Biology subjects

Yue, Q.

Publications and source records attributed to Yue, Q..

14 recordsLinked to original sources

bioRxiv2026

Systematic evaluation of structural connectome thresholding in whole-brain network modelling

Large-scale whole-brain network models rely on structural connectomes to constrain simulated neural dynamics, yet the optimal processing of these anatomical scaffolds is not fully established. Here, we investigate the impact of structural connectome thresholding on whole-brain model performance to advance precision individual modelling. We measure model goodness-of-fit to both static functional connectivity and dynamic functional connectivity across a comprehensive spectrum of network densities, spatial parcellations, and model complexities using neuroimaging datasets of healthy individuals and a clinical cohort of post-stroke patients. We demonstrate that the optimal structural sparsity is highly resolution dependent. In coarse-grained parcellations, proportional thresholding enhances the model's fit to static functional connectivity but relies on denser connectome to maintain dynamic functional fits. Conversely, fine-grained models require stringent connectome thresholding which simultaneously optimizes both static and dynamic functional fits. Taken together, these results indicate that the uncritical use of raw structural connectomes introduces suboptimal dynamical regimes, establishing resolution-tailored thresholding as an indispensable step for constructing precision brain network models.

neuroscience↗

bioRxiv2025

Identification of Vector Organisms and Their Carried Pathogens by Metagenomic Sequencing

Vector surveillance is vital for public health, yet traditional methods often face limitations. This study assessed the use of metagenomic sequencing for analyzing mosquitoes, cockroaches, flies, and rodents from Zhongshan, China. The results revealed a high concordance between metagenomic and Sanger sequencing for species identification (Kappa = 0.667, P = 0.011). Metagenomic analysis identified vector-specific dominant bacteria, including Wolbachia in mosquitoes, Blattabacterium sp. in cockroaches, Bartonella tribocorum and Leptospira interrogans in rodents, and Vagococcus teuberi in flies. It also detected numerous classical pathogens, such as Enterococcus faecalis, L. interrogans, and Klebsiella pneumoniae. Among the identified fungi and viruses, 19 were human pathogens, while seven posed a threat to agriculture, notably Pepper mild mottle virus and Tomato brown rugose fruit virus. These findings systematically characterize the microbial communities associated with various vectors, highlight the potential of metagenomics for broad pathogen screening, and underscore its utility in large-scale vector surveillance and public health protection. ImportanceVectors are major carriers of numerous diseases and present risks fot cross-border transmission. Existing detection methods for vectors and their pathogens remain inefficient, insensitive, and prone to difficulties in species identification. Despite extensive efforts in vector identification, the potential threats posed by their associated pathogens remain unclear, demonstrating the need for more effective diagnostic strategies. Metagenomic sequencing offers a promising solution to this challenge. In this study, we applied metagenomic sequencing to vectors collected from urban and port areas in Zhongshan, China, to evaluate its efficacy in pathogen detection. Overall, our work contributes to a better understanding of the public health risks posed by vector-borne pathogens.

microbiology↗

bioRxiv2025

MPKaDB: A pKa Database for Exploring pH Dependence in Membrane Proteins

The biological activities of many membrane proteins are pH-regulated, yet mapping their pH dependence experimentally is slow and expensive. In this work, we present MPKaDB (http://computbiophys.com/DeepKa/mpkadb), a comprehensive pKa database for membrane proteins that instantly decode the protonation states of ionizable residues under a specified pH. Leveraging MPKaDB, we performed pH-coupled electrostatic characterization of trans-membrane proteins. To facilitate use, a user-friendly search engine was developed to retrieve a protein of interest and returns its pKa values, isoelectric points of both cytoplasmic and extra-cytoplasmic faces, and an automated screening of active-site residues. In the end, two case studies were proposed to demonstrate how pKas from MPKaDB could be applied to explore the pH-dependent relationship between membrane protein structure and function. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/688495v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@f90726org.highwire.dtl.DTLVardef@1448ac2org.highwire.dtl.DTLVardef@f1e4f4org.highwire.dtl.DTLVardef@ee57dc_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Development of high-affinity, single-domain protein binders for neutralizing household allergens

