Biology subjects

Liu, Y.

Publications and source records attributed to Liu, Y..

At least 721 records · Page 40Linked to original sources

bioRxiv2025

Modular, reconfigurable fiber-based neural probe (MoRF probe) with interchangeable and tunable optical waveguide, microfluidic channel, and microelectrodes

Neuroscience is at an exciting juncture at which large-scale in vivo electrophysiology, including in humans, is intersecting symbiotically with revolutionary computational and statistical methods. Maintaining this relationship requires increasingly advanced neural probes for multimodal interrogation of neural circuitry (e.g. perturbation experiments are of value to computational modeling). Here, we developed a low cost modular and reconfigurable recording and stimulation fiber-based neural probe (MoRF) fabricated via a first step thermal drawing process (TDP) and a second step thermal tapering process (TTP). We demonstrated the device modularity and reconfigurability in several functional variations of the same device, as well as the ability to adjust the distance between different sensing elements. We validated the electrical, optical and microfluidic drug delivery performance of the MoRF probe and demonstrated its in vivo electrophysiological recording and optogenetic stimulation capabilities in awake mice.

bioengineering↗

bioRxiv2025

Lysosome-like structures in the nucleolus mediate H2Aub degradation under glucose starvation

Glucose starvation leads to the degradation of intracellular proteins to generate amino acids for energy production. However, it remains unclear which proteins undergo rapid degradation to supply amino acids as energy sources during glucose starvation. To investigate the molecular mechanism underlying the transition of carbon source from glucose to proteins under glucose starvation, we first employed quantitative proteomics to examine the impact of glucose deprivation on protein levels. We discovered that histone degradation produces the highest amount of glutamine during glucose starvation. Further investigation revealed that histone H2A undergo degradation in the nucleolus in the form of mono-ubiquitination (H2Aub). The nucleolus contains lysosome-like structures that degrade monoubiquitinated histones, potentially participating in the carbon source shift from glucose to amino acids for energy production. Through preliminary screening, we identified Midnolin as the receptor for H2Aub, mediating its degradation in nucleolar lysosome-like structures. Dysregulation of carbon source transition from glucose to proteins, through knockdown of Midnolin results in cell cycle arrest, affecting cellular growth and proliferation. In conclusion, our findings demonstrate that nucleolar lysosome-like structures degrading monoubiquitinated histones exist during glucose starvation, which may play crucial roles in the carbon source transition from glucose to proteins, providing new potential therapeutic targets for metabolic disorders.

cell biology↗

bioRxiv2025

The Drosophila proventriculus lacks stem cells but compensates for age-related cell loss via endoreplication-mediated cell growth

The Drosophila proventriculus is a bulb-shaped structure at the juncture of the foregut and the midgut, which plays important roles in ingestion, peritrophic membrane synthesis, and the immune response to oral pathogens. A previous study identified a population of cells in the proventriculus which incorporate bromodeoxyuridine (BrdU), a marker of DNA synthesis, and proposed that these cycling cells are multipotent stem cells that replace dying cells elsewhere in the tissue. Here, we re-investigate these cycling cells and find that they do not undergo mitosis, do not generate clonal lineages, and do not proliferate in response to tissue damage, and are therefore not stem cells. Instead, we find that these cells continually endocycle throughout the flys life, increasing their ploidy and size, while at the same time cells in this tissue are lost into the gut lumen as the fly ages. Functionally, these cells play a critical role in the synthesis of peritrophic membrane components, and we show that when endocycling in these cells is experimentally increased or decreased, there is a concomitant change in ploidy, tissue size, and peritrophic membrane synthesis. Further, we show that inhibition of endocycling makes flies more susceptible to orally infectious bacteria. Altogether, we show that continual endocycling of these cells is critical for maintaining tissue size and function in the face of cell loss due to aging or tissue damage.

genetics↗

bioRxiv2025

Ecogenomics and functional biogeography of the Roseobacter group in the global oceans based on 653 MAGs and SAGs

