Biology subjects

Li, B.

Publications and source records attributed to Li, B..

At least 199 records · Page 11Linked to original sources

bioRxiv2025

CellScope: High-Performance Cell Atlas Workflow with Tree-Structured Representation

Single-cell sequencing enables comprehensive profiling of individual cells, revealing cellular heterogeneity and function with unprecedented resolution. However, current analysis frameworks lack the ability to simultaneously explore and visualize cellular hierarchies at multiple biological levels. To address these limitations, we present CellScope, an innovative framework for constructing high-resolution cell atlases at multiple clustering levels. CellScope employs a two-step manifold fitting process for gene selection and noise reduction, followed by agglomerative clustering, and uniquely integrates UMAP visualization with hierarchical clustering to intuitively represent cellular relationships simultaneously at multiple levels--such as cell lineage, cell type, and cell subtype levels. Compared to established pipelines such as Seurat and Scanpy, CellScope comprehensively improves clustering performance, visualization clarity, computational efficiency, and algorithm interpretability, while reducing dependence on hyperparameters across a multitude of single-cell datasets. Most importantly, it can reveal new biological insights that other contemporary methods are unable to detect, thereby deepening our understanding of cellular heterogeneity and function, and potentially informing disease research.

bioinformatics↗

bioRxiv2025

Microglia regulate neuronal activity via structural remodeling of astrocytes

Neuron-glia interactions play a central role in regulating synaptic transmission and neuronal excitability. Structural plasticity of astrocytes is associated with numerous physiological and pathological conditions, however, the mechanism underlying this process remains unknown. To examine the basis for structural astrocyte plasticity, we used the classic example of the loss of astrocytic processes that takes place in the hypothalamic magnocellular system during chronic high-salt intake. We discovered that a high-salt diet triggers a local accumulation of reactive microglia around vasopressin-secreting neurons, but not in other brain areas. Microglia phagocytose astrocytic processes, reducing astrocytic coverage of vasopressin neurons. The pruning of astrocytic processes impairs synaptic glutamate clearance, enabling activation of extrasynaptic glutamate NMDA receptors and increasing the activity of vasopressin neurons. Inhibiting microglia-mediated astrocyte pruning attenuates the increased neuronal activity and vasopressin-dependent hypertensive phenotype of rats fed high-salt diet. Thus, microglia orchestrate neuron-glia interactions and regulate neuronal activity through astrocyte pruning.

neuroscience↗

bioRxiv2025

Pneumo-Typer: a high-throughput capsule genotype visualization tool with integrated serotype and sequence type prediction for Streptococcus pneumoniae

BackgroundStreptococcus pneumoniae persists as a leading global pathogen, with current capsule-based vaccines like PCV13 offering limited coverage against its extensive serotype diversity (>100 serotypes). This restricted coverage drives the emergence of non-vaccine serotypes. Moreover, vaccine efficacy is further compromised by immune evasion caused by capsule genotype (CapT) variations within vaccine-covered serotypes, while existing genome-based tools lack robust analytical capabilities for CapT. ResultsWe developed Pneumo-Typer, a CapT visualization tool enabling rapid identification of CapT variations in S. pneumoniae. Application to 17,407 publicly available genomes from the NCBI database revealed widespread CapT variations across vaccine-covered serotypes, providing critical insights for optimizing vaccine formulations. In addition, Pneumo-Typer integrates high-accuracy serotype prediction (98.44% accuracy across 93 serotypes) and multilocus sequence typing (ST), facilitating comprehensive genomic surveillance. Besides, CapT and ST information can assist in serotype determination. Pneumo-Typer enables integrated analysis of serotype-CapT-ST relationships, demonstrating that while most serotypes associate with multiple STs and CapTs, ST and CapT lineages evolve independently. Strikingly, multi-serotype serogroups exhibited pronounced CapT diversity, suggesting evolutionary processes driving serogroup expansion through CapT plasticity. ConclusionsIn summary, Pneumo-Typer is an integrated platform for genomic surveillance of pneumococcal populations. By resolving previously underexplored serotype-CapT-ST linkages, the tool provides a framework for next-generation vaccine design, emphasizing the need for vaccine formulations that address both serotype replacement and CapT-driven immune evasion.

