Biology subjects

Jia, Y.

Publications and source records attributed to Jia, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Genome-wide screen identifies novel factors for surface protein cross-wall trafficking and cell envelope homeostasis in Staphylococcus aureus

Cell wall anchored surface proteins are integral components of the Gram-positive bacterial cell envelope and are vital for bacterial survival in different environmental niches. The trafficking of many surface proteins carrying a YSIRK/G-S signal peptide is synchronized with cell envelope biogenesis during cell division, whereby YSIRK proteins traffic to the septal membrane and anchor to septal peptidoglycan (cross-wall). Previous work demonstrated that LtaS-mediated lipoteichoic acid (LTA) synthesis restricts YSIRK proteins septal trafficking. Here we did a comprehensive immunofluorescence microscopy screen of the entire S. aureus Nebraska Transposon Mutant Library (NTML) for additional factors regulating cross-wall trafficking of staphylococcal protein A (SpA), an archetype of YSIRK proteins. We characterized the top nine major hits that drastically diminished SpA cross-wall localization, including ypfP and ltaA (LTA glycolipid anchor synthesis genes), lcpB (LytR-CpsA-Psr family protein), mprF (lysyl-phosphatidylglycerol synthase), lytH (cell wall hydrolase), scdA (nitrite reductase), yjbH (protease adaptor protein ), cbiO (cobalt transporter) and SAUSA300_2311 (LytTR regulatory system) along with {Delta}tagO (wall teichoic acid synthesis). Interestingly, unlike the ltaS mutant that delocalizes SpA at both the septal membrane and peptidoglycan (PG) layer, all the hits only delocalized SpA at the PG layer, suggesting that these mutants affect the late-stage SpA trafficking. In addition, mutants of lcpB, yjbH, cbiO and 2311 exhibit both transcriptional and spatial regulation. All the hits showed defects in cell cycle, cell morphology and spatially dysregulated PG synthesis. The shared phenotypes among the mutants suggest that impaired PG homeostasis and cell cycle defects are the mechanisms underlying dysregulated SpA localization. Overall, this work not only expands our understanding of YSIRK protein cross-wall trafficking but also identifies new leads that have a broader impact on the dynamics of cell cycle and cell envelope homeostasis. ImportanceSurface proteins of gram-positive bacteria are key virulence factors in human pathogen S. aureus. Most surface proteins carry a YSIRK/G-S type signal peptide that promotes cross-wall trafficking and attachment to septal cell wall during cell division. This study identified several new factors regulating this process through a comprehensive screen. The mutants identified here display dysregulated cell wall synthesis along with cell cycle defects. The results provide new insight into virulence factor trafficking and cell envelope homeostasis, which lays the foundation for development of new antimicrobial therapeutics.

microbiology↗

bioRxiv2025

Coxiella burnetii infects osteoclasts and alters their differentiation and function in a type IV secretion system-dependent manner

1Chronic Q fever is caused by persistent infection with the Gram-negative bacterium Coxiella burnetii. The mechanisms underlying this persistence remain elusive, but the presence of the bacteria in the bone marrow of C. burnetii-infected patients has been demonstrated. Therefore, we investigated the potential role of osteoclasts, the bone-resorbing cells, in harboring C. burnetii during the infection. The histological analysis of bones from a murine model of Q fever revealed the presence of C. burnetii inside osteoclasts. In vitro infection assays confirmed that osteoclasts can be infected with C. burnetii and supported bacterial replication in a type IVB secretion system (T4BSS)-dependent manner. Wild-type C. burnetii infection inhibited osteoclast differentiation and bone-resorbing activity, while the T4BSS mutant enhanced the differentiation and bone-degrading function of osteoclasts. Taken together, our findings identify osteoclasts as a potential host cell for C. burnetii, opening new perspectives on mechanisms that may underlie chronic Q fever. Additionally, infection-induced alterations in osteoclast function raise the possibility of alterations of the bone structure in affected patients.

