Biology subjects

Wang, F.

Publications and source records attributed to Wang, F..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Contrasting selective pressures shape human pepsinogen A gene copy-number variation across Eurasia

Diet has repeatedly shaped human genomes, yet adaptation of protein digestion remains poorly understood. Using 1,348 haplotype-resolved assemblies, we reconstructed the structural evolution of the human pepsinogen A (PGA) locus and found a west-to-east increase in copy-number across Eurasia that tracked regional reliance on plant-derived protein. Modern and ancient genomes further revealed a recent selective sweep in the East but signatures of balancing selection in the West. We traced this divergence primarily to expansion of PGA34A, the most proteolytically active paralog in vitro, and showed that recurrent nonallelic homologous recombination continually generated structural diversity in this locus. Independent PGA expansions were also enriched in plant-dominant mammals. These findings link paralog-specific dosage variation in protein digestion to dietary adaptation across human populations and diverse mammalian lineages.

genomics↗

bioRxiv2026

TROP2-targeting chimeras (TRTACs) for tumor-selective membrane protein degradation and enhanced drug delivery

Extracellular targeted protein degradation (eTPD) systems typically utilize lysosome-targeting receptors (LTRs) to mediate internalization and lysosomal degradation of extracellular and membrane proteins. While multiple LTRs have been discovered, there remains a compelling need to seek for new LTRs, particularly those with clear clinical relevance, to expand the therapeutic potential of eTPD. Here we report trophoblast cell surface antigen-2 (TROP2), a clinically validated tumor-associated antigen, as a promising tumor-selective LTR. We engineer TROP2-targeting chimeras (TRTACs) by genetically fusing a TROP2-binding nanobody to nanobodies against specific target proteins. We show that TRTACs can induce tumor cell-selective degradation of diverse membrane proteins, including epithelial growth factor receptor (EGFR), human epithelial growth factor receptor 2 (HER2), and programmed death-ligand 1 (PD-L1). The EGFR-targeted TRTAC significantly inhibits tumor cell proliferation and shows potent antitumor activity in vivo. We further design TRTAC-drug conjugates (TRTAC-DCs) by attaching cytotoxic payloads to TRTACs, enabling targeted protein degradation together with enhanced drug delivery. TRTAC-DCs show significantly enhanced activity against HER2- and EGFR-positive tumors both in vitro and in vivo, with minimal toxicity observed in normal tissues. These findings establish TROP2 as a robust LTR and provide a versatile eTPD platform with profound translational potential for tumor treatment.

cell biology↗

bioRxiv2026

Comprehensive analysis of mulberry genetic diversity based on 1-DNJ content and SNP markers

Mulberry trees have high economic and ecological value, and a robust molecular marker system plus germplasm genetic diversity analysis is critical for innovative utilization of high-quality medicinal and economic mulberry germplasm. Here, 51 mulberry samples were used to develop SNP primers via genome resequencing, with the SNP-PCR system optimized by single-factor and orthogonal assays. The phenotypic diversity and SNP molecular marker genetic diversity of 1-deoxynojirimycin (1-DNJ) in mulberry leaves were analyzed respectively, and the genetic correlation between molecular markers and phenotypic traits was evaluated by Mantel test. Tested germplasm showed marked 1-DNJ variation (0.4805-2.5300 mg/g, CV=0.4241), reflecting rich genetic diversity. The optimal SNP-PCR system included Buffer (containing Mg{superscript 2}+) 2.2 L, 2.5 mM dNTP 0.4 L, forward and reverse primers (10 mol{middle dot}L-1) totaling 2.75 L, Taq DNA polymerase (5 U{middle dot}L-1) 0.3 L, DNA (50 ng{middle dot}L-1) 1.1 L, and ddH2O 13.65 L. 23 highly polymorphic ones amplified 91 loci (81 polymorphic, 89.10% polymorphism rate). Genetic diversity analysis showed that the average genetic distance was 0.3010, and the average expected heterozygosity (H) and Shannon information index (I) reached 0.4667 and 0.3104 respectively, indicating that the genetic differentiation among the tested mulberry germplasms was significant and the population had a moderate to upper level of genetic diversity. UPGMA clustering divided 51 germplasms into 6 major groups at a genetic similarity coefficient of about 0.7, while phenotypic clustering based on 1-DNJ content divided them into 2 major categories and 4 subcategories, with high 1-DNJ germplasm clustered independently. Mantel correlation analysis showed that 6 SNP sites were significantly weakly correlated with 1-DNJ content (r < 0.3, p < 0.05), and can be used as candidate molecular markers for subsequent genetic analysis of 1-DNJ content.This study established a stable mulberry SNP-PCR system, Analyze the molecular genetic characteristics of mulberry germplasm and DNJ phenotypic variation rules respectively, and provide basic data for cluster comparison. and provided a scientific basis for marker database improvement, germplasm identification and molecular-assisted breeding.