bioinformatics↗

bioRxiv2025

LUMI-lab: a Foundation Model-Driven Autonomous Platform Enabling Discovery of New Ionizable Lipid Designs for mRNA Delivery

The complexity of molecular discovery requires autonomous systems that efficiently explore vast and uncharted chemical spaces. While integrating artificial intelligence (AI) with robotic automation has accelerated discovery, its application remains constrained in fields with scarce historical data. One such challenge is the design of lipid nanoparticles (LNPs) for mRNA delivery, which has relied on expert-driven design and is hindered by limited datasets. Here, we introduce LUMI-lab, a self-driving lab (SDL) system that enables efficient learning with minimal wet-lab data by integrating a molecular foundation model with an automated active-learning experimental workflow. Through ten iterative cycles, LUMI-lab synthesized and evaluated over 1,700 LNPs, identifying ionizable lipids with superior mRNA transfection potency in human bronchial cells compared to clinically approved benchmarks. Unexpectedly, it autonomously uncovered brominated lipid tails as a novel feature enhancing mRNA delivery. In vivo validation further confirmed that inhalation of LNPs containing the top-performing lipid, LUMI-6, achieved 20.3% gene editing efficacy in lung epithelial cells in murine models, surpassing the highest efficiency reported for inhaled LNP-mediated CRISPR-Cas9 delivery in mice to our knowledge. These findings demonstrate LUMI-lab as a powerful, data-efficient platform for advancing mRNA delivery, highlighting the potential of AI-driven autonomous systems to accelerate innovation in material science and therapeutic discovery.

biochemistry↗

bioRxiv2025

CDK8 remodels the tumor microenvironment to resist the therapeutic efficacy of targeted KRASG12D inhibition in pancreatic ductal adenocarcinoma

Mutations in KRAS are a dominant driver of pancreatic ductal adenocarcinoma (PDAC), with over 40% of PDAC patients presenting with KRASG12D mutations. The recent development of small molecule inhibitors targeting KRASG12D has enabled targeting of mutant KRAS signaling and suppression of PDAC; however, the contribution of the tumor microenvironment (TME) to the sustained therapeutic efficacy of KRASG12D inhibition and mechanism/s of resistance to KRASG12D suppression remain to be elucidated. Here, we employed spatial transcriptomics, single cell RNA sequencing, and CODEX-based spatial proteomics to evaluate cancer cell intrinsic and extrinsic responses to KRASG12D inhibition with MRTX1133. While KRASG12D inhibition initially increases CD11c+ cells with impactful T cell infiltration within proximity to cancer cells, long-term treatment with MRTX1133 resulted in reversal of the immune responses leading to KRASG12D therapy resistance promoted by CDK8, a multiprotein mediator complex associated kinase. CDK8 imparts resistance in part through induction of downstream CXCL2 chemokine secretion, inhibition of FAS expression, and remodeling of the TME to promote immune evasion. Targeting CDK8 by itself and in combination with CTLA-4 immunotherapy overcomes resistance to KRASG12D inhibition with prolonged survival with translational implications.

cancer biology↗

bioRxiv2025

Spatial gene expression of human coronary arteries revealed the molecular features of diffuse intimal thickening in explanted hearts

