Biology subjects

Duan, K.

Publications and source records attributed to Duan, K..

At least 19 recordsLinked to original sources

bioRxiv2026

NLR from soybean Rsv1 locus confers broad-spectrum resistance to soybean mosaic virus G1-G7 strains by recognizing viral P3 protein

Nucleotide-binding leucine-rich repeat (NLR) immune receptor genes are of significant value in disease resistance breeding and the control of viral diseases. Soybean mosaic virus (SMV) poses a serious threat to soybean production and the Rsv1 locus in soybean cultivar Suweon 97 confers broad-spectrum resistance against SMV strains G1 to G7; however, this locus harbors no fewer than 18 NLR genes, and thus the broad-spectrum antiviral mechanisms underlying the Rsv1 locus remain poorly understood to date. Here, we established a rapid and highly efficient screening system for cloning NLR genes from soybean Rsv1 locus and identified a broad-spectrum antiviral NLR gene 13g184900 from this highly complicated locus. The NLR encoded by 13g184900 can recognize viral P3 protein from all SMV strains (G1-G7) and another potyvirus Bean common mosaic virus (BCMV). The coiled-coil (CC) domain of this NLR directly interacts with viral P3 protein. Additionally, we showed that this NLR originated from wild soybean accession in East China and has been introduced into several soybean cultivars during domestication. Collectively, we developed a high-throughput screening system for identifying NLR genes in soybean and our study provides new mechanistic perspective on how the Rsv1 locus mediates the broad-spectrum resistance to all SMV G1-G7 strains.

plant biology↗

bioRxiv2026

Genetic insights on the mechanisms of human cortical folding

The unique and intricate pattern of human cortical folding is rooted in fetal neurodevelopmental processes and can now be comprehensively quantified by new neuroimaging-derived measures of sulcal complexity. Here, we provide the first genetic maps of human sulcal complexity. Beginning with large effects of rare variants, we survey nine different neurogenetic syndromes (n=615), detecting visible changes in sulcal complexity on a shared axis of sulcal change coupled to the prenatal timing of sulcation. Turning to common genetic variants, we use genome-wide association studies of complexity scores for 40 sulci in the UK Biobank (n[~]29,000) to (i) resolve variable heritability across sulci, (ii) reveal both local and remote shared genetic effects with cortical morphology, and (iii) identify complexity-associated genes and their embedding in brain maps of prenatal gene expression. These reference genetic maps uncover multiple new mechanistic pathways for cortical morphogenesis in health and disease.

neuroscience↗

bioRxiv2026

Metabolic exchange and siderophore sharing underlie emergent biofilm synergism

Biofilm communities exhibit emergent properties that exceed the sum of contributions from individual members of the community. Here, we describe a multilayered metabolic interaction that drives enhanced biofilm formation among three bacterial species from the plant rhizosphere. Comparative metatranscriptomic and metabolomic analyses reveal that Bacillus velezensis-secreted 5-aminovaleric acid promotes the growth of the other community members, Burkholderia contaminans and Acinetobacter baumannii. In return, B. contaminans supplies branched-chain amino acids for B. velezensis. Branched-chain amino acids and cell-cell signaling acyl-homoserine lactones from B. contaminans induce biosynthesis of the siderophore bacillibactin in B. velezensis, that is further enhanced by A. baumannii. In exchange, the B. velezensis-secreted siderophore promotes the growth of B. contaminans in iron-limited conditions, which benefits the multispecies biofilm community in vitro and promotes plant growth performance in iron-depleted soil. Our study reveals the molecular mechanisms underlying an emergent rhizosphere biofilm community function and demonstrates its importance in plant-microbe interactions.

microbiology↗

bioRxiv2025

norCBD disruption affects the H2-type six secretion system and multiple virulence factors in Pseudomonas aeruginosa

