Biology subjects

Qu, Z.

Publications and source records attributed to Qu, Z..

At least 19 recordsLinked to original sources

bioRxiv2026

TH1834-Mediated TIP60 Inhibition Protects Against Ischemia/Reperfusion Damage in Human iPSC-Derived Cardiomyocytes and Cardioids

Ischemia/reperfusion injury limits functional recovery after myocardial infarction through mitochondrial dysfunction, oxidative stress, energetic failure, impaired calcium handling, and contractile dysfunction. We previously identified the acetyltransferase TIP60/KAT5 as a maladaptive regulator of post-ischemic cardiac injury and showed that pharmacologic TIP60 inhibition with TH1834 mitigates myocardial infarction injury in mice. Here, we tested whether TH1834 promotes recovery in complementary 2D and 3D human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) and cardioid (hiPSC-CO) models. Maturation-enhanced hiPSC-CMs subjected to hypoxia/reoxygenation (H/R) reproduced key features of ischemia/reperfusion injury, including mitochondrial loss, oxidative stress, cell death, impaired calcium handling, and contractile dysfunction. RNA sequencing further showed activation of stress programs and suppression of oxidative-metabolic pathways. At a non-arrhythmogenic dose, TH1834 inhibited TIP60 acetyltransferase activity, improved post-H/R survival and beating recovery, preserved mitochondrial and myofibrillar integrity, reduced reactive oxygen species, restored calcium transient kinetics, normalized sarcoplasmic reticulum calcium reserve, and improved contraction and relaxation. A central effect of TH1834 was enhancement of metabolic flexibility: following H/R, treatment restored mitochondrial respiratory capacity while simultaneously increasing glycolytic capacity and reserve. Because CM calcium cycling and mechanical work are highly dependent on energetic supply, this recovery of complementary oxidative and glycolytic capacity provides an energetic basis for improved calcium homeostasis and contractile recovery. Transcriptomic analysis supported this phenotype, showing preferential counter-regulation of H/R-induced stress programs and attenuation of persistent HIF1A-ARNT-PDK1 hypoxic metabolic signaling. In 3D hiPSC-COs, TH1834 similarly enhanced mitochondrial respiratory reserve and glycolytic capacity while improving calcium dynamics, contractile performance, beating recovery, and survival. Together, these findings identify enhanced metabolic flexibility as a central feature of TH1834-mediated protection against H/R, linking restoration of energetic capacity to preservation of calcium signaling and contractile function, supporting TIP60 as a therapeutic target for ischemic heart disease.

cell biology↗

bioRxiv2026

ABISS: An Open-Source, Low-Cost Platform for Auditory and Visual Intrinsic Optical Signal Imaging

Defining the boundaries of functional cortical areas is increasingly important for targeted electro-physiology, optical imaging, viral delivery, and circuit manipulation. Intrinsic optical signal imaging (IOSI) provides a rapid and minimally invasive approach for mapping stimulus-evoked cortical activity, but its implementation often requires laboratory-specific combinations of stimulus-generation hardware, experiment-control software, synchronization devices, and data-acquisition systems. These requirements limit accessibility and hinder the use of IOSI as a routine functional mapping tool. Here, we present the Arduino-Based Intrinsic Stimulation System (ABISS), an open-source platform that integrates auditory and visual stimulus generation, trial timing, and image-acquisition triggering into a single programmable device. ABISS generates auditory tone stimuli, VGA-based visual stimuli, and tightly synchronized camera-trigger pulses without requiring a dedicated experiment-control system. Stimulus protocols are also fully modifiable in firmware. Performance was evaluated in auditory and visual cortices of mice. Engineering validation demonstrated accurate stimulus generation and synchronization between stimulus delivery and camera triggering over extended recording sessions. Biological validation showed that ABISS output results in auditory and visual intrinsic signal maps comparable to those obtained using highly specialized or commercial platforms. Together, these findings demonstrate the utility of a low-cost open-source platform for experimental control of intrinsic optical signal imaging. By reducing the technical and financial barriers associated with routine intrinsic optical imaging, ABISS facilitates broader adoption of functional cortical mapping as a tool for improved cortical localization in neuroscience experiments. Significance StatementFunctional cortical mapping is an increasingly important element of neuroscience experimental design as anatomical coordinates alone are often insufficient for defining cortical boundaries in individual animals. Intrinsic optical signal imaging provides an effective solution but traditionally requires specialized hardware, commercial stimulus-generation systems, and laboratory-specific synchronization workflows. We developed ABISS, an inexpensive, open-source platform that integrates auditory and visual stimulus generation with synchronized camera triggering in a single programmable device. ABISS produces functional cortical maps comparable to those obtainable with commercial or specialized systems while substantially reducing hardware complexity and cost. By making intrinsic optical signal imaging more accessible, ABISS lowers the practical barriers for routine functional mapping of the brain and promotes adoption of this important neuroscience technique.

