Biology subjects

Huo, C.

Publications and source records attributed to Huo, C..

5 recordsLinked to original sources

bioRxiv2026

Field-Based Characterization of Temporal Interference Stimulation: Beyond the Target-Centric Perspective

Temporal interference (TI) stimulation is a promising non invasive technique for deep brain neuromodulation, yet accurately characterizing its complex and spatially distributed electric fields remains a fundamental challenge. This study proposes a novel computational framework that integrates topological analysis with mesh-aware metrics to overcome the limitations of conventional global field descriptors. The method introduces three interconnected components: (1) connected component , which extracts spatially continuous field regions above thresholds; (2) discrete ellipsoid modeling, which quantifies the geometric centroid, directional spread, and anisotropy of each region; and (3) Local Moran's I to identify robust spatial clusters while suppressing numerical noise. Applied to TI simulations using individualized tetrahedral head models, the framework demonstrates that the few largest connected components above an elevated intensity threshold collectively provide a more accurate representation of the stimulation targets. The approach provides highly interpretable visual outputs that directly map field topology to brain anatomy, including layered component maps, discrete ellipsoids, and spatially weighted clustering landscapes. By offering a topologically coherent, noise robust, and visually intuitive analytical toolbox, this work advances the precision and interpretability of TI field assessment, supporting more reliable target localization, focality quantification, and parameter exploration in translational neuromodulation research.

neuroscience↗

bioRxiv2026

A Pangenome Centralized NLRome Drives Lineage Specific Diversification and Functional Differentiation in Solanoideae

The Solanoideae subfamily comprises numerous economically important crops that deploy a diverse repertoire of nucleotide-binding leucine-rich repeat receptors (NLRs) to defend against pathogens. However, the evolutionary trajectory of these NLR immune receptors remains poorly understood. Here, we dissect NLR family evolution across 23 Solanoideae species by integrating genomic and transcriptomic data. We uncover a distinctive pangenome-centralized architecture wherein a mere 11.56% of soft-core orthogroups contribute 67.81% of the total NLR repertoire, with copy-number variation driven by lineage-specific expansions rather than stochastic distribution or genome size. This finding indicates that Solanoideae plants counteract biotic stress through targeted amplification of specific key families rather than undergoing broad diversification. Phylogenomic analysis resolves NLRs into four subclasses, revealing CC-NLR dominance across all species alongside extreme TIR-NLR degeneration in certain lineages, suggesting profound immune adaptive shifts. Mechanistically, recent NLR expansions are primarily fueled by proximal and tandem duplications, whereas whole-genome duplications contribute in a ploidy- and time-dependent manner, with WGD-derived genes undergoing extensive loss during diploidization. Transcriptional profiling further demonstrates duplication-type-dependent expression patterns, enabling a robust, multilayered defense network upon pathogen infection. Collectively, our study delineates the asymmetric evolutionary trajectory of the Solanoideae NLRome and establishes a framework model that provides new insights into the adaptive evolution of plant immune systems and resistance gene discovery.

genomics↗

bioRxiv2026

Encounter-state over-anchoring governs productive PETase binding on PET surfaces

Polyethylene terephthalate (PET) hydrolysis by Ideonella sakaiensis PETase (IsPETase) begins at a heterogeneous solid-liquid interface, yet the molecular basis of productive surface recognition remains poorly resolved. Here, we combined a Martini 3 coarse-grained PET model with G[o]Martini protein dynamics to investigate IsPETase binding to an extended PET surface. A four-state kinetic model, comprising unbound, encounter, docked, and pre-catalytic states, shows that productive binding is not limited by adsorption itself, but by a post-adsorption re-registration step that converts surface-bound encounter complexes into productively aligned configurations. The simulations reveal a stage-dependent role of conformational flexibility: flexible surface loops facilitate early capture, whereas excessive flexibility promotes misregistered hydrophobic contacts, over-stabilizes non-productive encounter states, and lowers the overall probability of productive commitment. Analysis of productive trajectories further identifies three microscopic reorientation modes by which the enzyme reaches the pre-catalytic state after adsorption. Comparative simulations of engineered PETase variants uncover a flexibility-driven speed-yield trade-off, in which increased flexibility accelerates successful binding events but reduces productive yield through encounter-state over-anchoring. Guided by this mechanism, we formulated a landscape-based design strategy that either weakens encounter-specific anchors or reinforces product-like contacts, leading to mutations that improve productive-binding yield. These results identify post-adsorption alignment as the key kinetic bottleneck in PETase surface recognition and provide a mechanistic framework for designing enzymes that operate at heterogeneous polymer interfaces.

