Biology subjects

Gan, X.

Publications and source records attributed to Gan, X..

At least 19 recordsLinked to original sources

bioRxiv2026

The uplift of the Qinghai-Tibetan Plateau reshaped genome architecture and diversification of Asian torrent catfishes

Tectonic uplift and mountain building are major drivers of species diversification and adaptation, yet how they reshape genome architecture and promote evolutionary innovation remains poorly understood. Here, we generated multiple chromosome-level genomes for Asian torrent catfishes (Sisoridae) and performed phylogenomic and comparative genomic analyses. Our results support an Asian origin of Sisoridae and provide a refined phylogenetic topology for catfishes. Comparative analyses revealed extensive chromosomal rearrangements during sisorid evolution, indicating highly dynamic genome architectures. The timing of sisorid diversification overlaps with major phases of regional tectonic change, and analyses of phylogenetic discordance indicate heterogeneous contributions from incomplete lineage sorting and introgression. Elevational distribution was associated with variation in estimated molecular evolutionary rates, while exploratory scans identified lineage-specific candidates for selection and convergent evolution. Candidate coding and non-coding changes occur near genes with known roles in fin development, body patterning, and liver biology, but their effects on sisorid traits remain to be tested. Together, our results demonstrate how tectonic uplift reshaped genome architecture and diversification in Asian torrent catfishes and provide new insights into the genomic basis of adaptation in mountainous freshwater ecosystems.

evolutionary biology↗

bioRxiv2026

A neurofunctional signature of romantic love predicts rewards on social media, effects of oxytocin and drug-cue reactivity

Romantic love is a selective motivational state supporting pair bonding, yet its neural representation and relation to other affiliative-rewarding experiences remain unclear. Across eight fMRI studies (n=420) spanning naturalistic affiliative-reward, pharmacological and addiction-relevant experiments, we developed and evaluated multivariate whole-brain decoders of romantic love and friendship. Both signatures engaged mesocorticolimbic reward systems and the precuneus, yet were dissociable at the whole-brain level and in their recruitment of social-cognitive systems. The love signature generalized to reward on social media, was specific to positive valence, and did not track sweet-taste or monetary reward, indicating a distinct social-affiliative reward representation. Oxytocin selectively increased love - but not friendship - signature reactivity to the romantic partner. In an independent drug-cue-reactivity dataset, the love signature specifically identified heavy cannabis users. These findings establish a dissociable neurofunctional signature of romantic love in conserved bonding circuits that extend to digital affiliation and are co-opted in addiction.

neuroscience↗

bioRxiv2026

A distributed neural architecture of sustained affect across external and internal experience

AO_SCPLOWBSTRACTC_SCPLOWSustained affect shapes well-being, yet its neural architecture across externally elicited and internally generated experience remains unclear. Using whole-brain functional connectivity during minutes-long naturalistic movie viewing, we derived positive and negative affective experience signatures and their underlying neural architecture. These signatures predicted valence-specific affective intensity and generalized to independent movie-viewing data and internally generated affect, discriminating sad memory and rumination from neutral distraction while tracking subjective experience. Importantly, their expression showed little relation to vigilance or cognitive demand. Characterization of these signatures revealed coherent community structure and a shared distributed backbone, alongside valence-preferential components, consistent with a partially separable architecture. Extending beyond experimentally evoked states, in four resting-state depression cohorts, these signatures distinguished patients from controls with reduced positive and elevated negative signature expression, and predicted symptom burden and anhedonia. These findings identify a generalizable distributed architecture bridging external and internal affective experience and extending to clinically relevant affective dysregulation.

neuroscience↗

bioRxiv2025

In vivo vaccine generation with a topical small molecule cocktail to eradicates AML and PDAC

Using vaccine to cure cancer has been expected for over 130 years, but remains a big challenge. Here we present a novel in vivo personal and off-the-shelf vaccine generation strategy with unique mechanism, which is very simple but high efficacy, using a small molecule cocktail as antigen-agnostic vaccine. In mouse AML and PDAC models, this in vivo vaccine rapidly eliminated tumors via triggering inflamed immunogenic cell death to release antigens, activating NK and DC cells, inducing innate and adaptive immunity in blood, lymph node, spleen, bone marrow and TME, and elicited a robust long-term immune memory. Importantly, this small molecule cocktail-based platform holds the potential to make in vivo vaccine more personal and accessible. It might represent a promising avenue for pan-cancer immunotherapy.

