Biology subjects

Lan, Z.

Publications and source records attributed to Lan, Z..

13 recordsLinked to original sources

bioRxiv2026

Adolescent prodromal phenotypes of psychiatric disorders: insights from a novel DISC1-perturbed monkey model

Neurodevelopmental deficits frequently lead to mild but significant adolescent social and cognitive changes, representing prodromal manifestations of adult-onset psychiatric disorders in a cross-disease manner. Although experimental medicine utilizes animal models to address the mechanisms, rodent brains lack critical structures for human higher brain functions such as the dorsolateral prefrontal cortex. To fill this translational gap, we generated monkeys with an impaired DISC1 gene locus, targeting the multifunctional protein essential for neurodevelopment and involved in transdiagnostic mental health risks. Here we analyze the F0 animals by minimizing mosaicism. At ages equivalent to human adolescence, these monkeys exhibited blunted responsiveness to social stimuli and increased internal drives, mirroring altered social behaviors in the prodromal stage in humans. Resting-state functional MRI data indicated disrupted global functional connectivity and reorganization of network topology, marked by a shift in the dominance of brain hubs from prefrontal regions to sensory areas. This primate model provides a unique platform for studying psychiatric disorders, such as schizophrenia, across the developmental trajectory.

neuroscience↗

bioRxiv2026

Cross-Tissue Inflammatory Convergence Supports a Putative Muscle-Brain Axis in Alzheimer's Disease

Background Reduced muscle strength is associated with cognitive decline and Alzheimer's disease (AD), suggesting that skeletal-muscle aging and AD-related neurodegeneration may share biological mechanisms. Vascular dysfunction, immune activation, and extracellular-matrix remodeling have been implicated in both tissues, but the extent of shared cellular and molecular programs remains unclear. We investigated cross-tissue transcriptional programs in aging skeletal muscle and AD-related brain tissue and evaluated whether related signals are detectable in peripheral blood. Methods We analyzed independent, unpaired human transcriptomic datasets from skeletal muscle (23 donors), the SEA-AD middle temporal gyrus atlas (84 donors), and peripheral blood. Donor-aware models identified age-associated changes in muscle and transcriptomic changes across continuous pseudoprogression score (CPS) in brain. Cross-tissue comparisons focused on 30 brain donors within an early CPS window. Shared tissue-derived programs were assessed in peripheral blood mononuclear cells and independently tested in frailty bulk-blood and Alzheimer's Disease Neuroimaging Initiative (ADNI) whole-blood datasets. CellOracle simulations were used to prioritize candidate transcriptional regulators. Results Aging muscle showed increased inflammatory, extracellular-matrix, and stromal communication programs. During early AD-related brain progression, vascular and immune populations showed increasing inflammatory and matrix-associated activity together with shifts in intercellular communication. Cross-tissue analysis identified six concordantly enriched pathways comprising 109 leading-edge genes in endothelial populations and four pathways comprising 51 genes in myeloid populations. Related peripheral-blood signatures varied across cohorts and cell types. However, in independent frailty and ADNI mild cognitive impairment and AD datasets, 23 of 30 predefined tissue-derived pathway-subset tests showed significant positive enrichment after false-discovery-rate correction, whereas individual gene-level bulk-blood associations did not survive correction. CellOracle analyses prioritized ETS2 and BHLHE40 as exploratory endothelial regulators whose simulated perturbation consistently reduced selected shared program scores across tissues. Conclusions Aging skeletal muscle and AD-related brain tissue exhibit convergent endothelial and myeloid inflammatory programs, with related pathway-level signals detectable in peripheral blood. These cross-tissue programs and candidate endothelial regulators provide testable hypotheses for mechanisms linking systemic aging, muscle dysfunction, and AD-related neurodegeneration.

neuroscience↗

bioRxiv2026

Metagenomic Evidence for Horizontal Gene Transfer and Functional Convergence in the Oral Microbiome of Cohabiting Dogs and Owners