genetics↗

bioRxiv2026

Hidden genetic diversity in 320 nearly-complete East Asian genome assemblies

East Asian populations, representing over 20% of the global population, remain critically underrepresented in human genomic studies, limiting our understanding of population-stratified genetic variation and its implications for health and disease. Here we present the first phase of the Asian Pan-Genome project (APG), comprising 320 nearly complete, fully phased haploid genome assemblies from 160 East Asian individuals. These assemblies achieve unprecedented quality, with an average contig N50 of 144.3 megabase pairs and an average quality value of 64.5. Leveraging these superior assemblies, we reveal previously uncharacterized diversity in human repeatome, including population-stratified patterns in centromere satellites and rDNA arrays. Compared to existing global human genome assemblies, the newly generated genomes supplement 152 million base pairs of novel sequences, 355 gene gains, 18,300 structural variation loci and 26 large euchromatic inversions missing from current human pangenomes. We perform population stratification analyses of structural variations, and further resolve the structural haplotypes of complex genomic regions such as Major Histocompatibility Complex and Survival Motor Neuron loci across global pangenomes, exemplifying tandem-duplicate and inversion-rich complex locus architectures in the human genome, respectively. This resource provides a critical foundation for human genetic studies, especially for East Asian populations, promoting more accurate variant discovery, reducing bias, and ultimately advancing the equity and efficacy of genomic medicine.

genomics↗

bioRxiv2026

Multimodal transcriptomics and calcium imaging reveal a novel subset of polymodal nociceptors expressing the interleukin 1 receptor in mice

We previously established that sensory neurons in the mouse dorsal root ganglia (DRG) express a functional receptor for the proinflammatory cytokine interleukin (IL)-1. We also demonstrated that deletion of the IL-1 receptor type 1 gene, Il1r1, in TRPV1-expressing (+) neurons prevented pain in models of chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis and osteoarthritis. Here, we found a marked sex difference in the abundance of IL-1R1+ neurons, which represented approximately 10% of all DRG neurons in females but only 5% in males. However, male mice exhibited stronger, longer-lasting mechanical hypersensitivity than females after IL-1{beta} injection into the cerebrospinal fluid. In vivo calcium imaging revealed that IL-1{beta}- responsive DRG neurons responded to cutaneous mechanical and capsaicin stimulation. By integrating spatial transcriptomics with single-cell RNA sequencing (scRNA-Seq), we identified a gene signature uniquely marking IL-1R1+ neurons, including genes such as Ada, Cysltr2, Gpr139, Htr1a, Htr1f, Il31ra, Nppb, Npy2r, Nts, P2rx2, Pde4c, and Sst, with Ada and Sst validated at the protein level. Omics analysis revealed that IL-1R1+ DRG neurons form a subset of non-peptidergic type 3 (NP3) sensory neurons, which are linked to inflammatory pain and itch. However, Il1r1 deletion did not affect itch responses to serotonin, histamine, or chloroquine, and these mediators failed to induce calcium activity in IL-1{beta}-responsive DRG neurons. Finally, scRNA-seq identified several genes upregulated in NP3 neurons after IL-1{beta} injection, including Alkal2, Bdnf, and Lcn2, associated with chronic inflammatory pain. Thus, our study unveils novel markers for IL-1R1+ nociceptors and reaffirms their selective role in inflammatory pain.

neuroscience↗

bioRxiv2026

Structural basis for emetine inhibition of ribosome translocation in Toxoplasma gondii