cancer biology↗

bioRxiv2025

Disgust propensity, not disgust sensitivity, shapes the reactivity of a subjective disgust circuit in humans

Disgust constitutes an evolutionary adaptive defensive-avoidance response, yet humans vary markedly in their dispositional tendency to experience disgust (disgust propensity) and in their negative appraisal of such experience (disgust sensitivity). Conceptual frameworks and neuroimaging studies suggest that these traits may differentially modulate neural responses to disgust-eliciting stimuli; however, methodological constraints have left their precise roles unresolved. Our comparably large fMRI study (n = 142) therefore aimed to systematically determine how trait disgust modulates neural responses to carefully selected and validated disgust-specific visual stimuli across varying levels of subjective disgust experience. The whole-brain voxel-wise regression analyses revealed a neural dissociation between the two disgust traits, with disgust propensity, but not disgust sensitivity, modulating disgust-related neural activity in the anterior, middle, and posterior insula, as well as the caudate, putamen, thalamus, hippocampus, and parahippocampal gyrus. Mediation and network-level analyses further supported this dissociation by showing that disgust propensity shapes disgust experience via insula - striatal - hippocampal pathways. Together, these findings provide evidence for a neurofunctional dissociation of disgust propensity and sensitivity and elucidate how trait disgust shapes subjective experiences. They further suggest that disgust propensity and the identified systems may represent promising targets for the regulation of disgust-related pathology.

neuroscience↗

bioRxiv2025

LDL Signals Through Scarf1 to Drive a Pro-Fibrotic Secretory Response in Endothelial Cells

BACKGROUNDEndothelial cells lining the vasculature form a polarised secretory organ that releases proteins apically into the circulation and basally into the subendothelial matrix. While this secretion plays many critical roles in homeostasis, the potential roles for endothelial secretion in vascular disease remain under-studied. METHODSWe treated polarised monolayers of primary human endothelial cells with native and oxidised LDL and identified the proteins secreted from the apical and basal endothelial surfaces by tandem mass tag mass spectrometry. RESULTSTreatment with either native or oxidised LDL led to increased secretion of a cohort of 21 mostly pro-fibrotic proteins. We focussed on fibronectin, which was secreted apically or basally, depending on the direction of LDL treatment. LDL-stimulated fibronectin secretion did not require well-characterised endothelial LDL receptors but was instead mediated by the poorly characterised scavenger receptor Scarf1 and the cholesterol-sensitive SNARE proteins syntaxin 4 and 6. This LDL-stimulated secretion did not involve increased fibronectin expression but instead appeared to result from a decrease in fibronectin turnover and a re-routing of intracellular sorting. CONCLUSIONSThis novel endothelial secretory pathway links circulating LDL to the release of pro-fibrotic proteins from the endothelium, supporting a role for endothelial cell secretion in the progression of lipid-induced fibrotic disease.

cell biology↗

bioRxiv2025

An innovative approach in identifying a network of priority wetland sites in the East Asian-Australasian Flyway for a new sustainable management investment programme

The East Asian-Australasian Flyway (EAAF) is widely recognised to be the most threatened of the eight flyways in the world, with wetlands rapidly lost due to land cover change, unsustainable use, and the wider impacts of climate change. The recently established Regional Flyway Initiative aims to bring a network of priority wetlands in the EAAF under improved protection, management, and restoration in 10 Asian countries, while mobilising resources for sustainable agriculture, aquaculture, ecotourism, and other livelihoods for local communities. A major step in the development of this initiative is the identification of priority wetland sites through the application of international criteria, based on modern waterbird count data collated from wetland sites across Asia. Through existing analyses and stakeholder consultations, we short-listed 400 internationally important wetlands as candidate sites for further assessment. Count data of EAAF waterbird species was then assessed against international criteria aligned with the Convention on Wetlands (Ramsar Convention), the EAAF Partnerships Flyway Site Network and Important Bird Areas and Biodiversity for each site to iteratively identify a subset of priority sites, drawing on newly available species population thresholds. Each site was scored and ranked using a metric (Prioritisation Criterion1) calculated from the proportions of every occurring EAAF species against published population thresholds. We identified a total of 147 wetland sites of high conservation priority across the 10 countries, thereby representing the full suite of wetland landscapes and habitats in Asia, both freshwater and coastal, all critical sites for the conservation of migratory waterbirds in the flyway. At least 34 threatened species, including significant proportions of their global populations are represented in this network of 147 sites. To ensure that conservation opportunities are maximised for species and ecosystem services, there is a need to ensure that selected sites and landscapes are reconciled with the conservation and development priorities of each country, and to evaluate priority sites for their ecosystem services.

