Biology subjects

Zhang, H.

Publications and source records attributed to Zhang, H..

At least 181 records · Page 10Linked to original sources

bioRxiv2026

PAVR: High-Resolution Cellular Imaging via a Physics-Aware Volumetric Reconstruction Framework

The rapid convergence of advanced microscopy and deep learning is transforming cell biology by enabling imaging systems in which optical encoding and computational inference are jointly optimized for volumetric information capture and interpretation. However, broadly accessible three-dimensional imaging at high spatiotemporal resolution remains constrained by volumetric reconstruction throughput, susceptibility to artifacts, and the burden of collecting modality-matched training data. Here, we introduce PAVR, a physics-aware light-field imaging platform that integrates single-shot volumetric acquisition with fast, end-to-end volumetric reconstruction. PAVR is trained entirely using in silico system responses, avoiding reliance on external high-resolution ground-truth modalities and enabling sample-independent reconstruction across diverse biological contexts. Using fixed and live mammalian cells, we demonstrate multicolor volumetric imaging of subcellular organelles, three-dimensional tracking of autofluorescent particles, and high-speed visualization of organelle remodeling and interactions. We further extend PAVR to quantify coupled morphological and functional dynamics in beating human induced pluripotent stem cell-derived cardiomyocytes under pharmacological perturbation. Together, PAVR establishes a scalable hardware-software platform for high-throughput volumetric imaging and quantitative analysis of dynamic cellular systems in both basic and translational settings.

bioengineering↗

bioRxiv2026

Functional Locality-Aligned Learning Reveals Structure-Function Causality in Enzyme Kinetics

Accurate estimation of enzyme kinetic parameters is essential for enzyme engineering and industrial biocatalysis, yet their experimental measurement remains labor-intensive and costly. Although machine learning offers an efficient alternative, existing methods still struggle to generalize to unseen enzymes and substrates. In particular, current three-dimensional (3D) structure-aware approaches rely on whole-enzyme 3D geometric structures and neglect substrate 3D geometry, often yielding limited or even degraded performance. We identify a fundamental limitation underlying these methods: a mismatch between the structural representation learning scale and the functional locality scale, which weakens structure-function causality in enzyme kinetics. To address this issue, we introduce EnzymePlex, a functional locality-aligned framework that aligns inductive biases with the localized structural determinants of enzyme function by prioritizing catalytic pockets, integrating substrate 3D geometry, and modeling nuanced enzyme-substrate interplay under the guidance of pocket-level structural priors. EnzymePlex achieves state-of-the-art performance across multiple benchmarks and substantially improves generalization under stringent out-of-distribution evaluations. Beyond predictive accuracy, EnzymePlex learns mechanistically aligned representations, with attention enriched at catalytic pocket residues and substrate reaction centers despite receiving no explicit super-vision for either. Moreover, when applied to recently reported wet-lab data, EnzymePlex effectively prioritizes high-activity enzyme variants and identifies potent inhibitors, highlighting its potential to accelerate enzyme engineering and drug discovery.

biochemistry↗

bioRxiv2026

Stage-adaptive integration of polydopamine promotes hPSC-derived alveolar organoids differentiation and maturation

Human pluripotent stem cell (hPSC)-derived alveolar organoids (ALOs) have emerged as a powerful tool for modeling human lung development and disease, and accelerating respiratory drug discovery. However, achieving the functional maturation of ALOs remains challenging. Polydopamine (PDA) is a mussel-inspired polyphenolic biomaterial with antioxidant and adhesive properties that can be deployed as surface coatings and nanoparticles (NPs) in cell culture systems. Here, we integrate PDA coatings and NPs sequentially in a stage-adaptive manner throughout the hPSC-derived ALOs differentiation system and study their contributions to ALOs maturation. Our results demonstrated PDA coating yielded more anterior foregut endoderm (AFE) spheroids by strengthening the interaction between Matrigel and substrate. Bulk RNA-seq revealed enrichment of cell-cell and cell-extracellular matrix interactions by PDA. The subsequent incorporation of PDA NPs in Matrigel at lung progenitor cells (LPCs) stage significantly mitigated reactive oxygen species (ROS) accumulation and enhanced LPCs generation. Functionally, AT2 cells in ALOs exhibit characteristic lysosome-to-lamellar body (LB) maturation due to the traffic of internalized PDA NPs to endolysosome. Transcriptomics further indicated enrichment of endocytic-phagosome and epithelium development pathways by PDA treatment. Together, our study establishes a stage-adaptive-integrated PDA strategy throughout hPSC-to-ALOs differentiation and demonstrates that PDA robustly enhances ALOs maturation and secretory function. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/708928v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@88208dorg.highwire.dtl.DTLVardef@1111590org.highwire.dtl.DTLVardef@9ea9b0org.highwire.dtl.DTLVardef@969fad_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

