Biology subjects

Hong, Z.

Publications and source records attributed to Hong, Z..

At least 19 recordsLinked to original sources

bioRxiv2026

Brain organoid computing for robotic decision-making

Biomimicry has inspired the evolution of robotics toward greater autonomy, adaptability, and symbiosis with humans and dynamic environments. However, current robotic systems still face major challenges in recapitulating the high-efficiency decision-making capabilities of the human brain under complex and dynamic conditions. Here, we present Brainobot, a biohybrid robotic system that establishes a brain organoid controller as a high-level robotic decision-making layer for closed-loop embodiment. By leveraging brain organoid reservoir computing, Brainobot interacts with dynamic environments by receiving and processing sensory inputs and generating motor actions. As a proof-of-concept demonstration, Brainobot is implemented in a humanoid robotic system to perform real-world tasks, including object grasping and laser chasing. Interestingly, Brainobot exhibits unique features, including cross-task adaptivity, high computing efficiency, and low energy consumption. Thus, our approach may provide insights for advancing robotic embodiment and understanding biological decision-making.

bioengineering↗

bioRxiv2026

Targeting the Oxysterol Receptor GPR183 to Mitigate Fibrogenesis in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease with a median survival of 3-5 years after diagnosis. Current antifibrotic therapies slow disease progression, but do not halt or reverse fibrosis, underscoring the need for new therapies. We identified a dysregulated oxysterol-GPR183 axis as a driver of IPF. Oxidized cholesterols were elevated in lungs from IPF patients, with myofibroblasts representing the dominant source of 7,25-hydroxycholesterol (7,25-OHC), the endogenous high affinity ligand for the oxysterol-sensing receptor GPR183. IPF patients had increased GPR183 expression in interstitial and monocyte-like macrophages compared to controls. In a bleomycin-induced model of pulmonary fibrosis genetic deletion of GPR183 reduced disease severity characterized by reduced fibrosis, inflammation, and accumulation of macrophages and myofibroblasts. Pharmacological inhibition of GPR183 with the antagonist NIBR189 attenuated fibrosis when administered preventatively from day 1-7 after bleomycin exposure. Notably, therapeutic treatment with the GPR183 antagonist after commencement of fibrosis development at day 10 post-bleomycin also significantly reduced fibrotic pathology, achieving efficacy comparable to the approved antifibrotic nintedanib. However, the GPR183 antagonist was more potent in reducing inflammation and myofibroblast activation compared to nintedanib. Together, these findings identify an oxysterol-GPR183 signaling axis that contributes to pulmonary fibrogenesis and provide a strong preclinical rationale for targeting GPR183 as a novel therapeutic strategy for IPF. One Sentence SummaryTargeting GPR183 reduced lung fibrosis and inflammation in a preclinical model, supporting GPR183 as a promising new therapy.

immunology↗

bioRxiv2026

Patterns and correlates of invasive alien plant richness in China's abandoned croplands

Cropland abandonment is a widespread socio-ecological transition that can generate heterogeneous ecological outcomes, including opportunities for vegetation recovery as well as the accumulation of invasive alien plants (IAPs). Understanding broad-scale correlates of IAP richness in abandoned croplands is challenging because published studies differ in sampling design, spatial extent, and reporting detail. To provide an exploratory national-scale synthesis, we compiled literature-derived occurrence records of 57 IAP species reported from abandoned croplands across China and examined study-level recorded richness using generalized linear mixed models (GLMMs) with province as a random effect. Fourteen socio-economic and environmental predictors were screened for multicollinearity and standardized, and the number of Higher Education Institutions (HEIs) was included as a proxy for potential sampling-effort variation. Asteraceae accounted for 43.9% of recorded species, and more than 70% of taxa were classified as high-risk invaders (Levels 1-2). Recorded richness exhibited a pronounced southeast-northwest gradient, with higher values in economically developed coastal provinces. In the exploratory GLMM, regional GDP (IRR = 1.67, p < 0.05) and mean annual temperature (IRR = 1.49, p < 0.05) were positively associated with recorded richness, whereas other environmental, accessibility, soil, and sampling-effort variables showed no detectable associations. Model diagnostics indicated no evidence of overdispersion, zero inflation, or residual spatial autocorrelation. Given the heterogeneous nature of literature-derived data and the small number of study units, these results should be interpreted as broad-scale correlational patterns rather than causal drivers. The findings highlight regional socio-economic context and climatic conditions as key correlates of recorded IAP richness in abandoned croplands and provide an initial baseline for understanding invasion patterns in post-agricultural landscapes undergoing rapid land-use transitions..