The intimate cohabitation between humans and their pets facilitates bidirectional microbial exchange, yet the extent and functional consequences of this transfer within the oral niche remain underexplored. Here, we employed metagenomic sequencing to characterize the oral microbiome of dogs and their owners across distinct geographic regions in China, integrating taxonomic, gene-centric, and functional analyses using public databases (BacMet, CARD, eggNOG, KEGG) to assess microbe-host associations. We found that dog-owner pairs exhibited significantly higher gene-level similarity compared to unrelated individuals, indicating a strong cohabitation-driven microbial linkage. While no major taxonomic shifts were observed in the human oral microbiome associated with pet ownership, we identified a marked enrichment of antibiotic resistance genes (ARGs)--particularly those conferring resistance to peptides, fluoroquinolones, antiseptics, diaminopyrimidines, cephalosporins, and carbapenems--in cohabiting pairs. This enrichment, together with the identification of exclusively shared ARGs (e.g., mdtF, macB, RanA), suggests the potential for horizontal gene transfer (HGT) between pet- and human-associated microbiomes. Functional profiling further revealed greater similarity in microbial metabolic pathways between cohabiting pairs than between unrelated individuals, reinforcing the likelihood of HGT as a mechanism underlying functional convergence. Collectively, these findings reveal that cohabitation with dogs reshapes the human oral microbiome at the genetic and functional levels, with potential implications for antimicrobial resistance transmission. This study provides a foundational framework for assessing the health risks associated with pet-human microbial exchange in shared living environments.

microbiology↗

bioRxiv2025

The superficial white matter in language processing: Broca's area connections are bilaterally associated with individual performance in children and adults

While deeper white matter connections, such as the arcuate fasciculus and frontal aslant tract, are well known for their role in language and show leftward asymmetries in adults, the contribution of the short-range cortico-cortical superficial white matter (SWM) connections remains less understood. In this preregistered study, we examined white matter connections of Brocas area and its right hemisphere homolog in early adolescents and young adults using two large, publicly available datasets: the Adolescent Brain Cognitive Development Study and the Human Connectome Project Young Adult Study, totaling over 10,000 participants. We anatomically curated the ODonnell Research Group (ORG) tractography atlas to identify SWM fiber clusters intersecting Brocas area (pars opercularis and pars triangularis), confirmed through expert visual inspection. We investigated the microstructure, structural connectivity, and lateralization of Brocas area SWM and its relationship with language performance (Picture Vocabulary and Oral Reading Recognition assessments), in comparison to the deeper white matter connections of the frontal aslant tract and arcuate fasciculus. The arcuate fasciculus demonstrated the strongest and most consistent leftward lateralization of both microstructure (fractional anisotropy, FA) and structural connectivity (number of streamlines, NoS), with structure-function associations that were bilateral in adolescents and left-dominant in adults. Interestingly, despite weaker lateralization than the arcuate fasciculus, both the SWM and the frontal aslant tract demonstrated comparable associations with language performance. The frontal aslant tract showed greater leftward lateralization (FA and NoS) with age and was bilaterally associated with language performance, particularly in adolescents. Compared to these deeper tracts, Brocas area SWM demonstrated left-lateralized FA and right-lateralized NoS in both adolescents and adults, with stronger FA lateralization in adults. Bilateral SWM FA and NoS were significantly associated with language performance in both hemispheres and age groups. Overall, these results suggest that Brocas area SWM may support language in a more bilaterally distributed manner and highlight the importance of considering SWM connections in studies of language development and neurosurgical planning.

neuroscience↗

bioRxiv2025

Towards an informed choice of diffusion MRI image contrasts for cerebellar segmentation

The fine-grained segmentation of cerebellar structures is an essential step towards supplying increasingly accurate anatomically informed analyses, including, for example, white matter diffusion magnetic resonance imaging (MRI) tractography. Cerebellar tissue segmentation is typically performed on structural magnetic resonance imaging data, such as T1-weighted data, while connectivity between segmented regions is mapped using diffusion MRI tractography data. Small deviations in structural to diffusion MRI data co-registration may negatively impact connectivity analyses. Reliable segmentation of brain tissue performed directly on diffusion MRI data helps to circumvent such inaccuracies. Diffusion MRI enables the computation of many image contrasts, including a variety of tissue microstructure maps. While multiple methods have been proposed for the segmentation of cerebellar structures using diffusion MRI, little attention has been paid to the systematic evaluation of the performance of different available input image contrasts for the segmentation task. In this work, we evaluate and compare the segmentation performance of diffusion MRI-derived contrasts on the cerebellar segmentation task. Specifically, we include spherical mean (diffusion-weighted image average) and b0 (non-diffusion-weighted image average) contrasts, local signal parameterization contrasts (diffusion tensor and kurtosis fit maps), and the structural T1-weighted MRI contrast that is most commonly employed for the task. We train a popular deep-learning architecture using a publicly available dataset (HCP-YA), leveraging cerebellar region labels from the atlas-based SUIT cerebellar segmentation pipeline. By training and testing using many diffusion-MRI-derived image inputs, we find that the spherical mean image computed from b=1000 s/mm2 shell data provides stable performance across different metrics and significantly outperforms the tissue microstructure contrasts that are traditionally used in machine learning segmentation methods for diffusion MRI. Key pointsO_LIWe provide evidence about the performance of different dMRI contrasts for cerebellar structure segmentation using a deep learning neural network. C_LIO_LIThe diffusion MRI spherical mean provides improved and stable cerebellar structure segmentation performance. C_LIO_LIThe spherical mean is easy to compute and can be used for cerebellar structure segmentation on retrospective clinical diffusion MRI data. C_LI