immunology↗

bioRxiv2025

Embryonic Atrial Injury Programs an Anti-Fibrotic Atrial Fibrillation Substrate

Atrial myopathy is associated with atrial fibrillation in adults, yet the role of embryonic atrial injury in predisposing individuals to atrial fibrillation remains unclear. Using an inducible, cardiomyocyte-specific diphtheria toxin A-mediated injury mouse model, we found that injured embryonic atria exhibited upregulation of apoptosis and TNF signaling pathways, alongside downregulation of calcium handling and atrial fibrillation-associated genes. Single-cell RNA sequencing revealed two distinct cardiomyocyte populations with differential injury responses. Importantly, although myofibroblasts increased in the fibroblast population, these cells displayed an extracellular matrix gene expression profile distinct from the pro-fibrotic phenotype typically observed in fibrillating adult atria and showed no evidence of fibrosis. Concurrently, monocytes/macrophages were activated and showed upregulated expression of the anti-fibrotic factor GPNMB. These findings suggest that adaptive tissue remodeling is counterintuitively prevented from progressing to fibrosis, potentially through GPNMB-mediated mechanisms. This study elucidates molecular pathways linking developmental atrial injury to myopathy and proposes novel strategies to attenuate atrial fibrillation progression.

pathology↗

bioRxiv2025

Structure-Guided Design of a Bioactive Covalent Small Molecule Targeting a Riboswitch

Small molecule ligands targeting structured RNA elements hold promise for modulating RNA function, serving as chemical probes and potential therapeutics. In this study, the characterization of phenylglyoxal-based covalent probe designed to target unpaired guanine residues in structured RNAs is reported. A structure-guided design strategy was employed to modify covalently unpaired guanines critical for flavin mononucleotide (FMN) binding to the FMN riboswitch. Covalent modification occurs at the designed site and modulates riboswitch function in a cellular reporter system, highlighting the potential of covalent mechanisms of action for bioactive RNA ligands.

biochemistry↗

bioRxiv2025

Multifunctional Injectable GelMA Hydrogels with MSN-Mediated Spatiotemporal Icariin Release for Enhanced Osseointegration in Bone Defects

The repair of bone defects is faced with the dual challenges of limited autograft donors and single function of artificial materials. The development of new materials with mechanical adaptability, drug-controlled release and osteogenic induction has become a research hotspot in bone tissue engineering. Here, we developed an injectable photocrosslinkable hydrogel by integrating icariin (ICA)-loaded mesoporous silica nanoparticles (MSN) into gelatin methacryloyl (GelMA). The amino-functionalized MSN enhanced compressive modulus by 1.5-fold (p < 0.05) and enabled pH-responsive ICA release (91.2{+/-}4.2% cumulative release over 15 days). Our in vitro findings revealed the composite hydrogel promoted BMSC proliferation was 1.43{+/-}0.04 times that of GelMA group. And express excellent osteogenic differentiation ability (ALP activity: 3.25-fold; Mineralization: 5.01-fold). In vivo study, Micro-CT revealed significantly higher bone volume fraction (BV/TV) in rat calvarial defects at 12 weeks, with histology confirming mature trabecular bone formation. This MSN-mediated spatiotemporal delivery system synchronizes immunomodulation and osteogenesis, offering a promising strategy for non-load-bearing osseointegration.

bioengineering↗

bioRxiv2025

Modeling Post-Gastrula Development via Bidirectional Pluripotent Stem Cells

The absence of stem cells capable of efficiently generating both trophoblast and epiblast lineages has hindered precise recapitulation of embryonic development. Through high-content chemical screening, we established an AL medium to generate mouse and human bidirectional pluripotent stem cells (BPSCs) characterized by concurrent OCT4/CDX2 expression. Mouse BPSCs demonstrated high plastic differentiation into trophoblast, epiblast and primitive endoderm lineages in vitro within 48 hours without exogenous induction factors and efficiently contributed to the embryo and extraembryonic tissues in vivo. Mechanistically, hyperactivation of the Wnt signaling pathway breaks the early lineage differentiation barrier by initiating a Lef1-dependent bypass. Remarkably, BPSCs can efficiently generated E8.5 embryoids that completed gastrulation and displayed advanced features such as brain development, a closed neural tube, a beating heart, somite formation, and primordial germ cells. These findings highlight BPSCs as a powerful tool for investigating early lineage specification and post-gastrulation embryonic development, with potential applications across multiple species.

