Biology subjects

Zhuang, S.

Publications and source records attributed to Zhuang, S..

14 recordsLinked to original sources

bioRxiv2026

Cheetahs Combine Head Pitch Stabilisation with Predictive Yaw Tracking during High-speed Pursuit

Predators pursuing agile prey must coordinate locomotion with rapidly changing visual information, yet how they control head orientation during high-speed terrestrial pursuit remains poorly understood. We reconstructed three-dimensional head, torso, and lure target trajectories from synchronised multi-camera recordings of freely running cheetahs (Acinonyx jubatus) using model-based markerless reconstruction, and propagated reconstruction uncertainty through Monte Carlo analysis. Across 1,373 valid reconstructed pursuit frames, head pitch was more closely aligned with the target than torso pitch, and is tightly stabilised relative to target elevation. Head-on-torso counter-rotation nearly cancelled concurrent torso-pitch rotations, preserving target-relative head pitch despite locomotor oscillations. In yaw, cheetahs predominantly oriented their heads ahead of the target's instantaneous position while maintaining a distinct locomotor heading and continuing to close range. During steady-lateral pursuit, head yaw was best described by a short horizon constant-velocity extrapolation model with a cross-validated median prediction horizon of 45 ms. Together, these findings reveal complementary head orientation strategies during pursuit: robust sagittal stabilisation and predictive lateral tracking keep the head target-referenced while the torso generates a closing trajectory towards intersection.

animal behavior and cognition↗

bioRxiv2026

Hepatobiliary Progenitor-like Reprogramming in Liver Metastases

Metastatic progression requires cancer cells to adapt to the unique constraints of distant organ microenvironments, yet the mechanisms that drive organ-specific adaptations remain poorly understood. Here, we show that the liver actively rewrites metastatic cancer cell identity, driving tumor cells toward a hepatobiliary progenitor-like state. Through integrated transcriptomic, proteomic, metabolomic, and epigenomic analyses of patient-derived rapid-autopsy samples and experimental models, we identify this state as selectively enriched in liver metastases. It is characterized by co-activation of hepatic and biliary/progenitor regulators HNF4A and SOX9 and is observed across multiple epithelial cancers, indicating a conserved response to the hepatic niche. Mechanistically, hepatocyte-derived TGF-{beta} and hypoxia converge to activate a HIF-1-ACLY axis, increasing nuclear acetyl-coenzyme A availability and histone acetylation at hepatic lineage regulatory elements to drive hepatobiliary reprogramming. This coordinated niche-response program can be captured transcriptionally and is associated with inferior overall survival. Disruption of this pathway suppresses hepatic reprogramming and impairs liver metastatic fitness. These findings identify the liver as an active determinant of metastatic cell fate, linking microenvironmental signaling to metabolic and chromatin remodeling programs that enable lineage plasticity. More broadly, they reveal organ-specific reprogramming as a fundamental principle of metastasis and a therapeutic vulnerability in liver metastases.

cancer biology↗

bioRxiv2026

Force-Gated Thrombosis (FGT): A Non-Equilibrium Mechanical Theory of Shear-Induced Blood Clot Initiation

Arterial thrombosis is initiated when mechanical forces in flowing blood exceed the activation thresholds of platelets and von Willebrand factor (vWF). Despite extensive experimental characterization of shear-induced platelet aggregation, a unified theoretical framework that maps hemodynamic forcing onto clot nucleation is lacking. Here we present Force-Gated Thrombosis (FGT), a non-equilibrium mechanical theory that treats thrombus formation as a continuous phase transition driven by an effective mechanical forcing {Sigma} ={sigma} + |{nabla}{sigma}| + {beta}{varepsilon}, which combines local wall shear stress{sigma} , shear gradient |{nabla}{sigma}|, and extensional strain rate{varepsilon} . We introduce a dimensionless Thrombosis Number {Theta} = ({Sigma}/{Sigma}c)(P/P0)m(C/C0)n, which incorporates platelet concentration P and coagulation factor concentration C, and governs the transition between stable flow ({Theta} < 1) and active clot growth ({Theta} > 1). The thrombus density is represented by a scalar order parameter{varphi} whose dynamics follow a Ginzburg- Landau free energy functional. For a simplified stenosed artery we derive an analytic closed-form thrombosis onset criterion and a critical flow rate [Formula], where{delta} is stenosis severity. Linear stability analysis shows that perturbations grow at rate{omega} (k) = {Lambda}({Theta}) - D{varphi}k2, becoming unstable when {Theta} > 1. Near threshold the clot volume fraction scales as{varphi} [~] ({Theta} - 1)1/2, a mean-field critical exponent consistent with Ginzburg- Landau theory. Systematic comparison with fifteen published experimental and computational datasets spanning shear rates from 100 to 15,000 s-1 confirms that FGT correctly predicts the existence, location, and approximate severity of pathological thrombus formation across diverse vascular geometries. The theory provides a quantitative bridge between single-molecule mechanobiology and macroscale clinical thrombosis, and yields experimentally testable predictions distinguishing FGT from purely biochemical models.

