Biology subjects

Yang, S. H.

Publications and source records attributed to Yang, S. H..

5 recordsLinked to original sources

bioRxiv2026

Cascaded Nano-ring Dialyzer for Continuous Regenerative Peritoneal Dialysis

End-stage kidney disease (ESKD) requires lifelong kidney replacement therapy, yet conventional hemodialysis and peritoneal dialysis remain limited by intermittent treatment, restricted mobility, and repeated dialysate exchange. Here, we developed a continuous regenerative peritoneal dialysis platform based on a nano-ring-assisted nanoelectrokinetic dialyzer for portable artificial kidney applications. We first identified key geometric and electrokinetic parameters governing the removal performance of nano-ring meshes, including mesh dimension, nano-ring coating thickness, the number of cascaded nano-rings, and the relative orientation between fluid flow and the applied electric field. We then developed a single nano-ring dialyzer operating at 1.33 mL/min and scaled the treatment capacity to approximately 10 mL min/min through parallel integration of multiple modules. In a canine model, the closed-loop system achieved approximately 10 % reduction in circulating uremic toxin levels during continuous treatment. We further improved the biocompatibility of the regenerated dialysate by integrating plate-type electrodes, activated carbon, bicarbonate buffering, and UV-C treatment. In an unanesthetized canine model, the improved system sustained continuous toxin removal for 4 h while major hepatic and inflammatory markers remained within recoverable ranges. These results demonstrate that cascaded nano-ring enables continuous dialysate regeneration with scalable throughput, reduced dependence on fresh dialysate, and in vivo control of uremic toxins, providing a technological foundation for portable or wearable regenerative peritoneal dialysis systems.

bioengineering↗

bioRxiv2026

A self-limiting orexin-habenula circuit for stress resilience

Resilience requires neural systems that mobilise active coping during stress while limiting its persistence to preserve homeostasis under sustained challenge1-4. Here we identify a self-limiting orexin-habenula circuit in which lateral hypothalamic orexin neurons engage aromatic L-amino acid decarboxylase-expressing D-neurons (encoded by Ddc) in the lateral habenula via orexin receptor type 2 (OX2R)5-7. Activation of this pathway increased nucleus accumbens dopamine and promoted active coping and positive valence. Optotagging revealed rapid stress-evoked recruitment followed by post-stress suppression. In lateral habenula neurons, orexin peptides exerted dissociable effects: orexin-A engaged an OX2R-dependent inhibitory programme superimposed on a parallel inward current, whereas orexin-B did not reproduce this inhibitory profile and instead exerted a distinct membrane effect. Chronic stress disrupted this buffering system through coordinated inflammatory activation, promoter methylation and erosion of D-neuron identity and orexin responsiveness. Restoring orexin-A reversed behavioural and molecular deficits through OX2R-dependent suppression of nuclear factor kappa B signalling, preservation of Tet2 expression, and demethylation-linked maintenance of the Ddc programme. Together, these findings define a self-limiting orexin-habenula resilience circuit that enables adaptive coping while constraining stress-induced vulnerability.

neuroscience↗

bioRxiv2025

Synthetic collinearization of a chromosome segment enables genetic dissection of incompatibility between distant genera

Reproductive barriers and genomic structural differences hinder genetic analysis between highly divergent organisms. Here, we examined whether these challenges can be overcome by collinearization, the synthesis of chromosomes that retain the native gene content and organization of a host organism while incorporating the DNA sequences of another organism. We applied collinearization to Kluyveromyces marxianus, a yeast species that is both distantly related to and has a distinct genome structure from the model yeast Saccharomyces cerevisiae. We generated a [~]35-kb K. marxianus DNA segment that was collinear with one-sixth of a S. cerevisiae chromosome and contained 17 protein-coding genes. Although this synthetic chromosome segment successfully substituted for its native counterpart in an S. cerevisiae cell, it imposed a significant growth cost due to the incompatibility of two K. marxianus proteins with the host proteome. We predicted the disrupted protein-protein interactions using AlphaFold and alleviated their cost by supplementing orthologous protein partners from K. marxianus. Furthermore, we completely eliminated the growth cost by replacing the two incompatible K. marxianus genes with their S. cerevisiae orthologs. These findings demonstrate that collinearization can facilitate the creation of chimeric genomes to dissect the genetic basis of incompatibility and traits between organisms that cannot naturally hybridize. They also suggest that hundreds of genetic incompatibilities exist between S. cerevisiae and K. marxianus, reflecting disrupted protein-protein interactions that may be predictable in silico.

synthetic biology↗

bioRxiv2025

Nano-organization of synapses defines synaptic release properties at cortical neuron dendritic spines

Visualization of the submicron organization of excitatory synapses has revealed an unexpectedly ordered architecture consisting of nanocolumns of synaptic proteins that group into nanomodules which scale in number as spine size increases. How these features are related to synaptic function has remained unclear. Here, using super-resolution followed by live-cell line-scan imaging, we find that the size of the smallest miniature calcium and glutamate events are the same, regardless of whether spines have one or two nanopuncta of PSD-95, and that miniature synaptic response in all spines are best fit by a three term Poisson. Two nanomodule spines exhibit more large events without a significant change in event frequency, with the number of the largest events increasing disproportionately. These data support a model where nanomodules define sites of synaptic release and where the nanoarchitecture of synaptic proteins specifies subtypes of excitatory synapses, with increasing numbers of nanomodules increasing coordinated multivesicular release.

neuroscience↗

bioRxiv2022

Neural mechanism of acute stress management by trace aminergic signalling in the lateral habenula

Stress management is a prerequisite for the survival of vertebrates because chronic stress may cause depression and is known to negatively modulate the dopaminergic reward system1. Enhanced excitability of neurons in the lateral habenula (LHb) induced by chronic stress is essential for silencing dopaminergic neurons in the ventral tegmental area (VTA) via GABAergic neurons in the rostromedial tegmental nucleus (RMTg)2-10. However, the effect of acute stress on the LHb-RMTg-VTA pathway is unknown11-14. Here, we show that both aromatic L-amino acid decarboxylase (AADC)-expressing neurons (D-neurons)15 in the LHb and dopaminergic neurons in the VTA are activated by acute stress, whereas GABAergic neurons in the RMTg are not. Selective stimulation of LHb D-neurons and AADC knockdown of these neurons reverse-regulate the RMTg-VTA pathway. Circuit tracing and electrophysiology data demonstrate that trace aminergic signalling by LHb D-neurons directly suppresses RMTg GABAergic neurons. Furthermore, local activation of trace amine-associated receptor 1 (TAAR1; a trace amine receptor) in the RMTg is sufficient to rescue the despair-like behaviour produced by the loss of AADC expression. Our results identify a novel efferent pathway from the LHb to the RMTg whereby trace aminergic signalling allows the brain to manage acute stress by preventing VTA dopaminergic neuron hypoactivity. The TAAR1-mediated trace aminergic signalling in the LHb-RMTg pathway may hold promise as a therapeutic target for stress-mediated psychological diseases.

neuroscience↗