BackgroundDiffuse intimal thickening (DIT) is a pre-clinical stage of atherosclerosis characterized by thickened intima. The molecular basis of its susceptibility to atherogenesis is unknown, and mechanistic investigations cannot be performed in commonly used mouse models, in which DIT does not exist. Vascular smooth muscle cells (SMCs) are the predominant cell type that occupies the intima and media of DIT. The molecular differences between these two layers may reveal the earliest phenotypic changes in SMCs to promote atherosclerosis. MethodsWe benchmarked the RNA quality of human coronary arteries from autopsies (n=7) and freshly explanted hearts (n=7) and performed Visium spatial gene expression on tissue sections with DIT. SMC-enriched intima and media were compared to find differentially expressed genes. The gene ontology features of SMC-enriched intima in this study were also compared to those in the atherosclerotic lesions, as previously revealed by single-cell RNA-sequencing studies. ResultsAlthough autopsy samples met the RNA quality standard for Visium (DV200 [≥] 30%), only arteries from freshly explanted hearts exhibited reliable performance. Genes enriched in TGF-{beta}-mediated remodeling of the extracellular matrix were overrepresented in the intima, including versican and biglycan. SMCs enriched in the intima are dedifferentiated, but unlike those in the lesions, they are not proinflammatory. ConclusionsOur findings indicate that autopsy samples are not ideal to distinguish subtle differences among cell phenotypes. Dedifferentiated SMCs in the DIT are distinct from the proinflammatory SMCs in atherosclerotic lesions. SMCs in thickened intima may lead to lipid retention but not necessarily the onset of atherosclerosis. Research Perspective1) What is New? O_LIPostmortem coronary arteries, which are frequently collected by biobanks, have degraded RNA, which are not suitable for identifying subtle differences in the transcriptome profiles. C_LIO_LICoronary arteries from explanted hearts allow for more faithful representation of spatial gene expression across the vessel wall as compared to ones from autopsy hearts. C_LIO_LIThickened intima in diffuse intimal thickening, which exists in everyone, is unlikely to undergo atherogenesis without additional stimuli such as inflammation. C_LI 2) What Question Should be Addressed Next? O_LIThe current RNA quality standard of spatial transcriptomics needs to be carefully benchmarked in biobank samples to control sequencing performance and meaningful data interpretation. C_LIO_LIHow inflammation changes smooth muscle cell phenotypes may explain why everyone has diffuse intimal thickening, but those with chronic inflammatory disease have a high risk of coronary artery disease. C_LIO_LIFuture research should focus on the interplay between smooth muscle cell phenotypes and the extracellular matrix to understand the etiology of coronary artery disease. C_LI

pathology↗

bioRxiv2025

SpaIM: Single-cell Spatial Transcriptomics Imputation via Style Transfer

Spatial transcriptomics (ST) technologies have revolutionized our understanding of cellular ecosystems. However, these technologies face challenges such as sparse gene signals and limited gene detection capacities, which hinder their ability to fully capture comprehensive spatial gene expression profiles. To address these limitations, we propose leveraging single-cell RNA sequencing (scRNA-seq), which provides comprehensive gene expression data but lacks spatial context, to enrich ST profiles. Herein, we introduce SpaIM, an innovative style transfer learning model that utilizes scRNA-seq information to predict unmeasured gene expressions in ST data, thereby improving gene coverage and expressions. SpaIM segregates scRNA-seq and ST data into data-agnostic contents and data-specific styles, with the contents capture the commonalities between the two data types, while the styles highlight their unique differences. By integrating the strengths of scRNA-seq and ST, SpaIM overcomes data sparsity and limited gene coverage issues, making significant advancements over 12 existing methods. This improvement is demonstrated across 53 diverse ST datasets, spanning sequencing- and imaging-based spatial technologies in various tissue types. Additionally, SpaIM enhances downstream analyses, including the detection of ligand-receptor interactions, spatial domain characterization, and identification of differentially expressed genes. Released as open-source software, SpaIM increases accessibility for spatial transcriptomics analysis. In summary, SpaIM represents a pioneering approach to enrich spatial transcriptomics using scRNA-seq data, enabling precise gene expression imputation and advancing the field of spatial transcriptomics research.

bioinformatics↗

bioRxiv2025

Comparative Analysis of Phytochemical Constituents of Ginkgo Biloba Flowers and Leaves, and Evaluation of Their Biological Activities

