Biology subjects

Sun, J.

Publications and source records attributed to Sun, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Induced microfold cells are required for the function of pulmonary tertiary lymphoid organs that promote mucosal immunity

Tertiary lymphoid organs (TLOs) arise in response to infection and inflammation. We show that influenza-induced lung TLOs are comprised of inducible M cell (iM cell)-inducible bronchus-associated lymphoid tissue (iBALT) functional composites. iM cells are necessary for the appropriate architecture of adjacent immune follicles, which contain clonally expanded and sequence-diversified B cells. iM cell ablation results in fewer antigen-specific germinal center B cells, T follicular helper cells, and T helper memory cells, and a decrease in secretory IgA and IgG production accompanied by a loss of viral control. We find that the iM cells arise from epithelial progenitors that respond to a RANKL signal from infiltrating T cells, consistent with a model in which the patchy inflammation typical of pneumonia results in the unpredictable and varying distribution of coupled iM cells and adjacent iBALT. We propose that iM cells could be harnessed to promote infection control and enhance mucosal vaccination.

immunology↗

bioRxiv2026

Xenograft supervision and joint methylation-fragment-end encoding define a reusable molecular scoring layer for cell-free tumor DNA

Circulating tumor DNA is often scarce in plasma, and regional methylation summaries can obscure informative differences between individual molecules. Here we present ctDNA-BERT, a Transformer that scores individual bisulfite reads without predefined differentially methylated regions by jointly encoding CpG methylation state, nucleotide context and the fragment 3' end. Xenografts provide molecule-level tumor supervision. The resulting frozen scorer supported tumor-fraction estimation in synthetic and patient-derived xenograft mixtures and enriched tumor-concordant methylation and chromatin-accessibility signals in independent hepatocellular carcinoma and stage III pan-cancer plasma without cohort-specific retraining. Features derived from selected reads discriminated stage I cancers from healthy controls in a retrospective cohort of 1,477 specimens, achieving an out-of-fold area under the receiver operating characteristic curve of 0.884. By separating molecular scoring from sample-level inference, ctDNA-BERT provides a reusable read-level scoring layer for cell-free DNA methylation analysis.

bioinformatics↗

bioRxiv2026

Rotavirus NSP1 activates human NLRP1 inflammasome

While inflammasomes detect and defend against pathogens, the precise mechanisms by which enteric viruses trigger these complexes, and the specific viral components involved remain incompletely understood. In this study, we demonstrate that rotavirus infection robustly induced human NLRP1 inflammasome activation via p38 mitogen-activated protein kinase (MAPK)-dependent and -independent pathways. Utilizing cell lines reconstituted with NLRP1 signaling and reverse genetics-rescued recombinant rotaviruses, we identified non-structural protein 1 (NSP1), a well-characterized viral antagonist of host interferon signaling, as an activator of the NLRP1 inflammasome in the absence of double-stranded RNA. Domain mapping analysis revealed that the C-terminus of NSP1 but not the C-terminal IRF3-binding site was essential for triggering inflammasome activation. Mechanistically, we show that NSP1 induced the proteasomal degradation of NLRP1 to elicit its activation, a process dependent on host neddylation pathways and the Cullin-3/Elongin B/C ubiquitin ligase complex. Together, these findings suggest that RV engages parallel NLRP1 surveillance pathways, including a p38-dependent response to infection, and a novel NSP1-dependent pathway involving the ubiquitin-proteosome system, where a viral strategy aimed at host protein degradation inadvertently trips the human NLRP1 inflammasome wire.

