Biology subjects

Yu, Z.

Publications and source records attributed to Yu, Z..

At least 73 records · Page 4Linked to original sources

bioRxiv2026

Lethal permeabilization of host bacteria to small-molecule compounds during phage penetration

The tailed phages (Caudoviricetes) rely on specialized mechanisms to inject their double-stranded linear genomic DNA (gDNA) across the bacterial envelope. During this gDNA entry process, ionic fluxes and membrane depolarization may occur, potentially leading to increased vulnerability to antibiotic molecules. Here, we report that phage gDNA translocation combined with certain small molecules triggers a rapid and phage-specific cell permeabilization leading to growth arrest. Using live-cell fluorescence microscopy, we visualized the accumulation of otherwise excluded compounds such as anthracyclines and propidium iodide. We show that the influx and accumulation of these compounds depend on both the presence of an inner membrane (IM) receptor and persistent membrane depolarization. We further demonstrate that phage-induced permeabilization enhances the efficacy of certain antibiotics, enabling a synergistic elimination of antibiotic-resistant bacteria. Our results provide a mechanistic foundation for combining phages with small-molecule therapeutics and offer new insights into how phage entry relies on and alters host physiology.

microbiology↗

bioRxiv2026

Evolutionary genomics of local adaptation, climate vulnerability, and linarin metabolism in Opisthopappus longilobus

Global climate change and human activities are posing substantial threats to biodiversity. The genus Opisthopappus (O. taihangensis and O. longilobus), endemic to Chinas Taihang Mountains, possesses great ecological, ornamental and medicinal value. However, it is confronted with the pressures of habitat fragmentation and climate change. Here, we present the first haplotype-resolved, chromosome-scale genome assembly of O. longilobus ([~]2.95 Gb) and re-sequence 115 individuals across its range. Comparative analyses show Opisthopappus is sister to Artemisia-Chrysanthemum, with Opisthopappus and Chrysanthemum diverging at 5.15-5.18 million years ago. A profound genetic divergence is evident between O. taihangensis and O. longilobus, resulting in two distinct lineages within each species, driven by geography and climate. Our analyses indicate restricted gene flow, low diversity, and recurrent demographic bottlenecks collectively contribute to their endangerment. By integrating population genomics and environmental variables, we identified 4,437 core adaptive genes linked to water deprivation, and metabolism. Genomic offset predicts higher maladaptation risk in populations under drastic climate change. Furthermore, diverged promoters of two O-methyltransferase genes, OMT250 and OMT310, likely underlie the differential acacetin/linarin accumulation between C. morifolium and O. longilobus. These findings advance understanding of Opisthopappus evolution and climate vulnerability, offering a model for genomics-guided biodiversity conservation.

plant biology↗

bioRxiv2026

Urine Recirculation During Normothermic Kidney Preservation Improves Energy Balance Involving the Urea and TCA Cycles

