Biology subjects

Li, D.

Publications and source records attributed to Li, D..

At least 199 records · Page 11Linked to original sources

bioRxiv2025

A reference genome assembly of the alpine forage grass Elymus nutans

Elymus nutans Griseb. (Poaceae: Triticeae, 2n=6x=42) is a dominant perennial plant species in the Qinghai-Tibetan Plateau in China, which is an important forage resource in high-altitude and cold regions and is the most popular species used for high yield artificial grassland planting because of its rich nutritional value and good palatability for herbivorous ruminant animals. In this study, using advanced sequencing technology, we generated an allohexaploid reference genome for E. nutans, representing the three sets of chromosomes (subgenomes St, Y, and H). This is the first study to our knowledge to confirm the origin of the Y subgenome, which shares a close relationship with the V subgenome. We predict that E. nutans arose via two-step hybridization and that its speciation occurred [~]3.16 MYA. The whole genome in this study will update the Triticeae family genomics information and provide theoretical basis for the evolutionary of its related speicies.

plant biology↗

bioRxiv2025

Cerebellin-2 positive (Cbln2+) Neurons in the Parafascicular Thalamic Nucleus Regulate Self-Grooming Behavior

Self-grooming represents a stereotyped repetitive behavior which is commonly observed in various neuropsychiatric disorders. Deep brain stimulation (DBS) targeting the centromedian / parafascicular complex (CM/PF) has been shown to alleviate obsessive-compulsive disorder/behavior (OCD/OCB) symptoms in human. However, little is known about the neural circuits of the PF that are involved in the regulation of self-grooming behavior in rodents. Here, we report that cerebellin-2 positive (Cbln2+) neurons in PF bidirectionally encode self-grooming. Chemogenetic activation of Cbln2+ PF neurons significantly reduces both physiological and pathological self-grooming, and chemogenetic inhibition of Cbln2+ PF neurons increases physiological self-grooming. Moreover, activating synaptic excitatory inputs to Cbln2+ PF neurons inhibits self-grooming, while synaptic inhibitory inputs enhance it. Cbln2+ PF neurons independently transmit neural signals to the dorsal and ventral striatum. Activation of PF-dorsal striatum and PF-ventral striatum pathways both inhibit self-grooming behavior. Most excitingly, we alleviate excessive grooming in OCD mice by the activation of PF neurons using non-invasive ultrasound stimulation. Together, these data reveal that Cbln2+ PF neurons are integral components of a brain network involved in self-grooming behavior and highly promising targets in the non-invasive therapy of OCD.

neuroscience↗

bioRxiv2025

Fast in vivo deep-tissue 3D imaging with selective-illumination NIR-II light-field microscopy and aberration-corrected implicit neural representation

Near-infrared II (NIR-II) microscopy, which enables in vivo deep-tissue visualization of vasculature and cell activities, has been a promising tool for understanding physiological mechanisms. However, the volumetric image speed of the NIR-II microscopy is hindered by scanning strategy, causing limitations for observing instantaneous biological dynamics in 3D space. Here, we developed a NIR-II light-field microscopy (LFM) based on selective-illumination and self-supervised implicit neural representation (INR)-reconstruction, which allows ultra-fast 3D in vivo imaging (100 volumes/s). Through integrating INR with view-wise aberration correction, we could conquer the artifacts induced by the angular subsampling and refractive index variation, achieving single-cell resolution at a volume of 550 m diameter and 200 m thickness. The volumetric selective-illumination overcomes the influence of out-of-focus background, together with the low scattering advantage of NIR-II wavelength, extending the imaging depth to 600 m. The developed aberration-corrected implicit neural representation reconstruction (AIR) NIR-II LFM showcases its capability by monitoring hemodynamics of mouse brain under norepinephrine and flow redistribution of ischemic stroke in 3D vasoganglion, as well as noninvasively tracking immune cell activities inside subcutaneous solid tumor through intact skin. This approach represents a significant advancement in 3D in vivo imaging, holding great potential in biomedical research and preclinical studies.

