Biology subjects

Zhang, L.

Publications and source records attributed to Zhang, L..

At least 199 records · Page 11Linked to original sources

bioRxiv2026

Fully Automated and Noise-Robust SEEG Electrode Localization under Practical Clinical Conditions

Stereoelectroencephalography (SEEG) provides direct intracranial recordings of epileptic activity with high spatial and temporal resolution and is widely regarded as the gold standard for presurgical evaluation of drug-resistant epilepsy. Accurate localization of SEEG contacts is essential for seizure onset analysis and surgical planning. However, existing localization approaches are often semi-automated, sensitive to imaging quality, and require manual intervention, limiting scalability and routine clinical deployment. We present a fully automated and noise-robust SEEG contact localization pipeline that integrates adaptive artifact suppression, data-driven thresholding, and flexible geometry-based reconstruction. The method was evaluated on six patients from two centers, including diverse resolution CT acquisitions, comprising 57 electrodes and 652 contacts in total. The proposed framework successfully reconstructed all electrodes and achieved an overall recall of 98.3% and precision of 97.1% for contact localization compared with expert labeling, with a mean deviation of 0.248 {+/-} 0.066 mm. Processing time was approximately two minutes per subject on standard hardware. These results demonstrate reliable performance across heterogeneous imaging conditions. By reducing processing time from hours of manual effort to approximately two minutes per subject, the proposed fully automated workflow facilitates routine clinical deployment and scalable multi-center studies.

bioinformatics↗

bioRxiv2026

Elimination of intramuscular immunoglobulin accumulation alleviates Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disorder due to loss of dystrophin, a cytoskeletal protein critical for muscle integrity and functionality. Despite recent therapeutic advances, there remains a significant unmet need for more effective and accessible therapeutics. Here, we discovered an early accumulation of immunoglobulin G (IgG) in the sarcolemma, which exacerbates tissue inflammation and disease progression. The IgG accumulation primarily resulted from ectopic localization of Fc{gamma}R1, a high-affinity IgG Fc receptor, on dystrophin-deficient myofibers. In two independent murine models, eliminating IgG accumulation via B cell depletion provided sustained benefit to alleviate DMD progression. Our findings uncover a novel disease accelerator in DMD and demonstrate the potential to target this mechanism as therapeutics for broader population of patients with DMD.

immunology↗

bioRxiv2026

Identification and experimental verification of key genes related to the Ras signaling pathway and the Hippo signaling pathway in osteoarthritis based on transcriptome data

BackgroundOsteoarthritis (OA) is a chronic degenerative joint disease characterized by the progressive deterioration of articular cartilage, significantly impacting the quality of life in middle-aged and elderly populations. The Ras and Hippo signaling pathways play critical roles in regulating cell proliferation, differentiation, and stress responses; however, their interactive mechanisms in OA remain unclear. This study aimed to identify key genes associated with these two pathways using bioinformatic approaches and to elucidate their potential mechanisms in OA. MethodsTranscriptomic data of OA along with Ras signaling pathway-related genes (RSPRGs) and Hippo signaling pathway-related genes (HSPRGs) were obtained from public databases. Differentially expressed genes (DEGs) were identified, and key genes were screened through machine learning, expression validation, and receiver operating characteristic (ROC) curve analysis. Functional insights were further explored via gene set enrichment analysis (GSEA), subcellular localization, immune infiltration analysis, regulatory network construction, and drug prediction. Finally, the expression of key genes was validated in clinical samples. ResultsKIT and CSF1R were identified as key genes. GSEA indicated their involvement in pathways such as the lysosome pathway. Subcellular localization predicted that KIT and CSF1R are distributed in the nucleus, extracellular region, and plasma membrane. Immune infiltration analysis revealed that KIT showed a positive correlation with eosinophils and a negative correlation with immature dendritic cells, while CSF1R was positively correlated with macrophages and negatively correlated with CD56 natural killer cells. Drug prediction suggested interactions between the key genes and several therapeutic agents, including avapritinib and IMC-CS4. Subsequently, we validated our findings in cartilage tissue samples and discovered that compared to the control group, both CSF1R mRNA and protein expression was significantly upregulated in OA tissue, while KIT expression was significantly downregulated.The same results were also validated in immunofluorescence staining of chondrocytes. ConclusionThis study identified KIT and CSF1R as key genes in OA, providing new theoretical insights and potential targets for mechanistic research and targeted therapy.

