Biology subjects

Li, S.

Publications and source records attributed to Li, S..

At least 253 records · Page 14Linked to original sources

bioRxiv2025

FAM19A4 Enhances Neutrophil Respiratory Burst via p38 MAPK in Lethal Sepsis

Sepsis causes high mortality and resource strain, with neutrophil-derived reactive oxygen species (ROS) contributing to excessive inflammation. The secretory protein FAM19A4 modulates ROS release, but its role in sepsis was unclear. We measured elevated FAM19A4 levels in septic patients and cecal ligation and puncture (CLP) mice, correlating with increased mortality. Fam19a4-/- mice subjected to CLP showed significantly improved survival and attenuated multiorgan injury without impaired peritoneal bacterial clearance or altered circulating neutrophil counts. Deficiency reduced the cell counts of neutrophil (Ly6G+) and macrophage (F4/80+) in lungs and liver, diminished systemic ROS production tracked by bioluminescence, and decreased neutrophil extracellular trap (NET) formation in serum and lung tissue. In vitro, FAM19A4 enhanced neutrophil phagocytosis and ROS generation but did not affect lipopolysaccharide-induced chemotaxis. Mechanistically, bulk RNA sequencing, western blotting, and the p38 inhibitor SB203580 demonstrated that FAM19A4 drives neutrophil ROS release specifically through p38 MAPK signaling activation. These results indicate that FAM19A4 is upregulated during sepsis and exacerbates outcomes by enhancing neutrophil ROS production via p38 MAPK, representing a promising therapeutic target for this condition.

molecular biology↗

bioRxiv2025

Nurture over nature in new Micromonospora spp. strains metabolism: multi-omics analyses reveal fermentation conditions as the dominant driver over phylogeny

The genus Micromonospora, a key member of the actinomycetes, has demonstrated considerable potential for natural product biosynthesis. In this study, we isolated 15 Micromonospora spp. strains from desert soil and marine sediment samples, eight of which represent four novel species. To explore the biosynthetic capacity of this genus, we performed an integrated analysis of Micromonospora reference genomes. Pan-genomic analysis further unveiled the core biosynthetic characteristics of the genus responsible for producing terpenes and polyketides. Further multi-omics investigation, combining genomic and metabolomic data, uncovered a positive correlation between phylogenetic relationships and biosynthetic potential, alongside a decoupling of metabolic profiles. Notably, metabolomic findings emphasized the dominant influence of culture conditions on the expression of biosynthetic capabilities. Overall, our study provides a comprehensive elucidation of the biosynthetic potential of the genus Micromonospora and highlights the value of investigating novel strains and applying diverse cultivation strategies in natural product discovery. ImportanceOur study provides a comprehensive genomic and metabolomic elucidation of the significant biosynthetic potential within the genus Micromonospora. It reveals a core biosynthetic capacity for terpenes and polyketides that is phylogenetically linked, whereas the resulting natural product repertoire is subject to strong modulation by cultivation conditions. These findings underscore the critical importance of exploring novel species and employing diverse cultivation strategies to unlock the full potential of microbial resources for natural product discovery.

microbiology↗

bioRxiv2025

Human coronavirus HKU1 neutralization by glycan receptor mimicry

Entry of seasonal human coronavirus HKU1 (HCoV-HKU1) into host cells is facilitated by sequential binding to sialoglycans and transmembrane serine protease 2 (TMPRSS2) receptors. However, the neutralizing capacity of antibodies disrupting these receptor interactions have not been examined. Here, we describe the isolation and characterization of a human monoclonal antibody (mAb) HKU1-2 that recognizes the HCoV-HKU1 spike protein and exhibits dose-dependent neutralization of the virus. Epitope mapping and structural analysis revealed that HKU1-2 mAb targets the sialoglycan binding site in the N-terminal domain of the spike protein. A cryo-electron microscopy (cryo-EM) structure of the spike-Fab complex further demonstrated the ability of HKU1-2 to mimic sialic acid binding thereby effectively blocking sialoglycan receptor engagement. HKU1-2 binding is primarily mediated by CDRH3 recognition of NTD residues K80 and W89 that are known to be critical for sialic acid engagement. Overall, our results demonstrate antibody recognition and neutralization of HCoV-HKU1 by receptor mimicry.

immunology↗

bioRxiv2025

Molecular Dynamics-Guided All-Atom Reconstruction of Cryo-ET Maps Reveals Mechanisms of Histone Tail-Mediated Chromatin Compaction

