Biology subjects

Qin, Y.

Publications and source records attributed to Qin, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Limited cross strain CMV protection by a bivalent (gB/pp65) vaccine is based on an impaired gB antibody response and evasion of pp65 cell mediated immunity

Congenital CMV (cCMV) is a leading cause of hearing loss and cognitive impairment in newborns and a vaccine is a high priority. The guinea pig with species-specific guinea pig cytomegalovirus (GPCMV) is the only small animal model for cCMV. Prior GPCMV vaccine studies have focused on prototype strain 22122 and not evaluated cross-strain protection, an important vaccine benchmark. The essential viral entry gB glycoprotein is an immunodominant antibody target and considered a corner stone of a CMV vaccine. Trimeric gB antigen induces potent neutralizing antibody titers but a clinical strain of GPCMV (TAMYC) is highly cell-associated limiting gB antibody cross-strain protection. In HCMV and GPCMV tegument protein pp65 is a major T cell antigen and important for convalescent immunity. A defective adenovirus (Ad) vaccine strategy encoding GPCMV gB and pp65 (AdgB+AdGP83) was evaluated for cross-strain protection. Vaccinated animals induced a cell-mediated response via IFN{gamma} ELISPOT assay against pp65 peptides conserved between strains. Additionally, the combined vaccine produced similar anti-gB and prefusion gB titers to historical sera from a standalone trimeric gB vaccine (AdgB). However, antibody response to gB(AD-1) oligomerization domain was impaired in the combined vaccine compared to historical AdgB vaccine sera which resulted in reduced neutralizing titer that were more similar to naturally convalescent GPCMV infected animals. In a pathogenicity study, vaccinated animals had partial protection against clinical TAMYC GPCMV strain challenge (SQ) compared to non-vaccinated control group. However, the vaccine failed to prevent viremia or virus dissemination to target organs, including the salivary glands, a notable limitation. Potentially, TAMYC virus evades T cell response against pp65 by dramatically reducing levels of pp65 expression compared to prototype 22122 strain. Overall, results indicate that a combination vaccine offers limited cross-strain protection despite prior success of separate pp65 or gB vaccines against GPCMV (22122 strain) and conservation of antigens between strains.

microbiology↗

bioRxiv2026

Metagenomic insights into dose-dependent alterations in the tobacco rhizosphere microbiome by pyrroloquinoline quinone

Pyrroloquinoline quinone (PQQ) is known to promote plant growth, yet how the rhizosphere microbiome varies with PQQ concentration remains poorly understood. We applied metagenomic sequencing to characterize the taxonomic composition and functional potential of the tobacco rhizosphere microbiome across PQQ treatments at 0.5, 1 and 2 mol/L plus an untreated control. The rhizosphere microbiome was dominated by Pseudomonadota and Actinomycetota and differed among treatments in a concentration-associated, non-monotonic manner. The most pronounced differences were observed at 1 mol/L, where alpha diversity showed dimension-specific variation and beta-diversity analysis resolved the most distinct community profile. Taxonomic and functional profiles varied concurrently, with Streptomyces, Sphingomonas, Rhodanobacter and Lysobacter, together with functions related to biosynthesis, energy metabolism, colonization and environmental sensing, showing higher relative abundance at this concentration. No broad-spectrum antimicrobial effect was detected at the community level, and antibiotic resistance gene abundance showed no significant differences among treatments after correction for multiple testing. These findings provide a basis for further evaluation of PQQ in modulating the rhizosphere microbiome in continuous cropping systems.

microbiology↗

bioRxiv2026

A tRNA-derived second messenger mediates antiviral defense

CRISPR-Cas systems are RNA-guided nucleases that enable prokaryotic immunity; however, some loci encode additional associated genes that cooperate with CRISPR effectors to perform diverse biological functions. Here, we uncover a CRISPR-associated kinase (CASK) system that links the recognition of target RNA to protein phosphorylation. We show that the kinase Csx33 phosphorylates Csx34 following activation of Cas13, enabling Csx34 to bind DNA in a sequence-specific manner. Together, Csx33 and Csx34 function as a transcriptional activation module that upregulates cas13 and associated genes, revealing a positive autoregulatory circuit that potentiates the immune response upon detection of foreign RNA. At the molecular level, Csx33 is activated by CCA trinucleotide RNA generated by Cas13-mediated cleavage of tRNA 3' tails, uncovering a novel linear second messenger in bacterial immunity and a previously unrecognized signaling role of collateral RNA fragments. Together, these findings establish CASK systems as a new platform for RNA sensing and for engineering programmable phosphorylation-based signaling systems.