BackgroundsGinkgo biloba L. has attracted much attention for its unique chemical composition and pharmacological properties, and most of the research focused on Ginkgo biloba leaves (GBL). Our preliminary research found that Ginkgo biloba flowers (GBF) were superior to GBL in terms of anti-radiation activity, but the underlying cause of this discrepancy in activity remains elusive. ObjectivesThe aim of this study was to systematically compare the chemical and nutritional composition of Ginkgo biloba flowers and leaves, to further elucidate the material basis of the medicinal and nutritional value of Ginkgo biloba flowers, and to conduct further comparative studies on the anti-ferroptosis activity and anti-radiation activity of the two. MethodsIn this study, the chemical constituents of GBF and GBL were identified by UPLC-Q-orbitrap HRMS, and the contents of amino acids, fatty acids, inorganic elements, purines, and ceramides of both were determined. Meanwhile, the anti-iron death activity and anti-radiation activity of GBF and GBL were comparatively studied by cellular experiments. ResultsThe results showed that the content of chemical components such as flavonoids and other nutrients such as amino acids, fatty acids, and ceramides were richer in GBF than in GBL, and GBF was indeed superior to GBL in terms of anti-radiation and anti-ferroptosis activity. ConclusionThrough in-depth analyses of the chemical and nutritional compositions of Ginkgo biloba flowers and leaves, the present study reveals the possible material basis for the stronger activity of GBF and provides theoretical support for its application in nutraceuticals and pharmaceuticals, especially in the development of functional nutraceuticals and anti-radiation drugs with higher health benefits.

biochemistry↗

bioRxiv2025

Simultaneous, real-time tracking of many neuromodulatory signals with Multiplexed Optical Recording of Sensors on a micro-Endoscope

Dozens of extracellular molecules jointly impact a given neuron, yet we lack methods to simultaneously record many such signals in real time. We developed a probe to track ten or more neuropeptides and neuromodulators using spatial multiplexing of genetically encoded fluorescent sensors. Cultured cells expressing one sensor at a time are immobilized at the front of a gradient refractive index (GRIN) lens for 3D two-photon imaging in vitro and in vivo. The sensor identity and detection sensitivity of each cell are determined via robotic dipping of the probe into wells containing various ligands and concentrations. Using this probe, we detected stimulation-evoked release of multiple neuromodulators in acute brain slices. We also tracked endogenous and drug-evoked changes in cerebrospinal fluid composition in the awake mouse lateral ventricle, which triggered downstream activation of the choroid plexus epithelium. Our approach offers a first step towards quantitative, real-time, high-dimensional tracking of brain fluid composition.

neuroscience↗

bioRxiv2025

Lethal effects of phyllosphere fungi associated with local plants on invasive plant Ageratina adenophora seedlings

Native community resistance to plant invasion may reflect microbial effects on invader establishment. Here, we compared the effects of the aboveground and belowground microbes and leaf functional traits of 25 native plant species on the germination and survival of invader Ageratina adenophora. Results show that leaf physical and chemical traits vary among plant species and shape the aboveground microbial community. Local plants more phylogenetically close to A. adenophora harbour more similar pathogen communities to those A. adenophora. The aboveground tissue inoculations had more adverse effects on A. adenophora establishment by delaying germination time and decreasing the germination rate and seedling survival than did soil inoculations; aboveground tissues from local plants, which are more closely related to A. adenophora, cause longer germination times and greater seedling mortality of A. adenophora. Moreover, local plant aboveground fungi, rather than bacteria, adversely impact seedling survival, and most of the detrimental fungal pathogen ASVs are specialists. Several strains isolated from dead seedlings caused by aboveground tissue inoculations belonging to Alternaria, Fusarium and Stagonosporopsis were verified to kill more than 60% of A. adenophora seedlings and thus have great potential as biocontrol agents for A. adenophora. This is the first study to provide evidence for the effects of phylogenetic relatedness and leaf traits (both functional and microbial) on local community resistance to invaders through the regulation of germination and seedling survival.

ecology↗

bioRxiv2025

Diverse microtubule-destabilizing drugs induce equivalent molecular pathway responses in endothelial cells

