Biology subjects

Zhao, C.

Publications and source records attributed to Zhao, C..

At least 73 records · Page 4Linked to original sources

bioRxiv2025

Neural Dynamics Underlying Repeated Learning of Visual Image Sequences

Humans possess a remarkable ability to recognize visual objects with high fidelity, supported by complex neural mechanisms underlying memory retrieval. Event-related potential (ERP) studies have identified two key neural signatures of recognition memory: the parietal old/new effect and the frontal old/new effect. Despite extensive research on these ERP components, the extent to which these components reflect distinct memory processes remains debated. In the present study, we investigated how repetitive learning modulates these ERP components. Participants repeatedly studied a fixed list of 32 real-world images across up to five study-test repetitions while EEG was recorded. Additionally, a separate set size 1 condition served as a proxy for working memory. Our results showed that with increased repetitions, the parietal old/new effect exhibited enhanced amplitude and earlier peak latency, reflecting more efficient retrieval of well-learned memories. In contrast, the frontal old/new effect remained unchanged in both amplitude and timing. These findings suggest that the parietal old/new effect is a sensitive neural marker of learning-related changes in long-term memory representations, while the frontal effect is less influenced by repetition. Additionally, despite similarly high accuracy between the well-practiced set size 32 condition and the set size 1 working memory condition, both parietal and frontal old/new effects peaked significantly earlier for set size 1, suggesting that access to working memory is substantially faster than even well-practiced long-term memory. Together, our results highlight the unique role of the parietal old/new effect, but not the frontal old/new effect, in repetitive learning, despite both components being important for successful recognition of learnt visual stimuli.

neuroscience↗

bioRxiv2025

A novel 18F-labeled brain penetrant PET ligand for imaging poly(ADP-ribose) polymerase-1

Poly(ADP-ribose) polymerase-1 (PARP-1) is a key mediator of DNA repair, and its inhibition has become a validated therapeutic strategy in homologous recombination-deficient cancers. However, tools for non-invasive assessment of PARP-1-specific expression remain limited. Here, we evaluated [18F]AZD9574, a next-generation PARP-1-selective PET radiotracer. [18F]AZD9574 was tested in a panel of breast, glioblastoma, prostate, and pancreatic cancer cell lines. Uptake correlated with PARP-1 expression and was dose-dependently blocked by a variety of clinically relevant PARP inhibitors, confirming its binding specificity. In 22Rv1 xenograft mouse models, the tracer demonstrated significant tumor accumulation that was specific to PARP-1, and ex vivo biodistribution confirmed organ uptake consistent with specific tumor binding and PARP-1 expression. Together, these findings establish [18F]AZD9574 as a promising PARP-1-targeted imaging agent with strong potential for advancing cancer research and therapeutic monitoring.

cancer biology↗

bioRxiv2025

A unique neural signature of long-term memory encoding from EEG inter-electrode correlation

Classic memory models proposed that the encoding process involved in visual working memory (VWM) controls the bandwidth of encoding in long-term memory (LTM). Behaviorally, VWM and LTM accuracies are reliably correlated at the behavioral level, raising the question of whether LTM encoding uniquely engages processes that are distinct from VWM encoding. To investigate this, we recorded EEG activity as participants completed recognition memory tasks with set sizes of 32 and 128, far beyond typical VWM capacity. Using interelectrode correlation (IC) analysis, we found that IC patterns reliably predicted individual differences in LTM encoding across both set sizes, indicating a robust, domain-general neural signature. Importantly, this predictive power remained even after controlling for VWM and attentional control performance, suggesting that the model captures variance specific to LTM encoding. Temporally, predictive signals emerged only after stimulus onset and persisted for 500-600 ms. Early and late encoding phases involved distinct network structures, reflecting dynamic neural processes underlying individual differences in LTM encoding. Together, our findings reveal a unique and temporally dynamic neural signature that supports individual differences in LTM encoding, independent of general cognitive abilities. Significance StatementHumans maintain visual information using two distinct memory systems: visual working memory, which is capacity-limited, and long-term memory, which has virtually unlimited capacity. Despite their differences, individuals with better VWM performance often show superior LTM performance, raising the question of whether unique LTM encoding abilities exist beyond those accounted for by VWM. Here, we leveraged EEG data to examine interelectrode correlation patterns during memory encoding. Our results show that these neural patterns uniquely predict individual differences in LTM encoding ability, even after controlling for VWM performance. Furthermore, we showed that the interelectrode correlation patterns continuously track the temporal dynamics of LTM encoding over time.