Dynamics and physical state of chromatin are crucial in regulating gene expression, DNA replication, and repair. Intrinsically disordered histone tails were previously recognized as key modulators of chromatin states. However, detailed atomistic mechanisms by which histone tail dynamics are associated with chromatin compaction and higher-order chromatin organization remain poorly understood. In this work, we combine extensive all-atom molecular dynamics simulations of tri-nucleosomes with cryo-electron tomography (Cryo-ET) of native nucleosome arrays to investigate histone tail-mediated chromatin folding. Our approach offers distinct advantages as it elucidates realistic inter- and intra-nucleosomal interactions and DNA conformations derived from physics-based MD simulations, enabling a more accurate and physically grounded interpretation of Cryo-ET data. The results reveal that histone tails promote chromatin compaction and constrain tri-nucleosome unfolding via three major patterns: through histone-DNA interactions, histone H2A-H4 and H3-H4 tail-tail interactions. Notably, the distributions of MD-generated structural parameters of tri-nucleosomes with truncated histone tails were found to be in strong agreement with those of experimental open chromatin arrays with widely spaced nucleosomes, whereas the system with histone tails resembled more condensed chromatin. These findings provide mechanistic insights into how histone tails may mediate chromatin folding at the atomistic scale and underscore the dual role of histone tails in both structural compaction and inter-nucleosomal communication.

biophysics↗

bioRxiv2025

Predictive vision-language integration in the human visual cortex

Integrating linguistic and visual information is a core function of human cognition, yet how information from these two modalities interacts in the brain remains largely unknown. Competing frameworks, including the hub-and-spoke model and Bayesian theories such as predictive coding, offer conflicting accounts of how the brain achieves multimodal integration. To address this question, we collected a large-scale fMRI dataset and leveraged state-of-the-art AI systems to construct encoding models that probe how the human brain matches and integrates linguistic and visual information. We found that prior information from one modality can modulate neural responses in another, even in the early visual cortex (EVC). Integration neural response in EVC is governed by prediction errors consistent with predictive coding theory. Enhanced and suppressed neural responses to semantically matched cross-modal stimuli were found in distinct EVC populations, with suppression population carrying denser, behaviorally relevant semantic information. Both populations support semantic integration with distinct temporal dynamics and representational structures. These findings provide representational- and computational-level insights into how the brain integrates information across modalities, revealing unified principles of information processing that link biological and artificial intelligence.

neuroscience↗

bioRxiv2025

Blind Prediction of Complex Water and Ion Ensembles Around RNA in CASP16

Biomolecules rely on water and ions for stable folding, but these interactions are often transient, dynamic, or disordered and thus hidden from experiments and evaluation challenges that represent biomolecules as single, ordered structures. Here, we compare blindly predicted ensembles of water and ion structure to the cryo-EM densities observed around the Tetrahymena ribozyme at 2.2-2.3 [A] resolution, collected through target R1260 in the CASP16 competition. 26 groups participated in this solvation cryo-ensemble prediction challenge, submitting over 350 million atoms in total, offering the first opportunity to compare blind predictions of dynamic solvent shell ensembles to cryo-EM density. Predicted atomic ensembles were converted to density through local alignment and these densities were compared to the cryo-EM densities using Pearson correlation, Spearman correlation, mutual information, and precision-recall curves. These predictions show that an ensemble representation is able to capture information of transient or dynamic water and ions better than traditional atomic models, but there remains a large accuracy gap to the performance ceiling set by experimental uncertainty. Overall, molecular dynamics approaches best matched the cryo-EM density, with blind predictions from bussilab_plain_md, SoutheRNA, bussilab_replex, coogs2, and coogs3 outperforming the baseline molecular dynamics prediction. This study indicates that simulations of water and ions can be quantitatively evaluated with cryo-EM maps. We propose that further community-wide blind challenges can drive and evaluate progress in modeling water, ions and other previously hidden components of biomolecular systems.