Spin-State Modulation by Atom-Cluster Synergy Steers H2O2 Conversion toward a Catalase-like Decomposition Pathway for Anti-Inflammatory Therapy

Nanozymes have emerged as promising enzyme mimics for anti-inflammatory therapy. However, their catalytic efficiency and substrate selectivity generally remain inferior to those of natural enzymes. Single-atom nanozymes (SAzymes), with isolated metal centers resembling enzymatic active sites, represent an important advance toward rational design of nanozyme, but achieving enzyme-like selectivity remains challenging. Herein, we reported a spin-state modulation strategy to prepare Fe-N-C nanozyme with coexisting single atoms and nanoclusters (FeSA+NC) via reductive-gas pyrolysis. Experimental analyses and density functional theory calculations revealed that Fe nanoclusters induced local symmetry breaking and charge redistribution around FeN4 sites, shifting the Fe centers toward a higher spin configuration and thereby modulating the free energy changes of the H2O2 conversion pathway. As a result, FeSA+NC showed dramatically enhanced catalase (CAT)-like activity (333.79 U mg-1) and suppressed peroxidase (POD)-like activity (38.49 U mg-1), achieving superior selectivity compared to Fe SAzymes (FeSA), which showed comparable CAT- and POD-like activities (62.39 and 60.39 U mg-1, respectively). Moreover, FeSA+NC achieved a higher superoxide dismutase (SOD)-like activity (929.27 U mg-1) than FeSA (249.68 U mg-1), enabling efficient SOD-CAT cascade. FeSA+NC effectively scavenged excessive intracellular reactive oxygen species, suppressed M1 macrophage polarization, and enhanced the therapeutic efficacy of intra-articular stem cell injection in a rat model of rheumatoid arthritis, a representative chronic inflammatory disease. This work highlights an atom-cluster synergy strategy for steering H2O2 conversion towards antioxidant pathway, offering a general design principle for safer, more controllable and more efficient nanozyme-based anti-inflammatory therapeutics.

bioengineering↗

bioRxiv2026

Female iPSC X-chromosome inactivation (XCI) erosion and its transcriptomic effects during CRISPR gene editing and neural differentiation

Human induced pluripotent stem cells (hiPSC) and iPSC-differentiated neural cells, in combination with CRISPR editing, are commonly used for studying neurodevelopmental and other brain disorders. Female iPSCs undergo random X-chromosome inactivation (XCI) via epigenetic silencing by noncoding X inactive specific transcript (XIST). It is known that female iPSCs may lose XIST expression, leading to XCI erosion that affects both X-linked and autosomal gene expression. However, the effects of CRSIPR editing and neural differentiation on XCI erosion in iPSC-derived neurons and how this may confound a real-world transcriptomic analysis of differentially expressed genes (DEGs) are poorly understood. Here, leveraging bulk RNA-seq of hundreds of CRISPR-edited female iPSC lines from four donor lines for 66 genes and single-cell RNA-seq of iPSC-derived neurons of a subset of 42 edited genes, we investigated the effects of XCI erosion during CRISPR editing and in iPSC-derived neurons. We found that XCI erosion was variable in CRISPR-edited female iPSCs and largely preserved in iPSC-derived neurons. Like in iPSCs, XIST in neurons predominately influenced the expression of X-linked genes; however, its effect on autosomal genes was more pronounced in single neurons. Mechanistically, XIST epigenetically causes allelic imbalance of both X-linked and autosomal genes, with the former showing stronger allele-specific expression (ASE) bias. Notably, XIST-induced ASE bias exhibited a conserved positional pattern at loci affecting neurodevelopmental genes across different female lines and cell types. Finally, we demonstrated a confounding effect of XCI erosion on DEG analyses in iPSC-derived neurons. These results have significant implications in hiPSC modeling of neurodevelopmental and other brain disorders.

