Biology subjects

Xu, Y.

Publications and source records attributed to Xu, Y..

At least 217 records · Page 12Linked to original sources

bioRxiv2025

RNA viruses in water shape the viromes of shrimp and fish in aquaculture systems

Aquatic environments host immense RNA viral diversity, yet the extent to which waterborne viruses influence the virome of aquatic animals remains unclear. Here, we conducted a comprehensive longitudinal metatranscriptomic analysis of water, shrimp, and fish across multiple culture stages in aquaculture systems. We identified 3,211 RNA viruses spanning 21 viral supergroups, with 97.4% representing novel species. Water exhibited the greatest viral diversity (3,093 species), followed by shrimp (1,280) and fish (398), with most viruses detected in shrimp and fish also detected in water. Diversity analyses revealed increasing richness and significant compositional shifts in 92 high-abundance viruses (>1,000 RPM) across culture stages. Viral abundance in aquatic animals was strongly correlated with that in water, and the temporal trajectories of the 16 most abundant viruses were closely synchronized between water and shrimp. Furthermore, 337 virus species were shared among shrimp and two fish species, of which 309 were present in water. These findings demonstrated that RNA viruses in water shape the composition and dynamics of aquatic animal viromes, underscoring the importance of water virome surveillance and management for disease prevention in shrimp aquaculture.

microbiology↗

bioRxiv2025

SLOGEN: A Structure-based Lead Optimization Model Unifying Fragment Generation and Screening

Lead optimization plays an important role in preclinical drug discovery. While deep learning has accelerated this process, structure-based approaches that leverage 3D protein-ligand information remain underexplored. Existing models could improve predicted affinity but often yield synthetically inaccessible compounds, whereas screening-based methods limit chemical novelty by relying on fixed fragment libraries. To bridge the gap, we introduce Slogen--a Structure-based Lead Optimization algorithm unifying fragment Generation and screENing. To achieve this, Slogen integrates a transformer-based variational autoencoder, pretrained on the BindingNet v2 dataset, with an E(3)-equivariant graph neural network that models 3D protein-fragment interactions. This unified framework enables both fragment generation and similarity-based screening, simultaneously addressing synthetic tractability and structural diversity. Benchmarking study shows that Slogen matches or surpasses state-of-the-art methods while exploring broader chemical space. Case studies on the Smoothened and D1 dopamine receptors demonstrate its capacity to design high-affinity, drug-like molecules, providing a practical method for structure-guided lead optimization.

bioinformatics↗

bioRxiv2025

A Critical Rectal Temperature Defines Sex-Specific Leukocyte and Neutrophil Activation During Prolonged Passive Heat Exposure in Young Adults

BackgroundProlonged heat exposure disrupts immune homeostasis and can precipitate acute systemic inflammation. However, the core temperature threshold that triggers sex-specific leukocyte and neutrophil activation during passive heat stress remains undefined. MethodsWe studied 52 males and 58 females exposed to wet-bulb temperatures of 32-35 {degrees}C. Rectal temperature (Trec) was continuously monitored, and blood samples were collected at 0.5 {degrees}C increments up to 38.6 {degrees}C. Leukocyte and neutrophil counts were modeled using quadratic and segmented regression to identify inflection points of immune activation. ResultsBoth leukocytes and neutrophils increased nonlinearly with rising Trec (p < 0.05). A critical Trec of 38.1 {degrees}C--closely aligns with the 38.0 {degrees}C occupational core temperature limits--marked an inflection in leukocyte responses: below this point, females showed steeper increases; whereas above it, males showed accelerated activation. Neutrophils demonstrated consistently greater mobilization in males across the entire temperature range (36.9-38.6 {degrees}C). ConclusionsA distinct core temperature threshold ([~]38.1 {degrees}C) governs immune cell activation and reveals sex-dependent response patterns. This finding provides an immunological rationale for current occupational het limits and highlights the importance of integrating sex-specific considerations into protective guidelines under extreme heat. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/681783v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@9620dorg.highwire.dtl.DTLVardef@47beborg.highwire.dtl.DTLVardef@6396daorg.highwire.dtl.DTLVardef@44c890_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Sourdough starter-inspired living materials grown from probiotic consortia with engineered division-of-labor