microbiology↗

bioRxiv2026

Development of CYP8B1-specific inhibitors for metabolic diseases

Changes in bile acids (BAs) balance lead to various metabolic diseases, yet current treatment options targeting these changes remain severely limited. CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) is a liver-exclusive enzyme that controls the synthesis of 12-hydroxylated (12-OH) BAs. Inhibiting CYP8B1 is an attractive therapeutic strategy for attenuating 12-OH BA levels, remodeling the gut microbiota and thereby ameliorating metabolic diseases. CYP8B1-specific inhibitors are currently lacking due to structural similarities between the active site of CYP8B1 and other CYPs, and the lack of suitable high-throughput screening (HTS) assays. Herein, we developed a highly sensitive, and specific enzyme-coupled fluorescence assay to detect CYP8B1 activity, making it ideal for HTS. Employing this assay, structure-based drug design by protein X-ray crystallography, structure-activity relationship (SAR) analyses, and in vitro and in vivo validation, we developed novel CYP8B1-specific small molecule inhibitors. The lead candidate alters BA composition, favorably remodels the gut microbiota, and corrects metabolic disease in a metabolic dysfunction-associated steatotic liver disease (MASLD) mouse model. These findings reveal that pharmacologically inhibiting CYP8B1 is able to reshape the BA and gut microbiota profiles and effectively ameliorates metabolic diseases. Overall, CYP8B1-specific inhibitors represent a first-in-class promising, safe and effective therapeutic strategy against metabolic disorders.

pharmacology and toxicology↗

bioRxiv2026

Multiple non-redundant functions underlie the essentiality of lipopolysaccharide in Gram-negative bacteria

Lipopolysaccharide (LPS) is well known for its immunostimulatory activity and its contribution to the permeability barrier of the Gram-negative outer membrane. Yet LPS is essential for growth in nearly all Gram-negative bacteria, even under laboratory conditions where its barrier function should be less critical. LPS contributes to envelope mechanics, membrane biogenesis, and cell division, but whether any of these functions accounts for its essentiality remains unclear. Here, we systematically tested these possibilities by depleting LPS in Escherichia coli and Klebsiella pneumoniae. Osmoprotection largely preserved cell-envelope integrity but not viability, demonstrating that the mechanical contribution of LPS alone cannot explain its essentiality. Genetic perturbations that increase peptidoglycan rigidity or alter phospholipid homeostasis partially improved growth, supporting independent roles for LPS in envelope mechanics and membrane biogenesis. An unbiased suppressor screen further identified activation of the MarA regulon as a potent mechanism for surviving LPS depletion. Protection required transport by the AcrAB-TolC multidrug efflux pump, revealing an unexpected connection between efflux and cell-envelope homeostasis. Thus, LPS essentiality emerges from multiple non-redundant contributions to Gram-negative cell-envelope physiology.

microbiology↗

bioRxiv2026

Evolution-Guided Engineering of Non-conserved N-Glycosylation Sites Improves Heterologous Production of Sulfotransferases

Escherichia coli features low cost, mature fermentation technology and high recombinant protein output, but the expression of glycosylation-dependent eukaryotic proteins therein is severely limited. Many glycosylated proteins are key tool enzymes for the biosynthesis of various pharmaceutical molecules, such as glycosaminoglycan-related synthases, but there is a lack of universal protein engineering methods to enable the adaptive evolution of these enzymes in E. coli. We established an evolution-guided optimization strategy that targets non-conserved N-glycosylation sites (EGO-NGly). The core of this strategy lies in the phylogeny-guided selective reversion of evolutionarily acquired N-glycosylation sequons to naturally occurring non-glycosylated residues from early-divergent orthologs, thereby improving heterologous production and residual activity stability for selected sulfotransferases in E. coli. Using heparin 3-O-sulfotransferase 1 (3OST-1) as a model enzyme apparatus in eukaryotic organisms, EGO-NGly extended the residual activity half-life by 4.5-fold. Structural analysis and molecular dynamics simulations indicate that greater surface rigidity and remodeling of intramolecular interaction networks contribute to the improved conformational stability of M7 in an aglycosylated host. EGO-NGly was further applied to a panel of 3OST and 6OST homologs, demonstrating its applicability to a subset of the tested enzymes. Furthermore, EGO-NGly can be orthogonally integrated with other complementary protein engineering strategies, as exemplified by its combination with the machine learning-aided Protein Repair One-Stop Service, generating variants with 8-fold and 17-fold extensions in residual activity half-life. Collectively, these results establish EGO-NGly as a practical and potentially cost-effective engineering strategy for improving the prokaryotic expression and functional performance of selected glycosylation-dependent eukaryotic sulfotransferases.

biochemistry↗

bioRxiv2026

CHORUS: A proteome-scale atlas of membrane interaction interfaces constructed using cross-protein language model embeddings from sequences alone

