Biology subjects

Shao, R.

Publications and source records attributed to Shao, R..

9 recordsLinked to original sources

bioRxiv2026

Transforming the cytokine literature into a resource for experimental analysis and discovery

Cytokine biology is dispersed across hundreds of thousands of publications, making it difficult to use systematically when interpreting new experiments. Large language models (LLMs) can assist with focused literature interpretation, but ad hoc retrieval remains incomplete and unreliable. We present the Cytokine Effect Database (CytED), a framework for interfacing user-supplied experimental datasets with literature knowledge at scale. CytED uses a multi-step LLM pipeline to generate over a million cytokine-cell type-effect triples from 110,000 full-text publications, with annotations for experimental context and directional changes in genes, pathways, and cellular processes. This structure enables quantitative comparison between observed perturbation responses and prior literature across cytokines, cell types, and experimental contexts. Applied to in vitro IL-10 stimulation of PBMCs, CytED identifies unexpected pro-inflammatory features in monocytes and systematic in vivo-in vitro differences in cytotoxicity responses in CD8+ T cells. CytED infers cytokine signaling, distinguishes primary from secondary cytokine effects, and guides the design of combinatorial perturbation screens. Together, CytED establishes a general paradigm for converting unstructured domain literature into analytical tools that bridge literature and experiment.

immunology↗

bioRxiv2026

Modular organization and selective motifs in the insula provide structural priors for efficient learning

The insular cortex (IC) integrates diverse sensory and interoceptive signals to support emotional and cognitive functions, exhibiting topologically functional distinctions. Although long-range pathways of the IC have been extensively mapped, the contribution of intra-IC architecture to network-level information processing remains poorly understood. Here we reconstructed single-cell projectomes of 2,267 IC neurons, generating a comprehensive cellular-resolution map of intra-IC connectivity. Graph-theoretic analyses revealed a hierarchical, topographically organized modular network with a hub-and-spoke organization and selective motif enrichment. Embedding these anatomical priors into recurrent neural network models demonstrated that intrinsic IC topology confers a distinct computational advantage: across multiple cognitive tasks, IC-initialized networks learned faster and exhibited better robustness to perturbations than those initialized with shuffled, randomized, or neighboring somatosensory cortical architectures. Together, these findings identify the IC as a structurally specialized cortical hub whose internal wiring supports efficient learning and provides design principles for brain-inspired networks.

neuroscience↗

bioRxiv2025

Rapid and Complete Inactivation of Enveloped Viruses by Electrochemical Disinfection: Unraveling the Contribution of Reactive Chlorine Species

Waterborne viruses pose significant threats to global water safety. Electrochemical (EC) disinfection is considered a promising next-generation technology to address this challenge. However, its efficacy against enveloped viruses remains inadequately under-stood. In this study, we employed bacteriophage Phi6 as a surrogate to systematically eval-uate the inactivation efficiency and damage mechanisms of enveloped viruses in a flow-through EC reactor. Experimental results indicated that Phi6 was more susceptible to EC disinfection than common bacterial surrogates. Comprehensive damage was observed across all major viral components, including structural proteins, the lipid envelope, and the RNA genome. The electrogenerated reactive chlorine species (RCS) were identified as the primary agent responsible for this inactivation, exhibiting higher reactivity than conven-tional free chlorine. Furthermore, radical chlorine species were also confirmed to be pro-duced during EC disinfection, contributing to rapid and extensive viral inactivation. This study demonstrates the feasibility of EC disinfection for inactivating enveloped viruses and provides deeper mechanistic insights into its highly efficient viral inactivation performance. SYNOPSISOur results elucidate the rapid inactivation and thorough damage of the enveloped virus surrogate Phi6 by electrogenerated reactive chlorine species during electrochemical disinfection. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/688411v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@7e8c29org.highwire.dtl.DTLVardef@23fcedorg.highwire.dtl.DTLVardef@b26312org.highwire.dtl.DTLVardef@1864ab1_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Pooled overexpression screening identifies PIPPI as a novel microprotein involved in the ER stress response

Microproteins encoded by short open reading frames (sORFs) of less than 100 codons have been predicted to constitute a substantial fraction of the eukaryotic proteome. However, relevance and roles of the majority of microproteins remain undefined because only a small fraction of these intriguing cellular players have been in-depth characterized so far. Here we use pooled overexpression screens with a library of 11338 sORFs to overcome the challenge of elucidating which of the thousands of putative translated sORFs are biologically functional. As a proof-of-concept, we performed a phenotypic screen to identify sORFs protecting cells from treatment with the nucleotide analogue 6-thioguanine. With this approach, we identified two cytoprotective microproteins: altDDIT3 and PIPPI. PIPPI is encoded as part of the LC16a core duplicon/Morpheus gene cluster, a highly duplicated region of the human genome, which is undergoing rapid positive selection in primates. Our data show that PIPPI interacts with proteins of the endoplasmic reticulum, including protein disulfide isomerase ERp44. Besides providing mechanistic insights on a new microprotein, this study highlights the power of using pooled overexpression screens to identify functional microproteins.

cell biology↗

bioRxiv2021

3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib

Osimertinib sensitive and resistant NSCLC NCI-H1975 clones were used to model osimertinib acquired resistance in humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation were found in resistant clones. Resistant tumors in humanized mice were initially partially responsive to osimertinib, then aggressive tumor regrowth occurred accompanied by an immunosuppressive tumor microenvironment. 3-phosphoinositide-dependent kinase 1 (PDK1) was identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitized resistant clones and a patient derived xenograft (PDX) with acquired resistance to osimertinib. PDK1 knock-out dysregulated PI3K/Akt/mTOR signaling, promoted cell cycle arrest at the G1 phase, and inhibited nuclear translocation of yes-associated protein (YAP). Higher expression of PDK1 was found in patients with progressive disease following osimertinib treatment. PDK1 is a central upstream regulator of two critical drug resistance pathways: PI3K/AKT/mTOR and YAP.

