Biology subjects

Wang, J.

Publications and source records attributed to Wang, J..

At least 667 records · Page 37Linked to original sources

bioRxiv2025

Longitudinal Imaging of Experimental Intracerebral Hemorrhage Pathology with Iodine-enhanced Micro-CT

BackgroundIodine-enhanced micro-computed tomography (Micro-CT) enables high-resolution three-dimensional imaging of brain architecture. This study aimed to characterize both acute and chronic pathological changes following intracerebral hemorrhage (ICH) using iodine-enhanced micro-CT. MethodExperimental ICH was induced in 8- to 10-week-old C57BL/6 mice (n = 76) via stereotaxic injection of either 0.075 U collagenase IV or 30 l autologous blood. Iodine-enhanced micro-CT imaging was performed at 4 hours, 1, 3, and 7 days after intracerebral hemorrhage post-ICH to evaluate hematoma formation and erythrolysis. Chronic alterations, including ventriculomegaly and ipsilateral lesion, were assessed at 28 days post-ICH. In parallel, MRI was conducted at 1, 7, and 28 days following autologous blood injection, followed by micro-CT, to facilitate cross-modality quantitative analysis. Lesion volumes were compared between imaging modalities over time. ResultsMicro-CT enabled quantification of hematoma volume and erythrolysis in ICH models. Hematomas extended along perivascular pathways toward the cerebral surface in both collagenase- and autologous blood-induced ICH models. At 28 days post-ICH, micro-CT detected ventriculomegaly and hypodense lesions without concurrent expansion of the choroid plexus. Lesion volume measurements derived from micro-CT correlated with those from MRI, enabling quantitatively assessment of iron deposition and hematoma size alterations after ICH. ConclusionIodine-enhanced micro-CT provides a robust and high-resolution imaging platform for evaluating hematoma evolution, hemolysis, ventricular enlargement, and chronic brain lesions in experimental ICH. When integrated with MRI, these multimodal imaging approaches enhance the characterization of both hematoma volume and iron deposition following ICH.

neuroscience↗

bioRxiv2025

Evaluation of the nano Liquid Chromatography coupled with Zeno TOF 7600 Mass Spectrometer for Cell Type-Resolved Spatial Proteomics

In this study, we systematically evaluated the nanoLC-Zeno TOF platform using data-independent acquisition (DIA) and identified 3,142 to 7,059 protein groups from 1 to 200 ng of standard K562 digest. Additionally, a targeted acquisition strategy detected 184 peptides with enhanced signal using Zeno activation. To achieve spatial cell-type resolved proteomics, we developed a workflow integrating image-guided laser capture microdissection for analysis of gastric cancer tissue. A 30-minute nanoLC gradient facilitated the quantification of 2,514 proteins from 0.2 mm{superscript 2} regions representing cancer cells, cancer-associated fibroblasts (CAFs), and immune cells, as defined by multiplex immunohistochemistry. This spatial proteomics approach revealed cellular heterogeneity within the tumor microenvironment of a clinical gastric cancer sample, and targeted validation identified differential expression of 12 cancer-associated proteins comprising 103 peptides between cancer cell-enriched and CAFs-enriched regions. This workflow offers a practical strategy for spatial visual proteomic analysis in clinical tissue samples.

cancer biology↗

bioRxiv2025

Evolutionary implications of stipule occurrence in Permo-Carboniferous wetland forests dominated by Psaroniaceae

