Biology subjects

Yang, T.

Publications and source records attributed to Yang, T..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

A Comprehensive Computational Model of the Human head for Designing and Optimizing Visual Brain-Machine Interfaces

Brain-machine interfaces (BMIs) for vision restoration require models that accurately simulate the anatomy and electrical properties of visual pathways. However, current models focus only on isolated structures, such as the retina or brain, and overlook surrounding tissues. Here, we present a comprehensive computational model of the human head, incorporating the entire visual pathway--including the eye, optic nerve, and brain--along with critical neighboring tissues such as the orbit, paranasal sinuses, enabling precise simulations. Validation using human and large animal data demonstrated a strong correlation between the simulated and measured electrical potentials. Component elimination analysis revealed that the optimized comprehensive model outperformed simplified versions. The models utility was demonstrated through multiple applications: (1) comparative analysis of electrical neuromodulation technologies for optic neuropathy, revealing the filed intensity limitations of noninvasive approaches and the safety concerns of invasive intraorbital approach; (2) identification of optimal stimulation site, revealing that transnasal stimulation at the optic chiasm outperformed traditional approaches; and (3) in silico design of electrode arrays for optic nerve prosthetics, demonstrating theoretical advantages in invasiveness and visual field coverage compared to existing retinal and cortical prosthetics. This validated and versatile computational resource supports the development of neuromodulation strategies and visual BMI technologies.

bioengineering↗

bioRxiv2026

Osteoimmunomodulatory Stem Cell Nanoghosts as a Novel Nanotherapeutic for Bone Regeneration

Critical-sized bone defects and implant-associated complications are often exacerbated by chronic inflammation, which compromises tissue repair and implant integration. Mesenchymal stromal cell (MSC)-derived extracellular vesicles have emerged as promising immunomodulatory nanotherapeutics; however, their clinical translation remains constrained by low yield, heterogeneity, and poor scalability. Here we present a bioengineered MSC-derived nanoghosts platform designed to overcome these translational barriers while enabling tunable osteoimmunomodulatory function. By coupling high-yield nanoghost fabrication with biomimetic MSC conditioning, we demonstrate that oxygen tension (5 or 21% O2) and 3D culture substrates (5 or 15 wt-% GelMA) can reprogram MSC immunophenotype. Nanoghosts generated under hypoxic and 3D conditions displayed enriched anti-inflammatory cargo, preserved MSC viability under inflammatory stress, and partially rescued osteogenic mineralization in the presence of pro-inflammatory cytokines. Together, these findings showcase MSC nanoghosts as scalable and bioactive immunoregulatory nanotherapeutic capable of modulating immune-bone crosstalk, providing a translational strategy to mitigate inflammation-driven impairment of bone regeneration and implant integration. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/724218v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@f965deorg.highwire.dtl.DTLVardef@18f007borg.highwire.dtl.DTLVardef@168a194org.highwire.dtl.DTLVardef@4818fe_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

The Par complex regulates apical-basal cell polarity through modulation of FAK signaling homeostasis

Cell polarity complexes are essential for embryogenesis, but their regulatory mechanisms during early developmental transitions remain incompletely understood. Here, we individually deleted the Crumbs, Par, and Scrib polarity complexes in mouse embryonic stem cells (mESCs). While loss of any single complex did not affect pluripotency or proliferation, deletion of Par complex disrupted the naive-to-primed transition and impaired subsequent differentiation, particularly lumen formation in neural tube organoids. Mechanistically, Par complex deficiency led to hyperphosphorylation of focal adhesion kinase (FAK) at the primed stage, driving a morphological shift from flat monolayer clusters to dome-shaped colonies. FAK inhibition rescued the aberrant morphology. Upstream, Par complex loss increased AKT phosphorylation, which remodeled extracellular matrix (ECM) and regulated integrin signaling via FURIN-LEFTY, ultimately modulating FAK activity. In addition, conditioned medium from wild-type cells partially rescued differentiation defects in Par knockout cells in a LEFTY-dependent manner. These phenotypes were consistently observed in naive-to-primed transition, neural stem cell differentiation, embryoid body formation, teratoma assays, and neural tube organoid differentiation. Together, these findings establish a Par complex-AKT-FURIN-LEFTY-ECM-integrin-FAK signaling cascade that links apical-basal polarity to early lineage specification and morphogenesis, providing a mechanistic framework for how polarity cues are translated into developmental outcomes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/722465v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@179e0adorg.highwire.dtl.DTLVardef@8d83bdorg.highwire.dtl.DTLVardef@c425fforg.highwire.dtl.DTLVardef@19a8ee5_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance StatementThis study elucidates the molecular mechanism by which the Par complex regulates the establishment of cell polarity. The authors demonstrate that the Par complex promotes the expression of the protein convertase FURIN via AKT signaling, thereby enhancing the maturation and secretion of LEFTY protein. This process remodels the ECM and modulates integrin signaling, ultimately regulating FAK activity and controlling the establishment of cell polarity. These findings reveal how polarity cues govern early lineage specification and morphogenesis, with implications across multiple developmental contexts.