ecology↗

bioRxiv2024

Dissociable neurofunctional and molecular characterizations of reward and punishment sensitivity

While the hyper-and hypo-reward or punishment sensitivities (RS, PS) have received considerable attention as prominent transdiagnostic features of psychopathology, the lack of an overarching neurobiological characterization currently limits their early identifications and neuromodulations. Here we combined microarray data from the Allen Human Brain Atlas with a multimodal fMRI approach to uncover the neurobiological signatures of RS and PS in a discovery-replication design (N=655 participants). Both RS and PS were mapped separately in the brain, with the intrinsic functional connectome in the fronto-striatal network encoding reward responsiveness, while the fronto-insular system was particularly engaged in punishment sensitivity. This dissociable functional connectome patterns related to RS and PS were also specific in differentiating decisions driven by social or monetary reward and punishment motivations. Further imaging transcriptomic analyses revealed that functional connectome variations for RS and PS were associated with topography of specific gene sets enriched in ontological pathways, including synaptic transmission, dopaminergic metabolism, immune response and stress adaptation. On the neurotransmitter level, the serotonin neuromodulator was identified as a pivotal hub regulating the intrinsic functional connectome patterns of RS and PS, with this process critically dependent on its interactions with dopaminergic, opioid and GABAergic systems. Overall, these findings indicate dissociable neural connectome mapping of RS and PS and highlight their linkage with transcriptomic profiles, which may offer valuable insights into the treatment evaluation for symptomatology relevant to reward/punishment processing deficits.

neuroscience↗

bioRxiv2024

Does Unfairness Evoke Anger or Disgust? A Quantitative Neurofunctional Dissection Based on 25 Years of Neuroimaging

Over the last decades, the traditional Homo economicus model has been increasingly challenged by convergent evidence underscoring the impact of emotions on decision-making. A classic example is the perception of unfairness operationalized in the Ultimatum Game where humans readily sacrifice personal gains to punish those who violate fairness norms. While the emotional mechanism underlying costly punishments has been widely acknowledged, the distinct contributions of moral emotions (anger or disgust) remain debated, partly due to methodological limitations of the conventional experiments. Here, we capitalize on a quantitative neurofunctional dissection approach by combining recent developments in neuroimaging meta-analyses, behavioral-level, network-level, and neurochemical-level decoding and data from 3,266 participants from functional neuroimaging studies to determine the common and distinct neural representations between unfairness and the two moral emotions. Experience of unfairness engaged a widespread bilateral network encompassing insular, cingulate, and frontal regions, with dorsal striatal regions mediating the decision to reject unfair offers. Disgust engaged a defensive-avoidance circuit encompassing amygdalar, occipital, and frontal regions, while anger engaged non-overlapping systems including mid-cingulate, thalamic, and frontal regions. Unfairness and anger or disgust respectively commonly engaged the anterior and mid-insula, while the latter additionally showed common recruitment of ventrolateral prefrontal and orbitofrontal cortices. Multimodal network, behavioral, and serotonergic decoding provided a more granular and convincing dissection of these results. Findings indicate a shared neuroaffective basis underlying the impact of emotions on unfairness-induced punishment behavior and suggest a common brain circuit has been evolutionarily shaped to protect individuals from personal harm and enforce societal norms.

neuroscience↗

bioRxiv2024

State and trait serotonin variations interact to shape the intrinsic connectivity and gradient architecture of the brain: a combined TPH2 genetics and tryptophan depletion study