The type six secretion system (T6SS) is a macromolecular weapon used by many Gram-negative bacteria. The T6SS functions as a needle injection system that delivers effector proteins directly into neighboring bacterial cells, thereby affecting their gene expression and physiological processes. Pseudomonas aeruginosa possesses three distinct T6SSs, designated as H1-, H2-, and H3-T6SS. Although extensive studies have been carried out on these T6SS systems in recent years, the regulatory mechanisms of T6SS remain incomplete. Here, we report the identification of norCBD as an operon that modulates the transcriptional activity of H2-T6SS. Both transposon insertion at norCBD and the deletion of the norCBD genes significantly reduced the CTX-H2-T6SS reporter activity. The norCBD operon encodes nitric oxide reductase (NorCBD), which reduces nitric oxide (NO) to nitrous oxide (N2O), a crucial step in reducing the toxic levels of intracellular NO and facilitating anaerobic respiration. As the transcriptional regulatory Dnr activates H2-type VI secretion system (H2-T6SS) in response to NO, experiments were carried out to examine whether norCBD deletion caused intracellular NO accumulation, which in turn disrupted Dnr-dependent regulation of H2-T6SS and virulence factors. The NO levels and Dnr-regulated gene expression were measured, and several virulence-related phenotypes were examined. The effects of NO donor sodium nitroprusside (SNP) and NO scavenger carboxy-phenyl-tetramethylimidazolineoxyl (CPTIO) were also tested. The data obtained indicate that deletion of norCBD led to intracellular NO accumulation, reduced H2-T6SS expression, and affected motility, pyocyanin production, and biofilm formation. Complementation of norCBD on a plasmid in the deletion mutant was able to restore H2-T6SS expression and the examined phenotypes to the wild-type levels. Treatment with CPTIO also restored H2-T6SS expression in the PAO1({Delta}norCBD). These results indicate that NorCBD plays a critical role in maintaining NO homeostasis that is necessary for effective Dnr-mediated gene regulation and multiple virulence-related traits, highlighting the importance of redox balance in coordinating respiration and pathogenesis in P. aeruginosa.

microbiology↗

bioRxiv2025

Why are so many fusogens rod-shaped?

Molecular fusogens catalyze membrane fusion for many basic biological processes. In eukaryotic cells, SNARE proteins drive membrane fusion for trafficking and for exocytic release in many contexts, from neurotransmission to enzymatic digestion, while other fusogens mediate cell-cell fusion for organ formation, placental development and gamete fusion. Enveloped viruses use glycoprotein fusogens for host cell entry and delivery of the viral genome. Despite this breadth of roles, a structural feature shared by many of these fusogens is their rod shape, conserved across the SNARE superfamily, the class I and II fusogen superfamilies and the class III fusogen family. Here we used highly coarse-grained molecular dynamics (MD) simulations to examine the collective behavior of rod-like fusogens on the microscopically long timescales of physiological membrane fusion. Rod-generated entropic forces maintained a cleared fusion site, squeezed and hemifused the membranes, and then expanded and ruptured the hemifused connection to yield fusion. More fusogens generated higher entropic forces and faster fusion, consistent with electrophysiological measurements at neuronal synapses. The required fusogenic feature was the rod shape, since simulated SNARE complexes, class II EFF-1 fusogens, and model rod-shaped complexes entropically drove fusion along similar pathways, whereas globular complexes failed. Thus, rod-like fusogens are optimally shaped generators of entropic forces that drive membrane fusion. These results suggest a universal rod-based fusion mechanism may have been the evolutionary driver of structural convergence among major classes of eukaryotic and viral fusogens. SignificanceLarge classes of eukaryotic and viral membrane fusion complexes are rod-shaped, a common structural feature despite a multiplicity of functions, from neurotransmission to organogenesis to cell entry. Here we used coarse-grained molecular dynamics to access the millisecond timescales of physiological fusion. Simulations revealed a universal mechanism whereby, regardless of structural details, rod-shaped fusogens generate entropic forces that drive fusion. This suggests the mechanism was a major evolutionary driver of structural convergence and multiple transmissions between eukaryotic hosts and viruses. Rod-mediated fusion is faster with more fusogens, explaining why release at presynaptic nerve terminals is enhanced or suppressed depending on the number of active SNARE fusogens. Thus, modulation of SNARE numbers and fusogenicities may represent a significant mechanism of synaptic plasticity.

biophysics↗

bioRxiv2025

aNy-way ICA and its application to estimate cortico-thalamo-cerebellar functional links in schizophrenia