molecular biology↗

bioRxiv2026

BCIJelly: An integrated ecosystem for brain-computer interface research

Brain-computer interface (BCI) research relies on multistage computational pipelines, but progress has been slowed by fragmented data formats, heterogeneous decoder implementations and hardware-specific deployment toolchains. Here, we introduce BCIJelly, a unified ecosystem that standardizes 18 BCI datasets into AI-ready inputs and integrates 15 benchmark decoders, 80 reusable modules, automated architecture search (AAS) and hardware-aware neuromorphic deployment. Our AAS constructs task-specific decoders without manual design and extends into a large language model (LLM)-driven closed-loop mode supporting single-task, multitask and cross-species decoder design. A single-command pipeline compiles trained decoders for neuromorphic hardware, reducing power consumption by 30 to 50 times while preserving decoding performance. An interactive visualization software enables code-free exploration of neural recordings and decoding outputs. BCIJelly is validated across five BCI paradigms (motor, visual, speech, emotion and auditory) in humans, macaques and mice, providing an extensible ecosystem connecting data standardization, decoder development, systematic evaluation and hardware-aware deployment for BCI research.

neuroscience↗

bioRxiv2026

Breast cancer ovarian metastases show increased activity of GPCR pathways

Treatment resistance and metastases occur in 10-20% of patients with invasive lobular carcinoma (ILC), the most common special histological subtype of breast cancer. ILC metastasizes to the ovary more frequently than no special type (NST) tumors, also known as invasive ductal carcinoma (IDC). To characterize the genomic landscape of breast cancer ovarian metastases, we analyzed 15,613 local breast cancers, 22,010 non-ovarian metastases, and 246 ovarian metastases sequenced using FoundationOne(R)CDx or FoundationOne(R) assays. Ovarian metastases had enriched CDH1, PIK3CA, and TBX3 mutations and depleted TP53 and MYC alterations relative to local breast cancers, with additional depletion of ESR1 mutations compared to non-ovarian metastases. CDH1 mutations were less frequent in ovarian metastases (47%) than local ILC (81.3%), with reduced 16q loss (64% vs 84%), indicating that ovarian metastases also arise from non-ILC tumors. We extended these findings to a UPMC cohort of 27 ovarian metastases (13 ILC, 8 IDC, 6 mixed ductal-lobular carcinoma) with patient-matched primary tumors in most cases. In both cohorts, patients with ovarian metastases were significantly younger than those with other metastatic sites. In the UPMC cohort, the most frequent mutations were in PIK3CA, CDH1, KMT2C, FOXA1, and RUNX1. Transcriptomic analysis identified upregulated G protein-coupled receptor (GPCR) pathways, including metabotropic glutamate receptor signaling. Functional studies showed that calcium-sensing receptor (CaSR), a GPCR overexpressed in ovarian metastases, drives MEK/ERK-dependent migration and F-actin reorganization in ILC cell lines, enhanced by estrogen and blocked by calcilytic, MEK, or anti- estrogen treatment. Our findings inform future therapeutic targeting of ovarian metastasis.