Stipules are specialized appendages borne at the leaf base with roles as diverse as sheltering of delicate growing tissues from environmental exposure, vegetative propagation and dispersal, and modification into climbing hooks or protective spines. Stipules are widely present in extant vascular plants, but their origins in geological history remain obscure and must have involved convergent evolution more than once, perhaps as early as the late Paleozoic emergence of forested terrestrial ecosystems. Based on extraordinary collections from the early Permian Wuda Tuff Flora, the earliest known stipule structure in the plant kingdom has been identified in marattialean tree ferns Psaroniaceae, the dominant element of Permo-Carboniferous wetland forests. Psaroniaceous stipules are consistent with protection of juvenile fronds and the stem apex as well as retention of a functional role in mature and withered fronds. Furthermore, the continued and perhaps indeterminate growth and the fully laminated stipules invite speculation of a potential role in vegetative propagation following detachment from the parent frond. However, no direct fossil evidence of stipules acting as vegetative propagules is currently available.

paleontology↗

bioRxiv2025

Computational Design of Next-Gen Peptide Biopesticides: Targeting the Nicotinic Acetylcholine Receptor in Rice Pests Class

The brown planthopper (Nilaparvata lugens) threatens global rice production, and conventional pesticides face resistance and environmental challenges. We present a computational framework integrating AlphaFold3-predicted structure of the nicotinic acetylcholine receptor 3 subunit (nAChR-3) with multi-force-field molecular dynamics (MD) refinements to design peptide biopesticides. Crucially, we introduce "Dipeptide Probing", a high-throughput MD-based screening strategy employing 20 phenylalanine-containing dipeptides (F-X) to map dynamic binding sites. Unlike rigid docking or static free energy calculations, this approach captures transient interactions and cooperative binding phenomena, identifying Phe-Met (FM) as the top binder through hydrophobic contacts and multiple hydrogen bonding, while{pi} -stacking contributed minimally to complex stability, contradicting conventional paradigms. Additionally, MD simulations revealed an unexpected Aggregation-Induced Hydrophobicity Binding (AIHB) mechanism: FM dipeptides self-assemble via hydrogen bonds, orienting hydrophilic groups toward solvent and exposing hydrophobic surfaces to the target, thereby stabilizing complex formation to the helix bundle surface of nAChR-3. This cooperative behavior, undetectable by docking (e.g., AutoDock Vina failed to predict FM binding) or static energy methods, resolves limitations of reductionist approaches. Our work establishes "Dipeptide Probing" as a generalizable paradigm for dynamic binding-site mapping and underscores AIHBs potential to revolutionize peptide-based agrochemical design by leveraging emergent intra-/intermulti-molecule interactions.

plant biology↗

bioRxiv2025

A porcine germ cell depletion model to investigate the role of germ cells in gonadal development.

The molecular mechanisms regulating the germ cell and gonadal somatic cell development are complex and are still poorly understood in non-rodent mammals. The Nanos family gene-NANOS3 is expressed in the migrating primordial germ cells (PGC) and has key roles in germ cell survival in several species. Herein, we investigated the role of NANOS3 in pigs-an animal model of dual agricultural and biomedical importance. Consistent with prior reports, we found that disruption of NANOS3 expression did not affect PGC specification. Similarly, migration of PGC to the genital ridge occurs normally, but soon followed by an increase in apoptosis and a loss of undifferentiated state by embryonic (e) day 20. Although NANOS3-/- gonads initiate development as ovaries or testes, they displayed structural defects. This is especially pronounced in the ovaries after the sex determination period (e35). Notably, we identified defects in pregranulosa and theca cell development at a single-cell resolution, suggesting that germ cells are important for gonadal somatic cell development. This germ cell depletion model therefore offers novel insights into the potential role of germ cells in the emergence of gonadal somatic lineages.

developmental biology↗

bioRxiv2025

Mitochondrial Genome Variants and Nuclear Mitochondrial DNA Segments in 7331 Individuals from NyuWa and 1KGP

