Biology subjects

Liu, P.

Publications and source records attributed to Liu, P..

At least 73 records · Page 4Linked to original sources

bioRxiv2025

Thermo-Dynamic Flux Balance Analysis, a novel approach to simulate circadian metabolism

Circadian metabolism arises from complex, time-dependent interactions across organs, yet experimental characterization in humans remains limited. Current whole-body metabolic models are either too large for dynamic simulation or insufficiently detailed to capture temporal physiology. We developed a multi-tissue human metabolic reconstruction, HGEM1.19+, an extensively curated model for dynamic simulation. We introduced Thermo-Dynamic Flux Balance Analysis (tdFBA), a novel formulation that integrates thermodynamic constraints, organ-specific enzyme capacities, solubility limits, osmotic balance and pH buffering. Murine circadian transcriptomics and metabolomics were integrated with human datasets to parameterize temporal dynamics. A genetic algorithm optimized internal parameters under CHOW diet conditions and model performance was evaluated using circadian metabolomics and gene-sage patterns. The framework recapitulated key metabolic oscillations under CHOW diet and partially reconstructed perturbed states including HFD, BMAL1 knockout, and tissue-specific re-entrainment. tdFBA enables physiologically grounded, multi-organ dynamic simulations and provides a foundation for exploring human circadian metabolism and perturbation responses.

systems biology↗

bioRxiv2025

Histone Succinylation-Driven LINE-1 Reactivation Links High-Fat Diet Stress to Hepatic Inflammation and Liver Disease

Endogenous retroelements such as LINE-1 (L1) are stress-responsive genomic elements increasingly implicated in stress induced inflammation and associated pathogenic states. Here, we uncover a novel mechanism whereby high-fat diet-associated palmitic acid stress triggers chromatin remodeling that derepresses L1 elements and an IRF3-dependent interferon response, leading to innate immune activation in hepatocytes. Mechanistically, we show that that palmitic acid exposure promoted p300/CBP-mediated H3K122 succinylation at L1 promoters, coupled with reduced sirtuin desuccinylase cofactor availability, thereby enhancing chromatin accessibility and transcription. Antisense oligonucleotide-mediated L1 silencing abrogated this response by resetting chromatin homeostasis, demonstrating a causal role for L1 in palmitate-induced inflammation. In vivo, L1 knockdown in a fructose-palmitate-cholesterol (FPC) diet-induced mouse model of MASLD/MASH improved insulin sensitivity, reduced hepatic inflammation, and ameliorated fibrosis. These findings identify L1 derepression as a key epigenetic and inflammatory effector of dietary lipid stress and establish L1 inhibition as a potential therapeutic strategy for metabolic liver disease.

molecular biology↗

bioRxiv2025

Detection of Mid-parent Heterosis Genes in Large-Scale Unreplicated RNA-Seq Experiments

Mid-parent heterosis (MPH), characterized by hybrid trait values deviating from the mid-parent average, is a well-documented phenomenon whose genetic basis remains poorly understood. Identifying genes associated with MPH is crucial for uncovering the molecular mechanisms underlying heterosis. Recent large-scale RNA-sequencing (RNA-seq) experiments enable the evaluation of heterosis genes across numerous families; however, replication is often infeasible due to cost and labor constraints, resulting in unreplicated large-scale datasets and posing statistical challenges for dispersion estimation and reliable inference. To address this issue, we propose a novel two-stage likelihood ratio test (2sLRT) for detecting MPH genes in unreplicated RNA-seq experiments. In the first stage, genes and families without evidence of differential expression across varieties are identified, and the corresponding varieties are used as pseudo-replicates to estimate dispersion. In the second stage, a likelihood ratio test based on the negative binomial distribution is employed to test for MPH. Simulation studies demonstrate that 2sLRT achieves higher power and better false discovery rate control compared to existing approaches. Application of 2sLRT to a maize RNA-seq dataset with 599 families further highlights the methods effectiveness in revealing meaningful patterns of MPH gene expression.