BackgroundThe Roseobacter group is a major component of prokaryotic communities in the global oceans. Information on this group is based predominantly on isolates and their genomic features and on the 16S rRNA gene. Assessments of prokaryotic communities in the pelagic of the global oceans indicated an unveiled diversity of this group but studies of the diversity and global biogeography of the entire group are still missing. Hence, we aimed at a comprehensive assessment of the Roseobacter group in the global oceans on the basis of MAGs and SAGs. ResultsThe obtained 610 MAGs and 43 SAGs of high quality were subjected to in-depth analyses of their phylogeny, genomic and functional features. The recruitment locations range from the tropics to polar regions, include all major ocean basins. The phylogenetic analysis delineated the known RCA cluster and five pelagic clusters, two of which were completely novel: TCR (Temperate and Cold Roseobacter), AAPR (Arctic-Atlantic-Pacific Roseobacter, novel), AAR (Arctic-Atlantic Roseobacter, novel), COR (Central Oceanic Roseobacter), LUX (Cand. Luxescamonaceae) cluster. These clusters account for [~]70% of all Roseobacter MAGs and SAGs in the epipelagic. The TCR, AAPR, AAR and LUX clusters are among the most deeply branching lineages of the Roseobacter group. These clusters and several sublineages of the RCA and COR clusters exhibit distinct features of genome streamlining, i.e. genome sizes of <2.9 Mbp and G+C contents of <40%. The clusters exhibit differences in their functional features and also compared to other lineages of the Roseobacter group. Proteorhodopsin is encoded in most species of the AAPR, AAR, TCR and RCA clusters and in a few species of the COR cluster, whereas in most species of the latter, the LUX cluster and in a few species of the RCA cluster aerobic anoxygenic photosynthesis was encoded. Biogeographic assessments showed that the AAPR, AAR, TCR and RCA clusters constitute the Roseobacter group in the temperate to polar regions to great extent whereas the COR and LUX clusters in the tropics and subtropics. ConclusionsOur comprehensive analyses shed new light on the diversification, genomic features, environmental adaptation, and global biogeography of a major lineage of pelagic bacteria.

microbiology↗

bioRxiv2025

Genome-wide extraction of differentially methylated DNA regions using adapter-anchored proximity primers

The epigenetic deregulation of CpG islands (CGIs) plays a crucial role in cancer initiation and progression. CGIs comprise 1-2% of the human genome and are rich in differentially methylated regions (DMRs) that can serve as cancer biomarkers in clinical samples and liquid biopsies. Focusing epigenetic sequencing on CpG-rich sequences, including CGIs and avoiding non-informative regions, offers an efficient and sensitive approach for cancer identification and tracking, especially within samples containing excess of unaltered, normal DNA. To this end, we have developed Adaptor-anchored Methylation amplification via Proximity Primers (aMAPP), a versatile PCR-based enrichment method. aMAPP employs specially designed primers to selectively enrich either methylated or unmethylated CpGs, depending on the upstream methylation conversion method employed. aMAPP achieves high coverage of genome-wide CGIs and detects hundreds of DMRs in tumor samples compared to adjacent normal tissue using ultra-low depth sequencing ([~]300,000 reads). It enables tracing of aberrant methylation down to allelic frequency 0.01% in dilutions of tumor DNA and in cell-free DNA samples, can be applied using picogram amounts of DNA, and can be adapted to enrich either small panels of cancer-specific DMRs, or the majority (>90%) of genomic CGIs and CpGs. aMAPP offers a simple, cost-effective, and highly sensitive approach for capturing the epigenetic footprint of genome-wide CpGs and identifying aberrantly methylated or un-methylated genomic regions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/660377v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@b8b303org.highwire.dtl.DTLVardef@1f0a70corg.highwire.dtl.DTLVardef@67391dorg.highwire.dtl.DTLVardef@d6ac75_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

In-situ calibration of passive samplers for monitoring host-associated fecal markers in an urban river

