Biology subjects

wang, q.

Publications and source records attributed to wang, q..

9 recordsLinked to original sources

bioRxiv2026

Disease stage-sensitive MFSD2A-caveolae axis insigates hippocampal blood-brain barrier disruption in Alzheimer's disease

Blood-brain barrier (BBB) malfunction contributes to pathophysiology of Alzheimer's disease (AD), yet the mechanisms that confer hippocampal endotheliocytes vulnerability remain unclear. Here we identify loss of endothelial major facilitator superfamily domain-containing protein 2A (MFSD2A), a suppressor of caveolae-mediated transcytosis, as an early and hippocampus-specific feature of AD-associated vascular impairment. In post-mortem human AD brains, reduction in hippocampal MFSD2A was accompanied with increased levels of caveolin-1 and perivascular albumin extravasation. Analysis of human single-nucleus transcriptomic data further demonstrated that vascular expression of MFSD2A declined during transition from mild cognitive impairment to established AD. In APP/PS1 mice, MFSD2A loss occurred early in hippocampal microvessels and coincided with disproportionately high hippocampal BBB leakage and reductions in GLUT1 and claudin-5, despite broader amyloid deposition throughout other brain regions. Restoration of endothelial MFSD2A using an AAV-BR1-based vascular vector during early stage of amyloid pathology, reduced albumin extravasation and preserved GLUT1 and claudin-5. Early intervention also reduced amyloid plaque burden and plaque-associated neuritic dystrophy, whereas this treatment during established amyloid pathology, although modifying selected endothelial markers, failed to reverse BBB leakage, amyloid pathology, or cognitive impairment. Sustained MFSD2A restoration from the early disease stage provided the greatest protection, preserving hippocampal BBB integrity, reducing amyloid and neuritic pathology, improving long-term potentiation and ameliorating spatial learning and memory deficits. These findings define endothelial MFSD2A loss as a disease stage-sensitive mechanism of hippocampal BBB vulnerability and highlight the MFSD2A-caveolae axis as a therapeutic target for early-stage AD.

neuroscience↗

bioRxiv2026

Nuclear Cx43 restrains microglial neurotoxicity during brain development

Microglia are essential for sculpting the developing brain, yet the molecular mechanisms that select beneficial overreactive phagocytosis remain incompletely understood. Connexin 43 (Cx43, encoded by GJA1 in humans) is best known as a gap junction and hemichannel protein, although its non-canonical, channel-independent functions are increasingly recognized. We found that Cx43 is highly expressed in microglia during the perinatal period in human and mouse, whereas proportion of full-length multimeric Cx43 unexpectedly localizes to the nucleoplasm. Deletion of microglial Cx43 in mice during development instigates a transient neurotoxic state with microgliosis, upregulated phagocytic and complement pathways, excessive neuronal apoptosis, translating into depressive-like and cognitive deficits in the adulthood. Notably, neither microglia-specific deletion of Cx43 in adulthood nor hemichannel blockade recapitulate these changes, indicating a channel-independent, developmental stage-specific neuroprotective mechanism. Nucleus-targeted Cx43 overexpression suppresses neurotoxic markers and neural apoptosis. Nuclear Cx43 interacts with transcriptional regulators to restrain proinflammatory gene programs, nuclear import of Cx43 is driven by neurogenic niche-derived bFGF, which triggers AKT-mediated phosphorylation of a C-terminal nucleus localization signal (NLS), 14-3-3 binding, and importin-dependent nucleus translocation. These findings reveal a developmentally restricted nuclear Cx43 function that restrains microglial neurotoxicity while promoting microglial physiological functions thus expanding connexin biology to transcriptional co-regulation and pointing to a potential avenue for therapeutic intervention.

neuroscience↗

bioRxiv2025

Spatial Flavonoid Accumulation in Soybean Pericycle Restricts Phytophthora sojae Invasion

Root immunity relies on coordinated defenses across distinct tissues, yet the underlying cellular mechanisms remain unclear. Here, we integrated single-cell transcriptomics, spatial metabolomics, and genetic manipulation to dissect soybean (Glycine max) interactions with Phytophthora sojae. In resistant Williams82 (Wm82) roots, P. sojae hyphae were excluded from the stele, exhibiting negative tropism toward the pericycle. scRNA-seq revealed that this resistance is mediated by infection-induced pericycle cells expressing high levels of flavonoid biosynthetic genes, including GmCHS7 and GmCHI4A. CRISPR-Cas9 knockout of these genes compromised resistance, whereas overexpression enhanced immunity in susceptible cultivars. Metabolomic and spatial metabolic analyses identified naringenin, a flavonoid phytoalexin, as a key antimicrobial compound that specifically accumulates in pericycle-adjacent tissues of Wm82 during infection. Naringenin directly inhibited hyphal growth in vitro and enhanced resistance when applied exogenously. These findings uncover a spatially targeted immune strategy where pericycle-localized activation of flavonoid synthesis forms a chemical barrier to safeguard vascular integrity, highlighting pericycle-centered metabolic immunity as a target for engineering durable resistance.