developmental biology↗

bioRxiv2025

Monalisa: An Open Source, Documented, User-Friendly MATLAB Toolbox for Magnetic Resonance Imaging Reconstruction

PurposeAn open-source, user-friendly MATLAB framework for Magnetic Resonance Imaging (MRI) reconstruction was developed to simplify the reconstruction process, with a specific focus on non-Cartesian imaging and dynamic applications in the presence of motion. MethodsMonalisa is decomposing the reconstruction pipeline into clear modular steps, including raw data reading with flexible file-type abstraction, trajectory computation, density compensation, advanced coil sensitivity mapping, and tailored binning strategies through its "mitosius" preprocessing stage. The framework supports a suite of reconstruction methods, including iterative-SENSE (also named CG-SENSE), GeneRalized Autocalibrating Partial Parallel Acquisition (GRAPPA) reconstructions, and regularized reconstructions supporting both spatial and temporal regularization using l1 (Compressed Sensing (CS)) and l2 techniques, accommodating both Cartesian and non-Cartesian acquisitions. We performed benchmark experiments comparing Monalisa with the Berkeley Advanced Reconstruction Toolbox (BART) toolbox on simulated 2D radial acquisitions. ResultsResults of the comparison demonstrate competitive performance, yielding higher Structural Similarity Index (SSIM) and lower l2 error. Notably, Monalisa reconstructions exhibited fewer visible artifacts than BART. ConclusionBy providing comprehensive documentation, Monalisa serves not only as a powerful tool for research and clinical imaging but also as an educational platform to facilitate innovation in MRI reconstruction.

bioinformatics↗

bioRxiv2025

Towards Unified Neural Decoding with Brain Functional Network Modeling

Recent achievements in implantable brain-computer interfaces (iBCIs) have demonstrated the potential to decode cognitive and motor behaviors with intracranial brain recordings; however, individual physiological and electrode implantation heterogeneities have constrained current approaches to neural decoding within single individuals, rendering interindividual neural decoding elusive. Here, we present Multi-individual Brain Region-Aggregated Network (MIBRAIN), a neural decoding framework that constructs a whole functional brain network model by integrating intracranial neurophysiological recordings across multiple individuals. MIBRAIN leverages self-supervised learning to derive generalized neural prototypes and supports group-level analysis of brain-region interactions and inter-subject neural synchrony. To validate our framework, we recorded stereoelectroencephalography (sEEG) signals from a cohort of individuals performing Mandarin syllable articulation. Both real-time online and offline decoding experiments demonstrated significant improvements in both audible and silent articulation decoding, enhanced decoding accuracy with increased multi-subject data integration, and effective generalization to unseen subjects. Furthermore, neural predictions for regions without direct electrode coverage were validated against authentic neural data. Overall, this framework paves the way for robust neural decoding across individuals and offers insights for practical clinical applications.

neuroscience↗

bioRxiv2025

How Good is AlphaFold3 at Ranking Drug Binding Affinities?

Accurate affinity ranking of small molecules is pivotal for drug discovery. We investigate whether structure prediction models like AlphaFold3, pretrained on protein-ligand interactions, can address this task. Zero-shot evaluation of Protenix (an AlphaFold3-like model) demonstrates superior prioritization of active compounds over conventional scoring functions and state-of-the-art deep learning models. By further fine-tuning Protenix on structure-agnostic protein-ligand bioactivity data from ChEMBL and BindingDB, we develop AlphaRank that predicts pairwise affinity relationships. AlphaRank achieves prediction accuracy comparable to computationally intensive free energy perturbation (FEP+) workflows on standard benchmarks, while requiring substantially less computational resources. Our findings highlight the emergent potential of AlphaFold3-derived models in affinity ranking tasks and emphasize the necessity for targeted methodological exploration to fully harness their capabilities in drug discovery applications.

bioinformatics↗

bioRxiv2025

H3K79 methylation and H3K36 tri-methylation synergistically regulate gene expression in pluripotent stem cells