Genetic circuits enable precise control over cellular behavior. As circuits become more complex, implementing them within a single cell population becomes difficult. Tasks can instead be distributed in engineered consortia. However, selecting appropriate consortia and harnessing the natural traits of each species for such a division of labor remain unsolved challenges. Here, we report the creation of SINERGY, an engineered synthetic sourdough starter in which functional modules are distributed between the two constituent species. These modules, consisting of sensing, communication, and response, enable in vitro biosensing and in vivo drug delivery and modulate the gut ecosystem in an animal disease model. SINERGY not only preserves the safety and health-promoting properties of the natural components but also endows microbes with programmable functionalities, facilitating broad applications in biomedicine.

synthetic biology↗

bioRxiv2025

RUNX1T1-HDAC Reprogramming of the HOX Code Signaling Drives a Targetable Pan-Cancer Lineage Plasticity

Cancer remains a leading cause of death worldwide, with lineage plasticity emerging as a hallmark that drives therapy resistance and tumor progression by enabling cancer cells to alter identity and evade targeted therapies. Although genomic and transcriptomic aberrations correlate with lineage plasticity, the absence of pan-cancer markers to rapidly identify plastic subtypes has limited predictive utility. Homeobox (HOX) genes encode transcription factors that define tissue identity through distinct expression patterns, or HOX codes, in specific lineages. By analyzing multi-omics data, including 39 HOX genes from over 80,000 RNA-seq samples across 114 cancer types, we discovered that HOX code expression robustly represents cancer cell lineages and reveals multiple previously unrecognized lineage-plastic subtypes in prostate cancer, lung cancer, and acute myeloid leukemia (AML), each displaying altered HOX patterns compared to non-plastic subtypes. Differential analysis further identified RUNX1T1 as a novel and consistent marker of plasticity, elevated across all three cancer types and correlating with HOX code and lineage-plastic marker genes. We validated these correlations in bulk and single-cell RNA-seq from extensive preclinical and clinical cohorts and provided direct functional evidence that RUNX1T1 is required for lineage-plastic programs in prostate cancer. Using AI-based modeling, we identified NCOR/HDAC as RUNX1T1 binding partners forming a co-repressor complex that regulates HOX codes and plasticity. Finally, pharmacologic HDAC inhibition selectively suppressed the growth of plastic cells, revealing a novel therapeutic vulnerability. These findings establish ectopic RUNX1T1 as a pan-cancer biomarker and critical mediator of lineage plasticity and identify the RUNX1T1-HDAC complex as a druggable target.

cancer biology↗

bioRxiv2025

A secreted citrus protease cleaves an outer membrane protein of the Huanglongbing pathogen

Plants secrete a variety of proteases as a defense response during infection by microbial pathogens. However, the relationship between their catalytic activities and antimicrobial functions remains largely unknown. Particularly, few biologically relevant substrates of these proteases have been identified. Huanglongbing (HLB) has been a major threat to the citrus industry worldwide. The HLB-associated bacterium, Candidatus Liberibacter asiaticus (Las), was previously shown to deploy an inhibitor of papain-like cysteine proteases (PLCPs) to promote disease in citrus. In this study, we identified an outer membrane protein (OMP) of Las, LasOMP1, as a substrate of the citrus PLCP CsRD21a. LasOMP1 is one of the most highly expressed genes in Las. CsRD21a cleaves LasOMP1 and produces cleaved peptide products, which could be detected in vitro and in HLB-diseased citrus plants. We found that CsRD21a targets the N-terminal portion of LasOMP1, potentially at an extracellular loop region. Importantly, transgenic sweet orange overexpressing CsRD21a showed reduced Las titers and delayed disease symptoms, highlighting that engineering this protease is a promising strategy to enhance HLB resistance in citrus. Together, our work reveals a pathogen-derived substrate of plant PLCPs and highlights bacterial OMPs as direct targets of plant defense. Significance StatementHuanglongbing (HLB) is the most devastating disease of citrus with no resistance having been identified in commercial cultivars. Previous work implicated papain-like cysteine proteases (PLCPs) as an important hub of defense in citrus; however, their precise role in HLB tolerance remained unclear. Here, we identify and characterize an outer membrane protein (OMP) from the HLB-associated bacterium as a substrate of the citrus PLCP RD21a. We demonstrate a specific cleavage of the bacterial OMP by citrus RD21a, which may impair pathogen growth and/or activate plant immunity. Importantly, overexpression of RD21a enhances HLB tolerance in sweet oranges. This work identifies OMPs as substrates of plant PLCPs and provides insights into protease defense functions.

