Biology subjects

Jiang, X.

Publications and source records attributed to Jiang, X..

At least 55 records · Page 3Linked to original sources

bioRxiv2026

Brain Structure Shapes Function through higher-order Functional Interactions

Brain function is deeply embedded within multiscale structural architecture. Conventional studies predominantly utilize pairwise connectivity networks to investigate structure-function relationships. However, this low-dimensional perspective overlooks multi-region collaborations for complex cognition. Consequently, whether and how anatomy constrains such higher-order functional networks remains unresolved. To address this pivotal question, we utilize an information-theoretic O-information approach to characterize higher-order functional interactions (HOIs). By reconstructing individual-level HOIs from multimodal structural networks, we directly validate the structural constraint on HOIs. The resulting reconstruction coefficients are defined as structural-functional constraint strength (SFCS), serving as a quantitative vehicle to decipher how anatomy shapes these higher-order networks. SFCS uncovers a highly heterogeneous structural constraint landscape across data modalities, spatial regions, and informational interaction modes. Crucially, individualized SFCS robustly predicts multi-domain cognitive phenotypes, showing higher sensitivity for informant-reported than patient-reported assessments. Finally, we show that this landscape undergoes pathological, mode-specific reorganization in Alzheimers disease. Cross-scale alignment with spatial transcriptomics further demonstrates that this macroscale network remodeling is coupled with microscale metabolic and regulatory gene pathways. Collectively, our findings not only validate the structural constraint on higher-order functional networks but also decipher its precise underlying mechanisms. This constraint paradigm plays a pivotal role in shaping diverse cognitive capabilities, while its pathological disruption in Alzheimers disease highlights the potential of SFCS as a biomarker for tracking neurodegenerative network impairments.

neuroscience↗

bioRxiv2026

Testing the waters of macrophyte biodiversity with multiscale spatial analysis of public lake monitoring data

Freshwater monitoring programmes like the European Unions Water Framework Directive (WFD) provide a wealth of data on European lake status, including water quality and macrophytes (aquatic plants) as critical habitat features that support health of humans and wildlife. Easier WFD data access can enable external management and research to better safeguard human and natural freshwater use. We demonstrate a replicable workflow to easily download and process multi-year (2007-2024) observations of lake macrophytes (425 sites) and complementary water quality variables (202 sites) from Swedish WFD data. Then, we illustrate the value of improved data access to address ecological questions that drive conservation, investigating how spatial scales influence macrophyte richness and associated water quality relationships using a spatial random intercept model. Decomposing the spatial intercept links small scales (<10 km) to site-level gradients and large scales (>100 km) to biogeographical drivers. Stochastic and environmentally-structured processes coexisted at intermediate scales (10-100 km). Adding water quality rarely improved overall predictive performance of macrophyte diversity models but consistently influences the role of different spatial scales. Water quality variables showed consistent spatially structured variation at intermediate scales and unique spatial patterns in tandem, overlapping with large-scale biogeographical influences. Altogether, we show context-dependencies for spatial model interpretation and provide guidance in accounting for spatial confounding to improve inferential and predictive performance. Our workflow and results show a clear way forward for accessing high-quality macrophyte and water quality data sets and their utility for addressing ecological questions that guide macrophyte protection under the WFD. HighlightsO_LIyears Swedish of macrophyte and water quality monitoring data were extracted. C_LIO_LIrichness showed scale-specific patterns linked to geographic gradients. C_LIO_LIbest predictive models for richness had no water quality at all. C_LIO_LIoverlap in their spatial scales and must be carefully separated. C_LIO_LIpen access data and multiscale analysis can apply to many ecological questions. C_LI

ecology↗

bioRxiv2026

Genetic Modeling of Dyadic Behavioral Traits: Implications for Estimation and Interpretation of Variance Components