neuroscience↗

bioRxiv2026

Brassinosteroid-auxin crosstalk shapes rice flag leaf angle to boost dense planting yield

Flag leaf angle (FLA) critically determines rice yield potential under dense planting conditions. As two pivotal phytohormones determine rice FLA, the antagonistic interaction between brassinosteroid (BR) and auxin remains largely uncharacterized. We here demonstrate that BR signaling reduces auxin biosynthesis to control FLA via regulating the biosynthesis of secondary cell wall (SCW). Genetic evidence demonstrates OsYUC8 mutants disrupt SCW formation, leading to increased FLA. At the molecular level, the BR-related transcription factor OsBZR1 directly binds to and represses OsYUC8 promoter activity, thereby fine-tuning auxin-mediated SCW biosynthesis. Field evaluations reveal that osbzr1 mutants display optimized flag leaf architecture and improved yield performance under high-density cultivation. Our study not only delineates the antagonistic BR-auxin interaction governing FLA but also establishes a genetic strategy for manipulating crop architecture to maximize yield in dense planting conditions. One-sentence summaryOsBZR1-mediated repression of OsYUC8-driven auxin biosynthesis modulates secondary cell wall formation to optimize flag leaf architecture, providing a genetic strategy for maximizing yield under high-density cultivation.

plant biology↗

bioRxiv2026

Parvalbumin and somatostatin interneurons support distinct computations during auditory scene analysis

Auditory scene analysis requires cortical circuits to preserve target-sound representations while suppressing interference from competing sound sources. Although spatial separation between tar{-}get and masker sounds can substantially improve perception, the inhibitory circuit mechanisms that transform spatial separation into improved target sound representations remain poorly un{-}derstood. Here, we used a multi-speaker auditory environment to present target sounds alone (clean) or together with spatially distributed competing white noise (masked) trials while record{-}ing auditory cortical activity in awake mice. By combining electrophysiology, cell-type-specific optogenetic suppression, and spike-distance-based neural classifiers, we examined how parval{-}bumin (PV) and somatostatin (SST) interneurons contribute to spatial processing in complex auditory scenes. PV and SST interneurons made dissociable, context-dependent contributions. PV suppression broadly altered spatial tuning properties, including tuning width, modulation depth, centroid, and sparseness, and reduced target-sound discriminability under clean condi{-}tions. In contrast, SST suppression produced comparatively modest effects on spatial tuning but selectively impaired neural discrimination only during masked trials thereby weakening the im{-}provement in target discrimination normally associated with spatial release from masking. Thus, the interneuron population that most strongly altered spatial tuning was not the population that most strongly disrupted masked discrimination. This reveals a dissociation between cortical in{-}hibitory mechanisms supporting spatial receptive-field structure and those supporting target-masker segregation. Together, these findings suggest that PV-mediated inhibition refines the fi{-}delity of auditory cortical representations, whereas SST-mediated inhibition enhances separation of simultaneously spatially competing sound sources, providing complementary inhibitory mecha{-}nisms for auditory scene analysis.