neuroscience↗

bioRxiv2025

CDKL5 modulates structural plasticity of excitatory synapses via liquid-liquid phase separation

Activity-dependent synaptic remodeling, essential for neural circuit plasticity, is orchestrated by central organizers within the postsynaptic density (PSD), including the scaffolding protein PSD95. However, the molecular mechanisms driving this process remain incompletely understood. Here, we identify CDKL5, a protein associated with a severe neurodevelopmental condition known as CDKL5 deficiency disorder (CDD), as a critical regulator of structural plasticity at excitatory synapses. We show that CDKL5 undergoes liquid-liquid phase separation (LLPS) in vitro and in cultured neurons, forming co-condensates with PSD95. This LLPS-driven process spatially organizes synaptic components, specifically enabling the synaptic recruitment of Kalirin7 to promote dendritic spine enlargement. Pathogenic mutations disrupt condensate formation by impairing the LLPS capacity of CDKL5, directly linking phase separation defects to the pathogenesis of CDD. Our findings reveal a crucial role for CDKL5 in synaptic plasticity and establish LLPS as a fundamental mechanism by which CDKL5 coordinates molecular events to reorganize PSD architecture during synaptic remodeling.

neuroscience↗

bioRxiv2025

A rapid and efficient red-light-activated Cre recombinase system for genome engineering in mammalian cells and transgenic mice

The Cre-loxP recombination system enables precise genome engineering; however, existing photoactivatable Cre tools suffer from several limitations, including low DNA recombination efficiency, background activation, slow activation kinetics, and poor tissue penetration. Here, we present REDMAPCre, a red-light-controlled split-Cre system based on the {Delta}PhyA/FHY1 interaction. REDMAPCre enables rapid activation (1-second illumination) and achieves an 85-fold increase in recombination efficiency. We demonstrate its efficient regulation of DNA recombination in mammalian cells and mice, as well as its compatibility with other inducible recombinase systems for Boolean logic-gated DNA recombination. Using a single-vector adeno-associated virus (AAV) delivery system, we successfully induced REDMAPCre-mediated DNA recombination in mice. Furthermore, we generated a REDMAPCre transgenic mouse line and validated its efficient, light-dependent recombination across multiple organs. To explore its functional applications, REDMAPCre transgenic mice were crossed with the relative Cre-dependent reporter mice, enabling optogenetic induction of insulin resistance and hepatic lipid accumulation via Cre-dependent overexpression of ubiquitin-like with PHD and ring finger domains 1 (UHRF1), as well as targeted cell ablation through diphtheria toxin fragment A (DTA) expression. Collectively, REDMAPCre provides a powerful tool for achieving remote control of recombination and facilitating functional genetic studies in living systems.

synthetic biology↗

bioRxiv2025

Hemodynamic traveling waves transport musical codes faster than language codes via shared bilateral streams

What takes precedence in our brain: music or language? Here we used rapid phase-encoded fMRI to explore spatiotemporal brain dynamics during naturalistic music and language tasks, seeking to track down the entire perception-to-production process and compare the speed of information transfer between the two domains. We found largely shared streams of traveling waves bilaterally, along which musical codes were transported faster than language codes for identical visual input.

neuroscience↗

bioRxiv2025

Spatial distribution of the proteome in human body and cancers

A comprehensive spatial distribution of the proteome in human body and cancers is fundamental for understanding human biology and diseases including cancers. Here, we present an anatomically resolved human proteome derived from 1781 benign and malignant samples from 58 major tissue types encompassing 251 specific tissues and 25 carcinomas. Based on a spectral library covering over 75% of the human protein-coding genes with 208 understudied and 82 missing proteins characterized, we quantified over 13,000 proteins in these samples using data-independent acquisition proteomics. This data resource presents the so far most comprehensive quantitative proteomic landscape of human tissues and common carcinomas. It allows systematic evaluation of tissue-specific drug responses, identification of drug candidates that may be repurposed as antineoplastics, and discovery of novel targets for anticancer therapy. This resource, available as an online knowledgebase, refines our knowledge of spatial distribution of the human proteome and tumor-specific protein modulation.