Dysfunctional mitochondria are implicated in various diseases, while little is known about comprehensive characterization of mitochondrial DNA (mtDNA) in Chinese population. Here, we conducted a systematic analysis of mtDNA from 7331 samples, comprising 4129 Chinese samples (NyuWa) and 3202 samples from the 1000 Genomes Project (1KGP). We identified 7216 distinct high-quality mtDNA variants and classified them into 22 macrohaplogroups, and detected 1466 distinct nuclear mitochondrial DNA segments (NUMTs), with 88 mtDNA variants and 642 NUMTs being specific to NyuWa. The genome-wide association analyses revealed that 12 mtDNA variants were significantly correlated with 199 nuclear DNA variants. Our findings revealed that all individuals in both NyuWa and 1KGP harbored common NUMTs, and one-fifth possessed ultra-rare NUMTs, which tended to insert into nuclear gene regions. Compared to 1KGP, significant enrichment of nuclear breakpoints in long interspersed nuclear elements (LINEs) was observed for rare NUMTs in NyuWa. Overall, this study represents the first comprehensive profiling the landscape of Chinese NUMTs and offers the most extensive resource of Chinese mtDNA variants and NUMTs based on high-depth WGS to date, providing valuable reference resources for genetic research on mtDNA-related diseases.

genomics↗

bioRxiv2025

Neural correlates of evidence accumulation in social-affective decision-making under perceptual ambiguity

Evidence accumulation models have been widely used to explain decision-making in sensory and cognitive domains, but how this process explains social-affective decision-making under perceptual ambiguity remains unclear. Here, we integrate computational modeling with multimodal neuroscience to investigate how perceptual ambiguity in emotion judgment influences decision dynamics. Participants viewed ambiguous stimuli--morphed images blending emotional expressions--and made binary categorizations. Using drift diffusion modeling (DDM), we show that drift rate, a core index of evidence accumulation, decreases as ambiguity increases. Scalp EEG data reveal that the late positive potential (LPP) tracks drift rate in both emotional and non-emotional decisions, but only when perceptual ambiguity is relevant to the task. Likewise, single-unite recordings from the dorsomedial prefrontal cortex (dmPFC) and amygdala neurons show that trial-by-trial firing rates in both regions encode drift rate, with opposite encoding patterns. fMRI-based connectivity analyses further reveal that the strength of amygdala-dmPFC coupling correlates with individual differences in the modulator effect of perceptual ambiguity on drift rate. Together, these findings identify a corticolimbic network that dynamically modulates evidence accumulation during social-affective decision-making under perceptual ambiguity. By linking computational parameters to neural activity across multiple modalities, this work advances our understanding of how the brain resolves emotionally ambiguous perceptual information. It provides a translational framework for studying emotion recognition and decision-making impairments in clinical populations.

neuroscience↗

bioRxiv2025

Generative Phenomenology of form perception: Perceptograms and cortical models for amblyopic form distortions

What we see is generated by our cortical neurons processing sensory input. Amblyopia provides a perfect case for studying the neural generation of percepts because abnormal neural development of cortex leads to many amblyopes seeing more complex phantom forms than the viewed stimulus through their amblyopic eye (AE) but not through the fellow eye (FE). Using computer guided dichoptic displays, we showed that 92.6% of phantom percepts generated by single gratings shown to AE were matched exactly by plaids (sums of two gratings) shown to FE. A formal equation between the cortical signals generated by the gratings seen through AE and the signals generated by their matched patterns seen through FE, provided the derivation of AE cortical receptive fields as linear transforms of FE receptive fields. The transformed AE cortical model accurately generated the phantoms, was validated via reverse-correlation, and explained deficits in form detection and spatial localization. This study elucidates the close link between percepts and neuronal receptive fields. TEASERChanges in cortical neurons receptive fields can lead to amblyopes seeing phantom features that are not present in viewed images.

