Biology subjects

Sun, H.

Publications and source records attributed to Sun, H..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Neural mechanisms of impaired self-compassion in depressed adolescents during social exclusion

Background: Self-compassion has shown to be an effective emotion regulation strategy, but its neural mechanisms remain understudied in adolescents with depression who suffer from social exclusion. This study employed event-related potentials to investigate the psychophysiological mechanisms underlying impaired self-compassion in adolescents with depression during social exclusion. Methods: Thirty-seven adolescents with major depressive disorder (age = 16.46 +/- 2.02) and thirty-two demographically matched healthy controls (age = 16.54 +/- 2.29) completed a social exclusion scenario imagination task. This task presented participants with social exclusion scenarios, asking them to imagine themselves as the excluded individual and subsequently rate their negative emotions. The regulation session required participants to use self-compassionate statements to regulate their emotional responses while imagining and rate how much self-compassion they have engaged in; the non-regulation required them not to use those statements and rate their negative emotions immediately following imagination. EEG signals were recorded during the task, and the late positive potential (LPP) was analyzed to examine the neural responses associated with self-compassion regulation following social exclusion. Results: Compared with the non-regulation condition, both groups showed less negative emotion during the self-compassion regulation condition. Adolescents with depression exhibited significantly lower self-compassion ratings than healthy controls, and showed a significantly smaller decrease in negative emotions. Higher self-compassion ratings were correlated with greater emotion regulation effect, particularly in adolescents with depression. Furthermore, LPP amplitudes were significantly higher in adolescents with depression than in healthy controls during both regulation and non-regulation conditions. Conclusions: Adolescents with depression were characterized by impairment in using self-compassion to downregulate negative emotions when confronted with social exclusion. LPP amplitudes were consistently elevated in adolescents with depression, underscoring their potential as a critical focus for psychophysiologically-informed therapies.

neuroscience↗

bioRxiv2026

Phagocytic activity of perivascular cell promotes CNS injury pathology

Injury, stroke, and neurological diseases cause persistent accumulation of cellular debris that deteriorates lesion microenvironment and impedes central nervous system (CNS) repair. Debris clearance in the injured CNS has long been attributed primarily to microglia and infiltrating macrophages. Here, we identify perivascular cells as previously unrecognized phagocytes that expand after injury and exhibit robust phagocytic activity. Perivascular cell phagocytosis is conserved across multiple mouse models of CNS injury and human stroke lesions. These cells exhibit key hallmarks of phagocytosis, including LC3-associated phagocytosis for efficient lysosomal degradation. Mechanistically, phosphatidylserine serves as the eat-me signal and Axl mediates myelin debris uptake. Myelin phagocytosis drives perivascular cell proliferation, fibrosis and lesion progression. Genetic deletion of Axl in perivascular cells or pharmacological inhibition with the FDA-approved Axl inhibitor Gilteritinib reduces pathology and improves functional recovery after spinal cord injury. Together, these findings establish Axl-dependent perivascular cell phagocytosis as a therapeutic target for CNS repair.

neuroscience↗

bioRxiv2026

An integrated single-cell atlas of human lung across the lifespan

The healthy adult lung is largely quiescent but can respond to injury and replace damaged or lost cells. However, the identities and origins of regenerative cell states remain poorly understood. Here we present the Human Developmental Lung Cell Atlas (HDLCA), a curated single-cell reference atlas of the respiratory system across the lifespan, integrating 253 datasets from 225 studies, and comprising over 18 million cells from 3,198 samples and 2,460 individuals across 34 anatomical locations in both health and disease. The HDLCA defines 142 consensus lung cell types, including 13 rare and 8 previously undescribed ones. Notably, we identify a rare intermediate alveolar epithelial progenitor (Int AP) population in normal lungs, with transcriptional signatures shared by alveolar type 2 (AT2) and alveolar type 1 (AT1) cells. Trajectory inference indicates that Int AP cells arise from both AT2 and SCGB1A1+ secretory cells and give rise to AT1 cells, with Hippo-YAP/TAZ signalling governing lineage specification. Int AP cells are associated with genetic susceptibility to idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, and their dysfunction may contribute to abnormal alveolar repair and regenerative failure in both diseases. The HDLCA provides a unified atlas-level reference for mapping respiratory cellular diversity, uncovering reparative cell dynamics and informing regenerative and cell-based therapeutic strategies.