systems biology↗

bioRxiv2025

Deep-learning-based interpolation of longitudinal microbiome data powers biologically informative discovery

The human microbiome is a foundational and dynamic foundation for several health-related functions and disease processes. Advances in microbiome sequencing have enabled the characterization of microbial communities in several niches. Longitudinal microbiome studies further strive to discover clinically informative microbial community trajectories. However, these data are fraught with dropout events, high noise, and irregular sampling that limit and prevent the use of many available longitudinal analysis tools. To address these challenges, we introduce Bidirectional GRU-ODE-Bayes (BGOB), a deep learning framework developed for longitudinal microbiome interpolation. BGOB combines bidirectional information flow and ODE-based continuous modeling to jointly interpolate and smoothen trends across individual participants, providing uniform, denoised time intervals across patients. BGOB enables vastly improved performance in differential abundance testing and time-to-event analysis, and makes possible longitudinal analyses requiring uniformity, such as lead-lag detection and temporal clustering. After interpolation, previously low-powered datasets are able to broadly recapitulate known microbiology and elucidate interacting microbial communities. We highlight several associations between microbial taxa and disease, including novel species associated with Early Childhood Caries and disruption of key healthy gut microbiota in Inflammatory Bowel Disease. The BGOB package is publicly available at https://github.com/Rachel-Lyu/BGOB_n_test.

microbiology↗

bioRxiv2025

Unraveling the mechanism of 1-deoxynojirimycin (DNJ) accumulation: the role of SWEET3 in mulberry chloroplasts

Transporters are crucial for the accumulation and secretion of plant metabolic products. 1-Deoxynojirimycin (DNJ), a natural compound widely distributed in nature and known for its medicinal properties, has production limitations in microorganisms and herbaceous plants. Mulberry leaves, being easy to harvest and growing rapidly, are the main source of DNJ. However, the current production from mulberry is insufficient to meet the demand. Improving DNJ content in mulberry and thereby reducing production costs is a significant challenge. We first used a green fluorescent tag to visualize the localization of DNJ and found that DNJ highly accumulates in the chloroplasts of mulberry leaves but not in callus tissue. The sugar transporter gene SWEET3, which is highly expressed in mulberry leaves but not in callus, was shown to have DNJ transport capability. Molecular docking analysis revealed that the acidic amino acid residues E68 and D126 in the SWEET3 protein are potential binding sites for DNJ, and both neutral and basic mutations at these sites significantly reduced the ability to DNJ-transporting ability of SWEET3. Furthermore, transient overexpression or RNA interference of SWEET3 in mulberry leaves significantly increased or decreased DNJ content, respectively. Similarly, stable overexpression of the SWEET3 in mulberry hairy roots led to an enhancement in DNJ content within the roots. Our results demonstrated that SWEET3 is essential for DNJ accumulation in mulberry. The study represents a breakthrough in increasing DNJ yield in mulberry through the key role of transporters and identify specific molecular targets required for developing mulberry germplasm with increased DNJ levels.

plant biology↗

bioRxiv2025

Infectome Analysis of Small Mammals in Southern China Reveals Ecological Associations and Emerging Threats from Diverse Pathogens