cell biology↗

bioRxiv2026

Characterizing the metabolomes of microglia, astrocytes, and neurons in aging and Alzheimer's brains

Neurons and glia are distinct in their morphology, development, and function, possessing unique transcriptomes and proteomes, but little is known about their metabolomes. The challenge of brain cell metabolic profiling is to obtain a large number of cells for reliable analysis. Here, we purified microglia, astrocytes, and neurons from mouse brains, identifying >70 metabolites through targeted metabolomics and 9,854 metabolite features via untargeted metabolomics. We systematically characterized cell type-enriched metabolites and metabolic pathways, revealing an enrichment of glutathione (GSH) and polyamine metabolism in microglia. This enrichment was validated in vivo and showed significant decreases with aging and in an Alzheimers disease (AD) model. Notably, GSH and polyamine metabolism correlated strongly with chemokine-related gene expression. Disrupting the GSH pathway in microglia resulted in downregulation of chemokine-related genes, aberrant morphogenesis, and {beta}-amyloid deposition. Our results provide a valuable resource (https://metabolismocean.org/braincell) for metabolic studies related to aging, AD, and other neurological diseases.

neuroscience↗

bioRxiv2026

Defining Aeromonas species boundaries with large-scale average nucleotide identity analyses and genomic phylogeny

Aeromonas taxonomy has long been complicated by overlapping phenotypic, biochemical, and protein profiles. Here, we establish a robust genome-based framework for Aeromonas genomic species delineation. We analysed average nucleotide identity (ANI) across 4,366 available Aeromonas genomes and demonstrated that at 96% ANI threshold, skANI and fastANI generated too many clusters (65 and 57 respectively) and these clusters were not supported by core genome phylogeny. We identified 95.4% skANI (equivalent to 95.6% fastANI) as an operational threshold for the delineating Aeromonas genomic species. Using the 95.4% skANI threshold, we identified 44 ANI clusters among the 4,366 genomes, of which 43 clusters were genomic species supported by the core-genome phylogeny. Thirty-four of the 43 genomic species corresponded to existing taxonomic species, whilst the remaining nine are currently not recognised as taxonomic species. All recognised taxonomic species represented in the dataset retained their existing species designation except Aeromonas mytilicola, which was not separated from Aeromonas rivipollensis in both ANI clusters and the core-genome phylogeny. The digital DNA-DNA hybridisation (dDDH) values between the genomic species were below 70%, further supporting genomic species delineation. We further developed AeromonasGStyper, a genomic species typing tool that assigns query genomes based on ANI similarity to medoid genomes. In conclusion, this study establishes a genomic species framework for genome-based classification of Aeromonas and provides a practical approach for future genomic surveillance. Impact StatementAeromonas species have gained increased attention as emerging human enteric pathogens. Aeromonas taxonomy has long been complicated by overlapping phenotypic, biochemical, and protein profiles. Although a 96% average nucleotide identity (ANI) threshold was proposed previously for Aeromonas species delineation, analysis of 4,366 Aeromonas genomes demonstrated that this threshold generated excessive genomic clusters that were not supported by the core-genome phylogeny. We identified 95.4% skANI (equivalent to 95.6% fastANI) as an operational threshold for delineating Aeromonas genomic species, supported by core-genome phylogeny and digital DNA-DNA hybridisation (dDDH). The framework identified 43 genomic species, including 34 corresponding to recognised taxonomic species and nine genomic species that do not correspond to currently recognised taxonomic species. In addition, our data showed that Aeromonas mytilicola was not separated from Aeromonas rivipollensis by ANI clustering and core-genome phylogeny, supporting further taxonomic reassessment of the distinction between these two species.