plant biology↗

bioRxiv2025

Dissecting organoid-bacteria interaction highlights decreased contractile force as a key factor for heart infection

Bacterial endocarditis is a fatal cardiovascular disease exacerbated by weakened heart contraction, yet the direct impact of cardiac contractility on bacterial adhesion remains elusive. Here, we present a novel quantitative physics model integrating finite element analysis and live-cell imaging to uncover their strong correlation. Using this model, we quantified the real-time force magnitude generated by organoid-type cardiac microtissue derived from healthy donors and dilated cardiomyopathy patients - mimicking normal and suppressed heart contractility, respectively - to the approaching bacteria in a real fluidic system. The data revealed that weakened cardiac contractility facilitated bacterial invasion of the myocardium. Verifying this finding in a mouse transverse aortic constriction model demonstrated that increasing heart contraction efficiently mitigated bacterial invasion, with a 25% increase in heart contractility reducing endocarditis risk by 80%. Our findings demonstrate that patient-derived cardiac organoids provide a physiologically relevant platform for studying bacterial infections in vitro, offering high clinical fidelity. This platform establishes a valuable tool for drug screening and the development of novel therapeutic strategies.

bioengineering↗

bioRxiv2025

The Role of Microglia and Complement C5/C5a in the Pathogenesis of Rhegmatogenous Retinal Detachment with Choroidal Detachment

BackgroundRhegmatogenous retinal detachment with choroidal detachment (RRDCD) is an uncommon and sight-threatening disorder marked by fast development and significant inflammation. This study aimed to identify cellular and molecular signatures distinguishing RRDCD from typical rhegmatogenous retinal detachment (RRD) and to investigate the roles of microglia and the complement C5/C5a pathway in disease pathogenesis. MethodsSingle-cell RNA sequencing (scRNA-seq) was employed to analyze vitreous samples from patients with RRD and RRDCD, indicating its involvement in blood-retina barrier impairment. ResultsOur findings revealed a distinct cellular landscape in RRDCD, characterized by enhanced connectivity between microglia and dendritic cells, alongside a significant upregulation of the complement C5-C5AR1 interaction. In vitro experiments indicated that treatment with complement C5 promoted microglial proliferation and activation, induced apoptosis in RF/6A endothelial cells, and disrupted tight junctions in ARPE-19 epithelial cells, suggesting a role in blood-retina barrier dysfunction. ConclusionThe findings substantiate the inflammatory hypothesis regarding the pathogenesis of RRDCD, emphasizing the critical functions of microglia and the complement C5/C5a pathway in intensifying retinal inflammation and undermining vascular integrity.

bioinformatics↗

bioRxiv2024

Integrated Analysis Reveals Immunogenic Cell Death in Sepsis-induced Cardiomyopathy

BackgroundSepsis-induced cardiomyopathy (SIC) poses a significant challenge in critical care, necessitating comprehensive understanding and innovative diagnostic approaches. This study explores the immune-related molecular intricacies underlying SIC, employing bioinformatics analyses and machine learning techniques. MethodsRNA-seq and scRNA-seq datasets (GSE79962 and GSE190856) were obtained from the Gene Expression Omnibus (GEO). After initial quality control and preprocessing, scRNA-seq data (GSE190856) were analyzed using the Seurat package, including cell clustering and annotation. The CellChat package was then used to analyze immune cell interactions. Unsupervised clustering of SIC patients was performed based on differentially expressed ICD-related genes (GSE79962). Immune cell infiltration and gene set variation analysis were conducted, and weighted gene co-expression network analysis identified co-expression modules. A predictive signature for SIC was constructed through machine learning methods. ResultsTrough analyzing the GSE190856 scRNA-seq dataset, the communication between macrophages/monocytes and lymphocytes was found to be enhanced in mouse myocardial tissue during the early onset of SIC. Meanwhile, the expression level of ICD-related genes was upregulated in the monocytes infiltrating to the heart. These results suggestted that ICD may play a crucial role in the pathogenesis of SIC, which had been verified by the upregulated expression of ICD-related genes in the hearts of SIC patients in the GSE79962 dataset. The SIC patients were classified to 2 clusters, with cluster 1 exhibited an upregulation of the renin-angiotensin system, while cluster 2 displayed heightened activity in the RIG-I-like receptor signaling pathway. After comparing four machine learning models, the support vector machine (SVM) model exhibited better discrimination for SIC patients. By correlating the expression levels of the five crucial genes contained in this model with the clinical features of SIC patients, we found that JARID2 was negatively related to the Left Ventricular Ejection Fractions, while TNIP2 was negatively related to the variety of inotropes and vasopressors used in the SIC patients. ConclusionThis research unveils the correlation between ICD and SIC, offering insights into immune activity in the hearts during sepsis. The constructed SVM model with selected genes provides a promising molecular strategy for SIC diagnosis.

