Biology subjects

Xie, K.

Publications and source records attributed to Xie, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Differential subcortical-cortical circuit reorganization in autism and ADHD

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) often co-occur and share symptoms as well as genetic risk factors. While subcortical-cortical networks have been implicated in both conditions, particularly involving thalamic and striatal circuits, patterns of shared and diverging disruptions remain unclear. Here we integrated resting-state functional connectivity (FC) and regression dynamic causal modeling (rDCM) across a transdiagnostic multi-site cohort. We used statistical group comparisons and individualized normative deviation mapping to map network deviations in ASD and ADHD relative to neurotypical controls and against one another. Multivariate associative techniques examined associations to clinical and cognitive phenotypes. Our transdiagnostic analyses revealed significant differentiation of ASD and ADHD across subcortical-cortical circuits. While ASD was characterized by widespread thalamocortical hyperconnectivity and bidirectional elevated coupling across thalamic subdivisions, ADHD exhibited a focal pattern of striatocortical disruption, anchored predominantly within the caudate. Multivariate analyses identified shared and disorder-specific brain-behavior associations. Across both conditions, aberrant striatocortical signaling was associated with reduced overall intelligence measures. Clinically, ASD-related thalamocortical connectivity disruptions mapped onto generalized cognitive impairment, whereas ADHD-related subcortical alterations tracked hyperactive and inattentive symptom dimensions. Our findings differentiate ASD and ADHD through distinct patterns of functional and directional subcortical-cortical dysregulations.

neuroscience↗

bioRxiv2026

Pan-cancer remodeling of reactive oxygen species homeostasis: distinct roles of the ROS-generation and antioxidant arms in immune context and outcome

Reactive oxygen species (ROS) are double-edged in cancer: tumor cells sustain high ROS generation while up-regulating antioxidant defense, so that the net balance between the two arms, rather than absolute ROS abundance, is the biologically meaningful quantity. Whether that balance defines a conserved tumor state across cancer types has been unclear. Here an experimentally measured ROS phenotype, obtained from a three-channel gold-nanocluster array, was generalized to public transcriptomes through a 107-gene ROS program scored in a large cell-line panel and in pan-cancer tumor and adjacent-normal tissue. The optical readout was reproducible and fully discriminative between cell lines, establishing the fingerprint as a quantitative starting point. In tumors, the generation and antioxidant arms were coordinately up-regulated relative to normal tissue, yet the two arms dissociated in their biology. The composite balance score tracked reduced immune infiltration consistently across cohorts, but arm-level decomposition showed that it was carried by low generation-arm activity in immune-cold tumors and followed arithmetically from how the balance score is defined; the association does not implicate antioxidant defense in immune infiltration. The clinical association pointed the other way: adverse outcome was attributable to the antioxidant arm, whereas generation was null. In cohort-held-out validation, tumors were separated from adjacent normal tissue, with redox programs outperforming generic phenotypic programs, indicating that the same program transfers across tumor types. Tumor remodeling of ROS homeostasis is therefore widespread, but its two arms carry distinct meanings: the balance score, driven by its generation term, reports immune context, whereas the antioxidant arm reports clinical risk.

cancer biology↗

bioRxiv2026

Reciprocal control of the stomach and intestine by viscerosensory neurons in caudal brainstem

Digestion requires precisely timed transit of food through the gastrointestinal tract. Here we show that emptying of food from the stomach occurs in discrete pulses, separated by pauses that allow the proximal duodenum to clear before the next bolus arrives. By combining X-ray fluoroscopy of the gut with calcium imaging of the brainstem, we identify a population of neurons defined by expression of neuropeptide FF (NPFF) that tracks these duodenal dynamics. Stimulation of NPFF neurons induces a coordinated response that inhibits gastric emptying and accelerates intestinal transit, thereby clearing the proximal intestine for the next bolus of food. These neurons also bidirectionally control food intake through cholinergic signaling in the gut. These findings reveal a mechanism by which brainstem transforms the sensory detection of nutrients in the duodenum into the opposing control of the stomach and intestine. They also establish an experimental approach for dissecting gut-brain signaling in behaving animals.