neuroscience↗

bioRxiv2025

An atlas of cell type specific regulatory effects in cattle

Understanding the genetic and molecular architecture of complex traits and artificial selection is crucial for advancing sustainable precision breeding in cattle and other livestock. Yet, how genetic variation affects cellular gene expression remains elusive in cattle. Here, by integrating 8,866 bulk RNA-seq samples and 999,192 single cells of 81 cell types in 22 bovine tissues, we presented a comprehensive atlas of regulatory variants at the cell type resolution in cattle. By colocalizing with bulk-tissue expression quantitative trait loci (beQTL), we detected 57,043 novel cell-type stratified eQTL and cell-type/state interaction eQTL in 18,153 genes, which also exhibited a stronger tissue/cell-type specificity than beQTL. By examining genome-wide associations (GWAS) of 44 complex traits, these cell-resolved eQTL were colocalized with 505 (24%) additional GWAS loci compared to beQTL. Through integrating this resource with selection signatures between dairy and beef cattle, we provided tissue/cell-specific regulatory insights into cattle breeding. Overall, the current atlas of cell-type-specific regulatory variants will serve as an invaluable resource for cattle genomics and selective breeding.

genetics↗

bioRxiv2025

TaPGS1 Driven Flavonol Accumulation Delays Endosperm Cellularization and Enlarges Wheat Grains

Flavonols play a crucial role in seed development by regulating multiple physiological processes, including seed coat pigmentation, dormancy, fertilization, and endosperm formation. Notably, flavonols influence the polar transport of auxin, thereby affecting seed growth dynamics. In our previous work, we found that overexpression of the wheat bHLH transcription factor TaPGS1 results in increased grain size; however, the underlying mechanism remained unclear. In this study, metabolomic and transcriptomic analyses of TaPGS1 overexpressing wheat lines revealed enhanced flavonol accumulation and upregulation of key flavonol biosynthetic genes. Further investigations suggested that flavonol accumulation in the seed coat may disrupt auxin transport, leading to localized auxin buildup, delayed endosperm cellularization, and an increase in endosperm cell number. These changes collectively contribute to grain enlargement. Our findings uncover a TaPGS1 flavonol regulatory module that links auxin distribution to endosperm development and seed size control in wheat.

plant biology↗

bioRxiv2025

Application of machine learning in the discovery of antimicrobial peptides: Exploring their potential for ulcerative colitis therapy

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with rising global prevalence, yet existing treatments are not universally effective. Antimicrobial peptides (AMPs), produced by the immune system, have diverse antimicrobial and immune-regulatory functions, making them promising candidates for UC therapy. Using machine learning, we developed a machine learning-based prediction model to identify novel AMPs. The predicted peptides demonstrated significant biological activity in vitro and in vivo. In a dextran sulfate sodium-induced UC mouse model, engineered AMPs notably improved UC-related parameters, such as body weight, disease activity index (DAI), and colon length. These effects were likely mediated by modulation of Akkermansia muciniphila. This study highlights the potential of machine learning-identified AMPs as future therapeutic candidates for UC. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/660148v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@187dc6borg.highwire.dtl.DTLVardef@9800deorg.highwire.dtl.DTLVardef@1611c42org.highwire.dtl.DTLVardef@866406_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2025

COOKIE-Pro: Covalent Inhibitor Binding Kinetics Profiling on the Proteome Scale

Covalent inhibitors are an emerging class of therapeutics, but methods to comprehensively profile their binding kinetics and selectivity across the proteome have been limited. Here we introduce COOKIE-Pro (COvalent Occupancy KInetic Enrichment via Proteomics), an unbiased method for quantifying irreversible covalent inhibitor binding kinetics on a proteome-wide scale. COOKIE-Pro uses a two-step incubation process with mass spectrometry-based proteomics to determine kinact and KI values for covalent inhibitors against both on-target and off-target proteins. We validated COOKIE-Pro using the BTK inhibitors spebrutinib and ibrutinib, accurately reproducing known kinetic parameters and identifying both expected and novel off-targets. The method revealed that spebrutinib has over 10-fold higher potency for TEC kinase compared to its intended target BTK. We further demonstrate that COOKIE-Pro is compatible with streamlined cysteine activity-based protein profiling (SLC-ABPP) datasets, enabling efficient conversion of competition ratios to meaningful kinetic parameters. By providing a comprehensive view of covalent inhibitor binding across the proteome, COOKIE-Pro represents a powerful new tool for optimizing the potency and selectivity of covalent drugs during preclinical development.