Small mammals harbor a diverse array of zoonotic pathogens. To date, however, metagenomic surveys of these species have primarily focused on viral diversity, with limited attention paid to bacteria and eukaryotic pathogens. Additionally, the ecological determinants of pathogen diversity within these mammals have not been systematically examined. Herein, we employed a metatranscriptomics approach to survey the pathogen infectome of 2,408 individual samples, representing lung, liver, and gut tissues from 858 animals collected throughout Guangdong province, China, with a study design that accounted for host species, tissue, season, and geographic location. We identified 76 pathogen species, including 29 RNA viruses, 12 DNA viruses, 5 bacteria, and 30 eukaryotic pathogens, 33 of which were newly discovered. Tissue distribution analysis revealed distinct organotropisms, suggesting varied transmission routes, while host distribution analysis showed that each animal carried an average of one pathogen, with 10 pathogens widely distributed among mammalian orders. Our characterization of the geographic and seasonal patterns revealed that pathogen richness was primarily influenced by region, host species, and season, while pathogen composition was largely shaped by host genetic distance. Collectively, these data provide the first comprehensive insight into the dynamics of the pathogen infectome in these key mammalian disease reservoirs, highlighting the major factors driving pathogen diversity and transmission.

microbiology↗

bioRxiv2025

Differences between Scaly-sided Merganser (Mergus squamatus) and Common Merganser (M. merganser) feather microstructure

The microstructures of breast feathers, flank feathers, rectrices, and down feathers of both Scaly-sided Merganser (Mergus squamatus) and Common Merganser (M. merganser) were meticulously examined using scanning electron microscope. The observed data were subjected to the Mann-Whitney U test, followed by hierarchical clustering and Fishers discriminant analysis of indicators with significant differences in morphological structure. The findings revealed statistically significant differences between Scaly-sided Merganser and Common Merganser in terms of the length of the base handle from distal barbules in the breast feathers, the length of the base handle, the number of hooked barbules, the number of cilia from distal barbules, and the number of ventral teeth from proximal barbules in rectrices. Additionally, variations in the distance between nodules, the nodular diameter, and the length of the base nodular of the down feathers were noted. Hierarchical clustering successfully categorized Scaly-sided Merganser and Common Merganser into distinct groups, achieving a 100% accuracy rate. Moreover, Fishers discriminant analysis demonstrated a 100% correctness rate when the back-substitution method was used to test the discriminant equation. Consequently, the length of the base handle of distal barbules in breast feathers, along with all selected indicators from rectrices and down feathers, may provide references to identify Scaly-sided Merganser and Common Merganser.

zoology↗

bioRxiv2025

Role of Age in Mediating the Association Between the Vaginal Microbiota and Preterm Birth

The vaginal microbiota plays a crucial role in vaginal health and pregnancy outcomes. However, the influence of maternal characteristics, especially age, on the relationship between the vaginal microbiota and preterm birth is poorly understood. This study quantifies the effects of race, maternal age, and gestational age on vaginal microbiota composition. Our results demonstrate stronger associations between preterm birth and a less optimal vaginal microbiota in White and Asian women compared to Black or African American women. The microbiota difference between preterm and term births was more pronounced in older reproductive-age women, with Lactobacillus species increasing with age only in term births. Additionally, lower alpha diversity was observed in term pregnancies compared to preterm during both early and late pregnancy, particularly in women aged above 25 years. These findings highlight the mediating role of age in the relationship between the vaginal microbiota and preterm birth.

microbiology↗

bioRxiv2025

Global loss of responsiveness in key regulator metabolites and elevated enzyme proteins as metabolic dysregulation in skeletal muscle and liver of obese mice during starvation

Starvation induces complex metabolic adaptations in skeletal muscle, a key tissue for maintaining energy homeostasis; however, these adaptations are largely impaired in obesity. How obesity alters global metabolic adaptations to starvation in skeletal muscle remains unclear. Here, we analyzed the metabolic adaptations on a trans-omics scale during starvation in skeletal muscle from wild-type (WT) and leptin-deficient obese (ob/ob) mice. We measured multi-omics data during starvation and constructed global trans-omics networks in WT and ob/ob mice. We found that starvation induces "responsiveness" in WT mice, characterized by increases or decreases in key regulator metabolites, including ATP and AMP, as well as enzyme proteins, leading to global regulation of metabolic pathways, which was lost in ob/ob mice. In contrast, during starvation, ob/ob mice exhibit "difference" in comparison to WT mice, manifested by the persistently elevated expression of metabolic enzymes. These features were similarly found in liver, another key metabolic organ. Thus, global loss of responsiveness and elevated enzyme proteins are systemic features of metabolic dysregulation in ob/ob mice.