Studying the genomic control of dyadic social interactions is gaining traction in animal genetics. However, genetic modeling of social interactions poses several challenges, one of which is whether social interactions should be treated as dyadic traits or as aggregated traits at the individual level. In this study, we systematically compared two approaches: dyadic models using dyadic traits and marginal models using marginally aggregated traits and we derived the algebraic relationships between their variance components. In the application, we used a published dataset on post-mixing aggression in pigs, including both directed and undirected aggression records collected during the 9-hour period after mixing among 797 finishing pigs in 59 social groups, as an example to show how model choice can affect variance estimation. Results showed that dyadic models can estimate genetic effects and permanent environmental effects by exploiting repeated dyadic interaction records, thereby enabling a more complete understanding of the sources of variation underlying social interactions. In contrast, marginal models can bias the estimation and interpretation of genetic components, as the aggregated genetic variance may be confounded with other variance components due to the aggregation of dyadic traits. Marginal models may also lead to overestimation of social group and residual variance. These results can provide useful guidance for choosing appropriate modeling strategies for social interaction traits.

genetics↗

bioRxiv2026

BCMA/CD19 dual-targeting with FasTCAR: AZD0120 demonstrates potent preclinical efficacy in multiple myeloma

Chimeric antigen receptor (CAR)-T cell therapy has improved outcomes for patients with multiple myeloma (MM), but its broader use is restricted by manufacturing complexities and treatment-related toxicities. AZD0120 is a dual-targeting B-cell maturation antigen (BCMA)/CD19 CAR-T cell therapy manufactured via the rapid FasTCAR process. We developed a dual-targeting "loop" CAR that incorporates a novel humanized anti-BCMA single-chain variable fragment (scFv), clone SG, and an FMC63-derived anti-CD19 scFv. This AZD0120 CAR preserved functional binding to both antigens and conferred robust in vitro and in vivo cytotoxicity while maintaining single-antigen reactivity. Conventional manufacture of CAR-T cells with the AZD0120 CAR (AZD0120C) yielded cells with minimal tonic signaling, limited responsiveness to soluble BCMA, and preservation of naive/stem cell memory-enriched phenotypes, yet robust cytokine production upon BCMA+ target engagement. AZD0120C demonstrated cytotoxicity comparable to benchmark BCMA CAR-Ts across MM lines in vitro and showed strong in vivo expansion and tumor control in xenograft models. FasTCAR manufacturing - designed to shorten vein-to-vein timelines and enrich less-differentiated phenotypes - further enhanced in vivo performance: AZD0120 consistently achieved superior tumor control and greater CAR-T expansion vs AZD0120C across disseminated MM.1S, NALM-6, and JeKo-1 models, with superior efficacy observed at lower cell doses. Collectively, these data support clinical evaluation of AZD0120 as a differentiated BCMA/CD19 CAR-T cell therapy with the potential to improve disease control and patient access in MM. Key PointsO_LIAZD0120 is a dual-targeting CAR-T that displays a favorable anti-myeloma functional profile and co-targets a source of potential relapse C_LIO_LIThe FasTCAR process yields TN/SCM-rich CAR-T populations, promotes in vivo expansion and achieves potent tumor control in xenograft models C_LI

cancer biology↗

bioRxiv2026

Pseudomonas aeruginosa CRISPR-Cas primes a minimal proline-codon toxin to abort anti-CRISPR phages

Pseudomonas aeruginosa typically carries type I-F CRISPR-Cas systems, which are targeted by diverse (pro)phage-encoded anti-CRISPR (Acr) proteins. Here, we show that [~]26% of P. aeruginosa Cas effectors are reprogrammed by a regulatory RNA guide (CreA) to transcriptionally silence a conserved small RNA toxin (CreT) that arrests cell growth upon Cas inactivation. This toxin unprecedentedly employs two consecutive proline codons, thus termed "proline-codon toxin". Combined phylogenetic and genetic analyses unraveled that CreTA has forced P. aeruginosa to reject prophages whose Acrs disrupt Cas-DNA binding, which is essential for CreT repression. We further show that Acr-armed lytic phages designed to overcome CRISPR adaptive immunity can be instead aborted by CreTA-mediated defense in vitro and in a mouse model. Our findings unravel intra-genomic arms races between CreTAs and anti-CRISPR phages, and underscore the necessity of rational engineering of strain-specific therapeutic phages to penetrate the layered CRISPR and TA barriers of multidrug-resistant P. aeruginosa.

microbiology↗

bioRxiv2026

Discovery of BilV reveals a multienzymatic basis for bilirubin reduction across vertebrate gut microbiomes