Drugs that modulate microtubule (MT) dynamics are well-characterized at the molecular level, yet the mechanisms linking these molecular effects to their distinct clinical outcomes remain unclear. Several MT-destabilizing drugs, including vinblastine, combretastatin A4, and plinabulin, are widely used, or are under evaluation for cancer treatment. Although all three depolymerize MTs, they do so through distinct biochemical mechanisms. Furthermore, their clinical profiles and therapeutic uses differ considerably. To investigate whether differential modulation of molecular pathways might account for clinical differences, we compared gene expression and signaling pathway responses in human pulmonary microvascular endothelial cells (HPMECs), alongside the MT-stabilizing drug docetaxel and the pro-inflammatory cytokine TNF-. RNA-sequencing and phosphoproteomics revealed that all three MT destabilizers triggered equivalent molecular responses. The substantial changes in gene expression caused by MT destabilization were completely dependent on Rho family GTPase activation. These findings suggest that the distinct clinical profiles of the destabilizing drugs depend on differences in pharmacokinetics (PK) and tissue distribution rather than molecular actions. The washout rate of the three drugs differed, which likely translates to PK differences. Our data provide insights into how MT destabilization triggers signaling changes, potentially explaining how these drugs induce cell cycle re-entry in quiescent cells and how plinabulin ameliorates chemotherapy-induced neutropenia. Significance StatementMicrotubule (MT)-destabilizing drugs, despite their potential for toxicity, are used to treat a surprising range of diseases, including cancers, inflammatory disorders, and parasitic infections. To investigate how drugs with apparently similar actions on MTs achieve diverse clinical effects, we compared the molecular pathways that are activated by three drugs with different clinical profiles, vinblastine, combretastatin A4, and plinabulin. All three elicited similar gene expression responses via Rho GTPase activation. This finding suggests that their distinct clinical effects are not caused by different effects on MTs, but rather by differences in drug transport, pharmacokinetics or tubulin isotype affinity. Our findings provide insights into how plinabulin might protect the bone marrow and may help medicinal chemists design MT drugs for new applications.

pharmacology and toxicology↗

bioRxiv2025

Optimization of Extraction Process by Response Surface Methodology of Total Flavonoids from Ziziphus Jujube Flesh and its Sedative-Hypnotic Effects

Background & aimsThis study optimizes the extraction process of total flavonoids from Ziziphus jujube flesh (TFZJF) by response surface methodology and investigating its sedative-hypnotic effects and mechanisms in a para-chlorophenylalanine (PCPA)-induced insomnia mouse model. It provides theoretical support for the further comprehensive utilization of Ziziphus jujube fruit and flesh. MethodsSingle-factor experiment and Box-Behnken response surface design were used to study the ethanol reflux extraction process of TFZJF, with flavonoid extraction rate as the indicator, to obtain the optimal extraction process of TFZJF. An insomnia model in mice was induced via an intraperitoneal injection of PCPA, and the effects of TFZJF on this model, along with its underlying mechanisms, were assessed using various approaches, including sodium pentobarbital-induced sleep potentiation, HE staining of tissue sections, ELISA, RT-PCR, WB, and serum metabolomics. ResultsThe results showed that the optimized extraction conditions for TFZJF included a solid-liquid ratio (SLR) of 1:25 g{middle dot}mL-1, ethanol concentration of 60%, and extraction time of 60 min, yielding an extraction efficiency of 1.98%. Data from the experimental groups indicated dose-dependent sleep improvement in the insomnia model, with the high-dose TFZJF (TFZJF-H) group exhibiting the most significant effect, followed by the medium-dose (TFZJF-M) and low-dose (TFZJF-L) groups. Metabolomic analysis revealed that TFZJF administration positively impacted the metabolic profile of PCPA-induced insomnia, particularly affecting pathways related to phenylalanine, tyrosine, cytochrome P450, and alanine metabolism on non-targeted metabolomics. ConclusionsThe extraction process is stable and reliable, which can be used for the extraction of TFZJF; meanwhile, TFZJF demonstrated significant sleep-enhancing effects in the PCPA-induced insomnia mouse model, supporting its potential for resource development and the utilization of non-medicinal parts of Ziziphus jujube.

biochemistry↗

bioRxiv2025

Gut meta-virome reveals potential zoonotic pathogens and environmental RNA viruses carried by non-human primates