genomics↗

bioRxiv2023

Predication of the Post Mining Land Use Based on Random Forest and DBSCAN

Mine reclamation is one of the most important stages of the mining activities in line with the basic principles of sustainable development. In this study, different post-mining land uses are evaluated in the Hongliulin mining area, which is located in Shen mu country of China. 145 soil samples were collected in the May,2021 by using the soil auger, and the sampling depths were 0-20 cm. The sampling points contains 45 to be reclaimed samples and 100 existing classification land use types. 14 environmental factors including soil organic matter (SOM), total nitrogen (TN) and other soil nutrients and terrain factors were extracted and calculated based on laboratory test and digital elevation map. Meanwhile, random forest classier was utilized to determine the post-mining land use based on GINI index and 14 environmental factors by using 100 existing classification land use types. 82 of 100 samples were utilized to build the model and the other 18 samples were utilized to validate the accuracy of the classification model. Density-Based Spatial Clustering of Applications with Noise (DBSCAN) techniques were utilized to determine the specific land use types in cropland, shrub and grassland. the random forest classier showed a great prediction capability, with only 1 miss-classified sample in the validation data-set, the accuracy of the classification model was 95%. Among the 45 samples to be reclaimed, 15 samples were classified into cropland, 23 samples were classified into shrub and grassland, 5 samples were classified into arbor land, 2 samples were classified into solar station. By using DBSCAN, the 58 samples classified into cropland in terms of the post-mining were separated into cluster 1 and 2, cluster 1 comprises 24 samples while cluster 2 comprises 34 samples. Among the 61 samples classified into shrubland and grassland, Cluster -1 comprises 24 samples and Cluster 0 comprise 22 samples. The results could provide technological support for land reclamation determination. The content of TN of C1 is 5 times more than C2 and 4 times more than C3. Also, the K valve of C1 column is maximum and over 0.4, which means the soil particle is relatively smaller and the soil texture of it is sandy loam. The TWI of C1 is minimum, in consideration of a positive valve of profile curvature and a negative valve of plan curvature. In terms of the 45 to be reclaimed samples, 15 samples were classified into C1, 23 samples were classified into C2, 5 samples were classified into C3, 2 samples were classified into C4. The valve of K and content of soil nutrients of the samples classified to be C1 column(C1-C) is maximum. Simultaneously, the slope steepness({degrees}) is below 5{degrees} and is perceived as gentle surface. Cluster 1 comprises 24 samples and the average content of TN, AP and SOM is 0.566g/kg, 11.93mg/kg and 19.975g/kg respectively, while Cluster 2 comprises 34 samples and the average content of TN, AP and SOM is 0.304g/kg, 3.12mg/kg and 8.36g/kg respectively. The result may contribute to the land use planning and idle land utilization strategy.

ecology↗

bioRxiv2019

The Structural Basis for Glycerol Permeation by human AQP7

Human glycerol channel AQP7 conducts glycerol release from adipocyte and entry into the cells in pancreatic islets, muscles and kidney tubule, and thus regulate glycerol metabolism in those tissues. Compared with other human aquaglyceroporins, AQP7 shows a less conserved "NPA" motif in the center cavity, and a pair of aromatic residues at Ar/R selectivity filter. To understand the structural basis for the glycerol conductance, we crystallized the human AQP7 and determined the structure at 3.7 [A]. A substrate binding pocket was found near to the Ar/R filter and the bound glycerol molecule stabilized by R229. In vivo functional assay on human AQP7 as well as AQP3 and AQP10 demonstrated strong glycerol transportation activities at physiological condition. The human AQP7 structure reveals a fully closed conformation with its permeation pathway strictly confined by Ar/R filter at the exoplasmic side and the gate at the cytoplasmic side, and the dislocation of the residues at narrowest parts of glycerol pathway in AQP7 play a critical role in controlling the glycerol flux.

molecular biology↗

bioRxiv2019

Temperature dependence of allelopathy duality and its influence on boreal forest succession-A case analysis of Picea schrenkiana

Global warming in conjunction with various biotic or abiotic interferences has been jeopardizing the ecosystem of boreal forests. By integrating field inspection with experimental simulation, this work comprehensively investigated the allelopathic effects of a key allelochemical 3,4-dihydroxyacetophenone (DHAP) in the exudates of P. schrenkiana needles on its seed and seedling growth, endogenous hormone metabolism and antioxidant enzyme activity, identified the existence of DHAP allelopathy duality at a certain temperature with an inflection concentration point (e.g. about 0.25 mM at dark/light temperature of 4/12 {degrees}C) as the boundary between promotional and inhibitory effect, and verified that the inflection point of DHAP concentration would inevitably shift to a lower level as temperature increased. Consequently, this paper gives a scientific explanation into the intrinsic mechanism of P. schrenkiana degradation due to allelopathy, but also presents a new approach to explore the relationship between forest evolution and global warming.\n\nHighlightA quantitative description on the duality of 3, 4-dihydroxyacetophenone (DHAP) as a promoter or an inhibitor to affect the seed germination, seedling growth and root development of P. schrenkiana, as well as the antioxidant enzyme activities and hormone contents.\n\nThe new findings of DHAP inflection concentration as boundary to divide the promotional and inhibitory effect of allelopathy which would decrease as environment temperatures rise.\n\nAn explanation into the intrinsic mechanism of P. schrenkiana degradation due to allelopathy, and a new approach to explore the relationship between forest evolution and global warming.

plant biology↗