Biology subjects

Liu, Z.-X.

Publications and source records attributed to Liu, Z.-X..

14 recordsLinked to original sources

bioRxiv2026

A Novel and Evolutionarily Conserved Metabolic Axis for Efficient Hepatic Lipid Catabolism Governed by Mfn2-Hsl-Mediated Mitochondria-Lipid Droplet Coupling

Inter-organelle contact between mitochondria and lipid droplets (LDs) is crucial for hepatic lipid homeostasis, but the tethering complex underlying this interaction remains unclear. To address this, we aimed to characterize the molecular machinery governing mitochondria-LD coupling and evaluate the evolutionary conservation of its metabolic functions. Using hepatocyte models from multiple species and in vivo experiments in yellow catfish with differential lipid and creatine diets, we explored the mechanism and evolutionary conservation of mitochondria-LD coupling. The key findings were: (1) A novel complex formed by mitofusin 2 on mitochondria and hormone-sensitive lipase on lipid droplets via specific residues orchestrates efficient hepatic lipid catabolism by mediating mitochondria-LD coupling; (2) Creatine enhances this coupling by transcriptionally upregulating mfn2 via hnf4, thereby promoting peridroplet mitochondria formation and alleviating hepatic lipid accumulation; (3) The Mfn2-phosphorylated HSL axis is evolutionarily conserved across fish and mammals, representing a potential therapeutic target for hepatic steatosis.

cell biology↗

bioRxiv2026

Synora: vector-based boundary detection for spatial omics

Tumor-stroma boundaries are critical microenvironmental niches where malignant and non-malignant cells exchange signals that shape invasion, immune modulation and therapeutic response. Spatial omics platforms now resolve these interfaces at single-cell scale, but computational boundary detection remains challenging because heterogeneous neighborhoods can arise either from true compartment interfaces or from unstructured immune infiltration. Here we present Synora, a modality-agnostic computational framework that identifies tumor boundaries using only cell coordinates and binary tumor/non-tumor annotations, making it readily applicable across a broad range of spatial omics modalities. Synora introduces orientedness, a novel metric that quantifies directional neighborhood asymmetry and distinguishes true boundary cells, where neighbors are spatially segregated by type, from infiltrated regions where cell types intermingle randomly. By integrating orientedness with traditional diversity measures into a unified BoundaryScore, Synora achieves robust boundary identification across synthetic datasets with ground-truth boundaries, maintaining performance under realistic perturbations including 50% missing cells and 25% infiltration. Application to 15 Visium HD spatial transcriptomic datasets across multiple cancer types reveals consistent boundary-enriched gene signatures and cell-type spatial gradients. Validation on a CODEX multiplexed protein dataset demonstrates that Synoras precise boundary identification enables discovery of clinically relevant cellular neighborhoods and disease-associated spatial patterns missed by frequency-based approaches. Synora enables boundary-aware spatial analyses by making tissue interfaces quantifiable from minimal inputs, helping to standardize interface detection and comparison across spatial omics platforms and biological contexts.

bioinformatics↗

bioRxiv2025

Effective connectivity between the medial temporal lobes and early visual cortex modulated by unrestricted viewing predicts memory retrieval and gaze reinstatement

Memory and gaze behavior are intricately linked, guiding one another to extract information and create mental representations of our environment for subsequent retrieval. Recent findings from functional neuroimaging and computational modeling suggest that reciprocal interactions between the extended hippocampal system and visuo-oculomotor regions are functionally relevant for building these mental representations during visual exploration. Yet, evidence for the directionality of information flow during encoding within this reciprocal architecture in humans is limited. In the current study, we used dynamic causal modeling (DCM) to give a non-invasive account for the directional influences between these systems when new memories are created. Here, we provide novel evidence demonstrating how unrestricted, naturalistic visual exploration induces changes in this connectivity. Subsequent memory retrieval performance was also predicted by the pattern of connectivity modulated by unrestricted visual exploration, identifying the mechanism underlying a rich history of previous work linking increased gaze behavior during encoding to later memory. Together, these findings suggest that gaze behavior shapes the ways in which brain dynamics within and between the hippocampal system and early visual cortex unfold during encoding in humans. Importantly, these directional interactions support the building of coherent, lasting mental representations.

neuroscience↗

bioRxiv2024

Impact of a transient neonatal visual deprivation on the development of the ventral occipito-temporal cortex in humans