Disrupted large-scale brain network interactions are a hallmark of schizophrenia, yet the circuit-level mechanisms underlying cognitive deficits remain incompletely understood. In particular, cortico-thalamo-cerebellar circuitry has been implicated in "cognitive dysmetria," but its functional organization across subdomains has not been fully characterized. Here, we apply a flexible multimodal data fusion framework (aNy-way independent component analysis) to integrate 4D domain-specific resting-state fMRI data from the cortex, thalamus, and cerebellum. Using a large discovery cohort (FBIRN, N=311) and two independent replication datasets (COBRE, N=148; MPRC, N=364), we identify a robust cortico-thalamo-cerebellar circuit involving higher-order thalamic nuclei, visual cortex, default mode network, and cerebellar posterior regions. This circuit shows altered connectivity in schizophrenia, characterized by reduced anticorrelation between thalamus and cortex, and is consistently associated with cognitive impairments, including processing speed, working memory, and reasoning deficits across cohorts. Importantly, these findings are largely replicated across independent cohorts. Together, these results provide data-driven evidence for a cortico-thalamo-cerebellar mechanism underlying cognitive dysfunction in schizophrenia, supporting the cognitive dysmetria hypothesis. This work also demonstrates the utility of aNy-way independent component analysis for identifying clinically relevant brain circuits in psychiatric disorders. HighlightsO_LIIdentified cortico-thalamo-cerebellar circuits in schizophrenia C_LIO_LIAltered thalamocortical interactions differentiated schizophrenia C_LIO_LICircuit alterations were associated with cognitive impairment C_LIO_LIFindings are replicated across three independent multisite datasets C_LIO_LIMultidomain fusion enabled subdomain-specific circuit characterization C_LI

neuroscience↗

bioRxiv2025

A Domain-Specific Language Model Approach for Identifying Immunogenic Epitopes from Publicly Available Data: EpitopeMiner

Personalized cancer vaccines represent a transformative approach in immunotherapy, leveraging tumor-specific antigens, such as neoantigens, to stimulate durable and targeted immune responses. However, identifying immunogenic neoantigen epitopes through conventional approaches - relying on in silico predictions followed by experimental validation - remains a significant challenge due to limitations of computational tools and scattering of experiment data. To address these challenges, we introduce EpitopeMiner, a domain-specific large language model (LLM) enhanced with a Retrieval-Augmented Generation (RAG) framework, specifically designed to identify immunogenic epitopes predicted by existing computational tools. EpitopeMiner utilizes a custom database of MHC-I-associated epitope-related literature to provide domain-specific knowledge, enhancing the precision and relevance of LLM-generated responses. EpitopeMiner offers three key features: First, the ability to identify epitopes with similar sequences and potentially similar immunogenic effects, which is especially valuable for neoantigens that are patient-specific and rarely found in public datasets. Second, it supports multiple epitope searches with structured outputs, enhancing scalability. Third, it provides original text chunks and paper identifiers, significantly simplifying validation and further exploration of the retrieved knowledge. Applying EpitopeMiner to well-characterized MHC class I epitopes demonstrates its ability to consistently retrieve relevant papers, efficiently providing targeted insights on T-cell response and immunogenicity, outperforming a commercial AI-powered literature tool. Notably, when applied to lymphoma patient-derived neoantigens, EpitopeMiner successfully retrieves immune response information for a few similar epitopes, despite operating with a relatively smaller database compared to the benchmark tool. All in all, EpitopeMiner bridges the gap between computational prediction and experimental validation, providing a scalable solution for extracting knowledge from public data, fostering cross-study synergies, and accelerating the development of personalized cancer vaccines.

cancer biology↗

bioRxiv2024

A Novel Registration Framework for Aligning Longitudinal Infant Brain Tensor Images

Registering longitudinal infant brain images is challenging, as the infant brain undergoes rapid changes in size, shape and tissue contrast in the first months and years of life. Diffusion tensor images (DTI) have relatively consistent tissue properties over the course of infancy compared to commonly used T1 or T2- weighted images, presenting great potential for infant brain registration. Moreover, groupwise registration has been widely used in infant neuroimaging studies to reduce bias introduced by predefined atlases that may not be well representative of samples under study. To date, however, no methods have been developed for groupwise registration of tensor-based images. Here, we propose a novel registration approach to groupwise align longitudinal infant DTI images to a sample-specific common space. Longitudinal infant DTI images are first clustered into more homogenous subgroups based on image similarity using Louvain clustering. DTI scans are then aligned within each subgroup using standard tensor-based registration. The resulting images from all subgroups are then further aligned onto a sample-specific common space. Results show that our approach significantly improved registration accuracy both globally and locally compared to standard tensor-based registration and standard fractional anisotropy-based registration. Additionally, clustering based on image similarity yielded significantly higher registration accuracy compared to no clustering, but comparable registration accuracy compared to clustering based on chronological age. By registering images groupwise to reduce registration bias and capitalizing on the consistency of features in tensor maps across early infancy, our groupwise registration framework facilitates more accurate alignment of longitudinal infant brain images.