cancer biology↗

bioRxiv2026

Anionic lipids regulate PLCβ membrane recruitment

Phospholipase C-{beta} (PLC{beta}) enzymes are essential effectors of G protein-coupled receptor signaling that hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) at the plasma membrane to generate the second messengers inositol trisphosphate and diacylglycerol. PLC{beta}s play essential roles in diverse physiological processes, including cardiac and neuronal function, macrophage activation, and the pathogenesis of diseases such as hypertrophic cardiomyopathy. PLC{beta} enzymes are unique in that they are aqueous-soluble and must partition onto the membrane surface to access their substrate, making membrane association a critical regulatory step. For example, we recently demonstrated that G{beta}{gamma} activates PLC{beta} by membrane recruitment and orientation of the catalytic core on the membrane surface. Although PLC{beta} membrane recruitment is required for function, the molecular determinants governing this process remain incompletely understood. Using a quantitative membrane partitioning assay, we show that robust membrane association of PLC{beta} requires anionic phospholipids, whereas polar phospholipids cannot substitute. Membrane partitioning exhibits a steep dependence on anionic lipid abundance, which is mediated by electrostatic interactions between negatively charged lipids and basic residues within the distal C-terminal domain of PLC{beta}. We further demonstrate that anionic lipids cooperate with G{beta}{gamma} to regulate PLC{beta} membrane recruitment, such that the magnitude of G{beta}{gamma}-dependent recruitment is dictated by membrane anionic lipid content. These findings reconcile previous discrepancies regarding G{beta}{gamma}-mediated PLC{beta} membrane recruitment and establish membrane electrostatics as a key regulatory input that integrates lipid composition with G protein signaling to regulate PLC{beta} activity. SummaryMembrane association is a crucial component of PLC{beta} function and regulation, yet the mechanisms governing this process are poorly understood. The authors demonstrate that anionic lipids drive PLC{beta} membrane recruitment and influence G{beta}{gamma}-dependent activation, revealing how membrane composition shapes cellular signal transduction.

biophysics↗

bioRxiv2026

Expanding genetic code to generate human brain organoids with both vasculature and microglia

Brain organoids offer an invaluable model system for studying human brain development and disease. However, the establishment of high-fidelity brain organoids with multiple cell lineages including vasculature and immune cells remains a huge challenge. Here, we present a new strategy to generate human cerebral organoids with vasculature and microglia-like cells using genetic code expansion technology (GCE-T) via site-specific protein engineering. The strategy integrates orthogonal genetic translation machinery in hPSCs via PiggyBac transposon system, enabling temporally control of ETV2 expression and endothelial differentiation in hPSC-derived cerebral organoids. The vascularized human cerebral organoids (vhCOs) exhibit coordinated development of multiple cell lineages and blood-brain barrier (BBB) features. Moreover, vhCOs form perfusable vascular network after transplanted in the immune-deficient mice. Single-nucleus RNA sequencing reveals enhanced neurovascular interactions, multi-brain-regional identities, diverse neuronal subtypes and specialized endothelial subclusters in vhCOs, closely resembling human fetal brain. Strikingly, we identify enriched microglia-like cells comprising three distinct subtypes in vhCOs, which contribute to microglia-vascular interactions and synergistically modulate vascular development. Upon Zika virus (ZIKV) infection, vhCOs show neurovascular dysfunction and impaired microglia development, offering new insights into viral-induced neurodevelopmental disorders. This study offers a unique platform for producing more valuable brain organoids with vasculature and immune components, opening a new avenue to advance organoid research and applications.

bioengineering↗

bioRxiv2026

Microbial induction of MHC-II expression in colon cancer cells overcomes immunotherapy resistance and limits metastasis

Colorectal cancer remains a major cause of cancer mortality, and most microsatellite stable tumors derive little benefit from immune checkpoint blockade. Here, we identify a microbiome-dependent mechanism that converts immune-refractory colorectal cancer into a more immunologically responsive state. Using orthotopic mouse models spanning distinct genetic and immunologic contexts, we show that a Helicobacter-containing microbiome suppresses primary tumor growth and limits metastasis. This protective state is associated with increased intratumoral lymphocyte infiltration and stronger effector programs. Mechanistically, microbial exposure induces MHC class II expression in colon cancer cells to promote anti-tumor immunity. Tumor-intrinsic loss of CIITA abrogates microbial protection, whereas enforced CIITA expression is sufficient to increase intratumoral T cell accumulation, restrict progression and metastasis, and sensitize microsatellite-stable tumors to PD-1 and CTLA-4 blockade. In human microsatellite-stable patient-derived organoids, increased cancer-cell MHC-II enhanced interactions with autologous immune cells and increased tumor cell apoptosis. Together, these findings define a microbiome-cancer cell antigen presentation axis that restrains metastasis and overcomes immunotherapy resistance in colorectal cancer.