Gut bacteria reduce bilirubin to urobilinogen, allowing it to be excreted through feces and urine, but studies have long noted a heterogeneous mixture of partially reduced bilirubin-derived intermediates, suggesting that multiple enzymes are involved. Here we identify bilirubin vinyl reductase (BilV), a novel Old Yellow Enzyme family reductase encoded in the genomic neighborhood of the known bilirubin reductase (bilR). Using heterologous expression and LC-MS/MS, we show that BilR acts on the methine bridges in the bilirubin reduction pathway; co-expression with BilV enables vinyl-group reduction and complete conversion to urobilinogen. In bacterial genomes, bilV co-occurs primarily with the bilR-insertion subtype and is largely absent alongside bilR-short. Analysis of 1,197 gut metagenomes across 14 vertebrate species reveals that this differential co-occurrence shapes pathway availability across hosts: carnivores and omnivores carry balanced bilR and bilV, whereas avian microbiomes, dominated by bilR-short, are depleted for bilV. These findings establish that bilirubin reduction to urobilinogen involves two enzymes with complementary regioselectivity, and that their distribution across vertebrate gut microbiomes varies in concert with host bile pigment chemistry.

microbiology↗

bioRxiv2026

A biointegrated living brain stimulator evokes specific neural signalling

Implanted brain stimulators play a crucial role in treating various neurological disorders, including Parkinsons disease (PD), Alzheimers disease, epilepsy, and depression. However, none of the existing implanted brain stimulators can realize specific neuromodulation due to fundamental disparities in signal transmission between electrical signal-induced neuronal responses and neurotransmitter-evoked neural signalling in natural neural circuits, leading to persistent challenges in biosafety and therapeutic effectiveness. Inspired by the dopaminergic neural circuit, we report a biointegrated living brain stimulator (BBS) that integrates ferroelectric bioelectronics, dopaminergic cells, and a gelatin hydrogel matrix, enabling dopamine neurotransmitter-evoked neural signalling. In contrast to conventional brain stimulators, the BBS are capable of programmed secretion of physiological-level dopamine, specifically activating nigral dopamine pathways and restoring motor function in a rodent PD model. By integrating the advantages of both bioelectronics and medicine, this lifelike BBS offers a great promise for next-generation bioelectronics, medicine, and brain-machine interfaces.

bioengineering↗

bioRxiv2026

Activating adaptor-like sequences in pericentrin mediate its transport by dynein

Right before a cell divides, the centrosome rapidly increases its size and microtubule organizing activity through a process termed centrosome maturation. PCNT, a coiled-coil centrosomal protein, is synthesized and transported to the centrosome simultaneously by dynein. This dynein-mediated co-translational transport of PCNT facilitates centrosome maturation and mitotic spindle formation. How dynein engages and transports PCNT, however, remains unclear. Here we find that PCNT residues 1393-1525 are required for mediating dynein-dynactin interaction. PCNT (1393-1525) also shares similar sequence features with canonical dynein cargo adaptors. PCNT is predicted to interact with dynein heavy chains through similar contact sites used by canonical dynein cargo adaptors. Introducing point mutations at those contact sites abolishes dyneinmediated transport in a peroxisome motility assay. Our results suggest that PCNT contains adaptorlike sequences to bind and activate dynein directly during its transport to the centrosome. Our data also suggest that dynein may engage with some of its cargoes directly without an adaptor.

cell biology↗

bioRxiv2026

High-Speed AFM Reveals Ligand-Dependent Supramolecular Switching of Human Phosphofructokinase-1

Phosphofructokinase-1 (PFK-1) catalyzes the ATP-dependent conversion of fructose-6-phosphate (F6P) to fructose-1,6-bisphosphate (F1,6BP), the first committed step of glycolysis. Beyond classical allostery, the liver isoform PFKL forms higher-order assemblies, but how ligand binding redirects intermolecular interactions remains unclear. Here we use high-speed atomic force microscopy (HS-AFM), topology-based AFM image simulations, and molecular dynamics (MD) simulations to define ligand-dependent assembly switching of human PFKL. Wild-type PFKL (PFKL WT) forms lattice-like assemblies under APO and ATP conditions, whereas coordinated ATP and F6P loading redirects assembly toward filaments in a ligand-order-dependent manner. APO-PFKL WT also forms lattice-like assemblies on or near membrane-supported surfaces, suggesting that interfacial environments influence where assembly initiates. The filament-defective N702T mutant forms ordered double-layer lattices and preserves this geometry under APO, ATP, and ATP+F6P conditions. MD simulations suggest that lattice stabilization arises from distributed inter-tetramer contacts. These findings define a structural framework for ligand-dependent supramolecular regulation of glycolysis.