neuroscience↗

bioRxiv2026

Individual-level expression deconvolution and assessment of cross-sample variation

Recovering cell-type-specific gene expression from bulk RNA sequencing would facilitate the study of transcriptional variation among individuals. However, accuracy can differ substantially among genes and cell types. We describe a reference-informed Bayesian deconvolution framework and a score that identifies gene--cell-type pairs likely to have more accurate estimates of cross-sample variation. The score uses bulk counts, reference expression profiles, and estimated RNA proportions. Known component expression is used to train and evaluate the score, but is not needed to calculate predictions from a trained model. We evaluated the approach in a ROSMAP-derived simulation with 40 target donors, 2,000 genes, and seven cell types. Median gene-wise correlation was 0.801 for raw allocated counts and 0.296 after normalization within each donor and cell type. To evaluate the score, we divided genes into five sets, kept linked genes together, and scored each set using a model trained on the other four. Retaining approximately 20\% of pairs within each cell type increased the median normalized correlation to 0.622. Ranking pairs only by the estimated share of a gene's bulk RNA contributed by the cell type yielded 0.570 at the same retained count. These results show that observable information can help prioritize pairs with more accurately recovered cross-sample variation.

bioinformatics↗

bioRxiv2026

Multiscale alterations and cortex-wide organizational trends in focal cortical dysplasia

BACKGROUND AND OBJECTIVESFocal cortical dysplasia (FCD) is a leading cause of surgically remediable pharmaco-resistant epilepsy. Previous research has used various MRI sequences to profile FCD lesions, but multi-site studies using personalized features derived from sequences routinely used in the clinic are sparse. This study aimed to quantify changes in cortical morphology, myeloarchitecture, and function within FCD lesions, compare MRI signatures between lesion subtypes and outcomes, and investigate links to macroscale brain organization. METHODSThis cross-sectional study included patients with FCD-related epilepsy aggregated across 3 datasets from Canada and Germany. The 3T MRI acquisitions included T1-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, with the addition of a resting-state functional sequence for two datasets. We derived cortex-wide maps of patient-specific variations in morphology, myeloarchitecture, and function. Variations were quantified in lesions, ipsilateral cortex, and homotopic regions using age- and sex-adjusted normative models. Subgroup analyses explored the role of histological subtype and surgical outcome. Variations were also related to anterior-posterior and sensory-association organizational gradients. RESULTSWe included 159 patients with epilepsy and FCD (47 % female) and 183 healthy control participants (50 % female). Lesions exhibited changes in morphology (cortical thickness; FLAIR blurring) and in specific measures of depth-dependent intracortical myelin (variance and kurtosis of intracortical myelin profiles across depths), but not in local function (regional homogeneity; node strength). Spatial contextualization indicated more pronounced thickness changes in transmodal association cortices, while increased blurring of the gray-white matter interface co-localized with posterior cortical regions. FCD Type IIb lesions contained more marked changes in blurring and depth-dependent intracortical myelin (kurtosis of intracortical myelin profiles across depths) than Type IIa lesions. DISCUSSIONOur findings provide robust evidence that multiscale MRI profiling can identify FCD signatures and contribute to in-vivo subtyping. Furthermore, the novel use of myeloarchitecture profiling and contextualization with macro-scale brain gradients provides new avenues to understand intracortical alterations and the embedding of FCD lesions into broader organizational patterns.

neuroscience↗

bioRxiv2026

Synovium-Restricted Armored PD-1-Targeted CAR-T Cells Reprogram Immunity and Resolve Experimental Arthritis