microbiology↗

bioRxiv2026

Broadband backscattering confocal microscopy enables label-free 3D live cell nanoscale sensitive imaging

Fluorescence microscopy is a cornerstone of biological research. However, fluorescent labeling is challenging in live cells and is constrained by photobleaching and phototoxicity. Label-free methods allow cells to be studied in their native state, but most techniques have poor contrast, lack 3D capability, rely on complex optics, and fail to provide structural information. We present broadband backscattering confocal microscopy (BBCM), which employs a broadband supercontinuum laser and collects backscattered light in confocal geometry using a photomultiplier tube. Broadband illumination averages out size-dependent oscillations that confound monochromatic backscattering. This eliminates blind spots and intensity ambiguities, allowing all scatterers to be visible, with the signal increasing approximately linearly with scatterer size. BBCM is easy to retrofit to standard confocal microscopes, requires no specialized optics, and is straightforward for nonspecialists. It enables high-contrast, label-free 3D imaging of live cells with size sensitivity to subcellular structures without employing custom optics or complex data processing.

bioengineering↗

bioRxiv2026

MtDNA heteroplasmy controls tumor immune reprogramming through mitochondrial translation

Mitochondrial DNA (mtDNA) mutations are among the most frequent genetic alterations in human cancers, yet their molecular mechanisms in shaping tumor progression and metastasis under physiological conditions remain poorly understood. Here, we show that mtDNA heteroplasmy acts as a tumor cell-intrinsic rheostat that orchestrates fate decisions between progression and suppression. Moderate heteroplasmy induces a ribosomal storm of mitochondrial translation and ribosome biogenesis, driven by leucyl-tRNA synthetase 2 (LARS2). This response enhances metabolic fitness and licenses the secretion of S100A8/A9, enabling tumor cells to actively remodel the immune microenvironment through recruitment of myeloid-derived suppressor cells and exclusion of CD8 T cells, thereby promoting immune evasion and metastatic progression. In contrast, high heteroplasmy impairs tumorigenesis due to oxidative phosphorylation collapse. Disruption of LARS2, mitochondrial translation, or S100A9 signalling abrogates tumor progression. Our findings establish mtDNA heteroplasmy as a key regulator of cancer evolution, linking mitochondrial genetic variation to immune modulation, and reveal the LARS2-mitochondrial translation-S100A8/A9 axis as a therapeutically targetable programme within the pro-tumorigenic window of mtDNA heteroplasmy.

cancer biology↗

bioRxiv2026

Divergent mitochondrial and metabolic adaptations shape selective vulnerability in ALS

Neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) exhibit striking cell-type selectivity, yet the basis for this vulnerability remains elusive. Here, we uncover that even closely related neurons can harbor distinct mitochondrial properties that shape their response to disease. Using TOM-Tag, a circuit-based AAV-based strategy for cell type-specific mitochondrial immunopurification from projection neurons, we performed integrative proteomic, metabolomic, transcriptomic, and functional analyses of mitochondria from ALS-vulnerable corticospinal projection neurons (CSPNs) and resilient corticothalamic projection neurons (CTPNs) in vivo. We discovered that CSPNs and CTPNs exhibit divergent mitochondrial profiles at baseline, despite sharing cortical layer and developmental origin. CTPNs were primed for antioxidant buffering and fatty acid metabolism, whereas CSPNs were enriched for oxidative phosphorylation components. In ALS, CTPNs employed mitochondrial flexibility and redox defense, whereas CSPNs exhibited respiratory failure and metabolic stress. These findings reveal that intrinsic mitochondrial programs vary even between similar neurons, and that this hidden layer of diversity may critically shape susceptibility to neurodegeneration. By enabling high-resolution access to mitochondria in defined neuronal circuits, TOM-Tag offers a powerful new lens for dissecting disease mechanisms and identifying cell-specific therapeutic targets.

neuroscience↗

bioRxiv2026

Macrophage Antigen Presentation Is Unleashed by Pan-RAS Inhibition to Promote Antitumor Immunity