plant biology↗

bioRxiv2025

SpacGPA: annotating spatial transcriptomes through de novo interpretable gene programs

Spatial transcriptomes, especially those from high-density platforms (e.g., Visium HD, Stereo-seq, Xenium Prime 5K), enable detailed tissue mapping but remain challenging to annotate for spatial domains and spatially variable genes (SVGs). Most existing methods depend on companion single-cell datasets and are sensitive to cell segmentation. We present SpacGPA, a segmentation-free, single-cell-independent framework that identifies de novo interpretable gene programs--co-expressed gene modules capturing key biological processes--from spatial transcriptomes. Leveraging GPU-acceleration and block-matrix operations, SpacGPA efficiently detects gene programs based on a graphical Gaussian model in ultra-large datasets. These programs exhibit domain-specific spatial expression patterns and cell type-specific expression in independent single-cell datasets, serving as robust markers for spatial domains. Applied to four mouse and human spatial datasets, SpacGPA identified 58-109 gene programs per dataset, revealing refined tissue structures. Hub genes within these programs correlate with canonical cell type markers and SVGs, enabling systematic SVG identification. The programs are also functionally enriched and transferable across datasets and platforms. Built on AnnData, SpacGPA provides a scalable, low-hardware solution for high-resolution annotation of tissue organization and gene regulation.

bioinformatics↗

bioRxiv2025

Mapping Human Survivability at Extreme Wet-Bulb Temperatures 32-35°C

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/677706v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@70b72dorg.highwire.dtl.DTLVardef@9fbfeorg.highwire.dtl.DTLVardef@17f05a5org.highwire.dtl.DTLVardef@4b977b_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG HighlightsWe report the first empirical human survival map across wet-bulb temperatures of 32-35{degrees}C. HydraAon and behavior cooling extend survival beyond the 6-hour theoreAcal limit. Females consistently tolerate extreme humid heat longer than males in controlled trials. Our findings refine heat-health models and inform equitable climate adaptaAon strategies. In briefExtreme humid heat, measured by wet-bulb temperature (Tw), is nearing the threshold of human survivability under climate change. In controlled trials with 36 adults, we provide the first empirical survival map across Tw=32-35{degrees}C, showing that hydration and behavioral adaptations extend endurance beyond the theoretical 6-hour limit, with women tolerating heat longer than men. These findings refine human heat tolerance thresholds and inform equitable climate adaptation and heat-health strategies. SCIENCE FOR SOCIETYAs climate change accelerates, extreme humid heat events--measured by wet-bulb temperature (Tw)--pose a growing threat to human survival. This study provides the first empirical benchmarks of human survivability across Tw=32-35{degrees}C, clarifying how long healthy adults can endure these conditions under full hydration and minimal activity. We find that while the theoretical 6-hour survival limit at Tw=35{degrees}C is partly supported, both men and women can withstand these conditions for 7-8 hours when hydrated, with women demonstrating greater tolerance. At Tw=34{degrees}C, projected heatstroke onset extends beyond 12-16 hours, while conditions at Tw=32-33{degrees}C remain largely compensable for more than 30 hours. These results challenge prevailing heat tolerance models, underscore the role of behavioral and physiological adaptations, and provide critical data for designing equitable heat-health policies and early warning systems that account for sex differences and vulnerable populations. Climate change-driven extreme heat events increasingly threaten human health. Here, we provide the first empirical map of human survivability across four extreme wet-bulb temperatures (Tw=32- 35{degrees}C) in controlled trials. Thirty-six healthy young adults (20 males, 16 females) were exposed to twelve dry-bulb temperature and relative humidity combinations in shaded indoor settings under full hydration. Participants remained seated and performed light office tasks until core temperature (Tcore) reached 39{degrees}C or exposures lasted 8 hours. Clinical heatstroke threshold (Tcore=40.5{degrees}C) were projected by extrapolating from our direct Tcore measurements during controlled exposure trials. At Tw=35{degrees}C, males and females reached heatstroke in approximately 7.1-7.7 and 8.3-8.6 hours, respectively--partly supporting the 6-hour theoretical limit while revealing enhanced short-duration resilience when hydrated. At Tw=34{degrees}C, projected times are 12.5-12.9 hours (males) and 15.5-16.2 hours (females). Conditions at Tw=32{degrees}C and 33{degrees}C remained (quasi-)compensable, with projected heatstroke onset after 33-35 hours. Females consistently tolerated heat stress longer than males. These physiological benchmarks are critical for improving heat-health models and embedding sex-specific vulnerability in equitable adaptation strategies amid accelerating global warming.