bioinformatics↗

bioRxiv2026

RBM6-mediated alternative splicing facilitates the adaptation of Eurasian avian-like H1N1 swine influenza virus

The Eurasian avian{square}like (EA) H1N1 swine influenza virus (SIV), derived from avian influenza viruses (AIV), poses a serious threat to public health due to its capacity for cross{square}species transmission and pandemic emergence. The molecular determinants underlying its replication advantage over AIV remain poorly defined. Here, we identify RNA{square}binding motif protein 6 (RBM6) as a novel host factor that differentially regulates the replication of EA H1N1 SIV and AIV. Mechanistically, RBM6 binds to the critical M901 site of the viral M segment, thereby modulating RNA splicing. Substitution of M901C with M901T markedly reduced RBM6 binding, impaired M segment splicing, and attenuated viral replication both in vitro and in vivo. Conservation analysis revealed that M901T is common in avian strains, whereas M901C is predominantly maintained in swine strains, underscoring M901C as a determinant of swine adaptation. Complementation experiments further demonstrated that swine RBM6, but not avian RBM6, restored EA H1N1 SIV replication. Taken together, our findings uncover a previously unrecognized role of RBM6 in shaping influenza virus replication and highlight the RBM6-M901C axis may serve as potential targets for controlling influenza virus adaptation and interspecies transmission.

microbiology↗

bioRxiv2026

Host insect microRNAs are translocated to an obligate endosymbiont

Many insects rely on intimate interactions with bacterial symbionts housed in specialized cells called bacteriocytes. While host and symbiont gene expression in bacteriocytes appears highly integrated, the underlying regulatory mechanisms remain largely unknown. MicroRNAs regulate gene expression and are emerging as mediators of cross-kingdom communication. Here, in the pea aphid, Acyrthosiphon pisum, and the green peach aphid, Myzus persicae, we demonstrate cross-kingdom translocation of aphid miRNAs into their obligate endosymbiont, Buchnera aphidicola. miRNA fluorescence in situ hybridization in aphid embryos provides direct evidence that four out of five candidate miRNAs (miR-1, miR-10, miR-29, and miR-927) localize inside Buchnera cells. To investigate how these miRNAs may regulate Buchnera gene expression, we further demonstrated the cross-kingdom translocation of aphid argonuate 1 protein (Ago1), into Buchnera using immunolocalization. Given the translocation of both Ago1 and miRNAs, we applied a eukaryotic miRNA target prediction framework and found that all cross-kingdom-translocated miRNAs are predicted to target Buchnera genes involved in symbiotic functions. Although the precise in vivo functions of translocated miRNAs remain challenging to determine, our findings suggest a previously unrecognized layer of regulation between insect host and its obligate endosymbiont, offering new insight into the molecular dialogue that supports insect-microbe interactions, highlighting potential targets for miRNA-based pest management. Significance statementMany insects have evolved bacteriocyte cells to house essential bacterial endosymbionts. However, how bacteriocytes are specified and how gene expression is coordinated between host and symbiont remain largely unknown. Here, we identify that aphid microRNAs, along with an argonaute protein, are translocated into the obligate bacterial endosymbiont Buchnera, revealing a previously unrecognized regulatory layer mediating host and obligate endosymbiont interactions. This discovery provides evidence of miRNA cross-kingdom movement into an obligate endosymbiont, filling a key knowledge gap in how eukaryotic host small RNAs can influence microbial partners. Given the critical role of Buchnera in aphid survival and reproduction, these findings not only advance fundamental knowledge of insect-microbe interactions but also point to new molecular targets for innovative pest management strategies.