How does experience shape the development of visual brain regions? We demonstrate that a transient period of visual deprivation early in life in humans leads to permanent alteration in the function of the early visual cortex (EVC), while leaving the categorical coding of downstream ventral occipito-temporal cortex (VOTC) mostly unaffected. We used fMRI to characterize the brain response to five categories (faces, bodies, objects, buildings and words) in a rare group of cataract-reversal individuals who experienced a transient period of blindness early in life, and in matched participants with typical visual development. We show that the encoding of low-level visual properties is impaired in EVC in cataract-reversal participants, while the categorical response in the VOTC is preserved. When altering the visual properties of our stimuli to mimic in controls the deficit of EVC response of the cataract, we observe a cascading alteration of the categorical coding from EVC to VOTC that is not observed in the cataract-reversal group. Our results show that a typical visual categorical organization develops in VOTC despite a period of visual deprivation early in life and in the presence of impaired processing in EVC. A deep neural network exposed to a visual diet that emulates the experience of our participants reproduced our brain observations within an artificial system. These findings emphasize how specific visual regions are differently affected by a period of visual deprivation early in life, with information encoded in EVC being permanently affected, while the categorical coding in VOTC shows resilience to deprivation.

neuroscience↗

bioRxiv2024

Rapid evolution of fine-scale recombination during domestication

Recombination serves as a pivotal force propelling the evolution of genomic diversity in sexually reproducing organisms. Despite its fundamental role, the evolutionary dynamics of recombination rates and their implications for genome evolution remain largely elusive. The domestication of animals, which is characterized by dynamic selection pressures, offers a unique lens to explore this issue. Here, we constructed a fine-scale recombination map leveraging whole-genome data from domestic chickens, encompassing both contemporary commercial breeds and the wild progenitor, the Red Junglefowl (RJF). Our analysis revealed the rapid evolution of the recombination landscape within and across chicken populations, with significant variation in recombination coldspots and hotspots, particularly in commercial breeds. The occurrence of coldspots and the disappearance of hotspots are closely associated with selective sweeps.Contrary to prevailing observations in most species, we observed a weakly negative correlation between recombination rates and the frequency of introgressed ancestry from other RJF subspecies. Our findings provide valuable insights into the intricate interplay of evolutionary forces shaping the evolution of recombination.

evolutionary biology↗

bioRxiv2024

Remembrance with gazes passed: Eye movements precede continuous recall of episodic details of real-life events

Autobiographical memory entails reconstructing the visual features of past events. Eye movements are associated with vivid autobiographical recollection, but this research has yet to capitalize on the high temporal resolution of eye-tracking data. We aligned eye movement data with participants simultaneous free recall of a verified real-life event, allowing us to assess the temporal correspondence of saccades to production of episodic and non-episodic narrative content at the millisecond level. Eye movements reliably predicted subsequent episodic - but not non-episodic - details by 250-1100 ms, suggesting that they facilitate episodic recollection by reinstating spatiotemporal context during vivid recollection. Assessing the relationship of oculomotor responses to naturalistic memory informs theory as well as diagnosis and treatment of conditions involving pathological recollection, such as Alzheimers disease and post-traumatic stress disorder (PTSD).

neuroscience↗

bioRxiv2021

iHypoxia: an integrative database of the expression dynamics of proteins in response to hypoxia in animals

Decreased oxygen concentrations (hypoxia) outside of the physiological range may severely subvert cell, tissue, and organism survival. Mammals have evolved mechanisms to sense hypoxia and induce a series of hypoxic responses. In recent years, high-throughput techniques have greatly promoted global perturbation studies of protein expression during hypoxia, and these studies have contributed to the understanding of the complex regulatory networks of hypoxia. In this study, we developed an integrated resource for the expression dynamics of proteins in response to hypoxia (iHypoxia), which contains 1,629 expression events of 1,215 proteins identified by low-throughput experiments (LTEs) and 154,953 quantitative expression events of 36,194 proteins identified by high-throughput experiments (HTEs) from five mammals that exhibit a response to hypoxia. Various experimental details such as the hypoxic experimental conditions, expression patterns, and samples were carefully collected and integrated. In addition, we conducted an orthologous search and identified 581,763 proteins that may respond to hypoxia among 50 animals. An enrichment analysis of human proteins identified from LTEs showed that these proteins were enriched in certain drug targets and cancer genes. The annotation of known posttranslational modification (PTM) sites to proteins identified by LTEs revealed that these proteins underwent extensive PTMs, particularly phosphorylation, ubiquitination and acetylation. Based on the results, iHypoxia provides a convenient and user-friendly method for users to obtain hypoxia-related information of interest. We anticipate that iHypoxia, which is freely accessible at http://ihypoxia.omicsbio.info, will advance the understanding of hypoxia and serve as a valuable data resource.