ecology↗

bioRxiv2026

Total Biosynthesis of Pseudomonas aeruginosa-Derived Azabicyclocarbamates Identifies Distinct Dehydrating Condensation Family Proteins

Bacterial azabicyclocarbamates and related pyrrolizidine alkaloids play important roles in microbial interactions, and are scaffolds of therapeutic potential. Their biosynthesis involves a bimodular non-ribosomal peptide synthetase (NRPS), as well as a Baeyer-Villiger monooxygenase and tailoring enzymes, the latter contributing to the structural diversification of these compounds. Azetidomonamide A, a core metabolite produced by the major human opportunistic pathogen Pseudomonas aeruginosa, is a rare 4,7-bicyclocarbamate involved in modulating bacterial virulence that belongs to a unique family of natural products targeting ClpP proteases. In this study, we elucidated the full set of reactions leading to the 7-membered cyclocarbamate warhead, and reconstituted in vitro the biosynthesis of azetidomonamide A. Notably, this approach allowed for detailed characterization of a condensation (C) domain-catalyzed online dehydration via chemical capture of NRPS-tethered intermediates. Furthermore, we identified the dehydratase AzeD as the founding member of a distinct group of standalone proteins of the C domain family. Via combined structural, docking and biochemical analyses, we provided evidence that AzeDs catalytic mechanism is distinct from that of dehydrating C domains, further expanding the known chemistry of these key biosynthetic enzymes.

biochemistry↗

bioRxiv2026

A glycoRNA switch for malignancy: SNORA73B activates TIAR-dependent oncogenic signaling in lung adenocarcinoma

Although glycosylated small non-coding RNAs are emerging players in cancer, their functions in lung adenocarcinoma (LUAD) are largely unknown. We identify SNORA73B as a glycosylated small nucleolar RNA (glycol-snoRNA) that carries sialic acid-capped O-glycans in both normal lung epithelial and LUAD cells. SNORA73B is markedly elevated in LUAD, and its plasma levels distinguish early-stage LUAD from healthy controls with an area under the curve (AUC) of 0.7903. Subcellular fractionation reveals predominant nuclear localization. Functional assays demonstrate that SNORA73B depletion curbs LUAD cell proliferation, migration, and invasion, whereas its overexpression fosters these malignant phenotypes and accelerates tumor growth. Mechanistically, SNORA73B directly binds the T-cell-restricted intracellular antigen-related protein (TIAR), thereby enhancing TIAR protein abundance without affecting its mRNA levels. TIAR then recognizes the 3-untranslated region (3-UTR) of MYC mRNA to upregulate c-Myc, which subsequently augments AKT phosphorylation. Importantly, c-Myc knockdown largely rescues the oncogenic phenotypes and tumorigenesis induced by SNORA73B overexpression. Collectively, our data unveil a glycoRNA-dependent oncogenic axis SNORA73B-TIAR-c-Myc-AKT that drives LUAD progression. These findings position SNORA73B as a promising early diagnostic biomarker and a candidate therapeutic target in LUAD.