evolutionary biology↗

bioRxiv2026

A Promoter Competition Hub Orchestrates Runx1 Alternative Promoter Usage during Skeletal Muscle Stem Cell Activation

Alternative promoter (AP) usage profoundly expands transcriptomic and proteomic diversity, yet the regulatory principles governing promoter choice remain poorly understood. Here, using the dual-promoter Runx1 locus as a paradigm in skeletal muscle stem cells (MuSCs), we uncover a promoter competition hub that orchestrates AP selection during MuSC fate transition from activation to proliferation. We find antagonistic expression dynamics between the two Runx1 promoters, with the primary promoter (PP) active in the early activating stage and the secondary promoter (SP) induced later in proliferation. Combinatorial genetic perturbations in vitro and in vivo establish the non-redundant roles of PP- and SP-derived isoforms in MuSC lineage progression. Mechanistically, we find that PP and SP engage in reciprocal competition in a multi-connected enhancer-promoter (E-P) loop hub. Further dissection identifies a cohort of key enhancers that dynamically interact with PP/SP to orchestrate the competition. Moreover, we establish the transcription factor USF1 as a key factor driving the dynamic E-P interactions and PP/SP competition. Beyond Runx1, high-resolution Micro-C reveals promoter competition as a general mechanism regulating a subset of AP choices in MuSC activation/proliferation. Collectively, our study uncovers a dynamic promoter competition hub that governs AP selection in MuSC lineage progression, offering fundamental insights into how 3D genome architecture coordinates precise, stage-specific gene expression programs during cell fate transitions.

genetics↗

bioRxiv2026

Mechanically induced pre-mitotic nuclear deformations promote nuclear rupture through lamin B1 depletion

Disassembly of the nuclear lamina is essential for successful mitosis in eukaryotic cells, but the mechanism that triggers the lamina breakdown remains unclear. Using 3D fluorescence microscopy imaging combined with 3D curvature analysis, we found that microtubule-dependent invaginations trigger lamina remodelling and lamin B1 network disruption. Monte Carlo simulations provide mechanistic insight into how those invaginations induce a mechanical discontinuity between isotropic expansion and anisotropic shrinking forces at the rim of the nucleus, which correlated with lamin B1 depletion sites and the location of cytoplasmic protein influx within the nucleus. Our findings suggest that pre-mitotic modifications of the lamina function as a mechanical trigger to facilitate nuclear rupture and are thereby a key driver of mitotic entry, complementing established biochemical pathways.

cell biology↗

bioRxiv2026

Organic availability and microbial competition for acetate suppress methane emissions during the conversion of gypsum in sewage sludge

Conventional anaerobic digestion emits methane from organic waste. Here, we investigate a sulfate-based alternative that suppresses methane production and generates alkaline solutions that may sequester carbon by carbonate precipitation. Although methanogenesis is known to occur when reduced organic carbon is replete and sulfate is limiting, it remains unclear whether methane emissions during microbial conversion of waste gypsum are primarily driven by community composition or organic availability. By comparing fluxes of electrons from organic matter toward sulfate or methane in microbial communities grown on different organic loads, we show that community composition, microbial growth, and organic availability collectively determine sulfide and methane fluxes. Lower organic loads increase the importance of syntrophic interactions with fermenters and competition between sulfate reducing bacteria and methanogens due to scarcity of substrates. Microbes present in the original sewage sludge reduce less sulfate, produce more methane, and generate less alkalinity compared to the communities enriched by multiple cycles of growth in the presence of sulfate and sewage sludge. The inoculation of communities enriched at low organic loadings in the presence of sulfate decreases the production of methane by enabling the growth of sulfate reducing bacteria from the order Desulfobacterales that can oxidize acetate to CO2 and compete with methanogens for acetate. The use of such enrichments in sludge treatment systems can stimulate the removal of organic substrates and waste gypsum, while suppressing methane production, over timescales comparable to those in the current sludge treatment systems that do not contain sulfate.