genomics↗

bioRxiv2026

Sex-specific Genetic Regulatory Effects in Chickens

Sexual dimorphism is a defining vertebrate feature, yet its sex-specific molecular architecture remains poorly understood. Here we established a sex-balanced, uniformly reared chicken cohort to map this landscape, integrating individual whole-genome sequencing with 7,969 bulk and 779,380 single nucleus transcriptomes across 32 tissues from 280 birds. We identified 495,098 independent expression quantitative trait loci for 20,194 genes, including 10,937 loci modulated by cell-type composition. Notably, 340 genes were regulated by 449 loci in a sex-dependent manner, significantly enrichment in endocrine tissues like adipose and the adrenal gland. Furthermore, we fine-mapped 1,219 structural variants, demonstrating their unique roles to tissue- and sex-specific expression beyond SNPs. Ultimately, we showed the utility of these regulatory effects in elucidating the molecular basis of metabolism and complex traits in both chickens and humans. This comprehensive atlas of regulatory effects provides profound insights into the genomic and molecular basis of sexual dimorphism in vertebrates.

genomics↗

bioRxiv2026

Eubiota: Modular Agentic AI for Autonomous Discovery in the Gut Microbiome

The gut microbiome regulates many aspects of human biology, including immunity and inflammatory diseases, yet mechanistic discovery and translation remain constrained by fragmented workflows and manual hypothesis integration. Here, we present Eubiota, an open-source modular agentic framework that decomposes microbiome inquiry using specialized agents for planning, execution, verification, and grounded synthesis. Coordinated through shared memory and domain-specific tools, Eubiota employs reinforcement learning to optimize multi-turn reasoning, achieving 87.7% benchmark accuracy and outperforming GPT-5.1 by 10.4%. Across four case studies, Eubiota enabled end-to-end discovery with experimental validation. Screening nearly 2,000 bacterial genes, Eubiota identified the uvr-ruv DNA repair axis as a fitness determinant under inflammatory stress, validated using transposon mutants and IBD metagenomes. It further designed a four-strain consortium that attenuated colitis severity in mice and generated a commensal-sparing antibiotic cocktail, demonstrating its utility in addressing community-level design challenges at cellular and molecular levels. Finally, Eubiota discovered diet-associated metabolites that suppress NF-{kappa}B signaling. Together, these results establish Eubiota as a scalable, tool-grounded scientific copilot for mechanistically driven microbiome discovery.

bioinformatics↗

bioRxiv2026

BARTsc identifies key transcriptional regulators from single-cell omics data

Inference of transcriptional regulatory mechanisms from single-cell (sc) omics data, such as scRNA-seq, scATAC-seq, and scMultiome, remains an important problem in single-cell biology and functional genomics. Most existing methods for predicting functional transcriptional regulators (TRs) from single-cell data rely on co-expression between regulator and target genes and/or sequence motif enrichment, holding inherent limitations. Here, we present BARTsc, a computational method that accurately predicts functional TRs from clustered single-cell omics data by leveraging a large collection of public ChIP-seq profiles. BARTsc implements a novel framework to infer a cis-regulatory profile from differential genomic features from either unimodal (RNA or ATAC) or bimodal (scMultiome) single-cell profiling data and identify TRs whose binding profiles most associate with the cis-regulatory profile. BARTsc can quantify TR activity across cell clusters and predict key regulators for each cell cluster. We demonstrate that BARTsc can successfully identify active TRs in each cell type and cell-type-defining key regulators across diverse biological systems, including mouse cortex, human peripheral blood mononuclear cells (PBMCs), and human pancreatic ductal adenocarcinoma (PDAC). Using a generative-AI-assisted, literature-supported collection of cell-type key regulators as benchmarks, we show that BARTsc consistently outperforms existing state-of-the-art methods. We apply BARTsc to identify critical regulators in PDAC, including NEFLA, a novel PDAC key regulator, and validate its function in pancreatic tumor proliferation by experiments. As a robust and versatile computational method, BARTsc provides deeper insights into cell-type-specific regulatory programs, facilitating the discovery of key regulators across diverse biological systems.