biophysics↗

bioRxiv2026

Multimodal alignments of in vivo imaging and spatial biology datasets at cellular resolution

Parallel revolutions in intravital microscopy and spatial biology techniques have respectively enabled large-scale recordings of cellular dynamics in live animals and multi-dimensional molecular profiling at single-cell resolution. However, due to the challenges of aligning data from different modalities at cellular resolution, these two transformational approaches have generally been applied on separate biological samples, stymying the ability to link activity patterns and molecular attributes in the same exact cells. To enable routine, multimodal investigations of cells in vivo dynamics and molecular content, we created TRU-FACT (Total Registration Under Functional Activity, Connectivity, and Transcriptomics), a broadly applicable experimental and computational pipeline for registering large populations of individual cells across intravital imaging and spatial biology datasets. The pipeline combines three key innovations: an optomechanical tissue handling and alignment method to parallelize specimen planes, a graph-theoretic method to register individual cells based on their geometric relationships to neighboring cells, and a statistical framework that provides for each cell an a posteriori probability of correct registration. We validated TRU-FACT with several preparations for imaging neural Ca2+ activity in cortical and deep brain areas in head-fixed and freely behaving mice, RNA-barcode-expressing viruses for labeling neural projections, and low- and high-plex spatial transcriptomic methods. In mice performing a skilled reaching task, TRU-FACT alignments revealed the movement-related signaling patterns of intratelencephalic, extratelencephalic, and striatum-, superior colliculus-, and thalamus-projecting motor cortical neurons. Overall, TRU-FACT constitutes a scalable, multimodal discovery platform that is applicable to diverse tissue-types and spatial biology techniques, thereby enabling multiscale analyses of many complex biological systems.

neuroscience↗

bioRxiv2026

An Isoform-Centric, Structure-Aware Framework for Protein Function Prediction and Evaluation, Instantiated in 3DisoDeepPF

Understanding and accurately predicting function across protein isoforms has been a long-standing challenge with profound implications for both biological and translational research. However, most functional annotations and benchmarks remain tied to genes or reference protein sequences, leaving limited support for distinguishing protein isoforms from the same gene whose sequence, structure and domain composition may lead to different functions. To address this gap, we developed an isoform-centric framework for protein function and domain annotation that integrates a dense graph of sequence and structure similarity with protein features. We implemented this framework as 3DisoDeepPF, a graph-based multimodal model, and applied it to a breast cancer isoform atlas. Across canonical benchmarks and evaluations at isoform resolution, 3DisoDeepPF showed strong performance in predicting GO terms and Pfam domains and remained robust in tests with homology control. It further captured changes in Pfam domain composition among isoforms from the same gene, including reference-relative domain gain and loss. An evidence tracing module links predicted labels to supporting proteins in the graph, as illustrated by the calcium and integrin binding protein 1 (CIB1). Together, this study provides a framework informed by protein structure for function and domain annotation at isoform resolution, converting human protein isoform diversity into traceable functional evidence for cancer atlas interpretation.

cancer biology↗

bioRxiv2026

GlioVision: A Multi-Modal MRI Framework for Non-Invasive Glioma Molecular Biomarkers Prediction

