Biology subjects

Gu, N.

Publications and source records attributed to Gu, N..

9 recordsLinked to original sources

bioRxiv2026

Enhancing precision medicine for patients with breast cancer brain metastases through functional drug testing

Patient-derived organoids from breast cancer brain metastases enable real-time drug sensitivity testing integrated with genomic profiling. Drug response varied by subtype and molecular alterations. PI3K inhibitors showed activity regardless of PIK3CA mutation status. Pronounced tumor heterogeneity highlighted the urgent need for effective therapies personalized for each patient. Functional assays and molecular matching can help tailor therapy for patients who need the most effective next treatment quickly and warrant further translational evaluation to address this unmet need.

cancer biology↗

bioRxiv2025

Dynamic Contrastive Learning with Pretrained Deep Language Model Enhances Metagenome Binning for Contigs

Metagenomic binning is crucial for reconstructing microbial genomes from metagenomic sequencing samples. However, existing tools struggle in complex communities where short, low-abundance contigs predominate, thereby limiting the recovery of complete metagenome-assembled genomes (MAGs) and the identification of novel functions. Here, we introduce CompleteBin, a Transformer-based framework that integrates contig sequence context, pre-trained taxonomic embeddings from a genome language model, and dynamic contrastive learning to bin short contigs robustly. Across CAMI II datasets, CompleteBin increased near-complete MAG recovery by 38.5% over leading methods like COMEBin. Across diverse real-world datasets (marine, freshwater, plant-associated, cold seep sediment, and human gut), it achieved a 57.4% improvement on average. Applying CompleteBin to six cold seep sediment samples uncovered 129 strain-level genome bins across 30 phyla, including 13 phyla undetected by other tools, and taxonomically assigned 90,405 genes (32.1% of total), revealing previously unknown species in nitrogen and sulfur cycling. CompleteBin unlocks microbial dark matter in diverse environments, advancing our understanding of microbial ecology and biogeochemical processes.

bioinformatics↗

bioRxiv2025

Microglia regulate neuronal activity via structural remodeling of astrocytes

Neuron-glia interactions play a central role in regulating synaptic transmission and neuronal excitability. Structural plasticity of astrocytes is associated with numerous physiological and pathological conditions, however, the mechanism underlying this process remains unknown. To examine the basis for structural astrocyte plasticity, we used the classic example of the loss of astrocytic processes that takes place in the hypothalamic magnocellular system during chronic high-salt intake. We discovered that a high-salt diet triggers a local accumulation of reactive microglia around vasopressin-secreting neurons, but not in other brain areas. Microglia phagocytose astrocytic processes, reducing astrocytic coverage of vasopressin neurons. The pruning of astrocytic processes impairs synaptic glutamate clearance, enabling activation of extrasynaptic glutamate NMDA receptors and increasing the activity of vasopressin neurons. Inhibiting microglia-mediated astrocyte pruning attenuates the increased neuronal activity and vasopressin-dependent hypertensive phenotype of rats fed high-salt diet. Thus, microglia orchestrate neuron-glia interactions and regulate neuronal activity through astrocyte pruning.

neuroscience↗

bioRxiv2024

Physics-Informed Ellipsoidal Coordinate Encoding Implicit Neural Representation for high-resolution volumetric wide-field microscopy

Wide-field fluorescence microscopy through axial scanning provides a simple way for volumetric imaging of cellular and intracellular activities, but the optical transfer function (OTF) of wide-field microscopy suffers from axial frequency deficiencies, leading to strong interference from out-of-focus fluorescence signals and reduced imaging quality. Richardson-Lucy (RL) deconvolution and its variants are commonly employed to reduce inter-plane signal interference of wide-field microscopy. However, these methods are still affected by the "missing cone" issue inherent in the OTF, compromising both the axial resolution and optical sectioning capability. Existing deep learning methods could realize high-fidelity 3D image stack restoration, but relying on high-quality paired datasets or specific assumptions about sample distributions. Here, we propose a novel method named physics-informed ellipsoidal coordinate encoding implicit neural representation (PIECE-INR), to tackle the challenges of background signal interference and resolution loss in axial scanning image stacks using the wide-field microscopy. In PIECE-INR, we integrate the wide-field fluorescence imaging model with the self-supervised INR network for high-fidelity reconstruction of 3D fluorescence data without the need of additional ground truth data for training. We further design a novel ellipsoidal coordinate encoding based on the systems OTF constraints and incorporate implicit priors derived from the physical model as the loss function into the reconstruction process. Our approach enables block-wise reconstruction of large-scale images by using localized physical information. We demonstrate state-of-the-art performance of our PIECE-INR method in volumetric imaging of live HeLa cells, large-volume C. elegans whole-embryo, and mitochondrial dynamics.

cell biology↗

bioRxiv2024

Translational control in the spinal cord regulates gene expression and pain hypersensitivity in the chronic phase of neuropathic pain