bioinformatics↗

bioRxiv2026

Metabolic exchange and siderophore sharing underlie emergent biofilm synergism

Biofilm communities exhibit emergent properties that exceed the sum of contributions from individual members of the community. Here, we describe a multilayered metabolic interaction that drives enhanced biofilm formation among three bacterial species from the plant rhizosphere. Comparative metatranscriptomic and metabolomic analyses reveal that Bacillus velezensis-secreted 5-aminovaleric acid promotes the growth of the other community members, Burkholderia contaminans and Acinetobacter baumannii. In return, B. contaminans supplies branched-chain amino acids for B. velezensis. Branched-chain amino acids and cell-cell signaling acyl-homoserine lactones from B. contaminans induce biosynthesis of the siderophore bacillibactin in B. velezensis, that is further enhanced by A. baumannii. In exchange, the B. velezensis-secreted siderophore promotes the growth of B. contaminans in iron-limited conditions, which benefits the multispecies biofilm community in vitro and promotes plant growth performance in iron-depleted soil. Our study reveals the molecular mechanisms underlying an emergent rhizosphere biofilm community function and demonstrates its importance in plant-microbe interactions.

microbiology↗

bioRxiv2026

Type 2 diabetes amplifies environmental Pb toxicity and intergenerational risk

Type 2 diabetes (T2D) and environmental lead (Pb) exposure intersect as prevalent global health challenges. Prior studies report elevated blood Pb in T2D, but the underlying mechanism and directionality remain unresolved. Here we show that T2D fundamentally alters Pb toxicokinetics, converting otherwise modest exposure into progressive organ injury and heritable risk. In a human cohort, elevated blood Pb in T2D specifically associated with impaired renal function rather than glycaemic control or adiposity. In db/db mice, diabetes increased oral Pb absorption through delayed gastrointestinal transit and epithelial barrier dysfunction, leading to enhanced systemic retention. With sustained exposure, renal Pb accumulation induced tubular stress that reduced effective clearance, creating a feed-forward loop in which diabetes promotes Pb retention and retained Pb accelerates kidney injury. Chronic Pb exposure exacerbated diabetic kidney injury without inducing hyperglycaemia, and short-course chelation attenuated renal stress markers. Beyond somatic toxicity, combined paternal T2D and Pb exposure programmed renal and neurobehavioral phenotypes across generations via sperm RNA. These findings redefine Pb from a passive environmental exposure to a context-dependent driver of disease, identify T2D as a vulnerability state that reshapes toxicant handling, and establish a mechanistic link between metabolic disease, environmental exposure and intergenerational risk. This work highlights the need for vulnerability-informed clinical management and environmental regulation in populations burdened by T2D.

genetics↗

bioRxiv2026

Cell Type Architecture and Positional Gene Gradients in an Adult Animal at Subcellular Resolution

The spatial organization of cell types and gene expression underlies tissue architecture and organismal physiology. However, resolving complete cellular and molecular landscapes within a three-dimensional context remains challenging, particularly in organisms with high cellular heterogeneity and complex geometry. Here, we developed a semi-supervised workflow to reconstruct high-resolution three-dimensional spatial transcriptomic models of the planarian Schmidtea mediterranea at single-cell resolution. Planarians are basal bilaterians capable of regenerating body structures after injury. Our reconstruction maps the distribution of cell types and spatially patterned gene expression across the intact organism and identifies 119 candidate positional control genes (PCGs). These genes are expressed across muscle, neural, and epidermal populations. Functional perturbation of selected candidates, including pitx3, ptpn11, pi4ka, upf3b, and cul1, revealed roles in regeneration following injury. In addition, we identify intestinal cells as prominent components of the microenvironment surrounding adult tgs1 pluripotent stem cells (neoblasts). Together, these results demonstrate the utility of three-dimensional spatial transcriptomic reconstruction for mapping cellular architecture and positional gene regulation in complex adult organisms.

developmental biology↗

bioRxiv2026

The archaic CUP pilus SMF-1 uses an antiparallel bundling mechanism to initiate biofilm formation