neuroscience↗

bioRxiv2025

Consistent cerebellar pathway-cognition associations across pre-adolescents & young adults: a diffusion MRI study of 9000+ participants

The cerebellum, long implicated in movement, is now recognized as a contributor to higher-order cognition. The cerebellar pathways provide key structural links between the cerebellum and cerebral regions integral to language, memory, and executive function. Here, we present a large-scale, cross-sectional diffusion MRI (dMRI) analysis investigating the relationships between cerebellar pathway microstructure and cognitive performance in over 9,000 participants spanning pre-adolescence (n>8,000 from the ABCD dataset) and young adulthood (n>900 from the HCP-YA dataset). We assessed the microstructure of five cerebellar pathways--the inferior, middle, and superior cerebellar peduncles; the parallel fibers; and input/Purkinje fibers--using three dMRI measures of fractional anisotropy, mean diffusivity, and number of streamlines. Cognitive performance was evaluated using seven NIH Toolbox assessments of language, executive function, and memory. In both datasets, we found numerous significant associations between cerebellar pathway microstructure and cognitive performance. These associations showed a strong correlation across the two datasets (r = 0.47, p < 0.0001), underscoring the reliability of cerebellar dMRI-cognition relationships in pre-adolescents and young adults. In both datasets, the strongest associations were found between the superior cerebellar peduncle and performance on language assessments, suggesting this pathway plays an important role in language function across age groups. In young adults, but not pre-adolescents, parallel fiber microstructure was linked to inhibitory control, suggesting that contributions to attentional processes may emerge or strengthen with maturation. Overall, our findings highlight the important role of cerebellar pathways in cognition and the utility of large-scale datasets for advancing our understanding of brain-cognition relationships. SignificanceThis study provides strong evidence linking cerebellar pathway tissue microstructure to cognition across large populations of preadolescent children and young adults. By leveraging diffusion MRI tractography and cognitive performance data from two major datasets, we identify significant relationships between cerebellar pathway microstructure and cognitive performance. Importantly, findings are significantly correlated across datasets, pointing to the consistency of these relationships, bridging age groups and acquisitions. These results highlight the cerebellar pathways integral role in cognitive functioning and underscore the value of large-scale, population-based studies in advancing our understanding of brain-cognition relationships. Classification 1) Biological Sciences, Neuroscience; 2) Social Sciences, Psychological and Cognitive Sciences

neuroscience↗

bioRxiv2024

Fiber Microstructure Quantile (FMQ) Regression: A Novel Statistical Approach for Analyzing White Matter Bundles from Periphery to Core

The structural connections of the brains white matter are critical for brain function. Diffusion MRI tractography enables the in-vivo reconstruction of white matter fiber bundles and the study of their relationship to covariates of interest, such as neurobehavioral or clinical factors. In this work, we introduce Fiber Microstructure Quantile (FMQ) Regression, a new statistical approach for studying the association between white matter fiber bundles and scalar factors (e.g., cognitive scores). Our approach analyzes tissue microstructure measures based on quantile-specific bundle regions. These regions are defined in a data-driven fashion according to the quantiles of fractional anisotropy (FA) of a population fiber bundle, which pools all individuals bundles. The FA quantiles induce a natural subdivision of a fiber bundle, defining regions from the periphery (low FA) to the core (high FA) of the population fiber bundle. To investigate how fiber bundle tissue microstructure relates to covariates of interest, we employ the statistical technique of quantile regression. Unlike ordinary regression, which only models a conditional mean, quantile regression models the conditional quantiles of a response variable. This enables the proposed analysis, where a quantile regression is fitted for each quantile-specific bundle region. To demonstrate FMQ Regression, we perform an illustrative study in a large healthy young adult tractography dataset derived from the Human Connectome Project-Young Adult (HCP-YA), focusing on particular bundles expected to relate to particular aspects of cognition and motor function. In comparison with traditional regression analyses based on FA Mean and Automated Fiber Quantification (AFQ), we find that FMQ Regression provides a superior model fit with the lowest mean squared error. This demonstrates that FMQ Regression captures the relationship between scalar factors and white matter microstructure more effectively than the compared approaches. Our results suggest that FMQ Regression, which enables FA analysis in data-driven regions defined by FA quantiles, is more powerful for detecting brain-behavior associations than AFQ, which enables FA analysis in regions defined along the trajectory of a bundle. FMQ Regression finds significant brain-behavior associations in multiple bundles, including findings unique to males or to females. In both males and females, language performance is significantly associated with FA in the left arcuate fasciculus, with stronger associations in the bundles periphery. In males only, memory performance is significantly associated with FA in the left uncinate fasciculus, particularly in intermediate regions of the bundle. In females only, motor performance is significantly associated with FA in the left and right corticospinal tracts, with a slightly lower relationship at the bundle periphery and a slightly higher relationship toward the bundle core. No significant relationships are found between executive function and cingulum bundle FA. Our study demonstrates that FMQ Regression is a powerful statistical approach that can provide insight into associations from bundle periphery to bundle core. Our results also identify several brain-behavior relationships unique to males or to females, highlighting the importance of considering sex differences in future research.

