Biology subjects

Han, L.

Publications and source records attributed to Han, L..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

BrainBeacon: A Cross-Species Foundation Model for Single-cell Resolved Brain Spatial Transcriptomics

The brains functional complexity emerges from spatiotemporal heterogeneity in molecular, cellular, and circuit organization, shaped by evolution, aging, and disease. Single-cell spatial transcriptomics provides a transformative framework to decode this complexity, resolving cell-type-specific expression patterns, region-specific regulation, evolutionary divergence, and disease-associated disruptions. Despite recent advances in spatial transcriptomics, a unified foundation model capturing cross-species, whole-brain cellular architecture remains lacking. Here, we introduce BrainBeacon, the first cross-species foundation model for whole-brain spatial transcriptomics. Trained on 133 million spatially resolved cells covering a total area of 210194 mm2 from human, macaque, marmoset and mouse brains profiled across five major platforms, BrainBeacon integrates gene expression rankings, spatial cellular organization, and evolutionarily conserved genetic relationships into a unified transformer-based architecture. A two-stage training strategy captures both intra-cellular transcriptional dependencies and inter-cellular spatial interactions, yielding biologically grounded and interpretable representations of brain structure. Subsequently, BrainBeacon enables cross-species alignment of brain cell types and anatomical regions, facilitating integrative analyses of conserved and divergent cellular architectures. Moreover, it uncovers spatial regulatory mechanisms of aging by predicting bidirectional perturbation responses between cells and their local niche. Together, BrainBeacon serves as a foundational cross-species model for whole-brain spatial transcriptomics, enabling virtual brain atlas construction, systematic in silico perturbation studies, and mechanistic insights into brain disease pathogenesis.

bioinformatics↗

bioRxiv2025

Multi-omics characterization of the skin microbiota reveals the anti-aging roles of Stenotrophomonas maltophilia

Shifts in the skin microbiome have shown a close link to chronological age. However, the contribution of skin microbiome in skin aging phenotypes remains unclear. To explore this, we performed phenotypic, metabolomic, metagenomic, and functional analyses on a cohort with divergent skin aging phenotypes. Genome-scale metabolic models (GEMs) integrated with metabolomic analysis revealed that Stenotrophomonas maltophilia, enriched in the younger group (categorized by AI-predicted age and skin elasticity), utilizes the glutathione cycle to maintain redox homeostasis. Cellular experiments showed its metabolites enhanced GSH synthesis and alleviated oxidative stress-induced skin aging by upregulating key genes in fibroblasts, including GCLM, PGD, SOD2, and NQO1. Additionally, GEMs highlighted its potential anti-aging roles in regulating host metabolic pathways involving betaine, lysolecithin, and porphyrin. In parallel, Acinetobacter guillouiae was found to influence host melanin metabolism by degrading dopamine (DA) and 3-methoxytyramine (3-MT), offering potential therapeutic strategies for mitigating pigmentation. Our findings highlight the dynamic interplay between skin microbiota and the host in aging, offering new insights for designing targeted anti-aging interventions.

microbiology↗

bioRxiv2025

Glycolipid recognition and binding by Siglec-6 hinges on interactions with the cell membrane

Sialic acid-binding immunoglobulin-type lectins (Siglecs) regulate immune response through interactions with sialylated glycans on glycoproteins and glycolipids. Human Siglecs count 14 unique proteins and in all of those the recognition and binding of the sialic acid on the glycan target involves a conserved, or canonical, Arg residue. For a subset of human Siglecs, namely MAG, Siglec-6, and Siglec-11, this Arg appears not to be essential, suggesting that a different binding mechanism may be at play. In this work, we used all-atom molecular dynamics (MD) simulations, binding assays, and mutagenesis to investigate the structural, mechanistic and energetic details of the binding of Siglec-6 to monosialylated gangliosides. Our results show that Siglec-6 relies only partially on its conserved Arg122 for recognition of membrane-bound gangliosides and that it supplements its binding free energy through interactions with the phospholipids in the membrane surrounding the target epitope. We confirmed by mutagenesis assays that the loss of the key residues (Lys 126 and Trp 127) for membrane interaction abrogates binding. These results provide a step-change in our understanding of the diversification of human Siglecs as molecular precision tools to bind specific sialosides by adapting their structure to the biological environment where these are found.

