Biology subjects

yang, y.

Publications and source records attributed to yang, y..

16 recordsLinked to original sources

bioRxiv2026

VINTER: a generative vision-language model for annotating and interrogating spatial tissues

Spatial transcriptomics links gene expression to tissue structure, yet current models learn embeddings whose meaning is assigned afterwards or read histology without measured expression. Tissue decisions are therefore rarely made from morphology, genes and neighbourhood together, or examined through them. Here we introduce VINTER, a generative vision-language model aligned on 1.45 million histology-caption pairs that reads histology, measured gene expression and spatial neighbourhood as one sequence. It returns the probability of every tissue class, and because genes enter as text, its molecular evidence can be edited with the image held fixed. Reading all three sources together, VINTER annotated tissue more accurately than spatial-domain methods and a spatial foundation model, and transferred across cohorts without target labels. Editing only the neighbourhood resolved the follicular B-cell and plasma-cell programmes behind its reading of tertiary lymphoid structure (TLS) maturation in lung and kidney cancer. Its class probabilities exposed what single labels conceal in triple-negative breast cancer: immune heterogeneity within stroma and cancer hidden beneath benign labels. Without retraining, the same model transferred to Visium HD and single-cell Xenium data and resolved follicular architecture within colorectal cancer TLS. VINTER thus turns spatial annotation into an interrogable reading of tissue across platforms and resolutions.

bioinformatics↗

bioRxiv2026

Migrasomes May Originate from Cilia and Represent an Alternative Ciliary Form

Abstract Background Migrasomes, the newly discovered vesicular organelles, have long been speculated to originate from membrane dynamics during cell migration. Here we present integrated imaging and multi-omics evidence supporting a ciliary origin of migrasomes. The shared vesicular trafficking pathways between ciliogenesis and migrasome biogenesis (trans-Golgi/endosomal systems) prompted us to investigate their spatiotemporal coupling mechanism in disease models. Methods Using high-resolution SEM and fluorescence confocal microscopy (FCM), we visualized cilium-like structures with enlarged tips adjacent to migrasome-like vesicles across multiple cell types. TMT-based quantitative proteomics was used to identify proteins shared among migrasomes from different cell types and examine their associations with ciliary proteins. DMBA-induced breast cancer and femoral fracture models were used to investigate the cilia-migrasome association during tumor metastasis and fracture healing. Results Bioinformatics analysis showed a highly positive incidence correlation between cilia and migrasome genes in 31 types of 7858 human normal tissues and organs and various cell types. In 32 cancer tissues, cilia and migrasome genes were still strongly but abnormally correlated. Signaling enrichment by ARL13B and TSPAN4 showed that cilia-migrasome association is related to epithelial-mesenchymal transition (EMT). By analyzing the ARL13B and PIGK expression, we found the abnormal cilia-migrasome association in metastatic breast cancer and positive cilia-migrasome association in fracture healing bone. Conclusion Our findings support a ciliary origin of migrasomes, pointing to a previously unrecognized pathway of organelle biogenesis. Notably, the ciliary-migrasomal association correlates with two distinct pathological/physiological contexts: (1) aberrant epithelial-mesenchymal transition (EMT) in metastatic breast cancer, and (2) accelerated regeneration during fracture healing and tissue repair. This dual correlation not only establishes a mechanistic link between ciliary function and migrasome biogenesis but also highlights their divergent roles in disease progression versus tissue homeostasis. Investigating the spatiotemporal dynamics of this association may provide novel therapeutic targets for metastatic malignancies and regenerative medicine.

cell biology↗

bioRxiv2025

Comprehensive evaluation and interpretative insights of peptide-HLA binding prediction tools using explainable artificial intelligence

Accurate prediction of human leukocyte antigen class I (HLA-I) peptide binding is pivotal for immunological research, including vaccine development and immunotherapy. However, challenges such as tool performance variability, limited interpretability, and dataset quality hinder the broader applicability of existing models. Here, we conduct a comprehensive benchmarking of 17 prediction tools using a rigorously curated dataset of over 290,000 peptides across 44 HLA-I alleles. We assess model accuracy, robustness, and interpretability, incorporating explainability methods such as SHAP and LIME to elucidate prediction mechanisms. Our analysis reveals significant performance differences, with self-attention-based models (e.g., STMHCpan and BigMHC) demonstrating superior accuracy, while CapsNet-MHC_AN, a capsule network model, offers competitive performance. Models trained on eluted ligand data outperformed those using binding affinity data, highlighting the importance of high-quality training datasets. Ensemble and multi-algorithm strategies further enhanced prediction reliability. These findings emphasize the need for continued innovation in model design, the integration of diverse datasets, and the exploration of structural predictors, providing a framework for developing more accurate, interpretable, and clinically relevant HLA-I peptide binding prediction tools.