biophysics↗

bioRxiv2024

mTOR inhibition in Q175 Huntington's disease model mice facilitates neuronal autophagy and mutant huntingtin clearance

Huntingtons disease (HD) is caused by expansion of the polyglutamine stretch in huntingtin protein (HTT) resulting in hallmark aggresomes/inclusion bodies (IBs) composed of mutant huntingtin protein (mHTT) and its fragments. Stimulating autophagy to enhance mHTT clearance is considered a potential therapeutic strategy for HD. Our recent evaluation of the autophagic-lysosomal pathway (ALP) in human HD brain reveals upregulated lysosomal biogenesis and relatively normal autophagy flux in early Vonsattel grade brains, but impaired autolysosome clearance in late grade brains, suggesting that autophagy stimulation could have therapeutic benefits as an earlier clinical intervention. Here, we tested this hypothesis by crossing the Q175 HD knock-in model with our autophagy reporter mouse TRGL (Thy-1-RFP-GFP-LC3) to investigate in vivo neuronal ALP dynamics. In the Q175 and/or TRGL/Q175 mice, mHTT was detected in autophagic vacuoles and also exhibited a high level of colocalization with autophagy receptors p62/SQSTM1 and ubiquitin in the IBs. Compared to the robust lysosomal pathology in late-stage human HD striatum, ALP alterations in Q175 models are also late-onset but milder that included a lowered phospho-p70S6K level, lysosome depletion and autolysosome elevation including more poorly acidified autolysosomes and larger-sized lipofuscin granules, reflecting impaired autophagic flux. Administration of a mTOR inhibitor to 6-mo-old TRGL/Q175 normalized lysosome number, ameliorated aggresome pathology while reducing mHTT-, p62- and ubiquitin-immunoreactivities, suggesting the beneficial potential of autophagy modulation at early stages of disease progression.

pathology↗

bioRxiv2024

Unraveling the Interplay between Stability and Flexibility in Design of Polyethylene Terephthalate (PET) Hydrolases

The accumulation of polyethylene terephthalate (PET), a widely used polyester plastic in packaging and textiles, poses a global environmental crisis. Biodegradation presents a promising strategy for PET recycling, with PET hydrolases (PETase) undertaking the task at the molecular level. Unfortunately, due to its low thermostability, PETase can only operate at ambient temperatures with low PET depolymerization efficiency, hindering its practical application in industry. Currently, efforts to engineer PETase have primarily focused on enhancing its thermostability. However, increased stability often reduces the structural dynamics necessary for substrate binding, potentially slowing down the enzymatic activity. To elucidate the delicate balance between stability and flexibility in optimizing PETase catalytic activity, we performed theoretical investigations on both wild-type PETase (WT-PETase) and a thermophilic variant (Thermo-PETase) using molecular dynamics simulations and frustration analysis. Despite being initially designed to stabilize the native structure of enzyme, our findings reveal that Thermo-PETase exhibits an unprecedented increase in structural flexibility at the PET binding and catalytic sites, beneficial for substrate recruitment and product release, compared to WT-PETase. Upon PET binding, we observed that structural dynamics of Thermo-PETase are largely quenched, facilitating subsequent chemical reactions. Compared to WT-PETase, Thermo-PETase forms more extensive interactions with PET, resulting in a higher population of catalytically competent enzyme-substrate states, thus contributing to increased catalytic activity. Our theoretical results are consistent with experimental findings and further suggest that Thermo-PETase exhibits higher catalytic activity than WTPETase across a broad temperature range by leveraging stability and flexibility at high and low temperatures, respectively. Our findings offer valuable insights into how PETase optimizes its enzymatic performance by balancing stability and flexibility, paving the way for future PETase design strategies.

biophysics↗