systems biology↗

bioRxiv2025

Convergent flow-mediated mesenchymal force drives embryonic foregut constriction and splitting

The transformation of a two-dimensional epithelial sheet into various three-dimensional structures is a critical process in generating the diversity of animal forms. Previous studies of epithelial folding have revealed diverse mechanisms driven by epithelium-intrinsic or -extrinsic forces. Yet little is known about the biomechanical basis of epithelial splitting, which involves extreme folding and eventually a topological transition breaking the epithelial tube. Here, we leverage tracheal-esophageal separation (TES), a critical and highly conserved morphogenetic event during tetrapod embryogenesis, as a model system for interrogating epithelial tube splitting both in vivo and ex vivo. Comparing TES in chick and mouse embryos, we identified an evolutionarily conserved, compressive force exerted by the mesenchyme surrounding the epithelium, as being necessary to drive epithelial constriction and splitting. The compressive force is mediated by localized convergent flow of mesenchymal cells towards the epithelium. We further found that Sonic hedgehog (SHH) secreted by the epithelium functions as an attractive cue for mesenchymal cells. Removal of the mesenchyme, inhibition of cell migration, or loss of SHH signaling all abrogate TES, which can be rescued by externally applied pressure. These results unveil the biomechanical basis of epithelial splitting and suggest plausible mesenchymal origins of tracheal-esophageal birth defects.

developmental biology↗

bioRxiv2025

Catalytic degradation of circulating targets with FcRn-mediated cycling LYTACs

Circulating proteins are common targets for the discovery of occupancy-based inhibitors including monoclonal antibodies. Effective inhibition of target pathogenicity with blocking approaches, however, is often challenged by target parameters that lead to insufficient occupancy and/or incomplete pharmacology limited by only single site binding. Extracellular targeted protein degradation approaches, such as lysosomal targeting chimeras (LYTACs), offer an opportunity to minimize these challenges by an event-driven mechanism that selectively, thoroughly and irreversibly eliminates drivers of disease. First generation LYTACs, designed to traffic to the lysosome, show limited durability since the therapeutic is degraded along with the target protein of interest. Here we describe cataLYTACs, which overcome this limitation by combining stabilized asialoglycoprotein (ASGPR) ligands, pH-sensitive target binding and recycling via the neonatal Fc receptor (FcRn). These cataLYTACs degraded superstoichiometric levels of a target protein, IgE, in vitro and demonstrated deep and sustained clearance of human IgE in mouse models. In non-human primates, cataLYTACs resulted in >98% clearance of circulating endogenous IgE for 2 weeks and outperformed the standard of care blocking antibody, omalizumab (Xolair(R)), in both free IgE elimination and duration of action. CataLYTACs represent a new therapeutic modality for a wide range of disease states driven by circulating factors, with the potential for superior efficacy and duration of action compared to traditional inhibitors.

cell biology↗

bioRxiv2025

Ustilaginoidea virens suppresses floral immunity through promoting GA biosynthesis by the effector SCRE9

