Biology subjects

Jiang, Y.

Publications and source records attributed to Jiang, Y..

At least 55 records · Page 3Linked to original sources

bioRxiv2026

The Nematicide Tioxazafen Disrupts Proteasome Function via Cytochrome P450 Bioactivation

Tioxazafen is an effective nematicide whose commercialization was halted because handlers reportedly developed rashes after working with seeds coated with a tioxazafen-laced cocktail. Here, we show that tioxazafen is bioactivated into toxic products by nematode and human cytochrome P450s. Through systematic analyses, we found that bioactivated tioxazafen disrupts proteasome function, leading to the accumulation of the NRF1 transcription factor ortholog SKN-1A in the nematode C. elegans, and a bounce-back transcriptional up-regulation of proteasome components. Genetic upregulation of the C. elegans proteasome supresses tioxazafens lethality, indicating that proteotoxicity is a key contributor to death. A survey of human P450s revealed that skin-expressed CYP1A1 toxifies tioxazafen and may account for the reaction to tioxazafen-coated seeds. We also found that rabbit CYP1A1 fails to bioactivate tioxazafen, which may explain the pre-market failure to detect robust adverse skin reactions. Our work highlights vulnerabilities in pre-market toxicological assays and a provides potential solution to prospectively identifying P450 toxication events. One-Sentence SummaryTioxazafen is bioactivated by cytochrome P450s into a proteasome disruptor.

pharmacology and toxicology↗

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

Spatial Topology Reveals Biologically Distinct Recurrent Motifs in Colorectal Cancer

Most spatial transcriptomic analyses of solid tumors focus on individual cell states or single-sample spatial domains rather than on recurrent multicellular tissue architectures shared across patients, and typically depend on predefined cell-type annotations or compartment definitions. We developed STORM (Spatial Topology analysis of Recurrent Motifs), an unsupervised graph-attention variational autoencoder that learns recurrent spatial motifs directly from cell-level graph structure and molecular profiles without cell-type labels, manual annotation, or predefined compartments. We applied to 32 Xenium sections from 16 patients with paired early-onset (EOCRC) and average-onset (AOCRC) colorectal cancer, STORM identified 10 recurrent motifs that self-organized into tumor-parenchymal, stromal, and immune macro-compartments. Among these, the Desmoplastic Fibrotic Barrier (DFB) motif, a CAF- and ECM-rich boundary architecture, was associated with restricted CD8+ T-cell geodesic access to tumor cores independently of CD8+ abundance, as demonstrated by abundance-normalized neighborhood enrichment statistics and within-sample mixed-effects models. EOCRC selectively amplified this barrier-exclusion architecture, exhibiting tighter tumor parenchyma, denser DFB shells, and a DFB-specific ECM activation program that yielded an age-specific prognostic signature in TCGA-COAD. Translation of motif macro-classes to H&E images via a Vision Transformer classifier produced an image-derived DFB-barrier composite that predicted overall survival in advanced-stage TCGA colorectal cancer. STORM provides an annotation-free framework for discovering recurrent spatial motifs and identifies a fibroblast barrier architecture whose topological association with immune exclusion is independent of effector abundance, amplified in early-onset disease, and translatable to a deployable pathology-based prognostic biomarker.

bioinformatics↗

bioRxiv2026

A geometric and dynamical theory of latent computations in biological neural networks

Many neural recordings have revealed low-dimensional sets of behaviorally relevant variables encoded within large-scale neural activity patterns. However, dimensionality reduction analyses alone cannot yield causal explanations for how networks stably implement computations that are resilient to the substantial variability of single neuron dynamics. Further, existing methods for dimensionality reduction often rely on simplifying assumptions about network structure that limit their applicability and explanatory power. To provide a theoretical framework describing the dynamics of low-dimensional computation in high-dimensional neural networks, here we introduce the concept of latent processing units (LPUs), which are architecture-agnostic computational elements operating within biological neural circuitry. Six theorems governing coding and computation by LPUs collectively provide explanations for a range of common biological findings: low-dimensional sets of coding variables can generate high-dimensional neural dynamics; many neurons have activity patterns that represent behaviorally relevant variables but exert little influence on downstream circuits; linear readouts of neural population activity commonly permit near-optimal decoding; the drift of neural representations is often substantial even while network computations remain intact. Overall, our treatment of LPUs, as enacted in network dynamics, unifies the geometric and dynamical views of neural computation under a joint framework and provides systems neuroscience with a causal account of how the brain executes reliable computations.