Pan-RAS inhibitors have emerged as potent targeted therapies designed to suppress oncogenic signaling in RAS-mutant tumors. However, whether these inhibitors possess therapeutic utility beyond tumors with intrinsic RAS dependency remains unclear. Here we show that the clinical-stage pan-RAS(ON) inhibitor RMC-6236 (Daraxonrasib) induces robust regression of NRAS-wild-type B16 tumors in immunocompetent mice, a response mediated by a mechanism independent of direct tumor-cell targeting. Instead, RMC-6236 acts by remodeling the tumor microenvironment, specifically enhancing the antigen-presenting capacity of tumor-associated macrophages through upregulated MHC-I expression. This anti-tumor efficacy is abrogated in T cell-deficient hosts, identifying a macrophage-dependent, T cell-mediated mechanism of control. Mechanistically, RMC-6236 does not directly block canonical RAS signaling in macrophages. Rather, it suppresses a Myc-Hdac2 epigenetic program, leading to enhanced histone H4 acetylation at the Nlrc5 locus and subsequent activation of the MHC-I master regulator NLRC5. Together, our findings reveal a macrophage-centered, epigenetically wired immune mechanism for pan-RAS inhibition that broadens the therapeutic scope of targeting the "undruggable" RAS pathway beyond tumor genotype towards systemic immune modulation.

immunology↗

bioRxiv2026

Molecular mechanisms of mitochondrial Ca2+ exchanger NCLX

Mitochondrial Ca2+ homeostasis is maintained through coordinated influx and efflux processes, with NCLX long recognized as the primary Ca2+ extruder operating via Na+/Ca2+ exchange. Here, we report cryo-EM structures of rat NCLX in cytosolic-facing occluded and open states. The central transmembrane (TM) domain of NCLX comprises ten helices arranged in two inverted, structurally similar halves, with two -repeats forming a central ion-binding pocket. Peripheral TMs 1 and 6 are loosely associated with the core and likely mediate alternative access to this site. These structural features closely resemble those of NCXs, indicating a conserved ion exchange mechanism. While NCLX retains the canonical Ca2+-binding site, it lacks several key Na+-binding residues found in NCXs, suggesting broader ion selectivity. Consistently, cell-based Ca2+ uptake assays show that NCLX mediates Ca2+ exchange using Na+, K+, Li+, and potentially protons as counterions. Based on the structural symmetry of NCLX and its bidirectional exchange capability, we propose a matrix-facing model and an alternating-access mechanism in which TMs 1 and 6 undergo sliding motions to enable ion exchange between cytosolic and matrix sides, analogous to NCX. These findings provide a structural and mechanistic framework for understanding NCLX-mediated Ca2+ transport in mitochondria.

biophysics↗

bioRxiv2026

A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture

To probe drug mechanism of action (MOA) and interrogate the genetic architecture of human cells, we carried out isogenic genome-wide CRISPR/Cas9 knockout screens against 310 diverse drugs, bioactive compounds, and stress conditions. Stringent statistical correction for gene knockout fitness defects yielded a large-scale matrix of >12,000 high confidence chemical-genetic interactions (CGIs). This dataset revealed many previously unappreciated off-target effects for well-characterized compounds and novel MOAs for uncharacterized compounds. The CGI matrix uncovered dense genetic modules that yielded new biological insights into phospholipidosis, mitotic regulation, metabolism, the DNA damage response, and mTOR signaling. The dataset allowed identification of multi-drug sensitization and resistance mechanisms, inference of gene function, elaboration of cross-process connectivity, evaluation of the cell type specificity of CGIs, prediction of chemical synergism, and extensive annotation of understudied genes. This resource provides a map of the genetic landscape in human cells and a framework to help guide drug discovery.

systems biology↗

bioRxiv2026

Endothelin 2-Mediated Neuroinflammation Drives Hypertension-Associated Retinal Dysfunction