plant biology↗

bioRxiv2025

Lineage-wide evolution of 3D genome organisation and centromeres in brown algae

Although 3D genome architecture has been described for an increasing number of plant and algal species, comparative analyses across closely related lineages remain scarce. Consequently, fundamental questions persist about how chromatin organization is maintained or reshaped over deep evolutionary time, and how such changes relate to life-history traits, genome size, and linear genome features. Here, we present a comprehensive analysis of 3D chromatin architecture across six brown algae species and one outgroup, spanning the phylogenetic breadth and biological complexity of this key photosynthetic lineage. We show that compact genomes lack chromatin domains whereas larger, transposable element-rich genomes of morphologically complex taxa tend to exhibit structured organization including TAD-like domains. We investigate chromatin folding patterns and gene expression over evolutionary time and uncover 3D chromatin features associated with transitions in sexual systems. Moreover, we reconstruct the ancestral brown algal karyotype, revealing deeply conserved macrosynteny and providing a new framework for interpreting chromosome-scale genome dynamics. Finally, we uncover an ancient and highly conserved association between centromeres and chromodomain-encoding retrotransposons, revealing a remarkable example of convergence in centromere-transposon co-evolution between brown algae and angio-sperms, and one of the most stable examples of centromere-linked transposable elements known in eukaryotes. Together, our findings elucidate the evolutionary history of 3D chromatin and linear genome architectures across an entire eukaryotic lineage and highlight extreme centromere stability in brown algae, providing a powerful point of comparison with land plants and deepening our understanding of genome evolution in independent multicellular lineages. One sentence summaryWe present a lineage-wide evolutionary analysis of 3D genome architecture and organization across brown algae, revealing conserved chromosomal features, lineage-specific rearrangements, and long-term co-evolution of centromeres and retrotransposons that together illuminate how nuclear architecture evolves over hundreds of millions of years.

genomics↗

bioRxiv2025

LaCONIC: A Label-Aware and Graph-Guided Contrastive Multi-Omics Collaborative Learning Model for Cancer Risk Prediction

Investigating accurate cancer survival prediction models has important clinical value for optimizing therapeutic strategies and improving clinical outcomes. Although an increasing number of models have shifted from relying solely on clinical variables to integrating multi-omics data, there remains insufficient exploitation and integrative utilization of gene regulatory network (GRN) structures and cancer subtype information, which limits the predictive accuracy and biological interpretability of multi-omics models. Therefore, this study proposes label-aware and graph-guided multi-omics collaborative learning framework, termed LaCONIC, to achieve accurate and interpretable cancer survival prediction. To obtain biologically meaningful regulatory features of different molecular types, we first construct a gene regulatory network comprising multiple molecular entities and their relations, and design a heterogeneous graph self-supervised pre-training module to obtain unified graph-based gene representations. To fully leverage multiomics and multi-modal information, we develop an adaptive cross-omics representation learning module that performs intraomics modality alignment (i.e., graph and expression modals) and inter-omics representation alignment, thereby achieving synergistic integration of multi-source information. Moreover, to comprehensively capture global cross-omics molecular interactions, we present a graph-guided cross-omics interactive learning module that explicitly encodes gene regulatory network priors within a Transformer-based architecture. Finally, we introduce cancer subtype information to construct a label-aware constraint mechanism that improves predictive performance while enhancing inter-class separability and intra-class consistency of the learned representations. Experiments on multiple cancer datasets show that LaCONIC outperforms existing state-of-the-art methods in various metrics. SHAP-based interpretability analysis on breast cancer further identifies survival-associated regulatory modules and high-risk molecules (e.g., hsa-miR-148a-3p, ARMC1, TMEM242), highlighting its potential for biological mechanism elucidation and prognostic assessment. The source code is available at https://github.com/Liangyushi/LaCONIC.

bioinformatics↗

bioRxiv2025

Unraveling the archaeal virosphere: diversity, functional and virus-host interactions

