Biology subjects

Shi, Z.

Publications and source records attributed to Shi, Z..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

RNA G-Quadruplexes Function as a Tunable Switch of FUS Phase Separation

FUS undergoes liquid-liquid phase separation (LLPS) to support essential cellular functions, but aberrant phase transitions promote toxic aggregation in neurodegenerative disease. Short RNA oligonucleotides can reverse this behavior, yet the structural determinants that govern RNA activity remain poorly defined. Here, we identify RNA G-quadruplexes (rG4s) as tunable structural motifs that potently modulate FUS LLPS. rG4 activity depends on its concentration and is modulated by rG4 length and stability: increasing repeat number switches rG4s from inhibitor to nucleator of FUS assembly, whereas chemical modifications that stabilize rG4 enhance inhibitory function and render these activities resilient to ionic perturbation. Although short rG4s interact with both soluble and condensed FUS, they preferentially engage the soluble pool, likely shifting the equilibrium toward dispersion. Leveraging these mechanistic insights, we developed a bioinformatic pipeline that uncovered more rG4 inhibitors that robustly reverse FUS LLPS and aggregation. Our findings establish rG4s as chemically programmable regulators of protein phase behavior and provide a blueprint for engineering RNA-based therapeutics that dissolve pathogenic FUS assemblies. More broadly, this work directly links RNA secondary structure to distinct functional outcomes in phase behavior, establishing a structure-function paradigm for RNA control of condensates, demonstrating implications in both fundamental biology and therapeutic development. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/685846v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1db3ea8org.highwire.dtl.DTLVardef@eec825org.highwire.dtl.DTLVardef@96187eorg.highwire.dtl.DTLVardef@2204ce_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

Long-acting naltrexone restores network connectivity in subjects with co-morbid cannabis and opioid use disorder

Co-morbid substance use disorders (SUDs) are common but difficult to study due to the complex, interacting, and overlapping mechanisms through which they affect brain networks. Many datasets collected to investigate a specific SUD include participants with co-morbid SUDs. While most studies treat comorbid SUDs as covariates of no interest, these covariates also contain untapped information. This is particularly relevant as cannabis use disorder (CanUD) has become increasingly prevalent and co-morbid with other SUDs that have been more thoroughly studied. While treatments have been established for multiple SUDs, none have been approved for CanUD, although naltrexone (NTX) has been associated with reduced use. Here, we conducted a retrospective secondary analysis of functional magnetic resonance imaging (fMRI) data from individuals with primary opioid use disorder (OUD) with co-morbid CanUD, alcohol use disorder (AUD), or cocaine use disorder (CocUD), while controlling for opioid use. All participants underwent imaging prior to receiving a therapeutic dose of long-acting intramuscular NTX (Vivitrol(R)), an approved treatment for OUD and AUD but not for CocUD, and again two weeks post-administration. At baseline, OUD individuals with co-morbid CanUD, AUD, or CocUD exhibited distinct functional connectivity (FC) alterations compared to those with OUD-only. These differences were greater in younger participants and primarily involved the default mode network. Following NTX administration, FC differences between the co-morbid CanUD and OUD-only groups globally diminished. A similar FC response to NTX was observed in the parietal, subcortical, sensory, and cerebellar networks in the co-morbid AUD group. In contrast, little change in FC was observed in co-morbid CocUD. These findings, combined with prior evidence that NTX reduces cannabis use by dampening the experience of reward, suggest NTX may hold promise as a treatment for CanUD.

neuroscience↗

bioRxiv2025

Response-driven Serial Dependence: When Response Mode Consistency Matters More than Shared Memory Encoding

Serial dependence - the bias from recent experience on present response - is often linked to shared memory representations. Yet, it remains unclear whether this bias across tasks when stimulus features are shared but response modes differ. To test this, we interleaved temporal reproduction and bisection tasks using a post-cue design that held duration encoding constant while varying motor output across trials. Using structural equation modeling (SEM), we dissociated perceptual (stimulus-driven) and decisional (response-driven) components of serial dependence. With consecutive same tasks, we replicated repulsive perceptual serial dependence and attractive decisional carryover. Critically, these effects vanished across tasks, despite identical stimulus processing - suggesting that consistent motor responses, not shared memory alone, drive sequential biases. Moreover, SEM uncovered repulsive perceptual influences that standard regression missed, highlighting its power to isolate overlapping effects. Together, these findings reveal that response-specific reactivation underpins serial dependence, pointing to motor-context binding as a key factor in temporal decision-making.