biochemistry↗

bioRxiv2025

Alternating 2D and 3D Culture Reduces Cell Size and Extends the Lifespan of Placenta-Derived MSCs

Mesenchymal stem cells (MSCs) offer significant therapeutic potential, but traditional 2D culture on rigid substrates results in progressive cell enlargement and senescence, reducing proliferative capacity and therapeutic potency. This poses a major challenge for widespread clinical application. We explored a novel strategy for placenta-derived MSCs combining 2D expansion with 3D spheroid culture to address these limitations. Our research shows that culturing MSCs as 3D spheroids significantly reduces individual cell size and size distribution compared to 2D culture. Spheroid formation is feasible in chemically defined media with minimal cell death, and is enhanced by extracellular matrix protein supplementation. Although MSCs do not proliferate in 3D suspension, an alternating 2D/3D culture protocol, transitioning cells between 2D flasks and 3D spheroids after each passage, effectively slows MSC enlargement and senescence over long periods. This alternating method also preserves MSC immunomodulatory function, unlike continuous 2D culture which leads to its loss. For scalability, we developed an RGD-functionalized alginate hydrogel tube (AlgTube) system that mimics this alternating environment, supporting both adherent growth and chemically triggered spheroid formation. This alternating 2D/3D culture strategy and the scalable AlgTube platform provide a foundation for developing next-generation MSC manufacturing technologies to meet future clinical demands.

bioengineering↗

bioRxiv2025

Cervical Mucus Viscoelasticity and Sperm Velocity are Correlated and Concentration-dependent In Vitro

BackgroundMucus in the endocervix serves as fertility gatekeeper in the reproductive tract through hormonally regulated changes in biophysical properties. Cervical mucus can thicken to prevent ascension of sperm into the upper reproductive tract or thin to permit fertilization. Current reproductive studies of mucus viscoelastic properties rely on subjective visual appraisal of cervical mucus changes. Our goal was to use particle tracking microrheology (PTMR) to objectively assess cervical mucus viscoelastic properties and associate these measurements with in vitro measures of sperm velocity. MethodsUsing cervical mucus obtained from rhesus macaques (Macaca mulatta) at necropsy, we used to PTMR to measure viscoelasticity (*) under stepwise, serial dilutions. In parallel we measure sperm velocity using custom sperm tracking and analysis workflows. ResultsWe report that both mucus * and sperm velocity displayed a concentration-dependent behavior, where * increased as mucus concentration increased, and sperm velocity correspondingly decreased. Viscoelasticity and sperm velocity were strongly negatively correlated (p<0.001). ConclusionsPTMR and sperm tracking in mucus provide quantitative measure of viscoelastic mucus changes. PTMR is potentially a method for quantitatively assessing fertility potential in the cervix that could be applied to both infertility and contraceptives studies.

biophysics↗

bioRxiv2025

Click chemistry-based quantification of extracellular matrix turnover for drug screening and regenerative medicine

This study presents a sensitive and cost-efficient method to quantify extracellular matrix (ECM) synthesis and degradation using copper-free click chemistry reactions to fluorescently label new ECM components. The approach enables spatial visualization and longitudinal measurement of specific ECM turnover in vitro. We validated the method across multiple platforms, including native cartilage explants and monolayer cultures of human mesenchymal stem cells and breast cancer cells. The technique also proved effective for osteoarthritis drug screening by detecting compounds that mitigate inflammation-induced ECM degradation. Compared to traditional biochemical or histological assays, this click chemistry-based technique offers higher sensitivity, lower sample requirements, and improved temporal resolution. Its versatility supports broad applications in tissue engineering, regenerative medicine, disease modeling, and high-throughput drug evaluation.

bioengineering↗

bioRxiv2025

Intracellular Delivery of Bone Nanoparticles to Mitigate Irradiation-Induced Damage in Bone Marrow Mesenchymal Stem Cells