immunology↗

bioRxiv2026

Widespread phages exhibit depth-structured infection coupled with ammonia oxidation

Ammonia oxidation is a rate-limiting step in the nitrogen cycle, yet viral contributions to this process remain largely unresolved. Here, we identify three genomically distinct groups of amoC-encoding phages (155-338 kilobases in length; termed as amoC-phages) from multiple freshwater lakes in Europe and North America, including the Laurentian Great Lakes. These phages are highly divergent in phylogeny, genome architecture, and gene content, and are predicted to infect two distinct Nitrosomonadaceae ammonia-oxidizing bacterial lineages. The placement of phage-encoded amoC genes across these divergent viral clades indicates independent acquisition of amoC. Time-series and depth-resolved metagenomes and metatranscriptomes reveal persistent and depth-structured distributions of amoC-phages and their predicted hosts, with seasonal mixing periodically reshaping their co-occurrence patterns. Furthermore, virome data from Lake Mendota show that some of the amoC-phages occur as free viral particles, supporting active viral lysis and particle redistribution along the water column. Metatranscriptomes of the Laurentian Great Lakes reveal coordinated expression of phage structural genes (e.g., major capsid protein) together with phage-encoded amoC, indicating active infection in situ. Together, these results support a framework in which amoC-phage infection is depth-structured, seasonally dynamic, and coupled to ammonia-oxidizing bacterial host activity, highlighting viruses as previously overlooked components of freshwater nitrogen cycling.

microbiology↗

bioRxiv2026

Heat stress induces persistent placental dysfubction and fetal growth restriction via the ERS-MAPK-apoptosis axis

Maternal heat stress (HS) is an emerging risk factor for adverse pregnancy outcomes, yet how gestational heat exposure causes persistent placental dysfunction remains unclear. In the present study, we established a murine HS model (38.5{degrees}C, 2.5 h/day, E0-E12.5) followed by thermal recovery to E17.5. HS reduced fetal weight during early gestation and caused persistent fetal growth restriction after recovery, despite partial placental weight restoration. Histological analyses revealed early reductions in the junctional and labyrinth zones, followed by sustained labyrinthine deficiency and compensatory junctional zone expansion. Consistently, HS impaired placental vascularization, with reduced vessel length and area, decreased CD31 and -SMA abundance, and altered angiogenesis-related gene expression. HS also triggered oxidative stress, weakened antioxidant capacity, disrupted anti-inflammatory signaling, reduced tight junction protein expression, and compromised barrier integrity. Mechanistically, HS induced excessive endoplasmic reticulum stress, accompanied by increased CHOP, phosphorylated ERK, and cleaved caspase-3. In conclusion, our data unveil a heat-induced placental insufficiency program that restricts fetal growth through vascular, redox, barrier, and ERS-MAPK-apoptotic remodeling. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/730306v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@c73748org.highwire.dtl.DTLVardef@fe7b3eorg.highwire.dtl.DTLVardef@14d5e6dorg.highwire.dtl.DTLVardef@72572f_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2026

STID: A Standardized Spatial Transcriptomic Analysis Framework for Infectious Diseases