BackgroundSerotonin (5-HT) critically regulates cognitive and emotional functions, and both stable and transient variations in 5-HT signaling have been associated with emotional dysregulations. However, findings regarding the neurofunctional effects of transient 5-HT variations have been highly inconsistent. Therefore, we examined whether individual variations in a central 5-HT-regulating genetic polymorphism (tryptophan hydroxylase 2, TPH2) represent a vulnerability or resilience factor for the effects of acute tryptophan depletion (ATD) on functional brain architecture. MethodThe current study utilized a pharmacogenetic within-subject randomized placebo-controlled resting-state fMRI design with n=53 healthy male participants in combination with spontaneous intrinsic neural activity, functional connectivity, and connectome gradient analyses to compare the neurofunctional effects of ATD-induced transient reduction in central 5-HT signaling between TPH2 genotypes (a priori genotyping for rs4570625, GG n = 25 vs. TT n = 23). ResultsATD induced significant increases in spontaneous neural activity in hippocampal CA1 irrespective of genotype and enhanced communication of this region with the bilateral amygdala and the vmPFC specifically in GG carriers. ATD sharpened the intrinsic connectome gradient architecture in several large-scale networks, including the salience, frontoparietal, and default mode network. ConclusionsOur results identify a potential genetic marker for an increased vulnerability to the neural effects of transient variations in 5-HT signaling on the functional architecture of an anxiety- and stress-related brain circuit. Connectome gradient results underscore the regulatory role of 5-HT on the intricate organization of large-scale networks involved in emotional reactivity and regulation.

neuroscience↗

bioRxiv2024

GageTracker: a tool for dating gene age by micro- and macro-synteny with high speed and accuracy

With the advent of the Earth Genome Project, an increasing number of species' genomes presents exciting opportunities for exploring genetic and phenotypic diversity in organisms. Determining the origin time of genes facilitates the elucidation of crucial genetic mechanisms underlying significant biological evolutionary questions such as the transition from aquatic to terrestrial life, the emergence of mammals, the origin of humans, as well as the development of species- or lineage-specific traits. However, accurately determining the origin time of these genes in species separated by long evolutionary distances remains a major challenge in bioinformatics as these genes often undergo significant changes in their genome sequences, making it difficult to trace them back to their origin. Here, we proposed a new approach for dating gene age based on the micro- and macro-synteny algorithms. This approach employs the parallel computation of orthologous genome alignments across multiple species. Our method was integrated into the GageTracker (Gene Age Tracker) software, providing a fast and accurate way to trace gene age with minimal user input, available at https://github.com/RiversDong/GageTracker. Benchmarked against the simMammals dataset (Alignathon), GageTracker achieved the same high-quality genome alignments as the optimized LastZ aligner, but improved operation speed by 1.4-7 times. In a separate analysis of 12 Drosophila genomes, GageTracker efficiently assessed the ages of 23,720 genes (including ~13,965 protein-coding genes) in just ~22 hours with default parameters. When comparing with the GenTree database (recognized as the most comprehensive and accurate tool for evaluating gene age), GageTracker achieved an impressive ~94.4% accuracy and ~99% macro consistency in assessing the age of protein-coding genes. Moreover, for the ~5.6% conflicting genes, GageTracker displayed slightly higher support rates than GenTree, as evidenced by data from OrthoDB, FlyBase, and Ensembl ortholog databases. Notably, younger genes identified by GageTracker exhibited a preferential expression pattern in the testis, further reinforcing the reliability of GageTracker in accurately tracing gene age.

bioinformatics↗

bioRxiv2024

A neurofunctional signature of affective arousal generalizes across valence domains and distinguishes subjective experience from autonomic reactivity

Arousal is fundamental for affective experience and, together with valence, defines the core affective space. Precise brain models of affective arousal are lacking, leading to continuing debates of whether the neural systems generalize across valence domains and are separable from those underlying autonomic arousal or wakefulness. Here, we combined naturalistic fMRI with predictive modeling to develop a brain affective arousal signature (BAAS, discovery-validation design, n=60, 36). We demonstrate its (1) sensitivity and generalizability across mental processes and valence, and (2) neural distinction from autonomic arousal, wakefulness, and stimulation modality (24 studies, n=868). Affective arousal was encoded in distributed cortical-subcortical (e.g., prefrontal, PAG) systems with local similarities in thalamo-amygdala-insula systems between affective and autonomous arousal. We demonstrate application of the BAAS to improve specificity of established valence-specific neuromarkers. Our study provides a biologically plausible model for affective arousal that aligns with the affective space and has a high application potential.

