Biology subjects

Song, D.

Publications and source records attributed to Song, D..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Field evaluation of non-invasive sampling for monitoring nine swine pathogens in the Republic of Korea

BackgroundNon-invasive sampling methods, such as swine oral fluid (OF) and fecal boot (FB) sampling, have gained attention due to their animal welfare considerations, ease of collection, and cost effectiveness. However, comparative data regarding non-invasive and standard sampling methods remain limited, particularly in the Republic of Korea, where research on OF and FB sampling is sparse. Therefore, we investigated representative pig pathogens, including six porcine respiratory pathogens and three gastrointestinal pathogens, using OF and FB samples for pathogen surveillance across commercial farms in the Republic of Korea. MethodsThe results from targeted polymerase chain reaction (PCR) assays for major respiratory and gastrointestinal pathogens obtained using OF and FB samples were compared with those obtained from standard samples. Non-invasive samples included 30 OF ropes and 30 FBs collected from nine farms, and 360 standard samples (blood, fecal, oral, and nasal swabs) were also collected. PCR assays for the nine pathogens were conducted, and the results from OF, FB, and combined OF+FB were compared with those from standard samples at the pen level. ResultsOF sampling showed superior test concordance with respiratory pathogens than gastrointestinal pathogens, and FB sampling demonstrated superior detection of gastrointestinal pathogens compared with OF sampling. Additionally, the combination of OF+FB sampling improved the detection concordance for all nine target pathogens investigated. ConclusionsWe demonstrated the feasibility and potential applicability of OF and FB sampling under field conditions in Korean pig farms. Therefore, this study supports OF and FB sampling as useful tools for swine pathogen monitoring in both research and practical field applications.

microbiology↗

bioRxiv2025

Mcm10 and RecQL4 Synergize to Activate the Eukaryotic Replicative DNA Helicase

Chromosomes are copied from thousands of origins. At each origin, two replicative DNA helicases are first assembled, then activated to begin unwinding DNA. Several replication proteins are subsequently recruited to the active helicase, forming a replisome. The helicase must undergo dramatic conformational changes during its activation and this process is poorly understood, especially in metazoa. How the metazoan replicative helicase is activated, and which proteins promote this essential process are long-standing questions. Using a combination of single-molecule imaging and ensemble biochemistry, we show that Mcm10 and RecQL4 act in a concerted manner to activate replicative helicases. Mcm10 first binds to inactive helicases, then recruits RecQL4, which synergizes with Mcm10 to promote helicase activation. Mcm10 is not incorporated into replisomes and dissociates from origins during replication initiation. In the absence of Mcm10, RecQL4 is recruited to origins via an interaction with the Mcm7 subunit of the helicase. Our data reveal that Mcm10 and RecQL4 play partially redundant roles during helicase activation, help resolve long-standing controversies about the roles of Mcm10 and RecQL4 in DNA replication, and reveal replication initiation defects caused by pathologic RecQL4 mutations.

molecular biology↗

bioRxiv2025

Engineering a Juxtamembrane-Targeting CAR T-Cell Against Mesothelin: A Novel Binder Resilient to Shed Antigen in Ovarian and Pancreatic Cancer

Mesothelin is an attractive target for CAR-T therapy on a number of cancer types; however, the efficacy of this therapy is diminished because the bulk of the cell surface-expressed mesothelin is shed through naturally occurring proteolysis leaving behind a short juxtamembrane peptide "stump". The two problems this creates are (1) the bulk of the target protein is no longer on the tumor cell and (2), the free soluble shed mesothelin remains in the tumor microenvironment and becomes present in blood/other body fluids binding to the mesothelin-targeted CAR-T and interfering with their ability to target the mesothelin that remains on the surface of the tumor. These issues have likely contributed at least in part to the lack of desired efficacy of CAR-T cells that target membrane distal regions of mesothelin (i.e., the shed domain) such as those utilizing anti-mesothelin scFvs SS1 and M5. Here we describe CAR T cells that utilize novel antibodies specific for the mesothelin stump domain thus being unaffected by the natural process of mesothelin shedding. Mesothelin "stump" specific CAR T cells (ST4-22) had cytotoxicity and in vivo activity that was comparable to standard anti-mesothelin CAR T cells. Importantly, CAR T cells expressing ST4-22 were effective against tumor cells that were resistant to standard anti-mesothelin CAR T cells.

immunology↗

bioRxiv2025

Hyperspectral Imaging to Quantify Nodules and Detect Biological Nitrogen Fixation in Legumes