biophysics↗

bioRxiv2025

Evolutionary landscape of oral microbiome over 100,000 years

The human oral microbiome represents an intimate and enduring partnership between host and microbial communities, yet its evolutionary trajectory across deep time remains largely uncovered. Here we reconstruct the global history of the oral microbiome over 102,400 years using a global collection of 1854 oral samples spanning 61 countries. We reveal that major cultural transitions of the Neolithic Revolution, industrialization, and recent medical advances have driven a directional, globally coordinated co-evolution of oral microbial ecology, function, and population structure. Network analysis identifies two universal microbial modules of dental calculus modules: the commensal-enriched DCM1 module and the pathogen-enriched DCM2, both exhibiting progressive ecological polarization. DCM2 surged around 4,000 years ago with agricultural intensification but subsequently declined in modern European populations while persisting at high levels in African and some American groups, a geographic divide mirroring socioeconomic inequities. Species-level analyses demonstrate widespread directional changes, with obligate anaerobes declining as aerotolerant taxa expand, reflecting a carbohydrate-associated functional remodeling toward starch metabolism. Phylogenomic reconstruction reveals contrasting evolutionary trajectories. Pauljensenia mediterranea experienced near-extinction following a severe bottleneck, while Actinomyces israelii underwent a selective sweep with rapid population expansion 1,000 years ago. Critically, the oral resistome has accelerated in the antibiotic era, resulting in [~]33-50-fold surge of highly mobile, clinically relevant antimicrobial resistance genes in the last century, with Streptococcus acting as a central hub of dissemination. Collectively, these results position the oral microbiome as an active participant that has co-evolved with human subsistence, urbanization and medical practice, with direct implications for global oral health, antimicrobial resistance and interventions aimed at restoring resilient microbial states.

microbiology↗

bioRxiv2025

Integrating Genomics into Multimodal EHR Foundation Models

AO_SCPLOWBSTRACTC_SCPLOWThis paper introduces an innovative Electronic Health Record (EHR) foundation model that integrates Polygenic Risk Scores (PRS) as a foundational data modality, moving beyond traditional EHR-only approaches to build more holistic health profiles. Leveraging the extensive and diverse data from the All of Us (AoU) Research Program, this multimodal framework aims to learn complex relationships between clinical data and genetic predispositions. The methodology extends advancements in generative AI to the EHR foundation model space, enhancing predictive capabilities and interpretability. Evaluation on AoU data demonstrates the models predictive value for the onset of various conditions, particularly Type 2 Diabetes (T2D), and illustrates the interplay between PRS and EHR data. The work also explores transfer learning for custom classification tasks, showcasing the architectures versatility and efficiency. This approach is pivotal for unlocking new insights into disease prediction, proactive health management, risk stratification, and personalized treatment strategies, laying the groundwork for more personalized, equitable, and actionable real-world evidence generation in healthcare.

bioinformatics↗

bioRxiv2025

Identification and functional characterization of an AMD associated c-ABL binding SNP streak within the ARMS2 gene promoter region

BackgroundLarge-scale genome-wide association studies (GWAS) have identified the human 10q26 locus as a major genetic risk factor for age-related macular degeneration (AMD). The AMD-associated interval has been refined to a 5,196 bp segment flanking the ARMS2-HTRA1 region, excluding HTRA1 and the ARMS2 3' indel (443del54ins) variant by risk haplotype analysis. Although the missense SNP rs10490924 has been proposed as a functional variant, its role in AMD remains controversial, and the causative variants and underlying mechanisms within this region remain unresolved. MethodsAn unbiased bioinformatic screen identified a 5-SNP block within the 5,196 bp interval that potentially alters c-ABL protein binding. Protein-DNA interactions were validated using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Genetic association with AMD (dry and wet subtypes) was assessed in patient cohorts using blood genomic DNA. The regulatory effect of the 5-SNP block was further examined using luciferase reporter assays. FindingsWe identified a 5-SNP block located [~]556 bp upstream of the ARMS2 start codon, representing a cluster of predicted c-ABL tyrosine kinase binding sites. This block, in complete linkage disequilibrium with rs10490924 (A69S), showed a strong association with both wet and dry AMD (136 controls, 179 dry AMD, 251 wet AMD). EMSA and ChIP confirmed direct c-ABL binding, while luciferase reporter assays demonstrated reduced transcriptional activity mediated by the 5-SNP block in the presence of c-ABL. InterpretationOur results suggest that the c-ABL-responsive 5-SNP regulatory streak in the ARMS2 promoter region act as functional non-coding elements that may contribute to AMD pathogenesis through altered transcriptional regulation.

molecular biology↗

bioRxiv2025

Direct identification of de novo mobile element insertions from single molecule sequencing of human sperm