Cancer Biology↗

bioRxiv2026

The First 1,000 Days (1kD) Project - Collecting and Analyzing an Ultra-Dense Naturalistic Dataset of Human Baby Development

Human development unfolds in continuous, multimodal environments across seconds, days, and years, yet most developmental datasets capture sparse, context-limited samples of everyday life. We introduce the First 1,000 Days (1kD) Project, an initiative designed to collect ultra-dense, longitudinal, child-centered data that capture developmental trajectories within their full ecological context. Fifteen U.S. homes with 17 infants were recorded 12-14 hours per day over a median of 944 days, yielding [~]1.18 million hours of raw audiovisual data. We present an end-to-end framework for large-scale longitudinal naturalistic measurement and a scalable analysis pipeline of the collected data. In a case study, we describe how we utilized our pipeline to isolate child-centered speech, resulting in the collection of 2,000 to 6,000 hours of transcribed speech for each infant. We demonstrate that dense sampling within the home environment reveals a stable, household-specific lexical structure, which sparse sampling methods consistently fail to capture. The 1kD project offers a blueprint for teams aiming to collect and analyze natural behavior at scale in real-world settings.

neuroscience↗

bioRxiv2025

The structure of Egalitarian in complex with the K10 mRNA localization signal reveals a modular binding surface required for function

Asymmetric localization of mRNAs is a prevalent mechanism for spatial control of protein function and typically involves active transport by cytoskeletal motors. The mechanisms of recognition of localizing mRNAs by motor complexes are poorly understood. Egalitarian is an adaptor protein that binds localization signals in specific RNAs in Drosophila and recruits them to the dynein-dynactin complex for microtubule-based transport. We determined the crystal structure of Egalitarian in complex with the localization signal of the K10 mRNA. Three structural units of Egalitarian, a 3'-5'exonuclease domain, a linker and a C-terminal domain form shape-specific, base-directed and backbone interactions with the RNA. Based on the structure we identified conserved residues recognizing RNA in vitro. Genome-edited flies with mutations in these residues have deficits in Egalitarian function that are congruent with changes in in vitro RNA binding affinities. Our work demonstrates how a minimal RNA localization signal is recognized by an RNA localization factor.

biochemistry↗

bioRxiv2025

Target-Stabilized Base Editors Enable Robust High-Fidelity RNA Editing

RNA base editing using engineered deaminases expands target compatibility, offering a powerful tool to correct mutations at the RNA level. However, widespread off-target effects, primarily arising from dissociated free deaminases, remain a significant challenge. Here, we devised the RECODE (RNA editing with conditionally stable and enhanced ADAR1 deaminase variants) system, which employs designer degron-tagged ADAR1 deaminase (ADAR1d) with guide RNA (gRNA)-regulated stability. By promoting degradation of gRNA-unbound ADAR1d, RECODE markedly reduced transcriptome-wide edits while maintaining high on-target efficacy. Engineering gRNA for target RNA-induced conformational switching restricts ADAR1d stabilization, further enhancing editing precision. With structure-guided rational engineering of ADAR1d, RECODE achieved editing efficiencies of 90.3% and 58.8% for an Amyotrophic Lateral Sclerosis-relevant FUS mutation in vitro and in vivo, respectively. These findings establish RECODE as a highly stringent and efficient RNA editing technology and underscore a general principle for enhancing the specificity of RNA-guided protein effectors.

molecular biology↗

bioRxiv2025

Single-cell spatial transcriptome reveals pathological features of human hippocampus with sclerosis