Sensitization of spinal nociceptive circuits plays a crucial role in neuropathic pain. This sensitization depends on new gene expression that is primarily regulated via transcriptional and translational control mechanisms. The relative roles of these mechanisms in regulating gene expression in the clinically relevant chronic phase of neuropathic pain are not well understood. Here, we show that changes in gene expression in the spinal cord during the chronic phase of neuropathic pain are substantially regulated at the translational level. Downregulating spinal translation at the chronic phase alleviated pain hypersensitivity. Cell-type-specific profiling revealed that spinal inhibitory and excitatory neurons exhibited substantial changes in translation after peripheral nerve injury. Notably, increasing translation selectively in all inhibitory neurons or parvalbumin-positive (PV+) interneurons, but not excitatory neurons, promoted mechanical pain hypersensitivity. Furthermore, increasing translation in PV+ neurons decreased their intrinsic excitability and spiking activity. Conversely, reducing translation in spinal PV neurons prevented the nerve injury-induced decrease in excitability but did not alleviate mechanical hypersensitivity. Together, these findings advance our understanding of translational control mechanisms in the spinal cord during neuropathic pain and highlight their cell-type- and phase-specific contributions to gene expression and pain hypersensitivity.

neuroscience↗

bioRxiv2023

Primate origins of human event cognition

Human language relies on a rich cognitive machinery, partially shared with other animals. One key mechanism, decomposing events into causally-linked agent-patient roles, however, has remained elusive with no known animal equivalent. In humans, agent-patient relations in event cognition drive how languages are processed neurally and expressions structured syntactically. We compared visual event tracking between humans and great apes, using stimuli that would elicit causal processing in humans. After accounting for attention to background information, we found similar gaze patterns to agent-patient relations in all species, mostly alternating attention to agents and patients, presumably in order to learn the nature of the event, and occasionally privileging agents under specific conditions. Six-month-old infants, in contrast, did not follow agent-patient relations and attended mostly to background information. We conclude that event role tracking, a cognitive foundation of syntax, evolved long before language but requires time and experience to become ontogenetically available. Significance statementHuman adults and great apes, but not human infants, track natural events as agent-patient relations, a cognitive foundation for syntax.

animal behavior and cognition↗

bioRxiv2023

Positive Transfer of the Whisper Speech Transformer to Human and Animal Voice Activity Detection

This paper introduces WhisperSeg, utilizing the Whisper Transformer pre-trained for Automatic Speech Recognition (ASR) for human and animal Voice Activity Detection (VAD). Contrary to traditional methods that detect human voice or animal vocalizations from a short audio frame and rely on careful threshold selection, WhisperSeg processes entire spectrograms of long audio and generates plain text representations of onset, offset, and type of voice activity. Processing a longer audio context with a larger network greatly improves detection accuracy from few labeled examples. We further demonstrate a positive transfer of detection performance to new animal species, making our approach viable in the data-scarce multi-species setting.1

animal behavior and cognition↗

bioRxiv2019

Spinal Microglia Contribute to Sustained Inflammatory Pain via Amplifying Neuronal Activity

Microglia are highly dynamic immune cells of the central nervous system (CNS). Microglial processes interact with neuronal elements constantly on the order of minutes. The functional significance of this acute microglia-neuron interaction and its potential role in the context of pain is still largely unknown. Here, we found that spinal microglia increased their process motility and electrophysiological reactivity within an hour after the insult in a mouse model of formalin-induced acute, sustained, inflammatory pain. Using an ablation strategy to specifically deplete resident microglia in the CNS, we demonstrate that microglia participate in formalin-induced acute sustained pain behaviors by amplifying neuronal activity in the spinal dorsal horn. Moreover, we identified that the P2Y12 receptor, which is specifically expressed in microglia in the CNS, was required for microglial function in formalin-induced pain. Taken together, our study provides a novel insight into the contribution of microglia and the P2Y12 receptor in acute, sustained, inflammatory pain that could be used for potential therapeutic strategies.

neuroscience↗

bioRxiv2018

A Novel AuNPs-based Glucose Oxidase Mimic with Enhanced Activity and Selectivity Constructed by Molecular Imprinting and O2-Containing Nanoemulsion Embedding

In spite of the competitive advantages, inorganic nanoparticle mimic enzymes exhibit inherent disadvantages of limited catalytic efficiency and lacking selectivity. Here a AuNPs based mimic enzyme with significantly enhanced glucose selectivity and catalytic activity was constructed and demonstrated for the first time. Aminophenylboronic acid was employed to increase the affinity to glucose, as well as build molecular imprinted polymer shells to realize the selectivity for template molecules of glucose. Besides that, heptadecafluoro-n-octyl bromide nanoemulsion with the function of providing oxygen was introduced to gain a further improvement in catalytic activity, which successfully enhanced the catalytic efficiency (kcat/Km) up to about 270-fold. Based on the demonstrated catalytic properties, AuNPs based glucose oxidase mimics have been successfully applied in practical glucose detection of drinks and blood glucose.

biochemistry↗