developmental biology↗

bioRxiv2026

ExMODE: A Multi-Omics Repository for Extremophile Adaptation and Bioprospecting

Extreme environments, though hostile to most life forms, host specialized extremophile communities that have redefined biological cognition and emerged as vital biotechnological resources, with their unique adaptive traits and bioactive molecules driving advances in multiple scientific and industrial fields. However, research on extremophiles is hindered by limitations in culture-based methods, fragmented multi-omics data with non-uniform annotation standards across repositories, the lack of cross-extreme comparative research in existing resources, and the singularity of data dimensionality that neglects key structural information, all of which restrict the functional interpretation of extremophile microbes and the exploitation of their bioprospecting potential. To tackle these challenges, we developed ExMODE (https://db.genomics.cn/exmode/), a comprehensive multi-omics database platform dedicated to extremophiles. It centrally integrates multi-omics data from diverse extreme habitats with a standardized annotation framework, resolving data fragmentation and enabling systematic cross-environment comparative analyses to elucidate extremophile adaptive mechanisms. Moreover, ExMODE aggregates multi-dimensional datasets including genes, genomes, secondary metabolite sequences and protein structures, overcoming the constraints of single-dimensional data and significantly improving the efficiency of biotechnological resource discovery from extreme microorganisms.

microbiology↗

bioRxiv2026

Distinct HPO axis responses and ovarian aging trajectories to chronic unpredictable mild stress in reproductively young versus middle-aged female mice

Psychosocial stressors are key contributors to ovarian functional decline. Chronic unpredictable mild stress (CUMS) is widely used to model stress-induced premature ovarian insufficiency (POI) in mice; however, current animal models do not adequately reflect middle-aged women, who represent a key population exposed to chronic psychosocial stress, nor do they capture the dynamic progression toward POI. Here, female C57BL/6 mice aged 2 or 6 months were subjected to CUMS for 8 or 12 weeks. Estrous cyclicity, endocrine profiles, ovarian histology, and transcriptomic changes in HPO axis-related tissues were systematically analyzed. After 8 weeks of exposure, 2-month-old mice exhibited impaired pituitary responsiveness to estradiol negative feedback, as evidenced by dysregulated FSH secretion, indicating reduced stress tolerance compared with 6-month-old mice. Following 12 weeks of CUMS exposure, both age groups showed significant reductions in ovarian size and follicle numbers across all developmental stages. These findings demonstrate that CUMS induces an age-dependent progression toward POI, with short-term exposure eliciting compensatory phases preceding overt ovarian insufficiency, accompanied by distinct endocrine and reproductive alterations and differential responsiveness of the HPO axis. Transcriptomic analyses revealed age-dependent stress responses: ovaries of 2-month-old mice displayed marked activation of inflammatory and immune-related pathways, whereas 6-month-old mice showed sustained upregulation of protein kinase-related signaling networks. Notably, the 6-month-old CUMS model more closely recapitulates stress-associated reproductive aging in adult women. In briefCUMS has been widely used to establish mouse models of psychosocial stress-induced POI. However, current animal models do not adequately reflect middle-aged women, who represent a key population exposed to chronic psychosocial stress, nor do they capture the dynamic progression toward premature ovarian insufficiency (POI). In this study, we demonstrate that different durations of CUMS exposure induce distinct stages of ovarian dysfunction in both young and middle-aged mice, with short-term exposure driving age-dependent compensatory phases and prolonged exposure leading to overt POI, both accompanied by divergent endocrine and reproductive alterations, alongside age-dependent changes in HPO axis responsiveness to CUMS. Notably, the 6-month-old CUMS model shows greater clinical relevance in recapitulating chronic psychosocial stress and stress-related reproductive aging in adult women.

