Biology subjects

Ning, X.

Publications and source records attributed to Ning, X..

18 recordsLinked to original sources

bioRxiv2026

A brain-tumour axis links chronic stress to gastric cancer progression through NPY signalling

Chronic stress promotes gastric tumour growth, but the central neural pathways remain largely enigmatic. Here, we identify a brain-tumour axis, implicating the central amygdala (CeA) activity in promoting gastric cancer growth through sympathetic neuropeptide Y (NPY) signalling occurring within the tumour. Using clinical datasets, patient samples, pathway tracing, electrophysiology and chemogenetic manipulation, we demonstrate that stress selectively increases NPY Y1 receptor (NPY1R) synthesis in the patients gastric cancer tissue; moreover, the NPY1R density correlates with advanced cancer stage and poor prognosis. In mice, daily constraint chronic stress enhances CeA excitability and promotes sympathetic neurotransmitter norepinephrine release within the tumour microenvironment. Norepinephrine, in turn, increases tumour endogenous NPY/NPY1R production and the activation of downstream MAPK/Erk1/2 signalling pathway, which drives cancer cell proliferation and invasion. Manipulating CeA neuronal activity alone can regulate tumour growth, whereas selectively blocking tumour NPY1R prevents stress-induced tumour progression in vivo and cancer cell migration in vitro. This study identifies a central-to-peripheral circuit linking chronic stress to gastric cancer growth, and highlights NPY1R as a potential therapeutic target.

Cancer Biology↗

bioRxiv2026

BiOmics: A Foundational Agent for Grounded and Autonomous Multi-omics Interpretation

While AI has automated bioinformatic workflows, biological interpretation remains fragmented and often disconnected from mechanistic insights. Existing AI is bifurcated between statistical "black-box" models that lack logical grounding and simple agents restricted to shallow knowledge retrieval. To bridge this divide, we introduce BiOmics, a foundational agent that synthesizes multi-omics data with adaptive knowledge for biological interpretation. BiOmics introduces a novel dual-track architecture comprising a harmonized explicit reasoning space for grounded logic and a unified latent embedding space for high-dimensional association mapping. This architecture enables a transformative "Retrieving-Reasoning-Predicting" paradigm for purposeful, cross-scale inference traversing the biological hierarchy, from molecular variants to disease phenotypes. Empirical evaluations demonstrate that BiOmics surpasses state-of-the-art AI agents and specialized algorithms, markedly augmenting the granularity and depth of biological insights. Specifically, BiOmics exhibits unique superiority in uncovering indirect pathogenic variants, achieving reference-free cell annotation, and prioritizing drug repurposing candidates tailored to specific datasets. BiOmics further enriches the interpretive landscape of biological entities, leveraging its reasoning-grounded knowledge graph to uncover deep functional contexts. Ultimately, BiOmics provides a versatile engineering foundation to transition AI for Science from descriptive "data fitting" to autonomous, knowledge-driven interpretation.

bioinformatics↗

bioRxiv2025

Central nervous system atlas of larval zebrafish constructed using the morphology of single excitatory and inhibitory neurons

Single-neuron morphology mapping is fundamental for deciphering brain architecture and function, yet in vertebrates it remains limited in spatial coverage and cell-type information. Here we present a nervous system-wide single-neuron morphology atlas of larval zebrafish with annotated excitatory/inhibitory identity and dendrite-axon polarity. The atlas comprises >20,000 reconstructed neurons from >13,400 animals, spanning the central and peripheral nervous system and representing [~]24.5% of the total excitatory and inhibitory neurons in the brain, all integrated into a common physical space with neuroanatomical parcellations. We define >500 excitatory and inhibitory neuronal morphotypes and construct putative inter-cell-type and interregional connectomes. Projection and morphotype analyses reveal distinct laterality and directionality biases and modular innervation patterns in excitatory and inhibitory neurons, while network analyses uncover fundamental connectivity motifs, hubs, and sensorimotor pathways. Accessible through custom-built interactive platform ZExplorer, this atlas provides a foundational resource for multimodal data integration, circuit analysis, computational modeling, and hypothesis-driven research.

neuroscience↗

bioRxiv2025

An Adipose mTORC1 Effector Links Nutrient-induced Ribosomal Protein Translation to Lifespan in Drosophila

Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to orchestrate metabolic processes critical for physiological homeostasis and organismal ageing1. While mTORC1 preferentially regulates the translation of 5'-terminal oligopyrimidine (TOP) motif-containing mRNAs that predominantly encode ribosomal proteins (RPs) via the translational repressor 4E-BP 2, this mTORC1 function is resistant to rapamycin inhibition 3. TOP mRNAs are exceptionally abundant, thus imposing a major translational burden on cells; yet how their translation is physiologically tuned and linked to longevity remain unexplored. Here we identify Lsp2, originally known as a storage protein 4, as an adipose effector of mTORC1 that modulates lifespan in Drosophila. Lsp2 is induced by essential amino acids (EAAs) via mTORC1. Genetic ablation of Lsp2 to blunt organismal response to protein diets drives robust lifespan extension without compromising key life-history traits such as reproduction. Translatomic profiling reveals that loss of Lsp2 selectively reduces global TOP mRNA translation in a 4E-BP-dependent manner, thereby extending lifespan via a mechanism distinct from rapamycin inhibition that fails to reduce 4E-BP phosphorylation in vivo. Finally, Lsp2 adipokine promotes 4E-BP phosphorylation and acts systemically across tissues to shape the lifespan responses to dietary protein. Collectively, our findings establish Lsp2 as a novel translational regulator of TOP genes that mechanistically couples physiological ribosomal protein synthesis with organismal longevity.

physiology↗

bioRxiv2025

Environmental stress sensitivity determines bacterial Mn(II) oxidation

Bacterial Mn(II) oxidation is a widespread and ecologically significant process, with Mn oxides playing essential roles in biogeochemical cycling and environmental remediation. However, the environmental cues that initiate this microbial activity remain enigmatic. In this study, a spontaneous mutant was isolated from the previously characterized Arthrobacter strain that exhibited autonomous Mn(II)-oxidizing capacity, in contrast to the parental strain, which required cocultivation with other bacteria to initiate Mn(II) oxidation1. Comparative transcriptomic analysis suggested that a gene system encoding an environmental stress-sensing receptor controlled the transcription of boxA, a Mn(II)-oxidizing gene. These findings indicate that two conditions are required for bacterial Mn(II) oxidation: the presence of a Mn(II)-oxidizing gene and an environmentally responsive regulatory system capable of activating its expression. Based on this knowledge, eight additional bacterial strains were isolated that triggered Arthrobacter Mn(II) oxidation. Transcriptomic profiling revealed a robust positive correlation between boxA expression and genes encoding two-component signal transduction systems. Given their widespread distribution (approximately 23% of environmental bacterial genomes harbor Mn(II)-oxidizing gene homologs2) and constant exposure to diverse biotic and abiotic stressors, these bacteria are likely to undergo frequent Mn(II) oxidation triggered by microbial interactions or chemical signals. This study provides critical mechanistic insight into the environmental regulation of bacterial Mn(II) oxidation, addressing a longstanding gap in understanding its natural occurrence.

microbiology↗

bioRxiv2024

An applicable and efficient retrograde monosynaptic circuit mapping tool for larval zebrafish

The larval zebrafish is a vertebrate model for in vivo monitoring and manipulation of whole-brain neuronal activity. Tracing its neural circuits remains challenging. Here, we report an applicable methodology tailored for larval zebrafish to achieve efficient retrograde trans-monosynaptic tracing from genetically defined neurons via EnvA-pseudotyped glycoprotein-deleted rabies viruses. By combinatorially optimizing multiple factors involved, we identified the CVS strain trans-complemented with advanced expression of N2cG at 36 {degrees}C as the optimal combination. It yielded a tracing efficiency of up to 20 inputs per starter cell. Its low cytotoxicity enabled the viable labeling and calcium imaging of infected neurons 10 days post-infection, spanning larval ages commonly used for functional examination. Cre-dependent labeling was further developed to enable cell-type-specific input tracing and circuit reconstruction. We mapped cerebellar circuits and uncovered the ipsilateral preference and subtype specificity of granule cell-to-Purkinje cell connections. Our method offers an efficient way for tracing neural circuits in larval zebrafish.

neuroscience↗

bioRxiv2024

Single-cell landscapes of long non-coding RNAs in early vascular endothelial development and hemogenic specification

Understanding the molecular regulation of arterial and hemogenic specification during early embryonic vascular development is crucial for guiding vascular and hematopoietic regeneration. Accumulating evidence emphasizes the role of long non-coding RNAs (lncRNAs) in cell fate decision. However, the dynamic expression and the potential roles of lncRNAs in early vascular development are still unknown. Here, we first constructed a single-cell landscape of lncRNA expression based on the deeply sequenced tag-based single-cell transcriptome data of early embryonic vascular endothelial cells (VECs). We revealed the contribution of lncRNAs to VEC heterogeneity and identified 295 lncRNAs with specific expression in eight VEC populations. Furthermore, we identified a series of lncRNAs potentially involved in regulating the two waves of arterial specification and hemogenic specification. We uncovered a transient downregulation of H19 in the hemogenic endothelial population during endothelial-to-hematopoietic transition. Additionally, we constructed a transcription factor regulatory network composed of 287 regulons for early VEC development. We further revealed differential activation patterns of regulons and modules in the eight VEC populations, and predicted potential lncRNA-regulon regulatory network. Moreover, unsupervised analysis of the lncRNA expression profile revealed novel VEC subpopulations strongly associated with the maturation of VECs, suggesting the prominent roles of lncRNAs in endothelial maturation. In summary, our study fills the gap in understanding of lncRNA regulatory networks in early vascular development and provides insights into the fields of vascular and hematopoietic regeneration research.

