Biology subjects

Li, D.-X.

Publications and source records attributed to Li, D.-X..

3 recordsLinked to original sources

bioRxiv2026

Neural Arming Niche in Tumor-Draining Lymph Nodes Programs CD8⁺T Cell Cytotoxicity via GZMB Norepinephrinylation

Lymph nodes are densely innervated neuro-immune hubs where naive T cells are primed and "armed" with cytotoxic machinery, yet how local neural cues in tumor-draining lymph nodes (tdLNs) set CD8 T cell effector reserves remains unclear. Here we show that tdLN-local sympathetic norepinephrine (NE) instructs CD8 T cell cytotoxic capacity by stabilizing the granzyme B (GZMB) pool through covalent norepinephrinylation. Exercise, used as a physiological perturbation, increases GZMB selectively in tdLN and tumor CD8 T cells without altering T cell abundance or cytokine output; tdLN sympathectomy abolishes these effects and reduces tdLN NE enrichment. Mechanistically, NE enters CD8 T cells and norepinephrinylates GZMB at Gln43, limiting UHRF1-mediated ubiquitination and proteasomal degradation. Genetic attenuation of norepinephrinylation destabilizes GZMB, impairs cytotoxicity, and accelerates tumor growth. Brief ex vivo NE conditioning increases GZMB reserves and improves adoptive tumor control.

cancer biology↗

bioRxiv2026

Visualizing single base RNA mutations in living cells through DNA nanostructure mediated amplification

Capturing RNA dynamics in living cells would provide critical insights into transcriptional control and cellular adaptation, but remains technically formidable -- particularly at single-base precision. Here, we introduce a DNA tetrahedron based three-dimensional catalytic hairpin assembly (3D@CHA) nanoplatform that couples target recognition with catalytic activation in a spatially organized framework. Three cascaded hairpins (H-AN, H1, and H2) then enable localized and efficient signal amplification. Without external carriers or transfection, the platform exhibits robust biocompatibility, distinguishing highly homologous insulin I (Ins1) and insulin II (Ins2) mRNAs in living cells and tracking their redistribution and intercellular transfer during metabolic changes. Introducing a single-base mismatch site into H1 and coupling it with a Forster resonance energy transfer (FRET) readout yielded a KRAS-3D@CHA probe capable of detecting KRASG12D mutations at the RNA level with single-base resolution. This platform establishes a programmable framework for precise RNA imaging and mutation discrimination, opening new avenues for RNA-level diagnostics and precision oncology.

cell biology↗

bioRxiv2025

A neuroendocrine principle: Pancreatic islets actively shape sympathetic innervation

Survival critically depends on maintaining blood glucose levels to provide essential energy, especially during emergencies such as the fight-or-flight response, when timely glucose control via neural integration is vital. However, pancreatic islets constitute only a small fraction of the pancreas and are dispersed throughout the organ, raising the fundamental question of how the nervous system coordinates synchronized control of multiple islets. Using whole-organ clearing and 3D imaging, we mapped pancreatic sympathetic innervation, revealing specialized anatomical integration between sympathetic nerves and islets. Transplanted islets intrinsically attracted sympathetic nerves independent of their native environment. Chronic islet injury disrupted sympathetic innervation and markedly impaired nerve regeneration after denervation. Sympathetic denervation markedly elevated islet-derived Reg2 and Reg3{beta}; administration of these proteins accelerated sympathetic regeneration and improved islet graft function. Our findings identify an islet-sympathetic architecture actively maintained by islets, uncovering an endocrine-driven mechanism for neural regulation, highlighting Reg2 and Reg3{beta} as therapeutic candidates for diabetes management.

neuroscience↗