neuroscience↗

bioRxiv2026

A single-domain antibody targets aggregation-prone region of α-synuclein to reduce synucleinopathy, rescue neurodegeneration and improve function

Synucleinopathies are a group of neurodegenerative disorders characterized by the accumulation of aggregated -synuclein (-syn), including Parkinsons disease, Dementia with Lewy Bodies, and Multiple System Atrophy. These diseases are marked by locomotor and non-motor impairments, as well as mitochondrial dysfunction and the loss of dopaminergic (DA) neurons. We have developed several anti--syn single-domain antibodies (sdAbs) and demonstrated the diagnostic imaging potential of two of them and the acute therapeutic benefit of one in clearing -syn in a mouse model. However, whether these sdAbs can suppress -syn-mediated neuronal loss and locomotor impairment in vivo remains unclear. We evaluated the therapeutic potential of five anti--syn sdAbs to clear pathological -syn in mouse neuronal culture and then demonstrated their in vivo efficacy in a Drosophila model of synucleinopathy. The sdAbs differed in their efficacy to lower levels of phospho-serine 129 -syn, prevent loss of DA neurons, alleviate mitochondrial dysfunction, improve motor function, and prolong survival in synucleinopathy flies. The most effective sdAb, 2H1, has not been reported before. It binds strongly to the aggregation prone region of -syn and robustly improves all these disease parameters. Additionally, that sdAb is associated with -syn in the fly neurons, as shown through proximity dependent turboID biotinylation assays. The sdAb-turboID also biotinylated -syn-associated proteins involved in synapse/vesicle trafficking pathways, pinpointing the location of their intracellular interaction. Our findings provide an insight into the therapeutic mechanism of action of these sdAbs and strongly support their clinical development.

neuroscience↗

bioRxiv2026

Rett syndrome lifespan extension in mice via AI-guided ADAR editing

Rett syndrome is a severe neurodevelopmental disorder primarily caused by mutations in the MECP2 gene. A significant subset of severe cases are driven by nonsense mutations that generate premature stop codons, leading to loss of functional MeCP2 protein. Here, we describe a novel therapeutic strategy that uses endogenous adenosine deaminase acting on RNA (ADAR) enzymes to correct the R168X mutation at the RNA level. Using generative artificial intelligence trained on large empirical datasets, we engineered guide RNAs (gRNAs) that recruit endogenous ADAR to convert the mutant stop codon (UGA) into a tryptophan (UGG) to restore full-length MeCP2. Once incorporated into an optimized expression system based on endogenous small nuclear RNA regulatory elements and packaged into adeno-associated virus, these gRNAs enabled precise RNA editing at the target site with minimal off-target activity across the transcriptome while restoring full-length MeCP2 protein expression in patient-derived induced pluripotent stem cell neurons. Delivered intravenously to an R168X mouse model, the gRNAs achieved ~70% targeted RNA editing and substantially restored MeCP2 throughout the brain resulting in markedly improved Rett-like phenotypes and significantly extended lifespan. These findings demonstrate that AI-guided ADAR-mediated RNA editing is a precise and efficient technology for correcting nonsense mutations, with therapeutic potential for Rett syndrome and other genetic diseases.

neuroscience↗

bioRxiv2026

A missense mutation in FBXL3 links circadian regulation to out-of-season estrus in sheep