bioinformatics↗

bioRxiv2025

Protenix - Advancing Structure Prediction Through a Comprehensive AlphaFold3 Reproduction

In this technical report, we present Protenix, a comprehensive reproduction of AlphaFold3 (AF3), aimed at advancing the field of biomolecular structure prediction. Protenix tackles the challenges of predicting complex interactions involving proteins, ligands, and nucleic acids, while enhancing accessibility and reproducibility. Across diverse benchmarks, including PoseBusters V2, low-homology PDB sets, and CASP15 RNA, Protenix achieves state-of-the-art performance in protein-ligand, protein-protein, and protein-nucleic acid predictions. We also address limitations, such as potential memorization effects, and outline future directions for improvement. By open-sourcing Protenix, we aim to democratize advanced structure prediction tools and accelerate interdisciplinary research in computational biology and drug discovery.

bioinformatics↗

bioRxiv2025

Electrospinning of hydroxypropyl chitosan nanofibers for bone regeneration application

To study the effect of electrospinning nanofiber mats synthesized using hydroxypropyl chitosan in conjugation with poly (vinyl alcohol) on the osteogenesis in MC3T3 cell, we fabricated different ratios of hydroxypropyl chitosan (HPCH) and poly (vinyl alcohol) to electrospin the nanofiber mats, the mechanical and physical properties of nanofiber mats were tested by using SEM, FT-IR and conventional methods. Then the effect of the electrospinning mats on osteogenesis in MC3T3 cell were evaluated by Alizarin Red stain, ALP stain and expression of relevant genes. We found that the nanofiber mats fabricated by hydroxypropyl chitosan (50%) and poly (vinyl alcohol)(50%) can induce osteoblast differentiation apparently in MC3T3 cell.

biochemistry↗

bioRxiv2024

Adipocyte microRNA-802 promotes adipose tissue inflammation and insulin resistance by modulating macrophages in obesity

Adipose tissue inflammation is now considered to be a key process underlying metabolic diseases in obese individuals. However, it remains unclear how adipose inflammation is initiated and maintained or the mechanism by which inflammation develops. We found that microRNA-802 (miR-802) expression in adipose tissue is progressively increased with the development of dietary obesity in obese mice and humans. The increasing trend of miR-802 preceded the accumulation of macrophages. Adipose tissue-specific knockout of miR-802 lowered macrophage infiltration and ameliorated systemic insulin resistance. Conversely, the specific overexpression of miR-802 in adipose tissue aggravated adipose inflammation in mice fed a high-fat diet. Mechanistically, miR-802 activates noncanonical and canonical NF-{kappa}B pathways by targeting its negative regulator, TRAF3. Next, NF-{kappa}B orchestrated the expression of chemokine and SREBP1, which translated into strong recruitment and M1-like polarization of macrophages. Our findings indicate that miR-802 endows adipose tissue with the ability to recruit and polarize macrophages, which underscores miR-802 as an innovative and attractive candidate for miRNA-based immune therapy for adipose inflammation.

immunology↗

bioRxiv2024

Recombinant expression, purification, and antifungal activity of the novel antimicrobial peptide TaW662