neuroscience↗

bioRxiv2025

Dissecting Small Noncoding RNA Landscapes in Mouse Preimplantation Embryos and Human Blastoids for Modeling Early Human Embryogenesis

Small non-coding RNAs (sncRNA) exert regulatory functions in mammalian cells; however, their expression dynamics and contribution during preimplantation development are not entirely understood. In this study, we apply Small-Seq to generate a comprehensive single-cell atlas of sncRNA expression in mouse oocytes, sperm, and embryos (2-cell to 64-cell stages), and compare these dynamics with human embryos at equivalent stages. In both species, all sncRNA subtypes are expressed, but only microRNAs (miRNAs) and small nucleolar RNAs (snoRNAs) display cell type-specific patterns. In mice and humans, miRNAs and snoRNAs from the Dlk1-Dio3 locus were upregulated in the inner cell mass (ICM). Human trophectoderm (TE) is enriched with primate-specific C19MC miRNAs, which show relatively low expression in the ICM. In contrast, the mouse lacks a TE-specific hotspot, as C2MC miRNAs are higher in the ICM. Nonetheless, differentiation-associated miRNAs (e.g., miR-24-3p, miR-200c-3p) are high in the TE of both species. Further, we profile the sncRNAs of human blastoids (stem-cell-based embryo model) and determine that they largely recapitulate the human blastocyst. We envision broad utility of this dataset as a resource for future studies seeking to dissect the functions of individual sncRNAs in early development, and for advancing applications in stem cell-based embryo models and assisted reproductive technologies.

developmental biology↗

bioRxiv2025

Arousal increases locus coeruleus blood flow, salience-related brain responses, and modulates negative-valence attentional biases

The amygdala helps prioritize emotional over neutral information. However, it responds similarly to positive and negative stimuli, and so is unlikely to be the source of valence-specific effects within affective networks. We hypothesized that the locus coeruleus (LC) is a key contributor to negative biases in attention. Using ultra-high field 7T magnetic resonance imaging, we tested how arousal modulates processing of emotional faces during an oddball task in twenty-two young adults during two separate sessions. Arousal induced by isometric handgrip increased LC cerebral blood flow and amplified brain responses to target and angry faces, but not to happy faces. The amygdala exhibited valence-general responses that were not modulated by arousal. LC connectivity with the default mode network decreased during processing target and angry faces, and arousal further modulated responses in the salience network and visual cortex. Behaviorally, arousal enhanced recognition of angry faces only when allocating attentional resources and memory performance was linked to left LC brain activity. These findings highlight the LC as a key structure through which arousal shapes valence processing, biases attention, and informs mechanisms related to affective disorders.

neuroscience↗

bioRxiv2025

SLAE: Strictly Local All-atom Environment for Protein Representation

AO_SCPLOWBSTRACTC_SCPLOWBuilding physically grounded protein representations is central to computational biology, yet most existing approaches rely on sequence-pretrained language models or backbone-only graphs that overlook side-chain geometry and chemical detail. We present SLAE, a unified all-atom framework for learning protein representations from each residues local atomic neighborhood using only atom types and interatomic geometries. To encourage expressive feature extraction, we introduce a novel multi-task autoencoder objective that combines coordinate reconstruction, sequence recovery, and energy regression. SLAE reconstructs allatom structures with high fidelity from latent residue environments and achieves state-of-the-art performance across diverse downstream tasks via transfer learning. SLAEs latent space is chemically informative and environmentally sensitive, enabling quantitative assessment of structural qualities and smooth interpolation between conformations at all-atom resolution.

bioinformatics↗

bioRxiv2025

Consistent Induction of Broadly Neutralizing HIV Antibodies by a Novel Two-Step Mechanism Informs Immunogen Design

A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a novel two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.

immunology↗

bioRxiv2025

A Micro-Engineered Heart Tissue Model of Desmin-related Cardiomyopathy Caused by Mutant αB Crystalin