More than half of epileptic patients ultimately turned to intractable epilepsy. Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), the most common type of intractable epilepsies, whose pathological mechanism remains elusive. Here, using 42 human hippocampal samples from surgical donors of MTLE (32 with and 10 without HS) through single-cell resolution Stereo-seq and histologcial experiments, we revealed spatially pathological changes of gene expression and cell type composition with HS systematically. After precise parcellation of hippocampal subregions and differentially expressed gene (DEG) analysis between each region with and without sclerosis, we found Cornu Ammonis (CA) subregions with higher number of DEGs were vulnerable to sclerosis, especially CA1 and CA3. Within CA1, we found that CA1-superficial and proximal areas were more vulnerable than CA1-deep and distal areas in sclerosis. Meanwhile, after analyzing 350,795 segmented cells from Stereo-seq, we found dramatically increasing density of astrocyte accompanied with significantly decreasing density of excitatory neurons in CA1, especially superficial and proximal CA1, and CA3 in sclerosis. In these two vulnerable subregions, proliferative astrocyte (P_astrocyte) and reactive astrocyte (R_astrocyte) were found to be enriched whereas apoptotic subtype of astrocyte (A_astrocyte), related with apoptotic pathway, was mainly located in alveus, which strengthened cell communication with reactive microglia (R_microglia) in HS, revealing the novel pathological feature in our work. The pseudotime analysis indicated that CA excitatory neurons underwent synaptic impairment, energy dysfunction, aging, and finally losing cell identity until death through autophagy or apoptosis. Besides, we also found a resilient subtype, EX_CA2-4.3, highly expressed extracellular matrix related genes including PDYN, and was increasing the interaction of BDNF-NTRK, NFASC-CNTN1 to withstand the damage from sclerosis. Together, our study provided a reference of human hippocampus with and without HS caused by MTLE, and highlighted the potential pathological mechanism on molecular and cellular level of MTLE-HS.

neuroscience↗

bioRxiv2024

Gut microbiota-derived GlcNAc-MurNAc is a TLR4 agonist that protects the host gut

Gut microbiota-derived peptidoglycan fragments (PGNs) are key signaling molecules that regulate multiple aspects of the hosts health. Yet the exact structures of natural PGNs in hosts have not been fully elucidated. Herein, we developed an LC-HRMS/MS analytical platform for global quantification and profiling of natural PGN subtypes in host gut and sera, unexpectedly revealing the abundance of PGN-derived saccharide moieties that do not resemble canonical ligands of mammalian NOD1/2 receptors. Focusing on the disaccharide GlcNAc-MurNAc (GM), a natural gut PGN that does not activate NOD1/2 yet still exhibits robust immunostimulatory effects in host immune cells, we unambiguously established GM as a TLR4 agonist, adding to the growing knowledge of NOD-independent mechanisms of PGN sensing in hosts. Importantly, the administration of GM effectively mitigates colonic inflammation in the DSS-induced colitis model in mice via TLR4-dependent mechanisms, highlighting the in vivo significance of natural gut microbiota-derived PGNs in maintaining host intestinal homeostasis.

biochemistry↗

bioRxiv2024

Scale matters: Large language models with billions (rather than millions) of parameters better match neural representations of natural language

Recent research has used large language models (LLMs) to study the neural basis of naturalistic language processing in the human brain. LLMs have rapidly grown in complexity, leading to improved language processing capabilities. However, neuroscience researchers havent kept up with the quick progress in LLM development. Here, we utilized several families of transformer-based LLMs to investigate the relationship between model size and their ability to capture linguistic information in the human brain. Crucially, a subset of LLMs were trained on a fixed training set, enabling us to dissociate model size from architecture and training set size. We used electrocorticography (ECoG) to measure neural activity in epilepsy patients while they listened to a 30-minute naturalistic audio story. We fit electrode-wise encoding models using contextual embeddings extracted from each hidden layer of the LLMs to predict word-level neural signals. In line with prior work, we found that larger LLMs better capture the structure of natural language and better predict neural activity. We also found a logarithmic relationship where the encoding performance peaks in relatively earlier layers as model size increases. We also observed variations in the best-performing layer across different brain regions, corresponding to an organized language processing hierarchy.

neuroscience↗

bioRxiv2024

Label-Free Electrochemical Imaging of Single Extracellular Vesicles

Extracellular vesicles (EVs) are pivotal in various biological processes and diseases, yet their small size and heterogeneity pose challenges for single EV quantification. We introduce interferometric electrochemical microscopy (iECM), a sensitive label-free technique that combines interferometric scattering and electrochemical impedance imaging. This method enables the quantification of the impedance of single EVs, providing unique insights into their electrochemical properties, and allows for the simultaneous measurement of size and real-time monitoring of antibody binding. Notably, we discovered that the impedance spectra of EVs can serve as unique fingerprints to differentiate EVs from cancerous and healthy cells, offering potential advancements in clinical diagnostics and the profiling of extracellular biomarkers.