Blumeria graminis f. sp. tritici (Bgt) is a significant wheat fungal pathogen, posing threats to both yield and quality. Antimicrobial peptides, with their broad-spectrum activities, hold promise in combating Bgt-induced wheat fungal diseases.In this study, we identified TaW662, an antifungal peptide gene sourced from the wheat-Thinopyrum intermedium disomic alien addition line SN6306. Through third-generation transcriptome sequencing, we obtained the full-length transcript of TaW662. Notably, TaW662 exhibited upregulated expression in response to powdery mildew infection in SN6306. Subcellular localization analysis revealed TaW662s extracellular secretion, suggesting its role in defense mechanisms. Additionally, the TaW662 protein was expressed in Escherichia coli, and the purified protein could inhibit the growth of Bgt in vitro. Utilizing the online alphafold2 server, we predicted the three-dimensional structure of TaW662, aiding in understanding its fungicidal mechanisms. Analysis of TaW662s physicochemical properties further supported its potential efficacy as a fungicide against Bgt. In conclusion, TaW662 emerges as a promising candidate for combating Bgt-induced wheat fungal diseases, warranting further exploration for agricultural disease management strategies. HighlightsTaW662, a secreted protein homologous to TaWIR1, is induced in wheat by Blumeria graminis f. sp. tritici (Bgt). The expression pattern of TaW662 in wheat under induced by Bgt was analysed using RNA-Seq technology. The three-dimensional structure of TaW662 was predicted using AlphaFold2. The growth of Bgt is inhibited by recombinant TaW662.

plant biology↗

bioRxiv2024

Extracellular vesicles-based point-of-care testing for the diagnosis and monitoring of Alzheimer's disease

Alzheimers disease (AD) is a debilitating condition that affects millions of people worldwide. One promising strategy for detecting and monitoring AD early on is using extracellular vesicles (EVs)-based point-of-care testing; however, diagnosing AD using EVs poses a challenge due to the low abundance of EV-biomarkers. Here, we present a fully integrated organic electrochemical transistor (OECT) that enables high accuracy, speed, and convenience in the detection of EVs from AD patients. We incorporated self-aligned acoustoelectric enhancement of EVs on a chip that rapidly propels, enriches, and specifically binds EVs to the OECT detection area. With our enhancement of pre-concentration, we increased the sensitivity to a limit of detection of 500 EV particles/L and reduced the required detection time to just two minutes. We also tested the sensor on an AD mouse model to monitor AD progression, examined mouse A{beta} EVs at different time courses, and compared them with intraneuronal A{beta} cumulation using MRI. This innovative technology has the potential to diagnose Alzheimers and other neurodegenerative diseases accurately and quickly, enabling monitoring of disease progression and treatment response.

bioengineering↗

bioRxiv2024

Functional Diversification of Gene Duplicates under the Constraint of Protein Structure

Gene differentiation following duplication plays a crucial role in evolution, driving the emergence of new functional genes. This process involves changes in key gene traits, such as protein structure, expression patterns, subcellular localization, and enzymatic activity, which together contribute to the development of novel functions. Here, we identified a group of homologous Glycoside Hydrolase Family 50 (GH50) agarases in the deep-sea bacterium Agarivorans ablus strain JK6, providing an ideal model for studying gene differentiation following duplication. Phylogenetic analysis revealed that these enzymes arose through gene duplication and subsequent divergence. Experimental assays demonstrated that, while they retained similar glycoside hydrolase activity, their agarolytic activity diverged significantly. We further explored their structural variations constrained by the proteins 3D structural limitations, the development of specific localization linked to changes in enzymatic activity, and distinct expression patterns induced by different sugars. Notably, structural variations were primarily concentrated in the active site, while the overall backbone remained highly conserved. This study highlights gene differentiation following duplication as a key evolutionary strategy, facilitating the transition from single enzymes to complex functional systems.

evolutionary biology↗

bioRxiv2022

Designing a Minimal Artificial Glycolytic Pathway

The canonical glycolysis generates two molecules of acetyl-coenzyme A (acetyl-CoA) from one glucose through eleven cascade biochemical reactions. Here, we designed and constructed a Minimal Artificial Glycolytic (MAG) pathway consisting of only three types of biochemical reactions, with phosphoketolase as the core, combined with phosphatase and isomerase as auxiliary enzymes. It could theoretically achieve a 100% carbon yield to acetyl-CoA from any monosaccharide by integrating one-carbon condensation reaction. We tested the MAG pathway in vitro and in vivo, demonstrating the catabolism of typical C1-C6 carbohydrates to acetyl-CoA with yields from 82% to 95%. This novel glycolytic pathway provides a promising route for biomanufacturing with stoichiometric productivity from multiple carbon sources in the future.