Systemic hypertension is a significant risk factor for glaucoma, a leading cause of irreversible blindness, yet the mechanistic basis connecting the two conditions remains elusive. Here, we demonstrate that hypertensive rats develop accelerated retinal degeneration characterized by retinal thinning, functional impairment, reduced perfusion, and progressive neuroinflammation. Critically, these changes occur despite persistently lower intraocular pressure (IOP), indicating an IOP-independent mechanism of pathology. Transcriptomic and biochemical analyses identified a robust activation of the retinal endothelin system, with endothelin-2 (EDN2) being the earliest and most significantly upregulated component. AAV-delivered retinal Edn2 knockdown completely restored retinal function, ameliorated neuroinflammation, and enhanced retinal blood flow in hypertensive rats. Pharmacological blockade of endothelin receptor type A (EDNRA), but not type B, replicated these protective effects without altering IOP. Our findings establish EDN2 as a central, IOP-independent driver of hypertension-associated retinal neurodegeneration and identify the endothelin-EDNRA axis as a potential therapeutic target to prevent vision loss in hypertensive patients.

neuroscience↗

bioRxiv2026

Sonogenetic control of cardiomyocytes and cardiac pacing using exogenous Transient Receptor Potential A1 channels

Electronic cardiac pacemakers are the standard of care for treating arrhythmias but, even for wireless pacemakers, they require an intracardiac implant procedure and are invasive. Lead-related complications, including life-threatening infections, and limited suitability in pediatric patients restrict pacemaker use. Biological pacing has emerged as a hardware-free alternative, leveraging cell reprogramming approaches to generate pacemaker-like cardiomyocytes. Despite progress, biological strategies face challenges related to complex signaling pathways, intercellular coupling, durability of effect, efficacy, and safety. In addition, once ion channels or cells are implanted, biological pacemakers offer limited real-time programmability, whereas electronic pacemakers enable continuous adjustment of pacing output based on cardiac performance. Here we propose a hybrid approach that combines genetic sensitization with external control by exploring the feasibility of sonogenetic cardiac pacing. We express the ultrasound-sensitive ion channel hsTRPA1 in cardiomyocytes and use noninvasive ultrasound to modulate channel activity and cardiac function. Using calcium imaging, we show that hsTRPA1 potentiates ultrasound-evoked responses in cardiomyocytes. Furthermore, cardiac expression of hsTRPA1 in mice increases heart rate in response to ultrasound delivered noninvasively through the intact chest, without evidence of a thermal mechanism under the conditions tested. Together, these results establish a proof of concept for sonogenetic cardiac pacing and define an initial acoustic and genetic parameter space compatible with preserving baseline cardiac function. More broadly, this work positions sonogenetics as a minimally invasive, wireless strategy for cardiac rhythm control and motivates future optimization and safety studies toward translation.

bioengineering↗

bioRxiv2026

Structure-based design of soluble prefusion-stabilized herpes simplex virus type 2 glycoprotein B antigens

Herpes simplex virus type 2 (HSV-2) causes genital herpes through latent infection and periodic reactivation. Although antivirals alleviate symptoms, no prophylactic or therapeutic vaccines have been licensed. Glycoprotein B (gB) is a class III fusion protein that mediates entry by irreversibly transitioning from a metastable prefusion conformation to a stable postfusion conformation. Leveraging prior structure-based designs for human cytomegalovirus (HCMV) gB, we engineered amino acid substitutions in HSV-2 gB to stabilize its prefusion conformation. Cryo-EM of the engineered construct revealed a prefusion conformation and non-native dimers of gB trimers. Introduction of N-linked glycosylation sites resulted in the gB-G3 variant, which exhibited improved expression and reduced dimerization. Cryo-EM of gB-G3 bound to neutralizing antibodies yielded a 2.8 [A] resolution structure of the stabilized prefusion conformation in a closed state, which differs from the open states observed in recently published HSV gB structures. Both prefusion and postfusion gB variants were evaluated for immunogenicity in mice, delivered either as a protein subunit or mRNA vaccine. Each gB conformation elicited robust humoral and cellular responses. However, prefusion stabilization of gB did not improve neutralizing antibody titers relative to the postfusion construct, consistent with prior observations for HCMV gB. Collectively, these findings reveal insights into prefusion gB conformational dynamics, provide stabilized reagents for studying gB-directed immune responses and inform HSV-2 vaccine design.