Apicomplexan parasites, including Toxoplasma gondii and Plasmodium falciparum, are major human pathogens that cause toxoplasmosis and malaria, respectively. The existing structures of T. gondii translational machinery are from empty ribosomes that lack several key components, including ribosomal protein RACK1 (Receptor for Activated C Kinase 1). Here, we used cryo-electron microscopy (cryoEM) to determine high-resolution structures of T. gondii ribosomal complexes, including a translating 80S ribosome bound to mRNA and tRNA. These structures reveal that RACK1 occupies the conserved binding site on the 40S subunit observed in other eukaryotic ribosomes. We also determined the architecture of the ribosomal P-stalk and identified the ribosomal proteins uL10 and uL11, which were not observed in previous T. gondii ribosome structures. In addition, we determined structures of the 80S ribosome bound to mRNA, tRNA, and the translation inhibitor emetine in two distinct conformational states. These snapshots reveal two mechanisms by which emetine inhibits the translocation step of mRNA translation: either by dislodging the mRNA from the E-site of the ribosome or by acting as a molecular glue within the E-site, thereby stalling translocation. Together, these findings provide new insights into the molecular basis of protein synthesis in apicomplexan parasites and establish a structural framework for the development of future antiparasitic therapeutics. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/740346v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@18b69d5org.highwire.dtl.DTLVardef@1d125e5org.highwire.dtl.DTLVardef@efc11org.highwire.dtl.DTLVardef@1c6d088_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2026

Photo-thermal Bidirectional Coupling Model for Transcranial Photobiomodulation

BackgroundAccurate optical-field simulation is critical for precise dosage delivery in transcranial photobiomodulation (tPBM). Current simulations neglect photon absorption-induced tissue heating which leads to temperature-dependent alterations of the optical field, thus fails to account for the bidirectional photo-thermal coupling effect. ObjectiveThis paper aims to establish a dynamic photo-thermal couple model that rigorously quantifies the bidirectional interaction between tissue heating and light propagation, and improves the optical dose prediction. ModelWe propose a Photo-Thermal bidirectional coupling Model (PTM). First, the Pennes Bioheat Equation (PBE) is employed to model the thermal response induced by photon absorption. Second, a Real-time temperature-dependent Absorption coefficient Model (RAM) is newly developed to quantify the thermal effect. Third, the PBE and RAM are integrated into the photon diffusion equation, forming the PTM. Finally, this coupled framework is solved temporally by an unconditionally stable Crank-Nicolson scheme. SimulationsBenchmarking against an analytical solution (two-layer cylindrical domain) demonstrates that PTM reduces the temperature prediction error by over 2.35% compared to the uncoupled baseline. Simulations using a realistic head model reveal that, compared to PTM, uncoupled modeling underestimates energy deposition by 150 J/m3 and overestimates photon fluence by 3 J/m2 within just one minute, and such discrepancies will be amplified with increasing exposure duration and power. Furthermore, the PTM identifies a 1.43-mm advantage in penetration depth for pulsed-wave over continuous-wave modality under iso-energy conditions, a key insight enabled by the coupled modeling approach. ConclusionThe PTM provides a high-fidelity simulation framework that captures the dynamic, bidirectional photo-thermal coupling in tPBM, explicitly quantifying the thermal feedback ignored by current models and thereby enabling more reliable treatment optimization and safer clinical translation.

neuroscience↗

bioRxiv2026

A long-hidden prevalent PCR artifact and its application in DNA library screening

PCR artifacts can lead to aberrant DNA products and confound result interpretation, posing significant challenges in research and diagnostics. Traditionally, it has been blamed to misannealing of primers on unintended sites. However, by sequencing, we find that most PCR byproducts and artifacts actually have both primers bound correctly but lack a middle part of the target, a phenomenon we named as PCR leaping. The leaping occurs at random positions, is independent of sequence repeats and requires a single piece template, indicating an unprecedented mechanism. It is observed with various polymerases, template qualities, GC contents, and PCR programs, thus necessitating a reset of our PCR understanding and careful consideration in future studies, for example in CRISPR editing validations. On the other hand, it provides a simple way of DNA end pairing, based on which we develop a high throughput DNA library screening method for natural product discovery at substantially reduced cost.

molecular biology↗

bioRxiv2026

High glucose confers senescence resistance via GLUT1 epigenetic rewiring to blunt immunotherapy responses in esophageal squamous cell carcinoma