Passive sampling in aquatic environments has shown promise as a time- and cost-efficient method with improved sensitivity for detecting microbial pollution in dynamic and variable conditions. However, quantitative descriptions of its field performance have been scarce, impeding its broader application in environmental settings. The performance of two membrane-based passive samplers (Torpedo and MSTFlow) in quantifying human (Carjivirus, Pepper Mild Mottle Virus [PMMoV], Tomato Brown Rugose Fruit Virus [ToBRFV]) and avian (Helicobacter spp. GFD marker) fecal pollution markers in an urban riverine environment over a 72-h deployment was evaluated using a first-order kinetic model to characterize their microbial adsorption characteristics. Results were compared with those from parallel composite and time-weighted auto-sampling. Accumulation in passive samplers exhibited an initial lag phase (0 to 8 h for viruses) and reached equilibrium within 16 h of initial deployment, except for GFD. Sampling rates were highest for PMMoV (6.29 and 5.11 mL/h) for MSTFlow and Torpedo samplers respectively, followed by Carjivirus (4.63 and 3.63 mL/h), ToBRFV (2.17 and 1.22 mL/h) and GFD (0.68 mL/h in Torpedo sampler). At equilibrium, both sampler configurations accumulated more than 22-170 times the amount of target gene copies in each mL of grab water samples depending on sampler and virus. These findings highlight passive sampling as a promising, sensitive, cost-effective, and low-maintenance alternative for continuous microbial water quality monitoring in aquatic environments. Overall, this study advances the understanding of passive sampling kinetics and supports broader adoption of passive samplers for tracking fecal pollution in environmental waters.

microbiology↗

bioRxiv2025

The mechanism of oncogenic PI3K lipid kinase variants at the membrane and their cryptic pockets

Cancer-prone alleles exhibit single hotspot mutations. However, the combination of a cancer hotspot and a weak or moderate mutation (the one-two punch hypothesis) produces same-allele double variants with a significantly different and potentially graded clinical phenotypic spectrum. Oncogenic PI3K variants, which are also associated with benign tumors and neurodevelopmental disorders, offer statistical support for this model. Using atomistic molecular dynamics (MD) simulations, we revealed that PI3K variants with single and double mutations exhibit expanded conformational profiles. Double mutations significantly shift the conformational ensembles toward the active form--a more pronounced effect than a single mutation. These double mutants facilitate nSH2 release, iSH2 shift, and A-loop protrusion in solution, promoting PIP2 substrate recruitment at the membrane. We discovered that observable, potentially drug-targetable cryptic pockets are PI3K mutation-specific. Ab initio discovery of these pockets through simulations is essential for AI-aided virtual drug screening. A key challenge is that a single drug is often ineffective against PI3K variants due to their diverse conformational spectra. To address this, we propose a conformational selection strategy involving a combination of allosteric drugs for variants with graded conformational spectra, particularly those with strong double mutations; we identified such potentially targetable cryptic pockets in double mutants conformers.

biophysics↗

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

Early postnatal CA3 hyperexcitability drives hippocampal development and epileptogenesis in SCN2A developmental and epileptic encephalopathy

Developmental and epileptic encephalopathies caused by pathogenic variants in SCN2A (SCN2A-DEE), encoding the voltage-gated sodium channel Nav1.2, present with early-life seizures, developmental delay, and increased mortality. Using a novel Scn2a p.A263V gain-of-function (GOF) mouse model, we demonstrate gene-dose and background-dependent phenotypes ranging from self-limited neonatal seizures to chronic epilepsy with high mortality. In vivo electrophysiology revealed hippocampal seizures as early as postnatal day 2.5, with CA3-driven gamma oscillations preceding seizure onset. CA3 and CA1 pyramidal neurons exhibited transient hyperexcitability during early postnatal development, resolving by P24-30. Single-cell RNA sequencing uncovered gene dose-dependent accelerated maturation of hippocampal networks, peaking at P7, alongside widespread transcriptional changes in excitatory and inhibitory neurons. In adulthood, persistent hippocampal network alterations emerged, marked by reduced mid-gamma oscillations and theta-gamma coupling. Our findings establish hippocampal CA3 hyperexcitability as an early driver of epileptogenesis in SCN2A-DEE and highlight it as a potential therapeutic target to mitigate disease progression.