microbiology↗

bioRxiv2026

Epigenetic Programming of Macrophage Phenotypes by STING-IRF3 Drives Inflammation in Ascending Thoracic Aortic Dissection

BackgroundAscending thoracic aortic dissection (ATAD) is characterized by extensive macrophage (M{Phi}) accumulation and profound inflammation; however, the mechanisms sustaining pro-inflammatory M{Phi} activation remain incompletely defined. Emerging evidence indicates that epigenetically generated immune memory drives innate immune cells toward persistent inflammatory states. In this study, we investigated whether epigenetic reprogramming governs M{Phi} phenotypic fate and contributes to ATAD pathogenesis. MethodsWe performed single-cell RNA sequencing of human ascending aortic tissues from controls, patients with ascending thoracic aortic aneurysm (ATAA), and patients with acute ascending thoracic aortic dissection (ATAD). We also performed integrated single-cell RNA sequencing, single-cell ATAC sequencing, and spatial transcriptomics in an angiotensin II (Ang II)-infused mouse model. The role of the STING-IRF3 signaling axis in M{Phi} epigenetic programming was examined using M{Phi}-Sting -/- and M{Phi}-Irf3-/- mice. ResultsIn human and mouse aortic tissues, we identified multiple functional M{Phi} populations including pro-inflammatory, phagocytic/anti-inflammatory, proliferative, and reparative/healing M{Phi}s. Aortic M{Phi}s in both sporadic ATAD patients and Ang II-induced ATAD mice exhibited a pronounced pro-inflammatory bias with enhanced differentiation toward pro-inflammatory M{Phi}s and impaired differentiation toward phagocytic/anti-inflammatory states. Pro-inflammatory M{Phi}s were particularly abundant in dissection sites, whereas phagocytic M{Phi}s were enriched in discrete adventitial niches. Origin analyses revealed a substantial increase in CCR2 recruited M{Phi}s within the aortic wall, which preferentially differentiated into pro-inflammatory M{Phi}s. In contrast, LYVE1 resident M{Phi}s-- predominantly biased toward phagocytic phenotypes--were markedly depleted in ATAD. Single-cell ATAC sequencing identified coordinated chromatin remodeling with increased accessibility at pro-inflammatory gene loci and decreased accessibility at phagocytic gene loci. Among candidate transcriptional regulators identified, IRF family TFs, including IRF3 emerged as unique factors capable of simultaneously promoting pro-inflammatory gene programs while suppressing phagocytic gene expression. Mechanistically, STING-IRF3 signaling orchestrates this biased transcriptional state, likely through coordinated BRG1-dependent chromatin opening at pro-inflammatory gene loci and chromatin closing at phagocytic/anti-inflammatory gene loci. M{Phi} specific Sting -/- and Irf3-/- mice exhibited attenuated inflammatory reprogramming and reduced aortic destruction and dissection. ConclusionsThese findings identify STING-IRF3-mediated epigenetic programming of M{Phi}s as a fundamental mechanism driving aortic inflammation and ATAD development. Targeting M{Phi} epigenetic programming may represent a promising therapeutic strategy to prevent aortic dissection. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=189 HEIGHT=200 SRC="FIGDIR/small/701198v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@c97bcdorg.highwire.dtl.DTLVardef@1df0ca8org.highwire.dtl.DTLVardef@b7fd04org.highwire.dtl.DTLVardef@1443e16_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2026