cancer biology↗

bioRxiv2021

Verbena officinalis L. regulates killing efficiency of natural killer cells

Natural killer (NK) cells play a key role in eliminating pathogen-infected cells. Verbena officinalis (V. officinalis) has been used as a medical plant in traditional and modern medicine, exhibiting anti-tumor and anti-inflammation activities, but its roles in immune responses still remains largely elusive. In this work, investigated the regulation of inflammation and NK functions by V. officinalis extract (VO-extract). In an influenza virus infection mouse model, oral administration of VO-extract alleviated lung injury, promoted maturation and activation of NK cells residing in the lung, and decreased the levels of inflammatory cytokines (IL-6, TNF- and IL-1{beta}) in the serum. We further analyzed the impact of five bioactive components of VO-extract on NK killing functions. Among them, Verbenalin enhanced NK killing efficiency significantly as determined by real-time killing assays based on plate-reader or high-throughput live-cell imaging in 3D using primary human NK cells. Further investigation showed that treatment of Verbenalin accelerated killing processes by reducing the contact time of NK cells with their target cells without affecting NK proliferation, expression of cytotoxic proteins, or lytic granule degranulation. Together, our findings reveal that low doses of V. officinalis can achieve a satisfactory anti-inflammation effect against viral infection in vivo, and V. officinalis regulates activation, maturation and killing functions of NK cells. NK killing efficiency is enhanced by Verbenalin from V. officinalis, suggesting a promising potential of verbenalin to fight viral infection.

immunology↗

bioRxiv2021

Newly synthesized RNA Sequencing Characterizes Transcription Dynamics in Three Pluripotent States

Unique transcriptomes define naive, primed and paused pluripotent states in mouse embryonic stem cells. Here we perform transient transcriptome sequencing (TT-seq) to de novo define and quantify coding and non-coding transcription units (TUs) in different pluripotent states. We observe a global reduction of RNA synthesis, total RNA amount and turnover rates in ground state naive cells (2i) and paused pluripotency (mTORi). We demonstrate that elongation velocity can be reliably estimated from TT-seq nascent RNA and RNA polymerase II occupancy and observe a transcriptome-wide attenuation of elongation velocity in the two inhibitor-induced states. We also discover a relationship between elongation velocity and termination read-through distance. Our analysis suggests that steady-state transcriptomes in mouse ES cells are controlled predominantly on the level of RNA synthesis, and that signaling pathways governing different pluripotent states immediately control key parameters of transcription.

systems biology↗

bioRxiv2021

Genome-wide mapping of G-quadruplex structures with CUT&Tag

Single-stranded genomic DNA can fold into G-quadruplex (G4) structures or form DNA:RNA hybrids (R loops). Recent evidence suggests that such non-canonical DNA structures affect gene expression, DNA methylation, replication fork progression and genome stability. When and how G4 structures form and are resolved remains unclear. Here we report the use of Cleavage Under Targets and Tagmentation (CUT&Tag) for mapping native G4 in mammalian cell lines at high resolution and low background. Mild native conditions used for the procedure retain more G4 structures and provide a higher signal-to-noise ratio than ChIP-based methods. We determine the G4 landscape of mouse embryonic stem cells (mESC), observing widespread G4 formation at active promoters, active and poised enhancers. We discover that the presence of G4 motifs and G4 structures distinguishes active and primed enhancers in mESCs. Further, performing R-loop CUT&Tag, we demonstrate the genome-wide co-occurence of single-stranded DNA, G4s and R loops, suggesting an intricate relationship between transcription and non-canonical DNA structures.

genomics↗

bioRxiv2018

Genome Scale Epigenetic Profiling Reveals Five Distinct Subtypes of Colorectal Cancer

BACKGROUNDColorectal cancer is an epigenetically heterogeneous disease, however the extent and spectrum of the CpG Island Methylator Phenotype (CIMP) is not clear.\n\nRESULTSAn unselected cohort of 216 colorectal cancers clustered into five clinically and molecularly distinct subgroups using Illumina 450K DNA methylation arrays. CIMP-High cancers were most frequent in the proximal colons of female patients. These dichotomised into CIMP-Hl and CIMP-H2 based on methylation profile which was supported by over representation of BRAF (74%, P<0.0001) or KRAS (55%, P<0.0001) mutation, respectively. Congruent with increasing methylation, there was a stepwise increase in patient age from 62 years in the CI MP-Negative subgroup to 75 years in the CIMP-Hl subgroup (P<0.0001). There was a striking association between PRC2-marked loci and those subjected to significant gene body methylation in CIMP-type cancers (P<1.6xl078). We identified oncogenes susceptible to gene body methylation and Wnt pathway antagonists resistant to gene body methylation. CIMP cluster specific mutations were observed for genes involved in chromatin remodelling, such as in the SWI/SNF and NuRD complexes, suggesting synthetic lethality.\n\nCONCLUSIONThere are five clinically and molecularly distinct subgroups of colorectal cancer based on genome wide epigenetic profiling. These analyses highlighted an unidentified role for gene body methylation in progression of serrated neoplasia. Subgroup-specific mutation of distinct epigenetic regulator genes revealed potentially druggable vulnerabilities for these cancers, which may provide novel precision medicine approaches.

genomics↗