microbiology↗

bioRxiv2026

Development of the cognitive energy landscape from infancy to adolescence

Brain networks mature in a hierarchical sequence that parallels the emergence of cognitive functions. However, precisely how brain structural maturation supports the ordered development of cognitive functions remains largely unknown. Here, leveraging network control theory and 3712 developmental diffusion magnetic resonance imaging scans, we investigate how the brains structural effort to activate cognitive states -- quantified as control energy -- changes from infancy through adolescence. A total of 100 cognitive states were defined as meta-analytic activation maps from NeuroSynth, prioritized by their frequency in major neurodevelopmental behavioral assessments. We show that the control energy to drive most cognitive tasks decreases during development (for 96 out of 100 cognitive states). Ages to achieve optimal energy efficiency for each state concentrate around school age and late adolescence, whereas social and perceptual functions reach efficiency earlier (mean optimal age = 100.2 months) than higher-order cognitive functions (mean optimal age = 205.5 months). Further, we estimated the influence of molecular-level neurodevelopmental events on control energy by coupling control inputs to each events gene expression profile. We find that such influences vary in both temporal breadth and cognitive scope. Prenatal events (neuron differentiation and migration) exert effects mostly in infancy, while the prolonged process of myelination shapes the energy landscape across all developmental periods and the widest range of cognitive domains. Moreover, the transition energy architecture remains stable across development but becomes progressively modularized, such that transitions within the same category of cognitive states become increasingly favored. Together, these findings provide a comprehensive growth chart of how brain structural maturation supports the hierarchical emergence of cognitive abilities across early life, and establish a normative framework that enables systematic approaches to activate targeted brain circuits and facilitate selective cognitive transitions.

Developmental Biology↗

bioRxiv2026

Homeobox transcription factor MSX2 down-regulates ERα action to facilitate anti-estrogensensitivity in ERα+ breast cancer

Breast cancer is the most common malignancy among women worldwide. Estrogen receptor (ER)-positive breast cancer is about 70% in the total breast cancer. It has variable prognosis and high recurrent risk, frequently developing resistance to endocrine therapies. Herein, we have identified that a homeobox transcription factor MSX2 downregulated in ER-positive breast cancer is correlated with the advanced grade and poor survival outcomes. Our results have demonstrated that MSX2 interacts with ER to inhibit ER-mediated transactivation. Mechanistically, MSX2 associates with HDAC1/HDAC2 to form a protein complex. MSX2 is required for recruitment of HDAC1/HDAC2 complex to estrogen response elements (EREs) region on ER downstream target genes, reducing histone H3K9ac and H3K27ac levels to inactivate gene transcription. Functionally, ectopic expression of MSX2 suppresses cell growth and enhances the sensitivity to anti-estrogen treatment in ER-positive breast cancer cells. Our results indicate that MSX2 as a novel co-repressor of ER is involved in suppression of ER-positive breast cancer progression. Restoring MSX2 protein may provide a promising strategy to overcome endocrine resistance in ER-positive breast cancer.

Molecular Biology↗

bioRxiv2026

A genetic screen identifies O-antigen as essential for Rickettsia parkeri survival in macrophages by protecting from inflammasomes and interferon-stimulated genes