Ionizing radiation (IR)-induced bone damage presents a major clinical challenge by impairing bone marrow function and disrupting normal bone remodeling. Bone regeneration depends on bone marrow-derived mesenchymal stem cells (BMSCs), which are highly sensitive to IR that causes DNA damage, oxidative stress, apoptosis, and a shift from osteogenesis to adipogenesis, ultimately leading to bone loss and impaired healing. This study evaluated the therapeutic potential of intracellularly delivered bone-derived nanoparticles (BPs) in mitigating IR-induced BMSCs damage. We found that IR exposure caused significant BMSCs dysfunction, including reduced proliferation, increased apoptosis, persistent DNA damage, and a shift toward adipogenic differentiation. Treatment with BPs led to efficient intracellular uptake, improved cell morphology, enhanced proliferation, reduced apoptosis, and preservation of balanced differentiation capacity. Transcriptomic analysis via RNA sequencing revealed that BPs restored key molecular pathways disrupted by IR, particularly those involved in cell cycle regulation, extracellular matrix (ECM) remodeling, and apoptosis. By reversing these transcriptional impairments, BPs supported genomic stability and the regenerat ive function of BMSCs. Overall, these findings suggest that BPs effectively counteract IR-induced cellular damage and enhance the regenerative capacity of BMSCs, offering a promising therapeutic strategy for radiation -induced skeletal injuries.

bioengineering↗

bioRxiv2025

SCRIPT: predicting single-cell long-range cis-regulation based on pretrained graph attention networks

Single-cell cis-regulatory relationships (CRRs) are essential for deciphering transcriptional regulation and understanding the pathogenic mechanisms of disease-associated non-coding variants. Existing computational methods struggle to accurately predict single-cell CRRs due to inadequately integrating causal biological principles and large-scale single-cell data. Here, we present SCRIPT (Single-cell Cis-regulatory Relationship Identifier based on Pre-Trained graph attention networks) that infers single-cell CRRs from transcriptomic and chromatin accessibility data. SCRIPT incorporates two key innovations: graph causal attention networks supported by empirical CRR evidence, and representation learning enhanced through pretraining on atlas-scale single-cell chromatin accessibility data. Validation using cell-type-specific chromatin contact data demonstrates that SCRIPT achieves a mean AUC of 0.9, significantly outperforming state-of-the-art methods (AUC: 0.68). Notably, SCRIPT obtains a threefold improvement in predicting long-range CRRs (>100 Kb) compared to existing methods. Applying SCRIPT to Alzheimers disease and schizophrenia, we establish a framework for prioritizing disease-causing variants and elucidating their functional effects in a cell-type-specific manner. By uncovering molecular genetic mechanisms undetected by existing computational methods, SCRIPT provides a roadmap for advancing genetic diagnosis and target discovery.

bioinformatics↗

bioRxiv2025

Scalable Culture of Mammalian Cells in RGD Peptide-Modified Alginate Hydrogel Microtubes

Traditional livestock farming is resource-intensive and environmentally unsustainable, necessitating alternative methods for meat production. Cell cultured meat, produced by expanding and differentiating animal cells, offers great potential for substituting for conventional animal meat. Nevertheless, it is still limited by the scalability and efficiency of current cell culture technologies. In this study, we developed an RGD peptide-modified alginate hydrogel microtube microbioreactor (AlgTubes) to support the scalable culture of anchor-dependent cells, such as myoblasts and adipocytes, for cell-cultured meat production. AlgTubes provide a cell-friendly 3D microenvironment that enhances cell viability, growth, and yield while overcoming limitations of conventional bioreactors, such as shear stress, aggregation, and diffusion constraints. We successfully expanded mouse (C2C12) and quail (QM7) myoblasts in AlgTubes, achieving cell densities exceeding 1.0 x 10 cells/mL, far surpassing traditional stirred-tank bioreactors. Differentiation resulted in the formation of mature myotubes. Co-culturing myoblasts with mesenchymal stem cells or fibroblasts further improved yield and viability, particularly under differentiation conditions. By significantly increasing cell culture density, AlgTubes can substantially reduce culture volume, lowering labor requirements, reagent costs, equipment needs, facility space, and manufacturing expenses.

bioengineering↗

bioRxiv2025

Exploring Population Differences in the Human Gut Microbiome: from Microbial Abundance to Single Nucleotide Polymorphisms