Membrane proteins drive vital cellular signaling and bioenergetics yet resolving their physical interaction interfaces remains hindered by the paucity of experimental complexes and the breakdown of sequence alignments across hydrophobic bilayers. Here, we present CHORUS, a sequence-only deep-learning framework that decodes interaction sites across membrane proteins without requiring 3D structures, multiple sequence alignments (MSAs), or predefined partner identities. By systematically synthesizing complementary latent representations across diverse protein language model (pLM) families and functional layer depths, CHORUS outperforms 18 established sequence- and structure-based methods across 4,655 homology-isolated test contexts (average precision: 0.643), demonstrating amplified predictive capacity within the lipid-embedded core (0.746). We show that CHORUS delineates quaternary contact boundaries across megadalton respiratory supercomplexes directly from sequences alone (0.984). We deliver the CHORUS Atlas (https://chorus.atlas.sunnylab.org), providing precomputed, residue-resolved interaction landscapes for 80,619 reviewed transmembrane proteins spanning 4,918 species and 33.7 million residues to empower interactome-scale discovery and allosteric therapeutic design.

bioinformatics↗

bioRxiv2026

Scalable methylome-transcriptome profiling resolves clonal organization in human hematopoiesis

Understanding human tissue maintenance and remodeling requires linking clonal ancestry to molecular state, yet scalable joint measurement remains challenging. Here, we introduce Droplet-MT and an integrated computational workflow for joint transcriptome and methylome profiling at ~10,000 cells per library. Methylation epimutations enable mutation-independent clonal reconstruction from high-coverage methylomes, while reference-based label transfer assigns cells to established clones at ~0.2% CpG coverage, reducing sequencing cost. Clone-aggregated somatic variants provide genetic annotation without additional single-cell genotyping. Across ~21,000 paired profiles from healthy blood and longitudinal acute myeloid leukemia, we resolved small and expanded clones with heterogeneous lineage output. In leukemia, the framework distinguished changes in malignant clonal abundance, state remodeling within persistent clones, and recovery of healthy polyclonal hematopoiesis. Malignant monocytes remained transcriptionally and epigenetically distinct from healthy and recovery-associated cells despite treatment-associated remodeling. Droplet-MT enables scalable analysis of human tissues by linking clonal organization with molecular state and retrospective genetic annotation.

genomics↗

bioRxiv2026

Two new gastropod holobionts from Atlantic hydrothermal vents showing different levels of endosymbiosis dependence

Chemosynthetic symbioses underpin animal life at deep-sea hydrothermal vents, encompassing substantial variabilities in symbiont identity, metabolic capacity, and host dependence. Here, we characterise symbioses in two peltospirid snails from Mid-Atlantic Ridge vents, Peltospira gargantua and P. smaragdina, using 3D anatomical reconstruction, stable isotope analyses, fluorescence in situ hybridization, transmission electron microscopy, and metagenomics. Both species hosted abundant intracellular Campylobacterota within bacteriocytes of a hypertrophied oesophageal gland. Their dominant symbionts belonged to genus Sulfurimonas, but the two hosts were associated with distinct symbiont lineages. Symbiont genomes encoded carbon fixation through the rTCA cycle, sulfide oxidation, and Group I Ni-Fe hydrogenases, indicating combined thiotrophic and hydrogenotrophic capacities. Hydrogenase copy number varied across vent fields from one to three copies. The P. gargantua symbiont from the hydrogen-enriched Hydra vent field carried two divergent copies, including one with a truncated catalytic region, potentially reflecting local adaptation to vent geochemistry. Anatomical and isotopic comparisons further revealed contrasting host dependence, with P. gargantua having a proportionally larger oesophageal gland and ventricle coupled with a reduced radula, as well as a greater nitrogen-isotope enrichment between symbiotic and non-symbiotic tissues. The smaller oesophageal gland and larger feeding apparatus of P. smaragdina point to it being mixotrophic. Previously, all known peltospirid symbioses have partnered with Gammaproteobacteria, and we expand the known diversity of peltospirid symbioses. Our findings underscore how closely related hosts can exhibit different degrees of dependence on symbiosis, and that mixotrophic symbiosis may be prevalent in small vent species previously thought to be non-symbiotic.

ecology↗

bioRxiv2026

Comparison of sodium azide- and cooling-based immobilization methods for Caenorhabditis elegans chemotaxis assays