Despite major therapeutic advances, a substantial fraction of patients with autoimmune disease remains refractory to treatment. While B cell-targeted CAR-T therapies have shown considerable efficacy, the central contribution of pathogenic T cells to rheumatoid arthritis (RA) suggests that complementary T cell-directed strategies may enable deeper disease control. Using single-cell multi-omics of human RA and experimental models, PDCD1 was identified as a selective marker of synovial disease-associated T cells. We developed PD-1-directed CAR-T cells that potently eliminate these cells in vitro and in vivo, leading to marked attenuation of synovitis in RA models. To limit off-target activity, we engineered NR4A2-driven CAR-responsive biosensors to restrict CAR activity to inflamed synovium. To couple anti-PD-1 CAR-mediated cytotoxicity with microenvironmental modulation, we further engineered these CAR-T cells to secrete soluble TNF receptor II (sTNFRii), counteracting baseline inflammation and CAR-induced IFN response and promoting a tissue-reparative myeloid state. PD-1-targeted CAR-T therapy thus represents a promising, specific, and safe strategy for autoimmune diseases involving disease-associated T cells.

immunology↗

bioRxiv2026

FUNCTIONAL FRAGMENTATION AND STRUCTURAL DRIVERS OF THALAMO-CORTICAL CIRCUITS IN TEMPORAL LOBE EPILEPSY

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSObjectiveC_ST_ABSIn temporal lobe epilepsy (TLE), the thalamus acts as a nexus in a pathophysiological network that implicates mesiotemporal, subcortical, and neocortical regions. Studying a large multimodal and multicentre dataset, we profiled thalamic, hippocampal, and neocortical functional connectivity (FC), assessed structural mediators, and examined clinical associations. MethodsWe studied resting-state FC alongside structural and diffusion MRI data in 250 unilateral TLE patients and 259 healthy controls, with measures aggregated across four independent datasets. Data were processed using open-access neuroinformatics workflows and analyzed at a subregional level to maximize anatomical precision. Statistical analysis and mediation models assessed between-group FC changes, structural contributors, and clinical correlations. ResultsCompared to controls, TLE patients presented with reduced thalamo-cortical FC, which was most marked in mesiotemporal, fronto-central, and occipital regions. Thalamo-hippocampal FC was also reduced, with effects seen in all CA subfields. In the thalamus, FC reductions peaked in the ventral posterior nucleus when considering neocortical target regions and in the mediodorsal nucleus when considering hippocampal target regions. While ipsilateral hippocampal volume and diffusion changes mediated thalamo-hippocampal FC, thalamo-cortical FC appeared decoupled from structural alterations. Findings were consistent in left and right TLE patients, in patients with short and long disease duration, and across imaging sites, suggesting that thalamo-cortical FC imbalances are a consistent signature of TLE. Conversely, thalamo-hippocampal FC was elevated in patients with focal-to-bilateral-tonic-clonic seizures and FC alterations were more marked in the subgroup of operated patients that became seizure-free after surgery. ConclusionOur multi-site findings demonstrate marked thalamic circuit fragmentation in TLE. Ipsilateral findings robustly showed subdivision-specific effects, which point to both mesiotemporal co-lateralization as well as broader system-level involvement. Mediation analyses furthermore confirmed a key role of hippocampal pathology in disrupted thalamo-hippocampal connectivity in TLE, while broader thalamo-cortical fragmentation becomes increasingly independent of mesiotemporal compromise. Critically, thalamic FC represents a network substrate for seizure generalization and can serve as a prognostic indicator for surgical outcome. These results underscore the contribution of the thalamus as a hub in macroscale dysfunction in TLE.

neuroscience↗

bioRxiv2026

Opposing GIPR brainstem circuits differentially control feeding behaviour

Central glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling is required for the efficacy of GIP-based obesity therapeutics, yet how distinct subpopulations of GIPR neurons shape appetite remains undefined. Here we show that GIPR neurons in adjacent brainstem nuclei, the area postrema (AP) and nucleus tractus solitarius (NTS), exert opposing control over ingestion. We find GIPRAP neurons dampen post-ingestive satiation, permitting hyperphagia, whereas GIPRNTS neurons are anorectic. In line with this model, we show Gipr expression in AP, but not NTS, neurons is necessary for appetite suppression following GIPR antagonism. Additionally, we reveal that GIPR neurons in the AP and NTS occupy distinct gut-brain circuits, and are differentially sensitive to obesity-driven circuit remodelling. These data offer a framework for understanding how current GIPR agonist and antagonist strategies elicit weight loss.