bioengineering↗

bioRxiv2024

The Fem Cell-surface Signaling System is Regulated by ExsA in Pseudomonas aeruginosa and Affects Pathogenicity

Bacterial interspecies interactions shape the function and the structural dynamics of microbial communities and affect the progression of polymicrobial infections. The FemA-FemR-FemI (Fem) cell surface signaling system in Pseudomonas aeruginosa is known to be involved in the uptake of iron-chelating mycobactin produced by the Mycobacterium species. In this report, we present the data that indicates the femA-PA1909 operon was positively regulated by ExsA, a master regulator for the type three secretion system (T3SS), connecting the Fem system with T3SS. Intriguingly, the Fem system also influenced virulence factors in P. aeruginosa, including the quorum sensing systems, pyocyanin production, biofilm formation and the type six secretion systems (T6SSs). Using a Galleria mellonella infection model we observed that an femA deletion in PAO1 significantly increased the host survival rate while femI over-expression decreased it, suggesting a role for the Fem system in bacterial pathogenicity in vivo. Our data indicate the Fem system is a target of the T3SS master activator ExsA, and it affects P. aeruginosa pathogenicity.

microbiology↗

bioRxiv2024

Tradeoffs in ATP metabolisms via hypoxic gradient migration assays

Migration and scratch assays are helpful tools to investigate wound healing and tissue regeneration processes, especially under disease conditions such as diabetes. However, traditional migration (injury-free) assays and scratch (with injury) assays are limited in their control over cellular environments and provide only simplified read-outs of their results. On the other hand, microfluidic-based cell assays offer a distinct advantage in their integration and scalability for multiple modalities and concentrations in a single device. Additionally, in situ stimulation and detection helps to avoid variabilities between individual bioassays. To realize an enhanced, smarter migration assay, we leveraged our multilayered oxygen gradient (1-16%) to study HaCaT migrations in diabetic conditions with spatial and metabolic read-outs. An analysis of the spatial migration over time observed a new dynamic between hypoxia (at 4.16-9.14% O2) and hyperglycemia. Furthermore, in situ adenosine triphosphate (ATP) and reactive oxygen species (ROS) responses suggest that this dynamic represents a switch between stationary versus motile modes of metabolism. Thus, elevated glucose and hypoxia are synergistic triggers of this switch under disease conditions. These findings illustrate the benefits of spatial microfluidics for modeling complex diseases such as hypoxia and diabetes, where multimodal measurements provide a more deterministic view of the underlying processes.

bioengineering↗

bioRxiv2023

Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids

Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge of peri-implantation lineage developments as well as underlying mechanisms remain obscure. Using 3D-cultured human embryos, herein we report a complete cell atlas of the early post-implantation lineages and decipher cellular composition and gene signatures of the epiblast and hypoblast derivatives. In addition, we develop an embryo-like assembloid (E-assembloid) by assembling naive hESCs and extraembryonic cells. Using human embryos and E-assembloids, we reveal that WNT, BMP and Nodal signaling synergistically, but functionally differently, orchestrate human peri-implantation lineage development. Specially, we dissect mechanisms underlying extraembryonic mesoderm and extraembryonic endoderm specifications. Finally, an improved E-assembloid is developed to recapitulate the epiblast and hypoblast developments and tissue architectures in the pre-gastrulation human embryo. Our findings provide insights of the human peri-implantation development, and the E-assembloid offers a useful model to disentangle cellular behaviors and signaling interactions that drive human embryogenesis.

developmental biology↗

bioRxiv2023

Reduction in mRNA expression of the neutrophil chemoattract factor CXCL1 in Pseudomonas aeruginosa treated Barth Syndrome B lymphoblasts