neuroscience↗

bioRxiv2025

Differential transcriptomics and metabolomics analyses of the skin of coarse and fine Liaoning cashmere goats

Secondary follicles in cashmere goats determine cashmere yield and quality. The present study investigated the relationship between the regulatory factors and cashmere fiber diameter through transcriptomics and metabolomics methods. Diameters of the fibers of 400 (18 months old) female Liaoning cashmere goats were measured and categorized into coarse and fine hair types (200 goats per category). Six goats were selected as representatives of each group for further analysis. Fiber diameters were significantly different between groups (P < 0.05). Transcriptomic analysis revealed 211 differentially expressed genes between groups, including FGF18, KRT36, KRT79, AWAT2, and MOGAT1, which were enriched in the PPAR and glycerol-lipid metabolism signaling pathways that regulate hair follicle growth and sebum secretion. Metabolomics analysis revealed 50 differentially expressed metabolites in the skin, which regulate cellular ion channels and participate in neurological channels by enriching ABC transporter protein pathways, amino acid biosynthesis and metabolism, and arachidonic acid metabolism. The findings of the present study could facilitate improvement of cashmere quality in cashmere goats.

genetics↗

bioRxiv2025

Bio-Inspired Ultrasound-Driven Ultrafast Soft Microgripper

Acoustically actuated soft matter offers potential for agile microscale manipulation, yet acoustic-soft matter interaction at the microscale remains poorly understood. Here, we explore the mechanism of ultrasound-soft matter interaction by developing a bio-inspired ultrasound-driven soft hydrogel microgripper. This exploration allows to delve deeper into the understanding of nonlinear dynamics, mode coupling, and energy transfer. The developed microgripper ([≤] 120 {micro}m) overcomes key challenges of existing grippers, including complex fabrication, reliance on additives or external wiring, rigid structures, slow or poorly controllable responses, and risks of sample damage or contamination. Interacting with acoustic actuation, soft microgrippers oscillate and deform, while adjusting acoustic parameters and microgrippers structures allows for programmable interactions. The optimized acoustic actuation of the soft microgripper enables precise, ultrafast ([~]2 ms) gripping and handling of distinct delicate objects. This work advances the integration of soft matter with acoustic actuation especially at the microscale, offering a versatile, reliable, and scalable solution for microrobotics, targeted drug delivery, and lab-on-a-chip applications. TeaserAcoustic-soft matter interaction validated on bio-inspired ultrasound-driven ultrafast soft microgrippers.

bioengineering↗

bioRxiv2025

Genome-Wide Investigation of Transcription Factor Occupancy and Dynamics Using cFOOT-seq

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences. Notably, cFOOT-seq, combined with FootTrack analysis, predicts TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.

molecular biology↗

bioRxiv2025

Hidden structure in polygenic scores and the challenge of disentangling ancestry interactions in admixed populations

The extent to which genetic effects vary across ancestries remains a central question in human genetics, with direct implications for improving polygenic prediction. Recent studies have found that average causal effects are similar across ancestries, but empirical evidence and theoretical considerations suggest that interactions may still contribute to poor portability of polygenic scores. Here, we leverage the ancestry mosaicism of admixed individuals to develop models of genetic interactions with local and global ancestry. We show that these models capture epistasis but are also consistent with highly similar average causal effects, clarifying that the latter observation does not exclude the possibility of gene-ancestry interaction. Next, we investigate how models of local and global interactions differ in polygenic prediction. Focusing on continuous traits, we show that if causal variants are known and causal effects differ across ancestries, then the global and local models can be differentiated using partial polygenic scores -- scores computed on ancestry-specific genomic segments -- while standard polygenic scores remain indistinguishable under both models. However, if causal variants are unknown, differences in linkage disequilibrium (LD) patterns confound this analysis, and the models are not practically distinguishable without knowledge of the LD between causal and tagging variants. Our findings motivate future developments of model-sensitive strategies for individual-level genetic risk prediction.