Feline, canine, and human dust mite allergens drive significant IgE-mediated allergies in the household environment. Here, we describe the discovery and characterization of novel protein binders, termed AVA, which efficiently bind and disrupt major allergens from cats (Fel d 1), dogs (Can f 1, Can f 2), and dust mites (Der p 1, Der p 2). Leveraging camelid single-domain variable-heavy chain (VHH) antibodies, we identified and optimized VHH sequences with robust affinity towards the individual allergens. AVA disrupted critical allergen substructures (Fel d 1) and catalytic functions (Der p 1) in molecular dynamics simulations and in in vitro assays, respectively. Paired with robust thermostability and non-toxic in vitro viability profiles, AVA represents a promising approach for downstream household allergen mitigation.

bioengineering↗

bioRxiv2024

MED26-enriched condensates drive erythropoiesis through modulating transcription pausing

The Mediator complex regulates various aspects of hematopoietic development, but whether composition of the Mediator complex undergoes dynamic changes for diversifying transcription and functional outputs is unknown. Here, we found that MED26, a subunit in the core Mediator complex, played a distinctive role in facilitating transcription pausing essential for erythroid development. While most Mediator subunits drastically decreased during this process, MED26 remained relatively abundant. Intriguingly, in the early stages, more than half of MED26 occupancy sites did not co-localize with MED1, a representative Mediator subunit, suggesting these subunits exert context-dependent gene regulation. We revealed that MED26-enriched loci were associated with RNA polymerase pausing. MED26 manifested a markedly preferential recruitment of pausing-related factors, leading to an increase in Pol pausing critical for genome-wide transcription repression during erythropoiesis. Moreover, MED26 exhibited pronounced condensate-forming capability, which was necessary for its function in promoting erythropoiesis and recruiting pausing-related factors. Collectively, this study provides mechanistic insights into the functional coordination of distinct Mediator subunits during development and highlights the switch of transcription condensates towards a MED26 enriched form, which modulates transcription pausing to facilitate transcription repression and erythroid development.

cell biology↗

bioRxiv2024

The divergence of DHN-derived melanin pathways in Metarhizium robertsii

The important role of dihydroxynaphthalene-(DHN) melanin in enhancing fungal stress resistance and its importance in fungal development and pathogenicity are well-established. This melanin also aids biocontrol fungi in surviving in the environment and effectively infecting insects. However, the biosynthetic origin of melanin in the biocontrol agents, Metarhizium spp., has remained elusive due to the complexity resulting from the divergence of two DHN-like biosynthetic pathways. Through the heterologous expression of biosynthetic enzymes from these two pathways in bakers yeast Saccharomyces cerevisiae, we have confirmed the presence of DHN biosynthesis in M. roberstii, and discovered a novel naphthopyrone intermediate that can produce a different type of pigment. These two pigment biosynthetic pathways differ in terms of polyketide intermediate structures and subsequent modification steps. Stress resistance studies using recombinant yeast cells have demonstrated that both DHN and its intermediates confer resistance against UV light prior to polymerization; a similar result was observed for its naphthopyrone counterpart. This study contributes to the understanding of the intricate and diverse biosynthetic mechanisms of fungal melanin and has the potential to enhance the application efficiency of biocontrol fungi such as Metarhizium spp. in agriculture.

microbiology↗

bioRxiv2024

Control of Inflammatory Response by Tissue Microenvironment

Inflammation is an essential defense response but operates at the cost of normal tissue functions. Whether and how the negative impact of inflammation is monitored remains largely unknown. Acidification of the tissue microenvironment is associated with inflammation. Here we investigated whether macrophages sense tissue acidification to adjust inflammatory responses. We found that acidic pH restructured the inflammatory response of macrophages in a gene-specific manner. We identified mammalian BRD4 as a novel intracellular pH sensor. Acidic pH disrupts the transcription condensates containing BRD4 and MED1, via histidine-enriched intrinsically disordered regions. Crucially, a decrease in macrophage intracellular pH is necessary and sufficient to regulate transcriptional condensates in vitro and in vivo, acting as negative feedback to regulate the inflammatory response. Collectively, these findings uncovered a pH-dependent switch in transcriptional condensates that enables environment-dependent control of inflammation, with a broader implication for calibrating the magnitude and quality of inflammation by the inflammatory cost. HighlightsO_LIAcidic pH regulates a switch-like gene-specific inflammatory response in macrophages C_LIO_LIAcidic pH impacts chromatin remodeling and transcription circuits to control inflammatory programs C_LIO_LIBRD4 transcriptional condensates are regulated by intracellular pH via the histidine-enriched intrinsically disordered region C_LIO_LITissue inflammation decreases intracellular pH and disrupts BRD4 condensates as a negative feedback C_LI

immunology↗

bioRxiv2023

Bioengineering of a Lactococcus lactis subsp. lactis strain enhances nisin production and bioactivity.

