Biology subjects

Ning, H.

Publications and source records attributed to Ning, H..

6 recordsLinked to original sources

bioRxiv2026

Brain state locks silent memories in a trained fly connectome

Complete connectomes now exist for insect nervous systems, but whether a fixed wiring diagram can learn, and what its memories consist of, is unknown. Here, we trained a spiking model of the whole male Drosophila central nervous system, 167,106 neurons with fixed wiring, to plan moves and to remember a visual cue. Spikes write the cue into neuronal adaptation, which holds it silently until the next input reads it out. Cells that hold the trace are enriched for transcripts of a calcium-activated potassium channel in fly cell atlases. The learned readout recalls the trace only in the brain state of learning: the same trace evokes a different response at another delay, and a disease-like loss of potassium current rewrites the trace and changes how it is read. Learning in the new state is spared. Memory failure can arise from a change of state rather than a loss of storage.

neuroscience↗

bioRxiv2026

IEKB: a comprehensive knowledge base for inner ear genetics integrating curated associations, cochlear interactions, Bayesian candidate prioritisation, explainable dark-gene support relations, and a scientific entity network

Inner-ear genetics has expanded rapidly, yet the supporting evidence remains dispersed across a vast literature and across resources that typically emphasise loci, variants, or expression data rather than integrated biological interpretation. Here we present the Inner Ear Knowledge Base (IEKB; https://earkb.org), an open database that unifies curated associations, cochlear interaction evidence, candidate prioritisation, explainable support relations, and network exploration for inner-ear research. IEKB was built with an automated agent-assisted curation workflow that combines schema-constrained literature extraction, continuous human monitoring, and final expert review by inner-ear genetics researchers. By systematically analysing 250,696 PubMed-indexed records retrieved across 16,563 screened genes, IEKB curates 6,051 gene-phenotype-disease associations from 2,494 genes across 43 phenotype categories and 4,102 cochlear gene-gene interactions with pathway, cell-type, and experimental context. IEKB further includes a Bayesian "dark matter" module that prioritises 243,071 candidate gene-phenotype associations for 13,229 genes across all 43 phenotypes (global AUC-ROC = 0.8603; global AUC-PR = 0.1674), together with a supervised dark-relation layer that ranks phenotype-specific known-gene support for each candidate and a multi-entity scientific network containing nearly 4,000 entities, 28,616 deterministic edges, and 83,712 literature-derived relational links. The web resource supports interactive search, multi-parameter filtering, gene-detail pages, bibliometric exploration, domain-specific enrichment against IEKB phenotype and disease gene sets, network visualisation, bulk download in CSV, JSON, SQLite, and XLSX formats, and natural-language evidence-grounded question answering through a companion conversational interface (IEKB QA). To our knowledge, IEKB is the first openly accessible inner-ear resource that integrates curated associations, cochlear interactions, probabilistic candidate prioritisation, auditable known-gene support relations for novel candidates, and a multi-entity scientific network within a single database. All data are released without registration under the CC BY 4.0 license.

bioinformatics↗

bioRxiv2025

Brain endothelial PRMT5-ANGPTL4 axis regulates cerebellar inhibitory synaptogenesis and motor coordination

Brain vasculature is essential for central nervous system function, but its specific roles in synaptic development and motor function regulation are poorly understood. In this study, we identify a cerebrovascular signaling axis wherein endothelial PRMT5 critically regulates inhibitory synaptogenesis and motor coordination. Cerebrovascular-specific deletion of Prmt5 gene leads to excessive inhibitory synaptic input onto Purkinje cells and progressive motor deficits in mice. Mechanistically, PRMT5 deficiency epigenetically upregulates the expression of the secreted factor ANGPTL4 through reduced symmetric dimethylation of H3R8 and H4R3, along with increased H3K9 acetylation at the Angptl4 promoter, thereby driving excessive inhibitory synaptogenesis onto Purkinje cells. Importantly, Angptl4 deletion in brain endothelium normalizes inhibitory synaptic input onto Purkinje cells and restores motor coordination in PRMT5-deficient mice. Together, these findings define the endothelial PRMT5-ANGPTL4 axis as a key regulator of cerebellar inhibitory circuitry and motor function, highlighting cerebrovascular mechanisms as potential therapeutic targets for motor coordination disorders. Teaser Cerebrovascular PRMT5 prevents excessive inhibitory synaptogenesis via epigenetic repression of Angptl4.

neuroscience↗

bioRxiv2023

Therapeutic Targeting of TIM-4-L With Engineered T Cells for Acute Myeloid Leukemia

Disruption of the lipid asymmetric bilayer is a common feature observed in cancer cells. We utilized the natural immune receptor TIM-4 to interrogate for loss of plasma membrane phospholipid polarity in primary acute myelogenous leukemia (AML) samples. We performed FACs analysis in 33 patients and correlated TIM-4-L expression frequency and intensity with molecular disease characteristics. In normal tissues, TIM-4-L is confined to the internal leaflet of the plasma membrane. By contrast, 86% of untreated AML blasts in our analysis displayed upregulation of cell surface TIM-4-L. These observations were agnostic to AML genetic classification, as samples with mutations in TP53, ASXL1, and RUNX1, also displayed TIM-4-L upregulation similar to that seen in favorable and intermediate subtypes. This TIM-4-L dysregulation was also stably present in both Kasumi-1 and MV-4-11 AML cell lines. To evaluate the potential of upregulated TIM-4-L to serve as a target for adoptive T cell therapy (ACT), we constructed TIM-4-L-directed engineered T cells, which demonstrated potent anti-leukemic effects, effectively eliminating AML cell lines both in vitro and in vivo. This approach led to the eradication of AML cells across a range of endogenous TIM-4-L expression levels. These results highlight TIM-4-L as a highly prevalent and novel target for T cell-based therapy in AML. Further investigations into the role of TIM-4-L in AML pathogenesis and its potential as an anti-leukemic target for clinical development are warranted.

cancer biology↗

bioRxiv2021

Dysfunction of novel energy sensor NFE2L1 leads to uncontrollable AMPK signal and glucose metabolism reprogramming

NFE2L1 (also called Nrf1) acts a core regulator of redox signaling and metabolism homeostasis, and thus its dysfunction results in multiple systemic metabolic diseases. However, the molecular mechanism(s) by which NFE2L1 regulates glycose and lipid metabolism is still elusive. Here, we found that the loss of NFE2L1 in human HepG2 cells led to a lethal phenotype upon glucose deprivation. The uptake of glucose was also affected by NFE2L1 deficiency. Further experiments unveiled that although the glycosylation of NFE2L1 was monitored through the glycolysis pathway, it enabled to sense the energy state and directly interacted with AMPK. These indicate that NFE2L1 can serve as a dual sensor and regulator of glucose homeostasis. In-depth sights into transcriptome, metabolome and seahorse data further unraveled that glucose metabolism was reprogrammed by disruption of NFE2L1, so as to aggravate the Warburg effect in NFE2L1-silenced hepatoma cells, along with the mitochondrial damage observed under the electron microscope. Collectively, these demonstrate that disfunction of NFE2L1 triggers the uncontrollable signaling by AMPK towards glucose metabolism reprogramming in the liver cancer development.

molecular biology↗

bioRxiv2021

Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.

immunology↗