biophysics↗

bioRxiv2026

Mid-infrared light produces anti-ageing effects through resonant absorption by living organisms

Aging is commonly viewed as a consequence of cumulative molecular damage and declining stress resilience. However, this perspective overlooks the possibility that aging may primarily arise from an efficiency loss of integrated cellular operation. Here, we show that aging can be systemically prevented by enhancing cellular efficiency using frequency-specific mid-infrared (MIR) light, as revealed by organismal-, cellular- and molecular-level analyses of Caenorhabditis elegans. Remarkably, super-weak 34-THz MIR light ([~]1 W mm-{superscript 2}) prolonged the median lifespan of worms by 60%, delaying aging onset and preventing abrupt "cliff-edge" mortality, without detectable thermal effects. At the cellular level, MIR exposure enhanced global gene transcription in parallel with the establishment of a mitochondrial state of high-efficiency energy metabolism, together preserving youthful cellular homoeostasis during aging. These cellular effects were associated with vibrational modes of phosphate groups in nucleic acids and mitochondrial phospholipids within the 33-35 THz range, providing a frequency-matched molecular context for MIR modulation. Together, our results support an efficiency-first, systemic anti-aging model in which frequency-specific MIR light enhances the integrated kinetic efficiency of cellular systems, spanning gene transcriptional dynamics and mitochondrial bioenergetic flux, rather than the activation of damage-repair or stress-response pathways. These findings advance our understanding of light-matter interactions in living systems and establish a non-biochemical, physical strategy for modulating aging.

biophysics↗

bioRxiv2025

Embodied Intelligence Unlocks Autonomous Microscopy

Advanced microscopy is a cornerstone of modern science, yet its potential is constrained by a reliance on manual operation, which struggles with the complexity and reproducibility of long-term experiments protocols. While scripting offers a degree of automation, it lacks the generalizability to adapt to new samples or dynamic biological events. A fundamental challenge is the absence of an intelligent system that can interpret high-level scientific intent and ground it in the physical actions of the microscope. To bridge this gap, we introduce an Embodied Intelligent Microscope System (EIMS) with hierarchical reasoning structure that reimagines the microscope autonomous control. This system leverages the advanced reasoning of large models to interpret complex user commands and decompose them into actionable steps. To solve the critical grounding problem, we constrain the models output to the feasible action space, effectively serving as the models "hands and eyes" in the physical world. We demonstrate that our system achieves zero-shot generalization on complex, multi-step protocols and successfully automates challenging biological missions requiring expert-level judgment, such as capturing the sparse spatiotemporal events of cell mitosis and locating scatteredly distributed organoids. This work establishes a new paradigm for scientific instrumentation--fusing high-level intent understanding with grounded, dynamic execution--and provides a generalizable framework for deploying embodied intelligence to accelerate autonomous scientific discovery.

bioengineering↗

bioRxiv2025

Skeletal muscle TDP-43 aggregation drives progressive motor dysfunction and neurodegeneration with potential for functional recovery after clearance

Understanding the mechanisms driving TDP-43 pathology is essential for combating amyotrophic lateral sclerosis and other neurodegenerative diseases. To investigate the contribution of skeletal muscle to disease onset, progression, and recovery, we generated an inducible, muscle-specific TDP-43 mouse model. Cytoplasmic aggregation of exgogenous human TDP-43 protein in skeletal muscle led to muscle dysfunction, denervation, motor neuron loss, and dysregulation of mRNA markers related to myogenesis and neuromuscular junction stress at disease early-stage, along with muscle atrophy, neurodegeneration, and fatal motor decline at disease late-stage. Notably, this endogenous TDP-43 propagated from skeletal muscle to the spinal cord and brain, underscoring the vulnerability of the central nervous system to muscle-derived TDP-43 toxicity. Suppression of cytoplasmic TDP-43 in skeletal muscle improved survival and promoted substantial recovery of muscle dysfunction, motor deficits and neurodegeneration. These findings highlight the therapeutic potential of targeting skeletal muscle-derived TDP-43 toxicity as an approach to delaying neurodegenerative disease.