Lactococcus lactis subsp. lactis is a food bacterium that has been utilized for decades in food fermentation and the development of high-value industrial goods. Among these, nisin is produced by several strains of L. lactis subsp. lactis plays a crucial role as a food bio-preservative. The relative expression of the gene cluster involved in nisin production was evaluated using qPCR analysis. Additionally, a series of re-transformations of the strain introducing multi copies of the nisA and nisRK genes involved in nisin biosynthesis were developed. The simultaneous expression of nisA and nisZ genes was used to potentiate the effective inhibition of foodborne pathogens. Further, qPCR analysis revealed a low expression of the nisA and nisRK genes in wild-type L. lactis subsp. lactis. After several re-transformations of the strain with the nisA and nisRK genes, a high expression of these genes was obtained, contributing to improved nisin production. Also, the co-expression of nisA and nisZ genes results in highly efficient antimicrobial activity. Hence, this study would supply an approach to enhancing nisin production during industrial processes and antimicrobial activity.

microbiology↗

bioRxiv2022

Sequential functional differentiation of luminal epithelial cells regulated by maternal and embryonic signaling in the mouse endometrium

Embryo implantation requires temporospatial maternal-embryo dialog to regulate the interactions between an activated blastocyst and a receptive endometrium; however, the details of the related cell-specific coordination is largely unknown because of the cellular complexity and dynamic developmental processes of both the embryo and endometrium during peri-implantation. By comparing single-cell RNA (scRNA) data obtained from entire uteri of pregnant and pseudo-pregnant mice with embryos that were in the oviduct (dpc2.5 days post-coitum [dpc]) or had entered the uterus (after 3.5 dpc), we found a maternal estrogen and progesterone signaling-dependent functional differentiation process in which progesterone induced estrogen-responsive luminal epithelial cells to differentiate into two new types of epithelial cells: adhesion epithelial cells (AECs) and supporting epithelial cells (SECs) on 2.5 dpc. In addition to maternal signaling data, the uterine scRNA and corresponding embryo bulk sequencing data were obtained, and analyses revealed that embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, enhancing the attachment of embryos to the endometrium after implantation. Specifically, embryonic signaling induced additional transformation of AECs by preventing adjacent AECs, but not AECs away from the embryo in the implantation chamber, from undergoing apoptosis. Furthermore, we demonstrated that epithelial cell differentiation and related regulatory signaling were largely conserved in humans and mice. In the human endometrium, developmental defects of SOX9-positive epithelial cells similar to luminal epithelial cells were related to thin endometrium. Our work provides comprehensive and systematic information on endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is important for endometrial receptivity and embryo implantation.

cell biology↗

bioRxiv2022

Temporal and spatial dynamics mapping reveals follicle development regulated by different stromal cell populations

Follicle development is a complex dynamic process. The follicles are encapsulated in the stroma, and once the follicle develops, the follicle moves from the cortex to the medulla and finally to the cortex to ovulate in the process of continuous growth. Many of these processes cannot be explained with the follicle alone. Through single-cell and spatial transcriptome sequencing at key time points of follicular development in mice after birth, we found that ovarian stromal cells are not only one of the main cell groups that make up the ovary but that their cell population and spatial location are also closely related to follicular development. Through analysis of cell communication, it was found that ovarian stromal cells were the main transmitters of intercellular communication, and many of the signals they sent were received by granulosa cells and oocytes to participate in follicle development. Ovarian stromal cells are not a homogeneous cell population. We combined single cell types with their spatial location information to divide ovarian stromal cells into four types, namely, structural stromal cells, perifollicular stromal cells, stromal progenitor cells, and steroidogenic stromal cells, each of which plays a different function in follicle development. Indepth studies of the different spatial locations and different types of stromal cells will expand our understanding of follicle development dynamics, leading to new targets and novel approaches for the treatment of ovarian-related diseases.

developmental biology↗

bioRxiv2021

Crocin inhibited amyloid-beta (Aβ) generation via promoting non-amyloidogenic APP processing and suppressed ER stress UPR signaling in N2a/APP cells