Chemotaxis assays are widely used to quantify sensory-driven behavioral responses in Caenorhabditis elegans. Sodium azide is commonly used to immobilize animals at assay endpoints, although concerns have been raised that diffusion beyond the endpoint region could affect behavior before a choice is completed. We compared sodium azide-mediated immobilization with post-assay cooling using the repellent 1-octanol and attractant diacetyl. Wild-type animals showed robust avoidance of 30% 1-octanol and attraction to 0.5% diacetyl with either method, across multiple assay durations, and with or without worm food Escherichia coli OP50. These results support post-assay cooling as an alternative endpoint-scoring method.

animal behavior and cognition↗

bioRxiv2026

NexuST: A Hierarchical Foundation Model for Spatial Transcriptomics

Spatial transcriptomics captures molecular states within cells and their organisation in tissue. However, integrating fine-grained gene information with spatial context at scale remains challenging for existing foundation models. Here we present NexuST, a hierarchical foundation model that repeatedly interleaves gene-level molecular modelling with cell-level spatial modelling, allowing the two levels to refine one another during end-to-end pretraining. For pretraining, we curated HumanST-46M, comprising 45.7 million human cells from 72 datasets across 11 organs and three imaging-based platforms. Across four held-out datasets totalling approximately 2.6 million cells, NexuST achieved state-of-the-art or competitive performance in cell-type annotation, region prediction, gene recovery and neighbourhood-composition prediction. We find that cell-intrinsic expression remains informative even for spatial tasks, as shown by an expression-only PCA baseline, while NexuST shows particularly strong gains where spatial context is essential. Overall, NexuST establishes a hierarchical framework that can serve as a general backbone for future spatial transcriptomics foundation models.

bioinformatics↗

bioRxiv2026

Postnatal sensorimotor experience causally shapes hemispheric specialization across motor and language networks

The functional organization of the human brain is shaped by the interplay between innate constraints and postnatal experience. Hemispheric specialization, as a fundamental organizing principle of brain function, raises unresolved questions about how postnatal experience shapes lateralization and importantly, whether different lateralized cognitive systems develop through shared or independent mechanisms. We leveraged a natural experiment in individuals with obstetric brachial plexus injury (OBPI) in the right upper limb, resulting in lifelong left-hand dominance dissociated from the typical predisposition, to address these questions. Using functional MRI experiments during manual motor tasks, we found that altered hand-use experience selectively reshaped hemispheric organization in higher-order frontoparietal motor regions. Specifically, individuals with right OBPI showed reduced left-hemisphere dominance and rightward reorganization of abstract, hand-independent action representations relative to controls and individuals with left-side OBPI, whereas primary sensorimotor and subcortical regions preserved their canonical lateralizedl organization. Strikingly, experience-dependent motor reorganization extended beyond the motor system:individuals with right OBPI exhibited reduced left lateralization of the language network in Broca's area (BA44) during sentence listening. Crucially, language lateralization in BA44 covaried with the left lateralization of frontal motor areas, particularly for the compensatory, functional left hand. These findings demonstrate that postnatal bodily experience shapes the developmental emergence of hemispheric specialization, specifically in higher-order motor and language networks, and revealed coordinated organization between action and language systems.

neuroscience↗

bioRxiv2026

In utero barcoding of mouse mesoderm reveals the clonal architecture of organ mesenchyme

The mesoderm coordinates organogenesis and generates the cardiovascular, visceral and musculoskeletal systems, yet in mammals this germ layer is difficult to access, impeding its genetic manipulation and study. Here, we establish embryonic day (E) 7.5 exocoelomic cavity nano-injection as a scalable route for selective genetic targeting of mouse mesoderm. Combining in utero lentiviral barcoding with single-cell and spatial transcriptomics, we reconstructed mesodermal and neural crest clonal relationships across >590,000 cells and 31,000 multicellular clones from E9.5-E10.5 embryos and E16.5 livers and hearts. In liver, capsular mesothelium was closely related to hepatic stellate cells, whereas fibroblast and vascular smooth muscle lineages diverged earlier. In heart, epicardium was clonally coupled to three spatially restricted mesenchymal sub-lineages but not to cardiomyocytes, and lineage tracing separated epicardial- and neural crest-derived populations within transcriptionally convergent valve mesenchyme. This approach enables Cre-independent manipulation of mammalian mesoderm and resolves organ mesenchyme development at clonal resolution.