The human gut microbiota exhibits significant diversity across populations, influenced by factors such as geography, diet, and lifestyle, particularly between the Han Chinese and non-Chinese populations. While previous studies have predominantly focused on the taxonomic abundance of the gut microbiome, the impact of single nucleotide polymorphisms (SNPs) in driving population-specific differences remains largely underexplored. In this study, we systematically investigated gut microbial differences between the Han Chinese and non-Chinese populations using the Human Gut Microbiome Reference Genome Catalog (HGMRGC). HGMRGC includes 271,480 non-redundant genomes from 5,785 prokaryotic species, which was generated by metagenomic sequencing data from 9,320 publicly available samples across 22 countries and 3,584 newly sequenced samples from Han Chinese individuals across 29 provinces and regions in China. We observed geography was the primary driver of microbial variation of abundance and SNPs. We identified 625 novel population-specific genome clusters from HGMRGC with functional differences in carbohydrate utilization and 126 species exhibiting distinct prevalence related to vitamin biosynthesis, antibiotic resistance, and carbohydrate metabolism. Beta diversity analysis highlighted significant inter-population differences in both microbial abundance and SNPs, while alpha diversity analysis revealed that non-Chinese populations exhibited higher diversity in microbial abundance, and Han Chinese populations displayed greater diversity in SNPs. These results provide valuable insights into population-specific microbial diversity, laying the groundwork for future research on its functional and health implications.

microbiology↗

bioRxiv2025

A Comprehensive Reference Catalog of Human Skin DNA Virome Reveals Novel Viral Diversity and Microenvironmental Influences

IntroductionHuman skin serves as a dynamic habitat for a diverse microbiome, including a complex array of viruses whose diversity and roles are not fully understood. ObjectivesThis study aims to enhance our understanding of this skin viral diversity through the construction of a detailed, non-redundant DNA viral reference catalog. MethodsA total of 2,760 skin metagenomes from six published skin studies were collected. A skin virome catalog was constructed using methods independent of reference databases. Viral characteristics were identified through cross-cohort meta-analysis and used to characterize viral features across different skin environments. ResultsWe identified 20,927 viral sequences, which clustered into 2,873 viral operational taxonomic units (vOTUs). Among these, 2,610 represent previously unrecorded viral sequences, uncovering a substantial breadth of viral diversity on human skin. The results also highlight significant differences in viral communities that are associated with varying skin microenvironments. The oily skin is enriched in Papillomaviridae; the dry skin area is enriched in Autographiviridae, Inoviridae and Mitoviridae; and the moist skin is enriched in Herelleviridae, indicating the adaptive nature of viruses. We also investigated the relationship between bacteriophages and bacteria on the skin surface. We found that skin bacteria such as Pseudomonas, Klebsiella, and Staphylococcus are infected by phages from the class Caudoviricetes. ConclusionThis comprehensive skin DNA viral catalog significantly advances our understanding of the viromes role within the skin ecosystem. The findings highlight the adaptive nature of viruses to different skin microenvironments and their interactions with resident bacteria. This catalog serves as a valuable resource for further epidemiological and therapeutic research, potentially leading to better management and treatment of skin conditions influenced by the skins virome.

microbiology↗

bioRxiv2025

Multimodal brain cell atlas across the adult macaque lifespan

High-throughput single-cell omics of non-human primate tissues present a remarkable opportunity to study primate brain aging. Here, we introduce a transcriptomic and chromatin accessibility landscape of 1,985,317 cells from eight brain regions of 13 cynomolgus female monkeys spanning adult lifespan including exceptionally old individuals up to 29-years old. This dataset uncovers dynamic molecular changes in critical brain functions such as synaptic communication and axon myelination, exhibiting a high degree of cell type and brain region specificity. We identify the multicellular networks of the pons and medulla as a previously unrecognized hotspot for aging. Furthermore, comparative analyses with human neurodegeneration datasets highlight both shared and distinct mechanisms contributing to aging and disease. In addition, we uncover transcription factors implicated in monkey brain aging and pinpoint aging-regulated loci linked to longevity and neurodegeneration. This spatiotemporal atlas will advance our understanding of primate brain aging and its broader implications for health and disease.