Archaea, the third domain of life, play critical roles in global biogeochemical cycles. However, their virosphere, particularly the proviruses which integrated into host genomes, remains largely unexplored. To systematically reveal the landscape of archaeal proviruses, we conducted large-scale mining of public and in-house genomic datasets spanning all presently known archaeal phyla. We identified 9,697 archaeal proviruses across 19 archaeal phyla and 366 families, which clustered into 9,123 viral operational taxonomic units (vOTUs). Among these, 97.2% represent novel viruses, and 81.3% could not be classified at the family level, substantially expanding the known diversity of archaeal viruses. Host range analysis revealed that many proviruses exhibit broad infectivity across archaeal lineages, with some even capable of cross-domain infection. Genomic analysis identified 178 distinct types of antiviral systems in archaeal hosts, encompassing multiple CRISPR-Cas variants and restriction-modification (RM) systems. Meanwhile, we detected 747 anti-defense genes encoded by 710 proviruses, such as anti-CRISPR and anti-RM, directly corroborating the ongoing evolutionary arms race between archaeal hosts and their viruses. Additionally, we identified 532 auxiliary metabolic genes (AMGs) within archaeal proviruses that are involved in key processes including carbon, nitrogen, and sulfur metabolism, indicating their potential to reprogram host metabolic pathways and thereby influence biogeochemical cycling. This study establishes a systematic global genomic atlas of archaeal proviruses, advancing our understanding of their distribution and diversity while laying the groundwork for future investigations into how AMG-mediated processes influence archaeal metabolism and ecosystem functions.

ecology↗

bioRxiv2025

PROX1 loss in adult mouse Schlemm's canal causes permanent ocular hypertension

Glaucoma is associated with ocular hypertension and lowering intraocular pressure is a key objective of glaucoma therapies. Recent studies have established a role for the Schlemms canal endothelium in this pressure increase and have shown it to have a unique, lymphatic-like, hybrid phenotype. However, the role of these lymphatic phenotypes in the adult canal remains uncertain. Long-term functional studies have been limited by systemic importance of lymphatic genes and lack of Schlemms canal-specific animal models. Here, we designed and validated a strategy using 4OH-tamoxifen-loaded nanocarriers to generate targeted, Schlemms canal specific knockout mice lacking lymphatic phenotypes. Using this system, we selectively deleted Prox1, the master transcription factor governing lymphatic fate. Within four weeks, intraocular pressure significantly increased, and ocular hypertension was maintained for at least 24 weeks. Unlike lymphatic vessels, which degenerate following Prox1 deletion, Schlemms canal reverted to a less functional vein-like phenotype with no change in size or morphology. These results highlight the utility of nanocarriers for tissue-specific genetic recombination and demonstrate that changes in lymphatic phenotypes alter intraocular pressure, providing new targets for glaucoma therapy. Moreover, as we found that PROX1 was downregulated with age in human Schlemms canal, these canal-specific conditional Prox1 knockout mice are a valuable new adult-onset model of ocular hypertension that captures key features of age-related human disease.

physiology↗

bioRxiv2025

MitoEM 2.0 - A Benchmark for Challenging 3D MitochondriaInstance Segmentation from EM Images

We present MitoEM 2.0, a curated data resource for training and evaluating three-dimensional (3D) mitochondria instance segmentation in volume electron microscopy. The collection assembles multiscale vEM datasets (FIB-SEM, SBF-SEM, ssSEM) spanning diverse tissues and species, with expert-verified instance labels emphasizing biologically difficult scenarios, including dense mitochondrial packing, hyperfused networks, and thin filamentous connections with ambiguous boundaries. All releases include native-resolution volumes and standardized processed versions, per-volume metadata (voxel size, modality, tissue, splits), and official train/validation/test partitions to enable reproducible benchmarking. Annotations follow a consistent protocol with quality checks and instance reindexing. Data are provided in NIfTI with nnU-Net-compatible layout, alongside machine-readable split files and checksums. Baseline scripts support common training pipelines and size-stratified evaluation. By consolidating challenging volumes and harmonized labels, MitoEM 2.0 facilitates robust model development and fair comparison across methods while supporting reuse in bioimage analysis, algorithm benchmarking, and teaching.