neuroscience↗

bioRxiv2025

In vivo Calcium Imaging in the Near-Infrared II Window

Non-invasive deep-tissue calcium imaging of live mammals with high sensitivity and resolution is challenging owing to light scattering experienced by traditional calcium ion (Ca2+) indicators with excitation and emission wavelengths within 400-750 nm. Here, we report near-infrared II (NIR-II) calcium imaging beyond 1000 nm by exploring a natural protein derived from a bacterium (Thermochromatium tepidum) living in a calcium carbonate-rich environment. This highly photostable fluorescent protein enables NIR-II imaging of intracellular Ca2+ responses to stimulant drugs in cultured mammalian cells with sensitivity comparable to that of visible Ca2+ indicators. We achieve in vivo NIR-II imaging of Ca2+ transients in response to two different tumor treatment strategies in intact tumors with high sensitivity, resolution, and contrast, opening the possibility of non-invasive deep-tissue calcium imaging for assessing treatment efficacy longitudinally. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/661443v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@149504eorg.highwire.dtl.DTLVardef@37722borg.highwire.dtl.DTLVardef@2878a7org.highwire.dtl.DTLVardef@1091d0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Dynamics and Regulation of mRNA Cap Recognition by Human eIF4F

Efficient eukaryotic messenger RNA translation requires dynamic collaboration between the three subunits of initiation factor 4F (eIF4F, eIF4E*G*A), which recognises and activates mRNA at its 5' cap structure for ribosome recruitment. Despite its high biological and pharmacological importance, the dynamics of full human eIF4F-mRNA engagement remain largely uncharacterised, hindering mechanistic understanding of translation initiation and its regulation. Here we observed human eIF4F activity with single-molecule fluorescence assays that directly visualise mRNA cap recognition by its eIF4E subunit. Unexpectedly, we find that inherently transient eIF4E-cap binding is repressed by full-length human eIF4G, predominantly through its C-terminus, representing an unanticipated role for eIF4G as a central rate-limiting factor in the eIF4F complex. This repression is relieved by nucleotide-bound eIF4A in the eIF4F heterotrimer, placing eIF4A as a crucial determinant of efficient cap recognition for translation. Molecular dynamics simulations reveal that electrostatic modulation of eIF4E-mRNA interaction allows eIF4G to control the cap-recognition frequency. Our findings also indicate that intrinsic eIF4F- mRNA dynamics are insufficient to support cap-tethered ribosomal scanning to locate translation start sites. They illuminate fundamental design-principle differences for the overall mechanism and division of labour among eIF4F subunits during mRNA recognition in humans and yeast.

biophysics↗

bioRxiv2025

CRISPR-Based Gene Dependency Screens reveal Mechanism of BRAF Inhibitor Resistance in Anaplastic Thyroid Cancer

Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer. Despite recent advances in treating BRAFV600E-driven ATC, therapy resistance remains a significant challenge, often resulting in disease progression and death. Leveraging a focused CRISPR/KO screen in parallel with a CRISPR/activation screen, both tailored on response to BRAFV600E inhibitor treatment, we identified TAZ (encoded by the WWTR1 gene) deficiency as synthetically lethal with BRAF inhibitor in ATC. TAZ is overexpressed in ATC compared to well-differentiated thyroid tumors. We demonstrate that TAZ-deficient ATC cells display heightened sensitivity to BRAF inhibitors both in vitro and in vivo. Using gene essentiality score across a large panel of cancer cell lines, we found that BRAFV600E-driven cancers are highly sensitive to TAZ loss, unlike their counterparts with wild-type BRAF and non-BRAFV600E. Mechanistically, we demonstrate that dabrafenib triggers the Unfolded Protein Response (UPR) under ER stress and suppresses protein synthesis. TAZ loss represses the UPR, reverses the inhibition of protein synthesis, and triggers increased cell death by ferroptosis in dabrafenib-treated ATC. Collectively, our findings unveil TAZ as a new target to overcome resistance to BRAF inhibitors in undifferentiated thyroid cancer.