synthetic biology↗

bioRxiv2022

Effect of Puerarin on PI3K-AKT Signaling Pathway in OsteoclastEffect of Puerarin on PI3K-AKT Signaling Pathway in Osteoclast

objectiveThis study intends to explore the role of PI3K-AKT signaling pathway in the effect of Puerarin on the proliferation, activity, and function of osteoclasts from the perspective of antioxidation. MethodsRAW264. 7 cells were divided into control group, induction group treated with 20ng/mL M-CSF and 50ng/mL RANKL, puerarin group treated with 20ng/mL M-CSF, 50ng/mL RANKL, and 50mol/L puerarin. The staining of osteoclasts before and after puerarin intervention was measured by TRAP staining and cell count. The changes of related molecules before and after puerarin intervention in osteoclasts were detected by real-time fluorescence quantitative PCR and Western Blot, including TRAP, MMP-9, Cathepsin K, NFATc1, PTEN, Catalase, PI3K, AKT, P-AKT(ser473), FoxO1, P-FoxO1. ResultsTRAP staining showed that puerarin inhibited the proliferation and differentiation of RAW264.7 cells into osteoclasts. The results of qRT-PCR and WB showed that compared with the control group, the gene expression of TRAP, MMP-9, cathepsin K and NFATc1 in the induction group was up-regulated, while the gene expression of Catalase was down-regulated. PTEN gene had no significant changes before and after puerarin intervention. The expression of P-AKT (ser473) and NFATc1 protein was up-regulated, while the expression of PI3K and AKT protein had no change. Compared with the induction group, the gene expression of TRAP, MMP-9, Cathepsin K, and NFATc1 in the puerarin group decreased, the gene expression of Catalase increased, the protein expression of PI3K and AKT remained unchanged, the protein expression of P-AKT (ser473), P-FoxO1 and NFATc1 decreased, and the protein expression of FoxO1 and Catalase increased. ConclusionPuerarin may promote the transcriptional activity of FoxO1, increase the expression of catalase protein and exert its antioxidant activity by regulating the PI3K-AKT signal pathway, so as to inhibit the proliferation and differentiation of osteoclasts.

cell biology↗

bioRxiv2021

Kif9 is an active kinesin motor required for ciliary beating and proximodistal patterning of motile axonemes

Most motile cilia have a stereotyped structure of nine microtubule outer doublets and a single central pair of microtubules. The central pair microtubules are surrounded by a set of proteins, termed the central pair apparatus. A specific kinesin, Klp1 projects from the central pair and contributes to ciliary motility in Chlamydomonas. The vertebrate orthologue, Kif9 is required for beating in mouse sperm flagella, but the mechanism of Kif9/Klp1 function remains poorly defined. Here, using Xenopus epidermal multiciliated cells, we show that Kif9 is necessary for ciliary motility as well as leads to defects in the distal localization of not only central pair proteins, but also radial spokes and dynein arms. In addition, single-molecule assays in vitro revealed that Xenopus Kif9 is a processive motor, though like axonemal dyneins it displays no processivity in ciliary axonemes in vivo. Thus, our data suggest that Kif9 plays both indirect and direct role in ciliary motility.

cell biology↗

bioRxiv2021

Vibrio cholerae may be transmitted to humans from bullfrog through food or water

Bullfrog is one of the most important economic aquatic animals in China. It is widely cultured in southern China, and is a key breed recommended as an industry of poverty alleviation in China. During recent years, a fatal bacterial disease has often been found in cultured bullfrogs. The clinical manifestations of the diseased bullfrogs were severe intestinal inflammation and even anal prolapse. A bacterial pathogen was isolated from the diseased bullfrog intestines. The bacterium was identified as Vibrio cholerae using morphological, biochemical and 16S rRNA phylogenetic analysis. In this study, V. cholerae was isolated and identified from diseased bullfrogs for the first time, providing a basis for the diagnosis and control of the disease. At the same time, it was also found that V. cholerae may be transmitted to humans from bullfrogs through bullfrog food and aquaculture water, creating a serious threat for human health. Therefore, society should pay attention to the modes of transmission of Vibrio cholerae from bullfrog and formulate reasonable safety measures to avoid disasters.

pathology↗

bioRxiv2020

Allantoin induces pruritus by activating MrgprD in chronic kidney disease

Chronic kidney disease is a disease with decreased, irreversible renal function. Pruritus is the most common skin symptom in patients with chronic kidney disease, especially in end-stage renal disease (AKA chronic kidney disease-associated pruritus [CKD-aP]); however, the underlying molecular and neural mechanism of the CKD-aP in patients remains obscure. Our data show that the level of allantoin increases in the serum of CKD-aP and CKD model mice. Allantoin could induce scratching behavior in mice and active DRG neurons; the calcium influx and the action potential were significantly reduced in DRG neurons of MrgprD KO or TRPV1 KO mice. U73122, an antagonist of PLC, could also block calcium influx in DRG neurons induced by allantoin. Thus, our results concluded that allantoin plays an important role in CKD-aP, mediated by MrgprD and TrpV1, in CKD patients.