The majority of human infectious diseases originate from mammals and are inherently zoonotic. Non-human primates (NHPs) are not only carriers of many zoonotic pathogens, but also the best intermediary for virus shift from harmless to harmful due to their similar phylogenetic relationship with humans. Knowledge of NHP viral composition and its underlying information can therefore provide an assessment of the risk of cross-species transmission and spillover of zoonotic diseases. However, studies that have successfully eliminated the effects of different natural habitat environments on viral carriage have been limited, making it difficult to identify which zoonotic viruses and potentially species-barrier-crossing viruses are carried by widely distributed NHP hosts. Here, we analyze viruses excreted in feces from NHP hosts and reveal the presence of possible zoonotic pathogens. Most of the viruses found come from plants that are eaten by them. Analysis of the evolutionary relationships of potential pathogens suggests that other clinical isolates are genetically correlated to HIV, PBV, and EV we identified. This study provides foundational data for surveillance of NHP enteroviruses that could help to be challenging to track potential human viruses carried by NHP in the absence of clinical surveillance. ImportanceAs a result of internationalization and other factors, many viruses have broken through the limits of geographical units and spread into human society, causing many emerging and re-emerging infectious disease hazards. However, the virus spreads and is by no means infectious to humans overnight. There is a phenomenon of host shift, in which the virus does not necessarily cause disease in an intermediate host, but causes significant damage when transmitted to humans. We focus on captive non-human primates, close relatives of humans in cities, because the phenomenon of host shifts is related to both biological similarity and geographical proximity of the host. Primates may carry zoonotic viruses and viruses that are currently incapable of infecting humans but have evolved with pathogenic potential. In summary, comprehensive viral surveillance and screening of captive nonhuman primates is necessary.

ecology↗

bioRxiv2025

Hypoxia-Induced Active Dynamics Promotes Early Tumorigenesis

Understanding early tumor formation provides insights for cancer prevention. However, in vivo studies focus on later stages, leaving initial tumorigenesis poorly understood. Hypoxia is a key microenvironmental factor in cancer, yet its impact on single-cell tumor initiation and dynamics remains unclear. To address this, we developed an integrated live-imaging platform for hypoxic conditions, enabling first direct observation of 3D tumor spheroid development from a single cell. We show hypoxia accelerates tumorigenesis. Beyond growth, directional movement promotes spheroid fusion. This is driven by optimized actin polymerization and cell-cell adhesion. Hypoxia induces specialized, fusion-competent cells with outstretched F-actin and tiny nuclei that bridge spheroids. Concurrently, hypoxia triggers genetic instability, evidenced by tiny nuclei and aneuploidy. The interplay between dynamic and genetic instability optimizes spheroid mechanical properties, creating a positive feedback loop fuels proliferation. Our findings offer insight into hypoxias role in early tumorigenesis and highlight potential of targeting dynamic-genetic balance for prevention. Statement of SignificanceHypoxia accelerates early tumorigenesis by promoting directional 3D tumor spheroid fusion via optimized actin dynamics and mechanical balance, while inducing micronuclei formation and aneuploidy-linked genetic instability, forming a positive feedback loop that boosts proliferation and malignant progression.

cancer biology↗

bioRxiv2024

Identification and analysis of DEGs of mouse tumor cells by integrated bioinformatics methods

Mutations and genome instability are hallmarks of cancer. The advanced Next Generation Sequencing(NGS) technology now enables rapid and cost-effective analysis for tumoral and normal genomic translational research. In this research, mRNA sequencing was applied to get the whole transcriptome data of mouse B16F10 melanoma and CT26 colon carcinoma cells. Up regulation genes and down regulation genes were identified in tumor cells with differentially expressed genes(DEGs) analysis. The DEGs were analyzed with GO, KEGG and Reactome pathway enrichment study. Results demonstrated the DEGs and enriched pathways were mainly associated with cell proliferation and biosynthetic processing. Further, gene fusion and alternative splicing analysis reveled fusion genes and skipped exons were extensive exist within the chromosomes of tumor cells. Together, the integrated DEGs and bioinformatics analysis in this article may shed light on further research of cancer treating targets and molecular mechanisms of carcinogenesis.