neuroscience↗

bioRxiv2024

The penetration ring is a novel infection structure formed by the penetration peg for invading plant cell membrane in rice blast fungus

Many fungal pathogens develop specialized infection structures such as appressoria to penetrate plant cells. However, it is not clear whether special structures are formed after cell wall penetration before invading host plasma membrane in hemibiotrophic pathogens. Here, we showed that a penetration ring consisting of Ppe1 secreted proteins is formed after appressorium-mediated cell wall penetration and remained at the base of penetration site after invading plant plasma membrane by the rice blast fungus Magnaporthe oryzae. The same persistent Ppe1 ring is formed after the penetration of neighboring cells by transpressoria. PPE1 is specifically expressed during plant infection and the {Delta}ppe1 mutant is defective in penetration and invasive growth. Blockage of penetration peg formation impedes the development of the Ppe1 ring. Close examinations showed that the penetration ring is formed at the collar of penetration pegs between the plant cell wall and plasma membrane and it is persistent as a fixed ring even after invasive hyphae invaded neighboring cells. Furthermore, Ppe1 is a member of an expanded family of secreted proteins that are unique to fungal pathogens using extreme appressorium turgor for plant penetration. Other members of the Ppe1 family also localize to the penetration ring for anchoring on plasma membrane during plant infection. Taken together, a penetration ring consisting of a family of secreted proteins is formed between plant cell wall and plasma membrane, which may function as a novel physical structure at the interface between the tip of penetration pegs and plant plasma membrane before the differentiation of invasive hyphae. Significance StatementLike many other plant pathogens, the rice blast fungus forms melanized appressoria (specialized infection structures) to penetrate plant cells. In this study, we showed that a penetration ring is formed by penetration pegs after appressorium-mediated penetration of plant cell wall. This ring of secreted proteins is persistent at the point of penetration pegs invading plant plasma membrane to form invasive hyphae. Therefore, after the penetration of plant cell wall, the rice blast fungus forms a penetration ring that consists of a family of secreted proteins unique to pathogens using extreme appressorium turgor for penetration and may function as a physical structure for anchoring onto plant plasma membrane and developing invasive hyphae in penetrated cells.

pathology↗

bioRxiv2024

Signatures of social pain empathy: general and process-specific brain-wide representations of social exclusion and separation

Empathy can be elicited by physiological pain, as well as in social contexts. Although physiological and different social contexts induce a strong subjective experience of empathy, the general and context-specific neural representations remain elusive. Here, we combine fMRI with multivariate pattern analysis to establish neurofunctional models for pain empathy triggered by social exclusion and separation. Our findings revealed both overlapping and distinct neural representations for social exclusion and separation empathy across cortical and subcortical regions. This study established an evolutionary model that traces the progression from social pain to physiological pain empathy. In conclusion, this study establishes neural decoding models for pain empathy evoked by social exclusion and social separation, revealing their neural foundations and interconnectedness of empathy induced by social and physiological stimuli. These findings deepen our understanding of the neurobiological mechanisms underlying social pain empathy and provide robust neuromarkers to precisely evaluate empathy across physiological and social domains.

neuroscience↗

bioRxiv2024

Distinct neural computations scale the violation of expected reward and emotion in social transgressions

Traditional decision-making models conceptualize humans as optimal learners aiming to maximize outcomes by leveraging reward prediction errors (PE). While violated emotional expectations (emotional PEs) have recently been formalized, the underlying neurofunctional basis and whether it differs from reward PEs remain unclear. Using a modified fMRI Ultimatum Game on n=43 participants we modelled reward and emotional PEs in response to unfair offers and subsequent punishment decisions. Computational modelling revealed distinct contributions of reward and emotional PEs to punishment decisions, with reward PE exerting a stronger impact. This process was neurofunctionally dissociable such that (1) reward engaged the dorsomedial prefrontal cortex while emotional experience recruited the anterior insula, (2) multivariate decoding accurately separated reward and emotional PEs. Predictive neural expressions of reward but not emotional PEs in fronto-insular systems predicted neurofunctional and behavioral punishment decisions. Overall, these findings suggest distinct neurocomputational processes underlie reward and emotional PEs which uniquely impact social decisions.