biochemistry↗

bioRxiv2025

Transient Dietary Changes Modulate Inflammatory Disease Trajectory in the Lean State

Obesity potently alters immune responses across various inflammatory contexts1-7. However, it is unclear whether a transient high-fat diet (HFD) can affect immune function despite minimal effects on body weight. Here, we demonstrate that a short-term HFD regimen significantly exacerbates disease severity in a model of experimental psoriasis, comparable to what is observed in obese mice on long-term HFD. We find that a critical 4-day window of HFD coinciding with disease onset is sufficient to overactivate the immune response, leading to worsened disease outcomes. Mechanistically, we identify the CD4+ T cell compartment as an essential mediator of HFD-induced disease severity. Within the compartment, we functionally validate that disease exacerbation is driven by increased differentiation of a pathogenic population of T helper 17 (TH17) cells8 expressing IL1R1 (interleukin-1 receptor, type I)9, which is triggered by localized activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome10. This brief window of HFD at disease onset leads to immune-dependent sensitization, as disease severity is increased upon a subsequent flare, despite complete recovery and under a low-fat diet (LFD) regimen. Our data indicate that transient dietary changes during the initial stages of an inflammatory event can rewire the immune milieu, profoundly influencing disease progression and inflammatory memory11. This phenomenon may have broad implications for conditions where obesity, and not diet itself, is considered the primary risk factor.

immunology↗

bioRxiv2025

Feedback regulation of iron-sulfur cluster biogenesis

Iron-sulfur (Fe-S) clusters are ubiquitous cofactors in biological systems. Given their central role in bacterial metabolism and pathogenesis, the biogenesis of Fe-S clusters is tightly controlled. We reveal a feedback regulatory mechanism involving the sulfide producing SufS/SufU complex within the sulfur utilization (SUF) system of Mycobacterium tuberculosis, the bacterium that causes tuberculosis. In this mechanism, [2Fe-2S] clusters compete with zinc ions for binding to the sulfide transfer protein SufU. Cluster binding induces SufU tetramerization, which prevents its interaction with the cysteine desulfurase SufS, thereby inhibiting SufS activation and limiting sulfide supply for Fe-S cluster biogenesis. These findings uncover an unrecognized regulatory mechanism in M. tuberculosis, ensuring strict control of Fe-S cluster production.

biochemistry↗

bioRxiv2025

Metastatic niche mediated activation of metastasis initiating cells in ovarian cancer through miR-193b-3p downregulation via the ERK/EZH2/DNMT1 axis

Extensive metastasis at the time of diagnosis is a major contributor to the poor prognosis of ovarian cancer (OC) patients. There is a critical need to better understand the mechanism of regulation of metastasis to develop effective treatment strategies targeting the process. Metastasis initiating cells (MICs) have cancer stem cell-like properties along with the ability to invade. Their potential role in OC is unique as the dissemination from the primary tumors involves passive processes like exfoliation. However, the role of MICs during OC metastatic colonization is critical and poorly understood. Using an organotypic 3D culture model of the human omentum, we have studied the productive crosstalk between OC MICs and the metastatic microenvironment. We report the role of miR-193b-3p, a clinically relevant metastasis suppressor microRNA, which is downregulated in the OC by paracrine signals from the microenvironment, inducing the MIC phenotype. Using heterotypic coculture models, conditioned medium experiments, secretome analysis, inhibition, and rescue experiments, we show that bFGF and IGFBP6 secreted by mesothelial cells in the microenvironment induce miR-193b-3p downregulation in OC MICs via the ERK/EZH2/DNMT1 axis. The miR-193b-3p downregulation induced an increased expression of its target cyclin D1, which imparted a cancer stem cell phenotype. Urokinase, another target of miR-193b-3p, induced invasive growth. Together, these targets impart the MIC phenotype to the OC cells. miR-193b-3p replacement therapy could suppress metastasis in a patient derived xenograft model of OC metastasis, indicating the translational potential of this approach to target MICs in OC patients.