Seasonal breeding is a remarkable adaptive trait, but it constrains efficient production in the sheep industry. Recent studies have shown that seasonal breeding is associated with endogenous circannual rhythms, which are regulated in part by the circadian clock system. FBXL3, a pivotal component of the SCF (SKP1 - CUL1 - F-box) E3 ubiquitin ligase complex, is a known determinant of the mammalian circadian period. In this study, we identified a missense mutation, T183M, in FBXL3 through selective sweep analysis. The allele frequency of this mutation differed significantly between sheep breeds exhibiting year-round estrus and those showing seasonal breeding patterns. The association between the T183M mutation and seasonal breeding was further validated using an ovariectomized, estradiol-implanted sheep model. We then generated mice carrying the homologous T183M mutation and found that they exhibited significantly lengthened circadian periods, accompanied by reduced CRY1 expression and increased CLOCK expression. Co-immunoprecipitation assays confirmed that the mutation reduced the interaction between FBXL3 and CRY1. These findings demonstrate an evolutionarily conserved role of FBXL3 in the circadian clock system. We propose that the T183M mutation disrupts day-length recognition, thereby influencing seasonal estrus in sheep. Author summarySeasonal breeding limits sheep productivity and is regulated by circadian rhythms, yet the key genetic determinants remain poorly understood. Here, we identified an FBXL3 T183M missense mutation whose allele frequency differed markedly between year-round-estrous and seasonally breeding sheep, and validated its association with seasonal reproduction in a sheep population. Functional analyses in mutant mice showed that this variant lengthened the circadian period, disrupted the expression of core clock genes, and weakened the interaction between FBXL3 and CRY1. These findings suggest that the FBXL3 T183M variant impairs day-length perception, thereby modulating seasonal estrus in sheep. Our study reveals a conserved circadian mechanism underlying seasonal breeding and highlights FBXL3 T183M as a promising genetic target for improving reproductive performance in sheep.

genetics↗

bioRxiv2026

Intact learning and memory in mice incapable of de novo myelination

Motor skill learning stimulates and requires generation of oligodendrocytes (OLs) from their precursors (OLPs) in the adult mouse brain, but the functional role(s) of the newly formed OLs is not known. We asked whether new compact myelin sheaths are required, by genetic block of myelin basic protein (MBP) synthesis in adult OLPs and their newly-differentiating OL progeny, using tamoxifen-inducible Cre-lox recombination. Newly-differentiating OLs in these Mbp-cKO mice are unable to assemble compact myelin or normal nodes of Ranvier. Despite this, Mbp-cKOs learned a motor skill just as well as their wild type littermates. They also demonstrated normal contextual fear conditioning. Therefore, neither motor nor fear learning depends on rapid saltatory conduction in newly-myelinated circuits. Mbp-cKOs also formed normal long-term motor and contextual fear memories. Moreover, OL lineage-specific knockout of Monocarboxylate transporter-1 (Mct1), believed to be responsible for transferring metabolic substrates from OLs into axons, did not affect learning or memory consolidation. Myelin regulatory factor (Myrf)-cKOs, in which newly-differentiating OLs die and are rapidly eliminated, confirmed that newly formed OLs are required for learning and memory. Together, the data suggest that learning and memory depends on a non-canonical property of pre-myelinating or myelinating OLs, distinct from myelins cardinal role in speeding action potentials.

neuroscience↗

bioRxiv2026

Population-scale Y chromosome assemblies reveal recurrent remodeling within constrained architectures

The human Y chromosome is among the most structurally dynamic chromosomes in the human genome, yet much of its diversity remains unresolved because of extensive palindromes, ampliconic gene families, satellite-rich heterochromatin and large segmental duplications. What remained unclear was how these diverse forms of variation fit together across the full chromosome, how often similar structures recur in different lineages, and which aspects of organization remain constrained despite rapid sequence turnover. Here, we generated and analyzed 142 nearly complete human Y chromosome assemblies from 17 major haplogroups spanning approximately 180,000 years of evolution, creating a population-scale resource for studying Y chromosome biology and diversity. These assemblies show that structural change on the Y chromosome is recurrent but constrained, even in its most repetitive regions. In the fertility-associated azoospermia factor c (AZFc) region, recurrent inversions, deletions, and complex rearrangements generate a limited repertoire of structural haplotypes. Multicopy ampliconic gene families follow distinct evolutionary paths: DAZ paralogues differ in structural constraint, RBMY evolves within a modular array, and TSPY copy number varies mainly through local expansion and contraction. The centromere and Yq12 heterochromatin vary greatly in size but retain a stable higher-order organization, including a single hypomethylated centromeric core and conserved Yq12 repeat composition and orientation. Methylation across palindromic and ampliconic regions is likewise structured by repeat class, copy order and local architecture. Together, these results provide a population-scale resource for the human Y chromosome and show that its rapid structural evolution is repeatedly funneled into a limited set of architectural outcomes.