Mobile element insertions (MEIs) are a significant source of human genetic variation, yet the rates and properties of de novo MEIs are poorly characterized due to technical limitations in sequencing technology. Here, we directly sequenced individual gametes from sperm samples of 19 donors (aged 27-62) using highly accurate PacBio long-read sequencing to identify de novo retrotransposition events without familial inference. We developed a "self-alignment" strategy using personalized genome assemblies that enables high-precision, single-read detection of de novo MEIs. Using this method, we identified 43 de novo Alu insertions, revealing >9-fold variation in Alu retrotransposition rates between individuals (ranging from 0 to 0.148 insertions/gamete). We found a significant increase in Alu activity with paternal age, yielding a 4.67% increase in insertions per gamete per year of additional paternal age, representing a direct observation of age-associated increases in structural variant (SV) mutation rates. De novo Alu insertions predominantly represent evolutionarily young AluYa5 and AluYb8 subfamilies and bear characteristic molecular signatures of target-primed reverse transcription (TPRT). Our population-averaged rate of 4.52 insertions per 100 gametes aligns well with previous population genetic estimates, validating both direct observation and population approaches for estimating de novo MEI rates. These results establish direct gamete sequencing as a powerful method for characterizing germline mutation processes and reveal age as a significant determinant of de novo retrotransposition in the male germline.

genetics↗

bioRxiv2025

PIWIL3-piRNA Pathway Is Essential for Rabbit Oogenesis and Embryogenesis via Broad Regulation of the Transcriptome and Proteome

Female infertility represents a significant challenge in reproductive medicine. Although it is known to be primarily due to oogenic and early embryonic failures, the molecular mechanisms underlying these failures remain elusive. The Piwi-piRNA pathway is crucial for gametogenesis in diverse organisms. Yet, its role in mammalian female fertility is unclear. This is partly because most studies are done in mice, which contain only PIWIL1, PIWIL2, and PIWIL4 that are essential for spermatogenesis but not for oogenesis. PIWIL3 emerges in higher mammals and is highly expressed in human oocytes. Interestingly, female PIWIL3-knockout golden hamsters exhibit only reduced fertility without detectable defects in oogenesis. This has left the function of PIWIL3 in higher mammals, including humans, unexplored. Here, we discovered that PIWIL3 in the rabbit (Oryctolagus cuniculus) shares high homology with human PIWIL3. It is the predominant PIWI protein in oocytes in both species. Using CRISPR-cas9-mediated knockout, we demonstrated that rabbit PIWIL3 is essential for female fertility. Its loss leads to severe defects in oogenesis. Moreover, embryos lacking maternal PIWIL3 arrest developmentally at the 8-cell stage. Mechanistically, rabbit PIWIL3 binds [~]18-nucleotide piRNAs, mirroring the behavior of human PIWIL3, and is critical for piRNA biogenesis. Moreover, it regulates transcriptomic and proteomic landscapes and silences a broad array of transposons during late oogenesis yet activates another set of transposons during early embryogenesis. These findings establish PIWIL3 as a pivotal dual regulator of gene expression and transposon activity, which is essential for oogenesis and early embryogenesis in non-rodent mammals, potentially including humans.

developmental biology↗

bioRxiv2025

JAK1/2 Inhibition Delays Cachexia and Improves Survival through Increased Food Intake

Lung cancer is the leading cause of cancer-related death and is frequently accompanied by reduced food intake and cachexia, a debilitating syndrome characterized by weight loss and skeletal muscle wasting. We sought to identify contributors to cachexia using a murine model of lung cancer that reproduces key features of this syndrome. A multiplex cytokine screening approach, integrated with western blot and transcriptomic analyses, identified tumor-derived inflammatory mediators and downstream signaling pathways associated with cachexia. Notably, IL-6 superfamily members were elevated in the tumor and plasma of mice and patients with cachexia. The JAK-STAT3 signaling was upregulated in liver and skeletal muscle, driving the acute phase response and impairing lipid metabolism. Pharmacologic inhibition of JAK1/2 with ruxolitinib improved body weight, fat mass, and overall survival without altering tumor burden. These effects were driven primarily by blunted hypothalamic leptin receptor signaling, which increased food intake early in the disease course. In the liver, JAK inhibition reduced STAT3 activity, restored fatty acid oxidation, and decreased the production of acute-phase proteins. These findings support JAK inhibition as a therapeutic strategy for lung cancer-associated cachexia. Statement of SignificanceCancer cachexia is a lethal complication of lung cancer that lacks effective treatment. We show that JAK inhibition by ruxolitinib restores weight, fat mass, and prolongs survival in murine models of lung cancer. These effects were independent of tumor burden, underscoring the relevance of addressing cachexia to improve survival in cancer patients and supporting clinical testing of JAK inhibition for cancer cachexia

cancer biology↗

bioRxiv2025

Modeling Alzheimer's Disease with APOE4 Neuron-Glial Brain Assembloids Reveals IGFBPs as Therapeutic Targets