Protein quality control (PQC) is essential for maintaining sarcomere integrity in cardiomyocytes. Crystallin B chain (CRYAB) R120G mutation disrupts CRYABs chaperone activity, leading to aggregation of CRYAB and its client proteins (including Desmin), leading to Desmin-related cardiomyopathy (DRM). Prior experimental systems for modeling DRM linked to CRYAB require massive overexpression of CRYAB mutant isoforms, raising questions about translational relevance. Here, we establish the first model of CRYAB-linked DRM that uses genome-edited hiPSC together with isogenic controls, allowing us to study the impact of mutant CRYAB expressed at near endogenous levels. Within micro-engineered heart tissues (HT), CRYAB-R120G mutant hiPSC-derived cardiomyocytes recapitulated key DRM hallmarks, including Desmin and CRYAB aggregation, contractile dysfunction, and increased vulnerability to PQC pathway inhibition. CRYAB-R120G mutant HT also exhibited dysfunctional calcium-contraction coupling, which exacerbated contractile deficits at higher pacing frequencies. JAK1 inhibition with Itacitinib partially restored contractile function at higher pacing frequencies, suggesting JAK1 inhibition as a viable therapeutic strategy. By preserving human-specific structural and functional features, our {micro}HT platform enables mechanistic characterization of proteotoxic cardiomyopathies and offers a scalable system for targeted drug screening.

bioengineering↗

bioRxiv2025

Dual Targeting of IKKβ and NR4A1 for AML Therapy

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with poor clinical outcomes and limited therapeutic options. Aberrant activation of the IKK{beta}-NF-{kappa}B pathway occurs in approximately 40% of AML cases and contributes to leukemogenesis. However, pharmacological inhibition of IKK{beta} has been limited by serious toxicities, including neutrophilia. Here we identify IKK{beta} and NR4A1 as critical drivers of AML progression in certain models and develop a proteolysis-targeting chimera (PROTAC) capable of degrading the proteins. Although NR4A1 has previously been described as a tumor suppressor in AML, our findings demonstrate that NR4A1 exhibits oncogenic functions in some AMLs of the (pro)monocytic lineage. Notably, elevated expression of IKK{beta} and NR4A1 in AML is associated with poor clinical outcomes, playing non-redundant oncogenic roles in AML. To therapeutically target IKK{beta} and NR4A1, we designed and synthesized a series of celastrol-based PROTACs that exploit celastrols ability to bind both IKK{beta} and NR4A1. Among these compounds, the lead A9 induces potent cytotoxicity in multiple AML cell lines and primary AML samples through cereblon E3 ligase-dependent degradation of IKK{beta} and/or NR4A1. In vivo, A9 suppresses leukemia progression in a KMT2A::MLLT3 AML mouse model without inducing neutrophilia, supporting PROTAC-mediated degradation of IKK{beta} and NR4A1 as a promising therapeutic strategy. Plain language summaryAcute myeloid leukemia (AML) is a predominant form of blood cancer with devastating consequences in both young and adult populations. Despite some advances in AML treatment over the last decade, there is still an unmet medical need to develop new drugs for difficult-to- treat AMLs. We discover that two proteins, namely IKK{beta} and NR4A1, play important roles in promoting the AML disease and could be associated with more severe AML subtypes. To target and destroy those proteins within AML cells, we employ a novel targeted protein degradation approach, which involved design, synthesis, and screening of PROTAC drugs, to discover a drug possessing pronounced AML cell killing activity by virtue of IKK{beta} and NR4A1 degradations. The drug also significantly reduces AML progression in mice without any noticeable adverse effects. Our current efforts involve more comprehensively testing the benefit of the drug (and its analogs) in a wide range of clinically relevant AML models. Key PointsO_LIIKK{beta} and NR4A1 are clinically relevant drivers of AML pathogenesis. C_LIO_LIA novel celastrol-based PROTAC can effectively degrade IKK{beta} and/or NR4A1 to potentially treat AML. C_LI

cancer biology↗

bioRxiv2025

Genome-wide Identification, Structural Features and Single-Cell Expression Atlas of the Carbonic Anhydrase Gene Family in Maize (Zea mays L.)