RingNet: An Interactive Platform for Multi-Modal Data Visualization in Networks

The exponential growth of data in biomedicine has created an urgent need for intuitive visualization tools. These tools should effectively represent complex biological networks and remain accessible to domain experts without extensive computational training. Current network visualization approaches often require specialized programming skills and/or cannot handle the scale and complexity of modern biomedical datasets, which creates significant barriers to biological discovery. We develop RingNet, a web-based interactive visualization tool that integrates computational efficiency with flexible, user-driven exploration. This tool addresses the communitys need to visualize multi-modal datasets within a single, compact network representation, as well as identify patterns of interest in complex data. RingNet uses an R backend for network computation and coordinate optimization. This generates JSON data structures that feed into a JavaScript and HTML frontend, which provides real-time, interactive visualization functions. It offers dynamic layout adjustments, node and edge filtering, and customizable color schemes for representing data. It can export reproducible, publication-ready figures in SVG and PNG formats. In our case studies, we use RingNet to visualize breast cancer patients omics profiles in a gene regulatory network and a cell-to-cell communication network in atopic dermatitis. This demonstrates RingNets ability to reveal biological relationships across multiple data modalities. HighlightsO_LIRingNet enables intuitive, interactive visualization of multi-modal networks without requiring advanced computational or programming expertise. C_LIO_LIRingNet has two functions: one to identify patterns in complex data at the node level, and the other to identify samples with homogeneous and heterogeneous profiles within network nodes. C_LIO_LIRingNet integrates efficient backend computation with real-time, flexible frontend exploration in a single, web-based framework. C_LIO_LIRingNet reveals cross-modal biological relationships and produces reproducible, publication-ready figures. C_LI Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/700593v4_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@7c79f2org.highwire.dtl.DTLVardef@2a0c73org.highwire.dtl.DTLVardef@97845eorg.highwire.dtl.DTLVardef@1735352_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2026

Asarinin Inhibits RANKL-Induced Osteoclast Differentiation by Targeting the p38/ERK-c-Fos-NFATc1 Axis

Excessive osteoclast formation is a key contributor to pathological bone loss in disorders such as osteoporosis and rheumatoid arthritis. Asarinin, a natural lignan, has not previously been examined in the context of osteoclast differentiation. Here, we investigated the anti-osteoclastogenic effects of asarinin using RANKL-stimulated RAW264.7 cells. Asarinin significantly suppressed TRAP-positive multinucleated osteoclast formation under the tested conditions. Mechanistically, asarinin selectively inhibited RANKL-induced phosphorylation of p38 and ERK MAPKs, leading to reduced c-Fos expression and inhibition of NFATc1 nuclear translocation. In addition, asarinin disrupted actin ring formation in mature osteoclasts. Collectively, these findings identify asarinin as a pathway-selective inhibitor of osteoclast differentiation, targeting the p38/ERK-c-Fos-NFATc1 axis while sparing parallel signaling pathways.

pharmacology and toxicology↗

bioRxiv2026

Bayesian rhythmic model for jointly detecting circadian biomarkers and predicting molecular circadian time in human post-mortem brain transcriptome

Transcriptomic circadian analysis of human post-mortem brain provides a unique opportunity to characterize in vivo molecular circadian rhythms across brain regions implicated in aging and psychiatric disorders. A primary goal in such analyses is the detection of circadian biomarkers. However, this task is complicated by the frequent mismatch between a subjects recorded circadian clock time and their true molecular circadian time -- arising from observational or recording errors, as well as intrinsic biological variability. Existing methods typically address either biomarker detection or circadian time prediction in isolation. Because errors in one task can degrade performance in the other, the lack of a unified approach remains a key limitation. We propose BayCT -- a Bayesian model for simultaneous circadian marker detection and molecular circadian time estimation. The model extends naturally to repeated measurements from multiple brain regions or organs. For circular data, we employ a von Mises prior distribution, with slice sampling and reversible-jump Markov chain Monte Carlo (MCMC) for Bayesian inference. Through extensive simulations and applications to transcriptomic data from three human brain regions and from 12 mouse organs, BayCT demonstrates superior performance in both biomarker detection and circadian time estimation. Furthermore, we highlight the advantages of integrating data across brain regions, achieving substantial improvements in both tasks.

bioinformatics↗