Lipopolysaccharide (LPS) is highly immunostimulatory, yet it is evolutionarily conserved among many obligate intracellular bacteria for unknown reasons. We report a forward genetic screen to identify factors required for survival of the tick-borne obligate cytosolic pathogen Rickettsia parkeri in primary macrophages. The most critical factors were WecA and RmlD, which synthesize O-antigen, the outermost layer of LPS. wecA and rmlD mutants grew at similar rates to wild type bacteria in epithelial cells, yet in macrophages they were targeted by guanylate binding proteins (GBPs) and they hyperactivated inflammasomes. Survival of O-antigen-deficient mutants was restored >1,000-fold in macrophages lacking Caspases-1 and -11, interferon signaling, and nitric oxide production, suggesting a multifaceted role for O-antigen in protecting against innate immunity. O-antigen was essential for causing disease in mice and protected R. parkeri against complement in vitro. Despite O-antigen being known as a major target of antibodies, mice immunized with O-antigen-deficient mutants were protected from a lethal rechallenge, suggesting that protection can be elicited independently of O-antigen-targeting antibodies. Together, these findings help resolve a paradox as to why obligate cytosolic bacteria evolutionarily maintain LPS despite it being immunostimulatory, which is that it serves as a multifunctional shield against innate immunity. SignificanceEukaryotic innate immune systems evolved to detect conserved microbial structures as danger signals of infection. Intracellular pathogens, in turn, evolved to hide from innate immunity, yet these mechanisms remain incompletely understood. Here, we performed an unbiased forward genetic screen in macrophages that identified lipopolysaccharide O-antigen as a critical virulence determinant in the tick-borne obligate cytosolic pathogen Rickettsia parkeri. We found that O-antigen shields the bacteria from multiple innate immune defenses, including guanylate-binding proteins, inflammasomes, nitric oxide, and complement. These findings reveal why a highly immunostimulatory molecule such as lipopolysaccharide is maintained by an obligate intracellular pathogen and establish O-antigen as a central determinant of Rickettsia cytosolic survival with implications for vaccine development.

microbiology↗

bioRxiv2026

PanKbase Integrated Single-Cell Map: A Comprehensive Atlas of Human Pancreatic Islets

Single-cell RNA sequencing (scRNA-seq) of human pancreatic islet tissue is a powerful tool for investigating type 1 diabetes (T1D). However, individual datasets are limited in size and fragmented across donors, laboratories, and experimental conditions. To address this, we constructed a comprehensive, integrated scRNA-seq atlas of isolated human pancreatic islets by collating publicly available data generated from tissue provided by resources including the Human Pancreas Analysis Program, the Integrated Islet Distribution Program, and Prodo Labs. Systematic quality controls were implemented to select high-quality samples, reads, and cells. During integration, we accounted for important variables such as age, sex, body mass index, origin study, treatments, islet distribution resources, and sequencing chemistry. Our single-cell atlas comprises 191 high-quality samples from 140 donors (59 female, 81 male) across five phenotypic groups: no diabetes (controls, n=69), autoantibody positivity without diabetes (n=12), pre-diabetes (n=11), T1D (n=12), and type 2 diabetes (T2D) (n=36). In total, the atlas contains 448,935 cells, capturing 13 distinct populations, including alpha cells (43.3%) and beta cells (26.8%), as well as groups such as immune cells (0.6%). Publicly available at www.pankbase.org, this atlas provides a platform for hypothesis-driven investigation of diabetes pathophysiology and, given rigorous quality control, is well-suited for downstream machine-learning applications. Article HighlightsO_LICurrent scRNA-seq datasets of pancreatic islet tissue are limited in size and scattered across donors, laboratories, and experimental conditions, underscoring the need for a consolidated resource. C_LIO_LIWe harmonized datasets from multiple sources to build a comprehensive single-cell map of isolated human pancreatic islets. C_LIO_LIOur atlas captures 448,935 cells from 191 high-quality samples across 140 donors and multiple phenotypic groups, identifying 13 distinct cell populations. C_LIO_LIAvailable at www.pankbase.org, the atlas provides a scalable, rigorously curated platform to support hypothesis-driven diabetes research and can enable a broad range of downstream computational applications. C_LI

genomics↗

bioRxiv2026

Dietary fiber selectively regulates intestinal persistence of probiotic bifidobacteria

Bifidobacteria dominate the gut microbiota of breast-fed infants, and are strongly associated with human health, including immune regulation, colonization resistance, and protection against inflammation. However, bifidobacteria persist at high abundance after weaning in only a subset of individuals, and the factors that regulate intestinal persistence of bifidobacteria are poorly understood. Using gnotobiotic mouse models, we identified a common dietary fiber, raffinose, as a critical determinant of bifidobacterial persistence during microbial transitions associated with weaning. Bifidobacterial persistence depends on an intact raffinose utilization operon and is associated with disease resistance and restrained inflammation in adult mice. Specific dietary fiber recommendations commencing at weaning are a potential strategy to maintain bifidobacteria persistence beyond infancy, with potential long-term benefits for host resilience and reduced risk of inflammatory disease.

