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通过适应性天线实现无线原位催化电子信号介导的转录组重编程以促进神经元再生

Wireless In Situ Catalytic Electron Signaling-Mediated Transcriptomic Reprogramming for Neuron Regeneration via Adaptable Antennas.

作者信息

Iao Hoi Man, Chen Chih-Ying, Lin Ya-Hui, Pan Wan-Chi, Liang Chun-Yi, Liu Hsiu-Ching, Ching Lo-Jei, Weng Pei-Yu, Chiang Min-Ren, Hsu Ru-Siou, Chou Tsu-Chin, Lee I-Chi, Liao Lun-De, Chu Li-An, Chiou Shih-Hwa, Hu Shang-Hsiu

机构信息

Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 300044, Taiwan.

Department of Medical Research, Taipei Veterans General Hospital, Taipei, 112201, Taiwan.

出版信息

Adv Sci (Weinh). 2025 Jul;12(28):e2504786. doi: 10.1002/advs.202504786. Epub 2025 May 11.

Abstract

Electron signaling and oxygen level are vital for regulating neural-cell fate and brain recovery. However, clinical challenges arise from the short half-life and the difficulty of spatiotemporally controlled oxygen release and electric signals. In this study, a wireless-charging sustained oxygen release from conductive microgels (SOCO) served as an antenna and an on-demand O release for nerve regeneration is developed. Introducing "electromagnetic messenger", using external alternating magnetic field (AMF) to enhance catalytic oxygen release and electrical stimulation to promote the reconstruction of blood vessels and neurons in vivo. SOCO also reduces TBI glial scarring by reducing activated microglia and stellate cells, promoting infiltration of new neurons. In whole-brain analyses, effective somatostatin (Sst) production inhibits gamma-aminobutyric acid (GABA) synthesis in injured areas, thereby improving brain function and behavioral recovery. Furthermore, spatial multiomics combined with single-cell deconvolution analysis reveals the treatment reprogramming in vivo brain transcriptome of angiogenic markers (Il1a, Lgals3) and GABAergic pathway via modulation of GAD65/67 activity, guiding angiogenesis and neuronal regeneration. This in situ catalytic SOCO with noncontact AMF presents an "electromagnetic messenger"-based therapeutics for reprogramming the neuro-regeneration and brain function recovery in TBI.

摘要

电子信号传导和氧水平对于调节神经细胞命运和脑恢复至关重要。然而,临床挑战源于氧释放和电信号的半衰期短以及时空控制的困难。在本研究中,开发了一种从导电微凝胶进行无线充电持续氧释放(SOCO),其作为天线并按需释放氧气用于神经再生。引入“电磁信使”,利用外部交变磁场(AMF)增强催化氧释放,并通过电刺激促进体内血管和神经元的重建。SOCO还通过减少活化的小胶质细胞和星状细胞来减少创伤性脑损伤(TBI)后的胶质瘢痕形成,促进新神经元的浸润。在全脑分析中,有效的生长抑素(Sst)产生抑制损伤区域中γ-氨基丁酸(GABA)的合成,从而改善脑功能和行为恢复。此外,空间多组学与单细胞反卷积分析相结合,揭示了通过调节GAD65/67活性对血管生成标记物(Il1a、Lgals3)和GABA能途径的体内脑转录组进行治疗重编程,指导血管生成和神经元再生。这种具有非接触式AMF的原位催化SOCO提出了一种基于“电磁信使”的疗法,用于对TBI中的神经再生和脑功能恢复进行重编程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b550/12302649/29b5c4fd3791/ADVS-12-2504786-g008.jpg

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