physiology↗

bioRxiv2025

Principles of protein abundance regulation across single cells in a mammalian tissue

Protein synthesis and clearance are major regulatory steps of gene expression, but their in vivo regulatory roles across the cells comprising complex tissues remains unexplored. Here, we systematically quantify protein synthesis and clearance across over 4,200 cells from a primary tissue. Through integration with single-cell transcriptomics, we report the first quantitative analysis of how individual cell types regulate their proteomes across the continuum of gene expression. Our analysis quantifies the relative contributions of RNA abundance, translation, and protein clearance to the abundance variation of thousands of proteins. These results reveal a putative organizing principle: The contributions of both translation and protein clearance are linearly dependent on the cell growth rate. Further, we find that some proteins are primarily regulated by one mechanism (RNA abundance, translation, or clearance) across all cell types while the dominant regulation of other proteins is cell-type specific. Age related changes in protein abundance are cell-type specific and correlated to changes in protein clearance. Our reliable multimodal measurements enabled quantifying and functionally interpreting molecular variation across single cells from the same cell type. The protein-protein correlations are substantially stronger than the mRNA-mRNA ones both for directly interacting proteins and for functional protein sets. This difference is mediated by protein clearance regulation. Further, the protein correlations allow identifying cell-type specific functional clusters. These clusters vary across cell types, revealing differences in metabolic processes coordination, partially regulated by protein degradation. Our approach reveals organizing principles determining the relative contributions of translation and protein clearance and provides a scalable framework for investigating protein regulation in mammalian tissues.

systems biology↗

bioRxiv2025

KM-GPT: An Automated Pipeline for Reconstructing Individual Patient Data from Kaplan-Meier Plots

Reconstructing individual patient data (IPD) from Kaplan-Meier (KM) plots provides valuable insights for evidence synthesis in clinical research. However, existing approaches often rely on manual digitization, which is error-prone and lacks scalability. To address these limitations, we develop KM-GPT, the first fully automated, AI-powered pipeline for reconstructing IPD directly from KM plots with high accuracy, robustness, and reproducibility. KM-GPT integrates advanced image preprocessing, multi-modal reasoning powered by GPT-5, and iterative reconstruction algorithms to generate high-quality IPD without manual input or intervention. Its hybrid reasoning architecture automates the conversion of unstructured information into structured data flows and validates data extraction from complex KM plots. To improve accessibility, KM-GPT is equipped with a user-friendly web interface and an integrated AI assistant, enabling researchers to reconstruct IPD without requiring programming expertise. KM-GPT was rigorously evaluated on synthetic and real-world datasets, consistently demonstrating superior accuracy. To illustrate its utility, we applied KM-GPT to a meta-analysis of gastric cancer immunotherapy trials, reconstructing IPD to facilitate evidence synthesis and biomarker-based subgroup analyses. By automating traditionally manual processes and providing a scalable, web-based solution, KM-GPT transforms clinical research by leveraging reconstructed IPD to enable more informed downstream analyses, supporting evidence-based decision-making.

bioinformatics↗

bioRxiv2025

Iron Metabolism and Antioxidant Defense: The Role of LI-rTMS in Cerebral Ischemia-Reperfusion