developmental biology↗

bioRxiv2026

Independent tuning of outer membrane fluidity and mechanics in Gram-negative bacteria

The outer membrane (OM) of Gram-negative bacteria forms a protective barrier that combines selective permeability with mechanical load-bearing capacity, properties linked to its asymmetric bilayer structure with lipopolysaccharides (LPS) in the outer leaflet and phospholipids (PLs) in the inner leaflet. Unlike most PL bilayers, the OM typically exhibits limited lateral diffusion, resulting in a gel-like surface with spatially organized proteins and LPS. The molecular basis of this physical state and its relationship with envelope mechanics remain unclear. Here, we show that increasing PL levels in the outer leaflet or truncating LPS core oligosaccharides increases OM fluidity by disrupting LPS packing. In contrast, reduced LPS abundance or disruption of divalent cation-mediated crosslinking primarily reduces OM stiffness with little effect on fluidity. Thus, OM fluidity and mechanical stiffness can be tuned independently through distinct molecular interactions. This separation of physical control mechanisms provides a framework for understanding how Gram-negative bacteria modulate OM properties during environmental adaptation and envelope homeostasis.

microbiology↗

bioRxiv2026

Test-Retest Reproducibility of Single- and Cross-Population White Matter Atlases in Diffusion MRI Tractography

Diffusion MRI tractography enables noninvasive mapping of white matter fiber tracts. Atlas-based white matter parcellation supports automated tract identification by assigning individual streamlines to atlas-defined clusters and anatomical tract labels. Because clustering-based white matter atlases are constructed from cohort-specific tractography data, they capture common white matter organization represented in the atlas-construction population. Although major white matter anatomy is shared across populations, subtle population-related anatomical variability may influence atlas representation and test-retest correspondence. Therefore, the reproducibility and cross-population generalizability of tractography-based white matter atlases are important considerations for quantitative neuroimaging studies. In this study, we evaluated whether incorporating cross-population anatomical variability during atlas construction improves test-retest reproducibility. To do so, we compared a single-population ORG atlas constructed from a Western cohort with the cross-population East-West White Matter Atlas constructed from both Eastern and Western cohorts. Test-retest diffusion MRI scans from the Human Connectome Project Young Adult (HCP-YA) dataset and the Connectivity-based Brain Imaging Research Database (C-BIRD) were analyzed as independent Western and Eastern test-retest cohorts, respectively. Whole-brain tractography was reconstructed for each dMRI scan and parcellated using both atlases. Reproducibility was assessed using tract detection rate at both cluster level and anatomical tract level, weighted Dice coefficient, and the relative difference of mean fractional anisotropy (FA). Both atlases showed stable tract detection across test-retest scans in both cohorts. Compared with the ORG atlas, the East-West White Matter Atlas achieved higher overall spatial overlap and lower test-retest variability in mean FA, although atlas performance varied across individual tracts. These findings suggest that integrating cross-population information during atlas construction improves the reproducibility and generalizability of white matter atlas mapping across independent populations and imaging protocols.

neuroscience↗

bioRxiv2026

Pathogen-associated odor experience induces inherited olfactory avoidance in a parasitoid wasp

Odors allow animals to evaluate resources and risks, but the neural and inherited consequences of experience with ecologically meaningful odors remain poorly understood. Since both parasitoids and entomopathogenic fungi are widely used as agents in integrated biocontrol, we asked whether exposure to pathogen-associated volatiles can reassign odor value in a parasitoid wasp and whether the acquired bias is transmitted to descendants. Adult female Scleroderma guani were exposed, without host contact, to volatiles from Beauveria bassiana-infected hosts or to methyl cinnamate (MC), a representative component of the infected-host odor. Twelve-hour exposure shifted subsequent choices away from infected-host odor and MC, whereas shorter exposure produced different effects, indicating duration-dependent olfactory plasticity. The shift occurred without an explicit reward or punishment and is therefore consistent with non-associative learning. Unexposed F1 and F2 descendants of MC-exposed females expressed the same avoidance bias. MC stimulation elicited stronger calcium responses in mushroom-body regions of trained females and their descendants. Head transcriptomes identified reduced expression of the crustacean cardioactive peptide receptor (CCAPR) as a shared molecular signature, and CCAPR RNA interference phenocopied the odor-avoidance behavior. Finally, maternal treatment with sinefungin, a broad S-adenosylmethionine-dependent methyltransferase inhibitor, left maternal behavioral shift intact but abolished the F1 bias, implicating a methylation-sensitive process in transmission. Together, these results reveal that a pathogen-associated odor can induce durable, cross-generational reweighting of olfactory value in a non-model insect and identify candidate neural and neuropeptidergic mechanisms linking sensory experience to inherited behavior, and providing a new perspective on utilizing training in integrated biocontrol as well.