neuroscience↗

bioRxiv2026

Functional segregation of body-brain signals in the area postrema

Nausea arises from activation of specialized neurons in the area postrema (AP)1-8. The AP also mediates much of the satiety produced by GLP1R agonists9-12, suggesting a broader role in non-aversive physiology, yet the functions of AP cell types are not well understood. Here, we have used optical recordings in behaving mice to systematically define the natural regulation of an array of AP neurons, including the cell types that are principal targets of widely-used weight loss drugs. We discover that neurons expressing GFRAL, the receptor for the sickness-related hormone GDF15, are unexpectedly activated when mice consume food rich in fat. This fat-specific GFRAL neuron activation is required for fat satiation but does not involve GDF15 or canonical gut-brain pathways. Instead, "anti-nausea" neurons expressing GIPR, which directly inhibit GFRAL neurons, are selectively activated by sugar, enabling macronutrient-specific gating of GFRAL responses. In addition, we show that CALCR neurons link intestinal hyperosmolality to the suppression of feeding, whereas PRLHR neurons respond to changes in blood volume and pressure. These findings reveal a broad role for AP cell types in sensing and responding to physiologic signals unrelated to nausea. They also reveal that GFRAL and GIPR neurons, which are key targets of the weight-loss drug tirzepatide, have a natural function in sensing ingestion of fat and sugar, respectively.

neuroscience↗

bioRxiv2026

Host genetic regulation of fermentation-related cecal microbial taxa is associated with loin muscle deposition in meat rabbits

Loin muscle weight is an important indicator of carcass yield in meat rabbit production, but the host genetic and intestinal microbial factors associated with its variation remain poorly understood. Because the cecum is the primary site of hindgut fermentation in rabbits, we integrated whole-genome resequencing, cecal transcriptome profiling, and cecal and rectal 16S rRNA sequencing data from 321 Kangda meat rabbits, with rectal microbiome data used as a downstream comparative reference. Compared with the rectum, the cecum contained a richer microbial community, with more ASVs and genera and significantly higher microbial diversity, whereas predicted metabolic functions were largely conserved between the two segments. Loin muscle weight showed moderate SNP-based heritability (h{superscript 2} = 0.39), and the cecal microbiome explained a smaller but detectable proportion of phenotypic variation (m{superscript 2} = 0.13). Multi-strategy microbial screening identified 19 candidate cecal genera associated with loin muscle weight, with Methanosphaera showing the strongest negative association. Host GWAS prioritized candidate loci near MEX3C and TCF4 on chromosome 10, and integration of cecal cis-eQTL and GWAS summary statistics further prioritized GJB3 as a candidate gene associated with loin muscle weight. Consistent with the cecum-centered model, host genetic relatedness was weakly but significantly correlated with cecal microbial similarity, whereas no such global association was observed for the rectal microbiome. Microbial GWAS and SMR analyses further prioritized a cecal MRAP2-Methanobrevibacter association as the main host-regulated microbial signal, while rectal analyses identified distinct segment-specific signals, including SULF1-Roseburia. These findings suggest that host genetic variation may be linked to loin muscle deposition partly through cecal gene expression and fermentation-related cecal microbial taxa, with the rectal microbiome providing comparative evidence for hindgut segment specificity. This study provides candidate host and microbial targets for future functional validation and microbiome-informed nutritional strategies to improve carcass traits in meat rabbits.

genetics↗

bioRxiv2026

Sex-related structural alterations across common epilepsies: a worldwide ENIGMA study