neuroscience↗

bioRxiv2025

Blood originates in hypoblasts during embryonic development

Blood is essential for oxygen supply throughout life. The emergence of blood in the human embryo remains poorly understood. Our study leverages multiple stem cell embryo models and advanced lineage barcoding to unveil that hypoblast, originally regarded as forming the yolk sac wall, is heterogeneous and contributes to CDX2+ extraembryonic mesoderm, followed by hemoglobin+ cells as the first blood cells. CDX2 marks the hypoblast-to-hemoglobin+ cell trajectory that functionally sustains oxygen levels in embryo models. These hemoglobin+ cells molecularly and functionally resemble phagocytes. We show that the erythro-core regulatory network is poised in hypoblasts, and its boost endows erythropoiesis to both hypoblasts and phagocytes. Hypoblasts are the origin of the first blood in humans and non-human primates, providing a conceptual framework that earlier blood generation than expected fills the gap in the establishment of circulation. Further, the hypoblast is a place where primates may repurpose the phagocyte program to carry oxygen throughout embryos. HighlightsO_LIBarcode-traced hypoblast fate in human embryo models; C_LIO_LIThe first blood comes from the hypoblast that contributes to hemoglobin+ phagocyte-like cells; C_LIO_LICDX2 marks hypoblast blood that sustains oxygen supply in embryos before heart formation; C_LIO_LIErythro-core regulatory network endows erythropoiesis to human hypoblasts and phagocytes. C_LI

developmental biology↗

bioRxiv2025

Iterative immunogen optimization to focus elicited responses on a conserved, subdominant influenza hemagglutinin epitope

Designing effective vaccination strategies against genetically diverse viruses, such as HIV or influenza, is hindered by the ability of these pathogens to mutate and readily evade immune responses. While these viruses contain conserved regions that cannot easily mutate without affecting viral fitness, these sites are subdominant, meaning that they are not the primary target of antibodies elicited by natural infection or current vaccines. Here, we integrated recent advances in machine learning methods for protein structure prediction and design to engineer protein immunogens that focus immune responses on a conserved, subdominant HA epitope targeted by broadly cross-reactive influenza antibodies. Iterating between computation-guided optimization and in vivo analyses generated immunogens that faithfully displayed the target epitope and redirected humoral responses toward it upon vaccination. These results provide a blueprint for applying recent protein engineering approaches to immunogen design and may inform the development of broadly protective influenza vaccines.

immunology↗

bioRxiv2025

A multi-tissue atlas of genetic regulatory effects in sheep

Characterizing the impact of genomic variants on genome function and ultimately complex traits in livestock is essential for the development of sustainable precision agriculture and comparative genomics. Here, as part of the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we present the pilot phase of the SheepGTEx resource through analyzing 6,761 RNA-sequencing samples of 51 primary tissues in a multi-breed population of sheep. We identify millions of regulatory variants associated with seven types of molecular phenotypes, and fine-map 322,468 primary and 114,017 non-primary effects, revealing a high degree of regulatory allelic heterogeneity. We systematically characterize the pleiotropic effects of these variants on molecular phenotypes, assess their context-specific regulatory patterns across tissues, breeds, sexes, and developmental stages, as well as explore their evolutionary constraints across mammals. Finally, we demonstrate the substantial potential of the SheepGTEx resource (https://sheepgtex.farmgtex.org), by providing examples of regulatory mechanisms underpinning 34 complex traits, population divergence between European and Asian breeds, and adaptive evolution in sheep over the past ten millennia.

genomics↗

bioRxiv2025

The dominance of gene expression controlled by trans-eQTL hotspots contributes to phenotypic heterosis in maize