genomics↗

bioRxiv2026

rDNA breaks activate dsRNA pattern recognition through sense-antisense transcription

Myriad DNA damaging chemo- and radio- therapies interfere with ribosomal RNA (rRNA) transcription and processing, yet the biological consequences of these phenomena remain unclear. Here we show that aberrant transcripts emanating from rDNA breaks engage double-stranded RNA pattern recognition receptors, melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I (RIG-I) to activate immune signaling. rDNA damage abolishes full-length rRNA synthesis while generating truncated sense-antisense rRNA transcripts, whose accumulation is restrained by ATM and ATR kinase activities. Purification of the endogenous MDA5-filament coupled with sequencing identified complementary sense and antisense rRNA transcripts that terminate and initiate near the break site, respectively. This implicates aberrant rRNA species as a major source of damage induced endogenous ligands for dsRNA pattern recognition and establishes a mechanism by which nucleolar stress is coupled to immune signaling.

cell biology↗

bioRxiv2026

Aberrant cortical subcortical somatosensory network organization is associated with impaired tactile-motion perception in akinetic-rigid Parkinson's disease

BackgroundParkinsons disease (PD) is associated with somatosensory dysfunction, yet higher-order tactile-motion processing and its neural basis remain poorly understood. Here, we combined psychophysical assessment of tactile-motion perception with resting-state functional MRI (rs-fMRI) to investigate how altered sensorimotor network organization relates to tactile perceptual deficits in akinetic-rigid dominant PD (PDAR). MethodsForty-six participants (25 PDAR and 21 healthy controls, HCs) underwent clinical evaluation and resting-state functional MRI scanning. A subset of participants (15 PDAR and 15 HCs) additionally completed a tactile-motion perception task assessing directional bias and speed sensitivity. ROI-to-ROI functional connectivity analyses were performed within a customized 26-node sensorimotor and cortico-basal ganglia-thalamo-cortical (CBGTC) network. ResultsCompared with HCs, PDAR patients exhibited significantly altered tactile-motion perception, including greater directional bias (p = 0.047) and reduced sensitivity to dynamic tactile speed (p < 0.001), reflecting diminished sensitivity to mid-to-high speeds. Resting-state functional connectivity analyses revealed widespread reductions in connectivity within cortical somatosensory regions (Areas 1, 2, 3a, 3b, 5), particularly between primary somatosensory and motor cortices. In contrast, increased connectivity was observed between basal ganglia-thalamic structures and cortical sensorimotor regions, including thalamus-M1 and GPi-sensorimotor connections (all p-FDR < 0.05). ConclusionsThese findings demonstrate a dual pattern of sensorimotor network reorganization in PDAR, characterized by disrupted cortical somatosensory integration alongside enhanced subcortical-cortical coupling. The present study provides evidence that higher-order tactile-motion dysfunction in PD is associated with large-scale abnormalities in distributed sensorimotor networks and highlights the somatosensory system as a potential target for future therapeutic intervention.

neuroscience↗

bioRxiv2026

Spatially-Resolved Multiomic Atlas of Leiomyosarcoma Identifies Two Clinically Relevant Epigenetically-Driven Cell States

Leiomyosarcoma is a smooth muscle-derived malignancy marked by significant clinical heterogeneity. The extent and nature of cellular heterogeneity and molecular underpinnings remain poorly understood. To address this at transcriptomic and epigenomic levels, we performed single-nucleus multiome sequencing on untreated primary leiomyosarcoma tissues. Malignant cells segregated almost exclusively into two previously unrecognized and epigenetically distinct states: a dedifferentiated, mesenchymal-like subtype (MES) and a differentiated smooth muscle-enriched subtype (SMC). Chromatin accessibility profiling revealed strong enrichment of nuclear factor I (NFI) transcription factor motifs in MES cells, whereas AP-1 family motifs--most prominently FOSL2--were selectively accessible in SMC cells. Established leiomyosarcoma cell lines faithfully recapitulated these subtypes, and targeted depletion of NFI or AP-1 factors suppressed proliferation, invasion, and in vivo tumor growth, demonstrating functional dependency on these transcriptional programs. Spatial transcriptomics across 328 tissue cores from 128 leiomyosarcomas showed that immunosuppressive macrophages preferentially cluster around MES regions, revealing a subtype-specific tumor-immune niche. Clinically, MES-dominant tumors were associated with significantly worse patient outcomes. Through an epigenetic inhibitor screen, we identify and validate SMARCA4/2 inhibition as a promising therapeutic vulnerability for MES leiomyosarcomas. Together, this work defines two epigenetically driven, transcription factor-regulated, and clinically relevant states of leiomyosarcoma, revealing mechanistic underpinnings of tumor heterogeneity and uncovering actionable therapeutic strategies. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=93 HEIGHT=200 SRC="FIGDIR/small/726988v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@132928eorg.highwire.dtl.DTLVardef@133e3b7org.highwire.dtl.DTLVardef@1ab4398org.highwire.dtl.DTLVardef@e2de25_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2026