Maize is a cornerstone C{square} crop underpinning food, feed and bioenergy. Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the interconversion of CO{square} and HCO{square}{square}, underpinning photosynthesis, pH homeostasis and stress acclimation. Despite extensive work on plant CA families, a maize-focused synthesis integrating genome-wide cataloging, structural divergence, regulatory logic, and cell-type specificity is still lacking.Here we present a genome-wide census and a single-cell-resolved expression atlas of the maize CA family. We identified 18 CA genes partitioning into (8), {beta} (5) and {gamma} (5) subfamilies. Proteins span 206-452 aa, pI 6.09-10.58 and 22.67-49.36 kDa, with predominantly hydrophilic profiles. Phylogeny resolved three robust clades (UFboot >90%) and indicated closer affinity to rice than to Arabidopsis; synteny recovered 15 maize-rice and 3 maize-Arabidopsis orthologs. Promoters are enriched for ABRE, TCA-element and ARE, suggesting ABA, SA and redox regulation. Bulk RNA-seq across 21 tissues revealed strong tissue specificity ({tau} >0.7 for 12 genes), with {beta}-CAs elevated in leaves and -CAs in roots. Single-cell analyses further showed Zm{beta}CA3 enriched in mesophyll cells and ZmCA2 enriched in vascular/root-cap cells. Together, these data position {beta}-CAs as chloroplast-centered hubs for C4 photosynthesis, while /{gamma}-Cas support ion/pH buffering and mitochondrial metabolism. We nominate cell-type-specific CA members as candidates for genetic improvement toward stress resilience in maize.

plant biology↗

bioRxiv2025

A Dual-Action Mechanism to Prevent OX40 Signaling: The Structural Basis for the Differentiated Antagonist STAR-0310

Atopic dermatitis (AD) is a chronic inflammatory disease sustained by dysregulated T cell activity. The OX40/OX40L pathway drives effector and memory T cell proliferation, survival, and cytokine production, making it a key therapeutic target. STAR-0310, a novel anti-OX40 antibody, binds a noncanonical epitope that sterically blocks receptor trimerization without inducing agonism. Structural and functional studies demonstrated a dual mechanism: prevention of new OX40/OX40L interactions and efficient disruption of pre-formed complexes, outperforming comparator antibodies. The pure antagonism and complex disruption capacity of STAR-0310 support its clinical evaluation (NCT06782477) as a differentiated OX40-targeted therapy for AD. HighlightsO_LINovel binding mechanism: STAR-0310 engages OX40 distal to the OX40L site, sterically blocking receptor trimerization without inducing agonism. C_LIO_LIDual action: Prevents formation of new OX40/OX40L complexes and efficiently disrupts pre-formed complexes sustaining inflammation. C_LIO_LIDifferentiation from competitors: Achieves greater efficiency in complex disruption compared with rocatinlimab and IMG-007 with no partial agonist activity. C_LIO_LIClinical potential: Pure antagonist profile supports ongoing evaluation of STAR-0310 (NCT06782477) as a best-in-class OX40 therapy for atopic dermatitis. C_LI

pharmacology and toxicology↗

bioRxiv2025

Functional characterization of red-shifted rhodopsin channels from giant viruses explored by a machine-learning model for long-wavelength optogenetics

Channelrhodopsins (ChRs) are light-gated ion channels. These proteins are widely used in optogenetics to optically manipulate neural activity. However, manipulation using short-wavelength light to activate ChRs causes cell toxicity and is hampered by low tissue penetration. To overcome these difficulties, although several red-shifted ChR variants have been identified, further red-shift is required for more efficient and noninvasive neural control. While molecular screening of ChRs requires high-cost experiments, recent machine-learning-based protein functionality prediction enables more efficient selection of target proteins for characterization. Here, we constructed an elastic-net machine-learning model trained on 1,163 experimental data to predict the maximum absorption wavelength ({lambda}max) of uncharacterized ChRs. The model suggested several red-shifted candidates, and we identified a viral rhodopsin channel, ChR024, with the second-longest{lambda} max as a cation-conducting ChR ({lambda}max = [~]578 nm) after Chrimson ({lambda}max = [~]580 nm). This result demonstrates the high impact of ML on reducing the screening costs of functional proteins.