BackgroundDeceased donor kidneys experience cellular stress before undergoing transplantation. To alleviate this, preservation techniques were developed including normothermic machine perfusion (NMP). MethodsHere, we performed kidney NMP on discarded human kidneys for up to 24 hours. Volume management was regulated either by urine recirculation (UR) or urine replacement (NUR) with Ringers lactate. Notably, UR led to longer perfusion times compared to NUR. To investigate kidney NMP metabolic traits with or without UR over time, we performed longitudinal metabolomics analyses of perfusates of eight NMP kidneys by 2D-gas chromatography mass spectrometry (GCxGC-MS). ResultsOver 600 metabolic features were profiled, from which 74 were identified and 54 consistently quantified across 26 perfusate samples. Most notably, elevated levels of disaccharides (different isomers), hydroxy-purines, urea, glutamate and amino acids associated with the perfusion factor UR. Moreover, donor estimated glomerular filtration rate (eGFR) correlated significantly with the accumulation of lactate and gluconate. Most strikingly, lactate levels seemed to be more balanced in UR NMP perfusate, which otherwise accumulated rapidly within the first six hours. ConclusionsKidney preservation by NMP was previously limited to hours. UR-NMP affected kidney energy homeostasis, carbohydrate & purine metabolism and the Urea and TCA cycles. These insights add value to explain how urine-driven adaptations contribute to prolonged kidney function under NMP. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSDeceased donors provide kidneys that experience cellular stress during retrieval and during transplantation. To attenuate tissue damage, preservation techniques were optimised to offer the most optimal environment for kidney organs retrieved from donation after circulatory death and brain death patients. Normothermic machine perfusion (NMP) of donor kidneys has been considered feasible, safe, offers viability assessment and contributes to favourable outcomes. However, there has been a limit in the length of time that this preservation method could be applied to kidney organs, thereby potentially restricting functional recovery of the kidney before organ transplantation. Added value of this studyBefore urine recirculation (UR) was introduced, NMP time was limited to a few hours. Remarkably, NMP with UR led to longer perfusion times and more stable kidney organ function as compared to no urine recirculation (NUR). In order to find out why, we compared urine recirculation with Ringers lactate solution for volume management during NMP on discarded human kidneys for up to 24 hours. Kidney NMP metabolic traits with or without UR over time were measured. More than 600 metabolic features were profiled, Most strikingly, lactate levels seemed to be more balanced in UR NMP perfusate of the course of 24 hours, which otherwise accumulated rapidly within the first six hours. Taken together, UR-NMP affected kidney energy metabolic pathways and rendering these more balanced. Ultimately, these urine-driven adaptations contribute to prolonged kidney function under NMP. Implications of all the available evidenceNMP as a procedure to preserve kidney organs including urine recirculation is now becoming standard in many transplantation units around the world. Our study provided a molecular snapshot of why kidney organs preserved in this way are maintained longer with a functionally active metabolism. This provides the basis for additional improvements leading to better kidney organ preservation, ultimately resulting in benefits for kidney transplant recipients.

pathology↗

bioRxiv2026

p62 protein pleomorphism confers tissue-specific function

Protein structure dictate function, and proteins often perform the same function in different cell/tissue-type environments. Here, we report that in Drosophila melanogaster, the broadly expressed protein p62/SQSTM1 instead performs mutually exclusive functions across tissues - autophagy in midgut and mitochondria-associated proteostasis in muscle. These functional differences arise from tissue-specific secondary and tertiary structures adopted by the same p62 polypeptide, rather than protein abundance, isoforms, post-translational modification, or binding-partner availability. The tissue-specific structures are cell autonomous and resistant to environmental perturbation. Deletion of a short intrinsically disordered region converts muscle p62 to a midgut-like structural and functional state, but this forced switch causes muscle dysfunction, linking tissue-specific physiology to alternative structural states of the same polypeptide. We posit that Drosophila p62 exemplifies a mechanism for tissue-specificity in which intrinsic structural plasticity and the physiochemical/molecular environment of a tissue enable a broadly expressed protein to adopt tissue-specific structure and function.

cell biology↗

bioRxiv2026

Autoimmune CD4+T cells Cause Meibomian Gland Dysfunction

Sjogren disease (SjD) is an autoimmune disease driven by autoreactive CD4+T cells that leads to an immune-mediated loss of lacrimal glands. Meibomian glands are lipid-producing glands in the eyelids that help prevent tear evaporation. While the role of T cells in lacrimal gland-mediated destruction is well established, it is unknown whether pathogenic T cells can cause MG dysfunction (MGD). Herein, we investigated whether autoreactive CD4+T cells induce MGD and characterized the pathophysiologic mechanisms using an adoptive transfer model. T cells were isolated from CD25KO (CD4KO) or wild-type (CD4WT) mice, transferred into Rag1KO mice. Further, CD4KO cells were co-adoptively transferred with WT regulatory T cells (CD4KO+TregsWT). Our results demonstrate that CD4KO recipients had MG dropout, CD4+IFN-{gamma}+ infiltration, increased MHC II presentation within the periglandular area, MG fibrosis, and decreased lipid production and upregulation of pathways related to inflammation, including Type II interferon signaling. Rag1KO, CD4WT, and CD4KO+TregsWT recipients exhibited minimal inflammation in the periglandular MG area. These results indicate that autoimmune CD4+T cells are sufficient to cause MGD, and healthy young regulatory T cells can prevent T-cell-mediated damage. Taken together, our findings provide mechanistic insights into the pathogenesis autoimmune SjD, and could impact how patients are managed in the clinic.