neuroscience↗

bioRxiv2025

Leveraging mRNA platform for the development of vaccines against egg allergy

Food allergy has posed a major global health burden due to the rising prevalence and lack of effective prophylactic strategies. During the past decades, allergen-specific immunotherapy (AIT) has been used as a disease-modifying therapy for food allergic conditions, but due to the long-term treatment duration, poor patient compliance and unexpected adverse reactions, only a minority of patients benefit from AIT therapy. In this proof-of-concept study, using well-established mRNA platform, we developed mRNA vaccine candidates encoding for the major egg white allergen Gal d2 (also known as ovalbumin) and comprehensively evaluated the prophylactic efficacy against anaphylaxis in a Gal d2-induced allergic mouse model. Two vaccine formulations, Gal d2 mRNA vaccine and Gal d2-IL-10 mRNA vaccine, both demonstrated effective ability in preventing the onset of allergic disease, which is largely attributed to the versatilities of mRNA vaccine in eliciting allergen-blocking antibody, shifting Th2 towards Th1 immunity, as well as in generating peripheral tolerance.

immunology↗

bioRxiv2024

Classifying Irritable Bowel Syndrome Using Spatio-Temporal Graph Convolution Networks on Brain fMRI Data

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder marked by abdominal pain and changes in stool consistency or frequency. Recent studies have explored the link between IBS and various cognitive deficits using functional MRI. Despite these efforts, an effective diagnostic or predictive model for IBS remains elusive. This shortfall is twofold: firstly, the sample sizes in these studies are typically small, and secondly, the machine learning or deep learning models currently in use fail to adequately detect the subtle and dynamic pathological changes present in fMRI data for IBS. In this study, we extracted rs-fMRI of 79 subjects with IBS and 79 healthy controls, then put them into spatio-temporal graph convolution network (ST-GCN) for classification. We also incorporated a novel interpretability module into this model to identify potential regions of interest (ROI) associated with IBS. Our model outperformed other state-of-the-art ML and DL methods with the highest average accuracy of 83.51% on our dataset. Furthermore, based on the results of our interpretability module, the Inferior Parietal Lobule (IPL.R), Inferior Frontal Orbital part (ORBinf.R), Postcentral Gyrus (PCG.R), Middle Frontal Orbital part (ORBmid.R), and Superior Medial Frontal Orbital part (ORBsupmed.L) were identified as top 5 important brain regions for distinguishing IBS patients from the control group, which are consistent with the brain regions identified in previous literature reviews. We also conducted an external data-driven experiment to further validate the effectiveness of the interpretability module. The results indicate that the selected regions significantly impact IBS.

bioengineering↗

bioRxiv2024

Metastatic organotropism in small cell lung cancer

Metastasis is the leading cause of cancer-related deaths, yet its regulatory mechanisms are not fully understood. Small-cell lung cancer (SCLC) is the most metastatic form of lung cancer, with most patients presenting with widespread disease, making it an ideal model for studying metastasis. However, the lack of suitable preclinical models has limited such studies. We utilized rapid autopsy-derived tumors to develop xenograft models that mimic key features of SCLC, including histopathology, rapid and widespread development of metastasis to the liver, brain, adrenal, bone marrow, and kidneys within weeks, and response to chemotherapy. By integrating in vivo lineage selection with comprehensive bulk and single cell multiomic profiling of transcriptomes and chromatin accessibility, we identified critical cellular programs driving metastatic organotropism to the liver and brain, the most common sites of SCLC metastasis. Our findings reveal the key role of nuclear-cytoskeletal interactions in SCLC liver metastasis. Specifically, the loss of the nuclear envelope protein lamin A/C, encoded by the LMNA gene, increased nuclear deformability and significantly increased the incidence of liver metastasis. Human liver metastases exhibited reduced LMNA expression compared to other metastatic sites, correlating with poorer patient outcomes and increased mortality. This study introduces novel preclinical models for SCLC metastasis and highlights pathways critical for organ-specific metastasis, offering new avenues for the development of targeted therapies to prevent or treat metastatic disease.

cancer biology↗

bioRxiv2023

CRISPR-HOLMES-based NAD+ detection

Studies have indicated that intracellular nicotinamide adenine dinucleotide (NAD+) level is associated with the occurrence and development of many diseases. While traditional NAD+ detection techniques are time-consuming and may require large and expensive instruments. We recently found that the CRISPR-Cas12a protein can be inactivated by AcrVA5-mediated acetylation and reactivated by CobB, using NAD+ as the co-factor. Therefore, here in this study, we created a CRISPR-Cas12a-based one-step HOLMES(NAD) system for rapid and convenient NAD+ detection with the employment of both acetylated Cas12a and CobB. In HOLMES(NAD), acetylated Cas12a losses its trans-cleavage activates and can be reactivated by CobB at the presence of NAD+, cutting ssDNA reporters to generate fluorescence signals. HOLMES(NAD) shows both sensitivity and specificity in NAD+ detection and can be used for quantitative determination of intracellular NAD+ concentrations. Therefore, HOLMES(NAD) not only provides a convenient and rapid approach for target NAD+ quantitation but also expands the application scenarios of HOLMES to non-nucleic acid detection.