Cortical vasodynamics exhibit multiscale propagation structure in the awake mouse

Spontaneous vasomotor rhythms and fluctuations are recognized contributors to functional MRI (fMRI) signals. Yet the spatial evolution of vasomotor contributions, which bear on the interpretation of fMRI signals in terms of functionally connected brain regions, remains unresolved. To clarify this issue, we analyze the 0.01 - 0.20 Hz space-frequency modes of 14T cerebral blood volume (CBV)-weighted fMRI across the awake mouse cortex. High-resolution CBV-fMRI identified single-vessel-aligned, frequency-specific modes of vasodynamic propagation, and ultra-fast CBV-fMRI enabled mapping of phase-gradients along tangential and radial axes. Tangential gradients extended maps of vasomotor traveling waves across the entire cortical mantle, with a median speed of 0.9 - 1.3 mm/s. Radial gradients revealed approximately three-fold slower changes in timing that support lamina-dependent regulation of perfusion. Region-specific differences in propagation speed and direction occur across cortical areas and between mice. These findings reframe vascular fluctuations as a feature of brain-wide physiology, as opposed to residual noise.

neuroscience↗

bioRxiv2026

Immune Biomarkers of Islet Transplant Rejection Revealed by Synthetic Immunological Niche

Islet transplantation can restore glycemic control in type 1 diabetes, yet the heterogeneity of patient immune responses and transplant outcomes motivates the need for technologies to monitor the graft. Since transplanted islets are not readily accessible for biopsy due to their diffuse engraftment within the liver, clinical monitoring relies on measurements such as islet mass, blood glucose, and C-peptide levels, which are lagging indicators that change only after substantial graft injury. Here, we developed a minimally invasive synthetic immunological niche (IN) that captures graft-associated immune responses through serial subcutaneous biopsy. We evaluated the IN across murine syngeneic, allogeneic, and autoimmune islet transplant models, including CD40/CD154 costimulatory blockade with anti-CD40L. In syngeneic versus allogeneic recipients, IN identified immune populations and transcriptomic signatures that mirrored the graft and distinguished healthy from rejecting grafts. In anti-CD40L treated allografts, IN revealed innate macrophage- and dendritic cell-associated programs linked to graft acceptance versus rejection, whereas IN from untreated allografts showed stronger adaptive immune signatures. Longitudinal IN profiling further detected progressive inflammatory activation in accepted allografts, indicating persistent subclinical risk. Finally, in an autoimmune allograft model treated with anti-CD40L plus rapamycin, IN identified a 13-gene signature that separated early from late rejection trajectories and distinguished autoimmune-from alloimmune-associated rejection programs. Overall, these findings establish IN as a surrogate tissue for minimally invasive monitoring of islet graft and early detection of rejection-associated immune dysregulation. One Sentence SummaryAn engineered immunological niche captures distinct immune signatures of allo- and auto-mediated islet transplant rejection

bioengineering↗

bioRxiv2026

BiomniBench: Process-level Evaluation of LLM Agents for Real-world Biomedical Research