Spatial transcriptomic studies of infectious diseases still rely on fragmented data analysis processes. Here, we developed STID, a standardized framework for spatial transcriptomic analysis of infectious diseases that leverages the Seurat ecosystem and incorporates Python-based modules. STID provides an extensible infection-specific data structure and supports a full suite of analyses, such as pathogen background correction, infection-associated spot and niche identification, single-sample niche characterization, and multi-sample comparative and temporal analyses. Moreover, STID is broadly applicable to spatial transcriptomic data from infectious diseases caused by bacteria, viruses, and parasites, and enables systematic characterization of the structural features, cellular composition, molecular functions, and host-pathogen interactions within pathogen-infected and/or host-responsive niches. Overall, STID provides an accessible, reproducible, and extensible framework for analyzing infection-associated spatial transcriptomic data and for dissecting host-pathogen interactions in their native spatial microenvironments. MotivationSpatial transcriptomics technologies have emerged as powerful approaches for dissecting the structural and functional features of spatial microenvironments. However, the current general-purpose tools remain fundamentally inadequate for resolving the spatial heterogeneity of infectious disease samples, where the intricacies of host-pathogen interactions render spatial microenvironments both challenging to dissect and largely inaccessible. Tools tailored to infectious diseases are critically lacking, including those for reducing pathogen-derived background noise, identifying and isolating infection{square}associated spots or niches, dissecting host-pathogen interactions, and supporting systematic multi-sample analyses. We therefore developed STID, a unified framework that integrates standardized workflows and addresses the analytical bottlenecks in spatial transcriptomic analysis of infectious diseases. HighlightsO_LISTID standardizes spatial transcriptomic analysis in infectious diseases C_LIO_LISTID improves pathogen-infected spot detection by correcting pathogen background C_LIO_LISTID distinguishes pathogen-infected and host-responsive niches C_LIO_LISTID supports multi-sample comparative and temporal analyses of niches C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC="FIGDIR/small/727492v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@167d351org.highwire.dtl.DTLVardef@1628848org.highwire.dtl.DTLVardef@1e157aforg.highwire.dtl.DTLVardef@143ca1b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2026

Rhythmic temporal structure organizes recurrent dynamics to support sequential working memory

Rhythmic temporal structure improves working memory, but how this benefit emerges from recurrent dynamics remains unclear. Here, we trained excitatory-inhibitory recurrent neural networks with short-term synaptic plasticity to perform a sequential delayed match-to-sample task with either regular or jittered sample timing. Rhythmic input produced a small but reliable improvement in task accuracy and was associated with more differentiated population trajectories during encoding. This behavioral advantage was accompanied by an organization of population dynamics around the dominant input frequency: temporal regularity progressively brought stimulus arrivals closer to preferred encoding phases, modulated phase advancement during stimulus presentation, and reduced the deviation of inter-stimulus phase-progression frequency from the dominant input rhythm. As a result, internal oscillations increasingly tracked the temporal structure of the input across the sequence, providing a phase-based scaffold for encoding ordered information. This scaffold preferentially supported temporal-order representations rather than uniformly enhancing all stimulus features. Decoding analyses further showed that stronger temporal regularity increased the fidelity and persistence of stimulus information in both neuronal activity and synaptic efficacy, whereas perturbing synaptic efficacy produced the largest impairment during delay-period maintenance. These findings suggest that rhythmic input supports sequential working memory by imposing a reliable temporal structure on recurrent dynamics and stabilizing synaptic-state representations.

neuroscience↗

bioRxiv2026

Cytomegalovirus pentamer dependent endocytic cellular infection utilizes redundant entry receptors in the guinea pig model