neuroscience↗

bioRxiv2026

AI-enabled discovery of small molecules targeting complementary pathways for hair follicle rejuvenation

Hair thinning arises from multi-faceted dysfunction within the hair follicle, driven by both intrinsic cellular pathways and pathways responding to extrinsic hormonal and microenvironmental cues. Here, we present an AI-enabled discovery framework to discover small molecules that promote hair follicle rejuvenation. This framework integrates graph neural networks trained on phenotypic screening data with structure-based virtual screening to prioritize compounds that modulate complementary biological pathways. Through AI-enabled screening, hit-to-lead optimization, and medicinal chemistry, we identified four compounds that increase follicle dermal papilla cell viability, stabilize hypoxia signaling by inhibiting prolyl hydroxylase domain protein 2 (PHD2), and suppress androgen-mediated follicular miniaturization by inhibiting 5-reductases (5-ARs). RNA sequencing analyses confirmed pathway engagement, and functional validation across primary cells and a 3D hair follicle organoid model demonstrated high activity and cellular specificity. The lead compounds were incorporated into a water-based formulation, where they demonstrated robust solubility and combinatorial efficacy to increase sprouting length of follicle organoids. These results establish an AI-enabled platform for discovering multi-pathway modulators of hair follicle rejuvenation.

bioengineering↗

bioRxiv2026

Representations of spatial saliency in auditory cortex are selectively organized through temporal coordination

Selective processing of behaviorally relevant sounds in complex environments requires dynamic modulation of auditory representations. Here, we show that behaviorally relevant sound locations selectively organize auditory cortical activity through temporal coordination rather than changes in firing rate. Using laminar electrophysiology in mice, we recorded activity in primary auditory cortex (A1) activity during a task in which reward was associated with a specific sound location while neutral, non-rewarded sounds were presented across multiple spatial positions. Neurons exhibited increased response reliability, temporal precision, and spike-field coupling to gamma oscillations selectively for sounds presented from behaviorally relevant locations, even when those sounds were unrewarded. These effects were absent during passive listening. Neurons with stronger gamma coupling also had sharper spatial tuning and greater trial-to-trial reliability, linking temporal coordination to representational fidelity. These findings identify gamma-mediated synchronization as a mechanism through which spatial relevance dynamically reshapes auditory encoding.

neuroscience↗

bioRxiv2026

Validation of MHPC512: A Publicly Available Special-Purpose Supercomputer for Molecular Dynamics Simulations of Biomolecular Systems

MHPC512 is a massively parallel, special-purpose supercomputer designed primarily for atomic-level molecular dynamics (MD) simulations of biomolecular systems. It comprises 512 processor units interconnected by a high-speed three-dimensional torus network and employs a custom chip architecture that uses 35-bit fixed-point arithmetic to accelerate computation while controlling precision loss within an acceptable margin. The preprocessor is compatible with GROMACS and AMBER input formats and supports widely used biomolecular force fields (including CHARMM, AMBER, and OPLS/AA), the Neutral Territory method for short-range nonbonded interactions, the k-space Gaussian Split Ewald method for long-range electrostatics, and multiple thermostats, barostats, and integrators. We present a three-tier validation protocol--comparing static energy and virial components, examining ensemble distributions (NVE, NVT, NPT), and evaluating long-time statistical properties--demonstrating that MHPC512 reproduces results consistent with GROMACS and AmberTools. Application examples, including bulk water, dipeptide conformational sampling, folding of fast-folding peptides, membrane-protein systems, lipid self-assembly, and GPCR conformational transitions, further confirm its reliability. MHPC512 has been deployed at multiple supercomputing centers and is publicly accessible, representing a significant advance in high-throughput, large-scale biomolecular MD simulations.