Heterosis, or hybrid vigor, is a key phenomenon in genetics research and agricultural production, and has been primarily attributed to non-additive genetic effects such as dominance -- a prevailing consensus shaped by decades of empirical research and theoretical debate. Although dominance may arguably arise from distal modifiers, their selective advantage is debated due to presumably small individual effects. To address this long-standing question, particularly how genetic dominance manifests at the transcriptomic level and contributes to phenotypic heterosis, we integrated transcriptomic and phenotypic data from a large population of maize hybrids and their inbred parents. We found that [~] 30% of the expressed seedling genes in a significant proportion of hybrids exhibited expression patterns deviating from the average of the two parents, indicative of non-additivity. Further analysis suggests that while hybrid gene expression per se is primarily regulated by cis-eQTLs, expression dominance (or non-additivity) is disproportionately controlled by trans-eQTLs. These trans-eQTLs cluster into hotspots that regulate the non-additivity of hundreds of target genes, mostly within co-expression networks, and are notably enriched for transcription factors (TFs). Focusing on one such hotspot, we functionally validated a classical maize gene ZmR1, a basic helix-loop-helix (bHLH) TF associated with multiple seedling trait heterosis, as a candidate regulator of expression dominance across hundreds of genes. Overexpression of ZmR1 enhances expression dominance of downstream genes and increases phenotypic heterosis in both seedling and adult traits. Further experiments confirmed its direct regulatory role in modulating genes involved in anthocyanin biosynthesis and lignin metabolism, driving transcriptome-level dominance. These results provide empirical support for the modifier hypothesis under an omnigenic model, suggesting that heterosis arises not from the modification of a single genes inheritance but through the coordinated regulation of hundreds of phenotype-associated genes, thereby helping to reconcile the long-standing debate over the genetic basis of dominance in heterosis.

genetics↗

bioRxiv2025

A Human Hippocampal Organoid Model with Sustained Neural Stem Cells Reveals State Shifts Under Glucocorticoid Stress

The human hippocampus is a critical brain region for learning, memory, and stress regulation, distinguished by its ability to sustain neurogenesis after birth. This plasticity is driven by hippocampal neural stem cells (NSCs), which generate new neurons and maintain circuit integrity, but are highly sensitive to environmental and pathological influences. Mechanistic insight into human hippocampal development and neurogenesis remains limited by the absence of physiologically relevant models. Here, we establish an optimized protocol to generate human induced pluripotent stem cell-derived hippocampal organoids that recapitulate key features of hippocampal development. These organoids maintain organized NSC niches, support ongoing neurogenesis, and generate hippocampus-specific cell types. Cellular, transcriptomic, and electrophysiological analyses confirm progressive neuronal maturation, synapse formation, and functional activity, highlighting the physiological relevance of the system. Using this model, we modeled excess prenatal glucocorticoid exposure with dexamethasone, which perturbed NSC dynamics by reducing proliferation and inducing a precocious quiescent-like state. RNA sequencing revealed downregulation of NSC activation genes and upregulation of quiescence- and autophagy-associated programs, suggesting that glucocorticoid signaling enforces an early transition toward quiescence. These findings reveal a mechanism by which excessive glucocorticoid exposure may impair hippocampal growth. Together, this study introduces a robust human hippocampal organoid platform for dissecting the regulation of hippocampal development and for modeling the impact of environmental stressors on human neurogenesis.

neuroscience↗

bioRxiv2025

Biologically Inspired Deep Neural Network Models for Visual Emotion Processing

The perception of opportunities and threats in complex visual scenes represents one of the main functions of the human visual system. The underlying neurophysiology is often studied by having observers view pictures varying in affective content. While deep neural networks (DNNs) have shown promise in modeling visual recognition of objects, their capacity to model visual affective processing remains to be better understood. In this study, we proposed a biologically inspired deep neural network model, referred to as the Visual Cortex Amygdala (VCA) model, that integrates a vision transformer with an amygdala-mimetic module designed to reflect both the anatomical hierarchy and self-attention-based computational mechanisms of the human brain. We evaluated the model along three dimensions: (1) predictive accuracy for emotional valence and arousal, (2) representational alignment with human amygdala activity, and (3)neural mechanisms of emotion representation. Our results showed that (1) the model can predict with high accuracy human emotion ratings on 1,182 images from the International Affective Picture System (IAPS) dataset (valence: r {approx} 0.9; arousal: r {approx} 0.7), (2) the models internal representations aligned with functional Magnetic Resonance Imaging (fMRI) data from the human amygdala, and (3) at the single neuron level, the amygdala module evolved emotion selectivity, and at the neuronal population level, the representational geometry became progressively more aligned with psychological models of emotion. Additional issues explored included (1) the effect of visual encoding and (2) the effect of structure and computational mechanisms on emotional assessment.