pathology↗

bioRxiv2026

DeepKOALA: A Fast and Accurate Deep Learning Framework for KEGG Orthology Assignment

The KEGG Orthology (KO) system links DNA and protein sequences to biological functions and pathways, providing a curated, fundamental and consistent annotation framework across all domains of life. While accurate, traditional sequence alignment-based annotation methods are computationally expensive, which severely limits their application in large-scale datasets. To address this challenge, we introduce DeepKOALA, a deep learning approach based on Gated Recurrent Units (GRU), which frames KO annotation as an open-set recognition task. This design reduces false positives arising from out-of-scope sequences and, together with a lightweight GRU backbone, enables high-throughput annotation. The GRU-based model was benchmarked against four other deep learning architectures and showed the best balance between speed and accuracy. We further performed a cross-species evaluation of DeepKOALA in comparison with existing KO annotation tools, where it achieved an F1-score of 0.8653 and 37.5-fold acceleration compared with BlastKOALA. We also provide a specialized fragment model for handling incomplete sequences and an optional Multi-domain mode. Together, these features make DeepKOALA a scalable, efficient, and accurate solution for high-throughput function annotation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC="FIGDIR/small/698072v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@8c3b53org.highwire.dtl.DTLVardef@8acfa8org.highwire.dtl.DTLVardef@147398borg.highwire.dtl.DTLVardef@112d762_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

Epigenetic Coalitions Couple Tissue Growth to Generate Periodic Colour Patterns in Birds

Periodic patterning is fundamental to biological organization. In birds, colour stripes and spots on growing embryonic surface and elongating feather filaments provide a unique system to study continuous periodic patterning in expanding domains. Agouti-signaling protein (ASIP) directly reports epigenomic activity during colour patterning. Using a neural-network-like architecture, we show that ASIPs cis-regulatory landscape functions as hidden layers, integrating morphogen feedback, chromatin topology, and tissue geometry to generate discrete colour outputs. Single-nucleus multiome and Micro-C uncover stage- and context-specific enhancer-silencer coalitions. Epidermal Wnt ligands activate ASIP while inducing Wnt inhibitors in fibroblasts, forming a negative-feedback loop coupling periodic patterning to domain expansion. Comparative cross-tissue and cross-species analyses define cis-regulatory modules comprising an epigenetic grammar; functional assays highlight retrotransposon co-option expanding ASIPs cis-regulatory repertoire, potentially contributing to colour pattern evolution. Together, these findings motivate a Turing-principle-based communication model: ASIP reflects epigenetic coalitions shifting to drive diverse, environmentally tunable colour motifs for adaptation.

developmental biology↗

bioRxiv2025

NW-flex: flexible-block sequence alignment for short tandem repeats

Aligning sequencing reads to short tandem repeats (STRs) is challenging: the number of repeat copies in a read often differs from the reference, and small changes inside and around the repeat can lead to many competing alignments. We introduce NW-flex, a simple extension of classical sequence alignment that addresses this problem. NW-flex takes a reference with a designated internal block and, while allowing that block to contract to any shorter substring, identifies the best-scoring alignment. Apart from this substring choice, the alignment obeys the usual substitution scoring and gap constraints. For STRs, we design the flexible block with enough repeat copies to accommodate any expected repeat count. The alignment then contracts the reference to match the read while the unique flanks remain fully constrained. NW-flex requires a small modification to the Needleman-Wunsch/Gotoh algorithm, adds minimal computational overhead, and preserves optimality with respect to classical scoring. We provide open-source Python and Cython implementations, a set of worked examples, and notebooks that reproduce the figures and validate correctness against baseline alignments.

bioinformatics↗

bioRxiv2025

Mechanisms of HSV-1 helicase-primase inhibition and replication fork complex assembly

Herpesviruses are widespread double-stranded DNA viruses that establish lifelong latency and cause various diseases. Although DNA polymerase-targeting antivirals are effective, increasing drug resistance underscores the need for alternatives. Helicase-primase inhibitors (HPIs) are promising antivirals, but their mechanisms of action are poorly defined. Furthermore, how the helicase-primase (H/P) complex and DNA polymerase coordinate genome replication is not well understood for herpesviruses. Here, we report cryo-EM structures of the herpes simplex virus (HSV) H/P complex bound to HPIs, showing that these lock the helicase-primase complex in an inactive conformation. Single-molecule assays reveal that HPIs cause helicase-primase complexes to pause in unwinding activity on DNA. The structure of an HPI-bound replication fork complex, comprising the H/P complex (UL5, UL52, and UL8) and polymerase holoenzyme (UL30 and UL42), reveals a previously uncharacterized interface bridging these complexes. These findings provide a structural framework for understanding herpesvirus replisome assembly and advancing inhibitor development.