biophysics↗

bioRxiv2025

Assembly of the complete horse genome reveals variants associated with reproduction and temperamental traits

A high-quality horse genome assembly is crucial for genetic analysis of equine. Benefiting from long-read sequencing techniques and trio-binning strategy, we assembled a complete telomere-to-telomere horse genome (T2T-horse 1.0) with a size of 2.80 Gb and a base accuracy of more than 99.9999%, comprising a 34.11-Mb entire Y chromosome. T2T-horse 1.0 filled the gaps and corrected errors in previous assemblies, and added 180.30 Mb of previously unresolved regions and 77 new genes compared with the previous reference genome TB-T2T. We identified five types of centromeric satellites and revealed the features of the horse centromeric regions. We characterized the structure of the Y chromosome, and determined the borders of PAR transposed region, and annotated 59 novel genes on Y chromosome of T2T-horse 1.0. Using SNPs in the X-degenerate region of the Y chromosome of T2T-horse 1.0, we performed selection signatures analysis between indigenous horses and horses from intensively selected breeds, and detected the selected genes ARSF and NLGN4Y, which are closely associated with reproduction and temperamental traits, respectively.

genomics↗

bioRxiv2025

Expanding vaginal microbiome pangenomes via a custom MIDAS database reveals Lactobacillus crispatus accessory genes associated with cervical dysplasia

The vaginal microbiome plays a central role in reproductive health. Vaginal microbiome dysbiosis is associated with many adverse reproductive health outcomes, but most studies have focused on associations at the species level. The potential contribution of intraspecies microbial variation, especially gene content differences across bacterial strains, remains underexplored in reproductive health contexts. The Metagenomic Intra-Species Diversity Analysis (MIDAS) framework enables such analyses but depends on comprehensive reference databases. We constructed a MIDAS-compatible pangenome database from over 18,000 genomes in the Vaginal Microbiome Genome Collection (VMGC). Compared to the Genome Taxonomy Database (GTDB)-derived reference, the VMGC database expanded pangenomes of prevalent vaginal species, better capturing vaginal-specific intraspecies diversity. Applying this database to vaginal samples from a cervical dysplasia cohort, we identified thirteen Lactobacillus crispatus accessory genes significantly associated with cervical dysplasia, including a HicAB toxin-antitoxin system, three transcriptional regulators, and three phage-derived genes. These findings highlight the utility of body site-specific reference resources and shotgun metagenomic sequencing for uncovering intraspecies microbial variation relevant to reproductive health. IMPORTANCEThe vaginal microbiome plays a critical role in reproductive health, and different bacteria from the same species can carry different genes that influence how the strains interact with the host and other microbes. These strain-level differences are often overlooked when microbiomes are analyzed only at the species level. Existing genomic reference databases are heavily biased toward gut and environmental bacteria, leaving the genetic diversity of vaginal microbes understudied. We built a specialized reference database from over 18,000 vaginal bacterial genomes that better reflects this diversity. We then applied this resource to quantify gene-level variation in vaginal samples from a cervical dysplasia cohort. Focusing on Lactobacillus crispatus, a prevalent and often beneficial vaginal species, we identified thirteen genes that were more common in women with cervical dysplasia than in controls. This work demonstrates that body site-specific genomic resources are essential for uncovering strain-level bacterial differences relevant to reproductive health.

microbiology↗

bioRxiv2025

First Molecular Verification of the Cotton Jassid (Amrasca biguttula) in the United States

This report contains the first molecular record of the cotton jassid, Amrasca biguttula (Hemipter: Cicadellidae), in the United States. Nymphs across multiple instars and adult specimens were collected from a cotton (Gossypium hirsutum) field in Macon County, Alabama, in August 2025. While distinct paired dark spots were observed on forewings of adult specimens, this trait was present on wing pads of some nymphs but absent in others. Cytochrome oxidase I (COI) DNA barcoding confirmed the specimen identity. The United States sequence shared > 99% identity with Asian A. biguttula references and clustering placed the sequence within the A. biguttula clade with 100% posterior probability support in phylogenetic analysis. Although this pest was previously reported in 2023 from Puerto Rico based solely on morphological traits, our findings provide the first DNA-confirmed evidence of its presence in the continental United States. Given its well-documented role in damaging cotton across Asia and Africa, this report underscores the urgent need for monitoring and development of management strategies in United States cotton-growing regions.