Molecular Biology↗

bioRxiv2026

Reconciling Cooperativity Definition in PROTACs and Molecular Glues: Thermodynamic Dissection into PPI and Ligand Entropic Contributions

Douglass Cooperativity and Ciullis Cooperativity in induced-proximity systems, remains controversial with paradoxes such as path-dependent metrics and apparent universal negative Cooperativity. We noticed that in "partial-embedded" model, a substantial portion of giant ligand remains exposed outside and does not engage with the host proteins force field. It incurs an entropic cost due to the restriction of translational/rotational degrees of freedom. This large, mass-dependent unfavorable ligand entropy penalty normally shifts binding affinity to 104[~]108-fold. ITC thermodynamic cycles analysis confirmed the dramatic entropy loss among reaction pair. This reconciles the conflicting Cooperativity definitions, yielding true path-independent positive PPI Cooperativity from observed entropy loss subtracting ligand entropy penalty. ITC data showed rigid linkers appear superior to flexible linkers with respect to both oral bioavailability and safety profile in PROTAC design. "ligand entropy barrier wall/Cooperativity ladder" pair is not only impact induced-proximity systems but also constitute the physical basis for all biosystems.

biochemistry↗

bioRxiv2026

Molecular Mechanisms Associated With Amelioration Of Radiation Induced Gastrointestinal Mucositis By Compound Kushen Extracts

Radiation induced gastrointestinal mucositis (GIM) is a severe complication of radiotherapy that compromises patient quality of life and treatment efficacy. This study assessed the therapeutic potential and molecular mechanisms of two forms of herbal extracts, Compound Kushen Powder (CKP) and Compound Kushen Injection (CKI) in a rat model of GIM. Administration of either CKP or CKI to irradiated animals significantly reduced the severity of GIM symptoms. Transcriptomic analysis of jejunum and colon mucosa identified candidate mechanisms as well as common pathways between CKP and CKI. CKP modulated innate immune activation and inflammatory signalling, affecting genes such as Socs3 and Tlr4, while CKI promoted tissue repair and oxidative stress resistance through genes including Osm, Epha2, and Stat3. However, both forms of herbal extract enhanced stress response and stimulus regulation in our GIM model. These findings reveal common mechanisms shared by CKP and CKI that suppress symptoms of radiation induced GIM, along with extract specific effects on distinct pathways, acting on different set of genes.

molecular biology↗

bioRxiv2025

Cell size control emerges from the vein-dependent coordinated divisions of distinct cell groups in Drosophila wing

During morphogenesis, cell divisions are precisely regulated in space and time. The biological objectives achieved by such regulation are not fully understood. Here, by applying a newly developed lineage-reconstruction pipeline to Drosophila pupal wing, we reveal that the wing is composed of distinct cell groups that differ in division number, timing, and spatial positioning relative to wing veins. We show that the frequencies of these lineages, together with their initial cell sizes and growth profiles, converge to achieve a highly conserved average cell size. Our data further suggest that distance from veins provides spatial information that biases where distinct lineages arise, and that loss of veins caused by perturbation of EGFR signaling suppresses a specific lineage and disrupts cell-size control. Finally, our results point to a multiscale organization of division patterns, in which vein-associated spatial information is integrated with local neighbor effects in a manner that would mitigate mechanical instability within the tissue. Together, these findings delineate a cell-size control mechanism based on coordinated divisions of distinct cell groups that supports robust morphogenesis and functional tissue design.

developmental biology↗

bioRxiv2025

TUPAD: A Tn5-Mediated, Pre-amplification/Adapter-Dimer-Free Platform for Ultra-Uniform, One-Step PGT Profiling with High Stability and Broad Compatibility