genetics↗

bioRxiv2025

Amphiphilic protein surfactants reduce the interfacial tension of biomolecular condensates

Biomolecular condensates are protein-dense regions in cells that often arise from liquid-liquid phase separation. Interfacial tension is a key determinant of biomolecular condensate behavior, influencing condensate size and interactions with intracellular structures. Certain proteins and RNAs are known to selectively localize to the interface of condensates, where they can regulate condensate function in cells. Previously, we designed amphiphilic proteins that preferentially adsorb to the surface of condensates. These proteins contain one phase-separating domain (RGG) and one non-phase-separating domain (MBP or GST). Here, we demonstrate through direct quantification that these amphiphilic proteins act as surfactants, reducing the interfacial tension of RGG-RGG condensates from [~]260 {micro}N/m to [~]100 {micro}N/m in a concentration-dependent manner. Notably, the GST-based surfactant protein exhibits a 10-fold greater efficacy in lowering interfacial tension compared to the MBP-based surfactant. We show that this increased efficacy is due to its higher surface density, driven by GSTs ability to oligomerize. We also show that these surfactant proteins slow droplet fusion and reduce average droplet size, as would be expected of a typical surfactant. Our findings quantitatively show how surfactant proteins can play a critical role in regulating the behavior of biomolecular condensates by modulating their interfacial tension. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/660548v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@b0d206org.highwire.dtl.DTLVardef@acb567org.highwire.dtl.DTLVardef@b99e5dorg.highwire.dtl.DTLVardef@4bf12b_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Arousal-Driven Serial Dependence: Internal States Modulate Perceived Duration

Emotional experiences shape not only how we perceive the present but also how recent experiences inform our current judgments. This study examined whether emotional arousal and valence modulate serial dependence in time perception--the tendency for prior stimuli to bias ongoing estimates. Participants viewed affective images that induced high-arousal (positive or negative) or low-arousal (neutral) states and then reproduced each images duration. High arousal reliably lengthened perceived durations. More critically, it strengthened serial dependence, with the strongest biases emerging when high-arousal trials followed other high-arousal trials, showing a state-dependent amplification of temporal integration. Emotional valence, by contrast, exerted no measurable influence on either temporal distortion or sequential bias. These findings show that emotional arousal tunes how the brain weighs past against present, highlighting internal emotional states as a key driver of temporal continuity in perception.

neuroscience↗

bioRxiv2025

The abscisic acid could reverse the cuproptosis in sepsis-associated acute kidney injury through the inhibition of ferredoxin-1

Sepsis-associated acute kidney injury (S-AKI) is a grave clinical condition with a poor prognosis. Prior studies have observed a potential correlation between copper (Cu) and S-AKI, though the underlying mechanisms remain to be fully elucidated. The present study aims to investigate the underlying mechanism between Cu and renal dysfunction under sepsis conditions. Utilizing a cecal ligation and puncture (CLP) murine model, we observed a substantial upregulation of inflammatory factors and deteriorated renal function (p<0.05), concomitant with an augmented mortality rate (p<0..05). Concurrently, the renal tissue exhibited a series of pathological manifestations, including fibrosis and cell death. Concurrently, the expression of the cuproptosis-regulating protein FDX-1 (p<0.05) was found to be elevated in CLP mice. Collectively, these data indicated the activation of cuproptosis in CLP-induced S-AKI. Intriguingly, the application of abscisic acid (ABA), a FDX-1 inhibitor, led to a substantial alleviation of mortality rate and inflammatory factor level (p<0.05). Furthermore, a significant alleviation was observed in renal pathology and biofunction (p<0.05). Collectively, these observations suggest that ABA exerts a protective effect on renal function during cuproptosis promoted S-AKI. Consequently, it can be concluded that ABA has the potential to reverse cuproptosis in S-AKI by inhibiting FDX-1.