developmental biology↗

bioRxiv2023

Quorum-sensing gene regulates hormetic effects induced by sulfonamides in Comamonadaceae

Hormesis is a toxicological phenomenon whereby exposure to low-dose stress results in stimulation of various biological endpoints. Among these, the induction of cell proliferation by antibiotics is critical, but the underlying molecular mechanisms remain poorly understood. Here, we showed that sulfonyl-containing chemicals (e.g., sulfonamides) can induce cell-proliferation hormesis of Comamonas testosteroni. Investigation of the hormesis mechanism revealed that low-dose sulfonamides bind to the LuxR-type quorum sensing protein LuxR solo, thereby triggering the transcription of 3-ketoacyl-CoA thiolase, a key enzyme of the fatty acid {beta}-oxidation. This provides additional ATP, NADPH, and acetyl-CoA for purine and pyrimidine biosynthesis, allowing cells to synthesize sufficient nucleotides to support rapid cell growth. Our work reports on a previously unknown mechanism for the hormetic effect and highlights its generality in the Comamonadaceae family.

microbiology↗

bioRxiv2023

Manifold Learning Enables Interpretable Analysis of Raman Spectra from Extracellular Vesicle and Other Mixtures

Extracellular vesicles (EVs) have emerged as promising diagnostic and therapeutic candidates in many biomedical applications. However, EV research continues to rely heavily on in vitro cell cultures for EV production, where the exogenous EVs present in fetal bovine (FBS) or other required serum supplementation can be difficult to remove entirely. Despite this and other potential applications involving EV mixtures, there are currently no rapid, robust, inexpensive, and label-free methods for determining the relative concentrations of different EV subpopulations within a sample. In this study, we demonstrate that surface-enhanced Raman spectroscopy (SERS) can biochemically fingerprint fetal bovine serum-derived and bioreactor-produced EVs, and after applying a novel manifold learning technique to the acquired spectra, enables the quantitative detection of the relative amounts of different EV populations within an unknown sample. We first developed this method using known ratios of Rhodamine B to Rhodamine 6G, then using known ratios of FBS EVs to breast cancer EVs from a bioreactor culture. In addition to quantifying EV mixtures, the proposed deep learning architecture provides some knowledge discovery capabilities which we demonstrate by applying it to dynamic Raman spectra of a chemical milling process. This label-free characterization and analytical approach should translate well to other EV SERS applications, such as monitoring the integrity of semipermeable membranes within EV bioreactors, ensuring the quality or potency of diagnostic or therapeutic EVs, determining relative amounts of EVs produced in complex co-culture systems, as well as many Raman spectroscopy applications.

bioengineering↗

bioRxiv2022

Transparent and stretchable metal nanowire composite recording microelectrode arrays

Transparent microelectrodes have received much attention from the biomedical community due to their unique advantages in concurrent crosstalk-free electrical and optical interrogation of cell/tissue activity. Despite recent progress in constructing transparent microelectrodes, a major challenge is to simultaneously achieve desirable mechanical stretchability, optical transparency, electrochemical performance, and chemical stability for high-fidelity, conformal, and stable interfacing with soft tissue/organ systems. To address this challenge, we have designed microelectrode arrays (MEAs) with gold coated silver nanowires (Au-Ag NWs) by combining technical advances in materials, fabrication, and mechanics. The Au coating improves both the chemical stability and electrochemical impedance of the Au-Ag NWs microelectrodes with only slight changes in optical properties. The MEAs exhibit a high optical transparency >80% at 550 nm, a low normalized 1 kHz electrochemical impedance of 1.2-7.5 {Omega} cm2, stable chemical and electromechanical performance after exposure to oxygen plasma for 5 minutes and cyclic stretching for 600 cycles at 20% strain, superior to other transparent microelectrode alternatives. The MEAs easily conform to curvilinear heart surfaces for co-localized electrophysiological and optical mapping of cardiac function. This work demonstrates that stretchable transparent metal nanowire MEAs are promising candidates for diverse biomedical science and engineering applications, particularly under mechanically dynamic conditions.