Alzheimers disease (AD) research has been hindered by the lack of models that faithfully recapitulate the full profile of disease progression in a human genetic background. We developed a 3D assembloid model ("Masteroid") using iPSC-derived neurons, astrocytes, and microglia from APOE4/4 and isogenic control lines. Neurons were seeded with tau oligomers, then combined with astrocytes and microglia to form mature 3D Masteroids, followed by amyloid-{beta} oligomer exposure. After four weeks, AD-Masteroids exhibited hallmark pathologies, including extracellular amyloid-{beta} deposits, intracellular tau aggregation, neurodegeneration, astrogliosis, and microglial activation, with APOE4 exacerbating all phenotypes. Single-cell RNA sequencing further identified novel roles of IGFBP pathways in amyloid-{beta} and tau-mediated pathology. This innovative platform provides a robust system to dissect cellular and molecular mechanisms of AD progression and offers a powerful tool for therapeutic discovery. HighlightsO_LIThe 3D human neuron-glia assembloid ("Masteroid"), composed of neurons, astrocytes, microglia, and oligodendrocytes, faithfully recapitulates human brain ultrastructure and intercellular interactions. C_LIO_LIExposure to oligomeric tau and A{beta} induced hallmark Alzheimers pathologies, including amyloid deposition, tau aggregation, neurodegeneration, and gliosis. C_LIO_LIThe APOE4 genotype exacerbated all pathological features, highlighting its role in driving multicellular interactions that accelerate disease progression. C_LIO_LIThe IGF signaling axis was identified as a key mediator of A{beta}- and tau-induced pathology and a potential therapeutic target. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=183 SRC="FIGDIR/small/683162v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@f91740org.highwire.dtl.DTLVardef@165726eorg.highwire.dtl.DTLVardef@13b957forg.highwire.dtl.DTLVardef@d40307_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Functional and molecular rescue of aganglionic colon by human enteric nervous system progenitor transplantation in Hirschsprung disease

Hirschsprung disease (HSCR) is a devastating congenital disorder characterised by absence of the enteric nervous system (ENS) in the distal gut. Cell therapy, using human pluripotent stem cell-derived ENS progenitors, offers an attractive alternative to treat this life-limiting disorder. Here we provide an in-depth characterisation of the HSCR phenotype in the B6;129-Ednrbtm1Ywa/J mouse model including molecular analyses highlighting the wide-ranging molecular effects of aganglionosis in HSCR colon. We show that transplantation of hPSC-derived ENS progenitors leads to significant increases in contractile function with formation of extensive donor-derived neuronal networks in colonic explants. Moreover, post-transplantation, we show that integration of ENS progenitors rescues many of the biological pathways impacted in the HSCR aganglionic microenvironment. These novel results provide strong evidence that human ENS progenitor transplantation can modulate critical signalling pathways affected in HSCR and exert positive impacts on contractile function, in aganglionic tissue, supporting further translational development of this regenerative medicine approach.

cell biology↗

bioRxiv2025

Splicing of HPV16 E6 promotes aggressive invasion in oropharyngeal cancer via endocytosis of E-cadherin

Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) has become the most common HPV-associated cancer in developed countries, yet a significant subset of patients develops recurrence despite favorable treatment responses. Biomarkers that identify aggressive tumors at diagnosis are therefore needed. In HPV+ cancers, the viral E6 transcript can be expressed as two main variants, the full-length isoform (E6FL) and the spliced E6*I isoform. Here, we investigated the functional and clinical impact of E6FL and E6*I in HPV+OPSCC. Across multiple preclinical models, E6*I promoted migration and aggressive invasion relative to E6FL and was associated with redistribution of E-cadherin away from the cell membrane. In multi-institutional patient cohorts, a previously developed E6FL:E6ALL influence score, which captures E6 splicing-associated host transcriptional biology, was associated with clinical outcomes. Lower scores, reflecting greater E6*I impact, were associated with worse overall survival and recurrence-free survival. Multiplexed immunofluorescence of 75 primary pretreatment biopsies further showed that a lower influence score was linked to reduced membrane and increased cytoplasmic localization of E-cadherin, while a tissue-based E-cadherin localization score was associated with recurrence. Mechanistically, E6*I overexpression promotes E-cadherin internalization, likely through the Rab11-associated trafficking pathway. Splice-switching oligonucleotides that shifted endogenous E6 splicing toward E6FL reduced invasion in two HPV+ OPSCC models. Together, these findings position HPV E6 splicing as a regulatory axis underlying aggressive HPV+ OPSCC biology and support E6 splicing and membrane-to-cytoplasmic ECAD localization as candidate risk-stratification biomarkers.