LLM agents now perform real biomedical research, but evaluating them rigorously is hard. Outcome-only benchmarks fail in two ways. First, a correct final answer can come from memorization, reward hacking, or wrong reasoning that produces the right number by chance. Second, valid alternative analyses are marked wrong simply because they differ from the reference. We introduce BiomniBench, a process-level evaluation framework that scores the full agent trajectory against expert-designed, task-specific rubrics. Our first release, BiomniBench-DA, contains 100 data-analysis tasks across 17 task types, 5 disease areas, and a general-biology category, each based on a paper from journals such as Nature, Cell, and Science and co-developed with an original author or a domain expert. Benchmarking frontier and open-weight models across four agent harnesses reveals three findings. Frontier and open-weight bases cluster within a few points of each other, with substantial headroom for all models. The agent harness shifts scores by more than the gap between successive model generations. Agents reliably ground claims in real sources yet consistently fall short on method selection, biological interpretation, and scientific reasoning. BiomniBench is the first process-level benchmark for LLM agents in biomedical research, providing the dimension-level diagnostics that outcome scoring cannot. Datasethuggingface.co/datasets/phylobio/BiomniBench-DA

bioinformatics↗

bioRxiv2026

Structural brain networks shape individual-level progression of brain atrophy after stroke

Stroke starts as a focal vascular lesion, but its structural consequences often extend beyond the lesion site, resulting in distributed brain atrophy whose organizing principles remain unclear. Here, using longitudinal MRI data from two stroke cohorts spanning the hyperacute to chronic stages, we tested whether and how post-stroke grey matter volume (GMV) change over time is constrained by large-scale brain networks across individuals. Coordinated deformation modelling showed that longitudinal GMV atrophy patterns were more strongly shaped by structural than by functional connectivity, with structural constraints already detectable in the acute phase. Network diffusion modelling further showed that atrophy patterns at 3 and 12 months were consistent with lesion-initiated propagation on the structural connectome, whereas model performance was weak in the early acute stage. The model-derived propagation stage did not increase monotonically with chronological time, indicating that it reflects the degree to which observed atrophy conforms to a network-consistent diffusion-like pattern rather than elapsed biological time. Inter-individual variation in propagation stage was associated with lesion size and with the topological and molecular properties of lesioned regions. Finally, lesion information combined with network diffusion modelling supported individualized prediction of later GMV atrophy patterns. These findings provide a network-based account of secondary degeneration after stroke and may inform individualized characterization of post-stroke structural reorganization.

neuroscience↗

bioRxiv2026

A shared neural code for gender across faces, bodies, and objects in the human brain

Humans can readily infer gender from diverse visual categories, including faces, bodies, and objects, yet it remains unclear whether the brain constructs a shared, category-general representation of gender. To fill the gap, we measured neural responses using fMRI while participants viewed female and male stimuli across these three categories. Multivoxel pattern analyses revealed that gender information was encoded throughout distributed occipitotemporal regions for all categories. Critically, cross-category decoding and regression-based representational similarity analyses converged on a region of the right middle temporal gyrus (rMTG) that encoded gender independently of stimulus category. This region also carried category information, indicating mixed selectivity. Comparisons between neural representational dissimilarity matrices and those from a fine-tuned convolutional neural network (CNN) showed that rMTG activity most closely resembled intermediate CNN layers, suggesting that shared gender representations rely on mid-level visual features. Finally, functional connectivity analyses revealed that gender-related interactions among occipitotemporal regions were similar for faces and bodies but not for objects. Together, these findings identify a category-general neural hub for gender perception and illuminate how mid-level visual features and distributed networks support the abstraction of gender across heterogeneous visual inputs.

neuroscience↗

bioRxiv2026

Robotic perturbation proteomics and AI agents enable scalable drug mechanism discovery

Large-scale mass spectrometry-based proteomic screening could reveal cellular mechanisms of drug action at systems resolution but remains limited by experimental complexity and the difficulty of extracting insight from high-dimensional datasets. Here, we describe an end-to-end platform that combines semi-automated sample preparation, rapid LC-MS/MS, and AI agent-based data analysis to enable scalable proteomic screening. In a screen of 172 compounds in HepG2 cells, we generated 1,232 proteomes with more than 8,700 quantified proteins in approximately three weeks. Agentic AI reduced data analysis and interpretation time to less than one day while translating proteomic measurements into structured mechanism-oriented summaries and experimentally testable hypotheses. Guided by this framework, we validated: (1) a cholesterol-lowering effect of methylene blue in vitro and (2) an association between loratadine exposure and increased circulating iron in matched electronic health record analyses. This work establishes a scalable platform for generating proteomic drug perturbation data and automatically converting that data into mechanistic insights and candidate translational hypotheses using AI.

systems biology↗