In metazoans, nucleosomes harboring H3K79 methylation (H3K79me) deposited by the histone methyltransferase DOT1L decorate actively transcribed genes. Although DOT1L is implicated in transcription regulation and pathogenesis of human diseases such as leukemia and neurological disorders, the role of H3K79me in these biological processes remains elusive. Here, we reveal a novel functional synergism between H3K79me and H3K36 tri-methylation (H3K36me3), another histone modification enriched at active genes, in regulating gene expression and neural cell fate transition. Simultaneous catalytic inactivation of DOT1L and the H3K36 methyltransferase SETD2 via gene editing leads to the global loss of H3K79me and H3K36me3, hyperactive transcription, and failures in neural differentiation. Interestingly, the loss of H3K79me and H3K36me3 causes increased transcription elongation, gained chromatin accessibility at a group of enhancers, and increased binding of TEAD4 transcription factor and its co-activator YAP1 at these enhancers. Furthermore, YAP-TEAD inhibition partially restores the expression levels of hyperactivated genes upon H3K79me/H3K36me3 loss. Taken together, our study demonstrates a synergistic role of H3K79me and H3K36me3 in regulating transcription and cell fate transition, unveils novel mechanisms underlying such synergism, and provides insight into designing therapies that target diseases driven by misregulation or mutations of DOT1L and/or SETD2.

genetics↗

bioRxiv2025

Computational Assessment of Circularization Impact on Saxitoxin G-quadruplex Aptamer Performance

Although high-affinity and high-specificity aptamers can be obtained by SELEX (Systematic Evolution of Ligands by Exponential Enrichment), and have good activity in vitro, their performance in vivo is poor. This is mainly because of the degradation of linear nucleic acids by nucleases in body fluids and the difficulty of maintaining stable 3D structures in complex body fluid environments, which seriously hinders the clinical application of aptamers. This makes circular aptamers, which can resist degradation and are more stable in complex body fluid environments, an attractive option. However, the cyclization process may have a considerable impact on the structure of the original linear aptamer, and blind cyclization may lead to a decrease in its affinity. Here, we developed a new method to guide the cyclization of saxitoxin (STX) aptamers based on molecular computation, and verified the activity of circular aptamers through bioactivity experiments to further verify the authenticity and reliability of our methods. Consistent with the computational analysis, although circularization disrupts the G4 structure, circular aptamer not only has a higher affinity than the linear one but also provides certain protection to mice and greatly prolongs their survival, which proves the accuracy and reliability of the circular structure designed by our computational method. Our findings provide important ideas for better guidance in the design of circular aptamers and demonstrate their great potential in therapeutic applications.

biochemistry↗

bioRxiv2025

Optimized optogenetic anti-CRISPR for endogenous gene regulation in Drosophila

Optogenetic tools - whose engineering requires a structural understanding of the target proteins - are attractive approaches for achieving endogenous gene regulation under minimally invasive conditions. To build an optogenetic system for controlling endogenous gene expression, we first identified Anti-CRISPR (Acr) proteins that can inhibit CRISPRa-mediated transcriptional activation in Drosophila. Next, we inserted optogenetic protein LOV2 in these Acrs, tested for their ability to optogenetically modulate endogenous gene upregulation (EnGup) through the CRISPRa-based flySAM system in Drosophila, and found that the photoswitchability of these prototypes was weak. Hence, we engineered an Acr-LOV2 fusion module with refined length of intrinsically disordered and ordered regions (IDR and IOR) and optimized LOV2. This optimized variant, whose application yielded new findings in vivo, was significantly more sensitive for EnGup under blue light than the prototypes. In short, not only does this work introduce the application of Acr proteins in an animal model, but it also provides insights for in vivo characterization of the IDR and the IOR of these small-sized proteins. Together, these findings establish a robust optogenetic toolbox for precise, light-sensitive endogenous gene regulation in Drosophila. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/651826v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@8ee937org.highwire.dtl.DTLVardef@71401eorg.highwire.dtl.DTLVardef@128a930org.highwire.dtl.DTLVardef@7bcf88_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

ReCellTy: Domain-specific knowledge graph retrieval-augmented LLMs workflow for single-cell annotation

To enable precise and fully automated cell type annotation with large language models (LLMs), we developed a graph-structured feature-marker database to retrieve entities linked to differential genes for cell reconstruction. We further designed a multi-task workflow to optimize the annotation process. Compared to general-purpose LLMs, our method improves human evaluation scores by up to 0.21 and semantic similarity by 6.1% across 11 tissue types, while more closely aligning with the cognitive logic of manual annotation.

