Biology subjects

Liu, H.-L.

Publications and source records attributed to Liu, H.-L..

7 recordsLinked to original sources

bioRxiv2026

A multiscale cytoskeletal network model for shear rheological property and its evolutionary mechanism

The cytoskeleton is a dynamic biopolymer network whose shear rheological properties are crucial for cellular physiology and pathology. However, its mechanical behavior spans multiple spatiotemporal scales, and the coupling of dynamic remodeling and viscoelastic dissipation mechanisms poses a challenge for traditional models to comprehensively capture complex cellular responses. This study aims to establish a multiscale cytoskeletal network model that integrates the bio-chemo-mechanical properties of local linked proteins, the viscoelasticity of actin filaments, and their deformation states. Developing a boundary-modified finite element method with an incremental iterative algorithm, we demonstrated the dynamic remodeling of network and the resultant rheological properties of cytoskeleton by extending the predictive time scale to one thousand seconds. The results not only reproduced the short- and intermediate-term power-law creep behavior and long-term strain plateau response of the cytoskeletal network observed in shear rheological experiments, but also indicate that the synergy among the chemo-mechanical coupling of cross-linked proteins and the bending-to-tension transition of actin filaments govern both the network remodeling and its power-law response evolutionary, whereas the steady-state properties of actin filaments determine the long-term network behavior. Simulations of cancerous and drug effects show that cancer-induced softening and reduced filament viscosity lead to accelerated cytoskeletal responses and decreased apparent shear modulus, respectively; and drug-enhanced filament prestress, along with promoting association or inhibiting dissociation of cross-linked proteins, can effectively increase the steady-state shear modulus. These findings advance the understanding of the spatiotemporal evolution and pathological mechanisms of cellular mechanical responses and provide insights for regulating polymer network performance.

biophysics↗

bioRxiv2025

StCEL-based platform enables detection and sequencing of native sialoglycoRNA

Glycosylated RNAs (glycoRNAs) are an emerging class of biomolecules characterized by glycans attached to RNA molecules. Currently, glycoRNA detection remains largely confined to cellular models, substantially impeding its functional characterization and clinical translation. Here, we developed sialyltransferase-mediated chemical enzymatic labeling (StCEL), in which azido-modified sialic acid was transferred to the natural sialic acid on sialoglycoRNA, enabling the detection of native sialoglycoRNA across diverse biological samples with high specificity and sensitivity. Using StCEL, we found that sialoglycoRNA was significantly upregulated in multiple cancer types. StCEL combined with a microplate reader was applied to detect sialoglycoRNA in large-scale samples, revealing that elevated sialoglycoRNA levels correlate positively with tumor malignancy and poor patient prognosis. Furthermore, StCEL-based sialoglycoRNA enrichment and sequencing identified dysregulated sialoglycoRNAs in tumor tissues. Collectively, StCEL establishes a multifunctional platform that enables sensitive and specific detection of sialoglycoRNA, alongside sequencing analysis, demonstrating significant potential for clinical translation.

molecular biology↗

bioRxiv2025

Comprehensive Infectome Analysis Reveals Diverse Infectious Agents with Zoonotic Potential in Wildlife

Understanding wildlife-pathogen interactions is crucial for mitigating zoonotic risk. Through meta-transcriptomic sequencing we profiled the infectomes of 1,922 samples from 67 mammalian species across China, uncovering a remarkable diversity of viral, bacterial, fungal, and parasitic pathogens. Of the 195 pathogens identified, 62 were novel, including a bi- segmented coronavirus in diseased lesser pandas, which we propose represents a new genus - Zetacoronavirus. The orders Carnivora and Rodentia exhibited the highest pathogen diversity and were implicated in numerous host-jumping events. Comparative analysis of diseased versus healthy animals revealed a trend of higher pathogen loads in the former, with possible differences in tissue tropisms. In total, 48 zoonotic and 17 epizootic pathogens were identified, with frequent cross-species transmission, emphasizing the potential for emerging public health threats. This study highlights the urgent need for wildlife pathogen surveillance to inform proactive disease management strategies.

microbiology↗

bioRxiv2024

Non-Invasive Brain Mapping Localizes Essential Language Function in Surgical Glioma Patients