Legume root nodules are important for biological nitrogen fixation, a process critical for plants to gain additional nitrogen from the environment. Nodule quantification is valuable for evaluating nitrogen fixation efficiency, assessing symbiotic relationships, monitoring responses to nitrogen, and supporting genetic studies on legume adaptation and productivity. However, accurate quantification of root nodules is difficult and time-consuming due to the complexity of the root system and soil interference. Here, we explore the utility of hyperspectral imaging as a non-destructive tool to detect active fixing root nodules with minimal preparation and show that we can differentiate nodules and root tissues through unique spectral signatures while also distinguishing between fixing and non-fixing nodules. We applied deep learning techniques to develop an automated nodule counting pipeline adaptable across different legume species and under diverse growth conditions. This approach eliminates the need for labor-intensive counting and enables the detection of nodules embedded within dense root tangles with high accuracy. This automated hyperspectral approach offers a promising alternative to support assessments of nodule abundance and their activity across legume species grown under various environments.

plant biology↗

bioRxiv2025

APALORD: An R-based tool for differential alternative polyadenylation analysis of long-read RNA-seq data

Alternative polyadenylation (APA) is a critical co/post-transcriptional process that enhances RNA isoform diversity, regulating mRNA stability, localization and translation in a spatiotemporal manner. Over the past decade, long-read (LR) RNA sequencing techniques have advanced rapidly, producing datasets that could offer insights into APA mechanisms. Here we introduce APALORD (Alternative Polyadenylation Analysis of LOng-ReaDs), an R-based analysis tool for APA analysis of LR RNA-seq data. Leveraging precise 3 end information from 3-primed LR RNA-seq data, APALORD identifies polyadenylation sites (PASs) and quantifies PAS usage (PAU) at individual sites for each sample. It conducts APA analysis at the gene level (using Kolmogorov-Smirnov test) and at the level of individual PAS (using DEXSeq) across sample conditions. APALORD was applied to direct RNA-seq data from human embryonic stem cells (hESCs) and hESC-derived neurons. PASs were identified with high accuracy and a transcriptome-wide 3UTR lengthening trend was found, consistent with previous studies. APALORD analysis of PacBio cDNA data from human tissues confirmed a 3UTR lengthening trend in cortex compared to liver. R2C2 libraries generated on the Nanopore platform were analyzed with APALORD and it revealed APA change associated with polysome fractions in human neural progenitor cells. In summary, APALORD offers a comprehensive framework for differential APA analysis using LR RNA-Seq data, empowering researchers to investigate 3 end dynamics across diverse biological contexts.

bioinformatics↗

bioRxiv2025

PTP1B inhibition promotes microglial phagocytosis in Alzheimer's disease models by enhancing SYK signaling

Amyloid-{beta} (A{beta}) accumulation is a hallmark of Alzheimers disease (AD). Emerging evidence suggests that impaired microglial A{beta} phagocytosis is a key feature in AD, highlighting the therapeutic potential of enhancing this innate immune function. Here, we demonstrate that genetic deletion or pharmacological inhibition of protein tyrosine phosphatase 1B (PTP1B) ameliorated memory deficits and reduced A{beta} burden in APP/PS1 mice. Moreover, we show that PTP1B was highly expressed in microglia, and its deficiency promoted a transcriptional shift toward immune activation and phagocytosis. Consistently, PTP1B deletion in microglia enhanced phagocytosis and metabolic fitness, supported by increased AKT-mTOR signaling, a pathway essential for meeting the energy demands of activation. Mechanistically, we identified spleen tyrosine kinase (SYK), a key regulator of microglial phagocytosis, as a direct substrate of PTP1B. Inhibition of SYK showed that PTP1B modulates microglial activation in a SYK-dependent manner. These findings established PTP1B as a critical modulator of microglial activation and a potential therapeutic target for AD.