bioinformatics↗

bioRxiv2025

In vivo mRNA delivery to the lung vascular endothelium by dicationic Charge-Altering Releasable Transporters

Endothelial cells (EC) comprise the pulmonary vascular bed and play a significant role in health and disease. Consequently, the EC niche represents an attractive therapeutic target for treating a wide range of pulmonary vascular diseases. We have identified a new class of dicationic Charge-Altering Releasable Transporters. These single-component transporters selectively deliver mRNA to the lung upon intravenous administration without the use of a targeting ligand. Significantly, the number and spatial array of cationic charges within the repeating units of the CART polymer are found to control both mRNA delivery efficacy and tissue tropism. High-resolution imaging revealed efficient mRNA delivery to endothelial cells in pulmonary arteries, veins and capillaries. The selective lung tropism of these new CARTs, coupled with the efficient and tunable synthesis of this new family of CART amphiphiles, represents an enabling platform for research and clinical applications.

bioengineering↗

bioRxiv2025

Mis-localization of PBPs in Staphylococcus aureus gdpP mutant contributes to β-lactam resistance and surface protein cross-wall trafficking

Mutations in gdpP are frequently associated with {beta}-lactam resistance in Staphylococcus aureus. GdpP is a phosphodiesterase that degrades the second messenger c-di-AMP, which plays a key role in osmoregulation and antibiotic resistance in many Gram-positive bacteria. However, the mechanisms of {beta}-lactam resistance remain unknown. We show here that deletion of gdpP disrupted penicillin-binding proteins (PBPs)-mediated deposition of YSIRK+ surface protein SpA to septal peptidoglycan (cross-wall). In contrast to their septal localization in WT staphylococcal cells, all four PBPs (PBP1-4) were drastically mis-localized as distinct single foci in {Delta}gdpP. The mis-localization of PBPs is attributed to c-di-AMP accumulation as overexpression of c-di-AMP synthetase dacA phenocopied {Delta}gdpP. In addition, {Delta}gdpP exhibited severe cell cycle retardation deficient in cell division initiation. The aberrant foci formation of PBPs altered the spatial distribution of cell wall synthesis but did not affect the overall cell wall cross-linking. The foci formation of PBPs correlated with {beta}-lactam resistance: the foci gradually decreased with increased concentrations of penicillin. We concluded that the aberrant spatial distribution of PBPs and the cell division defects of {Delta}gdpP contribute to {beta}-lactam resistance and YSIRK+ protein cross-wall trafficking.

microbiology↗

bioRxiv2025

Highly sensitive chemiluminescence imaging of misfolded proteins in neurodegenerative models

Visualizing misfolded proteins would greatly facilitate early diagnosis, etiology elucidation, and therapy monitoring of neurodegeneration. Although several probes have been reported, simple and versatile detection in vivo is still challenging. We demonstrated that both generic and precise detection of misfolded proteins could be achieved with a chemiluminescence probe, ADLumin-1. For the generic aspect, ADLumin-1 was highly sensitive to various misfolded proteins, showing up to 127.73-fold higher signal-to-noise ratio than Thioflavin T. ADLumin-1 could also non-invasively visualize misfolded proteins in mouse models of Parkinsons disease, Alzheimers disease and amyotrophic lateral sclerosis. Furthermore, ADLumin-1 displayed precise detection value for -synuclein by combining with PMCA in vitro and bioorthogonal ChRET imaging technology in vivo. ADLumin-1 can selectively detect -synuclein in CSF at the femtomolar level and enables in situ monitoring of misfolded -synuclein in vivo. Combining generality and precision, our findings could be widely applied in preclinical and clinical studies of neurodegenerative diseases. TeaserA highly sensitive chemiluminescence probe enables both generic and precise detection of various misfolded proteins

biochemistry↗

bioRxiv2025

Topoisomerase IIα orchestrates secretion of IL-6 and IL-8 with human papillomavirus replication