cancer biology↗

bioRxiv2025

Stiffness sensing fuels matrix-driven metabolic reboot for kidney repair and regeneration

Kidney repair after acute kidney injury (AKI) relies on a finely tuned extracellular matrix (ECM) that provides structural integrity and mechanical cues. As primary ECM architects, fibroblasts and pericytes rapidly mobilize to the injury site post-AKI, yet the ECM-driven repair mechanisms remain incompletely defined. Here, leveraging tissue engineering, genetic and pharmacological models, and multi-omics, we profiled the proteome landscape of decellularized kidney matrix scaffold post-AKI and highlighted microfibrillar-associated protein 2 (Mfap2) as a key core matrisome component primarily sourced from fibroblasts and pericytes. Mfap2 loss disrupted kidney architecture and metabolism, aggravating AKI. Global proteomics revealed that Mfap2 deficiency suppressed tubular 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) expression via estrogen receptor 2 (Esr2)-mediated transcriptional repression and increased protein succinylation. Phosphoproteomics and spatial transcriptomics further demonstrated a shift in mechanical signaling, with Mfap2 loss hyperactivating mitogen-activated protein kinases and upregulating large tumor suppressor kinase 1 (Lats1) in tubular cells without altering integrin receptor activities. In turn, Lats1 suppressed Esr2 transcription independent of its canonical Yap/Taz effectors, without affecting ubiquitin-mediated Esr2 degradation. Therapeutically, Esr2 agonists restored kidney function in Mfap2-deficient models. These findings position Mfap2 as a key regulator of ECM dynamics and mechanosignaling, linking tissue stiffness to metabolic reprogramming required for kidney repair.

cell biology↗

bioRxiv2025

Genome Mining and Characterization of a Heme-Dependent Enzyme Catalyzing Intermolecular Nitrogen-Nitrogen Bond Formation in Hydrazinosuccinic Acid Biosynthesis

Nitrogen-nitrogen (N-N) bond-forming enzymes are rare but play vital roles in both primary and secondary metabolism. Guided by a nitric oxide synthase (NOS)-based genome mining strategy, we report the discovery and characterization of a new heme-dependent enzyme system that catalyzes intermolecular N-N bond formation. Using both in vivo and in vitro reconstitution approaches, we demonstrated that a protein complex, comprising a heme enzyme and a 2[4Fe-4S] ferredoxin partner, mediates the coupling of the -amine group of L-aspartate with inorganic nitrogen oxide species, such as nitrite or nitric oxide, to generate hydrazinosuccinic acid, a key biosynthetic precursor in several natural product pathways. Structural modeling and site-directed mutagenesis suggest a plausible catalytic mechanism involving the formation of a reactive nitrogen intermediate, potentially a heme-bound nitrene species. These findings reveal a new family of N-N bond-forming biocatalysts that leverage inorganic nitrogen sources, offering valuable tools for genome mining and the synthetic biology.

biochemistry↗

bioRxiv2025

Phosphoinositide 3-kinase regulates wild-type RAS signaling to confer resistance to KRAS inhibition

Despite the availability of RAS inhibitors and the dependence of >90% of pancreatic ductal adenocarcinomas (PDAC) on oncogenic KRAS mutations, resistance to KRAS inhibition remains a serious obstacle. We show here that phosphoinositide 3-kinase (PI3K) plays a major role in this resistance through upstream activation of wild-type RAS signaling - beyond its known KRAS effector function. Combining proximity labeling, CRISPR screens, live-cell imaging, and functional assays we found that PI3K orchestrates phosphoinositide-mediated GAB1 recruitment to the plasma membrane, nucleating assembly of RAS signaling complexes that activate mitogen-activated protein kinase (MAPK) in an EGFR/SHP2/SOS1-dependent manner. We further demonstrate that inhibiting PI3K enhances sensitivity to mutant-specific KRAS inhibitors in PDAC cells, including cells with clinically identified PIK3CA mutations. Our findings refine RAS-PI3K signaling paradigms, reveal that PI3K-driven wild-type RAS activation drives resistance to KRAS inhibition, and illuminate new avenues for augmenting KRAS-targeted therapies in PDAC.