physiology↗

bioRxiv2026

sPRR signaling in macrophages via the AT1R/Yap/Taz axis to induce renal fibrosis

BackgroundWithin the kidney, (pro) renin receptor (PRR) is abundantly expressed in the collecting duct (CD) and modulate physiological and pathophysiological processes. We have recently reported that activation of CD PRR mediates obstructive renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO). The current study addresses the underlying mechanisms by examining the profibrotic pathway mediated by soluble PRR (sPRR)-dependent alternative macrophage activation. MethodsWe performed UUO or sham surgery on mice with CD-specific deletion of PRR (CD PRR KO) and floxed controls. After 7 days, we assessed fibrosis-related parameters, inflammatory cytokines, M1/M2 macrophage markers, other gene expression markers of kidney injury, and the concentration of plasma sPRR. We also administered vehicle or site-1 protease (S1P) inhibitor PF-429242 (PF) to C57BL/6 mice with UUO to determine the role of sPRR. Experiments were performed in vitro to examine the mechanism of sPRR-His-mediated macrophage M2 polarization and activation of potential target genes in bone-marrow-derived macrophages (BMDMs). ResultsCompared with the floxed control, CD PRR KO decreased macrophage accumulation, M2 polarization, and Yap/Taz expression while improving renal fibrosis and suppressing plasma sPRR levels following UUO. In BMDMs, sPRR-His treatment promoted macrophage M2 polarization, fibrosis, and Yap/Taz expression, which was dependent on angiotensin type 1 receptor (AT1R). ConclusionCD PRR-derived sPRR acts via ATR to promote macrophage M2 polarization and stimulates the AT1R/Yap/Taz axis, which leads to renal fibrosis during UUO.

pathology↗

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

Time-Resolved Single-Molecule FRET Reveals Length-Dependent Nucleosome Decompaction by Poly(ADP-ribose)

Highly charged chains of poly(ADP-ribose) (PAR) are synthesized in the cell as part of their central role in DNA damage response. However, the effects of PAR on nucleosome structure and dynamics remain incompletely understood. Here we combine droplet-based microfluidic mixing with single-molecule Forster resonance energy transfer spectroscopy to resolve the kinetics of PAR-induced nucleosome decompaction in non-equilibrium measurements with millisecond time resolution. This approach avoids surface-adhesion and enables the tether-free observation of nucleosome remodeling. We find that PAR triggers nucleosome decompaction via a length-dependent kinetic threshold: Chains with less than ten ADP-ribose units act slowly and weakly, whereas longer PAR polymers induce efficient and rapid nucleosome opening. The extent and reversibility of decompaction further depend on PAR concentration and ionic strength, reflecting a mechanism dominated by electrostatic interactions. Enzymatic PAR digestion demonstrates that PAR can promote both reversible linker DNA opening and irreversible nucleosome disassembly. Coarse-grained molecular simulations suggest that these effects arise from a competition between PAR and DNA for histone tail binding. Altogether, our results establish PAR length as a key factor controlling chromatin accessibility during DNA repair and highlight droplet-based microfluidics as a powerful platform for studying such biomolecular interactions.

biophysics↗

bioRxiv2026

The Herbicide Glyphosate Promotes Hypertension via Gut Microbiota-Mediated Mechanisms

Glyphosate, the active ingredient in herbicide Roundup, is the most widely used environmental contaminant that has been extensively studied for its potential carcinogenic effects. In the US alone, a staggering 81% of the US population [≥]6 years of age is exposed to glyphosate. Notably, this coincides with the alarming rise in the incidence of hypertension, the single largest risk factor for global mortality through cardiovascular diseases. Here we asked if there is a link between glyphosate exposure and hypertension, the premise being that glyphosate targets the shikimate pathway present in gut microbiota coupled with more recent knowledge that gut microbiota causally regulate blood pressure. We hypothesized that glyphosate elevates hypertension through microbiota-mediated mechanisms and document a highly concerning detrimental effect of glyphosate by demonstrating a causal link between oral glyphosate exposure and significant elevation in blood pressure. Gut microbiota was identified as the central mediator of this effect. Mechanistically, glyphosate-mediated elevation in blood pressure was through disruption of both gut-liver and gut-vascular homeostasis via FXR-signaling and accumulation of the microbial metabolite shikimic acid, respectively. Together, these findings underscore the need to reconsider the unabated use of this herbicide, which adversely affects a cardinal sign of health.