Therapeutic resistance and undefined predictive biomarkers severely hinder the clinical popularization of immunotherapy in esophageal squamous cell carcinoma (ESCC). Herein, we identify the glucose transporter 1 (GLUT1) as a critical determinant of immunotherapy resistance. Elevated expression of GLUT1 correlates with poor immunotherapy response and unfavorable prognosis in ESCC patients. GLUT1 deletion or inhibition enhances CD8 T cell infiltration and cytotoxicity, and sensitizes ESCC tumors to anti-PD-1 (-PD1) therapy. Importantly, dietary glucose restriction exhibits equivalent antitumor efficacy to GLUT1 inhibition when combined with -PD1. Mechanistically, GLUT1 establishes a positive feedback loop with HAT1 and FOXM1, which epigenetically remodels chromatin accessibility to suppress tumor cell senescence, thereby impeding CD8 T cell-mediated antitumor immunity. Our findings highlight GLUT1 as a predictive biomarker of immunotherapy resistance and suggest dietary glucose restriction as a viable strategy to potentiate immunotherapy efficacy in ESCC. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=188 HEIGHT=200 SRC="FIGDIR/small/738372v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@c2c5d5org.highwire.dtl.DTLVardef@14a34c7org.highwire.dtl.DTLVardef@cf05e4org.highwire.dtl.DTLVardef@18bc354_HPS_FORMAT_FIGEXP M_FIG C_FIG SHORT SUMMARYDong et al. identify glucose transporter 1 (GLUT1) as a predictor of poor response to immunotherapy in esophageal squamous cell carcinoma. GLUT1 promotes immune evasion by forming a positive feedback loop with the HAT1/FOXM1 anti-senescence axis, thereby epigenetically remodeling chromatin accessibility. GLUT1 inhibition or dietary glucose restriction restores CD8 T-cell-mediated antitumor immunity and improves the efficacy of anti-PD-1 therapy in preclinical models.

cancer biology↗

bioRxiv2026

Water as a thermal contrast agent for artificial-intelligence-enhanced in vivo mid-infrared thermography

In vivo infrared thermography is limited by the inherently poor spatial resolution at long wavelengths, low contrast, and the lack of biocompatible contrast agents. Here, we present 3-5 m mid-wave infrared (MWIR) thermography enhanced by an artificial intelligence (AI) network and cold phosphate-buffered saline (PBS) as a thermal contrast agent for noninvasive in vivo imaging with high contrast and resolution. MWIR imaging enabled high thermal sensitivity with microscale spatial resolution, strong relative thermal contrast, and facilitated visualization of the subcutaneous vasculature in the human arm, hand, ankle, the femoral artery and vein in rats, and the femoral vessels in mice, with image contrast further enhanced by AI networks. In a 4T1 tumor-bearing mouse model, AI-enhanced MWIR resolved early-stage tumors of [~]2.3 mm and metastases as small as [~]1.7 mm. Using cold PBS as a MWIR thermal contrast agent, we achieved precise tumor boundary visualization and real-time imaging-guided tumor resection. AI-enhanced MWIR offers a promising solution for early diagnosis and improved surgical precision.

bioengineering↗

bioRxiv2026

Near-Infrared II Scintillator for High-Resolution X-ray Imaging

Light scattering in scintillators is a pervasive problem and a key factor limiting X-ray imaging resolution. Here, we shift scintillator radioluminescence from the traditional visible range into the short-wave infrared (SWIR) or near-infrared II (NIR-II, 1000-3000 nm) window to mitigate light scattering and thereby enhance light penetration and X-ray imaging resolution. We present an NIR-II MgGa2O4:Ni2+ scintillator with peak emission at 1340 nm, achieving a threefold improvement in X-ray imaging resolution compared with visible scintillators owing to reduced light scattering. This heavy-metal-free NIR-II scintillator exhibits intense radioluminescence comparable to that of conventional visible-emitting CsI:Tl, achieving a detection limit of 56 nanograys per second, [~]100-fold lower than typical doses used in medical imaging. We show that this NIR-II scintillator enables high-resolution X-ray radiography of electronic circuit boards and biological tissues.

biophysics↗

bioRxiv2026

Systematic Quantitative Proteomics Defines Age, Sex, and Region-Dependent Remodeling of Lung Extracellular Matrix

The lung extracellular matrix (ECM) governs tissue architecture, mechanics, and function, yet how it remodels with age across sex and anatomical regions remains poorly understood. Here, we performed a systematic multi-factor proteomic analysis of rat lungs to define age-, sex-, and region-dependent remodeling across the tissue landscape. Age emerged as the dominant source of variation, with a conserved aging signature modified by region- and sex-specific effects. Young lungs showed coordinated ECM assembly, balanced proteolysis, and active biosynthetic programs consistent with structural adaptability and mechanical resilience. In contrast, aged lungs exhibited accumulation of mature collagen crosslinks and a more stabilized matrix architecture, indicating progressive matrix maturation and reduced structural plasticity. These changes were accompanied by proteomic signatures of metabolic stress and immune activation, suggesting coordinated remodeling across ECM, metabolic, and immune pathways during lung aging. Aging effects varied across anatomical regions and were more pronounced in females, highlighting context-dependent trajectories within the broader aging program. Age also partially reshaped spatial proteomic heterogeneity across lung compartments. Together, these findings identify matrix stabilization as a central feature of lung aging that links structural remodeling to metabolic-inflammatory imbalance and increased pulmonary vulnerability.