neuroscience↗

bioRxiv2025

Structural basis of ZP2-targeted immunocontraception

Monoclonal antibody IE-3 prevents mouse fertilization by binding ZP2, a major component of the oocyte-specific zona pellucida (ZP). We show that an IE3-derived single-chain variable fragment (scFV) is sufficient for blocking fertilization in vitro and determine the structural basis of IE-3/ZP2 recognition. The high-affinity of this interaction depends on induced fit of the epitope, offering insights for non-hormonal immunocontraceptive design without off-target effects.

biophysics↗

bioRxiv2025

Dynamic early recruitment of GAK-Hsc70 regulates coated pit maturation

Clathrin-mediated endocytosis (CME) is the process by which clathrin assembles on the plasma membrane to form clathrin-coated pits (CCPs), which then invaginate, accumulate cargo and are released by fission from the membrane to form clathrin-coated vesicles (CCVs). A transition of nascent CCPs from flat-to-curved has been observed by various methods. However, what drives this transition remains unknown and controversial. GAK and its chaperone protein, Hsc70, are well-known to mediate clathrin release from CCVs and several studies have observed a late burst of GAK recruitment as CCVs form. Other studies have proposed that early recruitment of GAK-Hsc70 could function to provide the necessary energy source to remodel nascent flat clathrin lattices, replacing hexagons with pentagons and enabling a gain of curvature and invagination of the growing CCP; however, direct functional evidence is lacking. Here we show that GAK knockdown inhibits CCP formation and invagination. Furthermore, mutations in the J domain of GAK that abolish Hsc70 recruitment to and activation at CCPs, lead to the accumulation of GAK at CCPs, hinder CCP stabilization and invagination and result in a striking increase in the proportion of short-lived, abortive CCPs. These findings support the hypothesis that GAK-Hsc70 promotes the turnover and remodeling of nascent clathrin assemblies required for curvature development during CME. Significance StatementGAK and its chaperone protein, Hsc70, are known to be recruited to clathrin-coated vesicles (CCVs) to mediate clathrin uncoating. Previous studies have proposed that early recruitment of GAK-Hsc70 to CCPs could function to remodel nascent flat clathrin lattices, replacing hexagons with pentagons and enabling a gain of curvature of the assembling polymeric coat. However, there are conflicting views, and direct functional evidence is lacking. Here we show that GAK knockdown inhibits CCP formation and invagination. A detailed domain-specific mutational analysis of GAK pinpointed the importance of J domain-Hsc70 interactions in regulating crucial early steps of CME including CCP stabilization and invagination. These findings support a hypothesis that GAK-Hsc70 promotes turnover of clathrin at nascent CCPs required for curvature development.

cell biology↗

bioRxiv2025

Single-cell spatial transcriptome reveals pathological features of human hippocampus with sclerosis

More than half of epileptic patients ultimately turned to intractable epilepsy. Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), the most common type of intractable epilepsies, whose pathological mechanism remains elusive. Here, using 42 human hippocampal samples from surgical donors of MTLE (32 with and 10 without HS) through single-cell resolution Stereo-seq and histologcial experiments, we revealed spatially pathological changes of gene expression and cell type composition with HS systematically. After precise parcellation of hippocampal subregions and differentially expressed gene (DEG) analysis between each region with and without sclerosis, we found Cornu Ammonis (CA) subregions with higher number of DEGs were vulnerable to sclerosis, especially CA1 and CA3. Within CA1, we found that CA1-superficial and proximal areas were more vulnerable than CA1-deep and distal areas in sclerosis. Meanwhile, after analyzing 350,795 segmented cells from Stereo-seq, we found dramatically increasing density of astrocyte accompanied with significantly decreasing density of excitatory neurons in CA1, especially superficial and proximal CA1, and CA3 in sclerosis. In these two vulnerable subregions, proliferative astrocyte (P_astrocyte) and reactive astrocyte (R_astrocyte) were found to be enriched whereas apoptotic subtype of astrocyte (A_astrocyte), related with apoptotic pathway, was mainly located in alveus, which strengthened cell communication with reactive microglia (R_microglia) in HS, revealing the novel pathological feature in our work. The pseudotime analysis indicated that CA excitatory neurons underwent synaptic impairment, energy dysfunction, aging, and finally losing cell identity until death through autophagy or apoptosis. Besides, we also found a resilient subtype, EX_CA2-4.3, highly expressed extracellular matrix related genes including PDYN, and was increasing the interaction of BDNF-NTRK, NFASC-CNTN1 to withstand the damage from sclerosis. Together, our study provided a reference of human hippocampus with and without HS caused by MTLE, and highlighted the potential pathological mechanism on molecular and cellular level of MTLE-HS.