bioengineering↗

bioRxiv2022

A Proposal for Finite But Unbounded Human Lifetimes

Close analysis of an extensive data set combined with independent evidence prompts our proposal to view human lifetimes as individually finite but collectively unbounded. We formulate a model incorporating this idea whose predictions agree very well with the observed data. In the model, human lifetimes are theoretically unbounded, but the probability of an individual living to an extreme age is negligible, so lifetimes are effectively limited. Our model incorporates a mortality hazard rate plateau and a late-life mortality deceleration effect in conjunction with a newly observed advanced age mortality acceleration. This reconciles many previously observed effects. The model is temporally stable: consistent with observation, parameters do not change over time. As an application, assuming no major medical advances, we predict the emergence of many individuals living past 120, but due to accelerating mortality find it unlikely that any will subsequently survive to an age of 125.

systems biology↗

bioRxiv2021

Improving MHC Class I antigen processing predictions using representation learning and cleavage site-specific kernels

In this work, we propose a new deep learning model, MHCrank, to predict the probability that a peptide will be processed for presentation within the MHC Class I pathway. We find that the performance of our model is significantly higher than two previously published baseline methods: MHCflurry and netMHCpan. Gains in performance result from the utilization of cleavage site-specific kernels and learned representations for amino acids. By visualizing the site-specific amino acid enrichment among top-ranked peptides, we find MHCranks top-ranked peptides are enriched at biologically relevant positions with amino acids that are consistent with previous work. Furthermore, the cosine similarity matrix derived from MHCranks learned embeddings for amino acids correlate highly with physiochemical properties that have been experimentally shown to be important in determining a peptides favorability to be processed. Altogether, the results reported in this work indicate that the proposed MHCrank demonstrates strong performance compared to existing methods and could have vast applicability to aid drug and vaccine development.

bioinformatics↗

bioRxiv2021

L-citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia

Preeclampsia, characterized by hypertension, proteinuria, and fetal growth restriction, is one of the leading causes of maternal and perinatal mortality. By far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of L-citrulline supplementation in Dahl salt-sensitive rat, a model of superimposed preeclampsia. Parental DSSR were treated with L-citrulline (2.5 g/L in drinking water) from the day of mating to the end of lactation period. Blood pressure of the rats was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant DSSR was assessed by wire myograph. L-citrulline supplementation significantly reduced gestational hypertension, proteinuria, and levels of circulating soluble fms-like tyrosine kinase 1 in DSSR. L-citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium-derived hyperpolarizing factor-mediated vasorelaxation in resistance arteries. L-citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition, L-citrulline downregulated genes involved in the toll-like receptor 4 and nuclear factor-{kappa}B signaling pathway. In conclusion, this study shows that L-citrulline supplementation reduces gestational hypertension, improves placentation and fetal growth in a rat model of superimposed preeclampsia. L-citrulline supplementation may represent an effective and safe therapeutic strategy for preeclampsia that benefit both the mother and the fetus.

pharmacology and toxicology↗

bioRxiv2021

A Mixture Model Incorporating Individual Heterogeneity in Human Lifetimes

Analysis of some extensive individual-record data using a demographically informed model suggests constructing a general population model in which the lifetime of a person, beyond a certain threshold age, follows an extreme value distribution with a finite upper bound, and with that upper bound randomized over the population. The resulting population model incorporates heterogeneity in life-lengths, with lifetimes being finite individually, but with extremely long lifespans having negligible probability. Our findings are compared in detail with those of related studies in the literature, and used to reconcile contradictions between previous studies of extreme longevity. While being consistent with currently reported analyses of human lifetimes, we nevertheless differ with those who conclude in favour of unbounded human lifetimes.

systems biology↗

bioRxiv2020

Characterization of miRNAs encoded by Autographa californica nucleopolyhedrovirus