molecular biology↗

bioRxiv2025

Uev1A counteracts oncogenic Ras stimuli in both polyploid and diploid cells

Oncogenic Ras is known to induce DNA replication stress, leading to cellular senescence or death. In contrast, we found that it can also trigger polyploid Drosophila ovarian nurse cells to die by inducing aberrant division stress. To explore intrinsic protective mechanisms against this specific form of cellular stress, here we conducted a genome-wide genetic screen and identified the E2 enzyme Uev1A as a key protector. Reducing its expression levels exacerbates the nurse cell death induced by oncogenic Ras, while overexpressing it or its human homologs, UBE2V1 and UBE2V2, mitigates this effect. Although Uev1A is primarily known for its non-proteolytic functions, our studies demonstrate that it collaborates with the E3 APC/C complex to mediate the proteasomal degradation of Cyclin A, a key cyclin that drives cell division. Furthermore, Uev1A and UBE2V1/2 also counteract oncogenic Ras-driven tumorigenesis in diploid cells, suppressing the overgrowth of germline tumors in Drosophila and human colorectal tumor xenografts in nude mice, respectively. Remarkably, elevated expression levels of UBE2V1/2 correlate with improved survival rates in human colorectal cancer patients harboring oncogenic KRAS mutations, indicating that their upregulation could represent a promising therapeutic strategy.

cell biology↗

bioRxiv2025

High-throughput protein target mapping enables accelerated bioactivity discovery for ToxCast and PFAS compounds

Chemical pollution is a global threat to human health, yet the toxicity mechanism of most contaminants remains unknown. Here, we applied an ultrahigh-throughput affinity-selection mass spectrometry (AS-MS) platform to systematically identify protein targets of prioritized chemical contaminants. After benchmarking the platform, we screened 50 human proteins against 481 prioritized chemicals, including 446 ToxCast chemicals and 35 per-and polyfluoroalkyl substances (PFAS). Among 24,050 interactions assessed, we discovered 35 novel interactions involving 14 proteins, with fatty acid-binding proteins (FABPs) emerging as the most ligandable protein family. Given this, we selected FABPs for further validation, which revealed a distinct PFAS binding pattern: legacy PFAS selectively bound to FABP1, whereas replacement compounds, PFECAs, unexpectedly interacted with all FABPs. X-ray crystallography further revealed that the ether group enhances molecular flexibility of alternative PFAS, to accommodate the binding pockets of FABPs. Our findings demonstrate that AS-MS is a robust platform for the discovery of novel protein targets beyond the scope of the ToxCast program and highlight the broader protein-binding spectrum of alternative PFAS as potential regrettable substitutes.

pharmacology and toxicology↗

bioRxiv2025

Learning single-cell spatial context through integrated spatial multiomics with CORAL

Cellular organization is central to tissue function and homeostasis, influencing development, disease progression, and therapeutic outcomes. The emergence of spatial omics technologies, including spatial transcriptomics and proteomics, has enabled the integration of molecular and histological features within tissues. Analyzing these multimodal data presents unique challenges, including variable resolutions, imperfect tissue alignment, and limited or variable spatial coverage. To address these issues, we introduce CORAL, a probabilistic deep generative model that leverages graph attention mechanisms to learn expressive, integrated representations of multimodal spatial omics data. CORAL deconvolves low-resolution spatial data into high-resolution single-cell profiles and detects functional spatial domains. It also characterizes cell-cell interactions and elucidates disease-relevant spatial features. Validated on synthetic data and experimental datasets, including Stero-CITE-seq data from mouse thymus, and paired CODEX and Visium data from hepatocellular carcinoma, CORAL demonstrates robustness and versatility. In hepatocellular carcinoma, CORAL uncovered key immune cell subsets that drive the failure of response to immunotherapy, highlighting its potential to advance spatial single-cell analyses and accelerate translational research.

bioinformatics↗

bioRxiv2025

Worm Perturb-Seq: massively parallel whole-animal RNAi and RNA-seq

The transcriptome provides a highly informative molecular phenotype to connect genotype to phenotype and is most frequently measured by RNA-sequencing (RNA-seq). Therefore, an ultimate goal is to perturb every gene and measure changes in the transcriptome. However, this remains challenging, especially in intact organisms due to different experimental and computational challenges. Here, we present Worm Perturb-Seq (WPS), which provides high-resolution RNA-seq profiles for hundreds of replicate perturbations at a time in a living animal. WPS introduces multiple experimental advances that combine strengths of bulk and single cell RNA-seq, and that further provides an analytical framework, EmpirDE, that leverages the unique power of the large WPS datasets. EmpirDE identifies differentially expressed genes (DEGs) by using gene-specific empirical null distributions, rather than control conditions alone, thereby systematically removing technical biases and improving statistical rigor. We applied WPS to 103 Caenhorhabditis elegans nuclear hormone receptors (NHRs) to delineate a Gene Regulatory Network (GRN) and found that this GRN presents a striking pairwise modularity where pairs of NHRs regulate shared target genes. We envision that the experimental and analytical advances of WPS should be useful not only for C. elegans, but will be broadly applicable to other models, including human cells.