molecular biology↗

bioRxiv2025

Multiple evolutionary events in host plant adaptation in Lepidoptera

The evolution of insect host adaptation is a key component of insect-plant coevolution, a complex process often shaped by multiple evolutionary events. In this study, we identified two UDP-glycosyltransferase (UGT) genes, SfruUGT33T10 and SfruUGT33F32, in the fall armyworm Spodoptera frugiperda, which play critical roles in the tolerance of benzoxazinoids (BXs), secondary metabolites in maize. These two detoxification enzymes exhibited distinct glycosylation patterns for BXs and varying detoxification efficiencies, reflecting independent evolutionary trajectories. Phylogenetic analyses revealed that SfruUGT33T10 originated independently within Noctuidae, while SfruUGT33F32 resulted from tandem duplication within the UGT33F gene family and may have undergone neofunctionalization within the Spodoptera genus. Our findings provide evidence that the evolution of these two UGT paralogs contributed to the variation in the tolerance to maize BXs among different Lepidopteran species. This research underscores the significance of multiple independent evolutionary routes in host plant adaptation and offer new insights into the complex evolutionary processes underlying insect-plant interactions.

evolutionary biology↗

bioRxiv2025

Brain Network Segregation is Associated with Drug Use Severity in Individuals with Opioid Use Disorder

Opioid use disorder (OUD) is associated with altered brain network connectivity, particularly in the fronto-parietal (FPN), default mode, and salience (SN) networks. At rest, brain networks that are distinct from each other but are partially connected can optimize neural efficiency and support cognitive performance. Previous research found lower network segregation in people with cognitive impairment, alcohol use disorder, and as people age. Here, we examined "brain network segregation"--a graph theory-based metric of the network integration/segregation balance--in individuals with OUD and hypothesized that recent drug use severity would be linked to reduced network segregation. Forty adults with OUD completed resting-state functional magnetic resonance imaging, the drug use severity subscale of the Addiction Severity Index, and measures of cognition (IQ and working memory), mood, and affect. We grouped 264 brain regions into 10 networks, categorized as "association" (higher-order cognition) or "sensorimotor" (sensory and motor) networks. Regression analyses showed that drug use severity predicted lower brain network segregation in the association networks, with the FPN and SN driving this effect. Age predicted lower brain network segregation in the sensorimotor networks, while an interaction with age showed that drug use severity only predicted lower sensorimotor network segregation in younger adults. Cognition did not relate to brain network segregation, but positive affect related to greater SN segregation. Brain network segregation remained stable across OUD treatment. These findings elucidate alterations in brain network segregation related to drug use severity in people with OUD, which may contribute to cognitive impairment and accelerated brain aging.

neuroscience↗

bioRxiv2025

The lysine side chain's swing motion in AapA1 toxin promotes water transport through transmembrane pores

The rising antibiotic resistance of Helicobacter pylori and the emergence of multi-drug-resistant strains pose significant challenges to its eradication. Understanding the molecular mechanisms driving this resistance is critical. This study investigates how AapA1, a toxin protein, may inhibit H. pylori growth and cause morphological changes by forming transmembrane pores in its inner membrane. Using experimental data and molecular dynamics simulations, we analyzed the pore structure and its formation mechanism. Results show that AapA1 forms pores on liposomes and exists stably in the membrane as -helices through different multimers, creating hydrophilic pores of varying sizes. Dynamic oscillation of K16/23 side chains in the membrane affects water transport through these pores, and restricting their movement significantly reduces transport. AapA1 monomers adopt three distinct conformations, with the K16/23 residues showing an up-down swing motion, potentially facilitating accelerated transport of substances. This study provides a new perspective on the dynamic structure-function relationship of AapA1-membrane interaction and highlights the role of positively charged residues in AapA1. Understanding the multimeric AapA1-membrane structure and the mechanism underlying AapA1-induced transmembrane pores is particularly crucial to develop new drugs and treatment options to reduce drug resistance emergence and combat any new emergence development.