biochemistry↗

bioRxiv2026

Lineage Memory and Convergent Adaptation Dictate the Single-Cell and Spatial Architecture of Brain Malignancies

How diverse cancer lineages navigate the draconian central nervous system environment--whether constrained by ancestral ontogeny or driven by convergent adaptation--remains a fundamental biological paradox. To decode this, we integrated extensive in-house and public resources to construct the largest single-cell atlas of primary and secondary brain malignancies (>550,000 cells). We demonstrate that malignant cells balance strict lineage imprinting with shared brain-adaptive programs, powerfully converging upon a dominant pan-cancer mesenchymal (MES)-like state alongside a SYT1+ pioneer subpopulation exploiting neuronal mimicry. Concurrently, the microenvironment undergoes lineage-constrained divergence. The myeloid landscape shifts from a resident-dominated architecture in gliomas to extensive blood-borne infiltration in metastases. Lymphoid responses parallel this, crowning laryngocarcinoma as an ultra-hot subtype and revealing that massive T cell influx in highly infiltrated niches is paradoxically driven into terminal exhaustion, contrasting with severe immune exclusion in cold tumors. Furthermore, stromal-vascular adaptation couples pro-angiogenic tip-endothelial activation with a dynamic opposition between structural extracellular matrix (ECM) deposition and focal proteolytic degradation. Anchored by the pan-cancer MES adaptation, we leveraged subcellular spatial transcriptomics to redefine the microenvironment around four MES-like architectural niches, mapping an evolutionary trajectory from perivascular entry to immunosuppressive stromal remodeling. Finally, projecting these architectures onto independent clinical cohort establishes the MES-S2 proliferative niche as the primary driver of severe clinical deterioration across both transcriptomic and proteomic dimensions.

Cancer Biology↗

bioRxiv2026

Same-section spatial metabolo-transcriptomics using Stereo-meta-seq reveals DHA-driven kidney maturation

A central unresolved question in developmental biology is whether local metabolites merely accompany, or actively instruct, tissue maturation. Addressing this question requires direct spatial coupling of metabolic states with genome-wide transcriptional programs in situ at high spatial resolution, which existing approaches do not readily achieve. Here, we introduce Stereo-meta-seq, a workflow that integrates quantitative MALDI-MSI with Stereo-seq spatial transcriptomics within a single tissue section. A conductive adapter was designed to overcome the electrical incompatibility of non-conductive Stereo-seq chips with vacuum MALDI platforms, improving efficiency of MSI detection that preserves RNA integrity. MALDI laser-ablation marks are retained in downstream Stereo-seq data and serve as intrinsic fiducials for direct co-registration at 10 m or 20 m resolution, enabling fine grained spatial metabolite-transcript integration. Applying Stereo-meta-seq to human kidney development, we uncover selective enrichment of docosahexaenoic acid (DHA) in maturing proximal tubules. Functional studies in human kidney organoids demonstrate that DHA activates PPAR-and HNF4-driven transcriptional programs and promotes proximal tubule maturation in vitro and after transplantation in vivo. These findings identify lipid metabolism as an instructive regulator of human nephrogenesis and establish Stereo-meta-seq as a practical platform for dissecting metabolite-gene coupling and tissue heterogeneity in situ.