2.The guinea pig with guinea pig cytomegalovirus (GPCMV) is the only small animal model for congenital CMV (cCMV). GPCMV cell entry is dictated by specific viral gH/gL-based complexes: gH/gL/gO trimer (direct entry); pentamer complex, PC (endocytic entry). GPCMV gB as the fusogenic protein is also essential for all entry pathways. PDGFRA and NRP2 are receptors for direct and endocytic virus entry respectively based on strain 13 animal fibroblast ATCC cell line studies. All non-fibroblast guinea pig cell lines are derived from Dunkin-Hartley animals, the focus of cCMV studies. GPCMV infection of Dunkin-Hartley embryo fibroblasts (GEFh) and epithelial cells were compared. Knockout of PDGFRA on GEFh cells prevented GPCMV(PC-) direct entry but not endocytic GPCMV(PC+) infection, demonstrating both pathways of infection. Fibroblast generated virus poorly infected epithelial cells compared to epithelial virus stock, which exhibited full tropism to all cell types. Guinea pig epithelial cell lines are NRP2-positive and PDGFRA-negative requiring PC for GPCMV infection. Epithelial and GEFh cells, but not strain 13 fibroblasts, additionally expressed ThBD. In immunoprecipitation assays, PC and ThBD interacted unlike CD46 receptor candidate targeting gH/gL. Double-knockout of NRP2/ThBD in epithelial cells impaired infection unlike single knockouts. Individual ectopic species-specific receptor expression restored infection on double-knockout epithelial (NRP2/ThBD) and fibroblast (PDGFRA/NRP2) cell lines. Knockout of NRP2/ThBD receptors did not enhance GPCMV neutralization by gB antibodies on PDGFRA-negative cells demonstrating a limitation of a gB vaccine strategy. Overall, GPCMV and HCMV similarity for receptors and cell tropism maintains the translational importance of this model. 3. Impact StatementA CMV vaccine is a high priority as congenital cytomegalovirus (cCMV) is a leading cause of hearing loss and cognitive impairment in newborns. CMV species-specificity requires animal studies to utilize species-specific virus. The guinea pig is the only small animal model for cCMV and guinea pig cytomegalovirus (GPCMV) encodes functional HCMV homolog glycoprotein complexes for cell entry including a gH/gL-based PC for endocytic cell entry. The viral fusogenic gB glycoprotein is required for GPCMV infection of all cell types but antibody based gB vaccines fail to fully protect against endocytic infection. The PC is potentially an important vaccine antibody target, but PC-based cell entry is only partially understood and poorly characterized for GPCMV. Identifying GPCMV cell entry receptors is critical to the understanding of virus tropism and disease especially since the PC is necessary for cCMV. Correlation with HCMV improves translational impact of guinea pig based cCMV intervention strategies.

microbiology↗

bioRxiv2026

Pupil and Neural Dynamics Reveal Belief-Dependent Decision Making Under Ambiguity

Humans make thousands of decisions under ambiguity every day, where most times the probabilities of getting beneficial outcomes are not fully known. Although ambiguity aversion is well characterized at the aggregate level, it remains unclear how individuals internally represent ambiguous outcomes and how these representations shape behavior and physiology. To address these questions, we investigate value-based decision-making under risk and ambiguity using a multimodal approach that combines behavioral, pupillometric, and electroencephalographic (EEG) data. We show that individuals adopt distinct decision strategies that reflect different internal beliefs about unknown outcomes. These belief differences are expressed not only in choice but also in pupil-linked arousal during decision formation. Crucially, physiological differences across strategies persist under an objective valuation rule for ambiguous options but disappear when valuation is computed using each individuals subjective beliefs, indicating that arousal tracks subjective belief rather than objective task structure. Together, our findings show that ambiguity aversion is not a uniform bias but reflects heterogeneous internal belief models, and that multimodal physiology provides a window into the mechanisms through which these beliefs guide value-based choice.

neuroscience↗

bioRxiv2026

A Haplotype-resolved Telomere-to-Telomere Pig Genome

Haplotype-resolved telomere-to-telomere (T2T) pig genomes have not been reported, but may be essential for xenotransplantation and interspecies chimerism. Here we describe fully phased paternal and maternal T2T assemblies of an Erhualian pig (Ssc_EHL), enabling chromosome-scale reconstruction at base resolution. We uncover 2,498 (paternal haplotype) and 2,577 (maternal haplotype) protein-coding loci previously unresolved in Sscrofa11.1, while maintaining high concordance for anchored gene models between haplotypes. Applying this haplotype-resolved T2T annotation to publicly available pig-to-human kidney xenograft transcriptomes further allows the resolution of xenograft cell states and reveals newly resolved, cell-type-enriched genes. Cross-species synteny and orthology analyses against human identified a subset of high-confidence pig-specific genes with limited human counterparts, thus, refining the genomic basis of interspecies divergence. By integrating these orthology features with organ transcriptomes, we further defined an Interspecies Chimerism Compatibility score to prioritize organ-enriched, highly conserved loci with minimal redundancy imbalance, providing haplotype consistent targets for engineering organ-deficient pigs. Together, this haplotype-resolved T2T pig genome provides a foundational resource for mechanistic studies and rational genome engineering in xenotransplantation and interspecies chimerism.