cancer biology↗

bioRxiv2025

Stc2a inhibits IGF-stimulated somatic growth in favor of organismal survival under hypoxia

In response to hypoxia, animals reduce somatic growth to shift energy resources toward the maintenance of vital functions and survival. Although this phenomenon is widespread in the animal kingdom, the factors and mechanisms involved remain poorly understood. Here we report that hypoxia causes major changes in zebrafish transcriptomic landscapes with hormonal activity or hormonal signaling identified as most prominently up-regulated GO term and KEGG pathway. Among the top in this group is Stanniocalcin 2a (Stc2a), a secreted glycoprotein that inhibits insulin-like growth factor (IGF) signaling by binding to pappalysin metalloproteinases and inhibiting their activities. The hypoxic induction of stc2a expression is attenuated in Hif2-deficient fish. Genetic deletion of Stc2a increased the developmental speed and growth rate, resulting in enlarged adult organ and body size. Under hypoxia, stc2a-/- fish grew faster than wild-type fish but showed reduced survival rate. These phenotypes were reversed by inhibiting pappalysin activity or blocking IGF signaling. These findings suggest that Stc2a limits IGF-mediated growth in favor of survival and that the induction of Stc2a is part of a conserved mechanism regulating the trade-off between somatic growth and survival under hypoxic stress.

physiology↗

bioRxiv2025

Single-Cell RNA and ATAC Sequencing Reveal Cellular Heterogeneity and Chromatin Accessibility Dynamics in Young Chinese Breast Cancer Patients across Pre- and Post-Neoadjuvant Therapy

Young breast cancer (YBC) patients (age [≤] 40) exhibit aggressive features and poor prognosis, while facing complex needs including breast-conserving surgery and fertility preservation. Neoadjuvant therapy (NAT) is important for tumor downstaging and breast-conserving surgery in YBC treatment, but the NAT response mechanisms in YBC patients remain unelucidated. Here, we analyzed pre- and post-NAT samples from Chinese YBC patients using scRNA-seq and scATAC-seq. We found that NAT reshaped cellular heterogeneity in the tumor microenvironment (TME), reducing epithelial and T cells while increasing endothelial cells and fibroblasts. Residual cancer cells showed enriched epithelial-mesenchymal transition (EMT) and stromal remodeling programs. NAT responders had fewer luminal-like cells and retained basal-like cells in an early hybrid EMT state, whereas non-responders maintained both populations with late hybrid EMT. We identified therapy-resistant genes and motifs (e.g., VTCN1, PROM1, MZB1, Fox family) and linked CXCL13 upregulation to poor NAT response and tumor-specific T-cell expansion. Cell-cell communication analysis revealed NAT reprograms the TME by suppressing VEGF and TNF signaling in basal cells, while residual luminal cells transmit EGFR and CD47-SIRPA signals.

cancer biology↗

bioRxiv2025

Spatially variable growth responses to warming in Atlantic Sea Scallops (Placopecten magellanicus)

Atlantic sea scallop is an important commercial species in the U.S., and its growth rate is strongly modulated by temperature. In this study, we quantified the interannual variations in scallop growth rate and thermal stress intensity in the Mid-Atlantic Bight (MAB) from 2000 to 2018. The results showed that the scallop growth rate variations were overall synchronized between the shallow (< 60 m) and deep ([≥] 60 m) MAB prior to 2015. The response of growth rate to warming in 2015 and 2016 showed marked spatial heterogeneity: scallops in the shallow subregions grew more slowly in the warm years, whereas higher temperature contributed to elevated growth rates in the deep subregions. We developed a dynamic energy budget model to explain the distinct growth rate response to warming at different depths. The model results showed that, in 2016, bottom temperatures in the shallow subregions exceeded the optimal range, limiting the energy available for growth. In contrast, warming created more favorable thermal conditions in the deep habitats. This work reveals the spatiotemporal patterns of scallop growth rates in the MAB and contributes a quantitative understanding of thermal stress and the development of science-based management strategies under future warming.

ecology↗