Cell Biology↗

bioRxiv2026

Generative design of antigen-specific T-cell receptor sequences with a conditional diffusion model

T cell receptor (TCR)-based immunotherapy holds immense potential for treating cancers, autoimmunity, and infectious diseases, where antigen-specific TCR recognition is crucial for adaptive immune responses. Engineering or de novo generation of the complementarity-determining region 3 (CDR3) loops of TCRs using artificial intelligence offers a powerful alternative to designing antigen-specific TCRs rather than laborious experimental screening. However, current in silico approaches are constrained by weak conditional guidance, limited flexibility, and a lack of rigorous functional validation. To address these limitations, we introduce TCRDiff, a generative diffusion framework for designing antigen-specific TCRs conditioned on peptide-MHC (pMHC) targets and germline-encoded TCR variable genes. By leveraging pre-trained knowledge from massive T-cell repertoires and TCR-pMHC recognition data, TCRDiff generates CDR3{beta} sequences that closely resemble native-binding TCRs via a denoising diffusion process. Furthermore, incorporating interface geometry features generated TCR-pMHC complexes with superior structural plausibility than models relying solely on sequence-based diffusion or structure-based modeling. As a proof of concept, we deployed TCRDiff in a systematic pipeline to design candidate TCRs against a clinically validated cancer antigen. In vitro activation assays validated that TCRDiff-generated TCRs efficiently recognize the MAGE-A3 epitope with minimal off-target reactivity. Thus, TCRDiff establishes a powerful, validated computational paradigm to accelerate the development of TCR-based immunotherapies.

bioinformatics↗

bioRxiv2026

Neural activity drives directional subarachnoid cerebrospinal fluid flow in the human brain

Neural activity is a potential driver of cerebrospinal fluid (CSF) dynamics and brain waste clearance, yet how neural activity shapes localized CSF flow in the subarachnoid space remains poorly understood in humans. Here we introduce an MRI framework that enables concurrent mapping of ultra-slow subarachnoid CSF flow at velocity scales of tens of micrometers-per-second together with hemodynamic activity measured by simultaneous functional MRI in the human brain. Using this framework, we found that neural activity drives spatiotemporally coherent, directional CSF flow in the subarachnoid space near sites of neural activation in awake humans. These flow responses were highly spatially specific, shaped by local cortical and subarachnoid anatomy, while exhibiting oscillatory temporal dynamics modulated by the stimulus cycle and strongly coupled to hemodynamic responses. These findings establish a link between neural activity, vascular dynamics, and localized subarachnoid CSF flow, and provide a framework for investigating neural-activity-driven CSF transport in humans.

neuroscience↗

bioRxiv2026

Mapping subarachnoid cerebrospinal fluid circulation in the human brain

The subarachnoid space is critical to cerebrospinal fluid (CSF) circulation and waste clearance, yet its flow organization in humans remains poorly characterized due to the lack of methods for direct, quantitative measurement of ultra-slow flow. Here we introduce slow-flow-sensitized phase-contrast imaging (SOPHI), which enables noninvasive quantification of ultra-slow flow velocities (e.g., [~]100 m/s) and directionality at high spatiotemporal resolution, allowing whole-brain mapping of complex CSF circulation in the human subarachnoid space. We found brain-wide, spatiotemporally coherent flow patterns characterized by strong cardiac-driven oscillations. Flow dynamics were closely coupled with vascular anatomy, exhibiting higher velocities and earlier responses in subarachnoid spaces near major arteries and a spatiotemporal propagative pattern to distal spaces. We further identified localized flow pathways associated with potential CSF efflux in ventricles and key subarachnoid regions. Together, SOPHI reveals a previously undercharacterized, highly organized CSF flow system, providing a macroscopic view of human CSF circulation and a framework for investigating brain fluid transport.

bioengineering↗

bioRxiv2026

Physiological trade-offs drive the archaeal dominance and carbon turnover in deep subsurface

Marine sediments host a vast deep biosphere, yet how microorganisms persist under severe energy limitation and govern long-term organic carbon (OC) preservation remains poorly understood. Here we show that archaea, primarily Bathyarchaeia, systematically displace bacteria with depth and form net growth zones across East China Sea shelf deep sediments. Multi-omics analyses and bioenergetic modelling reveal that this transition is driven by sustained archaeal metabolism of diverse recalcitrant OC compounds, and a physiological trade-off that prioritizes cellular maintenance over growth, minimizing mortality in deep sediments. This strategy triggers a fundamental shift in sedimentary carbon turnover: from rapid bacterial degradation of labile OC near the surface to persistent archaea-driven turnover of recalcitrant OC at depth. We estimate that Bathyarchaeia mediate [~]77% of total OC degradation after 1,000 years of burial, corresponding to [~]18% ([~]11.4 Pg C) of millennial OC degradation in global shelf sediments. These findings identify subsurface archaea as key microbial regulators of long-term OC preservation and reveal how physiological trade-offs sustain life and carbon turnover in the energy-limited deep biosphere.

microbiology↗