Barth Syndrome (BTHS) is a rare X-linked genetic disease caused by a mutation in TAFAZZIN, a cardiolipin transacylase. Approximately 70% of patients with BTHS exhibit severe infections due to neutropenia. However, neutrophils from BTHS patients have been shown to exhibit normal phagocytosis and killing activity. B lymphocytes play a crucial role in the regulation of the immune system and when activated secret cytokines known to attract neutrophils to sites of infection. We examined expression of chemokine (C-X-C motif) ligand 1 (CXCL1), a known chemotactic for neutrophils, in Epstein-Barr virus transformed control and BTHS B lymphoblasts. Age-matched control and BTHS B lymphoblasts were incubated with Pseudomonas aeruginosa for 24 h and then cell viability, CD27+, CD24+, CD38+, CD138+ and PD1+ surface marker expression and CXCL1 mRNA expression determined. Cell viability was maintained in lymphoblasts incubated with a ratio of 50:1 bacteria:B cells. Surface marker expression was unaltered between control and BTHS B lymphoblasts. In contrast, CXCL1 mRNA expression was reduced approximately 90% (p<0.05) in untreated BTHS B lymphoblasts compared to control cells and approximately 70% (p<0.05) in bacterial treated BTHS B lymphoblasts compared to control cells. Thus, naive and bacterial-activated BTHS B lymphoblasts exhibit reduced mRNA expression of the neutrophil chemoattractant factor CXCL1. We suggest that impaired bacterial activation of B cells in some BTHS patients could promote immune dysfunction, and this may contribute to infections.

biochemistry↗

bioRxiv2023

Transcriptional heterogeneity in diabetic foot wounds

Wound repair requires the coordination of multiple cell types including immune cells and tissue resident cells to coordinate healing and return of tissue function. Diabetic foot ulceration is a type of chronic wound that impacts over 4 million patients in the US and over 7 million worldwide (Edmonds et al., 2021). Yet, the cellular and molecular mechanisms that go awry in these wounds are not fully understood. Here, by profiling chronic foot ulcers from non-diabetic (NDFUs) and diabetic (DFUs) patients using single-cell RNA sequencing, we find that DFUs display transcription changes that implicate reduced keratinocyte differentiation, altered fibroblast function and lineages, and defects in macrophage metabolism, inflammation, and ECM production compared to NDFUs. Furthermore, analysis of cellular interactions reveals major alterations in several signaling pathways that are altered in DFUs. These data provide a view of the mechanisms by which diabetes alters healing of foot ulcers and may provide therapeutic avenues for DFU treatments.

cell biology↗

bioRxiv2022

Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages

SARS-CoV-2 variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding working mechanisms and developing therapeutic agents. In this study, we characterized previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-EM structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

biochemistry↗

bioRxiv2021

ON/OFF domains shape receptive fields in mouse visual cortex

In higher mammals, thalamic afferents to primary visual cortex (area V1) segregate according to their responses to increases (ON) or decreases (OFF) in luminance1-4. This organization induces columnar, ON/OFF domains postulated to provide a scaffold for the emergence of orientation tuning2,5-15. To further test this idea, we asked whether ON/OFF domains exist in mouse V1 - a species containing orientation tuned, simple cells, like those found in other mammals16-19. Here we show that mouse V1 is indeed parceled into ON/OFF domains. Revealingly, fluctuations in the relative density ON/OFF neurons on the cortical surface mirror fluctuations in the relative density of ON/OFF receptive field centers on the visual field. In each cortical volume examined, the average of simple-cell receptive fields correlates with the difference between the average of ON and OFF receptive fields7. Moreover, the local diversity of simple-cell receptive fields is explained by a model in which neurons linearly combine a small number of ON and OFF signals available in their cortical neighborhoods15,20. Altogether, these findings indicate that ON/OFF domains originate in fluctuations of the spatial density of ON/OFF inputs on the visual field which, in turn, shapes the structure of receptive fields10-13,21-23.

neuroscience↗

bioRxiv2021

iPSC-derived Vascular Smooth Muscle Cells in a Fibronectin Functionalized Collagen Scaffold Augment Endothelial Cell Morphogenesis

Tissue-engineered constructs have immense potential as autologous grafts for wound healing. Despite the rapid advancement in fabrication technology, the major limitation is controlling angiogenesis within these constructs to form a vascular network. Here, we aimed to develop a 3D scaffold that can regulate angiogenesis. We tested the effect of fibronectin and vascular smooth muscle cells derived from human induced pluripotent stem cells (hiPSC-VSMC) on the morphogenesis of endothelial cells. The results demonstrate that fibronectin increases the number of endothelial networks. However, hiPSC-VSMC in the presence of fibronectin further substantiated the number and size of endothelial networks. A mechanistic study shows that blocking v{beta}3 integrin signaling between hiPSC-VSMC and fibronectin impacts the endothelial network formation. Collectively, this study set forth initial design criteria in developing an improved pre-vascularized construct.

bioengineering↗

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↗

bioRxiv2021

Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response

Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+ monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.

immunology↗