cancer biology↗

bioRxiv2025

ZIPcnv: accurate and efficient inference of copy number variations from shallow whole-genome sequencing

Shallow whole-genome sequencing (sWGS), a rapid and cost-effective sequencing technology, has gradually been widely adopted for CNV analyses. However, with genome-wide coverage of only 0.1-5x, sWGS data exhibit a pronounced zero-inflation phenomenon, whereby a large fraction of loci contains zero sequencing reads. Zero-inflation causes read counts to fluctuate by several-fold between adjacent windows. As a result, random upward blips in coverage can be misinterpreted as copy-number gains (false positives), and true deletions often become indistinguishable from pervasive zero-coverage noise. In addition, existing CNV detection tools developed for sWGS data often struggle to adapt across different CNV sizes. These combined effects severely constrain the accuracy of CNV inference. To address above challenges, we propose ZIPcnv, a novel CNV detection tool specifically designed for sWGS data. First, we apply a large sliding window to smooth the raw read depth signal, which transforms the original zero-inflated statistical characteristics into approximately normal distribution characteristics. We then design a statistical process model that robustly detects persistent shifts under high background noise using a cumulative sum strategy, classifying genomic regions into candidate and non-candidate CNV regions. Finally, dynamic sliding windows are used for one-pass detection of CNVs of varying lengths, with window size adapting to the CNV region size. We evaluated the performance of ZIPcnv on simulated data and 190 real whole-genome sequencing samples. Experimental results show that ZIPcnv consistently outperforms currently popular CNV detection tools. The ZIPcnv source code is freely available at https://github.com/Nevermore233/ZIPcnv.

bioinformatics↗

bioRxiv2025

Identification of a conserved RNA structure in the TNFRSF1A 3'UTR: Implications for post-transcriptional regulation

Tumor necrosis factor receptor superfamily 1A gene (TNFRSF1A) encodes the TNFR1 protein, a critical regulator of inflammation implicated in various diseases. Using ScanFold with the Integrative Genomics Viewer (IGV) GUI, we identified novel RNA structural elements within the TNFRSF1A gene. Focusing on the 3UTR, these structures were characterized using reporter assays and targeted DMS-MaPseq. We identified a structured region that may play a role in regulating TNFR1 translation and that was also found to associate with HuR, a key regulatory RNA-binding protein. These findings provide a framework for identifying and characterizing potential functional RNA structures in therapeutically relevant genes, suggesting a new layer of post-transcriptional regulation for TNFR1 expression.

molecular biology↗

bioRxiv2025

Pathogen effector forms a hexameric phosphatase holoenzyme with host core enzyme to promote disease

Pathogen effectors play critical roles in pathogenesis by directly manipulating host cellular processes. The Ser/Thr protein phosphatase 2A (PP2A) is commonly targeted by pathogens. Effectors from devastating plant pathogen Phytophthora hijack the PP2A core enzyme in plant hosts, altering the host phosphoproteome. In this study, we present a series of cryo-electron microscopy structures of the Phytophthora effector PSR2 in complex with the host PP2A core enzyme to form a functional holoenzyme. The PSR2-PP2A complex adopts a unique hexameric architecture, driven by PSR2-mediated dimerization of two heterotrimers. This hexamer exhibits greater stability and features a more exposed catalytic pocket compared to the canonical trimeric form of PP2A, likely enhancing its virulence activity. Mutational analyses underscore the importance of this hexameric structure for PSR2s virulence function. These findings provide mechanistic insights into pathogen-mediated manipulation of a key host phosphatase and offer targets for developing disease resistance strategies.

biophysics↗