Two Autographa californica nucleopolyhedrovirus (AcMNPV) encoded miRNAs, AcMNPV-miR-1 and -miR-3, have been reported in 2013 and 2019. Here, we present an integrated investigation of AcMNPV-encoded miRNAs. Six candidate miRNAs were predicted through small RNA deep sequencing and bioinformatics, of which, five validated by experiments. Three miRNAs perfectly matched the coding sequence of viral genes. The other two are located in coding sequences of viral genes. Targets in both virus and host were predicted and subsequently tested using dual-luciferase reporter assay. The validated targets were found mainly in AcMNPV, except for the targets of AcMNPV-miR-4, which are all host genes. Based on reporter assays, the five miRNAs predominantly function by down-regulating their targets, though individual target is slightly up-regulated. The transcription start sites of these miRNAs were analyzed. Our results suggest that AcMNPV-encoded miRNAs function as fine modulators of the interactions between host and virus by regulating viral and/or host genes. Author summaryVirus-encoded miRNAs have been widely reported as modulators participating in almost all biological processes. However, among Baculoviridae, which consists of a large family of dsDNA viruses that infect numerous beneficial insects and agricultural pests, only several have been reported encoding miRNAs. To clarify the roles of AcMNPV-encoded miRNAs in host-pathogen interactions, we employed RNA deep sequencing and series of experimental approaches identifying AcMNPV-encoded miRNAs, followed by target validation and function deduction. Among them, AcMNPV-miR-1 and AcMNPV-miR-3 have been reported in 2013 and 2019, respectively. This study reveals the sites of these miRNAs in the genome, both in coding sequences and complements, suggesting diverse functions. These miRNAs target genes in the virus itself and in the host, largely by suppressing expression, with some enhancing it. The transcription initiations of the miRNAs were analyzed. Our results provide some insight into the finely regulated process of baculovirus infection.

microbiology↗

bioRxiv2020

Siderophores provoke extracellular superoxide production by carbon-starving Arthrobacter strains when carbon sources recover

Superoxide and other reactive oxygen species (ROS) in the environment shape microbial communities1 and drive transformation of metals2,3 and inorganic/organic matter4,5. Taxonomically diverse bacteria and phytoplankton can produce extracellular superoxide during laboratory cultivation6-11. Understanding the physiological reasons for extracellular superoxide production by aerobes in the environment is a crucial question yet not fully solved. Here, we showed that iron-starving Arthrobacter sp. QXT-31 (referred to as A. QXT-31 hereafter) secreted a type of siderophore (deferoxamine, DFO), which provoked extracellular superoxide production by carbon-starving A. QXT-31 when carbon sources were recovered. Several other siderophores also demonstrated similar effects. RNA-Seq data hinted that DFO stripped iron from iron-bearing proteins in the electron transfer chain (ETC) of metabolically active A. QXT-31, resulting in electron leakage from the electron-rich (resulting from carbons source metabolism) ETC and superoxide production. Considering that most aerobes secrete siderophore(s)12 and often suffer from carbon starvation in the environment, certain aerobes are expected to produce extracellular superoxide when carbon source(s) recover/fluctuate, thus influencing the microbial community and cycling of many elements. In addition, an artificial iron-chelator (diethylenetriamine pentaacetic acid, DTPA) was widely used in microbial superoxide quantification. Our results showed that DTPA provoked superoxide production by A. QXT-31 and highlighted its potential interference in microbial superoxide quantification.

microbiology↗

bioRxiv2019

Intra-familial phenotypic heterogeneity and telomere abnormality in von Hippel-Lindau disease

Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome with poor survival. The current recommendations have proposed uniform surveillance strategies for all patients, neglecting the obvious phenotypic varieties. In this study, we aim to confirm the phenotypic heterogeneity in VHL disease and the underlying mechanism. A total of 151 parent-child pairs were enrolled for genetic anticipation analysis, and 77 sibling pairs for birth order effect analysis. Four statistical methods were used to compare the onset age of patients among different generations and different birth orders. The results showed that the average onset age was 18.9 years earlier in children than in their parents, which was statistically significant in all of the four statistical methods. Furthermore, the first-born siblings were affected 8.3 years later than the other ones among the maternal patients. Telomere shortening was confirmed to be associated with genetic anticipation in VHL families, while it failed to explain the birth order effect. Moreover, no significant difference was observed for overall survival between parents and children (p=0.834) and between first-born patients and the other siblings (p=0.390). This study provides definitive evidence and possible mechanisms of intra-familial phenotypic heterogeneity in VHL families, which is helpful to the update of surveillance guidelines.

genetics↗

bioRxiv2019

Drug Recommendation toward Safe Polypharmacy

Adverse drug reactions (ADRs) induced from high-order drug-drug interactions (DDIs) due to polypharmacy - simultaneous use of multiple drugs - represent a significant public health problem. Unfortunately, computational effects to facilitate future polypharmacy, particularly to assist safe multidrug prescription, are still in their infancy. We formally formulate the to-avoid and safe drug recommendation problems when multiple drugs have been taken simultaneously. We develop a joint model with a recommendation component and an ADR label prediction component to recommend for a prescription a set of to-avoid/safe drugs that will induce/will not induce ADRs if taken together with the prescription. We also develop real drug-drug interaction datasets and corresponding evaluation protocols.

bioinformatics↗