cancer biology↗

bioRxiv2025

Harnessing cell-encapsulated hydrogels to study astrocyte mechanoresponse in 4D

In glaucoma, the optic nerve head (ONH) is exposed to increased biomechanical strain, impacting the resident astrocytes that maintain neural homeostasis. During disease progression astrocytes exhibit morphologic and metabolic shifts; however, the specific impact of glaucoma-related biomechanical strains on astrocyte behavior remains poorly understood. To address this, we used our previously established 3D cell-encapsulated extracellular matrix (ECM) hydrogel to investigate ONH astrocyte cellular and transcriptomic responses to varying biomechanical strain levels over time. Murine ONH astrocyte were encapsulated within an ECM hydrogel made from photocrosslinkable collagen type I and hyaluronic acid, and subjected to 0, 3, or 10% cyclic compression for 4h and 24h. We found significant restructuring of cytoskeletal morphology, metabolic dysregulation, and astrocyte-mediated ECM modulation that were strain-, duration- and hydrogel subregion-dependent. These phenotypic alterations were associated with diverse transcriptional changes in genes related to cell cycle and morphology, inflammation, metabolism and matrix remodeling that were driven by compressive strain intensity and duration. Our work reveals the direct role of compressive strain in eliciting a complex astrocyte response, supports targeting mechanosensation to prevent these pathologic astrocyte responses, and establishes ECM-based hydrogels as a platform to test mechanisms driving astrocyte mechanodysfunction. Altogether, our study offers new insights into astrocyte responses to biomechanical insult and demonstrates the use of a tunable 3D ECM hydrogel for future mechanistic studies of neurodegeneration. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/660800v2_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@f355fborg.highwire.dtl.DTLVardef@191e096org.highwire.dtl.DTLVardef@2fae32org.highwire.dtl.DTLVardef@55913c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

IFN-inducible Human Phospholipid Scramblase 1 (PLSCR1) ProteinRestricts HIV-1 Infection by Inhibiting Membrane Fusion

Human phospholipid scramblase 1 (PLSCR1) is an interferon-stimulated gene (ISG) that inhibits viral infections through various mechanisms. Here, we identify PLSCR1 as a host restriction factor that inhibits HIV-1 entry by impairing membrane fusion mediated by the envelope glycoprotein (Env). Using multiple cell types including the human SupT1 T cell line and purified CD4+ T cells, we demonstrate that PLSCR1 inhibits the replication of HIV-1 with diverse tropisms and subtypes, as well as HIV-2 and SIV. Mechanistically, we find that PLSCR1 blocks viral entry and cell-to-cell transmission by restricting HIV-1 virion-cell and cell-cell fusion without affecting CD4 or CXCR4 expression or virus binding to the cell surface. Notably, PLSCR1-mediated restriction of viral entry is independent of type I interferon signaling. Collectively, these findings establish PLSCR1 as a broad-spectrum lentiviral restriction factor that acts at the membrane fusion stage, thereby expanding our understanding of ISG-mediated antiviral defense.

microbiology↗

bioRxiv2025

Application of machine learning in the discovery of antimicrobial peptides: Exploring their potential for ulcerative colitis therapy

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with rising global prevalence, yet existing treatments are not universally effective. Antimicrobial peptides (AMPs), produced by the immune system, have diverse antimicrobial and immune-regulatory functions, making them promising candidates for UC therapy. Using machine learning, we developed a machine learning-based prediction model to identify novel AMPs. The predicted peptides demonstrated significant biological activity in vitro and in vivo. In a dextran sulfate sodium-induced UC mouse model, engineered AMPs notably improved UC-related parameters, such as body weight, disease activity index (DAI), and colon length. These effects were likely mediated by modulation of Akkermansia muciniphila. This study highlights the potential of machine learning-identified AMPs as future therapeutic candidates for UC. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/660148v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@187dc6borg.highwire.dtl.DTLVardef@9800deorg.highwire.dtl.DTLVardef@1611c42org.highwire.dtl.DTLVardef@866406_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