Epilepsy is characterized by widespread structural brain alterations extending beyond the epileptic zone, involving both cortical and subcortical regions. Importantly, the clinical manifestation of epilepsy, including seizure types, psychiatric comorbidities, and treatment responses, has been shown to differ between sexes. However, sex differences in structural alterations in epilepsy have been seldomly reported in neuroimaging studies, partly due to limited sample sizes and single-center designs. Here, we systematically investigated sex differences in common epilepsies and their related clinical variables using structural neuroimaging biomarkers in an international multi-center cohort of 1,253 epilepsy patients and 1,077 healthy controls. We studied cortical thickness and subcortical volume in two types of epilepsy: temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE). Both male and female patients with TLE showed widespread cortical and subcortical thinning compared with controls. In GGE, when compared separately to controls, male patients showed only subtle structural alterations, whereas female patients exhibited more widespread structural alterations. Sex-stratified analyses revealed some variation in the extent and distribution of cortical thickness and subcortical volume alterations between male and female patients in both epilepsy cohorts. Yet, we did not find significant sex-by-diagnosis interaction effects in TLE and GGE. Similarly, no significant interaction effects were observed between sex and age of onset or disease duration in either patient group. Overall, although we observed some differences in regional cortical thickness and subcortical volume between male and female patients with epilepsy, we did not find significant sex-by-diagnosis interactions. Our findings indicate that sex differences in behavioral and clinical outcomes of epilepsy may involve biological or functional processes that require further investigation.

neuroscience↗

bioRxiv2026

MICAFlow: Fast and Robust MRI Preprocessing Bridging Research Neuroimaging and Clinical Practice

MICAFlow is a fully automated MRI preprocessing pipeline designed to translate advanced neuroimaging workflows from research into routine clinical practice. The pipeline emphasizes speed, robustness, and ease of use, focusing on structural and diffusion MRI. Key innovations include a Label-Augmented Modality-Agnostic Registration (LAMAReg) technique driven by deep learning segmentations for reliable cross-modal alignment, integration of state-of-the-art distortion corrections, and adherence to reproducible standards (Snakemake workflow, BIDSApp specifications). We describe the design of MICAFlow and evaluate its performance across heterogeneous datasets. First, accessibility: MICAFlow processes a multimodal MRI exam in minutes with clinically accessible hardware and without requiring GPU access, making it feasible for same-day clinical use. Second, registration accuracy: LAMAReg achieves cutting-edge multi-modal registration accuracy, yielding accurate alignment of diffusion MRI, FLAIR, and intra-subject T1-weighted images while remaining generally robust to common artifacts. Third, data reliability: Using identifiability, we show MICAFlow maintains consistent performance across diverse datasets, including subjects with pathology, and is closely comparable to contemporary pipelines. In sum, MICAFlows combination of machine learning and efficient workflows produces research-grade data quality with clinical-grade speed. This work demonstrates that advanced MRI preprocessing can be done fast and robustly, helping close the gap between research neuroimaging and broad clinical application of quantitative MRI techniques. The source code for MICAFlow is available here: https://github.com/MICA-MNI/micaflow, and for LAMAReg here: https://github.com/MICA-MNI/LAMAReg.

bioinformatics↗

bioRxiv2026

The discovery of missing taxane C13α-O-deacetylases re-delineates the biosynthetic pathway of paclitaxel

The prevalence of naturally occurring C13-acetoxy taxanes, together with the presence of a native C13-acetyltransferase in yew trees, suggests that the natural biosynthetic pathway for paclitaxel may involve a cryptic C13-O-deacetylation step. However, whether a putative taxane C13-O-deacetylase (T13dA) acts in the pathway of paclitaxel biosynthesis remains elusive. Herein, we functionally characterized two novel taxane C13-O-deacetylases (T13dA1 and T13dA2) from Taxus x media cell cultures, providing experimental evidence for the molecular and biochemical plausibility of C13-O-deacetylation in paclitaxel biosynthesis in Taxus species. Furthermore, T7dA1, a novel taxane C7{beta}-O-deacetylase with higher activity than the reported T7dA was discovered and characterized here. Notably, we reconstituted a new 19-gene pathway enabled by the integration of a C13-O-acetylation-deacetylation module for the de novo biosynthesis of baccatin III in Nicotiana benthamiana leaves, reaching a yield of 71{square} g{square} g-1 DW, much higher than that obtained from the 17{square} gene pathway lacking this module. These findings not only demonstrate the functional importance of the C13-O-acetylation-deacetylation module as a branch within the paclitaxel biosynthetic network, but also expand the multi-branched taxane metabolic network in Taxus and provide novel enzymatic tools and engineering strategies to facilitate heterologous pathway reconstitution and efficient paclitaxel production.