neuroscience↗

bioRxiv2024

Polyploid genome assembly of Cardamine chenopodiifolia

BackgroundCardamine chenopodiifolia is an amphicarpic plant that develops two fruit morphs, one above and the other below ground. Above-ground fruit disperse their seeds by explosive coiling of the fruit valves, while below-ground fruit are non-explosive. Amphicarpy is a rare trait that is associated with polyploidy in C. chenopodiifolia. Studies into the development and evolution of this trait are currently limited by the absence of genomic data for C. chenopodiifolia. ResultsWe produced a chromosome-scale assembly of the octoploid C. chenopodiifolia genome using high-fidelity long read sequencing with the Pacific Biosciences platform. We successfully assembled 32 chromosomes and two organelle genomes with a total length of 597.2 Mbp and an N50 of 18.8 kbp (estimated genome size from flow cytometry: 626 Mbp). We assessed the quality of this assembly using genome-wide chromosome conformation capture (Omni-C) and BUSCO analysis (97.1% genome completeness). Additionally, we conducted synteny analysis to infer that C. chenopodiifolia likely originated via allo-rather than auto-polyploidy and phased one of the four sub-genomes. ConclusionsThis study provides a draft genome assembly for C. chenopodiifolia, which is a polyploid, amphicarpic species within the Brassicaceae family. This genome offers a valuable resource to investigate the under-studied trait of amphicarpy and the origin of new traits by allopolyploidy.

plant biology↗

bioRxiv2023

Dynamic model of carbon dioxide-induced stomatal closure reveals a feedback core for cellular decision-making

Stomata are pores on plant aerial surfaces, each bordered by a pair of guard cells. They control gas exchange vital for plant survival. Understanding how guard cells respond to environmental signals such as atmospheric carbon dioxide (CO2) levels is not only insightful to fundamental biology but also relevant to real-world issues of crop productivity under global climate change. In the past decade, multiple important signaling elements for stomatal closure induced by elevated CO2 have been identified. Yet, there is no comprehensive understanding of high CO2 induced stomatal closure. In this work we assemble a cellular signaling network underlying high CO2-induced stomatal closure by integrating evidence from a comprehensive literature analysis. We further construct a Boolean dynamic model of the network, which allows in silico simulation of the stomatal closure response to high CO2 in wild-type Arabidopsis thaliana plants and in cases of pharmacological or genetic manipulation of network nodes. Our model has a 91% accuracy in capturing known experimental observations. We perform network-based logical analysis and reveal a feedback core of the network, which dictates cellular decisions in closure response to high CO2. Based on these analyses, we predict and experimentally confirm that applying nitric oxide (NO) induces stomatal closure in ambient CO2 and causes hypersensitivity to elevated CO2. Moreover, we predict a negative regulatory relationship between NO and the protein phosphatase ABI2 and find experimentally that NO inhibits ABI2 phosphatase activity. The experimental validation of these model predictions demonstrates the effectiveness of network-based modeling and highlights the decision-making role of the feedback core of the network in signal transduction. We further explore the models potential in predicting targets of signaling elements not yet connected to the CO2 network. Our combination of network science, in silico model simulation, and experimental assays demonstrates an effective interdisciplinary approach to understanding system-level biology.

systems biology↗

bioRxiv2023

Rotten to the core - a neurofunctional signature of subjective core disgust generalizes to socio-moral contexts

While disgust originates in the hard-wired mammalian distaste response, the conscious experience of disgust in humans strongly depends on subjective appraisal and may even extend to sociomoral contexts. In a series of studies, we combined functional magnetic resonance imaging (fMRI) with machine-learning based predictive modeling to establish a comprehensive neurobiological model of subjective disgust. The developed neurofunctional signature accurately predicted momentary self-reported subjective disgust across discovery (n=78) and pre-registered validation (n=30) cohorts and generalized across core disgust (n=34 and n=26), gustatory distaste (n=30), and sociomoral (unfair offers; n=43) contexts. Disgust experience was encoded in distributed cortical and subcortical systems, and exhibited distinct and shared neural representations with subjective fear or negative affect in interoceptive-emotional awareness and conscious appraisal systems while the signatures most accurately predicted the respective target experience. We provide an accurate fMRI-signature for disgust with a high potential to resolve ongoing evolutionary debates.

neuroscience↗