microbiology↗

bioRxiv2025

Synchronized Latency Reversal and Immune Clearance by a Multifunctional Fusion Protein Enables HIV-1 Reservoir Reduction

Strategies that concurrently reactivate latent reservoirs and enhance immune-mediated clearance hold significant promise for achieving an HIV cure. Here, we developed hyperIL-15xsCD4-Fc (15xsCD4-Fc), a fusion protein that integrates latency reactivation, targeted immune engagement, and effector-mediated killing into a single molecule. This agent not only potently reverses HIV-1 latency in CD4+ T cells from people living with HIV-1 (PLWH) through coordinated IL-15 receptor signaling and sCD4-mediated HIV-1 envelope (Env) engagement, but also enhances antigen-specific CD8+ T cell response in PBMCs derived from PLWH. Furthermore, 15xsCD4-Fc enables Env-specific elimination of reactivated latently infected cells by NK cells while preventing off-target cytotoxicity. In PBMCs from PLWH, 15xsCD4-Fc reduced replication-competent HIV-1 DNA by 93.8%. In antiretroviral treated HIV-1-infected humanized mice, the molecule demonstrated both safety and efficacy in diminishing viral reservoir in lymphoid organs. This spatiotemporally coupled approach to reservoir exposure and immune recognition establishes a clinically viable strategy for clearing the HIV-1 reservoir. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC="FIGDIR/small/693434v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@8f8f0org.highwire.dtl.DTLVardef@10f63f7org.highwire.dtl.DTLVardef@16c1de2org.highwire.dtl.DTLVardef@11e1787_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

EMCF ecosystem: Towards pretrained foundation model for electron microscopy image analysis

Volume electron microscopy (vEM) enables nanoscale visualization of three-dimensional (3D) cellular ultrastructure, providing critical insights into physiological processes and pathological alterations. However, its application to large-scale biological tissues remains constrained by two major bottlenecks: prolonged image acquisition and inefficient data processing. Here, we present EMCF ecosystem (EMCFsys), an integrated ecosystem designed to overcome these challenges through three key components: a large-scale benchmark dataset (EMCFD) comprising 4,002,802 high-quality images across 14 EM modalities and 6 biological kingdoms; a foundation image restoration model (EMCellFiner); and a scalable image analysis foundation model (EMCellFound). Together, these modules systematically enhance image quality and substantially improve analysis efficiency. Our results show that EMCellFiner outperforms specialist models in restoring degraded images, even surpassing original ground truth sharpness in certain artifact regions, and reduces imaging time by 16-fold by enabling low-resolution and low dwell time acquisition. EMCellFound exhibits exceptional feature discriminability, outperforms specialist models in classification, semantic segmentation and instance segmentation. It also enables high-precision 3D reconstruction of organelles (e.g., endoplasmic reticulum) with minimal labeled data (0.01% of total volume). We validated the EMCFsys on unseen datasets across diverse biological contexts and imaging platforms. By publicly releasing both the dataset and models, we establish a scalable paradigm for automated, high-throughput vEM data interpretation, accelerating exploration of lifes nanoscale structure and function across biology.

cell biology↗

bioRxiv2025

Elucidation and engineering of arabinofuranosyltransferase to enable total de novo biosynthesis of paris saponins in yeast

