential for routine pesticide residue monitoring in vegetables.