bioinformatics↗

bioRxiv2024

A Systematic Comparison of Single-Cell Perturbation Response Prediction Models

Predicting single-cell transcriptional responses to perturbations is central to dissecting gene regulation and accelerating therapeutic design, yet the field lacks a rigorous, task-spanning assessment of model behavior. We present a large-scale benchmark of 13 representative methods and baselines across 25 datasets spanning diverse perturbation modalities and species, including two primary immune-cell drug-response resources. We evaluated three core tasks--generalization to unseen single-gene perturbations, prediction of combinatorial interactions, and transfer across cell types--using 24 metrics covering expression-level accuracy, relative changes, differential expression recovery, and distributional similarity. Across tasks, performance depended strongly on perturbation effect size and evaluation perspective: expression-level agreement was highest for small-effect perturbations resembling controls, whereas delta- and DE-based metrics improved with larger effects, providing clearer signals. Models shared a conservative bias, with fine-tuned foundation models compressing variance and underestimating synergistic effects in combinations. PerturbNet showed superior recovery of DE signatures in Tasks 1 and 2, while no method consistently generalized across cell types in Task 3, where biological consistency dominated outcomes. This benchmark establishes current methodological limits, clarifies that different metrics probe distinct biological signals rather than redundant summaries of the same prediction problem, and provides a foundation for developing virtual-cell models that more faithfully capture heterogeneous perturbation responses. Teaser: A large-scale benchmark reveals strengths and limits of models predicting single-cell perturbation responses.

bioinformatics↗

bioRxiv2024

Non-invasive diagnosis of early chronic colitis cancerization via amplified sensing of miRNA-21 in NIR-IIb window

Early diagnosis of the colitis-associated colorectal cancer (CRC) is of great significance for improving prognosis and survival rates. However, the clinical used colonoscopy and biopsy methods are invasive and lack of sensitivity at early stage of cancerization. Herein, we present an amplified sensing strategy in the second near-infrared b (NIR-IIb, 1500-1700 nm) window for non-invasive in situ visualization of early cancerization biomarker miRNA-21. A CRC nanosensor composed of Er3+ doped lanthanide nanoparticles, DNAzyme, and IR820 dye is designed as a NIR-IIb ratiometric luminescence reporter, providing rapid feedback and high sensitive miRNA-21 detection with limit of detection (LOD) of 1.26 pM. This strategy enables a non-invasive detection of colitis-associated cancerization up to [~]4 weeks ahead of the clinically used biopsy analysis, providing a promising alternative for early diagnosis of chronic colitis cancerization and guidance for therapeutic management.

bioengineering↗

bioRxiv2024

FABP5 in Skin Macrophages Mediates Saturated Fat-Induced IL-1β Signaling in Obesity-Associated Psoriasis Development

High fat diet (HFD)-induced obesity increases the risk and severity of psoriasis. However, the immunoregulatory effects of different HFD-induced obesity on psoriasis pathogenesis remains poorly understood. Here, mimicking human dietary fat profiles, four HFDs - saturated, monounsaturated, omega-6 and omega-3 fats - were designed and used to induce obesity in mice. Despite comparable obesity levels across groups, only the saturated HFD exacerbated imiquimod (IMQ)-induced psoriasis. This exacerbation correlated with elevated levels of IL-1{beta}-producing macrophages, IL-17A-producing {gamma}{delta} T cells, and neutrophils within psoriatic lesions. Mechanistically, saturated fatty acids (FAs) promoted IL-1{beta}/IL-17 signaling via fatty acid-binding protein 5 (FABP5)-mediated mitochondrial FA oxidation and extracellular ATP release in skin macrophages. Deletion of FABP5, either globally or specifically in macrophages, attenuated IL-1{beta}/IL-17A signaling and alleviated IMQ-induced psoriasis. These findings identify FABP5 as a key mediator of saturated HFD-driven psoriasis via the IL-1{beta}/IL-17 axis, offering insights into the interplay between dietary fats, obesity and psoriasis. HighlightsO_LISaturated, but not unsaturated, high-fat diets (HFDs) drive the development of obesity-associated psoriasis. C_LIO_LISaturated fats enhance IL-1{beta}/IL-17 signaling in psoriatic skin. C_LIO_LIFABP5 mediates saturated fat-induced IL-1{beta} signaling by promoting ATP production and release. C_LIO_LIDeletion of FABP5 in macrophages alleviates the development of saturated HFD-associated psoriasis. C_LI Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/628705v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@93fedaorg.highwire.dtl.DTLVardef@409fa2org.highwire.dtl.DTLVardef@b08362org.highwire.dtl.DTLVardef@81abcc_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