molecular biology↗

bioRxiv2023

SonoPrint: Acoustically Assisted Volumetric 3D Printing for Composites

Advancements in additive manufacturing in composites have transformed various fields in aerospace, medical devices, tissue engineering, and electronics, enabling fine-tuning material properties by reinforcing internal particles and adjusting their type, orientation, and volume fraction. This capability opens new possibilities for tailoring materials to specific applications and optimizing the performance of 3D-printed objects. Existing reinforcement strategies are restricted to pattern types, alignment areas, and particle characteristics. Alternatively, acoustics provide versatility by controlling particles independent of their size, geometry, and charge and can create intricate pattern formations. Despite the potential of acoustics in most 3D printing, limitation arises from the scattering of the acoustic field between the polymerized hard layers and the unpolymerized resin, leading to undesirable patterning formation. However, this challenge can be addressed by adopting a novel approach that involves simultaneous reinforcement and printing the entire structure. Here, we present SonoPrint, an acoustically-assisted volumetric 3D printer that produces mechanically tunable composite geometries by patterning reinforcement microparticles within the fabricated structure. SonoPrint creates a standing wave field that produces a targeted particle motif in the photosensitive resin while simultaneously printing the object in just a few minutes. We have also demonstrated various patterning configurations such as lines, radial lines, circles, rhombuses, quadrilaterals, and hexagons using microscopic particles such as glass, metal, and polystyrene particles. Furthermore, we fabricated diverse composites using different resins, achieving 87 microns feature size. We have shown that the printed structure with patterned microparticles increased their tensile and compression strength by [~]38% and [~]75%, respectively.

bioengineering↗

bioRxiv2021

Reversible regulation of Cas12a activities by AcrVA5-mediated acetylation and CobB-mediated deacetylation

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated (Cas) system protects bacteria and archaea from the invasion of foreign genetic elements. To cope with the host CRISPR systems, phages have evolved many strategies, including the anti-CRISPR (Acr) proteins, to inactivate the Cas nucleases. Recently, it has been reported that the type V-A Cas12a effector can be acetylated and inactivated by AcrVA5, which is a GNAT-family acetyltransferase. However, it is unclear whether the host has any coping strategies to reactivate the defense system. Here we show that the AcrVA5-acetylated Cas12a can be deacetylated by bacterial deacetylase CobB, reactivating Cas12a for both in vitro cleavage of target DNA sequences and in vivo protection of the host from invasion of foreign nucleic acids. Therefore, this study not only shows the reversible regulation of Cas12a activities by post-translational modification but also reveals CobB as a secondary safeguard to bacterial CRISPR defense systems. In addition, we demonstrate that AcrVA5 is a wide-spectrum acetyltransferase, acetylating a large number of target proteins besides Cas12a, and the AcrVA5-acetylated targets can also be deacetylated by CobB.

molecular biology↗

bioRxiv2020

Sequence Characterization and Molecular Modeling of Clinically Relevant Variants of the SARS-CoV-2 Main Protease

The SARS-CoV-2 main protease (Mpro) is essential to viral replication and cleaves highly specific substrate sequences, making it an obvious target for inhibitor design. However, as for any virus, SARS-CoV-2 is subject to constant selection pressure, with new Mpro mutations arising over time. Identification and structural characterization of Mpro variants is thus critical for robust inhibitor design. Here we report sequence analysis, structure predictions, and molecular modeling for seventy-nine Mpro variants, constituting all clinically observed mutations in this protein as of April 29, 2020. Residue substitution is widely distributed, with some tendency toward larger and more hydrophobic residues. Modeling and protein structure network analysis suggest differences in cohesion and active site flexibility, revealing patterns in viral evolution that have relevance for drug discovery.

molecular biology↗

bioRxiv2020

Dynamics of replication origin over-activation

We determined replication patterns in cancer cells in which the controls that normally prevent excess replication were disrupted ("re-replicating cells"). Single-fiber analyses suggested that replication origins were activated at a higher frequency in re-replicating cells. However, nascent strand sequencing demonstrated that re-replicating cells utilized the same pool of potential replication origins as normally replicating cells. Surprisingly, re-replicating cells exhibited a skewed initiation frequency correlating with replication timing. These patterns differed from the replication profiles observed in non-re-replicating cells exposed to replication stress, which activated a novel group of dormant origins not typically activated during normal mitotic growth. Hence, disruption of the molecular interactions that regulates origin initiation can activate two distinct pools of potential replication origins: re-replicating cells over-activate flexible origins while replication stress in normal mitotic growth activates dormant origins.

genomics↗