physiology↗

bioRxiv2026

Kindlin-2-Moesin interaction orchestrates sprouting angiogenesis via modulating endothelial membrane mechanics and VEGF signaling

Membrane mechanics play a crucial role in cellular signaling and fate determination, yet their impact on angiogenesis remains poorly understood. Here, we identify Kindlin-2 as a key regulator of sprouting angiogenesis via regulating endothelial membrane tension through its interaction with Moesin, a crucial linker protein between the cell membrane and the actin cortex. Mechanistically, Kindlin-2 binds to the N62 residue of Moesin, limiting its overactivation and maintaining proper membrane tension to facilitate VEGFR2 endocytosis and downstream signaling. Using both developmental and pathological models, we demonstrate that the interaction of Kindlin-2 and Moesin is enhanced in high angiogenic conditions, and endothelial Kindlin-2 deletion reduces angiogenesis. Furthermore, mutation of Moesin at N62 phenocopies the effects of Kindlin-2 loss. Together, these findings uncover a previously unrecognized mechanism linking membrane tension regulation to angiogenesis and provide new insights into targeting the Kindlin-2-Moesin axis for therapeutic intervention in neovascular diseases.

developmental biology↗

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

Stemona genomes illuminate fatty acid partitioning between seeds and elaiosomes mediating wasp dispersal

O_LISeed dispersal by wasps (vespicochory) is documented in five angiosperm families, with phylogenies suggesting that most vespicochorous lineages evolved from ant-dispersed (myrmecochorous) ancestors. While recent work has identified cues attracting wasp dispersers, the molecular basis remains unclear. C_LIO_LITo shed light on the molecular basis of vespicochory, we generated chromosome-level genomes for the wasp-dispersed Stemona tuberosa, and its close ant-dispersed relative S. mairei. Combining comparative genomic, transcriptomic, lipidomic, and functional analyses, we ask (i) how chemical elaiosome differentiation occurs during seed development, and (ii) how key mutualism-associated genes evolved in Stemona. C_LIO_LIWe show that elaiosomes up-regulate stearoyl-ACP {Delta}9 desaturases (SAD) and accumulate oleic acid and 1,2-diolein, which serve both as food rewards and as precursors for CER1/3-mediated biosynthesis of (Z)-9-tricosene, the key wasp attractant. By contrast, high expression of FatB and DGAT1 in seeds is associated with medium-chain fatty acids (MCFAs) production. Comparative genomics indicates conservation of these genes across Stemona, with S. tuberosa-specific FatB expansion and SAD/CER1/3 repertoire divergence. C_LIO_LIOur work supports a model for elaiosome-seed fatty-acid differentiation linking recruitment and nourishment in vespicochory. Given that oleic acid and 1,2-diolein are also key cues in myrmecochory, this shared biochemical basis may help explain how vespicochory evolves from ant-dispersed ancestors. C_LI

evolutionary biology↗

bioRxiv2026

A biofidelic Goat Model of Traumatic Optic Neuropathy with Optic Canal Fracture via Transnasal Endoscopy

Traumatic optic neuropathy (TON) is a major cause of irreversible vision loss following blunt cranial trauma, yet the absence of clinically relevant large animal models that faithfully recapitulate human TON has significantly impeded translational research. Current rodent models do not reproduce optic canal fracture, a key injury mechanism in many patients with TON. Here, we combined high-fidelity finite element analysis (FEA) with iterative engineering to establish a reproducible goat model of TON. We first built a high-resolution human-head finite element model to characterize force transmission to the optic nerve. Across clinically relevant periorbital impacts, stress preferentially concentrated in the intracanalicular segment, reaching a peak force density of approximately 500 N/m2 at 50.6 ms, about fivefold higher than in the intraorbital segment. Simulations further showed that direct optic canal impact reproduced comparable intracanalicular stress with a markedly lower input force: 195 N, compared with 3900 N for periorbital impact. Guided by these insights, we developed transnasal endoscopic impact systems capable of inducing optic canal fractures in goats. TON was confirmed within 24 hours by a characteristic relative afferent pupillary defect (RAPD), and at 1 month post-injury goats (n = 14) exhibited a 10%-20% reduction in ganglion cell complex (GCC) thickness and 40%-65% reductions in flash visual evoked potential (FVEP) and pattern electroretinogram (PERG) amplitude ratios (all P [≤] 0.001), with structural and functional preservation of the fellow eye. This study presents a robust, standardized, and clinically relevant large-animal platform for investigating TON pathophysiology.