biochemistry↗

bioRxiv2026

Cardiac oxidative stress monitoring enabled by hierarchical mechanical adaptation

Soft bioelectronics have advanced cardiac monitoring through electrophysiological tracking, yet this alone cannot resolve the metabolic pathology essential to surgical decision-making. However, real-time molecular sensing on beating hearts remains unresolved due to deformation-induced sensor failure and stress-induced metabolite artifacts. This challenge is exemplified by ischemia-reperfusion injury (IRI), a major cardiac surgery complication characterized by reactive oxidative species (ROS) bursts, where true pathological ROS signals being confounded by mechanotransduction-induced ROS artifacts. Herein, we propose an enzymatic cardiac oxidative stress biosensor (E-cardiac) with hierarchical mechanical adaptation: macro-scale biofluid-mediated contact, micro-scale fiber reorganization, and nano-scale enzymatic confinement within gold nanoarches dissipate interfacial stress. This produces ultrathin ([~]460 nm), soft (0.79 kPa) E-cardiac with robust electrochemical stability (100% strain), low detection limit (380 nM), rapid adhesion (<3 s), stable biosensing on beating heart, as well as minimal invasive deployment capability. Mechanical analysis and cellular studies confirm mitigated stress-induced ROS and absent PIEZO channel activation. Validated across cardiomyocytes, ex vivo tissues, multi-species ischemia models (mouse, rat, rabbit, pig), rat ischemia-reperfusion injury, and Langendorff hearts simulating graded perfusion deficits, E-cardiac quantitatively differentiates IRI severity (sham < ischemia < reperfusion) as well as detecting the "ECG blind window". The E-cardiac platform provides real-time metabolic feedback for surgical guidance during cardiac procedures, enabling timely intervention before irreversible damage.

bioengineering↗

bioRxiv2026

Effect of dietary Chitosan supplementation on Intestinal Barrier Function and Growth Performance in weaned piglets challenged by Enterohemorrhagic haemolytic Escherichia coli

Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is an important zoonotic pathogen that disrupts intestinal epithelial barrier integrity and induces excessive inflammatory responses, thereby leading to impaired growth performance and intestinal injury. EHEC is also an important cause Hemolytic Uremic Syndrome (HUS) in children and older adults. In pig production, chitosan is considered a promising alternative to antibiotics due to its bioadhesive and antimicrobial properties, but the effects and underlying mechanisms of chitosan (COS) under pathogenic challenge remain to be elucidated. One hundred and eight pigs were randomly divided into three treatments: an unchallenged control group (CON), an EHEC-challenged control group (ECON), and an EHEC-challenged group supplemented with 100 mg/kg COS (ECOS). Results show that EHEC challenge increased the feed conversion ratio (FCR), increased inflammatory cytokine levels, disrupted intestinal morphology, and downregulated tight junction and nutrient transporter gene expression (P<0.05). Dietary COS supplementation significantly improved average daily gain (ADG) and FCR during day 6-14 (P<0.05). Moreover, COS reduced fecal shedding of total E. coli (P = 0.085) and EHEC, attenuated systemic inflammation by decreasing serum TNF- and IL-6 levels, and enhanced humoral immunity as indicated by increased IgA and IgM concentrations (P<0.05). Importantly, COS alleviated EHEC-induced intestinal injury by restoring villus height and villus-to-crypt ratio, with enhanced mucosal digestive enzyme activities, and upregulated expression of tight junction proteins (ZO-1 and occludin) and nutrient transporters (SGLT-1 and PEPT1) (P<0.05). In conclusion, these findings indicate that dietary COS improves growth performance in EHEC-challenged weaned pigs, with enhanced intestinal barrier integrity and nutrient transport capacity.