Paris saponins (PSs) are structurally complex steroidal saponins that, due to their diverse glycosylation patterns, exhibit a range of significant pharmacological activities, including anti-tumor and antibacterial effects. However, incomplete characterization of the key enzymes responsible for glycosylation modifications has hindered their efficient heterologous biosynthesis. In this study, we reprogrammed the sugar donor specificity of a steroidal rhamnosyltransferase (UGT93M3) to enable the transfer of arabinofuranose (Araf). Through structural analysis, we identified key amino acid residues (368H/Q) that play an important role in determining Araf donor specificity. Guided by this insight, we successfully reconstructed the paris saponin I (PSI) biosynthetic pathway in Saccharomyces cerevisiae using engineered enzymes. To address challenges related to donor availability, we introduced UDP-sugar biosynthetic modules (UDP-Rha and UDP-Araf) into yeast. With this integrated platform, we were able to de novo produce a range of paris saponins, including diosgenin-3-O-glucosyl-(1[->]6)-glucoside (DGG), diosgenin-3-O-rhamnosyl(1[->]2) [glucosyl(1[->]6)]glucoside (DRGG) and paris saponin II. This work establishes a novel microbial platform for the sustainable production of paris saponins, particularly PSI, advancing the biosynthesis of steroidal glycosides and providing a potential strategy for the industrial-scale production of bioactive saponins. TeaserIn this study, we report the first complete de novo biosynthesis of four bioactive PSs, PSI, PSII, DGG and DRGG, in Saccharomyces cerevisiae from simple carbon source. Key advances include: (i) A single amino-acid switch (N368H) in the rhamnosyltransferase UGT93M3 endowed high-efficiency transfer of the rare five-membered arabinofuranose, solving a bottleneck in PS I biosynthesis; (ii) Elucidation of the molecular basis for sugar-donor specificity through AlphaFold3 docking and 300-ns molecular-dynamics simulations, revealing a histidine "latch" that stabilizes UDP-Araf in the catalytic pose; (iii) Construction of a 16-gene yeast chassis that integrates plant P450s, optimized glycosyltransferases, and de novo modules for UDP-rhamnose and UDP-arabinofuranose supply, achieving de novo microbial production of PS II, DGG, DRGG and PS I from glucose alone.

synthetic biology↗

bioRxiv2025

Analytical Solutions for the Time-Dependent Dynamics of Stochastic Gene Expression with mRNA-sRNA Interactions

The antagonistic interaction between small RNAs (sRNAs) and messenger RNAs (mRNAs) constitutes a fundamental regulatory mechanism of gene expression in both prokaryotic and eukaryotic cells. However, the stochastic nature of transcription renders mean-field approximations inadequate for quantitative analysis of such systems. In the regime of strong sRNA-mRNA antagonism, we generalize the conventional probability-generating-function (PGF) framework and derive a novel approximate solution in the form of a generalized PGF, which can be analytically transformed into the time-dependent joint distribution of sRNA and mRNA via Laurent series expansion. The proposed approximation accurately captures the full stochastic dynamics across diverse systems exhibiting strong antagonism, while incorporating key biological features such as transcriptional burstiness, translation and sRNA recycling over the entire temporal range. Building on this analytical foundation, we further develop a generalized-PGF-based parameter-inference method that enables efficient and precise estimation of kinetic parameters, achieving inference speeds up to three orders of magnitude faster than traditional maximum-likelihood estimation approaches.

systems biology↗

bioRxiv2025

Cold Atmospheric Plasma for Alzheimer's disease

Lightning has been proposed as a pivotal energy source driving prebiotic chemical evolution and early life processes. Similarly, external physical stimuli such as sound and light have been shown to modulate neurophysiological activity and mitigate Alzheimers disease (AD) pathology by promoting amyloid-{beta} (A{beta}) clearance. Here, we demonstrate that cold atmospheric plasma (CAP) acts as a joule-level analog of lightning, integrating light, sound, and reactive species to modulate AD progression in a mouse model. Using multimodal analyses, we show that CAP treatment enhances key neuroimmune signaling pathways in an AD murine model, including microglial activation, without inducing pathological alterations at the functional, transcriptomic, or proteomic levels in healthy mice. These findings highlight CAP as a safe and efficacious modality for modulating neurodegenerative processes, establishing a foundation for its therapeutic translation in AD and related disorders.

bioengineering↗

bioRxiv2025

Network modularity reveals context and state-dependent reorganization of time-varying functional connectivity in single-cell resolved neural activity recordings