High-throughput sequencing stands as a cornerstone of clinical molecular diagnostics, particularly in preimplantation genetic testing (PGT)--a key application where the selection of chromosomally normal embryos is critical to enhancing in vitro fertilization (IVF) success rates. A fundamental challenge inherent to PGT, however, lies in the ultra-low gDNA input (typically <100 pg) from embryo biopsies. To mitigate this limitation, traditional workflows rely on whole genome amplification (WGA) technologies, such as MDA, PicoPlex, and MALBAC. Yet these WGA-based protocols inherently entail pre-amplification of gDNA prior to standard library construction---a step that introduces significant coverage bias and compromised uniformity. These are intrinsic flaws irreparable by downstream library preparation or bioinformatics analysis, ultimately leading to clinical uncertainty in the interpretation of copy number variations (CNVs). In this study, we developed TUPAD (Tn5-Mediated, Uniform Pre-amplification-free and Adapter-Dimer-Free Library preparation), a transformative technology that bypasses the limitations of traditional WGA. By engineering a novel adapter-dimer-free transposon system, TUPAD enables high-efficiency library construction from as little as 1 picogram (pg) of gDNA. This breakthrough allows for a pre-amplification-free workflow, effectively eliminating the primary source of amplification bias. Compared to existing WGA standards, these advantages are fully retained in embryo biopsy and positive sample testing, TUPAD consistently generates highly uniform library data, significantly enhancing the detection limit and accuracy of CNVs and other genomic variants. Beyond these performance advantages, TUPAD also cuts wet-lab processing time by 50%. Practical validation confirms TUPAD results are stable, reliable, with proven practical utility in PGT testing.

molecular biology↗

bioRxiv2025

PDLIM2 in Lung Adenocarcinoma Metastasis

Human and mouse studies have established the unique PDZ-LIM domain-containing protein PDLIM2 as a common tumor suppressor that is especially vital for suppressing the tumorigenesis and therapeutic resistance of lung cancer, the leading cause of cancer-related deaths among both men and women. However, the role of PDLIM2 in tumor metastasis, the predominant cause of cancer morbidity and mortality, is yet to be determined. Here, we report that PDLIM2 repression was positively associated with the metastasis of human lung adenocarcinoma, the major type of non-small cell lung cancer that accounts for more than 40% of all cases of human lung cancer. Interestingly, PDLIM2 repression was also correlated with oncogenic KRAS and/or TP53 mutations, two common drivers of human lung adenocarcinoma that often co-occur. In mice, in comparison to concurrently inducing mutant KRAS expression and TP53 deletion, additional co-ablation of PDLIM2 significantly increased the number and size of lung adenocarcinomas in the lung, and more importantly, the distant metastasis of lung tumor cells. The increased metastasis was accompanied by decreased anti-tumor immunity and increased pro-tumor inflammation. These data demonstrate the role of PDLIM2 in suppressing lung adenocarcinoma metastasis, thereby improving our understanding of this crucial tumor suppressor and lung cancer. They also provide a useful model for studying metastasis and testing new lung cancer treatments in vivo.

cancer biology↗

bioRxiv2025

Injury-induced nuclear export of RNA-binding proteins drives mRNA stabilization and translation to promote dendrite regeneration

Dendrite regeneration is critical for restoring neuronal connectivity after injury, yet the underlying molecular mechanisms remain poorly understood. Using C. elegans as a model and through a forward genetic screen, we identified the conserved insulin degrading enzyme idr-1 and the RNA-binding protein rbm-42 as key regulators of dendrite regeneration, where idr-1 functions upstream of rbm-42. We further show that ced-7, one of the core components of the phagocytosis pathway, acting down stream of rbm-42, while other components of this pathway dont play significant roles in dendrite regeneration. In addition, we demonstrate that upon injury IDR-1 can promote RBM-42 nuclear export following injury, enabling its dendritic localization. RBM-42, in turn, promotes the translation of ced-7 and facilitates microtubule assembly. In conclusion, our findings define a novel conserved signaling cascade coupling injury-induced nuclear export of RNA binding proteins to local regulation and dendrite regeneration, providing new mechanistic insight into neuronal repair.

neuroscience↗

bioRxiv2025

Synergistic effects of deleting the tyrosine phosphatases Shp1 and Shp2 on megakaryopoiesis and thrombopoiesis in mice