BACKGROUNDTreating cerebral ischemia/reperfusion injury (CIRI) is challenging, with iron metabolism imbalances and oxidative stress worsening the condition. While low-intensity repetitive transcranial magnetic stimulation (LI-rTMS) shows potential in brain protection, its effects on iron processing and antioxidant use are unclear. This study explored LI-rTMSs role in regulating iron homeostasis and antioxidant defense for potential therapeutic use in CIRI. METHODSA rat model of CIRI was established using a filament insertion technique, followed by neurological and infarct volume assessments. In PC12 cells, oxidative damage was induced with H2O2 or ferric ammonium citrate (FAC), then treated with LI-rTMS or deferoxamine (DFP). Parameters measured included oxidative stress markers, iron metabolism markers, and mitochondrial integrity. Gene knockdown and overexpression experiments explored mechanisms involving LI-rTMS and ACSL4. RESULTSLI-rTMS improved neurological deficits by boosting GPX4 activity and inhibiting the ACSL4-LPCAT3-LOX axis, reducing lipid peroxidation. It restored iron balance by lowering TFR and DMT1, decreasing ferritin and hepcidin, and increasing FPN for better iron efflux. LI-rTMS also prevented the Fenton reaction, reduced ROS production, and maintained mitochondrial structure and transmembrane potential. CONCLUSIONSLI-rTMS offers neuroprotection by regulating iron homeostasis through dual pathways: boosting export (via FPN) and reducing uptake/storage (via TFR/DMT1/FE). It also provides ACSL4-dependent antioxidant benefits, suggesting its potential to prevent ferroptosis in CIRI.

biophysics↗

bioRxiv2025

A ratio-based framework using Quartet reference materials for integrating long- and short-read RNA-seq

Long-read RNA sequencing (lrRNA-seq) enables full-length transcript profiling but is confounded by technical batch effects that compromise quantification and prevent data integration across platforms, protocols, and laboratories. The lack of a transcriptome-wide biological ground truth has hindered objective benchmarking. To address these dual challenges, we leveraged certified Quartet reference materials to generate one of the largest multi-center lrRNA-seq resources to date: over one billion long reads from 144 libraries across four PacBio and Nanopore protocols in four independent laboratories. We first establish that ratio-based quantification against built-in reference samples effectively removes technical noise, revealing underlying biological signals. We then constructed the first ratio-based reference datasets for full-length transcripts-- comprising 10,218 isoforms and 6,032 alternative splicing (AS) events--and orthogonally validated them with RT-qPCR. Finally, a comprehensive benchmark using these ground truths reveals that a hybrid strategy integrating long- and short-read data (hybrid-seq) achieves the highest quantification accuracy for both isoforms and AS events. Our work provides a foundational framework and resource for evaluating lrRNA-seq technologies and accelerating the standardization of full-length transcriptomics for research and clinical applications.

genomics↗

bioRxiv2025

Insectivores exhibit superior microbial transmission efficiency and elevated zoonotic risk by 2035 relative to rodents and bats

Wild small mammals represent critical sources of zoonotic infections due to their high diversity, global distribution, and proximity to humans. Nevertheless, significant knowledge gaps persist in characterizing pan-taxonomic microbial richness and sharing dynamics, particularly regarding ecologically critical yet understudied Eulipotyphla (true insectivores). Here we take a macroecological approach to compare how microbial hosting and transmission differ across insectivores, rodents, and bats, and what ecological factors drive such disparities. We find that insectivores host comparable microbial richness to rodents and bats while exhibiting superior intra- and cross-order transmission efficiency. Urban adaptation, geographic range area, and longevity are shared drivers of microbial richness and transmission across these host orders, while greater body mass and shorter gestation time specifically are positive predictors of these outcomes within insectivores. Climate change projections identify insectivores as primary transmission hosts in new high-latitude hotspots by 2035, including parts of the US, Canada, and Russia, posing greater zoonotic threats than rodents or bats. Our findings challenge the prevailing paradigm that prioritizes rodents and bats as special zoonotic reservoirs, establishing insectivores as critical but overlooked players in disease ecology. Collective proactive surveillance of insectivores, rodents, and bats is imperative for forecasting emerging zoonotic threats and informing global risk assessment frameworks.