animal behavior and cognition↗

bioRxiv2026

Reconstruction of the gastropod ancestral karyotype reveals lineage-specific chromosomal evolution and adaptations during habitat transitions

Gastropoda is the most diverse class of molluscs, with spectacular adaptive radiations across shallow to deep marine, freshwater, and terrestrial environments, yet the role of chromosomal restructuring behind these habitat transitions remain largely unexplored. This is in part due to most chromosomal genomes available are in the subclasses Caenogastropoda and Heterobranchia, with few representatives from the other four subclasses. Here, we assembled chromosome-level genomes for five representatives from those four subclasses: Vittina coromandeliana (Neritimorpha), Shinkailepas gigas (Neritimorpha), Turbo cornutus (Vetigastropoda), Neomphalus fretterae (Neomphaliones), and Cellana toreuma (Patellogastropoda), and reconstructed the ancestral gastropod karyotype consisting of 20 linkage groups (GLGs) as well as the ancestral karyotype of each subclass. Integrating macrosynteny and phylogenomic analyses across all six subclasses, we show that different lineages have adopted fundamentally different chromosomal strategies to colonize novel habitats: freshwater caenogastropods genomes are characterized by extensive end-to-end fusions, terrestrial heterobranchs by whole genome duplications, freshwater neritimorphs by lineage specific fissions plus fusion with mixing, and deep sea hydrothermal vent vetigastropods by widespread chromosomal restructuring, whereas hydrothermal vent neomphaliones and caenogastropods retain remarkably conserved ancestral karyotypes. Rearrangement breakpoints preferentially reside within topologically associating domains (TADs) rather than at boundaries, preserving higher order chromatin architecture. Functionally, convergent enrichment of the mucin type O glycan biosynthesis pathway in both freshwater and hydrothermal vent lineages is accompanied by lineage specific modifications, enhanced immune modulation in freshwater versus reinforced physicochemical shielding in the deep sea, reflecting divergent adaptive applications of this pathway. Our findings demonstrate that habitat transitions in gastropods are facilitated not by a uniform genomic mechanism, but by a diverse repertoire of lineage specific chromosomal strategies, highlighting the extraordinary genomic flexibility that underpins the remarkable gastropod diversity seen today.

evolutionary biology↗

bioRxiv2026

An orally administered peptide hydrogel disentangles immune-microbiota crosstalk for long-term ulcerative colitis therapy

Ulcerative colitis (UC) is a global health challenge driven by immune dysregulation and gut microbiota imbalance.1 Current treatments, limited by insufficient efficacy and systemic toxicity during prolonged use, fail to resolve the intertwined immune-microbial pathology.2 Here, we report an orally administered self-assembled hydrogel C2-(IIRR)2I-NH2 (CIR), engineered from host defense peptides, which disrupts the immune-microbiota entanglement. The CIR hydrogel exhibits structural transformation at the inflamed sites rich in liposaccharide (LPS), a pro-inflammatory molecule derived from pathogenic bacteria. Stable {beta}-sheet nanofibers can transfer to bioactive -helix conformations, enabling localized therapeutic action with minimal off-target toxicity. In murine colitis models, CIR restores mucosal integrity and suppresses disease severity, outperforming the first-line drug 5-aminosalicylic acid (5-ASA). Microbiome profiling reveals its capacity to rebalance gut microbiota, depleting LPS produced pathogenic bacteria like Prevotellaceae. Transcriptomic analyses further indicate that CIR silences TLR4-mediated signaling pathway. By synergistically targeting immune dysregulation and microbial dysbiosis, this self-assembled peptide hydrogel establishes a paradigm-shifting strategy for UC, offering clinically translatable potential for multifactorial gastrointestinal disorders.

bioengineering↗