The Src homology 2 (SH2) domain-containing non-transmembrane protein-tyrosine phosphatases 1 and 2 (Shp1 and Shp2) have been implicated in regulating signaling from a variety of receptors and cell types, including the thrombopoietin (Tpo) receptor Mpl in megakaryocytes (MKs) and platelets. We previously showed that deletion of Shp1 and Shp2 in the MK/platelet lineage in mice using the Pf4-Cre transgene/loxP system impairs megakaryopoiesis and thrombopoiesis. However, we also observed unexpected phenotypes including a motheaten-like phenotype in Shp1-deficient mice and severe myelofibrosis in mice lacking both phosphatases. To determine whether these were lineage-specific effects, we utilized the Gp1ba-Cre transgenic mouse to delete loxP-flanked Shp1 and Shp2 in mice. Bone marrow-derived MKs from these mice expressed approximately 20-25% of Shp1 and Shp2, whereas platelets contain 5-10% of each phosphatase compared with controls. Minor MK/platelet defects were observed in mice lacking either Shp1 or Shp2 alone, however mice lacking both Shp1 and Shp2 exhibited macrothrombocytopenia, mild bleeding following tail injury, and impaired GPVI-mediated platelet aggregation and Syk phosphorylation, associated with reduction GPVI and integrin 2 subunit expression. Reduced Shp1 and Shp2 expression resulting in a significant reduction in ploidy, a block in MK maturation and proplatelet-producing MKs. Tpo-mediated Ras/MAPK signaling was reduced in Shp1/2-deficient MKs. Treatment of MKs with structurally distinct Shp2 allosteric inhibitors recapitulated key aspects of the Shp2-deficient phenotype, including aberrant megakaryopoiesis and reduced Mpl signaling. Our study highlights the synergistic functions of Shp1 and Shp2 in the MK/platelet lineage, and identifies Shp2 as a potential therapeutic target in myeloproliferative neoplasms. Key PointsO_LIDeletion of Shp1 and Shp2 in the MK/platelet lineage in mice results in macrothrombocytopenia and minor effects on platelet function. C_LIO_LIDefects can be partially explained by reduced Mpl signaling and aberrant megakaryopoiesis in the absence of Shp2 activity. C_LI

cell biology↗

bioRxiv2025

A Genome-Based Pipeline for Digital Siderophore Typing in Pseudomonas Iron-Interaction Network

Siderophores are key mediators of microbial interactions, especially in iron-limited environments. While traditional experimental methods for siderophore typing are time-consuming and low-throughput, we present a genome-based pipeline for high-throughput digital siderophore typing in Pseudomonas. Our approach integrates profile Hidden Markov Models (pHMMs), substrate-specific motif identification, and co-evolutionary analysis to predict both the structure of pyoverdines and their corresponding uptake receptors from any given Pseudomonas genome. By this approach, we developed pHMM from 94 previously defined receptor groups and validated their accuracy and robustness across 14,230 Pseudomonas genomes. Application of our method to this large dataset demonstrated the potential of our algorithm for identifying both novel "lock-key" receptor groups and previously uncharacterized pyoverdine structures. Notably, our pipeline corrected long-term misclassifications in classical strains and proposed a new reference for the canonical Group III pyoverdine. Furthermore, interaction network analysis supports the observation of distinct siderophore utilization patterns between pathogenic and non-pathogenic strains. This standardized, user-friendly platform offers a robust tool for annotating siderophore behaviors in Pseudomonas and demonstrates the potential of digital siderophore typing in exploring iron-mediated ecology across microbes. Impact statementIron is vital for microbes. In most environments, they secrete diverse siderophores to scavenge iron. The types of siderophores a strain produces and uptakes shape its interactions, from cooperation to cheating and competition; characterizing this is called "siderophore typing." While traditional methods are limited by experimental capacities, our genome-based digital pipeline revolutionizes the process by predicting siderophore structures and receptor types directly from genomes, enabling large-scale analysis of 14,230 Pseudomonas strains. The results reveal novel groups, correct historical misclassifications, and link patterns to pathogenicity, providing a standardized software for ecological studies, antibiotic design, and bioremediation.