ecology↗

bioRxiv2025

Unexpected diversity of Isidoides (Anthozoa: Octocorallia: Isidoidae) revealed by morphology and phylogenomics analysis with descriptions of four new species

Isidoidae Heestand Saucier, France & Watling, 2021 is a rare octocoral family currently represented by a single genus and species, Isidoides armata Nutting, 1910 recorded in the western Pacific Ocean. The taxonomic status and diversity of Isidoides is unclear, due to the lack of diagnostic taxonomic features and limited taxon sampling. Based on 23 Isidoides specimens obtained from the northwestern to southwestern Pacific, we carried out morphological and phylogenetic analyses to reveal the taxonomic status of new species and develop reliable features for species identification. The 23 specimens could be classified into four well-supported clades by the phylogenomic analysis of ultraconserved elements (UCEs), four groups by 28S rDNA, and two groups by mtMutS-cox1. Integrating morphology and molecular data, we uncovered unexpected diversity of Isidoides composed of the known species Isidoides armata and three new species, viz., I. elegans sp. nov., I. gracilis sp. nov. and I. pseudarmata sp. nov. The morphological analysis showed high intraspecific morphological variation in colony color and the size, shape and arrangement of polyps. By contrast, sclerite forms with their surface sculpturing are more diagnostic features for species identification. Our phylogenetic and species delimitation analyses indicate that UCEs have higher resolution than the nuclear 28S rDNA and the mitochondrial genes mtMutS and cox1 for species discrimination within Isidoidae. ZooBank: urn:lsid:zoobank.org:pub:392485F5-502E-4383-B153-45B167571190

zoology↗

bioRxiv2025

Application of MT3 in the Development and Immunogenicity Evaluation of GnRH Vaccines

Research on immune castration vaccines is of great significance for animal management. In this study, five copies of GnRH were linked to two MT3s by a flexible linker, GGGGS, to construct a recombinant plasmid, pET30a-GnRH5-MT3, which was expressed and purified using E. coli BL21(DE3) cells. The recombinant protein was best expressed under the induction conditions of 25 with 0.25 mM IPTG, with a purity of up to 80% after purification. It was mixed with the external adjuvant ISA 206 and immunized mice by subcutaneous injection. Serum levels of GnRH-specific Antibody, T, FSH and LH were detected by ELISA, and testicular tissue morphology was observed by HE staining. The results showed that GnRH5-MT3 recombinant protein combined with external adjuvant could efficiently induce GnRH-specific antibody production in male mice (P < 0.01-0.001) and significantly reduce the Serum LH, FSH and T concentrations (P < 0.01-0.001). The immunized mice had sparse cells in the seminiferous tubules of the testis, significantly reduced cells at various developmental stages, and almost no mature spermatozoa. This study provides experimental basis for further application of the vaccine in animal immune castration.

immunology↗

bioRxiv2025

Scaling Personalized TMS: A Scalp-Based MRI-guided Alternative to Neuronavigation

BackgroundPersonalized transcranial magnetic stimulation (TMS) has shown promise in treating psychiatric and neurological disorders, but its accessibility is limited by reliance on costly and complex neuronavigation systems, particularly in resource-constrained clinical settings. ObjectiveTo develop and validate a scalp-based alternative to neuronavigation for personalized TMS targeting. MethodsWe developed a Continuous Proportional Coordinate (CPC) system-based approach for personalized TMS targeting and validated its performance through three operators across ten participants, using individualized DLPFC-SGC targets as an example. The validation framework included targeting consistency assessment, reproducibility evaluation, and cross-cortical generalizability analysis. ResultsThe CPC-based approach demonstrated comparable performance to neuronavigation, achieving 99.4% of its electric field strength (74.80 vs. 75.14 V/m; r = 0.962) and 93.9% of DLPFC-SGC functional connectivity (-0.216 vs. -0.230; r = 0.949), with high inter-operator reliability (ICC [≥] 0.903). Reproducibility analysis showed strong correlation between sessions (r = 0.948-0.957) with high reliability. Further simulations across 1,125 uniformly distributed cortical targets supported generalizability of this approach, with stable electric field preservation (99.07 {+/-} 1.54%) across different brain regions. ConclusionsThe CPC-based approach offers a practical alternative to neuronavigation, maintaining targeting accuracy and providing a more accessible option for personalized TMS implementation.