genomics↗

bioRxiv2025

A cationic liposome-formulated Toll Like Receptor (TLR)7/8 agonist enhances the efficacy of a vaccine against fentanyl toxicity

The U.S. opioid epidemic is an extraordinary public health crisis that started in 1990 and significantly accelerated in the last decade. Since 2020, over 100,000 fatal drug overdoses have been reported annually, and 75% of those involved fentanyl and its analogs (F/FA). Accelerating the translation of innovative, effective, and safe treatments is needed to augment existing measures to counteract such a crisis. Active immunization against F/FA and other opioids represents a promising therapeutic and prophylactic strategy for opioid use disorder (OUD) and opioid-induced overdose toxicity. Previously we demonstrated that the anti-fentanyl vaccine comprising a fentanyl-based hapten (F) conjugated to the diphtheria cross-reactive material (CRM), admixed with the novel lipidated toll-like receptor 7/8 (TLR7/8) agonist INI-4001 adsorbed on Alhydrogel(R) (alum) induced high-affinity fentanyl-specific polyclonal antibodies that protected against fentanyl-induced pharmacological effects in mice, rats, and mini-pigs. Here, INI-4001 was formulated into liposomes with different surface charges, and their impact on F-CRM adsorption, INI-4001 adjuvanticity, and vaccine efficacy were explored. Additionally, as the role of innate immunity in mediating the efficacy of addiction vaccines is largely unknown, we tested these formulations on the activation of innate immunity in vitro. Cationic INI-4001 liposomes surpassed other liposomal and aluminum-based formulations of INI-4001 by enhancing the efficacy of fentanyl vaccines and protecting rats against bradycardia and respiratory depression by blocking the distribution of fentanyl to the brain. Fentanyl vaccines adjuvanted with either cationic INI-4001 liposomes or the aqueous INI-4001 adsorbed to alum induced significant surface expression of co-stimulatory molecules and maturation markers in a murine dendritic cell line (JAWS II), while the former was superior in enhancing the macrophages surface expression of CD40, CD86 and inducible nitric oxide synthase (iNOS), indicative of maturation and activation. These results warrant further investigation of liposome-based formulations of TLR7/8 agonists for improving the efficacy of vaccines targeting F/FA and other opioids of public health interest. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/631964v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@178c8fdorg.highwire.dtl.DTLVardef@d38c09org.highwire.dtl.DTLVardef@8ec41forg.highwire.dtl.DTLVardef@edcf82_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Constructing structural and functional brain networks from regional brain profiles

Brain network analysis has become an important approach to understanding brain function. Given the human brains complexity and dynamic nature, traditional brain networks based on temporal synchronization may not capture all the nuances of brain activity. The emerging trend is to construct brain networks from regional information, creating pathways that connect regional profiles to network-level insights to better understand brain function. In this study, we constructed structural networks based on regional brain structural information, specifically gray matter volume (GMV), and functional networks based on regional brain activity, measured by brain entropy (BEN). We compared these newly constructed networks with traditional networks: functional connectivity networks (FCN) based on temporal synchronization, structural connectivity networks (SCN) derived from fiber tracking, and MEG-derived functional networks. Our results reveal that GMV network (GMVN) and BEN network (BENN) show correlations with these networks but also exhibit distinct differences. Furthermore, we conducted connectome gradient analyses, uncovering meaningful brain function distribution patterns in both GMVN and BENN. Finally, we used GMVN, BENN, and traditional FCN to predict cognitive and emotional scores. The results showed that BENN, in the resting state, provided the best prediction of both cognitive and emotional scores. This study systematically evaluates the relationship between brain networks constructed from regional brain information and existing networks, as well as their ability to predict behavioral phenotypes. It demonstrates that networks built from regional information capture aspects of brain activity that traditional networks cannot represent and may even provide superior predictive power for behavioral phenotypes. This opens a new path for understanding brain function from regional to network-level information and lays the foundation for future applications in brain development, individual differences, and clinical research.

neuroscience↗

bioRxiv2024

Establishment of age-specific intervals based on the hematological and immunological parameters of commercial pigs in the Republic of Korea