IntroductionGlioma patients with tumors near critical language regions present significant clinical challenges. Surgeons often lack the tools to understand how each unique surgical approach may impact linguistic ability, leading to subjective decisions and unpredictable outcomes. ObjectiveWe aim to develop an approach that uses data-driven preoperative brain mapping to quantitatively predict the impact of planned resections on long-term language function. MethodsThis study included 79 consecutive patients undergoing resection of language-eloquent gliomas. Patients underwent preoperative navigated transcranial magnetic stimulation (nTMS) language mapping to identify language-positive sites ("TMS points") and their associated white matter tracts ("TMS tracts") as well as formal language evaluations pre and postoperatively. The resection of regions identified by preoperative mapping was correlated with persistent postoperative language deficits (PLDs). ResultsThe resection of TMS points did not predict PLDs. However, a TMS point subgroup defined by white matter connectivity significantly predicted PLDs (OR=8.74, p<.01) and exhibited a canonical group-level anatomical distribution of cortical language sites. TMS-derived tracts recapitulated normative group-level patterns of white matter connectivity defined by the Human Connectome Project (HCP). Subcortical resection of TMS tracts predicted PLDs independently of cortical resection (OR=60, p<.001). The resected TMS tract segments in patients with PLDs co-localized with normative, language-associated subcortical pathways, in contrast to the resected TMS tract segments in non-aphasic patients (p<.05). Accordingly, resecting patient- specific co-localizations between TMS tracts and normative tracts in native space predicted PLDs with an accuracy of 94% (OR=134, p<.001). Co-localization between individualized and normative tracts precisely predicted the linguistic performance of a patient intraoperatively in response to direct electrophysiological stimulation of subcortical brain. ConclusionThis study outlines a data-driven brain mapping approach that provides surgical insight by preoperatively predicting the impact of individual glioma resection on long-term language function. Key PointsO_LIWhite matter connectivity determines the long-term functionality of cortical language sites mapped by TMS. C_LIO_LILong-term deficits in language processing result from resecting individualized subcortical regions within language-associated white matter tracts. C_LIO_LINon-invasive TMS language mapping combined with routine preoperative imaging can predict language outcomes of individual surgical approaches with an accuracy of 94%. C_LI

neuroscience↗

bioRxiv2024

A site-wise reliability analysis of the ABCD diffusion fractional anisotropy data, impact of the scanner and analytical pipeline

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce non-biological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation coefficients (ICC). We developed a site-wise adaptive ICC (AICC) to evaluate the reliability of imaging-derived phenotypes while accounting for ongoing brain development. AICC iteratively estimates the population-level age-related brain development trajectory using a weighted mixed model and updates age-corrected site-wise reliability until convergence. We evaluated the test-retest reliability of regional fractional anisotropy (FA) measures from diffusion tensor imaging and cortical thickness (CT) from structural MRI data for each site. The mean AICC for 20 FA tracts across sites was 0.61{+/-}0.19, lower than the mean AICC for CT in 34 regions across sites, 0.76{+/-}0.12. Remarkably, sites using Siemens scanners consistently showed significantly higher AICC values compared to those using GE/Philips scanners for both FA (AICC=0.71{+/-}0.12 vs 0.46{+/-}0.17, p<0.001) and CT (AICC=0.80{+/-}0.10 vs 0.69{+/-}0.11, p<0.001). These findings demonstrate site-and-scanner related variations in data quality and underscore the necessity for meticulous data curation in subsequent association analyses.

neuroscience↗

bioRxiv2021

Multiscale mechanical models of DNA nanotubes: A theoretical basis for the design and tuning of DNA nanocarriers

DNA nanostructures are one of potential candidates for drug carriers due to their good biocompatibility and non-specificity in vivo. A reliable prediction about mechanical properties of artificial DNA structures is desirable to improve the efficiency of DNA drug carriers, however there is only a handful of information on mechanical functionalities of DNA nanotubes (DNTs). This paper focuses on quantifying the multiscale correlations among DNT deformation, packaging conditions and surrounding factors to tune mechanical properties of DNTs. By combining WLC statistical mechanics model, Parsegians mesoscopic liquid crystal model and Eulers continuum beam theory, we developed a multiscale DNA-frame model; then theoretically characterize the initial packed states of DNTs for the first time, and reveal the diversity mechanism in mechanical properties of DNTs induced by interchain interactions and initial packed states. Moreover, the study of parameters, such as packaging conditions and environmental factors, provides a potential control strategy for tuning mechanical properties of DNTs. These conclusions provide a theoretical basis for accurately controlling the property and deformation of DNT in various DNT dynamic devices, such as DNA nanocarriers.

biophysics↗

bioRxiv2019

CsHscB as a novel TLR2 agonist from carcinogenic liver fluke Clonorchis sinensis modulates host immune response

Clonorchis sinensis-a fluke dwelling on the intrahepatic bile ducts causes clonorchiasis. During C. sinensis infection, worm-host interaction results in activation of PRRs and further triggers immune responses which determine the outcome of infection. However, the mechanisms by which pathogen-associated molecules patterns from C. sinensis interacted with TLRs were poorly understood. In the present study, we identified a [~]34 kDa lipoprotein CsHscB from C. sinensis which physically bound with TLR2. We also found that recombinant CsHscB (rCsHscB) potently activated macrophage to express various proteins including TLR2, CD80, MHCII, and cytokines like IL-6, TNF-, and IL-10 in a TLR2-dependent manner but rCsHscB failed to induce IL-10 in macrophages from Tlr2-/- mice. Moreover, ERK1/2 activation was required for rCsHscB-induced IL-10 production in macrophages. In vivo study revealed that rCsHscB triggered a high induction of IL-10 in the wild-type (WT) but not in Tlr2-/- mice. Our data thus demonstrate that rCsHscB from C. sinensis is an unidentified TLR2 agonist with immune regulatory activities, and may have some therapeutic implications in future beyond parasitology.

immunology↗