Bacterial biofilms represent a survival strategy that enables microbial communities to withstand environmental stress. Stenotrophomonas maltophilia is an emerging, antibiotic-resistant, Gram-negative, opportunistic pathogen that frequently colonizes the lungs of individuals with cystic fibrosis. Its chaperone-usher pathway (CUP) pilus, SMF-1, is present in nearly all clinical isolates and is essential for biofilm development; however, its molecular architecture has remained unknown. Here, we present a 4.0 [A] cryo-EM structure revealing that SMF-1 is an archaic, rather than a classic, CUP pilus. SMF-1 forms thin, zigzag filaments that assemble into defined antiparallel "pili-couples," which further aggregate into thick bundles. These bundles act as robust intercellular tethers, facilitating the rapid cell-to-cell aggregation required for biofilm initiation. Despite high sequence and structural similarity to classic CUP systems, SMF-1 lacks the interfaces required to form a rod-like architecture, suggesting it may represent an evolutionary intermediate between the CUP classes. Finally, we demonstrate that SMF-1 producing bacteria initiate biofilm formation within 24 hours and that flagella can further accelerate this process. Together, these findings uncover a conserved bundling mechanism that promotes bacterial colonization and may contribute to pathogenicity.

microbiology↗

bioRxiv2026

Super-resolution single-cell spatial atlas of plant de novo regeneration

Plant de novo regeneration, a capacity absent in animals, relies on stem-cell-niche formation rather than pre-existing reservoirs. Growth hormones such as auxin and cytokinin, together with numerous genetic regulators, participate in regeneration, but the architectural principles coordinating extensive cellular reprogramming at the individual-cell scale remain elusive. Using super-resolution multimodal spatial transcriptomics to 1.16 million cells, we tracked tomato regeneration across temporal intervals from wounding to organogenesis. Datasets are available at http://www.single-cell-spatial.com.

cell biology↗

bioRxiv2026

4D Single-Cell Spatial Transcriptomics Reveals Dynamic Morphogenetic Gradients and Regenerative Domains in Planarians

Regeneration relies on precise spatiotemporal gene expression and cellular responses to establish tissue identity and body patterning. Using high-resolution Stereo-seq (715 nm) on 353 sections from 16 whole animals at 8 regeneration timepoints, we constructed a 4D spatiotemporal transcriptomic map of planarian regeneration. Our analysis captured 36 refined cell types from 3,508,004 segmented cells, enabling genome-wide transcriptional imputation of gene expression dynamics across body axes at cellular, tissue, and organismal scales. We identified dynamic positional gradients and distinct spatially distributed cell types during regeneration, including an injury-induced Anterior Regenerative Zone (ARZ). The ARZ exhibited enriched positional signals in epidermal, muscle, and neural cells and was regulated by Mediator 8, which is crucial for polarity remodeling and blastema formation. This study provides a comprehensive spatial molecular and cellular map of regenerative processes, highlighting injury-induced spatial domains and key regulatory factors in planarian regeneration. We also provide an interactive web portal, offering a valuable resource for exploring and analyzing regeneration mechanisms in a spatiotemporal context.

developmental biology↗

bioRxiv2026

Oxidation-Driven mtDNA B-Z Transition Activates ZBP1 to Mediate Acetaminophen Hepatotoxicity

Acetaminophen (APAP) overdose induces mitochondrial damage in hepatocytes, leading to secondary toxicity that resists to N-acetylcysteine (NAC) treatment and culminates in hepatocyte death and acute liver failure (ALF)1. The underlying mechanisms remain poorly understood, often necessitating liver transplantation2. Here, we identify oxidative modification-driven B-to-Z transitions in mtDNA as the central pathological driver of APAP-induced ALF. Upon APAP exposure, oxidized mtDNA fragments leak into the cytosol, activating ZBP1 signaling via its Z domain. Genetic inhibition of ZBP1 mitigates liver damage and improves survival. Using synthetic 12-bp dGdC duplexes, we demonstrate that 8-oxoG substitution, even under physiological salt concentrations, is sufficient to induce Z-DNA formation, enabling specific ZBP1 binding through its Z domain. The 8-oxoG repair enzyme OGG13, activated by TH107854, removes 8-oxoG modifications and reverses Z-DNA to B-DNA conformation. In mice with lethal APAP toxicity, delayed NAC treatment results in 50% mortality. In contrast, TH10785 monotherapy increases survival to 90%, while its combination with NAC achieves 100% survival. These results define the oxidized mt Z-DNA-ZBP1 axis as a critical driver of APAP hepatotoxicity, providing fundamental insights into DNA conformational dynamics and therapeutic opportunities in drug-induced liver failure.