neuroscience↗

bioRxiv2024

A curated collection of transcriptome datasets to study the transcriptional response in blood and nasal samples following viral respiratory inoculation and vaccination

Our understanding of the human immune systems response to viral respiratory tract infections (VRTIs) and vaccines, including the molecular mechanisms and correlates of protection, remains incomplete. Extensive transcriptomic data from inoculation and vaccination studies have been deposited in publicly available databases. However, these studies are often separate and difficult to locate. We provide a curated compendium of public gene expression data repositories for researchers to reanalyze transcriptomes from human whole blood, peripheral blood mononuclear cells (PBMCs), and nasal swab samples. This enables the study of transcriptional responses to viral inoculation or vaccination. This collection includes 18 datasets from inoculation studies and 37 datasets from vaccination studies, sourced from the NCBI Gene Expression Omnibus (GEO), ImmPort Shared Data, and ArrayExpress.

genomics↗

bioRxiv2024

Design of PEG-based hydrogels as soft ionic conductors

Conductive hydrogels have gained interest in biomedical applications and soft electronics. To tackle the challenge of ionic hydrogels falling short of desired mechanical properties in previous studies, our investigation aimed to understand the pivotal structural factors that impact the conductivity and mechanical behavior of polyethylene glycol (PEG)-based hydrogels with ionic conductivity. Polyether urethane diacrylamide (PEUDAm), a functionalized long-chain macromer based on PEG, was used to synthesize hydrogels with ionic conductivity conferred by incorporating ions into the liquid phase of hydrogel. The impact of salt concentration, water content, temperature, and gel formation on both mechanical properties and conductivity was characterized to establish parameters for tuning hydrogel properties. To further expand the range of conductivity available in these ionic hydrogels, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) was incorporated as a single copolymer network or double network configuration. As expected, conductivity in these ionic gels was primarily driven by ion diffusivity and charge density, which was dependent on hydrogel network formation and swelling. Copolymer network structure had minimal effect on the conductivity which was primarily driven by counter-ion equilibrium; however, the mechanical properties and equilibrium swelling was strongly dependent on network structure. The structure-property relationships elucidated here enables the rationale design of this new double network hydrogel to achieve target properties for a broad range of applications.

bioengineering↗

bioRxiv2023

Eyes on nature: Embedded vision cameras for multidisciplinary biodiversity monitoring

Global environmental challenges require comprehensive data to manage and protect biodiversity. Currently, vision-based biodiversity monitoring efforts are mixed, incomplete, human-dependent, and passive. To tackle these issues, we present a portable, modular, low-power device with embedded vision for biodiversity monitoring. Our camera uses interchangeable lenses to resolve barely visible and remote subjects, as well as customisable algorithms for blob detection, region-of-interest classification, and object detection to identify targets. We showcase our system in six case studies from the ethology, landscape ecology, agronomy, pollination ecology, conservation biology, and phenology disciplines. Using the same devices, we discovered bats feeding on durian tree flowers, monitored flying bats and their insect prey, identified nocturnal insect pests in paddy fields, detected bees visiting rapeseed crop flowers, triggered real-time alerts for waterbirds, and tracked flower phenology over months. We measured classification accuracies between 55% and 96% in our field surveys and used them to standardise observations over highly-resolved time scales. The cameras are amenable to situations where automated vision-based monitoring is required off the grid, in natural and agricultural ecosystems, and in particular for quantifying species interactions. Embedded vision devices such as this will help addressing global biodiversity challenges and facilitate a technology-aided global food systems transformation.