neuroscience↗

bioRxiv2025

An ultra-long acting insulin enables glucose-synchronised release

Delayed and weak glucose-responsive kinetics, coupled with short plasma exposure and complicated formulation, remain major obstacles to the clinical translation of glucose-responsive insulin formulations. Here we report a rapidly absorbable, ultra-long acting, and glucose-responsive insulin analogue via engineering recombinant human insulin with two phenylboronic acids. The insulin analogue has a long circulating half-life (t1/2{beta} [~]150 h) due to its unique, unprecedented, glucose-responsive binding to blood circulation-associated proteins. This interaction drives the formation of a unique systemic reservoir that allows synchronised dynamic response in insulin levels to glucose fluctuations. In type 1 diabetic mice and minipigs, a single subcutaneous dose can maintain normoglycaemia for over one week (47.5-fold compared to insulin glargine). After the last injection of four consecutive weekly administrations in mice, the glucose-lowering effect can last 800 hours. Administering this glucose-responsive insulin analogue with a fully automated insulin delivery system can leverage dual closed loops and achieve a glucose time in range of over 85% and a coefficient of variation of approximately 30%, better than the recommended targets for human therapy. Importantly, no toxicity was identified in the study.

bioengineering↗

bioRxiv2025

Cryoprotectants-assisted plunge freezing of thick brain tissue specimens for targeted physiologically relevant cryo-imaging in situ

In situ cryoET (cryoelectron tomography) and cryo-FIB/SEM (cryo-focused ion beam/scanning electron microscopy) volume-EM (electron microscopy) imaging provide spatiotemporal snapshots of biological systems in their near-native aqueous environment. Freezing and subsequent thinning of thick biological specimens prior to cryo-imaging is a time-consuming and challenging task that requires state-of-art methodology. As a result, cryo-imaging reports obtained from non-trivial specimens including mammalian brain tissues are scarce and their physiological relevance remains to be determined. Here, we benchmarked plunge freezing with a variety of cryoprotectants that allow for mouse brain tissue vitrification of up to about 100 microns thick and across several brain regions while keeping the tissue functional. By utilizing the knock-in (KI) mouse model with fluorescent astrocytes we have performed targeted cryo-FIB/SEM volume-EM imaging as well as targeted high-resolution cryoET imaging. Prior to cryoET, we have successfully generated lamellae in a semi-automated fashion on both LMIS (liquid metal ion source)- and plasma-based cryo-FIB/SEM instrumentation thus expanding applicability of our pipeline. We visualized the NVU (neurovascular unit) and astrocytes processes and validated the physiological relevance of our outputs based on the morphology of the corresponding cellular and subcellular features. The pipeline utilizes common vitrification setups and can be potentially extended toward alternative tissue specimens. Ultimately, we expect our approach to become an important step towards democratization of physiologically relevant in situ cryo-imaging studies.

biophysics↗

bioRxiv2025

Chronic kidney disease exacerbates hyperlipidemia and atherosclerosis via miR-148a-3p targeting SIK1/AMPKα1 in liver

BackgroundCardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). As a major risk factor for atherosclerotic cardiovascular disease (ASCVD), hyperlipidemia is a common sequela of CKD, which is linked to increased lipid synthesis, impaired lipoprotein clearance, and maladapted reverse cholesterol transport. Because exosomes can transport miRNAs to modulate intercellular and tissue communication, we hypothesized that exosomal miRNAs can act as endocrine-like molecules to modulate the CKD-associated hyperlipidemia and ASCVD. MethodsSmall RNA-seq and qPCR were used to determine the differential plasma level of exosomal miR-148a-3p in ASCVD patients with and without CKD. RNA-seq and in silico analysis were used to establish the regulation of lipid metabolism via miR-148a-3p/salt-inducible kinase 1 (SIK1)/AMP-activated protein kinase alpha 1 subunit (AMPK1) in the liver. Inhibition of miR-148a-3p or overexpression of SIK1/AMPK1 in ApoE-/- mice with 5/6 nephrectomy was used to elucidate the role of the miR-148a-3p/SIK1/AMPK1 axis in CKD-related hyperlipidemia and atherosclerosis. ResultsThe plasma level of exosomal miR-148a-3p was significantly elevated in patients with ASCVD and CKD (ASCVD/CKD) and ApoE-/- mice with 5/6 nephrectomy. Via circulating exosomes, kidney-generated miR-148a-3p was delivered to the liver, where it targeted SIK1/AMPK1 transcripts, thereby upregulating SREBP2/PCSK9 and reciprocally downregulating LDLR. Levels of SIK1 and AMPK1 were decreased in hepatocytes transfected with miR-148a-3p or treated with plasma exosomes from ASCVD/CKD patients, with attendant SREBP2 activation and attenuated LDL-C binding. The decreased LDL-C binding was rectified by SIK1/AMPK1 or LNA-miR-148a-3p overexpression. LNA-miR-148a-3p or AAV8-SIK1/AMPK administration in 5/6 nephrectomy/ApoE-/- mice significantly ameliorated hyperlipidemia and atherosclerosis. ConclusionIn ASCVD/CKD patients and nephrectomy/ApoE-/- mice, kidney-originating miR-148a-3p targeted hepatic SIK1/AMPK1 mRNA. This exosome-mediated endocrine effect upregulated SREBP2/PCSK9 and reciprocally reduced LDLR level, which elevated plasma LDL-C level and exacerbated ASCVD. These findings underscore a kidney-liver-artery axis involved in cardiovascular-kidney-metabolic syndrome.

pathology↗

bioRxiv2025

Metabolite Profiling of Epimedium sagittatum Bee Pollen: Identified Bioactive Flavonoids with Multi-Disease Functional Food Potential

Epimedium sagittatum bee pollen (EBP) is a bee pollen product of a medicinal plant, but its chemical characteristics remain unclear. In this study, EBP was systematically characterized by biochemical analysis and UPLC-MS/MS, using Brassica rapa bee pollen (BBP), Camellia sinensis bee pollen (CBP), and Epimedium leaves for compari-son. A total of 1,073 secondary metabolites were identified in EBP, mainly flavonoids (330, 30.8%) and phenolic acids (165, 15.3%). EBP showed the highest total flavonoid content among the three bee pollen types (4.75 mg/g) and was clearly separated from BBP and CBP in multivariate analysis. EBP contained 19 unique metabolites, fewer than CBP (271), but these included several high-content flavonoid compounds, such as cacticin, brassicin, and tricetin-4'-methyl ether-3'-{beta}-D-glucoside. Differential metabolite analysis identified 449 and 1,085 metabolites that differed between EBP and BBP, re-spectively, with flavonoid compounds forming the main differential class. Among the shared differential metabolites, 45 flavonoids were consistently higher in EBP, in-cluding kaempferol, tamarixetin, and sinensetin. Network pharmacology screening further suggested that flavonoid metabolites, especially kaempferol, tamarixetin, and sinensetin, deserve particular attention in future studies of EBP. Compared with Epimedium leaves, characteristic leaf flavonoids such as icariin and epimedins A-C were present at very low levels or were not detected in EBP. Overall, EBP is charac-terized by a distinct, relatively concentrated flavonoid chemical profile, distinct from both common commercial bee pollens and Epimedium medicinal tissues. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/679240v2_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@1587d35org.highwire.dtl.DTLVardef@8461d6org.highwire.dtl.DTLVardef@1336149org.highwire.dtl.DTLVardef@381ae8_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