biophysics↗

bioRxiv2024

popDMS infers mutation effects from deep mutational scanning data

Deep mutational scanning (DMS) experiments provide a powerful method to measure the functional effects of genetic mutations at massive scales. However, the data generated from these experiments can be difficult to analyze, with significant variation between experimental replicates. To overcome this challenge, we developed popDMS, a computational method based on population genetics theory, to infer the functional effects of mutations from DMS data. Through extensive tests, we found that the functional effects of single mutations and epistasis inferred by popDMS are highly consistent across replicates, comparing favorably with existing methods. Our approach is flexible and can be widely applied to DMS data that includes multiple time points, multiple replicates, and different experimental conditions.

bioinformatics↗

bioRxiv2023

Spartin-mediated lipid transfer facilitates lipid droplet turnover

Lipid droplets (LDs) are organelles critical for energy storage and membrane lipid homeostasis, whose number and size are carefully regulated in response to cellular conditions. The molecular mechanisms underlying lipid droplet biogenesis and degradation, however, are not well understood. The Troyer syndrome protein spartin (SPG20) supports LD delivery to autophagosomes for turnover via lipophagy. Here, we characterize spartin as a lipid transfer protein whose transfer ability is required for LD degradation. Spartin co-purifies with phospholipids and neutral lipids from cells and transfers phospholipids in vitro via its senescence domain. A senescence domain truncation that impairs lipid transfer in vitro also impairs LD turnover in cells while not affecting spartin association with either LDs or autophagosomes, supporting that spartins lipid transfer ability is physiologically relevant. Our data indicate a role for spartin-mediated lipid transfer in LD turnover. SignificanceThe Troyer syndrome protein spartin was proposed to function as a lipophagy receptor that delivers lipid droplets, organelles key for energy storage and membrane lipid homeostasis, to autophagosomes for degradation. We identify an additional function for spartin as a lipid transfer protein and show its transfer ability is required for lipid droplet degradation, including by lipophagy. Our data support that protein-mediated lipid transfer plays a role in lipid droplet turnover. Moreover, in spartins senescence domain we have discovered a new lipid transport module that likely also features in still undiscovered aspects of lipid droplet biology and membrane homeostasis.

cell biology↗

bioRxiv2022

Lactate-derived HDAC6 Lactylation as a new target for neuronal protection in cerebral ischemic reperfusion injury

Lactylation is a newly found lactate-derived post-translational modification, which is firstly reported on histone protein lysine residues to regulate gene expression. Here, we provided evidence that higher serum lactate level was possibly associated with better prognosis in ischemic stroke patients. Meanwhile, inhibition of endogenous lactate increased the infarct volume and decreased protein pan-lactylation in the affected brain tissue in cerebral ischemia mice. We further demonstrated that downregulating lactylation level of Hdac6 (Histone Deacetylase 6) in neurons exacerbated ischemic neuronal injury. The underlying mechanisms involved Hdac6 lactylation disturbing calcium homeostasis through binding BiP (Binding immunoglobulin protein), an endoplasmic reticulum-related protein. Collectively, our findings identified a new effect of lactate for neuroprotection through Hdac6 lactylation during cerebral ischemic reperfusion injury which introduced a potential therapeutic approach against ischemic stroke.

neuroscience↗

bioRxiv2022

Parallel Activation of Src and Hif1α Increases Localized Glycolytic ATP Generation for Re-assembly of Endothelial Adherens Junctions