microbiology↗

bioRxiv2026

Connectome-wide mega-analysis identifies a reproducible functional network signature of temporal lobe epilepsy

Resting-state functional magnetic resonance imaging (MRI) studies have reported abnormal intrinsic functional connectivity (FC) across distributed circuits in patients with temporal lobe epilepsy (TLE), indicating a system-level impact of the disorder. However, findings remain inconsistent due to limited sample sizes and methodological heterogeneity, leaving the structural determinants and clinical relevance of FC alterations unresolved. To identify a robust and reproducible FC signature, we conducted a data-driven, connectome-wide mega-analysis in a large multicentre cohort of 652 participants (297 TLE, 73 disease controls, and 282 healthy controls) with multimodal 3T MRI and deep clinical phenotyping. We identified convergent FC reconfigurations at both group and individual levels that preferentially involved densely connected hubs, manifesting as hyperconnectivity in frontoparietal association systems and hypoconnectivity in temporal and paralimbic systems. Integrating structural cortical wiring features further revealed that these extensive alterations were constrained by corticocortical proximity, microstructural similarity, and white matter connectivity. Clinically, the FC phenotype tracked symptom burden and disease progression, informed postsurgical seizure outcome, and distinguished TLE from other focal epilepsies. Collectively, these findings systematically delineate a neurobiologically grounded, hub-centric pattern of intrinsic network disruption in TLE, anchored in temporolimbic and adjacent transmodal systems, with potential utility for individualized phenotypic stratification and outcome prognostication.

neuroscience↗

bioRxiv2026

Precision mapping and molecular contextualization of surgical outcome epicenters in temporal lobe epilepsy

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy is the most common drug-resistant epilepsy, with surgical resection offering the primary path to seizure freedom. Despite standardized approaches, a substantial proportion of patients experience seizure recurrence, and the neurobiological substrates underlying these divergent outcomes remain unclear. We applied an individualized normative modeling framework to multimodal preoperative MRI data in a group that subsequently underwent surgical resection, to characterize patient-specific structural deviations and identify disease epicenters. Patients who became seizure-free exhibited spatially coherent abnormalities localized to the hippocampus and ipsilateral association regions, anchored in agranular limbic territories and enriched for genes linked to calcium-dependent signaling. Non-seizure-free patients, on the other hand, showed a more heterogeneous and distributed pattern of deviations, consistent with a "temporal-plus" network organization, and broader neuromodulatory dysregulation. Crucially, overlap between resected tissue and network-defined epicenters was closely associated with seizure freedom, independent of total resection volume. These findings provide a multiscale framework for precision surgical planning, shifting the focus from standardized tissue removal to targeted disconnection of patient-specific pathological hubs.

neuroscience↗

bioRxiv2026

Sex-specific Genetic Regulatory Effects in Chickens

Sexual dimorphism is a defining vertebrate feature, yet its sex-specific molecular architecture remains poorly understood. Here we established a sex-balanced, uniformly reared chicken cohort to map this landscape, integrating individual whole-genome sequencing with 7,969 bulk and 779,380 single nucleus transcriptomes across 32 tissues from 280 birds. We identified 495,098 independent expression quantitative trait loci for 20,194 genes, including 10,937 loci modulated by cell-type composition. Notably, 340 genes were regulated by 449 loci in a sex-dependent manner, significantly enrichment in endocrine tissues like adipose and the adrenal gland. Furthermore, we fine-mapped 1,219 structural variants, demonstrating their unique roles to tissue- and sex-specific expression beyond SNPs. Ultimately, we showed the utility of these regulatory effects in elucidating the molecular basis of metabolism and complex traits in both chickens and humans. This comprehensive atlas of regulatory effects provides profound insights into the genomic and molecular basis of sexual dimorphism in vertebrates.

genomics↗