Health monitoring based on hematological and immunological parameters is crucial for optimizing performance in the swine industry. This study was conducted to address the lack of comprehensive reports on these parameters in commercial pigs in the Republic of Korea (ROK). To fill this gap, blood samples from 764 healthy pigs across 32 farms in the ROK were analyzed, with the pigs categorized into specific age groups, including weaners, growers, finishers, gilts, and sows. Complete blood counts (CBC) and immunoglobulin G (IgG) concentrations were measured, revealing significant differences across all age groups (p<0.0001). These findings allowed us to establish age-specific Reference Intervals (RIs) at a 95% confidence level and Confidence Intervals (CIs) at a 90% confidence level for each group. This study provides robust guidelines for evaluating the health status of commercial pigs at different stages of growth and development in the ROK. The established RIs and CIs offer valuable insights for future research and practical applications, ensuring reliable health assessments. Routine monitoring of these parameters represents a critical tool for early detection and improved health management in commercial pig populations.

immunology↗

bioRxiv2024

Reproducible Brain Entropy (BEN) Alterations During Rumination

Rumination, characterized by recurrent and repetitive thinking, is closely associated with mental disorders such as depression. However, the neural mechanisms underlying this mental state remain poorly understood. In this study, we use a relatively novel neuroimaging analysis method-Brain Entropy (BEN) to quantitatively assess the irregularity, disorder, and complexity of brain activity, providing new insights into the neural mechanisms of rumination. We utilized a publicly available MRI dataset from three different scanners. The dataset included 41 healthy adult participants who completed identical fMRI tasks on IPCASGE, PKUGE, and PKUSIEMENS scanners. The time interval between the two visits was 22.0 {+/-} 14.6 days. The fMRI session included four runs: resting state, sad memory, rumination, and distraction. Whole brain voxel-wise BEN differences of task state and resting state, rumination and sad memory, distraction and sad memory, and rumination and distraction were tested and overlap regions after thresholded (p<0.05) across the three scanners were identified as exhibiting significant differences. The results demonstrate distinct alterations in BEN across mental states. Compared to the sad memory condition, decreased BEN was found in the visual cortex (VC) during rumination and decreased BEN in the posterior cingulate cortex/precuneus (PCC/PCu) during distraction. However, when compared to distraction, rumination showed increased BEN in the PCC/PCu. These findings suggest that rumination involves heightened internal focus and reduced processing of external environmental information. This study highlights BEN as a valuable metric for elucidating the neural mechanisms underlying rumination and its role in depression.

neuroscience↗

bioRxiv2024

Age-dependent effects of intranasal oxytocin administration were revealed by resting brain entropy (BEN)

Brain entropy (BEN) reflects the irregularity, disorderliness, and complexity of brain activity and has gained increased interest in recent years. The demonstrated sensitivity of BEN to caffeine and medicine suggests the existence of neurochemical effects of BEN. Oxytocin (OT), a neuropeptide associated with childbirth and lactation, affects both social behavior and brain activity. The purpose of this study was to examine whether OT affects BEN in young and old adults. A randomized, double-blind, placebo-controlled, two-factor (Age x OT) between-subjects design was used, and a total of seventy-five eligible healthy participants were included in the experiment. In the young adult group (YA), 23 participants received intranasal OT administration, while 18 received a placebo (PL) administration. In the older adult group (OA), 16 participants received intranasal OT administration, and 18 received PL administration. Using fMRI-based BEN mapping, we found the age-dependent effect of intranasal OT in the left temporal parietal junction (TPJ), where BEN increased in YA and BEN decreased in OA. A whole-brain functional connectivity (FC) analysis with the left TPJ as the seed and we found that FC between the left TPJ and right TPJ increased in both YA and OA. FC of left and right TPJ and plasma OT contribute to left TPJ BEN just found in YA with intranasal OT administration. These results indicate that BEN is sensitive to age-related effects of neurochemical signals and highlight plasma OT on the effects of intranasal OT in young adults.