pathology↗

bioRxiv2020

Accurately Clustering Single-cell RNA-seq data by Capturing Structural Relations between Cells through Graph Convolutional Network

Single-cell RNA sequencing (scRNA-seq) technologies promise to characterize the transcriptome of genes at cellular resolution, which shed light on unfolding cell heterogeneity and diversity. Fast-growing scRNA-seq profiles require efficient clustering algorithms to identify the same type of cells. Although many methods have been developed for cell clustering, existing clustering methods are limited to extract the representations from expression data of individual cells, while ignoring the high-order structural relations between cells. Here, we proposed GraphSCC, a robust graph artificial intelligence model to cluster single cells by accounting for structural relations between cells. The representation learned from the graph convolutional network, together with another representation output from a denoising autoencoder network, are optimized by a dual self-supervised module for better cell clustering. The experimental results indicate that GraphSCC model outperforms state-of-the-art methods in terms of various evaluation metrics on both simulated and real datasets. Further visualizations show that GraphSCC provides representations for better intra-cluster compactness and inter-cluster separability.

bioinformatics↗

bioRxiv2019

Degradation of miR-466d-3p by JEV NS3 facilitates viral replication and IL-1β expression

Previous studies revealed that Japanese encephalitis virus (JEV) infection alters the expression of miRNA in central nervous system (CNS). However, the mechanism of JEV infection contributes to the regulation of miRNAs in CNS remain obscure. Here, we found that a global degradation of mature miRNA in mouse brain and neuroblastoma cells after JEV infection. In additional, the integrative analysis of miRNAs and mRNAs suggests that those down-regulated miRNAs are primarily targeted inflammation genes and the miR-466d-3p target the IL-1{beta} which in the middle of those inflammation genes. Transfection of miR-466d-3p decreased the IL-1{beta} expression and inhibited the JEV replication in NA cells. Interestingly, the miR-466d-3p level increased after JEV infection in the presence of cycloheximide, which indicated that viral protein expression reduces miR-466d-3p. Therefore, we generated all the JEV coding protein and demonstrated that NS3 is a potent miRNA suppressor. Furthermore, the NS3 of ZIKA virus, WNV, DENV1 and DENV2 also decreased the expression of miR-466d-3p. The in vitro unwinding assay demonstrated that the NS3 could unwind the pre-miR-466d and induce the disfunction of miRNA. Using computational models and RNA immunoprecipitation assay, we found that arginine-rich domains of NS3 are critical for pre-miRNA binding and the degradation of host miRNAs. Importantly, site-directed mutagenesis of conserved residues revealed that R226G and R202W significantly reduced the binding affinity and degradation of pre-miR-466d. Together, these results extend the helicase of Flavivirus function beyond unwinding duplex RNA to the decay of pre-miRNAs, which provides a new mechanism of NS3 in regulating miRNA pathways and promoting the neuroinflammation.\n\nAuthor SummaryHost miRNAs had been reported to regulate JEV induced inflammation in central nervous system. We found that the NS3 of JEV can reduce most of host miRNA expression. The helicase region of the NS3 specifically binds to precursors of miRNA and lead to incorrect unwinding of precursors of miRNAs which inhibits the function of miRNAs. This observation leads to two major findings. First, we identified the miR-466d-3p targets to the host IL-1{beta} and E protein of JEV, and NS3 degrades the miR-466d-3p to promote the brain inflammation and viral replication. Second, we proved that the arginine on the helicase of NS3 is the main miRNA binding sites, and the miRNA degradation by NS3 was abolished when the R226 and R202 were mutated on the NS3. These findings were also confirmed with NS3 of ZIKA virus, WNV and DENV which could decrease the expression level of miR-466d-3p to enhance the inflammation. Our study provides new insights into the molecular mechanism of encephalitis caused by JEV, and reveals several amino acid sites to further attenuate the JEV vaccine.

microbiology↗