neuroscience↗

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

Artificial Intelligence of Things-Enhanced Automated Surveillance System for Global Antimicrobial Resistance in Food Supply Chain

Antimicrobial resistance (AMR) threatens food safety across the farm-to-fork continuum. Real-time surveillance is crucial to mitigate its global escalation, yet conventional antimicrobial susceptibility testing (AST) remains slow, labor-intensive, and impractical for large-scale monitoring. We developed an Artificial Intelligence of Things (AIoT)-integrated multiplex microfluidic platform enabling automated AMR surveillance of pathogens in food supply chain. Each node combines a single-board AIoT controller (Orange Pi 5B), portable incubator, colorimetric microfluidic chips, and environmental sensors, reducing costs by 98% compared with standard AST. A lightweight YOLOv5 model embedded in the controller achieved >99% accuracy in identifying bacterial growth and inhibition under antibiotic pressure, showing 96% and 95% agreement with standard results for Salmonella and Campylobacter, respectively. Data are synchronized to a cloud server for real-time aggregation and early resistance warning. This fully automated and low-cost system minimizes human error and workload, providing a scalable sample-to-answer solution for AMR surveillance in global agri-food system.

microbiology↗

bioRxiv2026

Noncanonical loops regulated by EMF1 and cohesin-associated factors shape the distinct 3D genome architecture in plants

In mammals, cohesin-mediated chromatin loop extrusion is blocked at boundaries, where CTCF, WAPL, and PDS5s co-bind and regulate cohesin, establishing an impermeable barrier with no exceptions. In contrast, our study revealed that in Arabidopsis, some noncanonical contacts have emerged between the boundary flanking regions, which suggest that cohesin is not absolutely blocked but enables sliding beyond boundaries. We identified these interactions as noncanonical loops and clarified their regulatory proteins. Firstly, the plant-specific boundary binding protein EMF1 is essential for noncanonical loops formation. Surprisingly, although both Arabidopsis WAPLs and PDS5s inhibit loop extension as mammals, PDS5s do not co-bind and cooperate with WAPLs at boundaries. Instead, PDS5s bind to boundary-flanking regions enriched with H3K4me1 through their Tudor domains, restricting further extension of noncanonical loops. Consequently, pds5a/b/c mutants lose noncanonical loops, resulting in emergence of larger canonical loops but anchored on boundaries and co-upregulation of anchored gene pairs. Collectively, our findings reveal that the plant-specific noncanonical loop, regulated by plant-specific EMF1 and PDS5 proteins, is the fundamental structure of the distinctive chromatin organization of plants, which provides novel mechanistic insights into eukaryotic chromatin architecture regulation.

plant biology↗

bioRxiv2026

The genetic repertoire of the deep sea: from sequence to structure and function

The deep sea as the largest and maybe most hostile environment on Earth is still underexplored especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures, and used it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity, yet substantial structural conservation of proteins. Especially proteins involved in replication, recombination, and repair were identified to be under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as a unique evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.

bioinformatics↗

bioRxiv2026

Transcriptomic profiling of human γδ T cells reveals non-linear immune aging characterized by childhood transitions and relative stability in adulthood

{gamma}{delta} T cells are one of the first T cell subsets developing in early ontogeny and show various effector functions in immune homeostasis and response in the young and the old. However, their maturation trajectories from infancy to children, adults and elderly have not been systematically defined. Here, we generated a single-cell transcriptome atlas of 106,711 {gamma}{delta} T cells from 223 individuals spanning infancy to old age. Our analysis reveals that {gamma}{delta} T cell aging is non-linear, characterized by pronounced childhood transitions followed by relative stability throughout adulthood despite marked inter-individual variability. In childhood, changes from developmental and mitochondrial programs toward cytotoxicity and inflammaging were evident. This includes maturation trajectories from GZMK intermediates to GZMB+Perforin+ effectors at both RNA and protein levels. Taken together, our study delineates the aging trajectories of human {gamma}{delta} T cells, establishes {gamma}{delta} T cells as a cellular paradigm of non-linear immune aging, and provides a comprehensive resource for investigating {gamma}{delta} T cell biology across the human lifespan.

immunology↗