cell biology↗

bioRxiv2026

Cell-Autonomous AR Dependence in Luminal Prostatic Epithelium Governs Survival and Lineage Plasticity

Prostate cancer resembles differentiated secretory luminal cells and shows cell-autonomous dependence on androgen receptor (AR) signaling, yet normal luminal cells are often considered dependent on paracrine stromal AR signaling. To resolve this, we conditionally deleted Ar in luminal acinar cells in vivo. Ar-deleted luminal cells persisted short-term, in contrast to the rapid regression observed after castration, but were impaired in regeneration and progressively lost. Their depletion was accompanied by replacement through basal-to-luminal differentiation of AR intact basal cells. Transcriptomic and chromatin profiling showed cell-autonomous suppression of the secretory program with induction of stemness, inflammatory, and epithelial-to-mesenchymal transition signatures after AR loss. Mechanistically, the MAP kinase pathway and downstream AP-1 transcription factors were activated and functionally validated, and MAP kinase inhibition selectively depleted AR-deleted luminal cells, indicating a compensatory survival pathway. These findings define intrinsic roles for luminal AR in maintaining differentiation, restraining plasticity, and sustaining regeneration and homeostatic turnover, providing a mechanistic basis for AR dependence in prostate cancer.

cell biology↗

bioRxiv2026

MATR3 is essential for oocyte growth and maturation quality through a dual molecular mechanism

The molecular mechanisms governing mRNA accumulation during oocyte growth, essential for developmental competence, remain poorly understood. This study investigates the role of Matrin-3 (MATR3), a highly expressed RNA-binding protein in growing oocytes (GOs), using oocyte-specific knockout mouse models and human oocyte maturation arrest (OMA) samples. The results showed that MATR3 was more abundant in GOs than fully-grown oocytes (FGOs), highly expressed in the nucleus of non-surrounded nucleolus (NSN) oocytes, and exited the nucleus during the NSN-to-surrounded nucleolus (SN) transition. In OMA patients, MATR3 nuclear localization was missed, with smaller oocytes than FGOs. Further, Matr3 deletion in mouse GOs caused restricted oocyte growth, global transcription disorders, follicle development failure, blocked GO-granulosa cell communication (via reduced Gdf9 and Radixin expression), and infertility. Mechanistically, MATR3 regulated transcription by recruiting H3K9me2-demethylating lysine-specific demethylase 3B or binding target gene promoters, like Radixin. These findings reveal a critical role of MATR3 in orchestrating transcription and paracrine signaling during oogenesis and suggest its potential as a diagnostic and therapeutic target for OMA.

physiology↗

bioRxiv2026

Nonanticoagulated Heparin Derivatives Mediate Goblet Cell Differentiation to Restore the Mucosal Barrier for Ulcerative Colitis Therapy

Epithelial mucus barrier dysfunction is a pathological hallmark of ulcerative colitis (UC), yet current clinical therapeutic strategies primarily suppress inflammation, lacking reliable approaches for restoration of the mucosal layer. Here, through a systematic screen of our established library of deanticoagulated heparins, we identified NALHP, a non-anticoagulant low-molecular-weight heparin derivative, and its representative fraction S6 as orally active epithelial repair-promoting glycans. NALHP/S6 restored crypt architecture, mucus production and epithelial barrier integrity in experimental colitis. In UC patient-derived colonic organoids, NALHP/S6 reduced aberrant stem/proliferative programs while promoting secretory, absorptive and junctional maturation. Single-cell transcriptomics and temporal validation identified a transient repair-secretory transitional state (RSTS) positioned between classical Wnt-associated stemness and mature barrier-forming epithelial states. Transcriptomic analysis revealed coordinated attenuation of Wnt and Notch signaling, whereas pharmacological reactivation of these pathways opposed NALHP/S6-induced epithelial state progression. These findings define mucosal repair as a regulated epithelial-state transition and identify NALHP/S6 as glycan-based modulators capable of restoring this progression in UC epithelium.

pathology↗