bioinformatics↗

bioRxiv2021

Unrestricted eye movements strengthen causal connectivity from hippocampal to oculomotor regions during scene construction

Scene construction is a key component of memory recall, navigation, and future imagining, and relies on the medial temporal lobes (MTL). A parallel body of work suggests that eye movements may enable the imagination and construction of scenes, even in the absence of external visual input. There are vast structural and functional connections between regions of the MTL and those of the oculomotor system. However, the directionality of connections between the MTL and oculomotor control regions, and how it relates to scene construction, has not been studied directly in human neuroimaging. In the current study, we used dynamic causal modeling (DCM) to interrogate effective connectivity between the MTL and oculomotor regions using a scene construction task in which participants eye movements were either restricted (fixed-viewing) or unrestricted (free-viewing). By omitting external visual input, and by contrasting free- versus fixed- viewing, the directionality of neural connectivity during scene construction could be determined. As opposed to when eye movements were restricted, allowing free viewing during construction of scenes strengthened top-down connections from the MTL to the frontal eye fields, and to lower-level cortical visual processing regions, suppressed bottom-up connections along the visual stream, and enhanced vividness of the constructed scenes. Taken together, these findings provide novel, non-invasive evidence for the causal architecture between the MTL memory system and oculomotor system associated with constructing vivid mental representations of scenes. HighlightsO_LIThe role of eye movements in mentally constructing scene imagery was investigated C_LIO_LIRestricting eye movements impaired vividness of constructed scene imagery C_LIO_LIMaking eye movements strengthened connectivity from memory to oculomotor regions C_LI

neuroscience↗

bioRxiv2021

Neural correlates of subsequent memory-related gaze reinstatement

Mounting evidence linking gaze reinstatement- the recapitulation of encoding-related gaze patterns during retrieval- to behavioral measures of memory suggests that eye movements play an important role in mnemonic processing. Yet, the nature of the gaze scanpath, including its informational content and neural correlates, has remained in question. In the present study, we examined eye movement and neural data from a recognition memory task to further elucidate the behavioral and neural bases of functional gaze reinstatement. Consistent with previous work, gaze reinstatement during retrieval of freely-viewed scene images was greater than chance and predictive of recognition memory performance. Gaze reinstatement was also associated with viewing of informationally salient image regions at encoding, suggesting that scanpaths may encode and contain high-level scene content. At the brain level, gaze reinstatement was predicted by encoding-related activity in the occipital pole and basal ganglia, neural regions associated with visual processing and oculomotor control. Finally, cross-voxel brain pattern similarity analysis revealed overlapping subsequent memory and subsequent gaze reinstatement modulation effects in the parahippocampal place area and hippocampus, in addition to the occipital pole and basal ganglia. Together, these findings suggest that encoding-related activity in brain regions associated with scene processing, oculomotor control, and memory supports the formation, and subsequent recapitulation, of functional scanpaths. More broadly, these findings lend support to Scanpath Theorys assertion that eye movements both encode, and are themselves embedded in, mnemonic representations.

neuroscience↗

bioRxiv2021

dSCOPE: a software to detect sequences critical for liquid-liquid phase separation

Membrane based cells are the fundamental structure and function units of organisms, while evidences were increasing that liquid-liquid phase separation (LLPS) is associated with the formation of membraneless organelles, such as P-bodies, nucleoli and stress granules. Many studies have been undertaken to explore the functions of protein phase separation, but these studies lacked an effective tool to identify the sequence segments that critical for LLPS (SCOPEs). In this study, we presented a novel software called dSCOPE (http://dscope.omicsbio.info) to predict the SCOPEs. To develop the predictor, we curated experimentally identified sequence segments that can drive LLPS from published literature. Then sliding sequence window based physiological, biochemical, structural and coding features were integrated by random forest algorithm to perform prediction. Through rigorous evaluation, dSCOPE was demonstrated to achieve satisfactory performance. Furthermore, large-scale analysis of human proteome based on dSCOPE showed that the predicted SCOPEs enriched various protein post-translational modifications and cancer mutations, and the proteins which contain predicted SCOPEs enriched critical cellular signaling pathways. Taken together, dSCOPE precisely predicted the protein sequence segments critical for LLPS, with various helpful information visualized in the webserver to facilitate LLPS related research.

bioinformatics↗

bioRxiv2020

Restricting visual exploration directly impedes neural activity, functional connectivity, and memory.