Endothelial adherens junctions (AJs) are critical for the regulation of vascular barrier integrity and undergo dis-assembly during inflammatory injury, thus causing vascular leakiness. AJ re-assembly is thus necessary for restoration of the endothelial barrier following the initial injury. Here we examine the metabolic underpinnings that drive restoration of vascular integrity. In response to inflammatory stimuli, the glycolysis regulatory enzyme PFKFB3 is activated, resulting in a rapid and sustained increase of intracellular glycolytic ATP, especially in the proximity of AJs at the plasma membrane. We engineered a novel chemo-genetic construct (RapT) which allowed for precise temporal control of PFKFB3 recruitment to the plasma membrane. Activation of RapT by rapamycin during the barrier restoration phase increased regional ATP and accelerated AJ re-assembly. Mechanistically, we observed that PFKFB3 is activated through two modes. Src-mediated post-translational phosphorylation rapidly increases PFKFB3 activity. Using another chemo-genetic approach to temporally control Src activity, we found that Src activates PFKFB3 by binding to and phosphorylating it at residues Y175, Y334, and Y363. Tyrosine-phospho-deficient mutants of PFKFB3 at these residues block the glycolytic activation upon inflammatory stimuli. In parallel, elevated reactive oxygen species generated during inflammatory stimulation create pockets of regional hypoxia and allow for increased Hif1-mediated transcription of PFKFB3, leading to sustained glycolytic activation. Moreover, inhibition of PFKFB3 delays AJ reassembly and restoration of vascular integrity both in vitro and in vivo. In conclusion, we show that while inflammatory activation acutely compromises the endothelial barrier, inflammatory signaling also concomitantly generates a metabolic milieu in anticipation of the subsequent re-assembly of AJs and restoration of the vascular barrier.

cell biology↗

bioRxiv2022

Mechanisms by Which Small Molecule Inhibitors Arrest Sec14 Phosphatidylinositol Transfer Protein Activity

Phosphatidylinositol transfer proteins (PITPs) promote phosphoinositide signaling by enhancing phosphatidylinositol (PtdIns) 4-OH kinase activities in producing signaling pools of PtdIns-4-phosphate. As such, PITPs are key regulators of lipid signaling in eukaryotic cells. While the PITP phospholipid exchange cycle is the engine that stimulates PtdIns 4-OH kinase activity, the protein and lipid dynamics associated with this critical process are not understood. Herein, we use an integrative structural approach that takes advantage of small molecule inhibitors (SMIs) directed against the major yeast PITP (Sec14) to gain new insights into the mechanics of the Sec14 phospholipid exchange cycle from the perspective of protein, phospholipid and SMI dynamics. Moreover, as Sec14 has emerged as an attractive target for next-generation antifungal drugs, the structures of Sec14 bound to SMIs of four different chemotypes reported in this study provide critical information required for structure-based design of next-generation lead compounds that target Sec14 PITPs of virulent fungi.

biophysics↗

bioRxiv2022

Mitoguardin-2 is a lipid transporter and its lipid transfer ability is required for function

Lipid transport proteins at membrane contact sites, where organelles are closely apposed, are critical in redistributing lipids from the endoplasmic reticulum (ER), where they are made, to other cellular membranes. Such protein mediated transfer is especially important for maintaining organelles disconnected from secretory pathways, like mitochondria. Here we identify mitoguardin-2, a mitochondrial protein at contacts with the ER and/or lipid droplets (LDs), as a lipid transporter. An X-ray structure shows that the C-terminal domain of mitoguardin-2 has a hydrophobic cavity that binds lipids. Mass spectrometry analysis reveals that both glycerophospholipids and free-fatty acids co-purify with mitoguardin-2 from cells, and that each mitoguardin-2 can accommodate up to two lipids. Mitoguardin-2 transfers glycerophospholipids between membranes in vitro, and this transport ability is required for roles both in mitochondrial and LD biology. While it is not established that protein-mediated transfer at contacts plays a role in LD metabolism, our findings raise the possibility that mitoguardin-2 functions in transporting fatty acids and glycerophospholipids at mitochondria-LD contacts.

cell biology↗