An important goal of neuroscience is to understand how biological neural networks organize activity at multiple scales to enable complex information processing and behavioral output. To address this challenge, large-scale neural activity datasets with increased resolution and wider coverage have become more prevalent across many model systems. However, bridging the gap in scale between changes in pairwise functional connectivity between neurons and changes in brain-wide organization of activity remains a key challenge. In this work, we demonstrate application of modularity-based community detection and network modularity to single-cell resolved recordings, for the first time, as a method to summarize complex changes in time-varying functional connectivity, facilitating comparisons across multiple time windows, recordings, and conditions. We apply these methods to both single-cell resolved multi-cell and whole-brain activity recordings. In the multi-cell recordings, we find that food odor changes functional connectivity between existing network modules in a C. elegans locomotory interneuron network, rather than reorganizing them. In spontaneous whole-brain activity, we identify several key hub neurons and combinations that significantly destabilize module assignments when silenced. Together, these results demonstrate community detection and modularity as a method for detecting context and network state-dependent changes in functional connectivity at the intermediate scale of network modules in single-cell resolved neural activity. Results from these analyses facilitate future investigation of mechanisms that mediate organization of neural activity at intermediate scales.

neuroscience↗

bioRxiv2025

Modified self-amplifying RNAs mediate robust and prolonged gene expression in the mammalian brain

Facile, non-genomic integrating gene delivery technologies are lacking for rapid onset and prolonged protein expression in the brain. Here we report the protein expression and cell type tropism for an advanced messenger ribonucleic acid (mRNA) technology, modified 5-hydroxymethylcytidine (hm5C) self-amplifying ribonucleic acid (saRNA), when injected into the mouse brain or applied to ex vivo human cortical brain slices. saRNA, encoding fluorescent proteins, encapsulated in an LNP formulation comprising ALC-0315 (present in Comirnaty(R)) efficiently mediates long-lasting protein expression in mouse brain cells beyond five weeks, with detectable expression in some neurons at three months. hm5C saRNA substantially outperforms N1m{Psi} mRNA. In addition to transfecting astrocytes and neurons at the injection site, hm5C saRNA-LNPs label neurons retrogradely. Excitingly, hm5C saRNA-LNPs afford protein expression in human cortical brain slices, with expression emerging within 24 hours and lasting beyond 76 days. Modified saRNA provides new opportunities for mechanistic neuroscience research and therapeutic development.

neuroscience↗

bioRxiv2025

Comprehensive benchmarking of somatic single-nucleotide variant and indel detection at ultra-low allele fractions using short- and long-read data

Mosaic mutations in normal tissues occur at low variant allele fractions (VAFs), complicating detection. To benchmark strategies, the SMaHT Network created a cell-line mixture (1:49) and produced ultra-deep whole-genome sequencing using short and long reads (five centers, 180-500x each). We assembled a reference of 44,008 mosaic SNVs and 2,059 Indels, cross-validation between platforms to expose limits of short-read analysis. We also partitioned the genome by mappability to examine the impact of genomic context, added a negative reference set, and accounted for culture-derived mutations. When seven institutions applied eleven algorithms to mixture data, call sets were largely discordant across tools and replicates, partly reflecting stochastic presence of low-VAF mutations in biological replicants. For >2% VAF SNVs, sensitivity and precision approached [~]80% at [≥]300x, with little gain from additional sequencing. This work provides a comprehensive framework for reliable detection of low-VAF mutations in non-cancer tissues and a valuable resource for the community.

bioinformatics↗

bioRxiv2025

In vivo colonic epithelial cell editing attenuates intestinal inflammation in mice

Engineered epithelial cells with enhanced efferocytosis capacity promote inflammation resolution and restore tissue homeostasis. Here, we developed a therapeutic approach to generate efferocytosis boosting epithelial cells in vivo by delivering mRNA in lipid nanoparticles (LNPs). We demonstrate that LNP-mediated delivery of mRNA enables efficient in vitro and in vivo functional editing of epithelial cells. In murine models of colitis, intraperitoneal administration of mRNA-loaded nanoparticles designed to boost efferocytosis markedly attenuated intestinal inflammation and halted disease progression. This strategy provides a proof of concept that epithelial cells can be functional engineered in situ and represents a promising therapeutic avenue for mitigating inflammatory tissue damage. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/678706v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@874991org.highwire.dtl.DTLVardef@1eefbfforg.highwire.dtl.DTLVardef@e22fa6org.highwire.dtl.DTLVardef@1a6480d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