biophysics↗

bioRxiv2025

SynBioGPT: A Retrieval-Augmented Large Language Model Platform for AI-Guided Microbial Strain Development

Synthetic biology seeks to engineer microbial cell factories for sustainable bioproduction, yet the optimization of these systems is impeded by the complexity of metabolic engineering and the protracted timelines of iterative design-build-test-learn (DBTL) cycles. Traditional computational approaches, such as constraint-based modeling, provide valuable insights but demand extensive manual curation. Large language models (LLMs) hold promises for automating knowledge extraction and strain design, yet conventional models like GPT-4 suffer from outdated corpora and hallucination errors in domain-specific tasks. SynBioGPT v1.0, a Retrieval-Augmented Generation (RAG)-enhanced LLM, enhanced knowledge retrieval using vector search but often retrieved semantically similar yet contextually irrelevant documents. Here, we introduce SynBioGPT v2.0 (https://synbiogpt.biodesign.ac.cn), which mitigates these limitations by decomposing queries into sub-questions and employing keyword-based searches. Tested on a 100-question synthetic biology benchmark, SynBioGPT v2.0 achieved 98% accuracy with the Claude-3.7-sonnet backend, a 10% improvement over v1.0s 88% with Llama3-8B-Instruct. This advance highlight the efficacy of query decomposition and precise retrieval in enhancing LLM utility for synthetic biology.

synthetic biology↗

bioRxiv2025

Modeling of hepatitis B virus infection spread in primary human hepatocytes

Chronic hepatitis B virus (HBV) infection poses a significant global health threat, causing severe liver diseases including cirrhosis and hepatocellular carcinoma. We characterized HBV DNA kinetics in primary human hepatocytes (PHH) over 32 days post-inoculation (pi) and used agent-based modeling (ABM) to gain insights into HBV lifecycle and spread. Parallel PHH cultures were mock-treated or HBV entry inhibitor Myr-preS1 (6.25 g/mL) was initiated 24h pi. In untreated PHH, 3 viral DNA kinetic patterns were identified: (1) an initial decline, followed by (2) rapid amplification, and (3) slower amplification/accumulation. In the presence of Myr-preS1, viral DNA and infected cell numbers in phase 3 were effectively blocked, with minimal to no increase. This suggests that phase 2 represents viral amplification in initially infected cells, while phase 3 corresponds to viral spread to naive cells. The ABM reproduced well the HBV kinetic patterns observed and predicted that the viral eclipse phase lasts between 18 and 38 hours. After the eclipse phase, the viral production rate increases over time, starting with a slow production cycle of 1 virion per day, which gradually accelerates to 1 virion per hour after 3 days. Approximately 4 days later, virion production reaches a steady state production rate of 4 virions/hour. The estimated median efficacy of Myr-preS1 in blocking HBV spread was 91% (range: 90-92%). The HBV kinetics and the predicted estimates of the HBV eclipse phase duration and HBV production cycles in PHH are similar of those predicted in uPA/SCID mice with human livers. ImportanceWhile primary human hepatocytes (PHH) are the most physiologically relevant culture system for studying HBV infection in vitro, comprehensive understanding of HBV infection kinetics and spread in PHH is lacking. In this study, we characterize HBV viral kinetics and employ agent-based modeling (ABM) to provide quantitative insights into the HBV production cycle and viral spread in PHH. The ABM provides an estimate of HBV eclipse phase duration, HBV production cycles and Myr-preS1 efficacy in blocking HBV spread in PHH. The results resemble those predicted in uPA/SCID mice with human livers, demonstrating that estimated HBV infection kinetic parameters in PHH in vitro mirrors that observed in in vivo HBV infection chimeric mouse model.

systems biology↗

bioRxiv2025

AAVone: A Cost-Effective, Single-Plasmid Solution for Efficient AAV Production with Reduced DNA Impurities