neuroscience↗

bioRxiv2025

A High Sensitivity Assay of UBE3A Ubiquitin Ligase Activity

UBE3A is an E3 ubiquitin ligase associated with several neurodevelopmental disorders. The development of several preclinical therapeutic approaches involving UBE3A, such as gene therapy, enzyme replacement therapy, and epigenetic reactivation, require the detection of its ubiquitin ligase activity. Prior commercial assays leveraged Western Blotting to detect shifts in substrate size due to ubiquitination, but these suffered from long assay times and have also been discontinued. Here we develop a new assay that quantifies UBE3A activity. It measures the fluorescence intensity of ubiquitinated p53 substrates with a microplate reader, eliminating the need for Western Blot antibodies and instruments, and enables detection in just 1 hour. The assay is fast, cost-effective, low noise, and uses components with long shelf lives. Importantly, it is also highly sensitive, detecting UBE3A levels as low as 1nM, similar to that observed in human and mouse cerebrospinal fluid. It also differentiates the activity of wild-type UBE3A and catalytic mutants. We also design a p53 substrate with a triple-epitope tag HIS-HA-CMYC on the N terminus, which allows for versatile detection of UBE3A activity from diverse natural and engineered sources. This new assay provides a timely solution for growing needs in preclinical validation, quality control, endpoint measurements for clinical trials, and downstream manufacturing testing and validation.

biochemistry↗

bioRxiv2024

The antigenic landscape of N1 neuraminidase in human influenza A virus strains isolated between 2009 and 2020

The clinical burden caused by influenza can be mitigated by the prophylactic use of seasonal influenza vaccines. Their immunogen composition is revised biannually to optimally match the antigenic drift of the hemagglutinin of circulating influenza virus strains. Antibodies directed against the influenza neuraminidase also correlate with protection against influenza, yet the antigenic evolution of influenza neuraminidase remains underexplored. To evaluate the antigenic diversity of N1 neuraminidase, we generated a panel of immune sera directed against 17 N1 neuraminidases derived from human H1N1 strains that were isolated between 2009 and 2020 and determined its neuraminidase inhibition titers against a panel of 15 HxN1 viruses. The resulting neuraminidase inhibition pattern revealed two antigenic groups that circulated in this period. A machine learning method identified K432E and I321V as key determinants of N1 neuraminidase antigenicity.

immunology↗

bioRxiv2024

Alveolar macrophages initiate the spatially targeted neutrophil recruitment during nanoparticle inhalation

Exposure to air pollution, including nanoparticles (NPs), is a major health concern associated with various diseases, triggered by subtle inflammatory responses in the lung. To investigate the dynamic immune response in vivo, lung intravital microscopy (L-IVM), was used to analyze the behavior of alveolar macrophages (AMs) and neutrophils, combined with ventilator-assisted inhalation of nebulized NPs in mice. Inhalation of fluorescent quantum dot NPs (cQDs) and soot-like carbon black NPs (CNPs, ambient pollutants), led to rapid spatially focused recruitment of neutrophils near alveolar deposited NPs. Neutrophil recruitment was initiated by NPs uptake by AMs, dependent on AM motility and AM NP surface recognition. Prior airway application of neutralizing antibodies against alveolar ICAM-1 and LFA-1, leading to reduced AM motility, inhibition of C5aR1 and Fc{gamma}RI receptor mediated NPs uptake by AMs, as well as neutralizing of TNF and application of a cellular degranulation inhibitor, abolished the early immune response induced by NPs. Overall, our data demonstrates the crucial role of AM activity (migration, phagocytosis, cytokine release) in the rapid and site-specific recruitment of neutrophils during the early phase of particle inhalation, suggesting these processes to be key events in mounting the immune response upon NP inhalation in the lung. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=175 HEIGHT=200 SRC="FIGDIR/small/623349v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@d67e38org.highwire.dtl.DTLVardef@1f8c139org.highwire.dtl.DTLVardef@55be9dorg.highwire.dtl.DTLVardef@1555042_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