High-risk human papillomavirus (HPV) replication requires deregulation of host DNA damage response (DDR) and inflammatory pathways. DNA topoisomerase 2{beta} (Top2{beta}) was previously shown to promote HPV replication, while the function of its paralog Top2 in the viral life cycle remains unknown. Elevated levels of Top2 are consistently observed in cervical intraepithelial lesions and the related carcinomas, as well as in HPV-positive cell lines. Silencing Top2 with shRNA severely suppresses HPV genome maintenance and amplification, but in a DDR-independent manner. Instead, Top2 facilitates secretion of interleukin (IL)-6 and IL-8, which are necessary for HPV replication. Mechanistically, this manipulation is regulated by toll-like receptor 4 (TLR4). Top2 binds to the TLR4 promoter to transcriptionally induce TLR4 expression. Blockade of TLR4 signaling by the specific inhibitor TAK-242 significantly reduces the secreted IL-6/IL-8 levels and HPV replication. Overall, our results reveal a novel role of Top2 to shape the inflammatory microenvironment that benefits HPV replication, making it a promising therapeutic target for HPV-associated diseases. IMPORTANCEHuman papillomaviruses (HPVs) are oncogenic pathogens responsible for many HPV-related diseases such as cervical cancer. HPV replication depends on the subversion of host cellular machineries, particularly pathways governing DNA damage response (DDR) and inflammation. However, the roles of enzymes that directly introduce DNA nicks or mediate strand rejoining remain poorly characterized. Here we highlight a novel role of DNA topoisomerase 2 (Top2) in promoting HPV genome maintenance and amplification but in a DDR-independent manner. Unlike its previously studied paralog Top2{beta}, Top2 supports HPV replication by driving the secretion of inflammatory molecules interleukin (IL)-6 and IL-8, which are critical for the viral genome persistence and copy number expansion. To our knowledge, this is the first evidence that a DDR-associated protein manipulates cytokine secretion, rather than expression, to support HPV replication. Furthermore, blocking toll-like receptor 4 (TLR4) activities significantly reduced Top2-dependent IL-6/IL-8 secretion and impaired HPV replication. These findings establish Top2 as a crucial player in HPV pathogenesis, with a therapeutic potential for treating HPV-associated malignancies.

microbiology↗

bioRxiv2025

Rare Subset of T Cells Form Heterotypic Clusters with Circulating Tumor Cells to Foster Cancer Metastasis

The immune ecosystem is central to maintaining effective defensive responses. However, how immune cells in the periphery blood interact with circulating tumor cells (CTCs) - seeds of metastasis - remains largely understudied. Here, our analysis of the blood specimens (N=1,529) from patients with advanced breast cancer revealed that over 75% of the CTC-positive blood specimens contained heterotypic CTC clusters with CD45+ white blood cells (WBCs). Detection of CTC-WBC clusters correlates with breast cancer subtypes (triple negative and luminal B), racial groups (Black), and decreased survival rates. Flow cytometry and ImageStream analyses revealed diverse WBC composition of heterotypic CTC-WBC clusters, including overrepresented T cells and underrepresented neutrophils. Most strikingly, a rare subset of CD4 and CD8 double positive T (DPT) cells showed an up to 140-fold enrichment in the CTC clusters versus its frequency in WBCs. DPT cells shared part of the profiles with CD4+ T cells and others with CD8+ T cells but exhibited unique features of T cell exhaustion and immune suppression with higher expression of TIM-3 and PD-1. Single-cell RNA sequencing and genetic perturbation studies further pinpointed the integrin VLA4 (4{beta}1) in DPT cells and its ligand VCAM1 in tumor cells as essential mediators of heterotypic WBC-CTC clusters. Neoadjuvant administration of anti-4 (VLA4) neutralizing antibodies markedly blocked CTC-DPT cell clustering and inhibited metastasis for extended survival in preclinical mouse models in vivo. These findings uncover a pivotal role of rare DPT cells with immune suppressive features in fostering cancer dissemination through direct interactive clustering with CTCs. It lays a foundation for developing innovative biomarkers and therapeutic strategies to prevent and target cancer metastasis, ultimately benefiting cancer care. Brief summaryOur findings uncover a fostering role of immune-suppressive T cells in contact with circulating tumor cells and identify therapeutic approaches to eliminate devastating cancer metastasis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/646421v1_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@13b7862org.highwire.dtl.DTLVardef@15c97b2org.highwire.dtl.DTLVardef@1eb4fd2org.highwire.dtl.DTLVardef@1c588e1_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