ecology↗

bioRxiv2025

A Novel 3D Visualization Method in Mice Identifies the Periportal Lamellar Complex (PLC) as a Key Regulator of Hepatic Ductal and Neuronal Branching Morphogenesis

The liver is a complex organ responsible for multiple functions, including metabolism, energy storage, detoxification, bile secretion, and immune regulation. Its highly organized vascular system plays a crucial role in maintaining functional zonation and tissue homeostasis. Within the liver, the hepatic artery, portal vein, hepatic vein, bile duct, and nerve networks intertwine to form an intricate three-dimensional architecture; however, traditional two-dimensional imaging fails to reveal their true spatial relationships, and current three-dimensional imaging methods remain insufficient to capture fine structural details. To achieve comprehensive visualization of these multi-ductal systems, we established a high-resolution three-dimensional imaging platform that combines multicolor perfusion of metallic compound nanoparticles (MCNPs) with an optimized tissue-clearing protocol (Liver-CUBIC), enabling simultaneous 3D reconstruction of the portal vein, hepatic artery, bile duct, and hepatic vein in mouse livers. Based on these data, we identified and defined a previously unrecognized structure located in the outer layer of the portal vein, termed the Periportal Lamellar Complex (PLC). The PLC encircles the portal vein between the vascular endothelium and the perisinusoidal region, exhibits low-permeability barrier characteristics, and contains a distinctive population of CD34Sca-1 endothelial cells. During liver fibrosis, the PLC extends from the portal vein toward the hepatic lobule, forming a structural scaffold that guides bile duct and nerve migration.

developmental biology↗

bioRxiv2025

Single-cell-level response to drought in Sorghum bicolor reveals novel targets for improving water use efficiency

Increasing drought threatens global agriculture, especially in water-limited regions. Sorghum bicolor, a drought-tolerant C4 grass, is a promising bioenergy crop for cultivation on marginal lands, yet its molecular drought responses remain poorly understood. To uncover single-cell-level transcriptional responses to drought, we performed single-nucleus RNA sequencing on mature sorghum leaves under well-watered and drought conditions. We identified major cell types and analyzed differential gene expression across mesophyll, bundle sheath, epidermal, vascular, and stomatal cells. Surprisingly, drought effects on transcriptomes exceeded differences due to cell identity, revealing a shared response across cell types. We leveraged this convergence to identify candidate regulators of drought-responsive gene expression. These findings advance our understanding of sorghum drought adaptation and offer new targets for engineering enhanced water use efficiency in bioenergy crops.

plant biology↗

bioRxiv2025

Network Modeling Predicts How DYRK1A Inhibition Promotes Cardiomyocyte Cycling after Ischemic/Reperfusion Injury

The adult mammalian heart has a limited ability to regenerate lost myocardium following myocardial infarction (MI), largely due to the poor proliferative capacity of cardiomyocytes (CMs). Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a known regulator of cell quiescence, though the mechanisms underlying its function remain unclear. Previous studies have shown that pharmacological inhibition of DYRK1A using harmine induces CM cell cycle re-entry after ischemia/reperfusion (I/R) MI. Here, we developed a computational network model of DYRK1A-mediated regulation of the cell cycle, which predicts how DYRK1A inhibition promotes CM re-entry. To validate these predictions, we tested selective DYRK1A inhibitors and observed robust induction of cell cycle activity in neonatal rat cardiomyocytes (NRCMs). Integrating our network model with bulk RNA-sequencing data from DYRK1A inhibitor-treated NRCMs, we identified E2F1 as a key transcriptional driver of cell cycle gene expression. Finally, we demonstrate that both pharmacological and post-developmental inhibition of DYRK1A enhances heart function and increases CM cycling following I/R MI. Our findings suggest that functional recovery induced by small molecule inhibitor of DYRK1A is mediated by the induction of cycling CMs. One Sentence SummaryInhibition of DYRK1A through LCTB-92 induces cardiomyocyte cycling and improved heart function in a mouse model of ischemic/reperfusion injury.

pharmacology and toxicology↗