Rice false smut caused by Ustilaginoidea virens has become one of the most important rice diseases. U. virens specifically infects rice florets through stamen filaments. However, it is mysterious how U. virens inhibits floral immunity for successful colonization. Here, we show that a small cysteine-rich effector SCRE9 is a key virulence factor in U. virens. Expression of SCRE9 in rice not only suppresses immune responses and false smut resistance, but also significantly increases expression of expansin and gibberellin (GA) biosynthetic genes and GA content in young rice panicles. We further demonstrate that OsSIP1 (SCRE9-interacting protein 1) in rice is targeted by SCRE9 and interacts with the OsMADS63 and OsMADS68 transcription factors that transcriptionally regulate the GA synthesis gene GA3ox1. Interestingly, the chloroplast-localized OsSIP1 recruits OsMADS63/68 into the chloroplast. SCRE9 causes OsSIP1 to be translocated into the nucleus, thereby releasing OsMADS63/68 from the chloroplast into the nucleus to promote GA3ox1 transcription. Therefore, SCRE9 promotes GA biosynthesis and expression of expansins in rice florets, thus loosening cell walls and overcoming the physical barrier during U. virens infection. The finding uncovers an unidentified floret infection strategy that offsets the deficiency in cell wall degrading ability in the unique floret colonizing fungus.

plant biology↗

bioRxiv2025

Mapping Early Brain Maturation: Anatomical Substrates of Cortical Connectivity Shifts in Neonates

Understanding the early development of brain connectivity is essential for unraveling the mechanisms of brain maturation. In this study, we utilized diffusion MRI data from 242 term neonates to chart the developmental trajectory of cortical connectivity in infants. We quantified interareal variations in connectivity and identified three distinct global connectopies (GCs) along the rostrocaudal, dorsoventral, and mediolateral axes by using gradient mapping techniques. A pivotal age-dependent shift between the dorsoventral and mediolateral GCs occurred at 40 postmenstrual weeks. This shift was diminished by virtual thalamic fiber lesions, underscoring the critical role of thalamic projections. A longitudinal analysis disclosed a delayed structural connectivity pattern development in preterm infants who failed to exhibit the anticipated shift. This research helps to clarify the topographic principles that shape infant brain organization and emphasizes the influence of thalamic connectivity on early brain development. Our findings elucidate the anatomical underpinnings of early brain development, providing critical insights into the formation of cortical hierarchies and highlighting the influence of thalamic connectivity on developmental trajectories. These findings are essential for understanding typical brain growth and the pathogenesis of neurodevelopmental disorders.

neuroscience↗

bioRxiv2025

Sequestration of SerRS through LLPS Impairs Localized Translation and Contributes to Antibiotic Persistence

Antibiotic-tolerant persisters contribute to the emergence of resistance, posing a significant challenge to the efficacy of antibiotic therapies. Despite extensive research, the mechanisms underlying persistence remain inadequately understood. By tracking the evolution of exponential-phase bacterial populations subjected to intermittent high-dose ertapenem exposure, we characterized the evolved strains in terms of tolerance. Mutant strains, harboring mutations in the seryl-tRNA synthetase gene (serS), exhibited abrupt growth arrest upon serine depletion during exponential growth, resembling the persistence phenotype induced by serine hydroxamate (SHX). Under serine starvation, the mutated SerRS protein was sequestrated into liquid-liquid phase separation (LLPS)-driven condensates, disrupting their composition and impairing localized translation. This event precipitated growth arrest and dormancy in the SerST strain, triggering persistence. Our findings reveal an unrecognized role for aminoacyl-tRNA synthetases (aaRSs) in modulating bacterial condensates and provide insights into the molecular mechanisms underlying bacterial persistence. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/630848v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@1a69521org.highwire.dtl.DTLVardef@188b087org.highwire.dtl.DTLVardef@fd897forg.highwire.dtl.DTLVardef@14e1b6a_HPS_FORMAT_FIGEXP M_FIG SerRS Recruitment Disrupts Localized Translation in DeaD-marked Condensates. Upon serine starvation, SerRST partitions into LLPS-driven DeaD-marked condensates, impairing their localized translation activity and suggesting mechanisms underlying persistence arising during exponential phase. These evolutionarily conserved condensates orchestrate a robust translation program to enable stress responses and instruct cell fate decisions in bacterial populations. C_FIG

microbiology↗