microbiology↗

bioRxiv2026

EnzOracle: Mechanism-aware prediction of enzyme environmental adaptation via a classification-guided mixture-of-experts framework

Industrial biocatalysis increasingly requires enzymes capable of operating under extreme physicochemical conditions, yet most natural sequence data reflect adaptation to mild environments, leading conventional predictive models to suffer from regression-to-the-mean effects in extremophilic regimes. Here we present EnzOracle, a classification-guided mixture-of-experts framework that enables distribution-aware prediction of enzyme melting temperature (Tm), optimal catalytic temperature (Topt), and optimal pH (pHopt) directly from sequence. EnzOracle demonstrated robust predictive accuracy across diverse benchmarks, achieving RMSE of 5.245{degrees}C for Tm, 11.458{degrees}C for Topt, and 0.781 for pHopt. Beyond predictive accuracy, we introduce a trait-resolved molecular simulation strategy to evaluate whether EnzOracle-derived attribution patterns correspond to independent physical mechanisms. Across representative systems, attention hotspots mapped onto rigidity-conferring interaction networks for Tm, dynamically preorganized active-site ensembles for Topt, and pH-dependent electrostatic and hydration networks for pHopt. These orthogonal validations indicate that EnzOracle captures transferable biophysical principles of enzyme environmental adaptation rather than merely exploiting dataset-specific correlations, positioning sequence-based learning as a mechanism-aware framework for discovering stability and activity determinants across diverse catalytic landscapes.

bioinformatics↗

bioRxiv2026

Graph-based pangenome provides insights into the adaptive evolution of Cucurbita pepo

Understanding how crops respond to environmental variation is crucial for biodiversity conservation and food security. Cucurbita pepo (pumpkin, squash, gourd) is one of the first domesticated crop species and exhibits remarkable phenotypic and ecological diversity, making it a powerful system for investigating the genomic basis of adaptation. Here, we constructed a graph-based C. pepo pangenome using nine chromosome-level assemblies and identified 229,431 high-confidence structural variants (SVs) that were genotyped across 206 wild and cultivated accessions. Our results demonstrate that C. pepo underwent parallel domestication, with two deeply diverged gene pools independently giving rise to the pepo and ovifera cultivated lineages, followed by expansion into diverse environments that produced strong signatures of differentiation largely mediated by young adaptive alleles. Single-nucleotide polymorphisms (SNPs) and SVs contribute complementary dimensions of environmental responsiveness. Biogeographical modeling predicts continued range contraction of wild relatives and elevated genetic offset in Eastern North American populations under projected future climates. Populations with higher genetic load harbor fewer adaptive variants and exhibit greater predicted maladaptation, indicating that deleterious mutations constrain adaptive potential. These findings highlight how genomic variants, adaptive diversity, and genetic load together shape environmental adaptation and inform conservation and crop improvement.

genomics↗

bioRxiv2026

EEG-Neurofeedback Targeting Gamma Oscillations at the Parieto-Occipital Region Reduces Pain Perception