microbiology↗

bioRxiv2025

PDLIM2 Repression: A Common Mechanism in Viral Lung Infection

BackgroundPDLIM2, a PDZ-LIM domain-containing protein expressed highest in the lung and immune cells, serves as a unique tumor suppressor and immune modulator, mainly by turning off the activation of the master transcription factors NF-{kappa}B and STAT3. While its role in cancer is established, the involvement of PDLIM2 in viral infection remains unclear. ResultsHere, we analyzed public gene expression data of blood leukocytes, bronchoalveolar lavage cells, and lung tissues from uninfected healthy humans and those infected with the respiratory virus SARS-CoV-2 or influenza. We found that PDLIM2 expression was repressed by viral infection, and notably, this repression correlated with the severity of infectious diseases. Consistently, the expression level of PDLIM2 was negatively associated with NF-{kappa}B and STAT3 activity across a diverse range of cell types, such as macrophages, monocytes, neutrophils, T cells, alveolar type 1 and 2 epithelial cells, airway epithelial cells, and fibroblasts. Accordingly, cells with low PDLIM2 expression exhibited aberrant activation of signaling pathways essential for cellular functions and immune responses. ConclusionsThese findings highlight PDLIM2 repression as a common mechanism underlying human viral infectious diseases and suggest PDLIM2 as a potential biomarker and therapeutic target for disease prognosis, prevention, and treatment.

pathology↗

bioRxiv2025

The Disruption and Normalization of Cortical Language Network Dynamics After Post-Stroke White Matter Disconnection

The human language network undergoes reorganization across different spatiotemporal scales, limited by its fixed structural neurobiological foundations. Although stroke often damages white matter, its effect on temporary language network reorganization is not fully understood. This study examined longitudinal behavioral and resting-state fMRI data from post-stroke patients with exclusive subcortical lesions at three time points: two weeks (n = 38), three months (n = 29), and one year (n = 27). Patients showed mild to moderate language impairments during the acute phase, which improved within three months. The extent of disconnection in several left-hemispheric white matter tracts was negatively associated with language deficits. Healthy controls (HC, n = 25) exhibited domain-segregation dynamics in the cortical language network, limited by the underlying white matter pathways. In patients, severe, state- and track-specific network disruptions were observed in the acute phase, characterized by hypo- and hyper-connectivity and abnormal topological features. As language recovery progressed, connectivity patterns began to return to normal, resembling those of HC, and the domain-segregation dynamics reappeared. These results deepen our understanding of structure-function coupling and indicate significant post-lesional plasticity within the cortical language network.

neuroscience↗

bioRxiv2025

Force Propagation in Active Cytoskeletal Networks

Conventional materials science establishes clear structure-function relationships: grain boundaries modulate strength by blocking dislocations, and defect density limits conductivity through electron scattering. Active matter presents a fundamentally different challenge, components continuously consume energy to generate forces, creating a dual identity as both structural elements and force-generating machines. This material-machine duality raises a fundamental question: which structural parameters govern functional behavior in systems where constituents actively generate forces rather than merely responding to external inputs? Here we demonstrate that percolation is the critical mechanism that transforms active cytoskeletal networks from energy-dissipating materials into work-performing machines. Using light-controlled microtubule-kinesin networks, we show that increasing bundle length from 0.9 {micro}m to 5 {micro}m triggers a percolation transition that enables global force organization. Networks below the threshold remain incapable of performing coordinated work, while networks above it develop correlation lengths exceeding 240 {micro}m, generate 25-fold stronger forces, and extract 1000-fold more mechanical work, powering transport of live cells across 800 {micro}m distances. Network simulations reveal that introducing just 5-10% longer bundles creates a connected component containing 90% of microtubules, establishing the precise threshold that drives this material-to-machine transition. Our findings establish percolation as the fundamental mechanism governing whether active matter systems function as passive materials or as coordinated machines--providing design principles for both synthetic and biological systems. increasing bundle length from 0.9 {micro}m to 5 {micro}m increasing bundle length from 0.9 {micro}m to 5 {micro}m

biophysics↗