Gliomas are aggressive primary brain tumors that necessitate critical molecular biomarker predictions for optimal clinical decision-making. Traditional assessment relies on surgical tumor specimens analysis, which carries procedural risks and sampling bias due to tumor heterogeneity. Existing deep learning methods for non-invasive prediction lack real-time applicability, remain resource-intensive, and are frequently trained on narrowly represented datasets. We present GlioVision, a framework built on the MONAI library to process multimodal data, including glioma MRI and molecular labels, to predict and identify, non-invasively, four major glioma molecular biomarkers: IDH mutation, 1p/19q co-deletion, MGMT methylation, and WHO grade. The core architecture comprises Spatially and Channel-wise Recalibrated 3D DenseNet (SCRU-DenseNet), which utilizes a computational attention gate and an Adaptive Contrast-Specific Processing Stream (ACPS) to tackle multi-site, heterogeneous datasets. We introduced the Confidence-Filtered Predictive Manifold (CFPM) to manage uncertainty by excluding predictions with low confidence. GlioVision is trained and validated on the largest multi-cohort datasets, achieving strong biomarker prediction with AUCs of (IDH 0.94, 1p/19q 0.87, MGMT 0.86, WHO grades 0.92), supporting molecularly defined glioma diagnosis under the WHO 2021 classification guidelines. Finally, we provide a Differential Training Integrity Assessment (DTI-A) to analyze routes of MRI data privacy protections through model obfuscation. Our results advance the codebase, model release, and leakage considerations around MRI data analysis literature.

neuroscience↗

bioRxiv2026

The tongue-brain axis mediates a hidden amino acid appetite

Selecting a diet containing all essential amino acids (EAAs) is critical for health. Following EAA deprivation, animals can select a nutritiously complete food source; however, the underlying mechanisms in vertebrates remain unclear. In mice, we show that leucine deficiency activates hypothalamic agouti-related protein (AgRP) neurons, which project to the paraventricular thalamus (PVT) via {gamma}-aminobutyric acid and are required for EAA deficiency-induced leucine appetite in mice. Furthermore, the peripheral tongue amino acid sensor general control nonderepressive-2 (GCN2) mediates acute EAA appetite via AgRP neurons. Together, these findings identify a tongue-AgRP-PVT circuit underlying EAA appetite, which is important for the rapid and accurate selection of essential nutrients.

neuroscience↗

bioRxiv2026

A cinnamyl alcohol dehydrogenase scaffold organizes monoterpenoid indole alkaloid biosynthesis

Biosynthesis of ~3,000 monoterpenoid indole alkaloids (MIAs), including the anticancer drug vinblastine, involves the highly unstable intermediate strictosidine aglycone. Its formation by strictosidine {beta}-glucosidase (SGD) and subsequent conversion by geissoschizine synthase (GS) occur in spatially separated compartments, representing a major biosynthesis bottleneck. Here we discover VinBLAST, a cinnamyl alcohol dehydrogenase-like protein repurposed as a scaffold for efficient processing of this labile intermediate. VinBLAST physically mediates SGD and GS interaction in the nucleus and allosterically enhances GS catalytic efficiency. VinBLAST homologues from diverse plant families enhance biosynthesis of several representative MIAs, with the production of catharanthine increased to ~160 mg L-1 in yeast, nearly 1,000-fold higher than previous studies. Our discovery provides a missing link in organizing MIA biosynthesis and enables scalable bioproduction of geissoschizine-derived therapeutics.

synthetic biology↗

bioRxiv2026

A transcriptomics-native foundation model for universal cell representation and virtual cell synthesis

Current single-cell foundation models rely on language-model architectures that ignore transcriptomic data distributions, often underperforming specialized methods. We introduce xVERSE, a transcriptomics-native foundation model coupling batch-invariant representation learning with the probabilistic generation of expression profiles. xVERSE outperforms the leading foundation and batch-effect correction methods in representation learning by 17.9% and 11.4%, respectively, successfully preserving biological heterogeneity while diminishing batch effects. Furthermore, xVERSE surpasses the second-best spatial imputation method by 34.3% and uniquely synthesizes virtual cells indistinguishable from biological data (AUROC{approx} 0.5). As a powerful data-augmentation engine, xVERSE utilizes these high-fidelity virtual cells to enable accurate clustering and marker detection in tiny datasets--resolving rare cell types with as few as four cells--while improving the generalizability of cross-modality predictions across diverse pathological states. These results establish xVERSE as a transformative framework unlocking analytical capabilities beyond conventional models.

cell biology↗

bioRxiv2026

FABP4 Couples Lipid Metabolism to PD-L1 Stabilization in Immunosuppressive Macrophages