ecology↗

bioRxiv2021

P4HA2-induced prolyl hydroxylation suppresses YAP1-mediated prostate cancer cell migration, invasion, and metastasis

Yes-associated protein 1 (YAP1), a key player in the Hippo pathway, has been shown to play a critical role in tumor progression. However, the role of YAP1 in prostate cancer cell invasion, migration, and metastasis is not well defined. Through functional, transcriptomic, epigenomic, and proteomic analyses, we showed that prolyl hydroxylation of YAP1 plays a critical role in the suppression of cell migration, invasion, and metastasis in prostate cancer. Knockdown (KD) or knockout (KO) of YAP1 led to an increase in cell migration, invasion, and metastasis in prostate cancer cells. Microarray analysis showed that the EMT pathway was activated in Yap1-KD cells. ChIP-seq analysis showed that YAP1 target genes are enriched in pathways regulating cell migration. Mass spectrometry analysis identified P4H prolyl hydroxylase in the YAP1 complex and YAP1 was hydroxylated at multiple proline residues. Proline-to-alanine mutations of YAP1 isoform 3 identified proline 174 as a critical residue, and its hydroxylation suppressed cell migration, invasion, and metastasis. KO of P4ha2 led to an increase in cell migration and invasion, which was reversed upon Yap1 KD. Our study identified a novel regulatory mechanism of YAP1 by which P4HA2-dependent prolyl hydroxylation of YAP1 determines its transcriptional activities and its function in prostate cancer metastasis.

cancer biology↗

bioRxiv2020

Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways

The mechanisms by which oligodendroglia modulate CNS angiogenesis remain elusive. Previous in vitro data suggest that oligodendroglia regulate CNS endothelial cell proliferation and blood vessel formation through hypoxia inducible factor alpha (HIF)-activated Wnt (but not VEGF) signaling. Using in vivo genetic models, we show that HIF in oligodendroglia is necessary and sufficient for angiogenesis independent of CNS regions. At the molecular level, HIF stabilization in oligodendroglia does not perturb Wnt signaling but remarkably activates VEGF. At the functional level, genetically blocking oligodendroglia-derived VEGF but not Wnt significantly decreases oligodendroglial HIF-regulated CNS angiogenesis. Interestingly, blocking astroglia-derived Wnt signaling reduces astroglial HIF-regulated CNS angiogenesis. Together, our in vivo data clearly demonstrate that oligodendroglial HIF regulates CNS angiogenesis through Wnt-independent and VEGF-dependent signaling. Our findings represent an alternative mechanistic understanding of CNS angiogenesis by postnatal glial cells and unveil a glial cell type-dependent HIF-Wnt axis in regulating CNS vessel formation.

neuroscience↗

bioRxiv2019

Title: Risk factors for postoperative meningitis after microsurgery for vestibular schwannoma

OBJECTIVEMeningitis after microsurgery for vestibular schwannoma (VS) is a severe complication and result in high morbidity. But few studies have focused on meningitis after VS surgery alone. The purpose of this study was to identify the risk factors for meningitis after VS surgery.\n\nMETHODSWe undertook a retrospective analysis of all VS patients, who underwent microsurgery of VS and at least live for 7 days after surgery, between 1st June 2015 and 30st November 2018 at West China Hospital of Sichuan University. Univariate and multivariate analyses were performed to identify the risk factors for postoperative meningitis (POM).\n\nRESULTSWe collected 410 patients, 27 of whom had POM. Through univariate analysis, hydrocephalus (p=0. 018), Koos grade IV (p=0.04), The operative duration (> 3 hours p=0.03) and intraoperative bleeding volume ([≥] 400ml p=0. 02) were significantly correlated to POM. Multivariate analysis showed that Koos grade IV (p=0.04; OR=3.19; 95% CI 1.032-3.190), operation duration (> 3 hours p=0.03 OR= 7.927; 95% CI 1.043-60.265), and intraoperative bleeding volume ([≥] 400ml p=0.02; OR=2.551; 95% CI 1.112-5.850) are the independent influencing factors of POM.\n\nCONCLUSIONSKoos grade IV, the duration of operation, and the amount of bleeding were identified as independent risk factors for POM after microsurgery of VS. POM caused a prolonged hospital stay.

neuroscience↗