Pain is closely associated with both spontaneous and stimulus-evoked gamma oscillations, which differ in their phenomenology and their relationship to pain perception. These associations make gamma oscillations a promising target for pain interventions, such as closed-loop real-time neurofeedback (NFB). While modulating stimulus-evoked gamma oscillations is technically challenging due to their concurrent occurrence with pain perception, targeting spontaneous gamma oscillations is both feasible and practical, as it could influence subsequent cortical nociceptive processing and reduce pain. To test this mechanistic hypothesis, we developed a novel NFB training protocol aimed at increasing spontaneous gamma oscillations in the parieto-occipital region to alleviate pain. Eight-eight healthy, right-handed subjects were randomly assigned to either an active or sham NFB group and completed three sessions of NFB training. During each session, subjects underwent EEG recording and received randomized laser stimulation while watching a video. After three training sessions, approximately 52% of subjects in the active group successfully increased the spectral power of spontaneous gamma oscillations in the parieto-occipital region. Crucially, the spectral power of spontaneous gamma oscillations was significantly and negatively correlated with subjective pain intensity after the third NFB session. Additionally, subjects who responded successfully to active NFB showed significant reductions in pain intensity, unpleasantness, and laser-evoked potentials compared to the sham group. Together, these findings establish a causal relationship between spontaneous gamma oscillations in the parieto-occipital region and pain perception, potentially offering a novel NFB-based therapeutic strategy for pain management.

neuroscience↗

bioRxiv2026

ReMind: A Retrospective Self-Report Paradigm for Studying Mind-Wandering Onset During Reading

Mind-wandering (MW) is a frequent and pervasive phenomenon, yet it is commonly assessed using self-reports or probe-based methods that offer limited temporal precision regarding its onset. In this study, we introduce a novel paradigm, ReMind, that estimates the onset and duration of MW episodes during natural reading by combining retrospective self-reports with eye-tracking. Participants indicated the words where they believed their mind started and stopped wandering, and these reports were aligned with gaze timestamps to estimate MW onset. Using data from 44 participants, we examined whether knowledge of MW onset improves the detection of MW from eye-tracking signals. To evaluate relevance for both self-report and thought-probe paradigms, we additionally simulated thought probes by randomly sampling time points during reading. Logistic regression classifiers trained on eye-tracking features extracted from time windows anchored to MW onset achieved AUROC scores of 0.659 and 0.621 under the self-report and simulated thought-probe paradigms, respectively, using leave-one-subject-out cross-validation. In both cases, onset-aligned windows outperformed classifiers trained using arbitrary MW windows. Sliding-window analyses further revealed systematic temporal changes around MW onset, with classification performance peaking at approximately 3 seconds after onset. Feature-level analyses showed reduced fixation rate and fixation dispersion, along with increased pupil size following MW onset. Together, these findings characterize the temporal progression from on-task reading to MW. Overall, ReMind provides a useful framework for studying the temporal dynamics of MW during naturalistic reading.

bioengineering↗

bioRxiv2026

TDP-43 regulates chromatin looping and gene transcription through binding and stabilizing DNA G-quadruplex structures

TAR DNA-binding protein 43 (TDP-43) is a multifunctional DNA/RNA-binding protein implicated in transcriptional and post-transcriptional regulation. Dysregulation of TDP-43 is closely correlated with human diseases such as cancer and neurodegenerative diseases. Although its roles in RNA metabolism are well characterized, its function in transcriptional regulation remains largely underexplored. DNA G-quadruplexes (dG4s) are non-canonical nucleic acid structures enriched at gene promoters and regulatory elements, where they facilitate chromatin looping and gene transcription. Here, we investigated the transcriptional regulatory role of TDP-43 by integrating multi-omics datasets, including Hi-C, dG4 ChIP-seq, TDP-43 ChIP-seq, RNA-seq and ATAC-seq from K562 and HepG2 cells. Our analyses demonstrate TDP-43 binding and dG4s formation are highly colocalized at chromatin loop anchors, particularly at promoter and enhancer regions. TDP-43 occupancy at these anchors correlates with increased dG4 stability, chromatin loop interaction frequency, elevated chromatin accessibility, and upregulated gene expression. Morover, TDP-43 knockdown in HepG2 cells revealed a significant reduction in dG4 formation and loop interaction strength, accompanied by widespread transcriptional dysregulation. Collectively, our findings highlight a novel regulatory role of TDP-43 in facilitating long-range chromatin interactions and transcriptional activation through binding to and stabilizing dG4 structures, providing a mechanistic basis for gene dysregulation driven by TDP-43 dysfunction in diseases.

bioinformatics↗