BackgroundCrocin is a major active component of saffron (Crocus sativus) with many beneficial effects. More recently, crocin has been proposed for management of neurodegenerative diseases such as Alzheimers disease (AD). Here, we demonstrated for the first time that crocin reduced amyloid-beta (A{beta}) generation through promoting -cleavage of APP processing and inhibited ER stress by attenuating UPR signaling in N2a/APP cells. MethodologyMouse neuroblastoma N2a cells stably transfected with the Swedish mutant APP (N2a/APP) was used as a cellular model for AD pathogenesis. Vector transfected cells (N2a/vector) were employed to serve as control. The toxicity of crocin was first evaluated and non-toxic treatment of crocin (>30 {micro}M for 24 h) was used for further investigations. A{beta} levels were determined by ELISA. Expression levels of UPR signaling proteins were determined by using Western blot. ResultsCrocin significantly inhibited the protein expression of total APP in N2a/APP cells and promoted -cleavage of APP processing to increase sAPP generation, but only modestly reduced BACE-1 and PS1, suggesting A{beta} reduction by crocin was mainly associated with the non-amyloidogenic APP processing. Further investigation on ER stress related protein expressions showed that GRP78, CHOP, p-PERK, p-eIF2, p-IRE1, XBP1, ATF6 and PDI were all significantly elevated in N2a/APP cells compared to N2a/vector. Crocin effectively reduced the levels of GRP78 and CHOP, and significantly inhibited p-PERK/p-eIF2 amd AT6 while slightly reduced p-IRE1. ConclusionThe present study showed that crocin was effective at blocking A{beta} generation and inhibiting ER stress associated overactivation of UPR signaling in AD cell model N2a/APP. The results provided evidence for crocin as useful natural product for the treatment of AD.

neuroscience↗

bioRxiv2019

An updated analysis of opioids increasing the risk of fractures

ObjectiveTo assess the relationship between opioid therapy for chronic noncancer pain and fracture risk by a meta-analysis of cohort studies and case-control studies.\n\nMethodsThe included cohort studies and case-control studies were identified by searching the PubMed and EMBASE databases from their inception until May 24, 2019. The outcome of interest was a fracture. This information was independently screened by two authors. When the heterogeneity among studies was significant, a random effects model was used to determine the overall combined risk estimate.\n\nResultsIn total, 12 cohort studies and 6 case-control studies were included. We used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included literature, and 14 of the studies were considered high-quality studies. The overall relative risk of opioid therapy and fractures was 1.78 (95% confidence interval (CI) 1.53 - 2.07). Subgroup analyses revealed sources of heterogeneity, sensitivity analysis was stable, and no publication bias was observed.\n\nConclusionsThe meta-analysis showed that the use of opioids significantly increased the risk of fracture.

pharmacology and toxicology↗

bioRxiv2017

Brain Modularity Mediates the Relation of Cognitive Performance to Task Complexity

Recent work in cognitive neuroscience has focused on analyzing the brain as a network, rather than as a collection of independent regions. Prior studies taking this approach have found that individual differences in the degree of modularity of the brain network relate to performance on cognitive tasks. However, inconsistent results concerning the direction of this relationship have been obtained, with some tasks showing better performance as modularity increases and other tasks showing worse performance. A recent theoretical model (Chen & Deem, 2015) suggests that these inconsistencies may be explained on the grounds that high-modularity networks favor performance on simple tasks whereas low-modularity networks favor performance on more complex tasks. The current study tests these predictions by relating modularity from resting-state fMRI to performance on a set of simple and complex behavioral tasks. Complex and simple tasks were defined on the basis of whether they did or did not draw on executive attention. Consistent with predictions, we found a negative correlation between individuals modularity and their performance on a composite measure combining scores from the complex tasks but a positive correlation with performance on a composite measure combining scores from the simple tasks. These results and theory presented here provide a framework for linking measures of whole brain organization from network neuroscience to cognitive processing.

neuroscience↗

bioRxiv2017

Static and dynamic measures of human brain connectivity predict complementary aspects of human cognitive performance

In cognitive network neuroscience, the connectivity and community structure of the brain network is related to cognition. Much of this research has focused on two measures of connectivity - modularity and flexibility - which frequently have been examined in isolation. By using resting state fMRI data from 52 young adults, we investigate the relationship between modularity, flexibility and performance on cognitive tasks. We show that flexibility and modularity are highly negatively correlated. However, we also demonstrate that flexibility and modularity make unique contributions to explain task performance, with modularity predicting performance for simple tasks and flexibility predicting performance on complex tasks that require cognitive control and executive functioning. The theory and results presented here allow for stronger links between measures of brain network connectivity and cognitive processes.

neuroscience↗