Metabolic dysregulation in obesity reshapes immune function, but how lipid signals drive immune suppression remains unclear. Here, we identify a FABP4-PD-L1 axis that links lipid metabolism to immune checkpoint regulation in monocytes and macrophages. Single-cell transcriptomics revealed a distinct FABP4high immunosuppressive macrophage subset enriched under high-fat diet (HFD) conditions, characterized by impaired antigen presentation and elevated PD-L1 expression. Mechanistically, palmitic acid (PA) induces FABP4 and promotes PD-L1 palmitoylation, leading to its stabilization on the cell surface independent of transcriptional regulation. FABP4 is essential for this process, which enables PD-L1 surface stabilization, immunosuppression and mammary tumor progression. In humans, a conserved CD14intCD16 monocyte population exhibits elevated FABP4-PD-L1 signaling and correlates with obesity and invasive breast cancer. These findings establish PD-L1 as a metabolically regulated protein and reveal a mechanism by which lipid excess drives immune evasion, suggesting that targeting FABP4 may enhance responses to immune checkpoint blockade. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/717546v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1fe3f2corg.highwire.dtl.DTLVardef@e587a7org.highwire.dtl.DTLVardef@12d0f75org.highwire.dtl.DTLVardef@151f916_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIFABP4 defines a lipid-responsive, immunosuppressive monocyte/macrophage subset C_LIO_LIFABP4 links lipid sensing to PD-L1 expression in macrophages C_LIO_LIFABP4 enables palmitic acid-dependent PD-L1 palmitoylation and stabilization C_LIO_LIFABP4-PD-L1 signaling correlates with obesity and invasive breast cancer in humans C_LI

immunology↗

bioRxiv2026

Dormant Bacteria's Fatal Attraction to RNA Bacteriophages

Phages are the most abundant biological entities on Earth, yet RNA phages are strikingly scarce compared to their DNA counterparts--a long-standing mystery in phage biology. Here, we use dsRNA phage phiYY as a model to demonstrate that while RNA phages efficiently infect growing bacteria, they are gradually eliminated inside dormant bacteria through weak and time-dependent ROS-mediated damage. The RNA phages decline over days rather than through immediate clearance inside dormant bacteria. Accordingly, scavenging ROS with mannitol or overexpressing ROS degradation enzymes AhpB/TrxB2 rescues RNA phages from elimination. Crucially, because the underlying ROS-mediated RNA damage is minimal, RNA phage survival hinges on genomic redundancy. In single-phage infections, the lone RNA genome is highly vulnerable to cumulative damage and is eventually inactivated. In contrast, during co-infection by multiple RNA phages, the presence of multiple genome copies provides functional redundancy, thereby allowing a fraction of RNA phages to survive inside dormant bacteria. Given that most environmental bacteria are dormant and subject to heterogeneous phage infection, this copy number-dependent vulnerability offers a possible explanation for the scarcity, but not perish, of RNA phages in nature.

microbiology↗

bioRxiv2026

MTB-KB: A Curated Knowledgebase of Mycobacterium tuberculosis Related Studies

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), has regained its position as the worlds leading killer among infectious diseases. Despite extensive research progress across epidemiology, diagnosis, drug development, treatment regimens, vaccines, drug resistance, virulence factors, and immune mechanisms, MTB-related knowledge remains fragmented across thousands of publications, limiting its effective use. To address this gap, we present MTB-KB, a literature-curated knowledgebase that systematically integrates high-impact findings from eight major sections of TB research. The current release contains 75,170 associations from 1,246 publications, covering 18,439 entities standardized using authoritative databases and WHO-endorsed classifications. A central feature is the interactive knowledge graph, which links cross-section associations to reveal and infer MTB-host interactions, treatment strategies, and vaccine development opportunities. MTB-KB also provides a user-friendly interface with browsing, advanced search, and statistical visualization. Overall, by consolidating dispersed MTB knowledge into a structured and accessible platform, MTB-KB provides a valuable resource for researchers, clinicians, and policymakers, supporting both basic and clinical TB research, enabling evidence-based TB prevention, diagnosis, and treatment, and contributing to global elimination efforts. MTB-KB is accessible at https://ngdc.cncb.ac.cn/mtbkb/.

bioinformatics↗