neuroscience↗

bioRxiv2024

The cell-type underpinnings of regional brain entropy (BEN) in human brain

Brain entropy (BEN) indicates the irregularity, unpredictability and complexity of brain activity. Research using regional brain entropy (rBEN) based on fMRI has established its associations with structural and functional brain networks, as well as their coupling. These relationships are influenced by the sensorimotor-association (S-A) axis and cytoarchitectural organization. Recent studies have also revealed links between functional connectome gradients and cell-type, suggesting that rBEN may have a biological basis at the cellular level. However, this possibility remains unexplored at specifically cellular level. In this study, we analyzed mean rBEN maps derived from 176 participants using HCP 7T data and correlated these with publicly available cell-type datasets. Our findings rBEN exhibited a positive correlation with oligodendrocytes (Oligo) and a negative correlation with parvalbumin-positive interneurons (PVALB) under both resting-state and movie-watching conditions at the whole-brain level. Furthermore, we observed that the S-A axis modulates the relationship between rBEN and cell-type. Specifically, L5 extratelencephalic neurons (L5 ET) showed a positive correlation with rBEN in unimodal cortex but a negative correlation in multimodal cortex and interneurons somatostatin (SST) was correlated with rBEN only in multimodal cortex. These results provide further evidence that rBEN has a biological foundation at the cellular level, with spatial heterogeneity in its associations with different cell types. Moreover, rBEN appears to capture information beyond functional connectivity network.

neuroscience↗

bioRxiv2024

Neuronal heterogeneity of normalization strength in a circuit model

The size of a neurons receptive field increases along the visual hierarchy. Neurons in higher-order visual areas integrate information through a canonical computation called normalization, where neurons respond sublinearly to multiple stimuli in the receptive field. Neurons in the visual cortex exhibit highly heterogeneous degrees of normalization. Recent population recordings from visual cortex find that the interactions between neurons, measured by spike count correlations, depend on their normalization strengths. However, the circuit mechanism underlying the heterogeneity of normalization is unclear. In this work, we study normalization in a spiking neuron network model of visual cortex. The model produces a range of neuronal heterogeneity of normalization strength and the heterogeneity is highly correlated with the inhibitory current each neuron receives. Our model reproduces the dependence of spike count correlations on normalization as observed in experimental data, which is explained by the covariance with the inhibitory current. We find that neurons with stronger normalization are more sensitive to contrast differences in images and encode information more efficiently. In addition, networks with more heterogeneity in normalization encode more information about visual stimuli. Together, our model provides a mechanistic explanation of heterogeneous normalization strengths in the visual cortex, and sheds new light on the computational benefits of neuronal heterogeneity.

neuroscience↗

bioRxiv2024

Regional Brain Entropy, Brain Network and Structural-Functional Coupling in Human Brain

Brain entropy (BEN) indicates the irregularity, unpredictability and complexity of brain activity. In healthy brains, resting-state fMRI-based regional BEN (rBEN) distribution has been shown to have potential relationships with functional brain networks. However, the relationship between rBEN and structural and functional networks, as well as how rBEN facilitates the coupling between structural and functional networks remains unclear. Additionally, network dimensionality reduction methods, such as the use of connectome gradients, have become popular in recent years for explaining the hierarchical architecture of brain function, and the sensorimotor-association (S-A) axis, as a major axis of hierarchical cortical organization, exerts a widespread influence on both brain structure and function. However, how this functional hierarchy affects the relationship between rBEN and brain networks remains unclear. In this study, we systematically examine the relationship between rBEN and both structural and functional networks, including BOLD-based functional networks and MEG-based functional networks. We also assess the impact of the BEN and network gradients, as well as the influence of the S-A axis, on the relationship between rBEN and brain networks. Our results reveal a negative correlation between BEN and the network efficiency of both structural and BOLD-based functional networks, as assessed by average connection strength, degree centrality, and local efficiency. Additionally, BEN shows a negative correlation with the coupling between structural and BOLD functional networks. In contrast, the relationship between BEN and MEG functional network efficiency varies from negative to positive across different frequency bands, with a shift from negative to positive correlation observed in the coupling between BEN and MEG-functional networks. Moreover, the coupling between BOLD and MEG functional networks is positively correlated with BEN. The relationship between BEN and network gradients is complex, and no consistent patterns were observed. Importantly, the relationship between BEN and brain networks is influenced by the S-A axis, and the connection between BEN and networks is further modulated by changes in cytoarchitectural organization. These results are consistent with the commonly observed relationship between elevated rBEN and impaired networks in psychiatric disorders. The negative correlation between BEN and the efficiency of both structural and BOLD functional networks, as well as their coupling, may suggest that lower rBEN is associated with higher information processing potential. Additionally, the positive correlation between BEN and high-frequency MEG functional networks, as well as the coupling between BOLD and MEG functional networks, may indicate that brain processes related to information acquisition and integration could increase rBEN. In summary, this complex relationship may reflect a dynamic process in which the brain continuously acquires external information for integration (increasing entropy) and internalizes it (decreasing entropy) as part of its information-processing mechanism in different timescales.

neuroscience↗