We move our eyes to explore the visual world, extract information, and create memories. The number of gaze fixations - the stops that the eyes make - has been shown to correlate with activity in the hippocampus, a region critical for memory, and with later recognition memory. Here, we combined eyetracking with fMRI to provide direct evidence for the relationships between gaze fixations, neural activity, and memory during scene viewing. Compared to free viewing, fixating a single location reduced: 1) subsequent memory, 2) neural activity along the ventral visual stream into the hippocampus, 3) neural similarity between effects of subsequent memory and visual exploration, and 4) functional connectivity among the hippocampus, parahippocampal place area, and other cortical regions. Gaze fixations were uniquely related to hippocampal activity, even after controlling for neural effects due to subsequent memory. Individual gaze fixations may provide the basic unit of information on which memory binding processes operate.

neuroscience↗

bioRxiv2019

Systematic Pan-Cancer Analysis Reveals the Functional Roles of Ferroptosis Across Cancers

Ferroptosis is a type of cell death that related to cancer, however, the characteristics of ferroptosis in cancers are still uncertain. Based on the data in The Cancer Genome Atlas, we found that most ferroptosis regulator genes (FRGs) were differentially expressed in tumors, copy number alterations (CNA) and DNA methylation contributed to their aberrant expression. We established the ferroptosis potential index (FPI) to reveal the functional roles of ferroptosis and noticed that the FPI was higher in tumors than in normal tissues in most cancers, and was associated with subtypes and clinical features. The FPI was negatively correlated with several metabolism pathways but positively associated with several important metastasis-related pathways and immune-related pathways. Higher FPI predicted worse prognosis in several tumors, while FPI and FRGs impacted drug sensitivity. Our study presents a systematical analysis of ferroptosis and its regulatory genes, and highlights the potential of ferroptosis-based cancer therapy.

cancer biology↗

bioRxiv2019

The Relationship between Parasitic Fleas and Small Mammals in Household of Western Yunnan Province, China

The Yunnan Province has one of the most serious outbreaks of the plague epidemic in China. Small mammals and fleas are risk factors for the occurrence of plague in commensal plague foci. Understanding the relationship between parasitic fleas and small mammals will help control fleas and prevent the onset of the plague. Four hundred and twenty-one small mammals, belonging to 9 species, were captured. Of these, 170 small mammals (40.4%) were infested with fleas. A total of 992 parasitic fleas (including 5 species) was collected. The number of Leptopsylla Segnis and Xenopsylla Cheopis was 91.0%. The final multiple hurdle negative binomial regression model showed that when compared with Rattus Tanezumi, the probability of flea infestation on Mus musculus and other host species decreased from 58% to 99%, while the infestation with fleas from other host species increased 4.7 fold. The probability of flea prevalence in adult hosts increased by 74%, while the number of fleas decreased by 76%. The number of flea infestations in small male mammals increased by 62%. The number of fleas in small mammals weighing more than 59 grams has been multiplied by about 4. Rattus Tanezumi is the predominant species in households in West Yunnan Province, while Leptopsylla Segnis and Xenopsylla Cheopis are dominant parasitic fleas. There is a strong relationship between the abundance of parasitic fleas and the characteristics of small mammals (e.g. Species, age, sex, and body weight).

zoology↗

bioRxiv2017

Differential spatiotemporal representations along the hippocampal long axis in humans

Increased place field size and signal autocorrelation along the dorsoventral hippocampal axis in rodents are considered a fundamental aspect of hippocampal organization, yet such evidence is lacking in humans. Using fMRI, we report corresponding evidence of increasing neural similarity from posterior to anterior hippocampus (dorsoventral homologues) in humans. These findings help account for observed shifting in representational granularity, from global context (anterior) to local details (posterior), along the hippocampal axis.

neuroscience↗