neuroscience↗

bioRxiv2025

Sexually dimorphic interzonal crosstalk reshapes the adrenal cortex in response to pathophysiological challenges

Structured Abstract BackgroundPrimary aldosteronism is the most common form of secondary arterial hypertension, due to autonomous aldosterone production from the adrenal cortex. Genome wide association studies discovered genetic risk loci associated with the disease, which may affect adrenal cortex renewal, differentiation and lineage conversion. Genetic susceptibility may be modulated by environmental challenges. MethodHere we investigate how environmental cues affecting mineralocorticoid output modulate adrenal cortex homeostasis, cell lineage conversion and zone-specific transcriptional landscape. We have used a newly developed Cyp11b2Cremouse model and characterised its adaptation to a high or low salt diet (HSD, LSD), as well as dexamethasone (DEX) treatment. To explore underlying mechanisms, deep functional and morphological phenotyping, lineage tracing and spatial transcriptomics of the adrenal cortex were performed. ResultsCyp11b2 expression was detected in Cyp11b2Cre-mTmG mice as early as day P1 in different areas of the ZG, associated with high plasma aldosterone levels, with lineage conversion of zona glomerulosa (ZG) into zona fasciculata (ZF) cells progressing between 2 and 9 weeks of age and a progressive reduction of ZG size and evolution of cell components of the adrenal cortex over time. Transdifferentiation progressed into the X-zone (ZX) in females, revealing a previously unrecognized connection between ZF and ZX cells in adult mice. A sexually dimorphic, reciprocal interaction between the ZG and the ZF in adapting to salt diets or DEX treatment was observed, involving changes in cell composition and transcriptional reprogramming of the three zones. ConclusionHSD, LSD and DEX induce a sexually dimorphic cellular and transcriptional response, involving all layers of the adrenal cortex, and the reciprocal contribution of ZG and ZF cells, indicating functional interaction between adrenocortical zones in adapting to external cues.

physiology↗

bioRxiv2025

A comprehensive RNA virome from molluscan transcriptomes reveals extensive diversity and modular genome evolution

Mollusca is the second-largest animal phylum and an important marine food resource for humans. While DNA viruses that threaten molluscan aquaculture have received much attention, molluscan RNA viromes remain poorly explored. Here, based on 223 molluscan metatranscriptomes covering eight animal classes, we identified 80 species-level RNA viruses spanning three viral phyla and nine viral families. Phylogenetic result combined structural modeling found a major increase in the number of Pisuviricota-related lineages. Extensive modular evolution in viral genomes was observed including gene rearrangements and co-evolution of capsid and RdRP genes. Host prediction linked 78% of the RNA viruses to a diverse range of eukaryotes, including vertebrates, invertebrates, and algae. These findings expand the known diversity of RNA viruses in molluscs and shed light on their phylogenetic relationships, highlighting molluscs as valuable models for RNA virus evolution. Graphical abstractRNA virus diversity within 223 molluscan transcriptome samples were analyzed based on RdRP identification. Viruses belonging to the phylum Pisoviricota were the most abundant; co-evolution between RdRP and capsid proteins of molluscan Picornavirales was revealed, and a complex virus-host interaction network was constructed. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC="FIGDIR/small/673676v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1ce8fc0org.highwire.dtl.DTLVardef@3f9068org.highwire.dtl.DTLVardef@121cc2forg.highwire.dtl.DTLVardef@1e431a0_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIComprehensive metatranscriptomic analysis found extensive RNA viral diversity in molluscs. C_LIO_LIPisuviricota dominate the molluscan RNA virome, substantially broadening known viral lineages. C_LIO_LIModular genome evolution involving gene rearrangements and conserved structural features characterize molluscan RNA viruses. C_LIO_LIMolluscs potentially serve as major ecological reservoirs for diverse RNA viruses infecting various eukaryotic hosts. C_LI

bioinformatics↗