genomics↗

bioRxiv2026

Estrogen receptor-positive cell line xenograft models recapitulate metastatic dissemination and endocrine response of invasive lobular breast carcinoma

HighlightsO_LIER+, CDH1-deficient ILC xenografts recapitulate single-file histology in vivo C_LIO_LISpontaneous metastases faithfully mirror unique ILC clinical dissemination patterns C_LIO_LIER+ leptomeningeal metastases confirmed histologically in ILC xenograft models C_LIO_LIFulvestrant inhibits ILC tumor growth and metastatic burden, improving survival C_LIO_LIER signaling is enriched in ILC brain metastases, with upregulation of RET C_LI Invasive lobular breast carcinoma (ILC), the most common special histological subtype of breast cancer, is characterized by nearly universal expression of estrogen receptor alpha (ER) and unique sites of metastases, neither of which is fully recapitulated by genetically engineered mouse models. Using reporter-labeled ILC mouse xenografts, herein we used mammary fat pad, tail vein and intracardiac orthotopic growth to analyze spontaneous and experimental metastasis and gene expression. We observed ER-positive primary tumors with single-file histology and collagen deposition, and spontaneous metastasis from the mammary fat pad to bones, ovaries, and brain including the leptomeninges, thereby closely mirroring the growth and metastatic spread of human ILC. Brain metastases showed strong ER staining, confirmed by sequencing analyses which identified estrogen signaling as top activated pathway, and the lesions exhibited robust response to endocrine therapy. In summary, we report endocrine responsive mammary fat pad, tail vein and intracardiac xenografts that faithfully demonstrate unique ILC features and can serve as invaluable pre-clinical translational platforms for validating candidate ILC genetic drivers and testing novel therapeutics.

cancer biology↗

bioRxiv2026

A distinct class of conjugative megaplasmids includes potential vehicles for prophage dissemination

Closely related prophages are frequently found in phylogenetically distant bacteria in the human gut, despite limited evidence of productive phage infections across broad host ranges. Thus, it remains unclear how the wide distribution of prophages could emerge. Here, we identify a potential mechanism of prophage dissemination. We describe two deeply diverged groups of conjugative megaplasmids (>300 kilobases) in the human gut microbiome, which we term Hodors. Hodors encode conserved replication, partitioning, and type IV secretion systems, together with a complex surface-associated gene module. A subset of Hodors harbor complete, intact prophage genomes, and closely related prophages are detected across phylogenetically distant Bacillota lineages, including both Bacilli and Clostridia. Further analysis indicates that Hodor-associated prophages can exist as extracellular particles and demonstrate their transcriptional activity. Our findings support a model in which conjugative megaplasmids act as composite mobile platforms that disseminate prophage genomes across bacterial lineages, providing a mechanistic explanation for the widespread occurrence of closely related prophages in phylogenetically distant gut bacteria and effectively decoupling lysogenic host range from infective host range.

microbiology↗

bioRxiv2026

Genomic insights into rapid diversification and adaptive introgression in the earthworm Amynthas aspergillum

How species diversify in highly fragmented landscapes while maintaining genetic connectivity remains a central question in evolutionary biology. The megascolecid earthworm Amynthas aspergillum exemplifies this paradox, showing deeply divergent mitochondrial lineages despite extensive nuclear gene flow across southern China. We conducted whole-genome resequencing across its core distribution in the Guangxi karst region to elucidate the population structure and processes underlying this cytonuclear discordance. Genome-wide analyses identified three genetically distinct groups shaped by fine-scale karst isolation, alongside pervasive historical and contemporary introgression. Demographic modeling revealed rapid diversification during the Late Pleistocene ([~]0.14LJMa) with pronounced fluctuations in effective population size. Although isolation increased inbreeding and mutational load in some lineages, introgression persisted even among deeply divergent mitochondrial clades. Notably, several introgressed regions showed strong signatures of positive selection, including genes involved in mitochondrial function and metabolism.Together, these results demonstrate that gene flow can simultaneously mitigate the genomic costs of isolation and promote functional innovation via adaptive introgression, providing a genomic framework for diversification with gene flow in subterranean invertebrates inhabiting fragmented karst landscapes.

genomics↗