Currently, the most common approach for manufacturing GMP-grade adeno-associated virus (AAV) vectors involves transiently transfecting mammalian cells with three plasmids that carry the essential components for production. The requirement for all three plasmids to be transfected into a single cell and the necessity for high quantities of input plasmid DNA, limits AAV production efficiency, introduces variability between production batches, and increases time and labor costs. Here, we developed an all-in-one, single-plasmid AAV production system, called AAVone. In this system, the adenovirus helper genes (E2A, E4orf6, and VA RNA), packaging genes (rep and cap), and the vector transgene cassette are consolidated into a single compact plasmid with a 13-kb backbone. The AAVone system achieves a two- to four-fold increase in yields compared to the traditional triple-plasmid system. Furthermore, the AAVone system exhibits low batch-to-batch variation and eliminates the need for fine-tuning the ratios of the three plasmids, simplifying the production process. In terms of vector quality, AAVs generated by the AAVone system show similar in vitro and in vivo transduction efficiency, but a substantial reduction in sequences attributed to plasmid backbones and a marked reduction in non-functional snap-back genomes. In Summary, the AAVone platform is a straightforward, cost-effective, and highly consistent AAV production system - making it particularly suitable for GMP-grade AAV vectors.

bioengineering↗

bioRxiv2024

PlantRing: A high-throughput wearable sensor system for decoding plant growth, water relations and innovating irrigation

The combination of flexible electronics and plant science has generated various plant-wearable sensors, yet challenges persist in their applications in real-world agriculture, particularly in high-throughput settings. Overcoming the trade-off between sensing sensitivity and range, adapting them to a wide range of crop types, and bridging the gap between sensor measurements and biological understandings remain the primary obstacles. Here we introduce PlantRing, an innovative, nano-flexible sensing system designed to address the aforementioned challenges. PlantRing employs bio-sourced carbonized silk georgette as the strain sensing material, offering exceptional resolution (tensile deformation: < 100 m), stretchability (tensile strain up to 100 %), and remarkable durability (season long), exceeding existing plant strain sensors. PlantRing effectively monitors plant growth and water status, by measuring organ circumference dynamics, performing reliably under harsh conditions and being adaptable to a wide range of plants. Applying PlantRing to study fruit cracking in tomato and watermelon reveals novel hydraulic mechanism, characterized by genotype-specific excess sap flow within the plant to fruiting branches. Its high-throughput application enabled large-scale quantification of stomatal sensitivity to soil drought, a traditionally difficult-to-phenotype trait, facilitating drought tolerant germplasm selection. Combing PlantRing with soybean mutant led to the discovery of a potential novel function of the GmLNK2 circadian clock gene in stomatal regulation. More practically, integrating PlantRing into feedback irrigation achieves simultaneous water conservation and quality improvement, signifying a paradigm shift from experience- or environment-based to plant-based feedback control. Collectively, PlantRing represents a groundbreaking tool ready to revolutionize botanical studies, agriculture, and forestry.

plant biology↗

bioRxiv2024

Identification and genomic characterization of a novel bisegmented coronavirus in the lesser panda

Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses and are renowned for their capacity to infect a diverse range of animals, including humans. In this study, we report the identification and characterization of a novel bisegmented coronavirus, designated LpCoV, from a dead lesser panda, which exhibited severe clinical manifestations and lesions in multiple organs. The LpCoV represents the first documented coronavirus with a unique bisegmented genome while maintaining the typical coronavirus morphology. One genomic segment encodes the ORF1ab polyprotein, while the other segment encodes the spike and nucleocapsid proteins, notably lacking the envelope (E) and membrane (M) genes. The pairwise patristic distances of the five concatenated domains in the replicase region (3CLpro, NiRAN, RdRP, ZBD, and HEL1) between LpCoV and -{delta} coronaviruses range from 1.19 to 1.70. Based on the classification criteria established by the International Committee on Taxonomy of Viruses (ICTV), LpCoV is proposed to constitute a new genus within the Coronaviridae family. An epidemiological investigation identified five LpCoV-like viruses in lesser pandas from two different provinces (Sichuan and Jiangsu) indicating the long-term circulation and expansion of bisegmented coronaviruses in wildlife. These findings highlight the imperative for comprehensive viral surveillance in wildlife, which is essential for understanding and mitigating the risk of animal diseases and zoonotic spillover.

microbiology↗